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Biomedical subjects

M S Peters

Publications and source records attributed to M S Peters.

At least 19 recordsLinked to original sources

Deposition of eosinophil granule proteins precedes blister formation in bullous pemphigoid. Comparison with neutrophil and mast cell granule proteins.

Eosinophils, neutrophils, and mast cells have all been implicated in the pathogenesis of bullous pemphigoid (BP). To comparatively characterize the involvement of these cells in BP, 10 lesional skin biopsy specimens were identified retrospectively and studied for tissue localization of eosinophil, neutrophil, and mast cell granule proteins. Subsequently, multiple skin biopsies of lesions in various developmental stages were obtained from 3 patients with untreated BP. Involved and uninvolved skin specimens were also obtained from 2 patients. Using indirect immunofluorescence, retrospectively identified lesions showed eosinophils and extracellular granule protein deposition prominently in areas of blistering. Evolving lesions showed eosinophil granule protein deposition in all stages but was most marked in early erythematous and prebullous (urticarial) lesions and was minimal in uninvolved skin. Vascular cell adhesion molecule-1, E-selectin, and P-selectin were detected on vessels and very late activation antigen-4 was detected on mononuclear cells and eosinophils by immunoperoxidase staining of lesions. Eosinophil granule proteins were increased in the peripheral blood, urine, and blister fluid. Blister fluids caused increased eosinophil survival that was inhibited by antibodies to interleukin-5 and interleukin-3. Although neutrophil and mast cell infiltration was observed, extracellular granule protein deposition from these cells was minimal except in two specimens. These results demonstrate that eosinophils infiltrate and deposit granule proteins early in the development of BP lesions, that eosinophil-activating cytokines are present in blister fluid, and that eosinophil-selective adhesion molecules are present. These studies strongly support a role for eosinophils in blister formation in BP.

Aged↗

Secondary amyloidosis complicating psoriasis.

BACKGROUND: Amyloidosis is a heterogeneous group of disorders characterized by extracellular deposition of fibrillar protein. Secondary amyloidosis occurs in patients with chronic infectious or inflammatory processes. Only 18 cases of secondary amyloidosis complicating psoriasis have been reported. OBJECTIVE: We characterized secondary amyloidosis complicating psoriasis. METHODS: We reviewed all cases of coexisting psoriasis and amyloidosis seen at the Mayo Clinic from 1950 to 1992. The clinical characteristics were summarized, and the literature was reviewed. RESULTS: There were 28 cases of coexistent disease, and in five of these psoriasis was the only inflammatory condition preceding the development of secondary amyloidosis. Histopathologic confirmation with Congo red staining was available in four cases, and immunohistochemical confirmation of the characteristic amyloid A subtype was performed in two. CONCLUSION: Follow-up of four patients supports the view that amyloidosis associated with psoriasis is an aggressive disease that may be fatal.

Aged↗

Kimura's disease and angiolymphoid hyperplasia with eosinophilia: new observations from immunohistochemical studies of lymphocyte markers, endothelial antigens, and granulocyte proteins.

Kimura's disease (KD) typically presents as large subcutaneous masses in young Oriental males. It is characterized by deep inflammation with vascular proliferation, lymphocytic nodules with subcutaneous germinal centers, fibrosis, and edema. In comparison, angiolymphoid hyperplasia with eosinophilia (AHLE) occurs in all races and the lesions usually are smaller and more superficial. The causes of these two diseases are debated. We compared histologic features of 4 cases of KD with 22 cases of ALHE and studied expression of endothelial antigens and lymphocyte markers as well as localization of eosinophil, mast cell, and neutrophil granule proteins in lesional tissue. T-cell lymphoid aggregates with well-formed B-cell germinal centers occurred in KD, and nodular and diffuse T-cell infiltration with small B-cell clusters occurred in ALHE. Endothelial proliferation was more pronounced in KD, lacking the atypical histiocytoid endothelial cells characteristic of ALHE. Many intact eosinophils infiltrated lesions in both diseases, although KD had less extracellular granule protein deposition than ALHE. Intact mast cells were seen in both diseases. There was neutrophil elastase staining of occasional scattered intact cells but no extracellular deposition. Compared with KD, ALHE is more varied in its clinical, histopathologic, and immunohistochemical features.

