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Biomedical subjects

P Cleary

Publications and source records attributed to P Cleary.

At least 19 recordsLinked to original sources
PubMed1992

Surface protein-CAT reporter fusions demonstrate differential gene expression in the vir regulon of Streptococcus pyogenes.

Streptococcus pyogenes expresses at least two virulence factors, the anti-phagocytic M protein and an inhibitor of chemotaxis, the C5a peptidase (ScpA), under control of the virR locus. To facilitate studies of this regulatory unit, we constructed a new shuttle vector with a staphylococcal chloramphenicol acetyl transferase (CAT) reporter box which replicates in S. pyogenes. We cloned polymerase chain reaction (PCR)-derived potential promoter regions of the virR, M protein (emm12), and ScpA (scpA) genes from an M type 12 S. pyogenes, strain CS24. Promoter activity was assessed by measurements of specific mRNAs, transacetylase activity, and minimum inhibitory concentrations (MICs) for chloramphenicol resistance. We demonstrated that VirR is a necessary but not always sufficient positive trans-acting regulator of emm12 and scpA expression; however, virR is not autoregulated. A potential virR-binding consensus sequence is postulated for emm12, scpA and other M-like protein genes. Promoter activity of the structural genes was found to be dramatically influenced by growth conditions such as anaerobiosis. Levels of control, over and above the requirement for virR, are realized. The virR and scpA promoters were mapped for the first time using primer extension analysis. The observed mRNA start sites did not completely agree within the sequence predicted start sites. Data suggest that scpA could be subject to transcription attenuation.

Antigens, Bacterial↗
PubMed1991

Epidemiology of delirium: an overview of research issues and findings.

This paper provides a review of research issues and findings on the epidemiology of delirium. Despite the fact that research on this important geriatric syndrome has been conducted for many decades, several methodological issues make it difficult to compare findings across studies. In this paper we first discuss broadly methodological issues related to diagnosis, case-finding, and populations studied. We next review data on the occurrence and consequences of the syndrome. A discussion of the design and preliminary results of the Commonwealth-Harvard Study of Delirium in Elderly Hospitalized Patients documents both how we responded to the methodological issues outlined and how these choices influenced our findings. We conclude with a discussion of the needs for further research on the epidemiology of delirium.

Aged↗
PubMed1991

Review of research instruments and techniques used to detect delirium.

Over the past several decades, numerous investigators have studied the syndrome of delirium. Researchers have relied on a number of different case finding methods to detect the syndrome. This paper provides an overview of instruments used in studies of delirium. We assess the validity and reliability of these instruments and compare the advantages and disadvantages of the different methods. We then present the rationale for the development of the Delirium Symptom Interview, an instrument constructed for use in the Commonwealth-Harvard Study of delirium in elderly hospitalized patients.

Aged↗
PubMed1988

Comparison of the leader sequences of four group A streptococcal M protein genes.

The 5' portions and flanking sequences of genes encoding types 1, 12, 24, and 6 M proteins were compared. Although the DNA sequences encoding the amino-termini of the mature M proteins had no obvious similarity, upstream sequences, and those encoding the signal peptides (leader sequences) of the four M protein genes had considerable similarity. In general, the 5' ends of all the leader sequences were more conserved than the 3' ends, although the M6 and M24 leader sequences had identical 3' ends. Sequence similarity among the deduced amino acid sequences of the four signal peptides was more extensive than the corresponding DNA sequences. We found that strict DNA similarity among all four sequences extended only to the ends of the hydrophilic amino-terminal regions of the signal peptides, but that amino acid sequence conservation continued to the ends of the respective hydrophobic cores. With the exception of the M6 and M24 sequences, the regions adjacent to the signal peptidase cleavage sites were highly variable.

Amino Acid Sequence↗
PubMed1988

The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex.

Infection with human immunodeficiency virus type 1 (HIV-1) is frequently complicated in its late stages by the AIDS dementia complex, a neurological syndrome characterized by abnormalities in cognition, motor performance, and behavior. This dementia is due partially or wholly to a direct effect of the virus on the brain rather than to opportunistic infection, but its pathogenesis is not well understood. Productive HIV-1 brain infection is detected only in a subset of patients and is confined largely or exclusively to macrophages, microglia, and derivative multinucleated cells that are formed by virus-induced cell fusion. Absence of cytolytic infection of neurons, oligodentrocytes, and astrocytes has focused attention on the possible role of indirect mechanisms of brain dysfunction related to either virus or cell-coded toxins. Delayed development of the AIDS dementia complex, despite both early exposure of the nervous system to HIV-1 and chronic leptomeningeal infection, indicates that although this virus is "neurotropic," it is relatively nonpathogenic for the brain in the absence of immunosuppression. Within the context of the permissive effect of immunosuppression, genetic changes in HIV-1 may underlie the neuropathological heterogeneity of the AIDS dementia complex and its relatively independent course in relation to the systemic manifestations of AIDS noted in some patients.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Screening for alcohol abuse using the CAGE questionnaire.

