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Biomedical subjects

T Cannon

Publications and source records attributed to T Cannon.

15 recordsLinked to original sources

Structural magnetic resonance imaging in patients with first-episode schizophrenia, psychotic and severe non-psychotic depression and healthy controls. Results of the schizophrenia and affective psychoses (SAP) project.

BACKGROUND: Structural brain abnormalities are prevalent in patients with schizophrenia and affective disorders. AIMS: To study how regional brain volumes and their ratios differ between patients with schizophrenia, psychotic depression, severe non-psychotic depression and healthy controls. METHOD: Magnetic resonance imaging scans of the brain on first-episode patients and on healthy controls. RESULTS: Patients with schizophrenia had a smaller left frontal grey matter volume than the other three groups. Patients with psychotic depression had larger ventricular and posterior sulcal cerebrospinal fluid (CSF) volumes than controls. Patients with depression had larger white matter volumes than the other patients. CONCLUSIONS: Left frontal lobe, especially its grey matter volume, seems to be specifically reduced in first-episode schizophrenia. Enlarged cerebral ventricles and sulcal CSF volumes are prevalent in psychotic depression. Preserved or expanded white matter is typical of non-psychotic depression.

Adult↗

A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM).

Motivated by the vast amount of information that is rapidly accumulating about the human brain in digital form, we embarked upon a program in 1992 to develop a four-dimensional probabilistic atlas and reference system for the human brain. Through an International Consortium for Brain Mapping (ICBM) a dataset is being collected that includes 7000 subjects between the ages of eighteen and ninety years and including 342 mono- and dizygotic twins. Data on each subject includes detailed demographic, clinical, behavioural and imaging information. DNA has been collected for genotyping from 5800 subjects. A component of the programme uses post-mortem tissue to determine the probabilistic distribution of microscopic cyto- and chemoarchitectural regions in the human brain. This, combined with macroscopic information about structure and function derived from subjects in vivo, provides the first large scale opportunity to gain meaningful insights into the concordance or discordance in micro- and macroscopic structure and function. The philosophy, strategy, algorithm development, data acquisition techniques and validation methods are described in this report along with database structures. Examples of results are described for the normal adult human brain as well as examples in patients with Alzheimer's disease and multiple sclerosis. The ability to quantify the variance of the human brain as a function of age in a large population of subjects for whom data is also available about their genetic composition and behaviour will allow for the first assessment of cerebral genotype-phenotype-behavioural correlations in humans to take place in a population this large. This approach and its application should provide new insights and opportunities for investigators interested in basic neuroscience, clinical diagnostics and the evaluation of neuropsychiatric disorders in patients.

Adult↗

A follow-up magnetic resonance imaging study of schizophrenia. Relationship of neuroanatomical changes to clinical and neurobehavioral measures.

BACKGROUND: Cross-sectional neuroanatomical studies have reported abnormalities in schizophrenia that relate to disease variables. Longitudinal neuroimaging investigations that integrate anatomical, clinical, and neurobehavioral measures may help clarify the pathogenesis of schizophrenia. METHODS: Magnetic resonance brain imaging and neurobehavioral studies were conducted at baseline and after 30.63 +/- 12.92 months (mean +/- SD) in 40 patients with schizophrenia (23 men and 17 women) and 17 healthy controls (13 men and 4 women). The schizophrenia group included 20 first-episode and 20 previously treated subjects. Volumes of whole-brain, cerebrospinal fluid, and frontal and temporal lobes were measured. The severity of negative and positive symptoms was assessed, medications were monitored, and neurobehavioral functioning in 8 domains was evaluated. RESULTS: Both first-episode and previously treated patients had smaller brains and frontal and temporal lobes than controls at intake. Longitudinally, reduction in frontal lobe volume was found only in patients, whereas temporal lobe reduction was also seen in controls. The association between volume reduction and symptom changes differed between patient groups, but volume reduction was associated with decline in some neurobehavioral functions in both groups. Exploratory analysis suggested that neuroleptic dose is correlated with changes in all 3 domains. CONCLUSIONS: The existence of neuroanatomical and neurobehavioral abnormalities in patients with first-episode schizophrenia indicates that the brain dysfunction occurred before clinical presentation. However, there is also evidence of progression, in which anatomical changes may affect some clinical and neurobehavioral features of the illness in some patients.

Adult↗

School teacher ratings predictive of psychiatric outcome 25 years later.