Adult↗

Human cutaneous allergic late-phase response is inhibited by soluble IL-1 receptor.

The late-phase allergic reaction (LPR) occurs 4 to 8 h after allergen exposure and probably causes the symptoms of chronic allergic disease. To determine the effects of soluble IL-1 receptor on the cutaneous LPR, we performed a prospective, randomized, double-blind, placebo-controlled study on 15 allergic subjects. Intradermal injections of allergen were placed on subjects' forearms, followed by immediate subcutaneous injections at the same site of either 1, 10, 25, 50, or 100 micrograms of rhu IL-1R to three subjects in each dosage group. Placebo was given to matched allergen-injected sites on the contralateral arm. Erythema, induration, and itching were recorded for each site. Sites were biopsied at 8 h for immunohistologic evaluations. Rhu IL-1R significantly reduced the clinical reaction at all concentrations. At 1 and 10 micrograms, measurements of LPR were significantly less (p < 0.05) than at placebo sites at several time points from 2 to 8 h. At higher concentrations, LPR was suppressed at rhu IL-1R and placebo sites, suggesting a systemic effect of rhu IL-1R. Histologic evaluation and indirect immunofluorescence for eosinophil granule major basic protein, neutrophil elastase, and mast cell tryptase showed no statistical differences between rhu IL-1R and placebo sites or among doses. IL-1 plays an important role in the generation of allergic LPR. While microgram quantities of rhu IL-1R inhibited the clinical signs and symptoms of LPR, its effects on the allergic inflammatory infiltrate are yet to be defined. In this short term trial, rhu IL-1R was neither immunogenic nor toxic.

Adult↗

Drug-induced linear IgA bullous dermatosis: report of six cases and review of the literature.

BACKGROUND: Linear IgA bullous dermatosis (LABD) is an autoimmune subepidermal blistering disease that may be associated with drug exposure. OBJECTIVE: Our purpose was to compare the clinical, pathologic, and immunofluorescence findings in drug-induced LABD with those in the idiopathic type. METHODS: Six patients with an acute drug eruption were identified who had linear IgA deposition at the basement membrane zone (BMZ). Lesional tissue was examined by brightfield microscopy, and perilesional tissue was examined by direct immunofluorescence (DIF). The presence of circulating BMZ antibody was assayed by indirect immunofluorescence (IIF) on monkey esophagus (ME) and salt-split human skin (SS). RESULTS: Histopathologic examination showed subepidermal bullae with varying numbers of inflammatory cells. DIF showed linear IgA at the BMZ; three of the patients also had weak deposition of C3 at the BMZ. Serum from five patients was studied by IIF. One patient had circulating IgA BMZ antibodies in a titer of 1:80 on ME, localized to the dermal side on SS. All patients were free of lesions within 5 weeks after discontinuation of the drug. CONCLUSION: Drug-induced LABD is a self-limited eruption characterized by linear deposition of IgA without IgG at the BMZ. Most patients lack circulating antibodies. The distribution of lesions and the course of the disease differ from those of idiopathic LABD.

Aged↗

The Midwest flood of 1993: surviving prolonged water loss.

The Midwest Flood of 1993 was one of the most devastating and challenging disasters in Iowa's history. The city's water supply became contaminated, leaving more than 250,000 residents and all seven metropolitan medical centers without water. Despite heroic sandbagging efforts, floodwaters invaded the Des Moines water treatment plant's filtration system. The major strategies used at this facility during the disaster provide a framework for effective, coordinated emergency response.

Disaster Planning↗

Alanine and leucine transport in unfertilized pig oocytes and early blastocysts.

