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Biomedical subjects

T Patterson

Publications and source records attributed to T Patterson.

70 records · Page 4Linked to original sources

A specialized host-vector system for the in vivo cloning of the trp operon of wild-type and mutant strains of Salmonella typhimurium by generalized transduction.

Using in vitro methods, a 14.2-kb EcoRI fragment of the Salmonella typhimurium chromosome containing the trp operon plus associated flanking sequences from deletion mutant delta trpDCB763 was cloned into the EcoRI site of plasmid pBR322 in a S. typhimurium host. An in vivo cloning vector was constructed from the recombinant plasmid by the in vitro excision of a SalI fragment that contains the entire trp operon. The derived plasmid (pSTP21) carries a hybrid insert made up of the 5.4-kb EcoRI-SalI upstream flanking sequence and the 3.2-kb SalI-EcoRI downstream flanking sequence. Plasmid pSTP21 has been used as a receptor plasmid to clone a variety of mutant and wild-type trp operons by RecA-dependent in vivo recombination between the insert DNA of the plasmid and the homologous trp flanking sequences of transducing DNA fragments transferred into the cell by bacteriophage P22. The host-vector system developed for the in vivo cloning permits the differentiation of plasmid transductants from chromosomal transductants on the primary selective medium. Expression of the cloned trp operons is regulated normally by tryptophan. A substantial amplification of trp enzymes is attainable upon derepression. The recombinant plasmids are stably inherited in RecA+ and RecA- S. typhimurium hosts. However, conditions of high expression of the trp operon lead to a rapid loss of cellular viability and of plasmid stability.

Cloning, Molecular↗

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History, Ancient↗

Bilateral skin conductance and the pupillary light-dark reflex: manipulation by chlorpromazine, haloperidol, scopolamine, and placebo.

Cholinergic blocking with scopolamine produces skin conductance orientating response (SCOR) nonresponding in normal subjects. This may be one of a number of causes for nonresponding in schizophrenic subjects. Blockade of dopamine with haloperidol produces an increase in amplitude and shortening of recovery time in the SCOR of normal subjects. This result closely resembles that of Nielsen and Petersen (1976) who found a similar pattern of responding in normal subjects who scored high on a scale of schizophrenism. These results, along with those for chlorpromazine and the pupillographic effects of the three drugs are discussed in terms of biochemical working hypotheses of schizophrenic subclassification.

Adult↗

Auditory vigilance: normals compared to chronic schizophrenic subgroups defined by skin conductance variables.

Three electrodermally distinct subgroups of chronic schizophrenics were identified by Patterson and Venables (1978). The present study investigated the auditory vigilance ability of these subgroups relative to a normal population. In one subgroup of schizophrenics (the fast habituators) no evidence could be found for a deficit in auditory vigilance ability relative to normal. Implications for further electrophysiological and biochemical research in schizophrenia are discussed.

Adult↗

Recent studies of psychophysiology in schizophrenia.

A general introduction is given and followed by a review of recent literature under the following subheadings: electrodermal activity, cardiovascular activity, smooth pursuit eye movement, electroencephalogram, and evoked potentials. An attempt is made to assess the clinical significance of the findings reported in each area and to indicate directions for future investigation. The feasibility of defining homogeneous subgroups in schizophrenia using psychophysiological parameters is also considered. The review concludes with the recommendation that peripheral psychophysiological studies entailing (1) comprehensive recording of brain electrical activity and (2) behavioral experimentation on variables thought to be influenced by schizophrenia (e.g., sustained attentional ability) are promising directions for future research. Relationships between behavioral and psychophysiological variables determined by such studies (and possibly subgroupings) may then become the basis for neurophysiological-neurochemical investigations of specific abnormalities underlying such relationships and subgroups.

Antipsychotic Agents↗

Skin conductance responding/nonresponding and pupiliometrics in chronic schizophrenia. A confirmation of Gruzelier and Venables.

In a number of reports, Gruzelier and Venables have demonstrated that about 50% of the schizophrenic population do not show the skin conductance orienting response (S.C.O.R.), while those that do respond, do not show normal habituation. Zahn (Orienting response in schizophrenics. J. Nerv. Ment. Dis., 162: 195-199, 1976) has questioned the bimodality of the S.C.O.R. in schizophrenia and suggests that responding/nonresponding could well be due to differential effects of phenothiazine medication. In two experiments (with equally medicated patients), in two different hospitals, the present report confirms the finding of a large proportion of nonresponding in schizophrenia but also suggests that both normal and nonhabituation are seen within schizophrenics and normals. Differential pupillary dilation and constriction parameters are seen in responders and nonresponders although both of these patient groups show tachycardia (the most usual effect of phenothiazines) in comparison to the normal group. The results do not fit easily into the differential effect of phenothiazines hypothesis proposed by Zahn.

Adult↗

An analysis of the skin conductance orienting response in samples of American, British, and German schizophrenics.

