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Biomedical subjects

T J Harrist

Publications and source records attributed to T J Harrist.

At least 19 recordsLinked to original sources
PubMed1995

Increased expression of vascular permeability factor (vascular endothelial growth factor) in bullous pemphigoid, dermatitis herpetiformis, and erythema multiforme.

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), plays an important role in the increased vascular permeability and angiogenesis associated with many malignant tumors. In addition, VPF/VEGF is strongly expressed by epidermal keratinocytes in wound healing and psoriasis, disorders that are also characterized by increased microvascular permeability and angiogenesis. In this study, we investigated the expression of VPF/VEGF in three bullous diseases with subepidermal blister formation that are characterized by hyperpermeable dermal microvessels and pronounced papillary dermal edema. The expression of VPF/VEGF mRNA was strongly up-regulated in the lesional epidermis of bullous pemphigoid (n = 3), erythema multiforme (n = 3), and dermatitis herpetiformis (n = 4) as detected by in situ hybridization. Epidermal labeling was particularly intense over blisters, but strong expression was also noted in areas of the epidermis adjacent to dermal inflammatory infiltrates at a distance from blisters. Moreover, the VPF/VEGF receptors, flt-1 and KDR, were up-regulated in endothelial cells in superficial dermal microvessels. High levels of VPF/VEGF (138-238 pM) were detected in blister fluids obtained from five patients with bullous pemphigoid. Addition of blister fluid to human dermal microvascular endothelial cells exerted a dose-dependent mitogenic effect that was suppressed after depletion of VPF/VEGF by immunoadsorption. These findings strongly suggest that VPF/VEGF plays an important role in the induction of increased microvascular permeability in bullous diseases, leading to papillary edema and fibrin deposition and contributing to the bulla formation characteristic of these disorders.

Adult↗
PubMed1991

Systematic underreporting of cutaneous malignant melanoma in Massachusetts. Possible implications for national incidence figures.

An independent tabulation of incidence of cutaneous malignant melanoma in Massachusetts indicates that 12% and perhaps as many as 19% of new cases of cutaneous malignant melanoma in Massachusetts are not recorded in the Massachusetts Cancer Registry, significantly more than the expected 5% (p = 0.0001). The increasing number of nonhospital medical settings in which melanomas can be diagnosed and/or treated appears to account for this discrepancy. We suspect that these findings in Massachusetts also apply to cancer reporting systems in other regions of the United States. We suggest that the true incidence of cutaneous malignant melanoma in Massachusetts, and perhaps in the United States, may be significantly higher than reported.

Humans↗
PubMed1987

Lymphomatoid papulosis following Hodgkin's disease.

Lymphomatoid papulosis has occurred in association with Hodgkin's disease. In all cases previously described, Hodgkin's disease has developed after, or concurrently with, the onset of lymphomatoid papulosis. Two patients who developed lymphomatoid papulosis 1 and 10 years after the diagnosis and therapy for advanced Hodgkin's disease are reported. The purpose of this report is to document this unusual sequence.

Adult↗
PubMed1986

Chondrosarcoma of the temporal bone. Diagnosis and treatment of 13 cases and review of the literature.

Chondrosarcoma of the temporal bone is a rare lesion. Clinically it has been confused with multiple sclerosis, glomus jugulare tumors, meningioma, and chordomas. The cranial nerve palsies frequently observed with the tumors are related to the anatomic locations of the tumors. Thirteen patients with this entity are presented and the eleven other cases in the literature are reviewed. Histologically the tumors are low grade and exhibit myxoid features. The myxoid features must be differentiated from chordoma and chondroid chordoma. The tumor locations preclude surgical excision and conventional radiation therapy can cause unacceptable neurologic sequelae. Proton beam therapy has been effective in short-term results and appears capable of avoiding serious neurologic side effects.

Adolescent↗
PubMed1986

Dermatitis herpetiformis. Cutaneous deposition of polyclonal IgA1.

Dermatitis herpetiformis (DH) is a pruritic papulovesicular skin disorder of unknown cause, characterized by granular IgA deposits in the dermis along the dermoepidermal junction. It is associated with gluten-sensitive enteropathy and increased IgA production by gut lymphoid tissue. We report four cases of immunologically documented DH studied by immunofluorescence technique. Monoclonal antibodies against the IgA subclasses IgA1 and IgA2 were used. IgA1 without IgA2 was found in the cutaneous deposits in each case. The IgA1 had both kappa and lambda light chains in approximately equal quantities. Because normal gut-associated lymphoid tissue produces 70% IgA1 and 30% IgA2, while circulating IgA is primarily IgA1, it could be concluded that the IgA in the skin of DH patients is not produced in the gut. However, the subclass restriction of the IgA produced by pathologic gut-associated lymphoid tissue is unknown. Alternatively, both IgA1 and IgA2 may be produced by the gut, but only IgA1 is involved in the production of cutaneous lesions.

