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D B Clifford

Publications and source records attributed to D B Clifford.

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

Nitric oxide inhibitors attenuate ischemic degeneration in the CA1 region of rat hippocampal slices.

We examined the involvement of nitric oxide (NO) in ischemic brain damage using hippocampal slices prepared from 30 day old albino rats and exposed to 20 min of oxygen/glucose deprivation (ischemia) followed by 90 min postincubation in oxygen- and glucose-containing media. Damage in the CA1 region was rated on a 0 (intact) to 4 (severe neuronal damage) scale by a rater blind to the experimental condition. Control slices exposed to ischemia were rated as 2.8 +/- 0.4 (N = 12). L-NG-Monomethylarginine (100 microM) and L-NG-nitroarginine (100 microM), non-selective NO synthase (NOS) inhibitors, diminished ischemic damage (0.6 +/- 0.3, N = 8, and 1.0 +/- 0.5, N = 4, respectively). An inhibitor of brain NOS, 7-nitroindazole (30 microM), was also effective against ischemic degeneration (0.7 +/- 0.3, N = 5). These results suggest that activation of NOS is involved in ischemic degeneration in the CA1 region.

Animals↗
PubMed1996

Magnetic resonance brain imaging lacks sensitivity for AIDS associated cytomegalovirus encephalitis.

Six patients are presented who died with active cytomegalovirus (CMV) encephalitis in whom brain MR scans within 25 days of death failed to reveal distinctive findings suggesting the diagnosis of CMV encephalitis. While MR scanning is crucial to evulation of AIDS patients developing neurologic complications, it is not sensitive to the presence of CMV encephalitis even when it is quite severe. The diagnosis of CMV encephalitis during life rests on characteristic clinical findings supported by a typical laboratory measures including the presence of CMV DNA in cerebrospinal fluid as detected by polymerase chain reaction.

AIDS-Related Opportunistic Infections↗
PubMed1995

Risk factors for dideoxynucleoside-induced toxic neuropathy in patients with the human immunodeficiency virus infection.

Dideoxynucleosides induce a dose-related toxic neuropathy; however, there is a paucity of information on whether other risk factors influence the development of neuropathy. We reviewed the records of 103 patients at an AIDS Clinical Trials Unit who were taking didanosine and/or zalcitabine to determine the risk factors for dideoxynucleoside-induced toxic neuropathy. Most were homosexual or bisexual (85%) men with a mean age of 39 years. The median CD4+ lymphocyte count was 59 cells/mm3, and 35% had a previous diagnosis of AIDS. Toxic neuropathy was more common in patients taking zalcitabine compared with those taking didanosine (14 of 51 versus seven of 55, p = 0.08). In the patients who took zalcitabine, those who had a low baseline serum cobalamin level, a history of heavy ethanol consumption, or a history of symptoms of peripheral nerve dysfunction were more likely to develop a toxic neuropathy (10 of 14 versus 12 of 37, p = 0.01). Conversely, there were no factors associated with the development of didanosine-induced toxic neuropathy. Dideoxynucleoside-induced toxic neuropathy is a common problem that can be disabling but is usually reversible. A history of symptoms of peripheral nervous system disease, heavy ethanol consumption, or a low serum cobalamin level may be useful in distinguishing patients at higher risk of developing zalcitabine-induced toxic neuropathy.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Level of cytomegalovirus (CMV) DNA in cerebrospinal fluid of subjects with AIDS and CMV infection of the central nervous system.

The objective of this study was to correlate cytomegalovirus (CMV) DNA levels in the cerebrospinal fluid (CSF) of subjects with AIDS with clinical and pathologic findings attributable to CMV infection of the central nervous system (CNS). CMV polymerase chain reaction (PCR) was done on serial dilutions of CSF samples from 24 AIDS patients with autopsy-proven CNS disorders. CMV DNA was detected in CSF from 12 of 13 subjects with evidence of CMV infection of the brain or spinal cord but in none of 11 subjects without autopsy evidence of CMV CNS infection. Subjects whose CSF contained > 10(3) CMV DNA molecules/8 microL of CSF had severe CMV CNS disease (e.g., ventriculoencephalitis). PCR appears to be more useful than clinical and neuroradiologic findings for documenting CMV infection of the CNS in patients with AIDS. Quantitation of CMV DNA in CSF shows promise for evaluation of the extent of involvement.

AIDS-Related Opportunistic Infections↗
PubMed1995

Neurologic opportunistic infections.

