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P Heald

Publications and source records attributed to P Heald.

At least 19 recordsLinked to original sources
PubMed1996

The immune response to class I-associated tumor-specific cutaneous T-cell lymphoma antigens.

In order to determine whether the neoplastic T cells from patients with cutaneous T-cell lymphoma express tumor-specific antigens that can serve as the targets of an immune response, we took advantage of family-specific monoclonal antibodies, magnetic bead technology, and recombinant cytokines, which provided the previously precluded ability to isolate and expand populations of purified tumor and autologous CD8 cytotoxic T cells. Four patients with advanced cutaneous T-cell lymphoma had CD8 cells that specifically killed autologous tumor in a class I limited fashion. Tumor cell cytolysis could be specifically enhanced by pre-culture with autologous gamma-irradiated tumor. The cytolytic T cells produced tumor necrosis factor-alpha in response to stimulation with autologous tumor. The presence of tumor-specific cytotoxic T cells recognizing distinctive class I associated molecules on cutaneous T-cell lymphoma tumor cells suggests that infiltration of early lesions by CD8 cells reflects host immunity to the neoplasm. These studies provide the foundation for the development of tumor vaccines through the use of cytotoxic T cells to isolate and characterize tumor-associated cutaneous T-cell lymphoma peptides.

Antibody Formation↗
PubMed1995

Malignant and normal T cells show random use of T-cell receptor alpha chain variable regions in patients with cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) is a malignancy of mature T lymphocytes, most of which express alpha/beta type T-cell receptors (TCRs). The cause of CTCL is unknown, but hypotheses postulating chronic stimulation of TCRs by superantigen or by a leukemogenic virus have been proposed. Either mechanism might produce bias in the TCR variable (V) region types used by the malignant cells. To determine if TCR alpha use is restricted in CTCL, we used reverse transcription and the polymerase chain reaction to determine V alpha and V beta usage by malignant cells purified from the peripheral blood of leukemic patients with CTCL. Usage of alpha chain V region segments appeared totally random; malignant lymphocytes isolated from each of six patients used different V alpha regions. As has been previously reported, no bias was found in beta chain V region usage either. In addition to productive (in frame) TCR V region mRNAs in malignant cells from each patient, we detected non-productive (out of frame) beta chain transcripts in these cells in two of six patients, and non-productive alpha chain transcripts in five of six. Residual normal peripheral blood lymphocytes from these patients showed a random, polyclonal or oligoclonal pattern of V region usage. We conclude that there is no bias in V region usage in CTCL, making it unlikely that interactions between superantigen or virus and the TCR V regions play a role in the pathogenesis of CTCL.

Aged↗
PubMed1995

The immunopathogenesis of cutaneous T-cell lymphoma.

A perplexing array of immune abnormalities have been described in cutaneous T-cell lymphoma. This article discusses the mechanisms underlying these immune abnormalities. The immune processes that have become disordered are examined with reference to the steps involved in generating the disease and how these steps can be corrected therapeutically.

Cytokines↗
PubMed1994

Detection of clonal T-cell receptor gamma gene rearrangements in early mycosis fungoides/Sezary syndrome by polymerase chain reaction and denaturing gradient gel electrophoresis (PCR/DGGE).

We used a gene amplification strategy to analyze T-cell receptor (TCR) gene rearrangements in 185 specimens, including mycosis fungoides/Sezary syndrome (MF/SS), other cutaneous neoplasms, inflammatory dermatoses, reactive lymphoid tissues, and normal skin. Genomic DNA was extracted from lesional tissues and rearrangements of the TCR-gamma chain gene were amplified using the polymerase chain reaction (PCR) with primers specific for rearrangements involving V gamma 1-8 or V gamma 9 gene segments. The resulting PCR products were then separated according to their nucleotide sequence as well as size by denaturing gradient gel electrophoresis (DGGE). Dominant clonal TCR-gamma gene rearrangements were detected in 61 of 68 MF/SS cases by PCR/DGGE. This sensitivity of 90% compared to a sensitivity of only 59% when dominant clonality was sought in 17 of these same cases by Southern blot analysis of TCR-beta gene rearrangements. This difference in sensitivity was greatest in early, minimally infiltrated skin lesions. PCR/DGGE was also more sensitive than Southern blot analysis for detecting peripheral blood involvement in two cases of early MF. Among 12 additional specimens of suspected MF/SS, nine (75%) showed clonal TCR-gamma gene rearrangements by PCR/DGGE including six of eight cases with a previously confirmed diagnosis of MF/SS and three of four cases without prior known MF/SS. Among 105 non-MF/SS specimens, dominant TCR-gamma gene rearrangements were detected in only six cases (6%). Four were diagnosed as chronic dermatitis and two were diagnosed as cutaneous lymphoid hyperplasia. We conclude that the large majority of MF/SS cases, including patch phase disease, possess dominant clonal TCR-gamma gene rearrangements. PCR/DGGE is more sensitive than Southern blot analysis for detecting dominant clonality and staging disease in patients with a confirmed diagnosis of MF/SS. However, because PCR/DGGE is sensitive enough to detect dominant TCR-gamma gene rearrangements in a subset of patients with chronic dermatitis, it cannot be used as the sole criterion for establishing a diagnosis of T-cell lymphoma. As with other molecular biologic clonality assays, clinicopathologic correlation is essential. Nevertheless, the detection of dominant clonality in some cases of histologically nonspecific dermatitis allows the identification of a previously unrecognized subset of patients, i.e., those with "clonal dermatitis." It will be important to determine the long-term risk of MF/SS among these patients because our study indicated that MF/SS can sometimes present with lesions indistinguishable from clonal dermatitis.