BACKGROUND: The current study examines teacher ratings as a tool for identifying students at risk of developing psychosis. Follow-up and follow-back studies have shown that teachers are capable of identifying individuals who later develop serious mental illness. METHOD: We examine the long-term outcomes for individuals at genetic risk who were identified as showing markedly deviant behaviour and those identified who did not show markedly deviant behaviour. RESULTS: Teachers were able to correctly anticipate 35% of students who developed schizophrenia. Furthermore, those identified as showing markedly deviant behaviour had poorer clinical and psychiatric outcomes 10 and 25 years later than those identified as not behaving with marked deviance. Their ratings also differentiated, within the group of people with schizophrenia, which individuals would show evidence of poorer functioning 25 years later. These results were replicated in a group of students not at genetic risk of schizophrenia. Within this low-risk group, teachers were able to predict which students would develop psychotic disorders. CONCLUSIONS: Teacher ratings were particularly useful in predicting clinical and psychiatric outcomes 10 and 25 years later. The applicability of these findings in early intervention and treatment research is discussed.

Adolescent↗

Apolipoprotein E genotype in schizophrenia: frequency, age of onset, and neuropathologic features.

Apolipoprotein E (ApoE) genotype has been found to affect the expression of a variety of neuropsychiatric disorders. We determined ApoE genotype frequencies and their relationship to clinical and pathological features in a diverse cohort of individuals with schizophrenia. There were no differences in ApoE genotype frequencies between schizophrenics and controls. However, the ApoE epsilon 4 genotype was associated with a younger age of onset of schizophrenia, and in an elderly subsample, individuals with the epsilon 4 allele more frequently exhibited co-existent dementia and had more neurofibrillary pathology (although none of the cases met criteria for Alzheimer's disease). This examination of ApoE in relation to clinical and neurobiological features of schizophrenia suggests that it modifies the phenotypic expression of the disease.

Adult↗

Vertebrate development in the environment of space: models, mechanisms, and use of the medaka.

With the advent of space travel, it is of immediate interest and importance to study the effects of exposure to various aspects of the altered environment of space, including microgravity, on Earth-based life forms. Initial studies of space travel have focused primarily on the short-term effects of radiation and microgravity on adult organisms. However, with the potential for increased lengths of time in space, it is critical to now address the effects of space on all phases of an organism's life cycle, from embryogenesis to post-natal development to reproduction. It is already possible for certain species to undergo multiple generations within the confines of the Mir Space Station. The possibility now exists for scientists to consider the consequences of even potentially subtle defects in development through multiple phases of an organism's life cycle, or even through multiple generations. In this discussion, we highlight a few of the salient observations on the effects of the space environment on vertebrate development and reproductive function. We discuss some of the many unanswered questions, in particular, in the context of the choice of appropriate models in which to address these questions, as well as an assessment of the availability of hardware already existing or under development which would be useful in addressing these questions.

Animals↗

Effect of spaceflight on human stem cell hematopoiesis: suppression of erythropoiesis and myelopoiesis.

Humans subjected to periods of microgravity develop anemia, thrombocytopenia, and abnormalities in red blood cell structure. The causes of these abnormalities are complex and unclear. The in vitro effects of spaceflight on hematopoietic cell proliferation and differentiation were investigated during the space shuttle missions STS-63 (Discovery) and STS-69 (Endeavour). CD34+ bone marrow progenitor cells were cultured in liquid suspension culture and on hematopoietic supportive stromal cells using hollow-fiber culture modules. One set of cultures was maintained at microgravity (flight cultures) for the last 8-10 days of culture and a second control was at full gravity (ground control). Over the 11- to 13-test-day period, ground control culture total cell number increased 41.0- to 65.5-fold but flight culture total cell number increased only 10.1- to 17.6-fold (57-84% decrease). Comparing ground control cultures and microgravity cultures, respectively, for progenitor cell content, myeloid progenitor cell numbers expanded 2.6- to 17.5-fold compared with 0.9- to 7.0-fold and erythroid progenitor cell numbers expanded 2.0- to 4.1-fold in ground control cultures but actually declined at microgravity (>83% reduction). Moreover, microgravity cultures demonstrated accelerated maturation/differentiation toward the macrophage lineage. These data indicate that spaceflight has a direct effect on hematopoietic progenitor cell proliferation and differentiation and that specific aspects of in vitro hematopoiesis, particularly erythropoiesis, involve gravity-sensitive components.

Antigens, CD↗

Functional activity of an HIV-1 neutralizing IgG human monoclonal antibody: ADCC and complement-mediated lysis.

The IgG1 kappa, human monoclonal antibody (HMAb), F105, was studied for functional activity in antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). F105 reacts with a discontinuous epitope on the CD4 binding site of the HIV-1 envelope glycoprotein, gp120, expressed on the surfaces of infected cells and neutralizes diverse viral strains at antibody concentrations readily achievable in humans. Neither F105 nor serum (diluted 1:50) from HIV seropositive donors mediate CDC against an SF2-infected cell line with rabbit or human sera as a source of complement. F105 and HIV-1 sera mediate ADCC against the SF2 strain. Normal human serum reduced spontaneous lysis of SF2 by peripheral blood monocytes (PBM). Although mixing of F105 with normal human serum reduced the lysis observed (36 +/- 8 vs. 42 +/- 8%), this still was significantly greater than lysis in media (30 +/- 5%) or normal human serum (23 +/- 6%) (p less than .05). A murine antibody to CD16 significantly reduced spontaneous lysis observed with media (30 +/- 5 vs. 18 +/- 3%) while normal mouse serum had no effect (31 +/- 7%). ADCC mediated by F105 is completely abrogated by the anti-CD16 antibody (42 +/- 8 vs. 22 +/- 4%), while only a fraction of ADCC mediated by HIV sera is inhibited by anti-CD16 (60 +/- 9 vs. 46 +/- 6%), suggesting that several populations of effector cells function in ADCC mediated by the polyclonal sera. Thus, F105, as opposed to polyclonal sera, mediates ADCC through a CD16+ PBM population.