Three common opportunistic infections in patients with the human immunodeficiency virus are being more accurately diagnosed and effectively treated as a result of recent advances. Toxoplasmosis may be prevented in some cases, and can be recognized and treated noninvasively in most cases. Cryptococcal therapy has been enhanced by successful development of oral azole therapy. Cytomegalovirus encephalitis is now an entity that can be diagnosed antemortem, and thus efforts to treat it can now be evaluated.

AIDS-Related Opportunistic Infections↗
PubMed1995

Detection of Epstein-Barr virus DNA in cerebrospinal fluid for diagnosis of AIDS-related central nervous system lymphoma.

The diagnostic utility of Epstein-Barr virus (EBV) DNA detection in cerebrospinal fluid for the diagnosis of central nervous system lymphoma was evaluated with two different PCR assays to test a collection of cerebrospinal fluid samples from 24 AIDS patients with central nervous system disorders. A PCR assay amplifying a fragment from the BamHI-W region had the highest clinical and analytic sensitivity. The BamHI-W PCR assay detected EBV DNA in cerebrospinal fluid from 83% (5 of 6) of patients with pathologically proven primary central nervous system lymphoma and 7% (1 of 16) of controls with autopsy-proven nonlymphomatous central nervous system disorders. EBV DNA was also detected in one patient with autopsy-proven systemic lymphoma involving the central nervous system and one patient with probable primary central nervous system lymphoma. EBV DNA was detected consistently when central nervous system lymphoma involved meningeal surfaces. PCR for EBV in cerebrospinal fluid appears to be useful for diagnosis of AIDS-related central nervous system lymphoma, but additional studies are required to better define the sensitivity of the assay and to understand the significance of a positive test in the absence of lymphoma.

Central Nervous System Neoplasms↗
PubMed1993

Electrophysiological properties of identified postnatal rat hippocampal pyramidal neurons in primary culture.

Electrophysiological experiments were performed on primary cell cultures of retrogradely labelled postnatal rat hippocampal neurons. Rhodamine microspheres injected into the dorsal fornix clearly labelled the pyramidal cell layer of the hippocampus while excluding the other hippocampal layers and the dentate gyrus. In dissociated cell culture, the labelled cells were easily identified by fluorescence microscopy. Anti-neuron-specific enolase and anti-glial fibrillary acidic protein antibody staining confirmed that the labelled cells were neurons. The input resistance decreased from 2 G omega to 450 M omega, the input capacitance increased from 25 pF to 75 pF, the percentage of cells showing repetitive action potentials increased from 6% to 30%, and both peak GABA and glutamate responses increased over 100% during the 0 to 10 days time period investigated. This increase in chemosensitivity can be accounted for by an increase in cell size without an increase in the specific amino acid gated channel density. The subset of hippocampal neurons identified by the retrograde tracer technique are similar to non-labelled neurons with respect to the electrophysiological and pharmacological variables investigated. Nevertheless, it is likely that identified neurons may possess unique properties not evident in this study and refinement of the dissociated cell culture system using identified neuronal subpopulations may facilitate investigations looking at neuronal interactions such as synapse formation.

Action Potentials↗
PubMed1993

Neurotoxic effects of sodium nitroprusside in rat hippocampal slices.

To investigate the possible role of nitric oxide (NO) in n-methyl-D-aspartate (NMDA)-induced neurotoxicity we examined the effects of sodium nitroprusside (SNP) in rat hippocampal slices. Incubation with 3 mM SNP for up to 2 h produced neuronal damage characterized by "nuclear ballooning" in CA3 and CA1 pyramidal neurons and interneurons. The nuclear ballooning was not blocked by lowering the external calcium concentration or coincubation with MK-801 and/or 6,7-dinitro-quinoxaline-2,3-dione. Two lines of evidence suggest that the SNP neurotoxicity is not mediated by NO. First, inactivation of SNP by UV light failed to prevent the nuclear ballooning. Second, the toxicity was not attenuated by coadministration of hemoglobin. Although cyanide can be released from SNP, potassium cyanide did not mimic the nuclear ballooning. In electrophysiological experiments, 100 microM SNP irreversibly diminished the CA1 population spike amplitude while having less effect on the field excitatory postsynaptic potential. The effect of SNP on population spikes was inhibited by hemoglobin and was not mimicked by light-inactivated SNP. These results suggest that active SNP and light-treated SNP have different effects on hippocampal neurons and that SNP induces damage that differs from that produced by NMDA or cyanide.