Base Sequence↗
PubMed1994

Health services for special needs children in Pennsylvania schools.

School health programs traditionally have involved health services, health instruction, and a safe school environment. Likewise, school health services have been provided by nurses, physicians, and appropriate administrative personnel. In the 1990s, increased integration of primary care services through school-based clinics expanded traditional activities of school health programs. Consequently, more chronically ill children, particularly technology dependent children, have entered the regular school setting, requiring that schools be prepared to manage these chronically ill students who come to school with new morbidities and technological dependencies. This statewide survey examined the number and kind of special needs children in the regular school setting in Pennsylvania, as well as the personnel, programs, policies, and resources available to support these children.

Child↗
PubMed1994

Photoinactivated lymphocyte therapy of cutaneous T-cell lymphoma.

The unique aspects of this therapy are presented in this article to provide background information critical to understanding the clinical results, which are then presented. The laboratory models discussed in the later parts of this article demonstrate the dependence of this response on the photoinactivation of lymphocytes by 8-methoxypsoralen in the presence of ultraviolet-A light.

Blood Transfusion, Autologous↗
PubMed1994

Profound deficiency in normal circulating T cells in erythrodermic cutaneous T-cell lymphoma.

BACKGROUND AND DESIGN: To accurately assess tumor burden in cutaneous T-cell lymphoma as well as to determine the number of residual normal circulating T cells, it is necessary to accurately distinguish malignant cells. Because cutaneous T-cell lymphoma cells regularly display many normal phenotypic markers of T cells (CD2+, CD3+, CD4+) these surface proteins have been of limited value. We have used a set of monoclonal antibodies with specificity for those T-cell receptor proteins containing variable regions on the beta chain to distinguish normal from malignant T cells in patients with cutaneous T-cell lymphoma. RESULTS: The results revealed an unanticipated and profound expansion of the malignant cell populations (59% to 87% of blood T cells) in six patients with total T-cell counts in the normal or near normal range. By subtracting the percentages of malignant T cells, identified in this manner, from the total T-cell counts, we found that the residual normal T-cell compartments were small (0 to 0.155 x 10(9)/L) in four of the six patients. Sézary cell counts by peripheral blood smear analysis by routine light microscopy underestimated the number of malignant T cells. Markedly elevated CD4/CD8 ratios (10 to 90) occurred in all cases, reflecting expansion of the CD4+ malignant population and parallel reduction of the normal residual CD8+ subset. CONCLUSIONS: Patients with erythrodermic cutaneous T-cell lymphoma often have markedly depressed levels of normal blood T cells, to the range seen in advanced acquired immunodeficiency syndrome, and absolute numbers of malignant cells substantially exceed those recognized with less sensitive techniques.

CD4-CD8 Ratio↗
PubMed1993

An outbreak of mupirocin-resistant Staphylococcus aureus on a dermatology ward associated with an environmental reservoir.

OBJECTIVE: To investigate a cluster of mupirocin-resistant Staphylococcus aureus on a dermatology ward. DESIGN: An outbreak of mupirocin-resistant S aureus was noted on the dermatology ward during a prospective epidemiologic study of methicillin-resistant S aureus (MRSA) and borderline methicillin-susceptible S aureus (BMSSA). Pulsed-field gel electrophoresis (PFGE) of whole-cell DNA digested with Sma I was used as a marker of strain identity. SETTING AND PATIENTS: An 850-bed university hospital with a 12-bed inpatient dermatology ward. Most patients have severe, exfoliating dermatologic disorders. RESULTS: MRSA or BMSSA were isolated from 13 patients on the dermatology ward over a 14-month period. Eleven of these isolates (84.6%) were mupirocin-resistant. Nine isolates were present on admission (81.8%); 8 of these patients had been hospitalized on the same ward within the last two months. Nasal and hand cultures from 36 personnel were negative for mupirocin-resistant MRSA or BMSSA. Extensive environmental culturing revealed that a blood pressure cuff and the patients' communal shower were positive for mupirocin-resistant BMSSA. PFGE of all mupirocin-resistant isolates demonstrated that the nine patients and both environmental sources had identical DNA typing patterns. INTERVENTIONS: Changing of blood pressure cuffs between patients and more stringent cleaning of communal areas was initiated. Repeat environmental cultures were negative. CONCLUSIONS: S aureus is not usually associated with an environmental reservoir; however, these patients all had severe desquamation, which may have prolonged environmental contamination.

