Effect of nitrofurans on cell wall synthesis and L-phase growth of Staphylococcus aureus.
Explore the source record for details and available documents.
Cell Wall↗
Biomedical subjects
R Freedman
Publications and source records attributed to R Freedman.
Genetic influences on the effects of alcohol on auditory evoked potentials.
Effects of alcohol on auditory evoked potentials were examined in 77 subjects without a history of alcohol abuse. Subjects were monozygotic twins, dizygotic twins, siblings, and adoptees, all same-sexed and reared together. Alcohol was administered to achieve 0.1 g/dl blood levels. Ten additional control subjects received placebo doses. The amplitude of the P50 wave of the auditory evoked response was reproducibly diminished in alcohol-treated subjects compared to controls. Evoked potentials were recorded in a conditioning-testing paradigm, which uses paired stimuli. The second or test response is decremented compared to the first or conditioning response. The paradigm thus examines gating of response to sensory stimulation. In addition to the alcohol-induced decrease of the P50 amplitude in the conditioning response already noted, the ratio of the P50 test response amplitude to the conditioning response amplitude increased after alcohol. This change, reflective of decreased sensory gating, was variable between subjects, but showed high test-retest reliability. These effects of alcohol on P50 amplitude and its decrement in the conditioning-testing paradigm were used to examine possible genetic influences on sensitivity to alcohol. The latter parameter showed significantly higher correlations in monozygotic twins than in siblings or adoptees; dizygotic twins had intermediate values. The results suggest that alcohol's effects on suppression of P50 in the conditioning-testing paradigm may be genetically influenced.
Adoption↗
Defects in auditory sensory gating and their apparent compensation in relatives of schizophrenics.
Auditory sensory processing is defective at several stages in schizophrenics, as revealed by electrophysiological recordings. The purpose of this study was to assess the relationship between two of these defects in schizophrenics and their relatives. One defect is illustrated by the failure to gate the P50 wave of the auditory evoked potential in the conditioning-testing paradigm. In this paradigm, paired clicks are presented to the subject. Normals suppress or gate the P50 response to the second or test click. Schizophrenics fail to suppress the test response. This defect has been related to schizophrenics' inability to filter out noise in their environment. A second defect is illustrated by schizophrenics' lower than normal N100 wave, which has been related to failure to attend to particular features of interest in the stimulus. The question addressed in this study was whether these two defects inevitably occur together. While they do occur together in schizophrenics, even in very good prognosis, mildly ill subjects, they do not occur together in the relatives of schizophrenics. The defect in the gating of P50 occurs in half these relatives, but N100 amplitudes are not diminished. Instead, relatives with abnormal P50 gating have N100 amplitudes which are larger than normal. One interpretation of the data is that the relatives with the sensory gating defect can compensate for that defect at a subsequent stage of information processing, as demonstrated by their large amplitude N100 wave, whereas schizophrenic patients cannot.
Adult↗
Lack of relationship of auditory gating defects to negative symptoms in schizophrenia.
The differences between schizophrenic patients with positive and negative symptoms have been the subject of extensive investigations. Psychophysiologists have proposed that there are elementary auditory sensory processing deficits in schizophrenia, but their prevalence in particular positive or negative subtypes has not been described. Our previous studies have shown that schizophrenics have impaired auditory sensory gating relative to normal controls, as demonstrated by the P50 auditory evoked potential conditioning-testing paradigm. In this paradigm, schizophrenics fail to show the normally expected diminished response to the second or 'test' stimulus. In the present study we assessed the possible relationship of this defect to negative symptoms in 20 schizophrenic patients treated with neuroleptics. Nine patients met the Andreasen criteria for predominantly 'negative schizophrenia'. 12 normal controls with no family history of schizophrenia were also studied electrophysiologically. Negative schizophrenics showed greater impairment than patients without such symptoms on the Trails B test of organic impairment, but there were no differences between groups on electrophysiological measurements of auditory sensory gating. Both schizophrenic groups showed impaired P50 auditory gating compared to normal controls. Both groups of schizophrenics also had a significantly diminished amplitude of the N100 waveform in the conditioning response, compared to normal controls. Auditory sensory processing defects in schizophrenia appear to be independent of negative symptoms.
Adult↗
Gating of auditory response in schizophrenics and normal controls. Effects of recording site and stimulation interval on the P50 wave.
Auditory evoked potentials were recorded using a paired stimulus, conditioning-testing paradigm from 14 schizophrenic patients and 13 normal subjects with no family history of psychotic disorder. Previous studies of the vertex P50 wave using this paradigm have demonstrated a possible sensory gating deficit in schizophrenics, as shown by their failure to diminish the response to a test stimulus presented 500 ms after a conditioning stimulus. Recordings were made at Cz, Fz, C3, T3, C4, and T4, to compare effects at different recording sites with this paradigm. Schizophrenics had significantly poorer sensory gating than normals, with the most significant difference between the groups at Cz. In addition to the 500 ms interval, subjects were also recorded at a conditioning-testing interval of 100 ms. Most schizophrenics showed normal sensory gating at the 100 ms interval, despite their abnormalities at 500 ms. The results indicate that Cz is optimal recording site for this paradigm, and that gating abnormalities in schizophrenic subjects are limited to specific interstimulus intervals.
