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Biomedical subjects

N A Soter

Publications and source records attributed to N A Soter.

At least 19 recordsLinked to original sources
PubMed1992

Photosensitivity, abnormal porphyrin profile, and sideroblastic anemia.

Cutaneous photosensitivity in a 43-year-old man with idiopathic sideroblastic anemia associated with an abnormal porphyrin profile is reported. This condition was associated with elevated free erythrocyte porphyrin, plasma protoporphyrin, urine porphyrins (predominantly coproporphyrin), stool porphyrins (predominantly protoporphyrin), decreased ferrochelatase activity, and deletion of portions of the long arms of chromosomes 18 and 20. Five other patients with sideroblastic anemia and abnormal porphyrin profiles have been described; all but one of these patients had photosensitivity. The porphyrin profile of this patient is similar to that of three other previously described patients.

Adult↗
PubMed1992

Ultraviolet-B phototherapy for early-stage cutaneous T-cell lymphoma.

BACKGROUND AND DESIGN--Cutaneous T-cell lymphoma (CTCL) is a slowly advancing disease that initially presents in the skin and may later progress to involve the lymph nodes and viscera. Since CTCL most often presents on non-sunlight-exposed regions of the body, a possible protective role for UVB irradiation has been suggested. Recent observations have also found that UVB irradiation serves an immunoregulatory role. Given that limited data are available regarding the use of UVB phototherapy in treating CTCL, a retrospective nonrandomized study of 37 nonconsecutive patients with early CTCL was performed to assess the efficacy of UVB phototherapy in the treatment of CTCL. RESULTS--Twenty-five (71%) of the 35 patients treated with UVB phototherapy (two were unavailable for follow-up) achieved a total clinical remission. Median time to remission was 5 months, and median duration of the remission was 22 months. Twenty-five (83%) of 30 patients with disease limited to patches achieved remission, whereas none of the patients with plaque-level disease achieved a remission. Of the 25 patients who achieved complete remission, five (20%) had a recurrence of CTCL. CONCLUSIONS--Phototherapy with UVB appears to be effective in patients with early patch-stage CTCL.

Adolescent↗
PubMed1991

Treatment of urticaria and angioedema: low-sedating H1-type antihistamines.

H1-type antihistamines are considered the therapeutic agents of choice for treating urticaria and angioedema. The use of traditional H1 antihistamines is limited by their side effects. In recent years low-sedating H1 antihistamines with reduced sedative and anticholinergic side effects have become popular choices for the treatment of urticaria and angioedema. Terfenadine and astemizole are currently available in the United States, and cetirizine and loratadine, currently under review at the Food and Drug Administration, are available in other countries. Terfenadine, cetirizine, and loratadine achieve rapid peak plasma concentrations in 1 to 2 hours, whereas astemizole has a slow onset of action. In double-blind, placebo-controlled studies of chronic idiopathic urticaria, low-sedating H1 antihistamines were more effective than placebo. The choice of a particular low-sedating H1 antihistamine depends on pharmacokinetic considerations and frequency of administration.

Angioedema↗
PubMed1991

Acute and chronic urticaria and angioedema.

Urticaria and angioedema are clinical manifestations of various immunologic and inflammatory mechanisms, or they may be idiopathic. The respiratory and gastrointestinal tracts as well as the cardiovascular system may be involved in any combination. Patients with urticaria and/or angioedema can be classified based on pathophysiologic mechanisms into those with IgE-dependent or complement-mediated immunologic disorders, those with nonimmunologic disorders in which there is a direct effect on the mast cell or on arachidonic acid metabolism, and those whose condition is idiopathic. Evaluation of patients should focus on a thorough history. Laboratory tests provide minimal additional information. About one half of patients with urticaria alone and 25% with urticaria and angioedema or angioedema alone are free of lesions within 1 year. With urticaria, angioedema, or both, 20% of patients experience episodes for more than 20 years.

Acute Disease↗
PubMed1991

C5a, cutaneous mast cells, and inflammation: in vitro and in vivo studies in a murine model.