Animals↗
PubMed1993

Blockade of ionotropic quisqualate receptor desensitization in rat hippocampal neurons by wheatgerm agglutinin and other lectins.

Previous experiments with wheatgerm agglutinin, an inhibitor of ionotropic quisqualate receptor desensitization, suggest that desensitization regulates quisqualate receptor-mediated synaptic transmission and excitotoxicity. Using whole-cell recordings from cultured postnatal rat hippocampal neurons, we have examined the wheatgerm agglutinin effect in further detail and compared it to other lectins. Wheatgerm agglutinin and other lectins belonging to the glucose/mannose, N-acetylglucosamine, and sialic acid classes inhibited desensitization. However, wheatgerm agglutinin was the most effective and had the most rapid onset of action. The inhibition was dose-dependent, and it was reduced and reversed by N-acetylglucosamine and N-acetylneuraminic acid. Treating neurons with neuraminidase, which cleaves sialic acid residues from the surface of cells, also diminished the effect. These results suggest that wheatgerm agglutinin reversibly inhibits ionotropic quisqualate receptor desensitization by interacting with carbohydrate residues on or near the quisqualate receptor complex. Future studies using the lectins may help to clarify the functional role of carbohydrate chains on the ionotropic quisqualate receptor.

Animals↗
PubMed1993

Long-term potentiation during whole-cell recording in rat hippocampal slices.

Factors involved in the production of long-term potentiation in the CA1 region of rat hippocampal slices were examined using whole-cell voltage clamp recordings. The pairing of postsynaptic membrane depolarization with tetanic stimulation produced a reliable long-lasting enhancement of synaptic currents provided that the pairing was performed within 15 min after establishing intracellular contact. This time could be extended to 30 min by including adenosine triphosphate and guanosine triphosphate in the recording pipette. Once established, the potentiation persisted for 3 h or more. The washout of long-term potentiation generating ability was not correlated with a rundown in baseline synaptic currents or in the N-methyl-D-aspartate receptor-mediated component of synaptic responses, but followed a time course similar to the loss of calcium spikes. Long-term potentiation could be reliably produced by depolarizing the postsynaptic membrane to -40 or -20 mV during the tetanus, but decreased when the membrane was held at membrane potentials greater than 0 mV. At -20 mV, 50 microM 2-amino-5-phosphonovalerate blocked the potentiation but this agent was ineffective at +40 mV. In contrast, 50 microM verapamil, a calcium channel blocker, failed to alter long-term potentiation at -20 mV but blocked the enhancement at +40 mV. These results suggest that whole-cell recording causes a washout of postsynaptic factors important in the initiation of long-term potentiation. However, these factors are less important in maintaining the potentiation. Furthermore, depending on the postsynaptic membrane potential during tetanic stimulation, voltage-gated calcium channels contribute to CA1 long-term potentiation.

2-Amino-5-phosphonovalerate↗
PubMed1993

Use of polymerase chain reaction to demonstrate cytomegalovirus DNA in CSF of patients with human immunodeficiency virus infection.

We used the polymerase chain reaction (PCR) to demonstrate cytomegalovirus (CMV) DNA in the CSF of a patient with the CMV radiculomyelopathy syndrome. To investigate the significance of this finding, we also performed PCR for CMV on CSF samples from 30 patients with human immunodeficiency virus (HIV) infection and neurologic disease, four patients with solid organ transplants including three with active CMV infection, and 10 patients with no clinical suspicion of HIV or CMV infection. There was CMV DNA only in patients with HIV, and it was present more often in patients with evidence of spinal cord dysfunction. Our results suggest that PCR may be useful in the rapid diagnosis of CMV infection of the CNS in patients with HIV and that the radiculomyelopathy syndrome may represent only part of a spectrum of CMV-induced spinal cord dysfunction in these patients.

Adult↗
PubMed1993

White matter lesions and cerebral atrophy on MR images in patients with and without AIDS dementia complex.