Amino acid transport is facilitated by specific transporters within the plasma membrane of the cell. In mouse oocytes and cleavage-stage conceptus Na(+)-dependent L-alanine and L-leucine transport are nearly undetectable. Sodium-dependent transport via system B0,+ in the mouse conceptus increases greatly between the 8-cell and blastocyst stages. By contrast, data presented here for the pig show that L-alanine and L-leucine transport is mainly Na(+)-dependent in the oocyte; this Na(+)-dependent component of transport becomes undetectable by the blastocyst stage. The Na(+)-dependent component of transport in oocytes is inhibited by BCH (2-aminoendo-bicyclo[2.2.1] hexane-2-carboxylic acid) and L-lysine and thus could be a form of system B0,+. In both oocytes and blastocysts Na(+)-independent L-leucine transport is inhibited by BCH, which is consistent with the presence of system L. The dramatic decrease in Na(+)-dependent amino acid transport activity could occur in pig conceptuses in association with the onset of RNA synthesis during the 4-cell stage. Regardless of the precise time during development at which it occurs, however, this dramatic, developmentally regulated decrease in Na(+)-dependent alanine and leucine transport activity contrasts sharply with the large increase in Na(+)-dependent system B0,+ activity that occurs during preimplantation development of murine conceptuses. Elucidation of the molecular mechanisms by which these changes occur should contribute to an understanding of regulation of gene expression during early development.

Alanine↗

Aspartate and glutamate transport in unfertilized pig oocytes and blastocysts.

Amino acid transport is facilitated by specific transporters within the plasma membrane of the cell. Mediated Na(+)-independent transport of L-glutamate can be easily detected in mouse oocytes, but it is nearly undetectable in blastocyst-stage embryos. In contrast, the Na(+)-dependent transport of L-aspartate is not detectable in oocytes, but it is detectable in eight-cell embryos and reaches relatively high levels by the blastocyst stage. It is believed that the amino acid transporters responsible are systems x-c and X-AG, respectively. Here we report the detection of Na(+)-dependent L-aspartate transport, which increased as pig blastocysts developed, although Na(+)-dependent aspartate transport was not detected in pig oocytes. Mediated Na(+)-independent L-glutamate transport was not detected in pig oocytes, in contrast to the mouse, nor in early or hatched pig blastocysts. Thus, while the developmental regulation of system X-AG is similar in both the pig and the mouse, system x-c was not detectable in pig oocytes or blastocysts. Elucidation of the molecular mechanisms controlling amino acid transport and other gene expression in early embryos should contribute to an understanding of whether and even why some aspects of developmental regulation of gene expression may need to differ among species.

Animals↗

Diacylglycerol-enhanced electrical activation of porcine oocytes matured in vitro.

This study was undertaken to examine the effect of second messengers added to the electroporation medium on electric pulse-induced artificial activation of meiotic Metaphase II porcine oocytes. Six separate experiments evaluated second messengers added to electroporation medium. When added to electroporation medium, neither phospholipase C (PLC: 0 to 2.5 Units/ml), D-myo-inositol triphosphate (IP(3): 0 to 10,000 muM), nor guanosine 5'-O-(3-thiotriphosphate; GTP-gamma-S: 0 to 100 muM) had any effect (P> 0.05) on activation rates. However, addition of 1,2-dioctanoyl-sn-glycerol (DiC(8)) increased activation rates in a dose-dependent response. At a level of 1,000 muM, DiC(8) resulted in a higher activation rate (P< 0,05) than 0.0, 0.1, 1 or 10 muM of DiC(8) with a pulse, and the 1,000 and 10,000 muM of DiC(8) no-pulse control groups. Effects of DiC(8) (1,000 muM) and IP(3) (100 muM) in combination or individually were investigated. At 1,000 muM, DiC(8) caused a higher rate of activation (P< 0.05) than 100 muM IP(3), but the result was not different from DiC(8) + IP(3). In another experiment, no difference (P> 0.05) was observed between DiC(8), GTP-gamma-S and IP(3), but DiC(8) + GTP-gamma-S + IP(3) + PLC yielded a higher (P< 0.05) activation rate than PLC or the rate of the controls. No significant development (blastocyst) was observed after 5 days of culture in any of the experiments. Protein profiles of activated oocytes, determined by 1D SDS-PAGE, were characteristic of pronuclear-stage embryos. These data indicate that the addition of DiC(8) to the electroporation medium synergistically enhances the rate of activation of electrically stimulated in vitro-matured porcine oocytes.

