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Biomedical subjects

D Perkins

Publications and source records attributed to D Perkins.

At least 19 recordsLinked to original sources
PubMed1996

Regulation of CTLA-4 expression during T cell activation.

T cell activation requires at least two distinct signals, including signaling via the Ag-specific TCR and a costimulatory pathway. The best characterized costimulatory pathway involves the CD28 molecule, which is expressed constitutively on T cells and binds the family of B7 counter-receptors on APCs. Inhibition of this costimulatory pathway prevents T cell activation and can lead to long-term T cell unresponsiveness or anergy. In contrast, CTLA4, which is homologous to CD28, has been shown to be a negative regulator of T cell activation. The CTLA4 molecule is not expressed on resting T cells, but is induced after the initial steps of T cell activation. To address the regulation of CTLA4 expression, we have analyzed CTLA4 at the level of cell surface expression, mRNA, rate of transcription, and rate of decay of message. Nuclear runoff results show an increase in the rate of transcription following T cell activation. Our analyses of non-T cells, including B cells, mastocytoma, and fibroblasts, by Northern blot analysis detect only T cell expression of CTLA4. Reporter gene analysis indicates that 335 bp of upstream CTLA4 sequence are sufficient to control inducibility. We have identified important regulatory regions that control inducible and cell-specific CTLA4 expression. These results also suggest that both positive and negative response elements modulate the transcriptional regulation of CTLA4 gene expression. Understanding the regulation of CTLA4 should provide insight into the regulation of T cell activation at the molecular level.

Abatacept↗
PubMed1994

The clinical utility of granulocyte colony-stimulating factor: early achievements and future promise.

Recombinant granulocyte colony-stimulating factor (rHuG-CSF) is a hematopoietic growth factor that acts selectively on the neutrophil lineage, and has had a major impact on clinical practice. Two forms are in clinical use: filgrastim has been approved for use in more than 45 countries for the amelioration of chemotherapy-induced neutropenia and restoration of granulopoiesis following bone-marrow transplantation and lenograstim has been approved in Europe and Japan. In some countries, rHuG-CSF is also approved for various other indications, such as severe chronic neutropenia. Infection and neutropenia are a major cause of morbidity and mortality following cytotoxic chemotherapy, and there is a known correlation between neutropenia and the risk of infection. Hematopoietic growth factors have been used successfully in the prevention and treatment of neutropenia. There is evidence to suggest that use of rHuG-CSF before the onset of neutropenia allows patients to receive the maximum benefit; however, patients who do not receive rHuG-CSF prophylactically still benefit from the use of rHuG-CSF for the treatment of febrile neutropenia. These patients have an accelerated neutrophil recovery and a shorter duration of febrile neutropenia. These effects seem to translate into a significant reduction in the number of patients requiring prolonged hospitalization. This paper reviews the use of rHuG-CSF in the treatment of febrile neutropenia and describes how it is routinely used by hematologists and oncologists in non-clinical trial settings.

Clinical Trials as Topic↗
PubMed1990

Institutes of Quality: Prudential's approach to outcomes management for specialty procedures.

The Prudential Institutes of Quality program was developed to respond to the growing interest in the quality of care available to patients through both indemnity and managed medical plans and clients' concern about the continued escalation of health care costs. The program is based on the premise that high-quality care is the most efficient care that utilizes resources appropriately because of the experience of both the hospital and the physicians. Hospitals and physicians are selected through a questionnaire and site-visit process based on criteria developed from a literature review and outside expert counsel. Networks of facilities meeting the criteria serve the Prudential patient population. The history and results through the third quarter of 1989 and the implications of selective contracting for health care policy are presented.

Health Care Rationing↗
PubMed1987

A monoclonal antibody to a cross-reactive idiotype on cationic human anti-DNA antibodies expressing lambda light chains: a new reagent to identify a potentially differential pathogenic subset.