To evaluate further the interactions of C5a and mast cells in cutaneous inflammation, the ability of human native C5a (nC5a) (10 to 500 ng/ml) and human recombinant C5a (rC5a) (10 ng/ml to 100 ng/ml) to induce histamine release from purified BALB/c cutaneous mast cells (CMC) and peritoneal mast cells (PMC) was analyzed. It was found that nC5a induced histamine release from CMC but not from PMC, with a maximal net release at 250 ng/ml nC5a (22.8 +/- 2.6%). Kinetic experiments demonstrated that nC5a-induced maximal net histamine release occurred 5 min after the presentation of this stimulus (25.8 +/- 6.0%). Using rC5a and CMC, dose-response studies indicated a maximal net release of 7.0 +/- 1.7% at rC5a of 10 ng/ml, and kinetic studies showed a maximal net release at 5 min of incubation (12.9 +/- 1.6%). Release induced by rC5a was calcium-dependent, and peaked at 30 degrees C. These results indicate that functional heterogeneity exists between the CMC and the PMC of BALB/c mice, that C5a is a relevant stimulus for characterization of this heterogeneity, and that CMC from these animals can serve as a convenient in vitro model for the study of human C5a-mast cell interactions. In vivo, injections of nC5a (25-100 ng) and rC5a (25-100 ng) into the skin of BALB/c mice induced an increase in cutaneous vasopermeability, as assessed by the extravasation of intravenously injected 125I-bovine serum albumin. nC5a induced a dose-dependent increase in vasopermeability, whereas alterations induced by rC5a plateaued at 50 ng. The C5a-induced vasopermeability was markedly enhanced in animals that had been previously treated with an inhibitor of serum carboxypeptidase, which converts C5a to the less potent derivative, C5a des Arg. These findings suggest that carboxypeptidase plays an important role in vivo in the modulation of C5a-induced cutaneous inflammation in murine skin.

Animals↗
PubMed1991

The skin in mastocytosis.

The most frequent site of organ involvement in patients with any form of mastocytosis is the skin. Cutaneous expressions include urticaria pigmentosa, mastocytoma, diffuse and erythrodermic cutaneous mastocytosis, and telangiectasia macularis eruptiva perstans. The cutaneous lesions tend to appear early in life. Although urticaria pigmentosa has been reported in 12 pairs of twins and one set of triplets, the majority of affected individuals have no familial association. Most patients with systemic mastocytosis have skin lesions; however, an occasional patient will have systemic disease with no other skin features than flushing. In lesional cutaneous sites and in non-lesional skin, there is an increase in the number of mast cells. Electron microscopy shows quantitative differences between lesional skin mast cells from patients with and without systemic disease. The mast cells from adult patients with systemic disease have a larger mean cytoplasmic area, nuclear size, and granule diameter. The granules contain predominantly grating/lattice structures. The cutaneous mast cells contain tryptase and chymase. They retain their functional reactivities to relevant secretory stimuli, such as C3a, morphine sulfate, and calcium ionophore A23187. Lesional skin contains histamine, leukotriene B4, prostaglandin D2, 5-hydroxyeicosatetraenoic acid, platelet-activating factor, and heparin. Treatment of the cutaneous manifestations includes the use of H1 and H2 antihistamines, oral disodium cromoglycate, psoralens plus ultraviolet A photochemotherapy, and potent topical corticosteroid preparations.

Dermatitis, Exfoliative↗
PubMed1991

Are topical corticosteroids useful adjunctive therapy for the treatment of psoriasis with ultraviolet radiation? A review of the literature.

Adjunctive topical corticosteroids are often administered with UV-B phototherapy or oral psoralen plus UV-A (PUVA) photochemotherapy for the treatment of psoriasis. Five studies comparing PUVA alone with PUVA and topical corticosteroid preparations showed more rapid rates of clearing and a smaller total UV-A exposure with the latter regimen. However, one study demonstrated a higher relapse rate in association with corticosteroid use. Further studies to better define these risks are recommended. Six of seven reports evaluating the use of topical corticosteroid preparations with UV-B phototherapy failed to demonstrate an advantage to this regimen when compared with UV-B phototherapy alone. Therefore, the use of a topical corticosteroid preparation with UV-B phototherapy for the treatment of psoriasis is not recommended.

Administration, Topical↗
PubMed1990

Chronic actinic dermatitis. Study of the spectrum of chronic photosensitivity in 12 patients.

Twelve patients with photodermatitis for longer than 3 months' duration were identified: 1 patient with chronic photocontact dermatitis, 1 with persistent photosensitivity following exposure to a systemic medication, 6 with persistent light reactivity, and 4 with actinic reticuloid. There were 10 men and 2 women, ranging in age from 27 to 81 years, with a mean age of 62 years. The duration of the eruption ranged from 6 months to 20 years. Persistence of photosensitivity to quinidine, which is analogous to persistent light reactivity, was documented in 1 patient, and evolution from photocontact dermatitis to actinic reticuloid was observed in 2 others. These data, along with those reported in the literature, indicate that chronic photocontact dermatitis, persistent photosensitivity to systemic agents, persistent light reactivity, photosensitive eczema, and actinic reticuloid should be considered as entities occurring along a continuum, and the term "chronic actinic dermatitis" is suggested to refer to these entities. Eight (67%) of the 12 patients had skin type VI and 2 others (17%) had skin type V, percentages markedly higher than those of the general patient population, demonstrating that chronic actinic dermatitis is not uncommon among individuals with dark skin.

