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Biomedical subjects

J R Stevens

Publications and source records attributed to J R Stevens.

At least 19 recordsLinked to original sources

Abnormal reinnervation as a basis for schizophrenia: a hypothesis.

Neuropathologic and neuroimaging studies reveal atrophy or dystrophy of the hippocampal region and enlarged ventricles indicative of tissue loss in many patients with schizophrenia. It is now widely recognized that brain damage can provoke regenerative collateral sprouting of axons, synaptic proliferation, and reorganization, even in the adult mammalian brain. The functional consequences of these plastic regenerative changes are largely unknown; they could be adaptive or cause further impairment. There is evidence of lesion-provoked aberrant synaptic regeneration in epilepsy and Alzheimer's disease. Data suggest that anomalous reinnervation could also have a significant role in the pathophysiology of schizophrenia. Histologic methods to test this hypothesis are in progress.

Adolescent

Numerical taxonomy of Trypanozoon based on polymorphisms in a reduced range of enzymes.

Numerical analyses of Trypanozoon taxonomy are presented, based on the isoenzyme data of Stevens et al. (1992). The previous study used a reduced range of enzymes compared with earlier work; the analyses indicate the value of this rationalized system. Both recently isolated trypanosome stocks and previously studied populations were included, allowing detailed comparison with earlier studies. Relationships between zymodemes were calculated with an improved similarity coefficient program, using Jaccard's coefficient (1908), and by Nei's method (1972). Dendrograms were constructed from the matrices produced with the group-average method. The groupings produced by both numerical methods were in close agreement, and the clusters of related principal zymodemes largely matched the species, subspecies and strain groups proposed by previous workers. Trypanozoon biochemical taxonomy is reviewed and the groupings reinforced by this study are: the mainly East African strain groups, busoga, zambezi, kakumbi, kiboko and sindo; T.b. gambiense and the bouaflé strain group from West Africa, and T. evansi; an intermediate bouaflé/busoga group was also recognized.

Africa, Eastern

A simplified method for identifying subspecies and strain groups in Trypanozoon by isoenzymes.

To characterize trypanosomes from the subgenus Trypanozoon, 272 stocks in 111 zymodemes were analysed by the polymorphisms seen in a rationalized range of nine enzymes, resolved by electrophoresis, mostly on cellulose acetate. Several highly polymorphic or invariant enzymes used previously were omitted, while two new enzymes, NHD and SOD were included; the isoenzymes seen for SOD were interpreted as two separate enzymes, SODA and SODB. Isoenzyme band patterns were analysed by two complementary numerical methods to elucide taxonomic relationships within the subgenus; groups of zymodemes corresponding to subspecies and strain groups were defined, which agreed closely with previous studies. Except for one zymodeme, Trypanosoma evansi could not be clearly distinguished from the bouaflé strain group. This strain group had enzymic features that overlapped to some extent those of the busoga group. Trypanosoma brucei gambiense and the zambezi, kakumbi, kiboko and sindo groups were clearly defined. Eight zymodemes could not be classified. A rapid identification system using a limited number of enzymes is presented.

Animals

Comparison of immunocytochemical and Holzer's methods for detection of acute and chronic gliosis in human postmortem material.

Immunocytochemical staining for glial fibrillary acidic protein (GFAP) allows more specific identification of astrocytes and their processes than classical histochemical techniques and has therefore recently been used by some investigators to quantify gliosis. However, although the immunocytochemical method is superior for delineation of reactive astrocytes, the examples presented here and previous work by others demonstrate that chronic fibrillary gliosis may be best detected by Holzer's method and not by GFAP immunocytochemistry. The authors' studies indicate that if, as in a recent study of gliosis in schizophrenia, computer-assisted densitometry is to be used to measure gliosis, the immunoperoxidase method may not be a sensitive technique to demonstrate glial changes in human postmortem material.

Brain

Analysing isoenzyme band patterns using similarity coefficients: a personal computer program.

A computer program in Fortran 77 was developed to analyse the isoenzyme patterns of trypanosomes isolated from African sleeping sickness patients, to allow biochemical relationships between populations of trypanosomes from different hosts and geographic areas to be elucidated. However, the generality of the design allows it to be used with presence/absence data from a variety of sources, including DNA fingerprints. The program reads in isoenzyme band patterns from an ASCII file and calculates a matrix of similarity coefficients. Four different similarity measures are offered, suitable for presence/absence data from a range of organisms and experimental procedures. The matrix of similarity values produced is suitable for analysis by ordination methods including principal coordinates analysis, and the production of dendrograms and icicle plots using SPSS/PC+.

