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Biomedical subjects

J T Wolfe

Publications and source records attributed to J T Wolfe.

At least 37 records · Page 2Linked to original sources
PubMed1996

Eosinophilic gastroenteritis presenting as a giant gastric ulcer.

We describe a 43-yr-old female with a giant gastric ulcer, refractory to medical treatment, that ultimately proved to be due to the mural form of eosinophilic gastroenteritis. The patient presented with a 6-month history of abdominal pain, diarrhea, and weight loss. Endoscopy showed a giant gastric ulcer, and biopsies revealed only chronic active ulcerative inflammation. The ulcer progressed on omeprazole therapy; therefore, a distal antrectomy with gastrojejunal anastomosis and bilateral vagotomy was performed. Pathology of the surgical specimen demonstrated the mural form of eosinophilic gastritis. To the best of our knowledge, this case is the first to demonstrate that refractory giant gastric ulcers may be a manifestation of the mural form of eosinophilic gastroenteritis.

Adult↗
PubMed1995

Successful ultraviolet B treatment of psoriasis is accompanied by a reversal of keratinocyte pathology and by selective depletion of intraepidermal T cells.

Skin irradiation with ultraviolet B (UVB) is a common and often durable treatment for psoriasis and other inflammatory skin disorders. We studied the effects of UVB on keratinocytes and leukocytes in psoriatic tissue and in culture. In nine patients treated repetitively, most of the cellular and molecular changes that typify the psoriatic epidermis reverted to normal. Keratinocyte hyperplasia, assessed by expression of the Ki-67 cell cycle antigen, decreased by 70%, and residual cell proliferation was appropriately confined to the basal layer. Epidermal thickening was reduced by 60%, and a granular layer reformed. Expression of keratin 16, as well as suprabasal integrin alpha 3 and insulin-like growth factor-1 receptors, was eliminated, whereas filagrin increased markedly. UVB also depleted > 90% of the CD3+, CD8+, and CD25+ T cells from the psoriatic epidermis, whereas dermal T cells were only minimally depressed. The latter finding parallels the known inability of these doses of UVB to penetrate the dermis. In tissue culture, UVB was antiproliferative and cytotoxic toward T cells and keratinocytes, but the T cells were 10-fold more sensitive. Furthermore, low doses of UVB induced apoptosis in lymphocytes but not keratinocytes, as detected by the TUNEL (TdT-mediated dUTP-biotin nick end labeling) technique. The selective effects of UVB on intraepidermal T cells in situ and in culture support the hypothesis that epidermal alterations in psoriasis can be normalized by a depletion of activated intraepidermal T cells.

Cells, Cultured↗
PubMed1995

Analysis of internucleosomal DNA fragmentation in apoptotic thymocytes by dynamic sieving capillary electrophoresis.

The analysis, by slab gel electrophoresis, of internucleosomal DNA cleavage or laddering, characteristic of apoptosis in many cell systems, is labour intensive, difficult to automate and at best only semi-quantitative. In this report we show that CE, using dilute solutions of hydroxyethylcellulose as a replaceable sieving matrix, can be applied to the relatively rapid analysis of DNA laddering in whole digests of apoptotic rat thymocytes. Also, using the sensitivity of laser-induced fluorescence detection and the highly sensitive nuclei acid stain YO-PRO-1, the CE method reported here can use 1000-2000 fold fewer cells than needed for traditional slab gel methods.

Animals↗
PubMed1995

Beneficial effect of low-dose systemic retinoid in combination with topical tretinoin for the treatment and prophylaxis of premalignant and malignant skin lesions in renal transplant recipients.

