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Biomedical subjects

J W Patterson

Publications and source records attributed to J W Patterson.

At least 19 recordsLinked to original sources

Evaluation of peptide vaccine immunogenicity in draining lymph nodes and peripheral blood of melanoma patients.

Many peptide epitopes for cytotoxic T lymphocytes (CTLs) have been identified from melanocytic differentiation proteins. Vaccine trials with these peptides have been limited mostly to those associated with HLA-A2, and immune responses have been detected inconsistently. Cases of clinical regression have been observed after peptide vaccination in some trials, but melanoma regressions have not correlated well with T-cell responses measured in peripheral blood lymphocytes (PBLs). We vaccinated stage IV melanoma patients with a mixture of gp100 and tyrosinase peptides restricted by HLA-A1 (DAEKSDICTDEY), HLA-A2 (YLEPGPVTA and YMDGTMSQV) and HLA-A3 (ALLAVGATK) in an emulsion with GM-CSF and Montanide ISA-51 adjuvant. CTL responses were assessed in PBLs and in a lymph node draining a vaccine site (sentinel immunized node, SIN). We found CTL responses to vaccinating peptides in the SIN in 5/5 patients (100%). Equivalent assays detected peptide-reactive CTLs in PBLs of 2 of these 5 patients (40%). CTLs expanded from the SIN lysed melanoma cells naturally expressing tyrosinase or gp100. We demonstrated immunogenicity for peptides restricted by HLA-A1 and -A3 and for 1 HLA-A2 restricted peptide, YMDGTMSQV. Immune monitoring of clinical trials by evaluation of PBLs alone may under-estimate immunogenicity; evaluation of SIN provides a new and sensitive approach for defining responses to tumor vaccines and correlating these responses with clinical outcomes. This combination of an immunogenic vaccine strategy with a sensitive analysis of CTL responses demonstrates the potential for inducing and detecting anti-tumor immune responses in the majority of melanoma patients.

Adult↗

Effects of external beam irradiation on the TRAM flap: an experimental model.

The rat model of the transverse rectus abdominis musculocutaneous (TRAM) flap was used in the present study to determine the effects of external beam radiation on myocutaneous flap histology and pathophysiology. A total of 57 adult Sprague-Dawley rats underwent a TRAM procedure. A pilot study with 17 animals was first performed to determine proper radiation dosages, and the remaining 40 rats were then used in the definitive study. In half of the definitive study group, the flaps were subjected to fractionated doses of external beam radiation, whereas the other half served as controls. Six weeks after the last radiation dose, all animals were killed and the flaps were harvested for mechanical assessment and histopathologic evaluation. All TRAM flaps survived in both groups. The irradiated and nonirradiated flaps were minimally distinguishable in viscoelastic properties, as well as by histopathologic examination. Growth of the flap in the irradiated animals was significantly diminished (48 percent average surface area increase in irradiated flaps, versus 92 percent increase in nonirradiated flaps, p < 0.05). These findings suggest that the myocutaneous flap is relatively resistant to some of the known adverse affects of radiation on living tissues.

Animals↗

Linear syringocystadenoma papilliferum of the thigh.

Syringocystadenoma papilliferum usually arises in the head and neck region. Linear lesions occurring in other locations are rare. We report such a case occurring on the thigh, documented by multiple biopsy specimens. The case is discussed in the context of other adnexal tumors that may form linear arrangements.

Adolescent↗

Onychomatricoma: report of a case and its comparison with fibrokeratoma of the nailbed.

Onychomatricoma was first described in 1992 by Baran and Kint. Twenty cases have been reported to date, all of which are from Europe. This tumor has characteristic clinical, light microscopic, and ultrastructural features which have recently been refined andjustify its categorization as a novel tumor of the nail matrix. We examined a specimen sent in consultation by a large reference laboratory; despite improper orientation and absence of the involved nail plate, it had microscopic characteristics consistent with onychomatricoma. Soon thereafter, a second patient presented with a tumor arising in the nailbed that bore a superficial resemblance to onychomatricoma but showed the microscopic features of fibrokeratoma. We discuss the differentiation between these two lesions and point out that a distinction can be made even when incomplete material is submitted for review. To our knowledge, this is the first example of onychomatricoma to be reported from North America.

Adult↗

Relationship of physical activity to fundamental movement skills among adolescents.