Animals

Astrocytosis in the molecular layer of the dentate gyrus: a study in Alzheimer's disease and schizophrenia.

Recently, several authors have claimed prominent abnormalities in the entorhinal cortex of both patients with Alzheimer's disease (AD) and schizophrenia. The entorhinal cortex is the origin of the perforant pathway, a major input to granule cells of the dentate gyrus of the hippocampus. The present study explored the possibility of a lesion in the entorhinal cortex of both AD and schizophrenic patients by quantitating astrocytic markers within the terminal fields of the perforant pathway. An increase in fibrillary astrocytes was found in half (3/6) of the AD patients while none of the schizophrenic (n = 6) or control (n = 7) brains exhibited gliosis. Since the redistribution and hyperplasia of astrocytes within the molecular layer of the partially deafferented dentate gyrus depend on the chronicity of the entorhinal lesion, the abnormalities observed in AD patients are consistent with the progressive course of the illness. Furthermore, the presence of gliosis in the subiculum of three out of six AD patients suggested pathology secondary to projections from the entorhinal region, amygdala, or prepyriform cortex. The absence of similar changes in schizophrenic patients does not disprove previous claims of entorhinal pathology but suggests that the lesion, if it exists, is either static in nature or occurred long before death.

Adult

Psychiatric consequences of temporal lobectomy for intractable seizures: a 20-30-year follow-up of 14 cases.

Between 1958 and 1968, 14 patients from the epilepsy clinic at the University of Oregon Hospitals and Clinics with a diagnosis of temporal lobe epilepsy (TLE) had a temporal lobectomy for medically intractable seizures. Nine of the 14 patients operated on remained seizure-free over the 20-30-year period of follow-up. Between 6 months and one year following temporal lobectomy, two women, previously healthy from a psychiatric standpoint, developed psychoses, and the previous psychiatric problems of four other patients worsened. Two patients, one with incapacitating paranoid personality disorder and the other with explosive rage attacks preoperatively, had marked improvement in their psychiatric status following temporal lobectomy. The remaining six patients, all psychiatrically healthy prior to surgery, have had no change in psychiatric status following surgery. Development of psychosis or deterioration in psychiatric status after surgery was more common in patients with later age of onset, unreality or déjà vu rather than epigastric aura, pre-operative evidence of bilateral brain damage, and persistence of EEG or clinical seizure activity. Development of a chronic psychosis in psychiatrically healthy individuals many months after temporal lobectomy, even when seizures are arrested or ameliorated, suggests that anomalous synaptic regeneration may follow the surgery in these cases. Careful analysis of histories and outcomes may contribute to better understanding of the pathophysiology and anatomical substrates of psychoses.

Adult

Oligoclonal bands in acute schizophrenia: a negative search.

Numerous immunologic abnormalities have been reported in patients with schizophrenia, suggesting that this disorder may in some cases represent a viral or immunologic disorder of the brain. To further examine this question, evidence for intrathecal production of immunoglobulin (IgG) and immunoglobulin oligoclonal bands (OCB) was sought in patients with acute or early schizophrenia. Using high resolution zone electrophoresis and immunofixation, there was no evidence for intrathecal IgG generation in 5 of 5 patients tested. One of 9 patients had OCBs in CSF. This man, although he had a typical history of schizophrenia, tested positive for human immunodeficiency virus antibody in serum.

Acute Disease

Isoenzyme characterization of Trypanosoma evansi isolated from capybaras and dogs in Brazil.

Trypanosoma evansi was seen in blood samples taken randomly from both wild and semi-captive capybaras caught in Mato Grosso do Sul State, Brazil and in sick dogs brought into local veterinary clinics. Trypanosome stocks from capybaras and dogs were significantly different in their patterns of growth in mice, while the trypanosomes from dogs were mostly dyskinetoplastic. By isoenzyme electrophoresis all the trypanosomes were of the most common type of T. evansi found elsewhere.

Animals

The expression of phosphorylated neurofilament epitopes in human brains.