Renal transplant recipients experience a greatly increased frequency of neoplastic skin lesions, including aggressive squamous cell carcinomas. Recent reports suggest that high doses of systemic retinoids may exert a chemotherapeutic and chemoprophylactic effect. Similarly, topical retinoid, especially tretinoin, has also been shown to be anti-tumoragenic in various settings. Because of the serious toxicity of high-dose systemic retinoid, a protocol was developed that combined topical tretinoin with low-dose etretinate (10 mg daily) for the treatment of frequently occurring dysplastic skin lesions in renal transplant recipients. Seven patients elected to receive combined tretinoin and etretinate therapy, and 4 were treated with tretinoin alone. Clinical evaluations were performed monthly. By 3 months of therapy, 9 of 11 patients exhibited at least a 25% decrease in the number of neoplastic growths. After 6 months, 6 of 8 evaluable patients, including 2 of 3 individuals receiving tretinoin alone, exhibited at least a 50% decrease. Three of 4 patients on the combined regimen and 2 of 3 receiving tretinoin alone for at least 9 months, exhibited a significant decrease in the rate of development of new squamous cell cancers. At the start of treatment, epidermal specimens were almost completely devoid of Langerhans cells (CD1+ cells). Their density increased greatly and in proportion to the duration of therapy. Long term topical tretinoin with or without low-dose oral etretinate seems to be an effective regimen to suppress the development of new tumors and to reduce the numbers of existing lesions in renal transplant recipients.

Administration, Topical↗
PubMed1995

IL-12 reverses cytokine and immune abnormalities in Sezary syndrome.

Cutaneous T cell lymphoma is a lymphoproliferative disorder typically characterized by skin invasion of clonally derived malignant CD4+ lymphocytes that phenotypically resemble mature Th cells. Sezary syndrome (SzS) represents an advanced form of cutaneous T cell lymphoma associated with generalized erythroderma and involvement of the peripheral blood by the malignant cell population. We have previously demonstrated aberrant cytokine production by PBMC in SzS characterized by increased IL-4 and deficient IL-2 and IFN-gamma production, as well as increased expression of mRNA for IL-4 and IL-5 within active skin lesions, suggesting that the clonal T cell population is derived from the Th 2 subset of helper T lymphocytes. These findings have been associated with a constellation of immune abnormalities that have been attributed to the cytokine abnormalities. Because IL-12 is a potent inducer of IFN-gamma production, and causes the activation of cytotoxic lymphocytes, we examined the production of IL-12 by PBMC from SzS patients and whether IL-12 could alter the unfavorable cytokine balance typical of SzS and thus lead to correction of immune defects. Despite normal numbers of peripheral blood monocytes and normal TNF-alpha production, mean Staphyloccus aureus and LPS-induced IL-12 p40 and p70 production by SzS PBMC was significantly decreased compared with PBMC from normal controls. Mean IFN-gamma production by patient PBMC in response to PHA alone was depressed, but increased to levels comparable with normal after addition of 1 ng/ml IL-12. Pretreatment of PBMC for 24 h with IL-12, IFN-alpha, or both together resulted in a decrease in PHA-stimulated IL-4 production from a base line of 1818 pg/ml to 1520, 1350, and 1058 pg/ml, respectively. Lastly, culture of patient PBMC with IL-12 for 24 h also resulted in significant increases in NK activity against K562 cells. These results indicate that PBMC from patients with SzS manifest a defect in IL-12 production and that the cytokine abnormalities associated with SzS can be favorably altered by IL-12.

Cytokines↗
PubMed1995

De novo development of psoriatic plaques in patients receiving interferon alfa for treatment of erythrodermic cutaneous T-cell lymphoma.

Presumably because of its potent immunomodulatory activity, the use of interferon has led to the development of autoimmune disease in susceptible individuals. Because psoriasis is considered to be, in part, an autoimmune phenomenon, it is plausible that interferon may influence disease activity. We describe the development of psoriatic plaques in two patients without a history of this disease while they were receiving interferon alfa and extracorporeal photochemotherapy for erythrodermic cutaneous T-cell lymphoma. Paradoxically, in both patients the erythroderma resolved with subsequent de novo onset of psoriasis. This clinical sequence provides support for disparate immune mechanisms in the pathogenesis of these disorders, both of which are typified by lymphoid infiltrates. A review of the literature reveals that all forms of interferons have been associated with the exacerbation of psoriatic plaques, but that only interferon alfa has induced de novo development of psoriasis.

Adult↗
PubMed1995

Large-cell transformation following detection of minimal residual disease in cutaneous T-cell lymphoma: molecular and in situ analysis of a single neoplastic T-cell clone expressing the identical T-cell receptor.