PURPOSE: To determine the relationship of participation in organized and nonorganized physical activity with fundamental movement skills among adolescents. METHODS: Male and female children in Grade 8 (mean age, 13.3 yr) and Grade 10 (mean age, 15.3 yr) were assessed on six fundamental movement skills (run, vertical jump, catch, overhand throw, forehand strike, and kick). Physical activity was assessed using a self-report recall measure where students reported the type, duration, and frequency of participation in organized physical activity and nonorganized physical activity during a usual week. RESULTS: Multiple regression analysis indicated that fundamental movement skills significantly predicted time in organized physical activity, although the percentage of variance it could explain was small. This prediction was stronger for girls than for boys. Multiple regression analysis showed no relationship between time in nonorganized physical activity and fundamental movement skills. CONCLUSION: Fundamental movement skills are significantly associated with adolescents' participation in organized physical activity, but predict only a small portion of it.

Adolescent↗

Merkel cell carcinoma (neuroendocrine carcinoma of the skin).

We review the literature on Merkel cell carcinoma (MCC; primary neuroendocrine carcinoma of the skin) and add 36 cases to the over 800 already described in the literature. Though generally considered a tumor of the elderly, MCC can also occur in young patients. Microscopically, there are dermal proliferations of small cells possessing nuclei with finely dispersed chromatin. The occasional presence of squamous or eccrine differentiation suggests a pluripotential stem cell origin. Immunohistochemistry is of great help in distinguishing these tumors from potential mimics such as malignant melanoma, lymphoma, or metastatic small cell (neuroendocrine) carcinomas. Recent chromosomal studies have enhanced our understanding of the biology of these tumors. Despite the high metastatic rate associated with Merkel cell carcinoma, spontaneous regression has been reported, and there have been some therapeutic successes. The high survival rate for stage I lesions indicates the importance of early recognition and treatment of these tumors.

Carcinoma, Merkel Cell↗

Analysis of a natural immune response against tumor antigens in a melanoma survivor: lessons applicable to clinical trial evaluations.

The long-term survival of some patients with metastatic melanoma may be attributable in part to cellular immune responses to melanoma antigens. However, little is known about the level of CTL reactivity in vivo that is required for immunological control of tumor progression. In the present report, T-cell responses were evaluated with lymphocytes obtained from tumor-involved nodes and peripheral blood of a long-term melanoma survivor. Using an ELISPOT assay, naturally occurring functional T cells, which recognize the peptide ALLAVGATK (gp100(17-25)) plus two other HLA-A3 restricted peptides, were detected in a tumor-involved lymph node. The ALLAVGATK-reactive T cells were also evaluated by MHC-tetramers staining and were found to be CD8+ CD45RO+ L-selectin(-) CD11a+, suggesting that they are antigen experienced and have a memory phenotype. Unstimulated peripheral blood lymphocytes from the same patient demonstrated no detectable T-cell responses; however, a single stimulation with ALLAVGATK peptide in vitro resulted in a dramatic expansion of peptide-reactive CTLs. This patient, with evidence of tumor-reactive CTLs targeted to several tumor antigens in a tumor-involved lymph node and with evidence of a circulating memory T-cell response, has remained disease-free for 6 years, despite prior bulky nodal metastasis. In contrast, three HLA-A3+ patients with rapidly progressive metastatic melanoma had no detectable T-cell response in tumor-involved nodes or peripheral blood lymphocytes, even after peptide stimulation ex vivo. The presented data are consistent with a systemic polyvalent immune response against tumor in this long-term survivor. These data provide an estimate of the level of CTL response that may be associated with protection from tumor recurrence.

Antigens, Neoplasm↗

Phase I trial of a melanoma vaccine with gp100(280-288) peptide and tetanus helper peptide in adjuvant: immunologic and clinical outcomes.

A melanoma vaccine composed of HLA-A2-restricted peptide YLEPGPVTA (gp100(280)), with or without a modified T-helper epitope from tetanus toxoid AQYIKANSKFIGITEL, has been evaluated in a Phase I trial to assess safety and immunological response. The vaccines were administered s.c. in either of two adjuvants, Montanide ISA-51 or QS-21, to 22 patients with high-risk resected melanoma (stage IIB-IV). Local and systemic toxicities were mild and transient. We detected CTL responses to the gp100(280) peptide in peripheral blood in 14% of patients. Helper T-cell responses to the tetanus helper peptide were detected in 79% of patients and had a Th1 cytokine profile. One patient with a CTL response to gp100 had a recurrence in a lymph node 2 years later; her nodes contained CD8+ cells reactive to gp100(280) (0.24%), which proliferated in response to peptide. The overall survival of patients is 75% (95% confidence interval, 57-94%) at 4.7 years follow-up, which compares favorably with expected survival. Four of 14 patients who completed at least six vaccines subsequently developed metastases, all of which were solitary and surgically resectable. They remain alive and clinically free of disease at last follow-up. Data from this trial demonstrate immunogenicity of the gp100(280) peptide and suggest that immune responses may persist long-term in some patients. The frequency and magnitude of the CTL response may be improved with more aggressive vaccination regimens. Although this Phase I study was not intended to evaluate clinical benefit, the excellent survival of patients on this protocol suggests the possibility of a benefit that should be assessed in future studies.

