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Biomedical subjects

W G Honer

Publications and source records attributed to W G Honer.

At least 109 records · Page 6Linked to original sources
PubMed1992

Characterization of a synaptic antigen of interest in neuropsychiatric illness.

Monoclonal antibodies exhibiting relative differences in binding to brain homogenates from diseased versus control brains may be useful probes into the molecular pathology of neuropsychiatric illness. To be of value, the antibodies must be useful in characterization of the antigens putatively involved in the illness. An antibody called EP10 showed some differences in binding to homogenates from a small sample of schizophrenia brains compared with controls. In the present study, the antigen for this antibody was characterized in control brains using quantitative, immunocytochemical, and biochemical techniques. The antigen is a 38,000 dalton synaptic vesicle protein, which is identical to synaptophysin by immunological criteria. However, the EP10 epitope is of interest, as this binding site does not appear to be present in rat or bovine synaptophysin. Brain regional studies using EP10 indicate that the antigen may be present in only a subset of synaptic terminals. Further studies are required to fully characterize the epitope, and to determine the significance of the earlier findings related to schizophrenia.

Animals↗
PubMed1992

Structural brain imaging abnormalities associated with schizophrenia and partial trisomy of chromosome 5.

Chromosomal abnormalities occurring in association with mental illness provide a unique opportunity to study the interaction of genetic abnormalities and the brain in mental illness. Four individuals from a family in which schizophrenia was found to cosegregate with a partial trisomy of chromosome 5 were studied with computed tomography and magnetic resonance imaging. Temporal lobe atrophy was found in the two trisomic males and in the asymptomatic balanced translocation female. In addition, a large cavum septum pellucidum and a cavum vergae were found in the older trisomic individual. Scans from the normal male were free of abnormalities. These results suggest that molecular studies of the translocation breakpoints in this chromosomal abnormality may be of interest, and encourage further studies of brain structure in other chromosomal abnormalities associated with psychosis.

Adult↗
PubMed1992

Diagnostic confusion in treatment-refractory psychotic patients.

BACKGROUND: Two surveys of diagnostic practices in the United States suggest that many clinicians base their diagnoses on presenting symptoms and pay little attention to course and exclusionary criteria. Failure to correctly diagnose patients may result in inappropriate therapy and poor treatment response. The purpose of the present study was to investigate diagnostic practices. METHODS: We made detailed assessments of 50 consecutively admitted treatment-refractory psychotic patients and carefully applied DSM-III-R criteria. RESULTS: Referral diagnoses were changed in 23 of the 50 patients. Diagnoses of schizophrenia and schizoaffective disorder were made far less frequently and mood disorders (bipolar disorder and major depression) were diagnosed far more frequently by our group than by referring psychiatrists. Patients whose diagnosis was changed were more likely to be given mood-stabilizing medication and tended to show more improvement than patients whose diagnosis was not changed. CONCLUSIONS: These findings raise the possibility that patients may not respond to treatment because incorrect diagnoses result in inappropriate treatment.

Adolescent↗
PubMed1990

A genotype-phenotype research strategy for schizophrenia.

A research strategy which integrates known biological aspects of schizophrenia is proposed. The strategy includes genotype and phenotype components and emphasizes interactions. Its central feature is the comprehensive diagnostic assessment of patients with schizophrenia. Clinical and laboratory based methodologies are applied within the genotype and phenotype components of the strategy. Examples of research from each area and the potential interactions with other aspects of the strategy are presented. The expectation is that a greater understanding of the pathophysiology of schizophrenia will result from the application of the genotype-phenotype strategy and that consequently more efficacious treatments will ultimately be developed.

Chromosome Aberrations↗
PubMed1989

Monoclonal antibodies to study the brain in schizophrenia.

Twelve monoclonal antibodies were developed which show selective reactivity with brain tissue homogenates from 4 patients with schizophrenia compared to 4 normal controls. Certain antibodies were more reactive with tissue from cases with schizophrenia, others with control tissue. Patterns of reactivity also depended on brain region tested. Differences in reactivity generally ranged from 2- to as much as 8-fold. This panel of monoclonal antibodies may be useful to investigate the pathophysiology of schizophrenia.

Adult↗
PubMed1989

Organic affective disorder and vascular dysregulation in systemic lupus erythematosus.

A case is reported in which an exacerbation of systemic lupus erythematosus presented as an organic depressive disorder with psychotic features. Brain imaging using regional cerebral blood flow techniques demonstrated vascular dysregulation in the left frontal lobe of this patient. The implications for understanding the pathogenesis of psychiatric disorders in lupus are discussed.