A prospective study of 518 patients admitted to the orthopedic and medical services of a community-based teaching hospital during a six-month period was performed to test the hypothesis that a short, easily administered questionnaire would improve the detection rate by physicians of alcohol abuse. The CAGE questionnaire--a mnemonic for attempts to cut back on drinking, being annoyed at criticisms about drinking, feeling guilty about drinking, and using alcohol as an eye opener--was utilized as a screening instrument. The mean corpuscular volume of red blood cells, liver transaminase levels, and the gamma-glutamyl transpeptidase level were also evaluated as screening tests. The presence or absence of alcoholism and alcohol abuse for a consecutive sample of CAGE-negative patients and all patients answering "yes" to one or more of the CAGE questions was established through the administration of the Michigan Alcoholism Screening Test, a detailed chart review, and analysis of quantity of alcohol consumed. Diagnostic criteria were those described in the Diagnostic and Statistical Manual III. The prevalence of alcohol abuse was 20 percent. The mean corpuscular volume, gamma-glutamyl transpeptidase value, and liver transaminase levels were very insensitive as screening tests. In contrast, the CAGE questionnaire had a sensitivity of 85 percent and a specificity of 89 percent. Only 63 percent of the alcoholic subjects and alcohol abusers were detected by their physicians, and in only 24 percent of these cases did a physician address the problem with the patient. The CAGE questionnaire is a simple, sensitive, and specific screening test for alcohol abusers.

Alcoholism↗
PubMed1987

A five-year survey of ocular shotgun injuries in Ireland.

Between November 1980 and September 1985 20 patients in Ireland sustained accidental ocular shotgun injuries severe enough to necessitate hospital admission. Eight patients had contusion injuries and 12 perforating injuries. Contusion damage was disproportionate to the size of the pellet. Through and through perforation of the globe occurred in eight patients; the remaining four patients in this group had retained intraocular pellets. Twelve patients sustained perforating eye injuries. Those that were treated by primary closure alone lost the sight in that eye. Those treated by vitreoretinal surgery recovered vision directly related to where the pellet had its exit from the eye. It was possible to contact 15 of the patients. All 15 were shooting pheasant. It was not possible to relate the distance of the patient from the gun to the severity of the ocular injury.

Adolescent↗
PubMed1986

Alcohol abuse in women seeking gynecologic care.

In several retrospective studies, alcoholic women have reported menstrual problems significantly more often than nonalcoholic women. There is no information, however, comparing the prevalence of alcohol abuse in women who receive periodic gynecologic care and those who seek care for menstrual disorders such as the premenstrual syndromes. This question was studied in two private practice settings. Women seeking periodic care were obtained from a suburban, general gynecology practice. Women seeking treatment for premenstrual syndrome (PMS) were obtained from a practice that specialized in the care of PMS. Ninety-five patients with PMS and 147 patients seeking periodic care were screened with the CAGE questions--a mnemonic for attempts to Cut back on drinking, being Annoyed at criticism about drinking, feeling Guilty about drinking, and using alcohol as an Eye-opener. Women who gave affirmative responses to one or more of the CAGE questions were evaluated for the presence of alcohol abuse. In the women seeking periodic care, 33% were CAGE positive and 12% were alcohol abusers. In the PMS practice, 51% were CAGE positive and 21% were alcohol abusers. Alcohol abuse is a common problem in gynecologic practice. Women who seek medical care for PMS are at much greater risk to be alcohol abusers.

Adolescent↗
PubMed1984

Small DNA deletions creating avirulence in Streptococcus pyogenes.

The M protein is the antigen on the surface of group A streptococci that allows these bacteria to resist phagocytosis. DNA encoding the M12 protein was cloned into Escherichia coli and used as an isotopically labeled hybridization probe to compare genomic DNA's isolated from M+ and M- isogenic cultures in an effort to elucidate the genetic basis of this variation. DNA's from two spontaneous, independent M- variants contained small (approximately 50 base pairs) deletions which were mapped to identical restriction fragments within or adjacent to the M protein coding sequence. Taken together with the pleiotropic nature of these deletions, this suggests that they define a regulatory switch.

Antigens, Bacterial↗
PubMed1983

Food and chemical sensitivity. Clinical and immunologic correlates.