Anti-double-stranded DNA antibodies are commonly found in the serum of patients with systemic lupus erythematosus (SLE). They are a heterogeneous group of antibodies thought to differ in pathogenicity. The degree of heterogeneity and the structural correlates of pathogenicity, however, remain poorly defined. To address these questions we have been generating anti-idiotypic antibodies to the anti-DNA antibodies found in the serum of SLE patients. In this paper we report the generation and characterization of a new murine monoclonal anti-idiotype, 8.12, that recognizes a subset of anti-DNA antibodies that is present in serum of approximately 50% of patients with SLE. The 8.12 anti-idiotype recognizes uniquely cationic anti-DNA antibodies, all of which express lambda light chains. In murine models of SLE, it has been suggested that cationic anti-DNA antibodies are preferentially deposited in the kidney. It may be, therefore, that 8.12 recognizes a subset of anti-DNA antibodies of particular pathogenic significance.

Antibodies, Anti-Idiotypic↗
PubMed1984

Sequence of the envelope glycoprotein gene of type II human T lymphotropic virus.

The sequence of the envelope glycoprotein gene of type II human T lymphotropic virus (HTLV) is presented. The predicted amino acid sequence is similar to that of the corresponding protein of HTLV type I, in that the proteins share the same amino acids at 336 of 488 residues, and 68 of the 152 differences are of a conservative nature. The overall structural similarity of these proteins provides an explanation for the antigenic cross-reactivity observed among diverse members of the HTLV retrovirus family by procedures that assay for the viral envelope glycoprotein, for example, membrane immunofluorescence.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Structure of 3' terminal region of type II human T lymphotropic virus: evidence for new coding region.

The sequence of the 3' terminus of the human T lymphotropic virus type II (HTLV-II) was determined and compared to the corresponding sequence of HTLV-I. The 1557-nucleotide-long sequence can be divided into a 5' region that is not conserved between the two viruses, and a 3', 1011-nucleotide-long region that is highly conserved and that corresponds precisely with a long open reading frame for both HTLV-I and -II. The proteins that could be encoded by these open reading frames have a molecular weight of about 38,000 and are closely related in primary amino acid sequence. The genomic structure in the 3' region of HTLV was found to be similar to that of bovine leukemia virus.

Base Sequence↗
PubMed1984

Long terminal repeat structure of an American isolate of type I human T-cell leukemia virus.

Variation in the structure of the long terminal repeat (LTR) element of human T-cell leukemia virus (HTLV) types has been noted (M. Seiki, S. Hattori, Y. Hirayama, and M. Yoshida (1983), Proc. Natl. Acad. Sci. USA 80, 3618-3622; K. Shimotohno, D. W. Golde, M. Miwa, T. Sugimura, and I. S. Y. Chen (1984), Proc. Natl. Acad. Sci. USA 81, 1079-1083; J. Sodroski, M. Trus, D. Perkins, R. Patarca, F. Wong-Staal, E. Gelmann, R. Gallo, and W. Haseltine (1984), Proc. Natl. Acad. Sci. USA 81, 4617-4621). To determine whether HTLV isolates with similar disease associations, but from different geographic locations, exhibit a conserved LTR structure, the nucleotide sequence of the LTR of an American HTLV isolate from a patient with adult T-cell leukemia/lymphoma was obtained. Comparison of this LTR sequence to that of two Japanese HTLV isolates associated with a similar disease reveals a highly conserved organization of the U3, R, and U5 regions. The U. S. isolate differs from the Japanese viruses by only 15-16 bases out of 754 bases in the LTR region. These results show that Japanese HTLV isolates from patients with adult T-cell leukemia/lymphoma are members of the HTLV-I family and that LTRs of HTLV-I isolates are highly conserved. A 50-nucleotide imperfect direct repeat element is also identified in the U3 of the HTLV LTR distant from the cap site. The position and conserved nature of this sequence make it a likely candidate for a transcriptional enhancer.

Base Sequence↗
PubMed1984

Repetitive structure in the long-terminal-repeat element of a type II human T-cell leukemia virus.