Adjuvants, Immunologic↗

Desmoplastic malignant melanoma of the palatal alveolar mucosa: sustained disease-free survival after surgery and postoperative radiotherapy.

Aggressive surgical and radiotherapeutic management of a patient with desmoplastic malignant melanoma arising from the mucosa of the oral cavity has resulted in disease-free survival of more than 2(1/2) years after diagnosis. This case represents only the tenth reported instance of desmoplastic malignant melanoma arising from the oral cavity and only the third for which survival has exceeded 2 years. Details of the clinical, histopathologic, and therapeutic features of the case are provided to augment the paucity of literature available to clinicians managing this rare disease.

Alveolar Process↗

Lipedematous alopecia: a clinicopathologic, histologic and ultrastructural study.

Lipedematous alopecia is a rare condition of unknown etiology characterized by a thick, boggy scalp with varying degrees of hair loss that occurs in adult black females, with no clearly associated medical or physiologic conditions. The fundamental pathologic finding consists of an approximate doubling in scalp thickness resulting from expansion of the subcutaneous fat layer in the absence of adipose tissue hypertrophy or hyperplasia. Observations by light and electron microscopy detailed in this report suggest that this alteration principally manifests by localized edema with disruption and degeneration of adipose tissue. Some diminution in the number of follicles as well as focal bulb atrophy is noted. Aberrant mucin deposition such as that seen in myxedema or other cutaneous mucinoses is not a feature. The histologic findings bear some resemblance to those seen in lipedema of the legs, a relatively common but infrequently diagnosed condition. We present a case of lipedematous alopecia with emphasis on histologic and ultrastructural features. The etiology is unknown.

Adipose Tissue↗

Squamous cell carcinoma arising in Hailey-Hailey disease.

Hailey-Hailey disease is a recurrent, autosomal dominant vesiculobullous dermatotis with a predilection for intertrigenous areas. We report what we believe to be the first case of squamous cell carcinoma arising de novo in a skin lesion of Hailey-Hailey disease. The occurrence of malignant neoplasms arising in the skin lesions of Hailey-Hailey disease and other acantholytic dermatoses is reviewed.

Carcinoma, Squamous Cell↗

Cutaneous deciduosis.

Cutaneous deciduosis is an exceedingly rare manifestation of endometriosis potentially mistaken for malignancy and thus far documented solely within surgical scars. We describe two additional cases, one occurring in a pregnant 21-year-old woman as a solitary flat erythematous vulvar papule, an extraordinary location not previously recorded. Histologic examination in that case revealed a subepithelial nodular aggregate of atypical large dyscohesive cells with accompanying edema and inflammation. An immunohistochemical panel showed positivity of the cells for vimentin and Ki-1 (CD30). Intracellular sulfated mucin and glycogen were also demonstrated. In a second case, a 27-year-old woman had a nodule at the umbilicus, removed incidentally during the course of cesarean section. Microscopically there were several circumscribed, multilobulated, intradermal nodules with variably sized lumens formed by crowded large epithelioid cells. The disparate histologic appearance of these examples highlights an essential challenge in their diagnosis. Clinical recognition is difficult unless suggested by more characteristic history or location.

Adult↗

Aortic angiosarcoma presenting with cutaneous metastasis: case report and review of the literature.

Aortic angiosarcoma is a rare malignancy. Clinical diagnosis is difficult, as the presenting symptoms mimic more common aortic lesions, particularly atherosclerosis. Dermatologists and dermatopathologists play a critical role in recognizing cutaneous metastases as a manifestation of this life-threatening tumor. We describe the fourth case of aortic angiosarcoma in the literature with initial presentation in the skin.

Aorta, Abdominal↗

Sudden onset of disseminated porokeratosis of Mibelli in a renal transplant patient.

Porokeratosis is a disorder of epidermal keratinization of uncertain cause. Five clinical variants of porokeratosis have been described. These include porokeratosis of Mibelli, punctate porokeratosis, linear porokeratosis, porokeratosis palmaris plantaris et disseminata, and disseminated superficial porokeratosis. Disseminated superficial porokeratosis and single plaque porokeratosis of Mibelli have each been documented to occur in association with immunosuppression. To our knowledge, only 5 cases of disseminated porokeratosis of Mibelli in transplant recipients have been reported. We present a patient who developed explosive onset of disseminated porokeratosis of Mibelli shortly after renal transplantation. It is important to differentiate this unusual variety of porokeratosis from other cutaneous manifestations in transplant patients so that appropriate therapy can be instituted.

Humans↗