Animals↗
PubMed1985

Congenital arrector pili hamartoma. A case report and review of the spectrum of Becker's melanosis and pilar smooth-muscle hamartoma.

Congenital pigmented arrector pili hamartomas are unique malformations of epidermis and pilar apparatus usually appearing as localized, lightly pigmented, hairy plaques. Characteristic microscopic features include smooth-muscle proliferation similar to irregularly disposed arrectores pilorum, and slight elongation of epidermal rete with hypermelanosis of the basal unit. An otherwise normally developed child who had this hamartoma at birth is described in an attempt to clarify the relationship between pilar smooth-muscle hamartomas and Becker's melanosis. We propose that these two entities belong at different poles of the same developmental spectrum of hamartomatous change.

Diagnosis, Differential↗
PubMed1985

Immunopathologic studies of adult linear IgA bullous dermatosis.

Three cases of adult linear IgA bullous dermatosis were examined to determine the types of IgA present in the basement membrane zone. IgA 1 subclass, without IgA2, was identified in all three cases; J chain was identified in only one case. Secretory component was absent in all cases. Two observations can be made from this study. First, the predominance of monomeric IgA1 is more compatible with the pattern of antibody secretion of plasma cells present in extragut sites than in intestinal sites. These findings are further evidence of the distinction between dermatitis herpetiformis, which has polymeric IgA1, and adult linear IgA bullous dermatosis and may suggest an extragut site for the origin of the antibodies. The second observation is that the antibodies in adult linear IgA bullous dermatosis show limited expression of heavy and light chains and molecular size that cannot be explained by origin in any compartment. The origin of this limitation cannot be determined from the present data, but possible explanations include a monoclonal or oligoclonal origin of the plasma cells secreting the anti-basement membrane antibodies, genetic restriction of either the immunoglobulin repertoire or helper T-cell response such that only an IgA subpopulation is permitted to be produced in response to the antigen, and selective absorption from the sera or deposition in the skin.

Adult↗
PubMed1985

A histologic comparison of congenital and acquired nevomelanocytic nevi.

A reliable microscopic differentiation of nevomelanocytic nevi (NMNs) as congenital or acquired would be useful in defining a histogenic relationship between cutaneous melanoma and congenital NMN. In order to delineate histologic differences between congenital NMN and acquired NMN, a standardized assessment was conducted blindly, using a sample of consecutive surgical specimens of NMN submitted to a children's hospital pathology file. Despite significant histologic differences between congenital NMN and acquired NMN, the lack of a reliable prevalence rate for the proportion of congenital NMNs among all NMN specimens submitted for pathologic examination precludes a precise estimate of predictive value for diagnosing a given NMN as congenital or acquired based on histologic features alone. The results of this study can be used neither to support nor to refute a histologic association between cutaneous melanoma and congenital NMN.

Adolescent↗
PubMed1984

"Microscopic satellites" are more highly associated with regional lymph node metastases than is primary melanoma thickness.

A multivariate analysis was performed on 20 clinical and histologic variables from 327 Stage I prospectively studied melanoma patients who underwent elective regional lymph node dissection (ERLD). Primary tumor thickness, microscopic satellites, and the elapsed interval between diagnosis and ERLD, were selected as the combination of variables that were most highly associated with clinically occult regional lymph node metastases (P = 10(-15), model chi-square). Microscopic satellites were defined as tumor nests, greater than 0.05 mm in diameter, in the reticular dermis, panniculus, or vessels beneath the principal invasive tumor mass but separated from it by normal tissue on the section in which the Breslow measurement was taken. The probability of finding nodal metastases for melanomas less than 0.75 mm thick was 0% (0/41 patients); for those 0.76-1.50 mm, 4% (4/108); 1.51-3.0 mm, 14% (14/102); and greater than 3.0 mm, 39.5% (30/76). Primary melanomas greater than 1.50 mm thick with microscopic satellites were more often associated with nodal metastases than those of similar thickness without satellites (30/57 (53%) versus 14/121 (12%), P = 0.01). Some satellites probably represent intraspecimen metastases, while others do not. Any predictive model for occult regional lymph node metastases based on data from ERLD done less than 50 days after diagnosis may underestimate the prevalence of metastases.