The majority of human T-cell leukemia virus isolates (HTLV-I) are associated with clinically aggressive adult T-cell leukemia/lymphomas. By contrast, HTLV-II has been isolated from a patient with a relatively benign hairy T-cell leukemia. To characterize differences in the viral genomes that might contribute to these different pathologies, we determined the nucleotide sequence of the long terminal repeat (LTR) of a HTLV-II provirus. Comparison with the type I HTLV LTR reveals that, whereas the overall structural features are similar, the two sequences differ markedly throughout most of the length of the LTR. Despite the overall differences, the sequences of several functional regions of the two LTRs are conserved. These include the 5' boundary of U3, the RNA cap site, and the tRNAPro-binding site immediately 3' to the LTR. Another point of similarity is a 21-base sequence that is repeated four times in the U3 region of HTLV-II and three times in the U3 region of HTLV-I. This sequence has a formal analogy to, but no common sequence with, viral transcriptional enhancers. The U3 region of HTLV-II possesses a series of imperfect tandem direct repeats, 42 bases long, 21 bases long, 19 bases long, and 7 bases long. These structures differ from those of HTLV-I except for the 21-base repeat sequence. Thus, the structure of HTLV-II differs substantially from that of HTLV-I in the region that governs transcriptional initiation and tissue specificity. Such differences may account for some of the differences in clinical presentation of HTLV-associated adult T-cell leukemia/lymphomas and hairy T-cell leukemia.

Base Sequence↗
PubMed1984

Effects of CO2 and bronchoconstriction on costal and crural diaphragm electromyograms.

To determine if neural control of the crural diaphragm is similar to that of the costal diaphragm, electrical activity was recorded from these two parts of the diaphragm in 10 anesthetized dogs during resting O2 breathing and during progressive hyperoxic hypercapnia. Within a breath, the onset of crural diaphragm inspiratory activity started significantly earlier than that of the costal diaphragm under both resting and CO2 stimulated conditions, although the relative delay in costal diaphragm activity was smaller during hypercapnia than during resting O2 breathing. Following hyperventilation to apnea, both parts of the diaphragm resumed activity on the same breath. During CO2 rebreathing, the maximal increase in crural diaphragm peak electrical activity was significantly greater than that of the costal diaphragm. We also examined the effects of histamine-induced bronchoconstriction on diaphragm activity. Following administration of histamine aerosol there was a transient of irregular breathing during which in three animals costal diaphragm activity became nearly quiet, although there was continued activity of the crural diaphragm. Once breathing became more regular, there was a significantly greater stimulation of crural diaphragm than costal diaphragm activity; this difference persisted for 15 min after histamine inhalation. These results support the concept that electrical activity can be distributed nonuniformly to the costal and crural diaphragm and demonstrate that the crural diaphragm has a greater gain with hypercapnia and bronchoconstriction than does the costal diaphragm.

Aerosols↗
PubMed1983

A refutation of the hypothesis of the superfidelity of caricatures relative to photographs.

The experiment was designed to test the hypothesis that caricatures, relative to photographs, are 'superfaithful' carriers of information for facial recognition. Subjects were shown fifteen picutres of people's faces and were then asked to pick those same people out of a set of fifty-four pictures. There were three sets of pictures: caricatures, profile-view photographs, and three-quarter-view photographs. There were nine groups of subjecs: for three groups the exposure and test stimuli were in the same medium, for six groups the test stimuli were in one of the media not previously seen. Points were scored for the number of people correctly identified and the number of false positives. Facial recognition within medium was very good, but was seriously disrupted by any medium shift, especially those involving caricatures. It is argued that the superfidelity of caricature may be manifest only when the task involves recognition of actual persons rather than their pictures.

Face↗
PubMed1981

Medical student attitudes toward geriatric medicine and patients.

This study examines the influence of factual knowledge of the aged, general attitudes toward the aged, and personal contact with the aged on first-year medical students' attitudes toward geriatric patients and geriatric medicine. Entering medical students indicated a preference for working with younger patients rather than aged patients. Students' attitudes toward the aged were associated positively with their knowledge of the aged, but their interest in geriatric medicine did not appear to be affected significantly by knowledge of, attitudes toward, or personal contact with the aged. The results suggest that factors beyond those considered in this study may need to be examined if there is to be an increase in the number of physicians wishing to care for the elderly.

Aged↗