Adult↗
PubMed1990

Urticaria: current therapy.

Although the ideal treatment for urticaria is identification and removal of its cause, no underlying cause can be discerned in the majority of instances. The chief clinical problem is the treatment of chronic idiopathic urticaria. H1-receptor antagonists are the major class of therapeutic agents used in the management of chronic idiopathic urticaria. The H1 antagonists have been divided into subgroups based on their chemical structure. The second-generation H1 antagonists now available are particularly advantageous for individuals who must remain alert while working. Terbutaline, a beta-adrenergic agonist, is of occasional benefit as an adjunct therapy in combination with an H1 antagonist. The oral administration of disodium cromoglycate is ineffective in patients with chronic idiopathic urticaria, although a few individuals with urticaria caused by food allergy may respond to this drug. It is best to avoid repeated injections of epinephrine and the systemic administration of corticosteroids. Urticaria has a capricious course: it may respond to the administration of placebos or it may resolve spontaneously. About 50% of the patients with urticaria are free of lesions within 1 year, but 20% continue to have episodes for more than 20 years.

Angioedema↗
PubMed1990

Mast-cell heterogeneity: functional comparison of purified mouse cutaneous and peritoneal mast cells.

To investigate the functional heterogeneity of mouse mast cells, we extracted and purified cutaneous and peritoneal mast cells from 10- to 18-week-old BALB/c mice and compared their responses to secretagogues. Cutaneous mast cells (CMC) were extracted from mouse ears after digestion with hyaluronidase and collagenase in MEM containing 25% fetal calf serum and purified on a discontinuous Percoll gradient. The histamine content of cells obtained from the 30/40% interface was 1.0 +/- 0.1 pg/cell (mean +/- SE), with a mast-cell purity of 68.6 +/- 4.4% and a viability of greater than 93%. Peritoneal mast cells (PMC) were obtained by lavage with modified Tyrode's buffer followed by purification on 22.5% and 3-9% metrizamide gradients. The histamine content of cells was 12.2 +/- 0.8 pg/cell, with a mast-cell purity of 95.9 +/- 0.6% and a viability of greater than 95%. Histamine release induced by A23187 from CMC peaked at 3.0 microM A23187 (19.1 +/- 4.2%), at 3.0 min (22.3 +/- 2.3%), and at 30 degrees C (17.6 +/- 2.6%). In contrast, histamine release from PMC peaked at 8.0 microM of A23187 (49.4 +/- 12.1%) and at 15.0 min (48.5 +/- 12.2%). Release of histamine from PMC was observed at all the temperatures tested from 22 to 45 degrees C. Histamine release from CMC and PMC induced by A23187 was calcium dependent. Histamine release induced by compound 48/80 from CMC peaked at 0.5 micrograms/ml of compound 48/80 (23.0 +/- 7.4%) and at 5.0 min incubation (16.3 +/- 2.0%), whereas release from PMC peaked at 10.0 micrograms/ml (31.9 +/- 2.6%); release from PMC was similar at all the time points examined (1-15 min). Histamine release induced by substance P (SP) from both CMC and PMC peaked at 5.0 microM (18.8 +/- 6.6% and 12.6 +/- 3.7%, respectively); however, the maximal release from CMC occurred at 3.0 min (18.2 +/- 3.2%) and from PMC at 30.0 min (11.4 +/- 2.0%). SP-induced histamine release from CMC was calcium dependent, whereas release from PMC was only partially inhibited by EDTA. This study demonstrated that functional heterogeneity exists between these two populations of mast cells.

Animals↗
PubMed1990

Cimetidine-induced augmentation of allergic contact hypersensitivity reactions in mice.