Adult↗
PubMed1984

Immunopathology of pityriasis lichenoides acuta.

Eleven biopsy specimens (five papules and six dusky or crusted lesions) from four patients with pityriasis lichenoides et varioliformis acuta ( PLEVA ) were studied by direct immunofluorescence and immunoperoxidase technics. Slight vascular deposits of IgM and C3 were present in most lesions. Slight perivascular deposits of fibrin were observed in early lesions; more extensive perivascular and interstitial deposits of fibrin were detected in advanced lesions. Most of the infiltrating cells were T lymphocytes; cells with cytotoxic/suppressor phenotype (T8-positive) were generally more numerous than cells with helper/inducer phenotype (Leu-3a-positive, T4-positive). A marked increase in epidermal T8-positive cells over epidermal Leu-3a/T4-positive cells was found in late lesions. Moreover, a reduction of the ratio of circulating T4-positive to T8-positive cells was observed in most cases. The number of epidermal T6-positive (Langerhans/indeterminate) cells was decreased in the lower as compared with the upper stratum spinosum. About 5% of perivascular infiltrating cells were T6-positive. These results suggest that cell-mediated immune mechanisms are probably important in the pathogenesis of PLEVA .

Adult↗
PubMed1984

Neutrophilic eccrine hidradenitis: a distinctive rash associated with cytarabine therapy and acute leukemia.

Neutrophilic eccrine hidradenitis (NEH) is a recently described neutrophilic dermatosis associated with acute myelogenous leukemia (AML) and chemotherapy. This disorder is a distinct clinicopathologic entity separate from leukemid reactions and other neutrophilic dermatoses. We describe two cases in which plaques or nodules developed in the second week after initiation of induction chemotherapy for AML. The lesions regressed in 1 week and recurred in one case when induction chemotherapy was given a second time. Histologically, the findings were similar in each case. Neutrophils palisaded about and infiltrated the eccrine coil in which necrosis of secretory epithelium was present. Focal mucinous degeneration of the eccrine adipose tissue cuff was the only other significant alteration. No vasculitis was observed. Cultures and histologic preparations for pathogenic organisms were negative. Cytarabine was the chemotherapeutic agent used in all three cases. NEH most likely represents either an unusual response caused by cytarabine or a manifestation of AML. Recognition of NEH is important in order to exclude other neutrophilic dermatoses associated with AML, such as sepsis and leukemia cutis, which may appear clinically similar.

Cytarabine↗
PubMed1984

Mucocutaneous lentigines, cardiomucocutaneous myxomas, and multiple blue nevi: the "LAMB" syndrome.

We describe a 13-year-old girl with a cardiocutaneous syndrome characterized by an atrial myxoma, pigmented lesions of the skin and genital mucosa, and opalescent papules and dermal nodules of the skin and tongue. Her pigmented lesions included black macules of the face and vulva, brown macules of the lips and perioral skin, multiple blue nevi, and a congenital nevomelanocytic nevus. The black and brown macules of the face and vulva consisted of lentiginous proliferations of large, intensely dopa-reactive melanocytes. The opalescent papules and dermal nodules had histologic, ultrastructural, and histochemical characteristics of myxomas. During follow-up, the patient developed thyroid nodules, which were composed of mixed papillary and follicular hyperplasia. This case emphasizes the necessity of a cardiac evaluation for a potentially fatal (and surgically treatable) atrial myxoma in individuals with multiple melanocytic and myxomatous tumors of the skin and mucosa.

Adolescent↗
PubMed1984

Linear IgA bullous dermatosis v dermatitis herpetiformis. Quantitative measurements of dermoepidermal alterations.

Linear IgA bullous dermatosis (LAD), also known as "atypical dermatitis herpetiformis," is a disorder that is distinct from classic dermatitis herpetiformis (DH). In eight patients with DH and six with LAD, quantitative assessment of a variety of histopathologic variables was made. The number of rete tips with neutrophils in basal vacuoles and the length of the epidermal basement membrane zone (BMZ) associated with these findings were greater in LAD than DH. The number of microabscesses of neutrophils in the dermal papillae and the length of epidermal BMZ associated with them were greater in DH than in LAD. By using the number of microabscesses and the number of rete tips with neutrophils in basal vacuoles in a probability model, we found by retrospective analysis that a correct diagnosis could be made for LAD in 75% of biopsy specimens with a probability of 97% and in all cases of DH with a probability of 92%. Using this model, we made no misdiagnoses. This is the first diagnostic probability model in dermatopathology that expresses a confidence level in diagnosis.