Journal Article↗

Deposition of membrane attack complex in cutaneous lesions of lupus erythematosus.

BACKGROUND: The membrane attack complex (MAC; C5b-9) localizes in the basement membrane zone (BMZ) of cutaneous lesions from patients with lupus erythematosus (LE) and has been implicated in the pathogenesis of this disease. OBJECTIVE: Our purpose was to compare the frequency of MAC deposition with that of immunoglobulin and C3 deposition (lupus band). METHODS: We studied 56 skin biopsy specimens from 42 patients with LE by direct immunofluorescence. RESULTS: MAC was deposited in a granular pattern at the BMZ in 29 of 38 biopsy specimens (76%) from lesional skin; 5 of 38 specimens (13%) had focal or weak segmental deposition and 4 of 38 (11%) were negative. In contrast, IgG, IgM, IgA, and C3 were detected in 16 of 38 specimens (42%), 30 of 38 (79%), 4 of 38 (11%), and 22 of 38 (58%), respectively. None of the uninvolved skin biopsy specimens was MAC positive, although 4 of 18 (22%), 5 of 18 (28%), 1 of 18 (6%), and 2 of 18 (11%) were positive for IgG, IgM, IgA, and C3, respectively. CONCLUSION: MAC deposition in lesional skin appears to be a relatively sensitive and specific marker for cutaneous LE and may be useful as an adjunct to the "lupus band" test.

Basement Membrane↗

Cutaneous mucormycosis resembling superficial granulomatous pyoderma in an immunocompetent host.

Primary cutaneous mucormycosis is uncommon and occurs mainly in immunosuppressed or diabetic patients or after localized trauma. We report a case of cutaneous mucormycosis in an immunocompetent man in whom no definite precipitating factors could be identified; initially, superficial granulomatous pyoderma was suspected clinically. The lesion was successfully treated with debridement, local wound care, parenteral administration of amphotericin B, and ultimately by surgical excision and split-thickness skin grafting.

Dermatomycoses↗

Expression of p53 protein in benign and malignant epidermal pathologic conditions.

BACKGROUND: p53 is an oncogene and a tumor-suppressor gene whose gene product regulates the cell growth cycle. Mutations in p53 are the most common genetic alterations in human cancer. OBJECTIVE: Our purpose was to define p53 expression and subcellular localization in normal and pathologic epidermis. METHODS: We examined sections of normal skin, psoriasis, squamous cell carcinoma (SCC), basal cell carcinoma (BCC), keratoacanthoma, and cultured epithelial cell lines with five antibodies to p53. RESULTS: Monoclonal antibody MAb421 and MAb1801 stained the cytoplasm of normal basal keratinocytes, suggesting that subcellular localization or sequestration of wild-type p53 regulates its activity. Polyclonal antibody reacted throughout normal epidermis, suggesting heterogeneity of species or conformational forms of p53 protein. Cytoplasmic reactivity to MAb421 was similar in normal epidermis, psoriasis, and cultured keratinocytes but was, diminished in SCC, BCC, and keratoacanthoma. CM-1 reactivity persisted in these tumors. Putative p53 mutations detected by MAb240 reactivity were present in 44% of SCC specimens. CONCLUSION: Epidermis expresses p53 and the gene may regulate epidermal keratinocyte growth and carcinogenesis.

Antibodies, Monoclonal↗

Lymphoma versus pseudolymphoma of the skin: gene rearrangement study of 21 cases with clinicopathologic correlation.