Acquired Immunodeficiency Syndrome↗

Phenomenology and functioning in first-episode schizophrenia.

One current view of schizophrenia is that its clinical and functional features show a deteriorating course, particularly for negative symptoms. However, this is difficult to study in chronic patients who have been exposed to pharmacologic treatment and institutionalization. Examining first-episode (FE) patients can help clarify which symptoms are present initially and how the symptom pattern is linked to functioning. We evaluated a sample of 37 FE patients with schizophrenia and compared them to 70 other schizophrenia (OS) patients on standard clinical scales, measures of premorbid functioning, and quality of life. FE patients showed a symptom profile similar to OS patients; in particular, there was no evidence that negative symptoms are less severe in the FE group. Analysis of the clinical data led us to the conclusion that the symptom profile of schizophrenia exists at the outset, that negative symptoms are associated with poor premorbid and current functioning, but that the role of positive symptoms is more complex and may vary in subtypes.

Adult↗

Neuroleptic malignant syndrome in a patient with neurosyphilis.

Neuroleptic malignant syndrome (NMS) is a catatonic-like syndrome of uncertain etiology occurring in patients taking dopamine blocking medications. The paper describes how NMS presents and is treated and reports the case of a patient with undetected neurosyphilis who developed NMS. The case highlights the need for a thorough organic evaluation of all patients with initial-onset psychotic features and suggests the possibility of a CNS cofactor--neurosyphilis--initiating the NMS as proposed by other researchers.

Adult↗

An IgG human monoclonal antibody that reacts with HIV-1/GP120, inhibits virus binding to cells, and neutralizes infection.

A human mAb (HmAb) termed F105 was obtained by fusion of antibody-producing EBV-transformed cells with the HMMA2.11TG/O cell line. F105 is an IgG1 kappa antibody that binds to the surfaces of cells infected with all HIV-1 strains tested: MN, RF, IIIB, and SF2, but not uninfected cells. The HmAb immunoprecipitates GP120 from all four strains. F105 does not react with denatured GP120 on Western blots, but does react with viral lysates and purified GP120 dotted onto nitrocellulose filter paper under nondenaturing conditions. rGP120 from SF2 and soluble rCD4 inhibit antibody binding to infected cells in a dose-dependent manner. F105 inhibits the binding of free, infectious virions to uninfected HT-H9 cells with 50% of maximal (100%) inhibition at approximately 1 microgram/ml. F105 inhibits infection of HT-H9 cells by 100 tissue culture infective dose 50% units of MN and IIIB strains with 50% inhibition at concentrations of HmAb readily achievable in man. It appears that the F105 HmAb reacts with a conformationally defined epitope on HIV-1/GP120 that is exposed on the free virion and is important for binding to the cell surface by the virion. The epitope, which is immunogenic in humans, appears to be within, or topographically near, the CD4-binding site. F105 and the F105 epitope are potentially useful in therapy and in the design of peptide or anti-Id based vaccines; monitoring of the expression of the Id may prove useful in evaluating immune responses in infected individuals or vaccinated volunteers.

Antibodies, Monoclonal↗

Neural and neurochemical mechanisms of pain inhibition.

Recent studies which suggest the existence of an endogenous neural substrate of pain inhibition are reviewed. Electrical stimulation of some areas of the medial brain stem in laboratory rats has produced a dramatic degree of analgesia. Such stimulation-produced analgesia is partially blocked by an opiate antagonist drug. This observation has proved seminal to those searching for endogenous opiate-like neurochemicals, the opioid peptides (enkephalins and endorphins). Particular attention is focused on studies of stimulation-produced analgesia, the underlying anatomy and physiology of endogenous analgesia systems elucidated by such work, and the relation of these findings to discoveries about opiate receptors and opioid peptides. Very recent work suggesting that certain forms of stress are natural triggers for activating endogenous analgesia mechanisms is described. Although certain stressors cause analgesia mediated by opioids, other stressors cause analgesia by neurochemically different means. Thus, multiple analgesia substrates, opioid and nonopioid, appear to exist.

Analgesia↗

A four-dimensional probabilistic atlas of the human brain.

The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype- phenotype-behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders.

Adolescent↗