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Biomedical subjects

C M Gray

Publications and source records attributed to C M Gray.

At least 37 records · Page 2Linked to original sources
PubMed1996

Preemptive cadaveric renal transplantation--clinical outcome.

Preemptive cadaveric renal transplantation (PCRT) maximizes the chance of maintaining high quality of life and may avoid the morbidity of dialysis and the associated financial costs. These benefits are offset by disadvantages, which include the possibility of transplantation many months before the need for dialysis, resulting in wasted organ function; an immediate risk of graft failure with conversion to a dialysis-dependent state; and uncertainty of the safety of PCRT. Patients who underwent PCRT between June 1976 and December 1994 at the Oxford Transplant Centre were compared with a matched cohort of first cadaveric transplant recipients who were dialysis-dependent when transplanted. The 116 patients in the PCRT cohort were well matched to the control group with respect to sex, age, blood group, HLA match, degree of sensitization, donor age, immunosuppression, and year of transplantation. Patient and graft survival were significantly better in the PCRT group. The difference in graft survival did not appear to be completely explained by better patient survival, as suggested by a trend toward better graft survival after excluding death with a functioning graft as a cause of failure. Among surviving grafts there were no significant differences in graft function as assessed by 1, 2, and 3 year plasma creatinine levels. In conclusion, PCRT appears to be safe and may even be associated with superior graft survival when compared with conventional transplantation. Early inclusion on a transplant waiting list with a view to PCRT can be justified with respect to the clinical outcome but the financial costs and implications for the utilization of cadaveric donor kidneys must also be considered.

Adolescent↗
PubMed1996

Chattering cells: superficial pyramidal neurons contributing to the generation of synchronous oscillations in the visual cortex.

In response to visual stimulation, a subset of neurons in the striate and prestriate cortex displays synchronous rhythmic firing in the gamma frequency band (20 to 70 hertz). This finding has raised two fundamental questions: What is the functional significance of synchronous gamma-band activity and how is it generated? This report addresses the second of these two questions. By means of intracellular recording and staining of single cells in the cat striate cortex in vivo, a biophysically distinct class of pyramidal neuron termed "chattering cells" is described. These neurons are located in the superficial layers of the cortex, intrinsically generate 20- to 70-hertz repetitive burst firing in response to suprathreshold depolarizing current injection, and exhibit pronounced oscillations in membrane potential during visual stimulation that are largely absent during periods of spontaneous activity. These properties suggest that chattering cells may make a substantial intracortical contribution to the generation of synchronous cortical oscillations and thus participate in the recruitment of large populations of cells into synchronously firing assemblies.

Action Potentials↗
PubMed1996

Identification of cell subsets expressing intracytoplasmic cytokines within HIV-1-infected lymph nodes.

OBJECTIVE: To describe the endogenous cytokine profile of HIV-1-infected lymph nodes (LN) and to identify the phenotype of individual cells expressing intracytoplasmic cytokines. DESIGN AND METHODS: Whole LN biopsies were collected from three HIV-seronegative controls and four HIV-1-positive individuals with persistent generalized lymphadenopathy. Three had established infection (Centers for Disease Control and Prevention 1993 criteria, stages A2, C1 and C3) and one was undergoing seroconversion illness. A combination of three methods was used to assess the impact of HIV-1 on LN architecture and endogenous cytokine expression. Immunocytochemistry was used to locate follicular dendritic cells (FDC), interdigitating cells and T and B cells. Reverse transcriptase-polymerase chain reaction was used to assess mRNA for interleukin (IL)-1 beta, IL-2, IL-4, IL-6, IL-10, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma in collagenase-digested LN cells. Three-colour flow cytometry was used to identify intracytoplasmic cytokine expression within cell subsets. RESULTS: Germinal center (GC) hyperplasia was observed in LN from two patients with established HIV-1 infection, and the third, coinfected with Mycobacterium tuberculosis, showed extensive necrosis. In the patient undergoing seroconversion, there was an extensive FDC network within the expanded and confluent GC which covered expansive areas of the LN. There was varied expression of IL-1 beta, IL-4, IL-6, IL-10 and TNF-alpha mRNA from the four HIV-1-infected LN and the patient undergoing seroconversion showed evidence for a mixed cytokine profile, which also included IL-2 and IFN-gamma. Flow cytometry revealed intracytoplasmic IL-1 beta protein restricted to cells expressing CD19, CD21 and CD38 antigens. CONCLUSIONS: Cytokines were detected in freshly isolated HIV-1-infected LN cells without requiring an exogenous stimulus. Seroconversion was associated with an expanded FDC network within enlarged GC, bounded by defined mantle zones containing B cells. There was diverse cytokine mRNA expression and IL-1 beta protein was restricted to cells expressing B-cell-associated antigens.