Adult↗
PubMed1984

Papular polymorphous light eruption. Fibrin, complement, and immunoglobulin deposition.

Biopsy specimens of papules taken from eight patients with polymorphous light eruption ( PMLE ) were examined by a direct immunofluorescence technique. Extensive intervascular and focal perivascular deposits of fibrin were detected in each case. Slight vascular deposition of C3 and IgM were observed in five and two patients, respectively. The lupus band test was negative in all cases. The findings suggest that venular injury with activation of the clotting system is involved in the development of lesions in PMLE .

Adult↗
PubMed1984

Chronic cutaneous effects of long-term psoralen and ultraviolet radiation therapy in patients with vitiligo.

Vitiligo is refractory to most therapeutic modalities. To assess the efficacy of a variety of PUVA therapies, we enrolled 596 subjects in a prospective study, and 230 were followed for up to 55 months. Various psoralen derivatives and dosage schedules were used. Each subject was examined at yearly intervals for therapeutic response and evidence of chronic PUVA toxicity. At 4 years after therapeutic inception, 29 (13%) developed lesions in remaining vitiliginous macules. Clinically, hyperkeratotic macules and hyperkeratotic, lichenoid, and telangiectatic papules were discerned. Histologic examination of these lesions revealed them to be actinic and lichenoid keratoses, verruca vulgaris, and hyperkeratosis with either hyperplasia or atrophy. No tumors were present. In perilesional skin, dermal collagen and elastic tissue degeneration, much greater in degree than reported in psoriatic skin, was observed. In this group of PUVA-treated patients, no increased risk of carcinoma was apparent during the follow-up period.

Adult↗
PubMed1984

Histologic alterations of psoralen- and longwave ultraviolet radiation-exposed skin.

Histologic changes in skin exposed to psoralen photochemotherapy (PUVA) may be classified as acute or chronic. The acute set of histologic alterations includes changes associated with lesion regression and PUVA toxicity. The chronic set of changes related primarily to the side effects of PUVA therapy. In psoriatic epidermis, morphologic evidence of cellular hyperactivity ceases with accompanying loss of psoriasiform hyperplasia, whereas in other inflammatory disorders the lymphocytic infiltrate is cleared in the epidermis and papillary dermis. In short-term therapy, changes include melanocytic hyperplasia and increased activity with marked keratinocyte hypermelaninosis. In skin chronically exposed to PUVA, all cutaneous compartments are affected with an epidermal maturation disorder, melanocyte activation, as well as dermal collagen and elastic tissue degeneration, some of which persist after cessation of therapy.

Humans↗
PubMed1984

Carcinogenic effects of monofunctional and bifunctional furocoumarins.

We initiated these studies to determine whether bifunctional (interstrand cross-linking) psoralens, such as 8-methoxypsoralen (8-MOP), are more carcinogenic than are the monofunctional, such as angelicin or isopsoralen derivatives, and 3-carbethoxysporalen (3-CP). Hairless mice (Skh:hr-1) in groups of 40 were treated three times weekly for 12 to 15 months. There were 17 groups, and the photocarcinogenic effects of 5 psoralens [8-MOP, 3-CP, 5-methylangelicin, 4,5'-dimethylangelicin (4,5'-DMA), and angelicin] were investigated. Ethanolic solutions of 0.01-0.1% psoralens were topically applied at 5.0 or 50 micrograms/cm2 from cervical to lumbar regions 45 minutes before exposure to UVA (320-400 nm) radiation (0.1, 2.5, or 7.5 joules/cm2). Control groups received either the drug application or UVA exposure only. The study revealed that isopsoralens, such as 5-methylangelicin or 4,5'-DMA, that form monofunctional adducts are more carcinogenic than bifunctional psoralens. The latency and time required for 50% prevelance of tumors was much longer with 8-MOP than with 4,5'-DMA or 5-methylangelicin. Mice treated with the latter 2 compounds had a greater number and larger tumors than mice treated with 8-MOP. The monofunctional angelicin was weakly carcinogenic, whereas 3-CP, also a monofunctional psoralen, was noncarcinogenic. Histologic examination revealed that tumors induced by 8-MOP, 5-methylangelicin, or 4,5'-DMA were all squamous cell carcinomas. Because of their skin-photosensitizing property and their ability to induce interstrand cross-links and severe damage to DNA in replication, bifunctional psoralens apparently produce more lethal damage in cells than do monofunctional isopsoralens.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