Blood Pressure Determination↗
PubMed1992

Correlations of unique clinical, immunotypic, and histologic findings in cutaneous gamma/delta T-cell lymphoma.

Cutaneous T-cell lymphoma is a malignancy of T cells that express a clone-specific heterodimer T-cell receptor for antigen. The second recognized case of an epidermotropic malignancy of T-cells expressing gamma/delta T-cell receptor-expressing cells is reported. The immunophenotype of the malignant T-cells was CD3+, CD2+, CD7+, gamma/delta T-cell receptor+, CD4-, CD8-, and alpha/beta T-cell receptor-. The clinical features were remarkable for extreme epidermotropism with a scant dermal lymphomatous infiltrate. Profound keratinocyte necrosis occurred in areas of malignant skin infiltrates. Despite cutaneous lesions covering more than 50% of the skin surface of the patient, no adenopathy or splenomegaly was detected. The intense epidermotropism of this patient's gamma/delta T-cell receptor-expressing cells and the putative cytolytic properties of CD4- CD8- gamma/delta contributed to the destruction of epidermis. Remission was induced with a combination of electron beam and extracorporeal photochemotherapy.

Antigens, CD↗
PubMed1992

Treatment of erythrodermic cutaneous T-cell lymphoma with extracorporeal photochemotherapy.

BACKGROUND: This original cohort of patients with erythrodermic cutaneous T-cell lymphoma (CTCL) was reported to have clinical improvement with photopheresis during the 12 months of the original study. No long-term follow-up data have been available to examine the impact of this therapy on the disease. OBJECTIVE: Our purpose was to provide long-term follow-up on the original 29 erythrodermic CTCL patients treated with photopheresis and to compare these results with historical controls. METHODS: Files of patients from the original photopheresis study centers were reviewed and their current status was documented. RESULTS: The median survival of the treated patients was 60.33 months from the date of diagnosis and 47.9 months from the date of the start of photopheresis therapy. A complete remission has been maintained in four of the six patients who achieved complete responses in the original study. The best responses were seen in patients with a lower CD4/CD8 ratio in the peripheral blood at the start of therapy. CONCLUSION: Photopheresis can influence the natural history of erythrodermic CTCL by inducing remissions and prolonging survival with minimal toxicity.

CD4-CD8 Ratio↗
PubMed1991

[The application of photopheresis in the therapy of cancerous and autoimmune diseases].

Photopheresis is an extracorporeal form of immunotherapy, recently approved by the FDA for the treatment of cutaneous T-cell lymphoma. During photopheresis lymphocytes are collected from the patients by leukapheresis and after exposure to psoralens and UVA reinfused to the host. The reinfused cells induce an immunological reaction against the neoplastic cells that seems to be clone specific. 37 CTCL patients have been initially treated; 1/4 showed a complete remission, 1/4 did not answer to the therapy and 1/2 showed a clinical improvement without complete remission. The best responders were patients in erythrodermic stage, particularly when photopheresis had been started early. The association with methotrexate induced a complete clinical remission in the cases with a partial answer to photopheresis. The average survival of patients treated with photopheresis was around 50 weeks in comparison with the Mycosis Fungoides Study Group data reporting for the same type of patients a 30 weeks survival using conventional therapies. Photopheresis has been recently used in the rejection control after heart transplantation and in the treatment of AIDS and several autoimmune diseases as pemphigus, sclerodermia, rheumatoid arthritis, LES. The preliminary therapeutic results are very encouraging for a larger use of photopheresis in the treatment of T cell mediated diseases.

Autoimmune Diseases↗
PubMed1987

Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results.

Systemically disseminated cutaneous T-cell lymphoma is generally resistant to chemotherapy and radiotherapy. We tested a treatment involving the extracorporeal photoactivation of biologically inert methoxsalen (8-methoxypsoralen) by ultraviolet A energy to a form that covalently cross-links DNA. After oral administration of methoxsalen, a lymphocyte-enriched blood fraction was exposed to ultraviolet A (1 to 2 J per square centimeter) and then returned to the patient. The combination of ultraviolet A and methoxsalen caused an 88 +/- 5 percent loss of viability of target lymphocytes, whereas the drug alone was inactive. Twenty-seven of 37 patients with otherwise resistant cutaneous T-cell lymphoma responded to the treatment, with an average 64 percent decrease in cutaneous involvement after 22 +/- 10 weeks (mean +/- SD). The responding group included 8 of 10 patients with lymph-node involvement, 24 of 29 with exfoliative erythroderma, and 20 of 28 whose disease was resistant to standard chemotherapy. Side effects that often occur with standard chemotherapy, such as bone marrow suppression, gastrointestinal erosions, and hair loss, did not occur. Although the mechanism of the beneficial effect is uncertain, an immune reaction to the infused damaged cells may have restricted the activity of the abnormal T cells. This preliminary study suggests that extracorporeal photochemotherapy is a promising treatment for widespread cutaneous T-cell lymphoma.

Administration, Oral↗