BACKGROUND: Diagnosis of cutaneous lymphoma in the absence of systemic lymphoma may be difficult. Reactive lymphoid lesions can mimic lymphoma clinically and histologically and have been designated pseudolymphomas. OBJECTIVE: Our purpose was to analyze lymphoid gene rearrangements in cutaneous lymphoproliferative lesions and to correlate these findings with the histologic, immunophenotypic, and clinical profile. METHODS: We examined 21 cases of lymphoproliferative lesions that developed in skin and performed molecular rearrangement analysis of T-cell receptor and immunoglobulin genes. We examined identical tissues by histologic and immunophenotypic criteria and conducted follow-up clinical evaluation of all patients. RESULTS: Clonal rearrangements of immunoglobulin (seven cases) or T-cell receptor (two cases) gene were detected in 9 of 21 patients. No specific histologic or immunophenotypic feature was consistently associated with a clonal lymphoid gene rearrangement. Systemic lymphoma developed in one patient in whom a clonal rearrangement within the immunoglobulin gene was identified. CONCLUSION: Gene rearrangement analysis may be helpful in differentiating primary cutaneous lymphoma from pseudolymphoma. The chronic clinical course of patients with clonal lymphoid gene rearrangements supports a lack of correlation between clonality and biologic aggressiveness.

Adult↗

Efficacy of vitamin D3 derivatives in the treatment of psoriasis vulgaris: a preliminary report.

The efficacy of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and the new analogue calcipotriene (MC 903) in the treatment of psoriasis was investigated. Eight patients with psoriasis were enrolled in a pilot study with systemically administered vitamin D3 and were given 1,25(OH)2D3 (Rocaltrol; Hoffmann-La Roche) in dosages from 0.5 microgram to 2 micrograms/day for a 6-month trial. In one patient, the psoriatic plaques resolved within 2 months after treatment (0.5 microgram/day) was initiated. Moderate improvement was noted in one other patient (1 microgram/day). The serum level of 1,25(OH)2D before treatment was not less than the normal range of the adult population. Side effects of systemically administered 1,25(OH)2D3 included a dose-dependent increase in the 24-hour urinary calcium excretion and a decrease in the total number of platelets. Seven patients with symmetric plaque-type psoriasis were treated topically with 2 micrograms/g of 1,25(OH)2D3 in petrolatum. During 3 months of follow-up, mild improvement was noted in three patients. Five patients in the calcipotriene study were part of a nationwide double-blind placebo-controlled trial by Bristol-Myers Squibb. Moderate to marked improvement was noted in the two patients who received 50 micrograms/g of calcipotriene topically. The three patients who received placebo showed no response. We conclude that a subset of patients with psoriasis responds well to 1,25(OH)2D3. Calcipotriene is efficacious and an excellent alternative to topically applied corticosteroids.

Administration, Oral↗

Paraneoplastic pemphigus: a subset of patients with pemphigus and neoplasia.

We reviewed the clinical, histologic, and immunofluorescence features of 20 patients with pemphigus and neoplasia and compared them with a control group of 17 patients with pemphigus without neoplasia. Patients with neoplasia were divided according to clinical, histologic, and immunofluorescence findings into those with paraneoplastic pemphigus syndrome (12 patients) and those with classic pemphigus vulgaris or pemphigus foliaceus with neoplasia (8 patients). The histologic findings in patients with paraneoplastic pemphigus included acantholysis, interface dermatitis, spongiosis, and satellite keratinocyte necrosis. Histologic findings in the 8 patients with classic pemphigus and neoplasia included acantholysis and spongiosis. Direct immunofluorescence in both paraneoplastic pemphigus and pemphigus with neoplasia showed IgG staining of cell-surface proteins (intercellular substance) and deposition of immunoglobulin at the basement membrane zone. Indirect immunofluorescence with rat bladder substrate was used to differentiate paraneoplastic pemphigus from classic pemphigus. Circulating IgG anti-cell-surface protein antibodies were detected in 4 patients with paraneoplastic pemphigus syndrome; they were absent in 2 patients with pemphigus and neoplasia. Immunoprecipitation of sera from the 4 patients with epithelial staining showed the complex of bands identified in studies of paraneoplastic pemphigus syndrome. We conclude that paraneoplastic pemphigus syndrome has distinct clinical, histologic, and immunologic features that differentiate it from classic pemphigus with underlying neoplasia.

Aged↗