Adult↗
Elementary neuronal dysfunctions in schizophrenia.
This paper describes an elementary deficit in sensory processing in people with schizophrenia. If paired sounds are presented to normal subjects, the response to the first sound, as measured by the P50 wave of the auditory-evoked potential, is much greater than the response to the second sound. The diminished response to the second sound is an example of a sensory gating mechanism that enables people to regulate their vigilance so that they can either detect all sounds in the environment or ignore most of them, in favor of narrowing the focus of their concentration. In schizophrenia, this mechanism is usually deficient; patients are in a state of hypervigilance and have diminished abilities to focus their attention. The deficiency appears to be genetically determined and to involve the brainstem control of sensory input to the hippocampus. Such sensory gating deficits may underlie more complex psychotic symptoms, such as hallucinations and delusions. Further studies of their neurobiology could lead to increased understanding of the pathophysiology of schizophrenia.
Arousal↗
Neurobiological abnormalities in the relatives of schizophrenics.
The inheritance of a complex illness such as schizophrenia likely involves the segregation of genetic factors, in combination with non-genetic or environmental abnormalities. This paper reviews several family studies of biological and clinical aspects of schizophrenia, that have attempted to observe such segregation in relationship to family history of schizophrenia to identify which factors appear to be related to the transmission of genetic risk.
Evoked Potentials, Auditory↗
Fetal dopamine-rich mesencephalic grafts in Parkinson's disease.
Explore the source record for details and available documents.
Brain↗
Age-related reduction in responses of rat hippocampal neurons to locally applied monoamines.
Age-related changes in the responsiveness of hippocampal pyramidal neurons to norepinephrine (NE) and serotonin (5HT) were investigated using electrophysiological techniques. Local application of each monamine via pressure micro-ejection was employed to establish the dose which elicited a 50% change in spontaneous discharge rate of single pyramidal neurons; these data were used to construct dose response curves for the population of neurons tested in 3-6, 11-13, 18-20, and 27-30 month old rats. The percentage of cells responding in rats 18-20 and 27-30 months old decreased for both NE and 5HT. There was also a progressive increase with age in the population ED50 for 5HT starting at 18-20 months. For neurons which demonstrated a response to NE, no decrease in the population ED50 was observed. Taken together these data indicate that there is a progressive age-related decline in the postsynaptic response to NE and 5HT in the rodent hippocampus.
Action Potentials↗
Age diminishes performance on an antisaccade eye movement task.
Tthe antisaccade eye movement task, which has been linked to frontal lobe function, presents a target in one visual field and asks subjects to move their eyes to the same location in the opposite field. The task requires inhibition of the reflexive prosaccade to the cue, initiation of the antisaccade to the opposite field, and visuo-spatial memory of the cue location. Forty-two subjects from 19-79 years of age performed this task and a control task, visually guided saccades to the cue itself, to determine which functions are affected by aging. The time to initiate antisaccades increased linearly with age at a rate greater than the time to initiate visually guided saccades. This difference suggests that the processing time to inhibit the incorrect movement to the cue is selectively increased with age. Older subjects also made more incorrect prosaccadic movements to the cue, a finding consistent with the loss of inhibitory processing capacity. The accuracy of movements did not change, which suggests that visuo-spatial memory is unaffected by aging.
Adolescent↗
Diffusion-relaxation distribution functions of sedimentary rocks in different saturation states.
We present diffusion-relaxation distribution functions measured on four rock cores that were prepared in a succession of different saturation states of brine and crude oil. The measurements were performed in a static gradient field at a Larmor frequency of 1.76 MHz. The diffusion-relaxation distribution functions clearly separate the contributions from the two fluid phases. The results can be used to identify the wetting and non-wetting phase, to infer fluid properties of the phases, and to obtain additional information on the geometrical arrangement of the phases. We also observe effects due to restricted diffusion and susceptibility induced internal gradients.
Diffusion↗
Protein chemistry. Folding into the right shape.
Explore the source record for details and available documents.
Animals↗
Correlation of Purkinje neuron depression and hypnotic effects of ethanol in inbred strains of rats.
The effect of locally applied ethanol on spontaneous discharge rates of cerebellar Purkinje neurons was compared in two inbred strains of rats which differ in their sensitivities to the acute hypnotic effects of this agent. Ethanol, applied locally to neurons by micropressure ejection with multibarrel micropipettes, was significantly more potent for reducing neuronal firing rates in Fischer 344 rats when compared to Brown Norway rats. The hypnotic effect of ethanol, measured by loss of righting reflex, lasted significantly longer in the Fischer 344 strain of rats. These results suggest that susceptibility to a behavioral effect of ethanol might correlate with an effect on firing rates of cerebellar Purkinje cells in rats. In mice, selective breeding has produced "long-sleep" and "short-sleep" strains of mice which differ not only in sensitivity to the hypnotic effect of ethanol, but also to the sensitivity of cerebellar Purkinje cells to depressant effects of this drug. Because electrophysiological investigations are in many ways easier to perform in rats than in mice, genetic differences in rats may provide an important means for analyzing central nervous system actions of acute ethanol administration.