OBJECTIVE: The objective of this study was threefold: to determine if the frequency of deep white matter changes and cerebral atrophy seen on MR images is significantly different between patients with and without AIDS dementia complex, to determine if certain patterns of white matter changes are more closely associated with AIDS dementia complex, and to determine if focal lesions within the white matter of the splenium are more common in AIDS dementia complex. MATERIALS AND METHODS: Forty-five patients with AIDS were clinically examined for AIDS dementia complex. MR images from these patients were retrospectively reviewed without knowledge of the clinical results. The presence or absence of white matter abnormalities and cerebral atrophy was evaluated by using graded scales and correlated with the presence or absence of AIDS dementia complex. RESULTS: Ten patients met the criteria for AIDS dementia complex. Eight of 25 patients in whom MR images showed abnormal signal intensity in deep white matter had dementia compared with two of 20 in whom MR showed no changes in deep white matter. The presence of these deep white matter abnormalities was not significantly different between groups with and without dementia (p = .08), although higher grades of deep white matter abnormality were more likely to be associated with AIDS dementia complex. Nine of 19 patients in whom MR images showed atrophy had dementia compared with one of 26 in whom MR showed no atrophy. Atrophy was significantly associated with AIDS dementia complex (p = .001). Eight of 15 patients in whom MR images showed abnormal signal intensity within the white matter of the splenium had dementia compared with two of 30 in whom MR showed normal signal intensity in this area. The degree of abnormality in the splenium was weakly associated with AIDS dementia complex (Kendall's tau = .471, p = .001). CONCLUSION: MR findings of cerebral atrophy and abnormal signal intensity in the splenium are associated with AIDS dementia complex. The presence of generalized deep white matter abnormalities does not differ significantly between patients with and without dementia, although more severe grades of white matter abnormality are more likely to be seen in patients with AIDS dementia complex.

AIDS Dementia Complex↗
PubMed1992

Inhibition of long-term potentiation by NMDA-mediated nitric oxide release.

Activation of N-methyl-D-aspartate (NMDA) receptors before tetanic stimulation blocks long-term potentiation (LTP) in the CA1 region of the hippocampus. This NMDA-mediated inhibition of LTP can be reversed by the nitric oxide (NO) inhibitors L-NG-monomethyl-arginine or hemoglobin and mimicked by sodium nitroprusside. These results indicate that the timing of NO release relative to high-frequency activation of CA1 synapses may be an important determinant of LTP generation and suggest that NO may play a positive or negative modulatory role in LTP depending on prior events at the tetanized synapse and the ambient concentration of excitatory amino acids.

Animals↗
PubMed1992

Norepinephrine reverses N-methyl-D-aspartate-mediated inhibition of long-term potentiation in rat hippocampal slices.

Application of 1 microM N-methyl-D-aspartate (NMDA) either immediately before or following tetanic stimulation inhibits the induction of CA1 hippocampal long-term potentiation (LTP). We have examined the effect of trans-amino-1,3-cyclopentanedicarboxylic acid (ACPD), norepinephrine and acetylcholine on this NMDA-mediated LTP inhibition using extracellular recordings from in vitro rat hippocampal slices. When NMDA is accompanied by 100 microM ACPD or 10 microM norepinephrine, the block of LTP is overcome. The norepinephrine effect is mimicked by phenylephrine and methoxamine and is blocked by phentolamine and prazosin suggesting the involvement of alpha 1-adrenergic receptors.

Adrenergic alpha-Antagonists↗
PubMed1992

Low concentrations of N-methyl-D-aspartate inhibit the induction of long-term potentiation in rat hippocampal slices.

We have examined the effects of excitatory amino acids on tetanus-induced long-term potentiation (LTP) in the CA1 region of rat hippocampal slices. Agonists acting at N-methyl-D-aspartate (NMDA) receptors, including NMDA, aspartate and glutamate, completely block the development of LTP when administered for 5 min prior to tetanic stimulation. Additionally, and unlike the NMDA receptor antagonist 2-amino-5-phosphonovalerate (APV), NMDA blocks LTP when administered for 5 min immediately following the electrical tetanus. The effective concentrations of NMDA are subthreshold for depolarizing CA1 neurons. These results indicate that under certain conditions NMDA receptor activation prevents CA1 LTP.

2-Amino-5-phosphonovalerate↗
PubMed1992

Nitric oxide inhibitors attenuate N-methyl-D-aspartate excitotoxicity in rat hippocampal slices.

To investigate whether nitric oxide (NO) plays a role in the neurotoxicity produced by N-methyl-D-aspartate (NMDA) we have examined the effects of NO inhibitors on NMDA-mediated neurodegeneration in the CA1 region of rat hippocampal slices. L-NG-Monomethylarginine, L-NG-nitroarginine and hemoglobin markedly diminished the toxicity produced by activation of NMDA receptors without interfering with NMDA receptor-mediated ion currents or synaptic responses. The neuroprotective effects are reversed by coapplication of L-arginine with the NO synthase inhibitors. These results suggest that activation of the NO system is an important component of the biochemical cascade leading to neurodegeneration produced by NMDA receptors.

Animals↗