PURPOSE: One of the unique characteristics of cutaneous T-cell lymphoma (CTCL) is its ability to undergo cytologic transformation in which the malignant T cells develop the morphologic appearance of a large-cell lymphoma. Reported to occur in up to 20% of advanced cases, large-cell transformation (LCT) is associated with an aggressive clinical course. Little is known about the risk factors or the molecular mechanisms of LCT. Before current immunohistochemical and molecular techniques, it was not possible to determine if LCT represented changes of the initial neoplastic T-cell clone or, in fact, was a distinct second malignancy. The goal of this study was to define the clonal evolution of LCT in CTCL. PATIENTS AND METHODS: Polymerase chain reaction (PCR) amplification of T-cell receptor-beta (TCR-beta) gene rearrangements and immunohistochemistry with monoclonal antibodies to TCR-V beta regions were used as markers of T-cell clonality to analyze the skin and peripheral blood of a patient with CTCL and LCT. RESULTS: We first detected the presence of minimal residual disease (MRD) in a CTCL patient with a complete clinical response to biologic response modifiers (BRMs). When clinical relapse occurred and demonstrated LCT, TCR-beta-PCR and in situ immunohistochemistry with a specific TCR-V beta monoclonal antibody identified a single neoplastic T-cell clone that expressed the identical TCR as the original clone. CONCLUSION: Our results confirm a common clonal origin for CTCL and LCT. We also provide evidence of MRD in CTCL by molecular analysis, implying that residual malignant cells maintain a potential for clinical relapse and possibly LCT. The role of MRD detection remains to be defined in the clinical assessment of CTCL. LCT in CTCL provides a unique model to investigate the molecular events that underlie terminal-stage tumor progression.

Amino Acid Sequence↗
PubMed1994

A role for metals and free radicals in the induction of apoptosis in thymocytes.

Recent reports have implicated a possible but undefined role for reactive oxygen species in the induction and mediation of apoptosis. In the present study, the role of free radicals and metal ions in apoptosis induced in rat thymocytes by dexamethasone and etoposide was examined. Copper chelators, but not iron specific chelators, inhibited apoptosis induced by both these stimuli. Several antioxidants also possessed potent inhibitory effects. We therefore propose that diverse agents may induce apoptosis in thymocytes by a common mechanism involving a copper mediated Fenton reaction, generating site specific hydroxyl radicals, possibly as a result of activation of the redox sensitive transcription factor NF-kappa B.

Animals↗
PubMed1994

DNA fragmentation into 200-250 and/or 30-50 kilobase pair fragments in rat liver nuclei is stimulated by Mg2+ alone and Ca2+/Mg2+ but not by Ca2+ alone.

Internucleosomal cleavage of DNA has often been regarded as the biochemical hallmark of apoptosis. We now demonstrate in isolated rat liver nuclei that DNA is initially cleaved into > or = 700, 200-250 kbp and 30-50 kbp fragments via a multi-step process, which is activated by Mg2+ and Mg2+(+)Ca2+ but not by Ca2+ alone. The subsequent internucleosomal cleavage requires both cations. These findings demonstrate that a key event in the apoptotic process is the fragmentation of DNA into large kbp fragments by either a Mg(2+)-dependent process (which can be potentiated by Ca2+) and/or by a Ca2+/Mg2+ activated endonuclease(s).

Animals↗
PubMed1994

Role of extracorporeal photopheresis in the treatment of cutaneous T-cell lymphoma, autoimmune disease, and allograft rejection.

Photopheresis is a pheresis-based therapy that is currently available at approximately 70 medical centers worldwide. Recent evidence indicates that extracorporeal photopheresis can significantly prolong life, as well as induce a 60-75% response rate among individuals with advanced cutaneous T-cell lymphoma (CTCL). Moreover, a 10-15% cure rate, in response to photopheresis alone, or in combination with interferon alfa, has been obtained at our institution. These complete responses have been characterized by the complete disappearance of morphologically atypical cells from the skin and blood. Southern blot analysis of peripheral blood specimens have also confirmed the indefinite disappearance of the malignant T-cell clone from the blood of patients with complete responses. Current immunological data obtained from in vitro human studies and from animal models suggest that the basis for the responses of CTCL patients are related to activation of treated macrophages resulting in release of cytokines, including substantial levels of TNF alfa, and, perhaps, to the induction of anti-clonotypic immunity directed against pathogenic clones of T-lymphocytes. In addition to the treatment of CTCL, a potential role for photopheresis in the therapy of autoimmune disease has been suggested by recent pilot studies of pemphigus vulgaris, rheumatoid arthritis, and systemic lupus erythematosus. Furthermore, a randomized, single-blinded trial involving 79 patients with early onset, aggressive systemic sclerosis suggested that photopheresis could beneficially effect the course of the cutaneous thickening in this form of the disease. Lastly, two independent pilot studies of cardiac transplantation have indicated that photopheresis can reverse acute cardiac allograft rejection and potentially suppress ongoing chronic rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoimmune Diseases↗
PubMed1994

Th2 cytokine mRNA expression in skin in cutaneous T-cell lymphoma.