Adult↗
PubMed1995

Tetrodes markedly improve the reliability and yield of multiple single-unit isolation from multi-unit recordings in cat striate cortex.

The majority of techniques for separating multiple single-unit spike trains from a multi-unit recording rely on the assumption that different cells exhibit action potentials having unique amplitudes and waveforms. When this assumption fails, due to the similarity of spike shape among different cells or to the presence of complex spikes with declining intra-burst amplitude, these methods lead to errors in classification. In an effort to avoid these errors, the stereotrode (McNaughton et al., 1983) and later the tetrode (O'Keefe and Reece, 1993; Wilson and McNaughton, 1993) recording techniques were developed. Because the latter technique has been applied primarily to the hippocampus, we sought to evaluate its performance in the neocortex. Multi-unit recordings, using single tetrodes, were made at 28 sites in area 17 of 3 anesthetized cats. Neurons were activated with moving bars and square wave gratings. Single units were separated by identification of clusters in 2-D projections of either peak-to-peak amplitude, spike width, spike area, or the 1st versus 2nd principal components of the waveforms recorded on each channel. Using tetrodes, we recorded a total of 154 single cells (mean = 5.4, max = 9). By cross-checking the performance of the tetrode with the stereotrode and electrode, we found that the best of the 6 possible stereotrode pairs and the best of 4 possible electrodes from each tetrode yielded 102 (mean = 3.6, max = 7) and 95 (mean = 3.4, max = 6) cells, respectively. Moreover, we found that the number of cells isolated at each site by the tetrode was greater than the stereotrode or electrode in 16/28 and 28/28 cases, respectively. Thus, both stereotrodes, and particularly electrodes, often lumped 2 or more cells in a single cluster that could be easily separated by the tetrode. We conclude that tetrode recording currently provides the best and most reliable method for the isolation of multiple single units in the neocortex using a single probe.

Action Potentials↗
PubMed1993

Clinical and socioeconomic benefits of serological HLA-DR matching for renal transplantation over three eras of immunosuppression regimens at a single unit.

The efficacy of HLA-DR matching in cadaveric renal transplantation is controversial in the cyclosporine (CsA) era. Reports have questioned both the reliability of serological HLA-DR typing as well as the benefit of matching in terms of improved graft survival. Analysis of 1,000 consecutive cadaver donor transplants performed at Oxford between 1975 and 1992 has shown that with improved immunosuppressive regimens and increased transplant success there has been a steadily diminishing influence of HLA-DR matching measured in terms of first graft outcome. For patients treated with azathioprine and prednisolone (n = 278) overall one-year first graft survival was 65%, but there was a 20% improvement associated with HLA-DR matching which has been maintained for up to 15 years. With the introduction of CsA, used either alone or in conjunction with low dose steroids (n = 96), one-year first graft survival was 69% and the difference between HLA-DR-matched and -mismatched transplants was 14%. Our current maintenance immunosuppressive protocol is triple therapy (N = 425) with an 81% one-year first graft survival for both matched and mismatched transplants. However, we do continue to find a marked correlation between HLA-DR matching and clinical course. HLA-DR-mismatched patients suffer more rejection episodes, spend a longer time in the hospital, and have higher creatinine levels at 3 months. This costs, on average, an extra 1,500 pounds for each mismatched transplant. The effect is most apparent in unsensitized males. For cadaveric regrafts, one-year graft survival for patients on triple therapy is 80% (n = 116) which does not differ from first graft survival rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Graft Rejection↗
PubMed1992

Visually evoked oscillations of membrane potential in cells of cat visual cortex.

In response to visual stimulation, cells of the cat visual cortex fire rhythmically at frequencies between 30 and 60 hertz. This rhythmic firing can be synchronized among cells in widespread areas of the visual cortex. The visual stimulus conditions under which this process occurs suggest that the synchronization may contribute to the integration of information across broadly displaced parts of the visual field. An intricate mechanism must control the regularity of firing and its synchronization. In vivo whole-cell patch recordings from cells in area 17 have now shown that robust oscillations of membrane potential underlie the regularity of firing seen extracellularly. In the cells studied, the characteristics of the oscillations of membrane potential suggest that such oscillations are produced by rhythmic activity in synaptic inputs. These rhythmic synaptic inputs form the most likely mechanism for the synchronization of activity in neighboring cortical cells.