The expression of phosphorylated neurofilaments (PNF) epitopes in hippocampal neurons was examined in 5 cases of Alzheimer's disease and 12 brains of schizophrenic patients. A control group (n = 17) consisted of 5 brains of patients with other acute or chronic neurologic disorders and 12 brains of persons who were free of any known neurologic disease. Immunocytochemistry with monoclonal antibodies to PNF was done on formalin-fixed, paraffin sections of hippocampus. Adjacent sections were impregnated with silver. Immunoreactivity to PNF was observed in tangles and plaques of the Alzheimer's brains and also in hippocampal pyramidal cells in 6 of the 12 schizophrenic brains and in 9 of the 17 control brains (2 with neurological disorders and 7 with non-neurological diseases). The positive PNF-stained cell bodies, in silver impregnated sections, generally did not show evident neurofibrillary abnormalities. Enzymatic dephosphorylation prior to immunostaining abolished PNF reactivity. These results suggest the widespread occurrence and relative non-specificity of perikaryonal PNF immunoreactivity in human post mortem brain tissue. We could not exclude the possibility that the hippocampal and brainstem neurons are predilection sites for normal perikaryonal phosphorylation in human brain.

Adult

Telemetered EEG-EOG during psychotic behaviors of schizophrenia.

In an effort to establish correlations between abnormal behaviors characteristic of schizophrenia and simultaneous cerebral electrical activity, EEGs and electro-oculograms (EOGs) were continuously recorded for 2 to 24 hours by radiotelemetry from 40 patients with schizophrenia and 12 normal control subjects. Trained observers recorded specific behavior patterns permitting visual and computer analysis of EEG during hallucinations, stereotypy, catatonia, psychomotor blocking, and other characteristic manifestations of schizophrenia. Electroencephalographic abnormalities consisting of focal slow or spike activity over either temporal region were found in nearly half of the patients so recorded. In contrast to the EEG during ictal episodes of epilepsy, the abnormal wave forms of schizophrenic patients seldom coincided with episodes of blocking, stereotypy, or other abnormal behaviors. Increased extraocular activity or blinking were recorded in a majority of patients, but were not consistently associated with the abnormal behavior or perceptual events.

Adult

Ontogeny of spontaneous blinking and of habituation of the blink reflex.

Habituation of the blink reflex to glabellar percussion was examined in 164 infants and children from ages 2 days to 18 years and in 18 adults aged 18 to 50 years. Spontaneous blink rates were measured in 269 children and 179 adults. The mean number of glabellar taps required for habituation of the blink reflex increased from 2.7 (SD 1.2) at 0 to 2 months of age to a peak of 13.3 (SD 5.6) at age 3 to 4, remained at more than 10 until age 6, after which a rapid decline occurred, reaching the adult level of 2 to 5 blinks to habituation at age 12 years. The mean rate of spontaneous blinking was less than 2 per minute in early infancy and increased steadily during childhood up to age 14 or 15. The inverse relationship of spontaneous blink rate and number of blink reflexes to habituation in early childhood and in disorders of dopamine transmission suggests that spontaneous blink rate and habituation of the blink reflex reflect maturation and integrity of dopaminergic circuits in the brain.

Adolescent

Disturbances of ocular movements and blinking in schizophrenia.

Neurological examination and electroencephalograms and electro-oculograms, recorded by telemetry, from unmedicated patients with acute and chronic schizophrenia demonstrate a number of abnormalities of extraocular movement including staring, abnormal blink rate, absent glabellar reflex, and increase in horizontal eye movements. As potential clues to the pathophysiology of schizophrenia, these disturbances are analysed in relation to anatomical substrate and dopamine modulation of ocular movement, rapid eye movement sleep, and the neurological disorders in which similar disturbances of ocular movement occur.

Adolescent

Eye blink and schizophrenia: psychosis or tardive dyskinesia?

The author found abnormalities of ocular movement including abnormal blink rate and blink reflex to glabellar tap in 34 of 44 medication-free schizophrenic patients. It is not clear whether these signs represent part of the pathology of schizophrenia or result from withdrawal of neuroleptic treatment.

Dyskinesia, Drug-Induced

Kindling of the mesolimbic dopamine system: animal model of psychosis.

In order to examine the behavioral and physiologic consequences of chronic activation of the mesolimbic dopamine system, the nucleus of origin in the ventral tegmental area was stimulated electrically for 2 seconds daily through chronically implanted intracranial electrodes in cats at the same point where instillation of the GABA blocking agent bicuculline induced a characteristic fear, staring, searching, and withdrawal response. None of the animals developed sustained after-discharge or seizures following daily stimulation for 2 months. Progressive fearfulness, hiding, loss of social behavior, and EEG spike or slow activity in the ipsilateral nucleus accumbens developed in three of six intact animals. Two cats with prior 6-hydroxydopamine lesions of catecholamine pathways did not develop behavioral change in response to local bicuculline or daily electrical stimulation of the ventral tegmental area but demonstrated pronounced after-discharge or EEG spike propagation during the kindling procedure.

Animals