We have previously demonstrated that peripheral blood mononuclear cells from patients with Sézary syndrome, the leukemic form of cutaneous T-cell lymphoma which is accompanied by erythroderma and lymphadenopathy, have a Th2 cell cytokine [interleukin 4 (IL-4) and interleukin 5] production pattern. In this study, we extend these observations to demonstrate a correlation of the presence of a Th2 cytokine pattern with a malignant T-cell clone in different stages of cutaneous involvement among patients with cutaneous T-cell lymphoma (CTCL). Skin biopsies were obtained from 12 CTCL patients with various disease stages (three patch, three plaque, six tumor), three patients with parapsoriasis, four patients with inflammatory dermatoses, including two psoriasis and two lichen planus, and 12 normal controls. Total RNA was extracted, reverse transcribed, and PCR amplified with IL-2, IL-4, IL-5, interferon gamma (IFN-gamma), and beta-actin oligonucleotide primers. Although all skin specimens tested had detectable IL-2 and IFN-gamma mRNA, only specimens from patients with CTCL or parapsoriasis had demonstrable IL-4 and/or IL-5 mRNA. Specifically, IL-5 mRNA was detected in skin biopsies from five of six tumor-stage CTCL, two of three plaque-stage CTCL, one of three patch-stage CTCL, and 1 of 3 parapsoriasis patients, whereas IL-4 mRNA was demonstrated to be present in five of six tumor-stage, one of three plaque stage, none of three patch-stage CTCL, and none of three parapsoriasis patients. These results indicate that in all stages of cutaneous involvement of CTCL, encompassing patch stage through tumor stage, IL-4 and IL-5 mRNA is variably detectable. In tumor-stage skin lesions, typically characterized by a dense dermal infiltrate of malignant T cells, Th2 cytokine mRNA is virtually always detectable. The ability to detect Th2 cytokine mRNA in the skin of patients with CTCL supports our previous findings that the malignant T cells in CTCL possess a Th2-helper cell phenotype.

Base Sequence↗
PubMed1994

Review of immunomodulation by photopheresis: treatment of cutaneous T-cell lymphoma, autoimmune disease, and allograft rejection.

Photopheresis is an apheresis-based therapy that is currently available at approximately 70 medical centers worldwide. Recent evidence indicates that extracorporeal photopheresis can significantly prolong life as well as induce a 60-75% response rate among individuals with advanced cutaneous T-cell lymphoma (CTCL). Moreover, a 10-15% cure rate, in response to photopheresis alone, or in combination with interferon-alpha, has been obtained at our institution. These complete responses have been characterized by the complete disappearance of morphologically atypical cells from the skin and blood. Southern blot analysis of peripheral blood specimens has also confirmed the indefinite disappearance of the malignant T-cell clone from the blood of patients with complete responses. Current immunological data obtained from in vitro human studies and from animal models suggest that the basis for the responses of CTCL patients are related to activation of treated macrophages resulting in release of cytokines, including substantial levels of tumor necrosis factor alpha (TNF-alpha), and perhaps, to the induction of anticlonotypic immunity directed against pathogenic clones of T lymphocytes. In addition to the treatment of CTCL, a potential role for photopheresis in the therapy of autoimmune disease has been suggested by recent pilot studies of pemphigus vulgaris, rheumatoid arthritis, and systemic lupus erythematosus. Furthermore, a randomized, single-blinded trial involving 79 patients with early onset, aggressive systemic sclerosis suggested that photopheresis could benefically affect the course of the cutaneous thickening in this form of the disease. Lastly, two independent pilot studies of cardiac transplantation have indicated that photopheresis can reverse acute cardiac allograft rejection and potentially suppress ongoing chronic rejection. Randomized, controlled trials for these new indications for photopheresis therapy are currently in the early stages of implementation.