Animals↗
PubMed1992

Synchronization of oscillatory neuronal responses in cat striate cortex: temporal properties.

Previously, we have demonstrated that a subpopulation of visual cortical neurons exhibit oscillatory responses to their preferred stimuli at a frequency near 50 Hz (Gray & Singer, 1989). These responses can selectively synchronize over large distances of cortex in a stimulus-specific manner (Gray et al., 1989; Engel et al., 1990 alpha). Here we report the results of a new analysis which reveals the fine temporal structure inherent in these interactions. We utilized pairs of recordings of the local field potential (LFP) activity from area 17 in the anesthetized cat which met two criteria. The LFP was correlated with the underlying unit activity at each site and the recording sites were at least 5 mm apart in cortex. A moving-window technique was applied to compute cross correlograms on 100-ms epochs of data repeated at intervals of 30 ms for a period of 3 s during each direction of stimulus movement. A statistical test was devised to determine the significance of detected correlations. In this way we were able to determine the magnitude, phase difference, frequency, and duration of correlated oscillations as a function of time. The results demonstrate that (1) the duration of synchrony is variable and lasts from 100-900 ms; (2) the phase differences between and the frequencies of synchronized responses are also variable within and between events and range from +3 to -3 ms and 40-60 Hz, respectively; and (3) multiple correlation events often occur within a single stimulus period. These results demonstrate a high degree of dynamic variability and a rapid onset and offset of synchrony among interacting populations of neurons which is consistent with the requirements of a mechanism for feature integration.

Animals↗
PubMed1992

Enhanced spontaneous and induced LAK function in baboons receiving total lymphoid irradiation (TLI).

TLI has potent immunosuppressive effects, but there is concern over its possible carcinogenic properties. The aim of the study was to assess to what degree TLI may compromise natural killer (NK) and lymphokine activated killer (LAK) cell function. There was a significant increase (P less than 0.0001) in both NK-cell function (measured against K562 targets) and spontaneous LAK-cell function (measured against DAUDI targets) in fresh blood lymphocytes throughout a course of 8 x 100 cGy fractionated TLI. This may be related to a three- and sevenfold increase, respectively, in CD16+ CD8- and CD56+ CD2- cell frequencies over the same period. Mitogen-induced interleukin 2 (IL-2) synthesis from blood lymphocytes was inhibited by up to 75% with as little as 100 cGy of TLI. Expression of IL-2 receptors on fresh lymphocytes did not vary and remained low. Therefore spontaneous LAK occurrence appeared to be triggered through an IL-2-independent pathway. The in vitro addition of IL-2 verified that cells retained their ability to respond to this lymphokine resulting in greatly enhanced induced LAK function. This was most probably mediated by CD56+ cells which were found to readily express IL-2 receptors upon mitogen stimulation. In conclusion, fractionated low-dose TLI appears to enhance MHC unrestricted immune surveillance in a manner independent of IL-2 production.

Animals↗
PubMed1989

Oscillatory responses in cat visual cortex exhibit inter-columnar synchronization which reflects global stimulus properties.

A fundamental step in visual pattern recognition is the establishment of relations between spatially separate features. Recently, we have shown that neurons in the cat visual cortex have oscillatory responses in the range 40-60 Hz (refs 1, 2) which occur in synchrony for cells in a functional column and are tightly correlated with a local oscillatory field potential. This led us to hypothesize that the synchronization of oscillatory responses of spatially distributed, feature selective cells might be a way to establish relations between features in different parts of the visual field. In support of this hypothesis, we demonstrate here that neurons in spatially separate columns can synchronize their oscillatory responses. The synchronization has, on average, no phase difference, depends on the spatial separation and the orientation preference of the cells and is influenced by global stimulus properties.

Animals↗
PubMed1989

Stimulus-specific neuronal oscillations in orientation columns of cat visual cortex.