Animals↗
Linkage analysis of schizophrenia: the D1 dopamine receptor gene and several flanking DNA markers.
Alterations in dopaminergic activity may play an important role in the pathogenesis of schizophrenia. The central effects of dopamine are mediated by at least five G protein-coupled receptors, D1, D2, D3, D4 and D5. The D1 receptor maps to 5q35.1 and it identifies an Eco RI as well as a Taq I RFLP. In the present study we undertook a linkage analysis between the D1 receptor RFLPs and schizophrenia in 9 multigenerational families in which segregation of disease was consistent with autosomal dominant inheritance and reduced penetrance. Several flanking DNA markers were also analyzed as the D1 receptor RFLPs were relatively uninformative in our families. Pairwise analyses of schizophrenia and several flanking markers indicate that inheritability of this region is unlikely to be involved in the pathogenesis of schizophrenia in the 9 families studied.
Chromosome Mapping↗
Human dopamine transporter gene not linked to schizophrenia in multigenerational pedigrees.
A large body of data suggests that perturbations in brain dopaminergic transmission play a role in the pathogenesis of schizophrenia. Recently, the gene for the human dopamine transporter has been cloned and polymorphisms have been identified. Because mutations of the dopamine transporter gene might underlie the cause of schizophrenia in a subset of families, we undertook a linkage analysis between schizophrenia in 9 families and a dopamine transporter gene polymorphism. Evidence of linkage was not found in most families assuming autosomal dominant or recessive inheritance.
Carrier Proteins↗
Linkage analysis between schizophrenia and index simple-sequence repeat loci for chromosome 21.
Nine multiplex schizophrenia families were genotyped with seven highly polymorphic microsatellite loci used in the construction of an index map of chromosome 21. Assuming either autosomal dominant or recessive transmission, evidence of linkage was not found. In addition, the nonparametric sib-pair test did not yield significant evidence of linkage.
Chromosome Mapping↗
Schizophrenia and nicotinic receptors.
Patients with schizophrenia often cannot respond to important features of their environment and filter out irrelevant stimuli. This dysfunction could be related to an underlying defect in inhibition--i.e., the brain's ability to alter its sensitivity to repeated stimuli. One of the neuronal mechanisms responsible for such inhibitory gating involves the activation of cholinergic nicotinic receptors in the hippocampus. These receptors are diminished in many specimens of hippocampal brain tissue obtained postmortem from schizophrenic patients. In living schizophrenic patients, stimulation of cholinergic receptors by nicotine transiently restores inhibitory gating of evoked responses to sensory stimuli. Many people with schizophrenia are heavy smokers, but the properties of the nicotinic receptor favor only short-term activation, which may explain why cigarette smoking is only a transient symptomatic remedy. This paper reviews the clinical phenomenology of inhibitory gating deficits in people with schizophrenia, the neurobiology of such gating mechanisms, and the evidence that some individuals with the disorder may have a heritable deficit in the nicotinic cholinergic receptors involved in this neurobiological function. Inhibitory gating deficits are only partly normalized by neuroleptic drugs and are thus a target for new therapeutic strategies for schizophrenia.
Antipsychotic Agents↗
Clinicopathologic analysis of mullerian adenosarcoma: the M.D. Anderson Cancer Center experience.
The records of 41 patients diagnosed with adenosarcoma of the female genital tract between 1982 and 1996 were reviewed. The median age at diagnosis is 51 years (range, 14-84). The most common symptom is vaginal bleeding (71%). Clinical signs at presentation include pelvic mass (37%), uterine polyps (29%), and enlarged uterus (22%). In 71% of patients, the tumor originates from the uterus. Other sites include ovary (15%), pelvis (12%), cervix (2%). A history of thyroid cancer, benign ovarian cyst, and polycystic ovarian disease is found more frequently than expected in this patient population, whereas no relationship to endometriosis is observed. Surgery is the mainstay of treatment, but platin-based chemotherapy given upfront in inoperable patient has definite efficacy. An overall response rate of 92.5% was observed after primary therapy (surgery with or without radiotherapy, and/or chemotherapy), with a median survival of 48 months (range, 1-174). Thirty-eight percent of patients had recurrent disease. The median time to recurrence is 12 months (range, 5-132). Although 60% of patients with recurrence achieved a complete remission after treatment, only 1 (8%) is alive without disease, and 3 (22%), with disease at the time of this analysis. In our series, histologic sarcomatous overgrowth is a predictor of poor prognosis (p<0.03), however myometrial invasion and stage of disease seem to be of less prognostic significance. Adenosarcoma is a tumor with a fair prognosis. Most tumor can be cured with surgery, but recurrence carries a bad prognosis.
Adenosarcoma↗