Animals↗
PubMed1993

Symptomatic gastric amyloidosis in patients with primary systemic amyloidosis.

We reviewed the clinical records of 769 patients with primary systemic amyloidosis who had been examined at Mayo Clinic Jacksonville (Jacksonville, Florida) or Mayo Clinic Rochester (Rochester, Minnesota) during a 12-year period (1978 through 1989). Of these 769 patients, 59 (8%) had biopsy-established gastrointestinal amyloidosis, and 8 (1%) had symptomatic gastric amyloidosis. All eight patients with symptomatic gastric amyloidosis had hematemesis or prolonged nausea and vomiting in association with weight loss. Additional findings were gastroparesis (in three patients), gastric tumor (in one), and gastric outlet obstruction (in one). Macroglossia was present in two patients, and multiple myeloma was diagnosed in three. Six of the eight patients had coexisting small bowel amyloidosis and weight losses of 6.5 to 22.5 kg. Congo red staining identified gastric amyloid in the media of blood vessels in all cases. All cases stained selectively for lambda (seven cases) or kappa (one) light chain. All eight patients died; the median duration of survival after diagnosis was 13.8 months (range, 0.5 to 39.5). Death was due to cardiac failure (three patients), renal failure (two), chronic gastrointestinal obstruction and severe cachexia (two), or hepatic failure (one). Chemotherapy was given to seven patients but was only partially effective for ameliorating symptoms in one.

Amyloidosis↗
PubMed1991

Tricuspid valve papillary fibroelastoma: echocardiographic characterization.

We report a tricuspid valve papillary fibroelastoma initially detected by transthoracic two-dimensional echocardiography and subsequently characterized by transesophageal two-dimensional echocardiography. The mass was excised during open heart operation, and the diagnosis was verified grossly and histopathologically. Transesophageal echocardiography usually provides images far superior to those from transthoracic echocardiography and may be a useful adjunct for intraoperative localization of intracardiac tumors for excision.

Aged↗
PubMed1988

Pathology of the cardiac conduction system in myotonic dystrophy: a study of 12 cases.

In 12 autopsy cases of myotonic dystrophy, the most frequently observed histopathologic lesions of the cardiac conduction system were fibrosis, fatty infiltration and atrophy. Fibrosis involved the sinus node in 6 cases, atrioventricular (AV) node in 7, AV bundle in 8, bundle branches in 10 and ventricular myocardium in 11. Fatty infiltration was observed in the sinus node in two cases, AV node in two, AV bundle in six, bundle branches in one and ventricular myocardium in nine. Atrophy was prominent in the AV bundle in five and bundle branches in eight. Lymphocytes infiltrated the conduction system in three cases and were associated with myotonic dystrophy in two and varicella myocarditis in one. Ventricular myocytes were hypertrophied in seven cases, vacuolated in three and exhibited disarray in two. The distribution and extent of conduction system lesions tended to correspond to antemortem electrocardiographic abnormalities, including prolonged PR interval in six cases, intraventricular conduction delay in six and bundle branch block in four. Cardiac involvement by myotonic dystrophy may have contributed to sudden death in four cases.

Adolescent↗
PubMed1988

Perioral keratoacanthomas with extensive perineural invasion and intravenous growth.

Four patients had squamous tumors of the perioral skin with clinical and microscopic hallmarks of keratoacanthoma. In addition, the lesions exhibited extensive perineural invasion and intravenous growth. Two of the tumors recurred soon after excision and required additional surgery. In another case, two subsequent keratoacanthomas developed in adjacent skin. There were no further recurrences after follow-up periods of 7, 24, 42, and 44 months. Lesions in two patients were extremely painful. Perineural invasion was found in each of nine pathologic specimens. The number of involved nerves in single sections of each lesion ranged from two to 59 and exceeded 20 in four specimens from three patients. Intravenous growth by keratoacanthoma was seen in five specimens from three patients. Nine veins were affected in one instance and four in another. Several of the tumors had a dispersed and deeply infiltrative pattern of growth. Measuring vertically from the surface of the lesion, the deepest focus of perineural invasion observed in the four patients ranged from 4.2 to 17 mm. Keratoacanthomas with this unusual constellation of findings may have a predilection for the central portion of the face.

Adult↗