The existing literature dealing with the phasic orienting response (OR) in schizophrenia, examining, for the most part, the skin conductance component (SCOR), reports conflicting results with divergent implications for the nature of the attentional dysfunction in these patients. The present authors have contributed to that literature and to its divergencies. The present report addresses this issue by applying a common set of response definitions and uniform statistical-analytic procedures to the previously gathered electrodermal data obtained independently in each author's laboratory. A total of 14 studies is involved, drawn from six laboratories in the U.S.A., the U.K., and West Germany. Collectively, these studies examine chronic and acute schizophrenics, males and females, those receiving neuroleptic drugs and those not receiving them, recording SCOR from either (or both) hands using a variety of instruments and somewhat differing instructions and conditions, to both auditory and visual stimuli of different intensities and rise-time properties. The authors' purpose is two-fold. First, to determine whether some 'universal' dysfunction can be demonstrated across laboratories, conditions, and samples. Given the heterogeneous origins of these data such a finding would offer fairly strong evidence of 'real' dysfunction in schizophrenia. Second, where disagreement exists, to describe the scope and nature of the disagreement, and to articulate more clearly the findings on each side of a disputed area. One such 'universal' dysfunction emerged. Consistently, schizophrenics displayed an abnormally high incidence of nonresponsiveness, involving nearly 50% of the schizophrenic sample on average. The next most common finding is that many of the schizophrenics who display an SCOR often habituate faster than do nonschizophrenic responders. This was seen in a majority of the studies and laboratories, but conflicting evidence was presented by a minority. Evidence for a dysfunction simultaneously involving SCOR hypo- and hyper-responsiveness within schizophrenia was obtained, but in a minority of studies. The possible effects of neuroleptic drugs, stimulus intensity and rise-time factors, and differential significance evaluation on these findings was discussed. The possibility that schizophrenic dysfunction involves the input-facilitating OR but not input-attenuating 'protective' responses is examined. The correlates of hyporesponsiveness in schizophrenia, including physiological response patterns, clinical symptom patterns, and specific input deficiencies, is also examined. Several areas are noted where systematic research has only begun, and further study is particularly needed.

Adolescent↗

Effects of chronic stress on beta-adrenergic receptors in the homeless.

This study examined the role of chronic life stress (homelessness), coping style, and hypertension on beta-adrenergic receptors in a sample of homeless men. Sixteen healthy normotensive subjects and nine untreated hypertensive subjects were studied. Life stress was measured with the Brown and Harris categorization; coping style was measured with the Ways of Coping Scale. Lymphocyte beta-adrenergic receptors were characterized in terms of receptor density (Bmax). Individuals with high life stress had lower Bmax (p < .005). In multiple regression analyses, 50% of the variance in Bmax was accounted for by life stress and coping style (p = .01). Receptor measures may be useful for characterizing the physiological response to continuing life adversity.

Adaptation, Psychological↗

Plasma catecholamine and lymphocyte beta 2-adrenergic receptor alterations in elderly Alzheimer caregivers under stress.

OBJECTIVE: The purpose of this study was to determine the effects of chronic stress on beta-adrenergic physiology in elderly spousal caregivers to Alzheimer patients. METHODS: Thirty-seven elderly spousal caregivers and matched noncaregiver controls (mean age 73 years, SD = 6) were studied. Life stress categorization (presence of marked threat) covering the previous 6 months was determined using a semistructured interview based on the Psychiatric Epidemiological Research Inventory and the Life Events and Difficulties Schedule. beta 2-adrenergic receptor sensitivity (isoproterenol-stimulated cyclic AMP accumulation) and density were determined in lymphocytes. RESULTS: Caregivers with high life stress had higher plasma norepinephrine levels (p < .04) but no change in plasma cortisol. For beta-receptor sensitivity, 30% of the variance was accounted for by high life stress rating, increased age, being male, and lower norepinephrine (p = .018); 17% of the variance in beta-receptor density was accounted for by plasma norepinephrine (p = .03). CONCLUSIONS: The findings demonstrate that chronic high stress may be associated with changes in adrenergic physiology and may provide a mechanism through which chronic stress alters cellular immunity.

Adult↗

Vulnerable caregivers of patients with Alzheimer's disease have a deficit in circulating CD62L- T lymphocytes.

OBJECTIVE: The cell adhesion molecule, L-selectin (CD62L), serves a crucial role in the migration of naive T lymphocytes and is typically shed on cell activation. The objective of this study was to determine the effects of chronic stress on L-selectin expression on peripheral lymphocytes in elderly spousal caregivers of patients with Alzheimer's disease. METHODS: Twenty caregivers (mean age, 73.5 years) had their lymphocytes and catecholamine levels sampled at rest and in response to an acute psychological stressor. Ten of the caregivers were classified as susceptible or "vulnerable" based on the large amount of care required by the patient relative to the amount of respite the caregiver received during the previous 6 months. RESULTS: At rest, vulnerable caregivers had 60% fewer L-selectin negative CD8+ T cells (CD8+CD62L-) (p=.01) but no difference in CD8+CD62L+ cells. Vulnerable caregivers also showed significantly fewer CD4+CD62L- T lymphocytes (p=.04) but no difference in CD4+CD62L+ lymphocytes. Resting plasma epinephrine levels were 44% higher in vulnerable caregivers as compared with nonvulnerable caregivers (p=.01). The acute stressor increased circulating levels of CD8+CD62L- and CD8+CD62L+ lymphocytes and catecholamines similarly in both groups. CONCLUSIONS: The findings suggest that caregivers who are more vulnerable to the chronic stress of caregiving show a decrement in circulating CD62L- T lymphocytes, possibly by adrenomedullary activation. The data also suggest the identity of lymphocyte subsets that may underlie prior observations of immunologic decrements associated with the chronic stress of caregiving.

Aged↗

The influence of HIV-related support groups on survival in women who lived with HIV. A pilot study.

To determine the effect of support groups on survival, the authors retrospectively studied 21 HIV-seropositive women who died during the course of participation in a natural history study of HIV. Groups were composed of women who self-selected HIV support groups before death (n = 11) and a comparison group (n = 10). Survival analysis found group participation to be associated with increased longevity (73 months vs. 45 months; P = 0.011). Proportional-hazards regression demonstrated that HIV-related support groups and smaller family size significantly influenced survival (P = 0.0002). Factors related to group participation and ways in which support groups might promote longevity are discussed.

Adaptation, Psychological↗