Six allergic patients and six normal controls were studied serologically before and after provocative challenge with allergic substances. The patients showed impaired modulation of the immune system prior to challenge. The challenge blood changes in patients with adverse clinical responses were consistent with type 1 and/or type 3 immune responses. Normal controls showed no abnormal laboratory or clinical changes. The data support the hypothesis that an abnormal immune reaction develops in allergic patients who sustain an adverse clinical response to ingestion of foods or inhalation of chemicals to which they are sensitive.

Adult↗
PubMed1983

Insensitivity of the cold pressor stimulation test for the diagnosis of coronary artery disease.

Cold pressor stimulation (CPS) was compared with supine bicycle exercise during radionuclide ventriculography as a procedure for diagnosing coronary artery disease (CAD). Thirty patients were studied. In the 18 patients with angiographically proved CAD, left ventricular ejection fraction (LVEF) decreased a mean of 5.0 +/- 1.0 ejection fraction units (+/- SEM) in response to CPS. Only two patients developed a new wall motion abnormality. In response to maximal supine exercise, the CAD group showed a mean decrease in LVEF from rest of 1.9 +/- 1.1%. Nine patients developed an exercise-induced wall motion abnormality. In the 12 patients with angiographically proved normal coronary arteries, LVEF decreased a mean of 5.8 +/- 1.3 units in response to CPS and increased a mean of 9.2 +/- 1.2% in response to exercise. Thus, the LVEF response to CPS was not significantly different in the CAD and normal groups (5.0 +/- 1.0 vs 5.8 +/- 1.3, NS). These same patients demonstrated the expected difference in LVEF response to exercise. We conclude that CPS produces similar changes in LVEF in patients with and without CAD, and therefore is not useful in diagnosing ischemic heart disease.

Adult↗
PubMed1982

The National Exercise and Heart Disease Project: Long-term psychosocial outcome.

Six hundred fifty-one men who suffered at least one myocardial infarction eight weeks to 36 months earlier were randomly assigned to participate for at least two years as control subjects or subjects in a prescribed, supervised exercise training program. Psychosocial results at baseline and at the sixth-month, one-year, and two-year follow-ups are presented. With minimal exception, no differences were noted between the control and exercise groups at any of the testing periods. Several explanations for the lack of exercise-induced psychosocial benefit are provided.

Adult↗
PubMed1979

Genetic variation in the M antigen of group A streptococci: reassortment of type-specific markers and possible antigenic drift.

The phylogenetic relationships of 73 strains of group A Streptococcus isolated over a six-year period from a population with a high prevalence of streptococcal infections were analyzed with use of four serotype-specific markers: the serum opacity factor (OF), the T antigen, the determinant of the M antigen that precipitates with antibody, and the M antiphagocytic determinant. OF inhibition tests divided the strains into five subtypes: a, b, c, d, and e. Strains within subtypes a, b, and c shared a previously unidentified M precipitin. The identification of this new common M precipitin was based on absorption studies, double agar immunodiffusion, and immunoelectrophoresis analysis. Antisera directed against representative strains from subtypes a, b, and c contained cross-reactive bactericidal antibody, and absorption studies indicated that determinants of the M precipitins were identical, whereas determinants of resistance to phagocytosis were closely related but not identical. The association of a common M precipitin with three different OF antigens, two different T antigens, and three different, yet similar, antiphagocytic determinants is discussed in light of the possibility that the genes that code for these antigens have reassorted or recombined. Moreover, the possibility that differences in the antiphagocytic determinants of these strains have resulted from antigenic drift in a common gene is considered.

Absorption↗
PubMed1979

Training adaptations in skeletal muscle of juvenile diabetics.

Skeletal muscles from 12 male, juvenile-onset diabetics (JD) and 13 nondiabetics (ND) were studied to determine the effects of endurance training on mitochondrial enzyme activities, lipoprotein lipase (LPL) activity, and the oxidation of lipids (14C-palmityl CoA) in vitro. Ten weeks of endurance running (30 min/day, 5 days/wk) resulted in 11.0 and 12.9% gains in aerobic capacity for the JD and ND groups (P greater than 0.05), respectively. Both groups showed significant (P less than 0.05) increases in muscle LPL, carnitine palmityl transferase, succinate dehydrogenase, and hexokinase activities with training. Though the pretraining capacities for 14C-palmityl CoA oxidation were similar for both ND and JD groups, the diabetics showed a 41% greater improvement in the measurement of muscle lipid oxidation after training than did the ND group. The principal finding of this research was that skeletal muscle of juvenile diabetics who are in moderate insulin balance shows adaptations to endurance training that are similar to those of nondiabetic men.

Adult↗