In areas 17 and 18 of the cat visual cortex the firing probability of neurons, in response to the presentation of optimally aligned light bars within their receptive field, oscillates with a peak frequency near 40 Hz. The neuronal firing pattern is tightly correlated with the phase and amplitude of an oscillatory local field potential recorded through the same electrode. The amplitude of the local field-potential oscillations are maximal in response to stimuli that match the orientation and direction preference of the local cluster of neurons. Single and multiunit recordings from the dorsal lateral geniculate nucleus of the thalamus showed no evidence of oscillations of the neuronal firing probability in the range of 20-70 Hz. The results demonstrate that local neuronal populations in the visual cortex engage in stimulus-specific synchronous oscillations resulting from an intracortical mechanism. The oscillatory responses may provide a general mechanism by which activity patterns in spatially separate regions of the cortex are temporally coordinated.

Animals↗
PubMed1988

Centrifugal regulation of neuronal activity in the olfactory bulb of the waking rabbit as revealed by reversible cryogenic blockade.

The influences of centrifugal projections to the olfactory bulb were examined on the bulbar EEG and mitral-tufted cell activity in waking rabbits. Each of 6 rabbits was implanted, under surgical anesthesia, with fine wire electrodes for recording of the EEG and mitral-tufted cell unit activity and for stimulating the lateral olfactory tract. Two cooling probes, for reversible cryogenic blockade, were implanted on either side of the left olfactory peduncle. Records of EEG and unit activity were taken for 200 s before, during and after cooling of the probes to 3 degrees centigrade. Antidromic evoked potentials were used to assess the efficacy of the blockade. During the cryogenic blockade bursts of EEG activity, evoked in the bulb by inspiration through the nose, were augmented in amplitude and reduced in frequency. Mitral-tufted cell unit activity was reduced in rate but was more highly correlated with the phase and amplitude of the EEG bursts. Analysis of individual EEG bursts revealed that the variance in frequency of bulbar activity was significantly reduced in the isolated state. The data demonstrate that oscillatory bursting activity in the olfactory bulb is intrinsically maintained within a relatively fixed frequency range during receptor input and does not depend on centrifugal projections for its electrogenesis. Changes in EEG frequency, amplitude and correlation with unit activity support the hypothesis that centrifugal projections act in part to inhibit mitral-tufted cell output by direct excitation of granule cells. These findings are supported by a theoretical model in which distributed feedback to the granule cells from more central olfactory structures acts to regulate the coherency of bulbar activity.

Action Potentials↗
PubMed1988

Field potential response changes in the rabbit olfactory bulb accompany behavioral habituation during the repeated presentation of unreinforced odors.

Experiments were performed on waking rabbits to investigate the changes in both sniffing behavior and local field potential responses in the olfactory bulb during repeated exposure to unreinforced odors. Six rabbits were each implanted with 2 pairs of electrodes for differential recording of the bulbar extracellular field potential. Each animal was given 3 sequential sessions to each of 2 separate odors on 6 consecutive days, while monitoring the bulbar field potential activity and sniffing behavior. Behavioral sniffing responses exhibited rapid within-session decrement in amplitude and long term decrement across sessions. The within-session decrement showed spontaneous recovery between sessions. Both decremental changes in sniffing behavior were accompanied by changes in the bulbar field potential responses. The responses to novel odors were characterized by a reduction in amplitude of high frequency activity (40-80 Hz) and a corresponding increase in amplitude of low frequency activity (15-25 Hz). The high frequency component of the responses showed an initial increase in frequency to a novel odor on the first 3 presentations followed by a rapid decrease in frequency on subsequent trials in the first session which stabilized thereafter. No change in frequency or relative amplitude was observed for the low frequency component. The absolute difference between the odor evoked activity and the preceding control activity measured on each trial showed a significant decrement across sessions with no evidence for spontaneous recovery. The results demonstrate that olfactory bulb responses to novel unreinforced odors show both rapid and long-term changes which parallel changes in sniffing behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1987

Induction and maintenance of epileptiform activity in the rabbit olfactory bulb depends on centrifugal input.

A technique of cryogenic blockade was used in waking rabbits to produce complete and reversible isolation of the olfactory bulb from the rest of the brain. During cooling of the olfactory peduncle epileptiform activity occurred spontaneously in the pyriform cortex in 3 out of 20 sessions, but never in the bulb. Following removal of the cryoblockade, during the seizure state, epileptiform discharges appeared simultaneously in the bulb and pyriform cortex. In the control state, without cooling of the peduncle, epileptiform activity could be evoked in the bulb and cortex by intense electrical stimulation of either the bulb or the lateral olfactory tract. During the cryoblockade, however, intense stimulation of the bulb failed to evoke seizure-like discharges. The results demonstrate a dependency on more central olfactory structures for the induction and maintenance of epileptiform activity in the olfactory bulb.

Animals↗