BALB/c mice were treated with cimetidine (100 mg/kg) or saline, intraperitoneally, twice daily, from days 0-2 or days 7-9 after sensitization with 0.1%, 2,4,6-trinitro-1-chlorobenzene (TNCB) on day 0. On day 7, the mice were challenged with 1% TNCB to one ear. Ear swelling responses (as an index of sensitization), serum histamine levels, and biopsy specimens of challenged ears were evaluated in groups of cimetidine- or saline-treated mice at 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after challenge. Additional controls included mice injected with saline or cimetidine and challenged with, but not sensitized to, TNCB (irritant controls). Treatment with cimetidine during the induction but not the elicitation of allergic contact hypersensitivity (ACH) produced a significant enhancement of the response throughout the first 48 h. There was no effect of cimetidine on antigen-presenting cells within the epidermis which might account for this enhancement. Similarly, no difference in mast cell morphology or serum histamine levels between cimetidine- and saline-treated groups was observed. Histologically, the cimetidine-treated animals showed a more intense cellular infiltrate, which was most noticeable at 24 to 48 h, at which time numerous subcorneal and perifollicular neutrophilic abscesses were observed. To further investigate the mechanism of action of cimetidine, mice were injected with cyclophosphamide (150 mg/kg) 2 d prior to sensitization. Mice treated with cyclophosphamide alone or in combination with cimetidine showed no additive or synergistic effect upon the ear swelling response. We conclude that enhancement of ACH by cimetidine is independent of any effect on mast cells or antigen-presenting cells, but may relate to a cimetidine-induced inhibition of the induction of T-suppressor cells at the time of sensitization.

Animals↗
PubMed1990

Acute effects of ultraviolet radiation on the skin.

The responses of normal skin to ultraviolet (UV) irradiation are an example of inflammation. The chromophores initiating the reaction are unknown. Characteristic clinical findings are erythema, heat, swelling, and pain. Histopathologic changes include epidermal keratinocyte damage with Langerhans cell depletion and dermal edema, endothelial swelling, mast cell degranulation, and cellular infiltration with neutrophils and monocytes. Biochemical changes include release of histamine, cyclo-oxygenase, and lipoxygenase-derived products of arachidonic acid, kinins, and cytokines, probably from a range of epidermal and dermal cell types. These substances very likely assist in mediation of the reaction. The response is more pronounced in young subjects. UVB (280 to 315 nm) and UVA (315 to 400 nm) radiation both produce inflammation, but with marked qualitative and quantitative differences. UVB having more effect on the epidermis, UVA more on the dermis.

Acute Disease↗
PubMed1990

Elevated plasma histamine levels in systemic sclerosis (scleroderma).

Systemic sclerosis is characterized by excessive deposition of collagen and other matrix proteins in the skin and internal organs. One hypothesis supports fibroblast stimulation for production of excess amounts of collagen by factors present in the blood or released by cells composing inflammatory tissue infiltrates. Increased numbers of mast cells are present in the involved skin of patients with systemic sclerosis, and histamine has been thought to be a possible mediator of fibrosis in this and other fibrotic conditions. We therefore measured plasma histamine levels in 32 patients with systemic sclerosis and found elevated levels in 18 patients (56%). Elevated plasma histamine levels were more common in patients with diffuse disease (74%), in contrast to limited disease (31%). The degree of clinical activity and the duration of disease could not be correlated with histamine levels.

Adult↗
PubMed1989

Cutaneous inflammation: effects of hydroxy acids and eicosanoid pathway inhibitors on vascular permeability.

Four metabolic products of arachidonic acid lipoxygenation, 5-hydroxyeicosatetraenoate (5-HETE), 12-HETE, 15-HETE, 5(S),12(S)-DiHETE, were injected intradermally into depilated dorsae of albino guinea pigs. The presence of intravenously injected 125I-bovine serum albumin (10uCi/kg) in 13-mm punch biopsy specimens served as a marker for altered vascular response; histologic changes were evaluated at 6 and 24 h after the injection in 1-micron-thick sections. Thirty minutes after the injections of 15 nanomoles and 60 nanomoles of 5-HETE, the ratios of radioactivity in HETE-injected to that in buffer-injected sites were 1.35 +/- 0.06 (mean +/- SE) and 2.80 +/- 0.27, respectively. Corresponding effects of 15-HETE were 1.39 +/- 0.17 and 1.63 +/- 0.21, respectively. Values for 60 nanomoles of 12-HETE and 5,12-DiHETE were intermediate in comparison with the above eicosanoids. The most notable histologic changes were a neutrophilic infiltrate induced by 12-HETE at 6 and 24 h, and neutrophilic and eosinophilic infiltrates in response to 5,12-DiHETE injection at 6 and 24 h. Effects of topically applied eicosanoid pathway inhibitors were also evaluated, using intradermally injected sodium arachidonate (AA) as agonist. Three mixed cyclooxygenase/lipoxygenase inhibitors, BW755C, phenidone, and nordihydroguaiaretic acid, suppressed vascular response by 9%, 9%, and 6% for 150 nmol of AA, and by 9%, 13%, and 12% for 300 nmol of AA, respectively. The cyclooxygenase inhibitor, indomethacin, induced suppressions of 39% for 150 nmol AA and 22% for 300 nmol AA, respectively. These data demonstrate that metabolites of both cyclooxygenase and lipoxygenase eicosanoid pathways are involved in alteration in vascular response accompanying cutaneous inflammation.

