Biomedical subjects

L A Pratt

Publications and source records attributed to L A Pratt.

27 records · Page 2Linked to original sources

PubMed1995

Identification of base pairs important for OmpR-DNA interaction.

OmpR, the transcriptional regulator of the ompF and ompC porin genes, is a member of a novel class of DNA-binding proteins. The mechanism(s) by which this class of proteins interacts with target DNA sites is not understood. To address this issue, we investigated the nature of the DNA sequences recognized by OmpR. A 36 bp DNA fragment was identified that is capable of supporting OmpR-DNA interaction in vivo. The base pairs within this region of DNA that are critical to this interaction were identified by isolating mutations within the fragment that hinder normal OmpR-DNA binding. The results obtained provide insights concerning the nature of the sequences recognized by OmpR and also support a model in which co-operative binding is involved in OmpR-DNA interaction.

Bacterial Outer Membrane Proteins↗

PubMed1994

OmpR mutants specifically defective for transcriptional activation.

In Escherichia coli, OmpR and EnvZ comprise a two component regulatory system that controls the relative expression of the outer membrane porin proteins, OmpF and OmpC. In this system, OmpR functions as a transcriptional regulator, serving as an activator of ompC, and as both an activator and a repressor of ompF. Previous evidence suggests that OmpR-mediated transcriptional activation involves direct interaction between OmpR and the C-terminal domain of the alpha subunit of RNA polymerase. However, it has remained unclear what region(s) of OmpR is directly involved in this proposed interaction. Moreover, little else is known about how OmpR activates transcription. To identify residues important for transcriptional activation, we screened for mutations in ompR that render the protein specifically defective in its ability to activate transcription. The isolated ompR alleles were characterized through haploid and diploid analyses at both the ompF and ompC promoters, and through an in vivo DNA binding assay. Through this approach, we have identified five amino acid residues in OmpR that are specifically required for transcriptional activation; R42, P179, E193, A196 and E198. We propose that these mutations define a region(s) in OmpR that may contact the C-terminal domain of alpha to mediate transcriptional activation.

Alleles↗

PubMed1994

Remission and relapse in subjects with panic disorder and panic with agoraphobia: a prospective short-interval naturalistic follow-up.

This article reports on the course of uncomplicated panic disorder and panic with agoraphobia on 309 patients participating in the Harvard/Brown Anxiety Research Project, a prospective longitudinal study of patients with DSM-III-R-defined anxiety disorders. At 1 year, there was a .39 probability of full remission for uncomplicated panic disorder and a .17 probability of full remission for panic disorder with agoraphobia Similar differences in time to remission for these syndromes were still found when criteria for remission were made less stringent. However, even requiring less improvement for remission left a large percentage of subjects in an episode, and for those that remitted, relapse occurred quickly, indicating a chronic and recurrent course of illness. This is the first longitudinal, prospective, naturalistic study on a large cohort of subjects with anxiety disorders to have regular, structured, short-interval follow-up. Our results are consistent with the view that panic disorder has a chronic course with high rates of relapse after remission and longer episodes when agoraphobia is a part of the constellation of symptoms.

Adult↗

PubMed1993

Trauma and posttraumatic stress disorder in subjects with anxiety disorders.

Trauma histories were obtained from 711 subjects in a large study of anxiety disorders, with the intent of determining the prevalence and nature of psychological trauma in this group. Twenty-seven percent of subjects reported significant trauma; 35% of these (10% of all subjects) met DSM-II-R criteria for posttraumatic stress disorder (PTSD). Subjects reporting sexual trauma were significantly more likely to have PTSD. The rate of PTSD was not higher in subjects with panic disorder than in those with other anxiety disorders.

Adult↗

PubMed1992

Pharmacotherapy observed in a large prospective longitudinal study on anxiety disorders.

Data concerning 331 subjects participating in a longitudinal study on anxiety disorders were collected over the first 6 months of the study. Preliminary analyses of somatic treatment according to diagnoses and study site were conducted. The comorbidity of one anxiety disorder with other DSM-III-R diagnoses and other types of anxiety disorders was extensive. Patients with panic disorder received significantly more treatment with a benzodiazepine than patients without panic disorder. Fewer than five percent of the sample were treated with a monoamine oxidase inhibitor. Comorbid depression increased the likelihood of treatment with a newer non-MAOI (non-monoamine oxidase inhibitor), nontricyclic antidepressant. Results suggest a strong effect of treatment site on the pharmacotherapy offered.

Adolescent↗

PubMed1989

Mortality risk and psychiatric disorders. Results of a general physician survey.

As part of the Stirling County Study (Canada), general physicians were interviewed to identify the psychiatric disorders experienced by a sample of adults selected in 1952. Based on information about vital status gathered 16 years later, we found that those with a psychiatric disorder at the beginning of the study experienced 1.6 times the expected number of deaths. The effect in regard to premature mortality and accidental deaths was particularly strong. Four of six categories of psychiatric diagnoses were significantly associated with mortality. In terms of standardized mortality ratios, depression had the highest and anxiety the lowest risk in this general population. The findings are discussed as providing historical background from the 1950s and 1960s for studying trends.

Cause of Death↗

PubMed1989

Prodromes of depression and anxiety. The Stirling County study.

A longitudinal investigation of psychiatric epidemiology in a general population (the Stirling County study) has indicated that the incidence of depression and anxiety disorders is low relative to prevalence, because these disorders have long durations. In an average year approximately nine adults among 1,000 experience a first-ever episode of one of these disorders. Incident cases over the course of a 16-year follow-up were more likely to have had premonitory symptoms than to have been asymptomatic at the beginning of the study. Among the relatively small number of people who exhibited the clearest prodromal manifestations, incidence was 20 per 1,000 annually. It might be possible to intervene before such disorders become fully formed and persistent if the precursors are given attention.

Adult↗

PubMed1989

Physiological consequences of human skin aging.

The expression and treatment of cutaneous disease in the elderly differ from those applicable to younger adults. Anatomical changes in aging skin result in altered physiological behavior and susceptibility to disease. Decreased epidermal renewal and tissue repair accompany the aging process. The rate of hair and nail growth declines, as well as the quantity of eccrine, apocrine, and sebum secretion. There are alterations in immune surveillance and antigen presentation with aging. The cutaneous vascular supply is decreased, leading to decreases in inflammatory response, absorption, and cutaneous clearance. Impaired thermal regulation, tactile sensitivity, and pain perception occur as one ages. We summarize the major changes that occur during the intrinsic aging process of the skin to facilitate the recognition and treatment of skin disease in the older patient.

Adult↗

PubMed1987

Treatment of junctional epidermolysis bullosa with epidermal autografts.

We have successfully treated chronic facial erosions in three boys with junctional epidermolysis bullosa. In each patient, keratinocytes were harvested from the roof of suction blisters created on clinically uninvolved skin. They were grown in tissue culture on collagen sponges and grafted onto facial erosions that were previously treated with 2% mupirocin ointment. This experimental antibiotic ointment has proved efficacy in eradicating cutaneous pathogens such as Staphylococcus aureus from chronic wounds. In two patients, complete reepithelialization was achieved over 7 and 10 months, respectively, and partial reepithelialization occurred in another patient in whom treatment is ongoing. Epidermal autografts are a promising means for improving function and appearance in eroded skin caused by junctional epidermolysis bullosa.

Adolescent↗