Adolescent↗
PubMed1988

Scopolamine reduces frontal cortex perfusion.

While the cognitive deficits of Alzheimer's disease are considered related to a cholinergic deficit, no attempt has yet been made to test the hypothesis that the characteristic regional cerebral blood flow (rCBF) pattern of Alzheimer's disease may also relate to such a deficit. We therefore measured rCBF using the [133Xe] inhalation technique in 15 young normal subjects before and after induction of reversible cholinergic blockade with scopolamine at doses of 6.1 and 7.3 micrograms/kg i.v. Significant cognitive impairment was observed at both doses, while rCBF changes occurred only at the higher dose. Global CBF was significantly reduced 25 min after scopolamine. The pattern of regional change in CBF was not similar to Alzheimer's disease. Rather than a focal parietotemporal deficit as seen in Alzheimer's disease, we observed a predominantly frontal reduction in flow of about 20%. These results suggest that the frontal but not the parietotemporal deficits seen in several dementing conditions may be related to cholinergic dysfunction.

Acetylcholine↗
PubMed1987

Temporal lobe involvement in multiple sclerosis patients with psychiatric disorders.

Patients with multiple sclerosis (MS) frequently develop psychiatric disturbances. The clinical histories and magnetic resonance imaging results from eight patients with MS and psychiatric disorders were compared with those from eight control MS patients matched for age, sex, duration and severity of illness, and clinical course. Both groups had widespread lesions on the magnetic resonance imaging scans; however, the psychiatric group had more clinically defined sites of MS involvement, possibly indicating a difference in the biologic activity of the lesions in this group. The total lesion area was not different between the groups. However, the distribution of lesions did differ; the psychiatric group had significantly more temporal lobe involvement than the control group. These results indicate a role for the cerebral lesions themselves, particularly those in the temporal lobes, in the genesis of psychiatric disorders in MS.

Adult↗
PubMed1986

No effect of naloxone on plasma oxytocin in normal men.

The role of endogenous opiates in the control of the secretion of oxytocin in the basal state in healthy male volunteers was investigated with the opiate antagonist naloxone. There was no change in plasma oxytocin levels, assessed for a 120 min period following the intravenous administration of naloxone (10 mg). Although there was no effect of opiate receptor blockade with naloxone in this basal situation, further studies are needed to evaluate the possible role of opioid regulation of oxytocin during lactation and parturition.

Adult↗
PubMed1985

Student-directed teaching of medical ethics at a Canadian medical school.

The medical faculty at Queen's University, Kingston, Ontario, Canada, in 1982 decided to omit the formal teaching of medical ethics from its curriculum. This decision led both students and faculty members to review the role of ethics in medical education. The outcome was the establishment of a minicourse of four three-hour sessions devoted to the examination and debate of selected ethical issues. The course was directed by students, who chose four general topics for discussion and three subtopics to be the focus in each session. They organized debates between faculty and community members from the fields of medicine, law, philosophy, and theology to be the core of instruction. The course resulted in a high level of satisfaction among the students, who felt that the issues chosen had been appropriately explored. The course, therefore, was continued in the same form by the following medical class.

Canada↗
PubMed1984

Measurement of the GH and other responses to clonidine at different times of the day in normal subjects.

The growth hormone response to clonidine may be impaired in some patients with endogenous depression. To determine whether or not this change is due to a circadian variation in the GH response to clonidine, this measure has been studied in normal subjects at 0900, 1800 and 2100 hr. Similar responses were obtained at 0900 and 1800 hr. The responses at 2100 hr could not be interpreted, as the baseline plasma GH was raised. At no time of day were there impaired GH responses similar to those found in endogenous depression. The effects of clonidine upon blood pressure and alertness were similar at the three times studied, providing no support for any circadian rhythm in the function of the alpha 2-adrenoceptors that mediate these effects of clonidine.

Adult↗
PubMed1983

PCO2 modulation of ventilation and HCO3- buffer during chronic metabolic acidosis.

Ventilation and acid-base balance were studied in 6 conscious dogs during chronic eucapnic and hypocapnic metabolic acidosis. The dogs had tracheostomas for respiratory studies, exteriorized carotid arteries for obtaining arterial blood and cannulae for sampling cisternal cerebrospinal fluid (CSF). Measurements were obtained on a control diet, and then, during metabolic acidosis induced by adding HCl (7 mmol/kg per day). Initially during metabolic acidosis, PaCO2 was maintained normal by having the dogs breathe 3% CO2 (eucapnia); then the dogs breathed air (hypocapnia). Chronically, arterial and CSF [HCO-3] were related to PCO2. No respiratory compensation occurred during chronic hypocapnic metabolic acidosis since [HCO-3] decreased more than PCO2; consequently, the acidosis worsened. At any [H+], ventilation was related to PCO2. Thus, during hypocapnic metabolic acidosis, ventilation was not increased relative to increase in arterial and CSF [H+]. Modulation of ventilation by PCO2 during severe acidosis may be crucial because stimulation of ventilation by [H+] of arterial blood or CSF would have progressively reduced PCO2 and [HCO-3], resulting in a worsening of the metabolic acidosis.