Animals↗
PubMed1989

Morphology of atopic eczema.

The routine examination of skin biopsy specimens embedded in paraffin and strained with hematoxylin-eosin has failed to allow differentiation of atopic eczema from other types of eczematous dermatitis. The use of 1-micron plastic-embedded sections permits the recognition of infiltrating cell types and blood vessel alterations, thus allowing a refined method to examine cutaneous lesions and permit better definition of cutaneous structures than can be achieved in routinely-processed specimens. Acute vesicular lesions exhibited marked epidermal intercellular edema (spongiosis) and a dermal inflammatory infiltrate of lymphocytes, and activated lymphocytes with normal numbers of mast cells that exhibited various degrees of hypogranulation. Only rare eosinophils, neutrophils, and basophils were noted. Venular alterations included endothelial cell hypertrophy without necrosis. In lichenified plaques there was epidermal hyperplasia with a dermal inflammatory infiltrate that included increased numbers of fully granulated mast cells and increased numbers of lymphocytes and monocyte-macrophages. Alterations of venules included marked endothelial cell hypertrophy and basement membrane thickening. Cutaneous nerves exhibited demyelination and fibrosis. Also, increased numbers of Langerhans' cells have been noted in the epidermis of chronic lesions. Despite the absence of eosinophils, major basic protein has been demonstrated in the dermis by direct immunofluorescence techniques. Studies of lymphocyte subsets have shown increased numbers of CD4+ T lymphocytes.

Adult↗
PubMed1989

The late phase of hematoporphyrin derivative-induced phototoxicity in mice: release of histamine and histologic changes.

This study was designed to directly examine the role of mast cells and the histologic changes in the late phase (4-48 h) of hematoporphyrin derivative-induced phototoxicity. BALB/c mice were rendered phototoxic by intraperitoneal injection of HpD, followed by exposure to 1.59 kJ/m2 of 396-406 nm radiation. Immediately before radiation, and at 4, 8, 12, 18, 24 and 48 h after radiation, the ear thickness, serum histamine levels and histologic changes of ears were examined. A maximal net increase in ear thickness of 33.5 +/- 0.3 X 10(-2) mm (mean +/- SE) was noted at 12 h, associated with a maximal net increase of serum histamine (43.3 +/- 11.6 ng/ml, mean +/- SE), and a maximal mast cell degranulation. Other histologic changes consisted of mild epidermal spongiosis at 18-24 h, and a predominant neutrophilic infiltrate, which peaked at 24 h (211.6 +/- 0.4 cells/mm2). No significant alteration was observed in control mice. These data indicated that mast cells participate in the late phase of HpD-induced phototoxicity in mice.

Animals↗
PubMed1989

Cutaneous late-phase response to allergen. Mediator release and inflammatory cell infiltration.

To better define the inflammatory infiltrates and kinetics of mediator release during the cutaneous late-phase reaction (LPR), we examined skin biopsies at 8 h, and skin chamber cell counts and mediator release for 12 h after antigen challenge. Compared with the control sites, the antigen-stimulated biopsy sites contained 14 times as many basophils (P less than 0.01) and six times as many eosinophils (P less than 0.001) with one to two fold more mononuclear cells (P less than 0.03) and neutrophils (P less than or equal to 0.01). Similar changes were found in the skin chambers. Although there were neutrophils in the control chamber, they were only twice as numerous in the antigen challenged site (P less than 0.01). Eosinophils were 35-fold (P less than or equal to 0.03) more prevalent in the antigen chamber than the control chamber for hours 8-12 and basophils were noted starting in the eighth hour and were 20-fold (P less than or equal to 0.03) more concentrated in the antigen chamber during the next 4 h. The mononuclear cells were not significantly different between antigen and control blisters. With respect to inflammatory mediators, there was an initial peak of histamine (13.2 +/- 2.9 ng/ml) in the blister fluid at 1 h. The level then fell to approximately 2 ng/ml, followed by a secondary rise starting at the eighth hour and increasing to 9.8 +/- 2.8 ng/ml by the twelfth hour. This secondary increase in histamine correlated significantly (r = 0.81, P less than 0.05) with the observed influx of basophils. PGD2 in the blister fluid rose to 371+/-25 pg/ml during the first 4 h and then slowly decreased to half this level during the last 4 h. Thus, the cutaneous LPR has been shown to manifest a secondary increase in histamine levels and a markedly specific increase in eosinophils and basophils with mediator release apparently being derived from the latter cells.

Adolescent↗