Acid-Base Equilibrium↗
PubMed1980

Mutagenic activity of swimming-pool water.

Swimming pool water, being chlorinated and exposed to trace organics from use was investigated as a possible source of mutagens using the Salmonella/mammalian-microsome test. Procedures previously described for the extraction of trace organics from water using XAD-2 macroreticular resin were modified to allow quantitative extraction of mutagens. These procedures were superior to freeze-drying and solvent-extraction. Using a base-pair histidine mutant, strain TA100, of Salmonella typhimurium significantly mutagenic responses were observed using concentrates from 3 variations of the extraction procedure. Acidified pool-water extracts eluted with ether or acetone were mutagenic, the former enhanced in the presence of the induced microsomal fraction from rat livers. Non-acidified pool-water extracts eluted with acetone were mutagenic without microsomal activation. These results indicate the presence of more than one mutagen in what is likely a complex mixture of organic molecules in swimming-pool water.

Drug Evaluation, Preclinical↗
PubMedDate not supplied

Regional synaptic pathology in Alzheimer's disease.

Synaptic pathology in Alzheimer's disease (AD) may occur diffusely or may have regional predilections. A new antibody called EP10 which detects synaptophysin-like immunoreactivity was used to study synapses in postmortem brain tissue. Four brain regions from cases of AD and controls were studied. Controls with a wide range of ages were used to investigate the possibility of age-related changes in synaptophysin-like immunoreactivity. A significant reduction in the EP10 antigen was observed to occur with age in the control caudate but not in the hippocampus or temporal or occipital cortices. Antigen levels were significantly reduced in the hippocampus (77%) and the temporal cortex (54%) in AD. The expected abnormal pallor of the outer two-thirds of the dentate gyrus molecular layer was observed with immunocytochemistry. In the temporal cortex, the reduction in synaptophysin-like immunoreactivity was inversely correlated with the neurofibrillary tangle count. No such relationship existed in the hippocampus. These results suggest that at least certain components of the synaptic loss in AD occur regionally and are disproportionately large in the hippocampus.

Alzheimer Disease↗
PubMedDate not supplied

Routine assessment of patient progress: a multiformat, change-sensitive nurses' instrument for assessing psychotic inpatients.

A new instrument, the Routine Assessment of Patient Progress (RAPP), is a standardized scale with a unique format that allows trained nurses to incorporate both interview and observational data into a comprehensive assessment of psychiatric inpatients. The scale was developed to accurately document treatment effects, assist in treatment planning, and provide ancillary judgments of psychopathology that may affect diagnosis. The RAPP demonstrates satisfactory interrater reliability and internal consistency. The RAPP total score and its two subscales correlated highly, where expected, with an observation-based nursing scale, global measures, and an interview-based psychopathology scale. RAPP scores demonstrated sensitivity to change over time in patient functioning. It reliably discriminated among patients discharged to settings with varying degrees of independent living. The use of the RAPP over several years on a psychiatric inpatient unit has shown it to be a practical clinical tool that eases nurses' charting demands, helps create care plans, and facilitates interdisciplinary communication.

Activities of Daily Living↗
PubMedDate not supplied

SNAP-25 deficit and hippocampal connectivity in schizophrenia.

Regional abnormalities of brain connectivity may be an important substrate for the expression of schizophrenia, a severe form of mental illness. Brain imaging and postmortem morphometric studies indicate hippocampal structure is abnormal in schizophrenia. To study molecular components of hippocampal connectivity the presynaptic proteins SNAP-25 and synaptophysin were assayed in postmortem samples. Immunocytochemical studies indicated reduced SNAP-25 immunoreactivity in schizophrenia compared to controls, particularly in the terminal fields of entorhinal cortex projections. Although there were no overall changes in synaptophysin immunoreactivity, in the granule cell layer of the dentate gyrus synaptophysin immunoreactivity was increased in schizophrenia. These results indicate that disconnection of a subset of hippocampal circuitry from the entorhinal cortex, as well as intrinsic changes in hippocampal connectivity, may contribute to the mechanism of illness in schizophrenia.

Adult↗