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Biomedical subjects

W P Su

Publications and source records attributed to W P Su.

At least 19 recordsLinked to original sources

Improved Monte Carlo sampling in a real space approach to the crystallographic phase problem.

A real space approach has been proposed to solve the x-ray phase problem formulated as a minimization problem. The cost function consists of two parts: one represents the usual crystallographical residual while the other enforces the probability distribution of the invariant phase triplets. Starting from a random real space structure, the atoms are moved one by one to gradually reduce the cost function (simulated annealing). In addition, the atoms are encouragd to preferentially sample the high density regions in space determined by an approximate density map which in turn is updated and modified by averaging and Fourier synthesis. Such a reduction of the configurational space has led to considerable improvement of the algorithm compared to an earlier version. Trial calculations for structures including hexadecaisoleucinomycin (HEXIL) and a collagenlike peptide (PPG) are presented.

Journal Article↗

A modified X-Y method.

The X-Y method seeks to solve the unknown phases of the X-ray reflections by minimizing a function (the X-Y function) of the phases. This cost function has been supplemented with a residual term. The total cost function is minimized by varying the positions of atoms. Simulated annealing is used to implement the minimization. Trial calculations for structures containing up to 176 non-H equal atoms have been carried out successfully.

Journal Article↗

Pseudoporphyria: a clinical and biochemical study of 20 patients.

OBJECTIVE: To describe the clinical and laboratory findings in patients with pseudoporphyria. PATIENTS AND METHODS: This retrospective review identified 261 patients with either porphyrin metabolism abnormalities or pseudoporphyria who were seen at the Mayo Clinic in Rochester, Minn, between 1992 and 1996. All patients with documented porphyria cutanea tarda (PCT), noncutaneous porphyrias, or variegate porphyria were excluded. RESULTS: Twenty patients had active cutaneous lesions resembling PCT with no diagnostic laboratory abnormalities. The major presenting clinical features were blistering in 19 patients (95%), scarring in 14 (70%), photosensitivity in 13 (65%), skin fragility in 13 (65%), and milia in 8 (40%). Histologically, of 17 patients tested, 12 (71%) had classic findings of subepidermal separation with festooning of dermal papillae. None of the 11 patients tested had hepatitis B or C. In all 20 patients, porphyrin profiles were nondiagnostic. Of 16 patients for whom follow-up was available, 11 reported persistent symptoms for a mean of 2.5 years after evaluation. Five patients were free of symptoms 1 week to 6 months after discontinuation of the presumed offending agent. CONCLUSION: Pseudoporphyria mimics the cutaneous symptoms of PCT in the setting of normal or near-normal porphyrin levels in the serum, urine, or stool. Despite efforts to discontinue an offending medication, symptoms may persist indefinitely.

Adult↗

A hybrid minimal principle for the crystallographic phase problem.

Simulated annealing is used to solve the X-ray phase problem formulated as a minimization problem. The cost function consists of two parts, one represents the discrepancy between measured and calculated intensities while the other monitors the probability distribution of the triplets. From a random real-space structure at the start, the atoms are moved one by one to gradually reduce the cost function until the best structure emerges. Trial calculations for structures including hexadecaisoleucinomycin (HEXIL) are presented. Comparison of this method with other related methods is made.

Crystallography, X-Ray↗

Late onset hyalinosis cutis et mucosae.

Two cases of non-familial, late onset (50 and 62-years-old) hyalinosis cutis et mucosae were studied and compared with classical early onset cases. Late onset cases showed essentially the same histological and ultrastructural features described for early onset cases. The late onset variety should be distinguished from other diseases; they resemble systemic amyloidosis and sometimes the adult form of colloid milium.

Age Factors↗

Dowling-Degos disease (reticulate pigmented anomaly of the flexures): a clinical and histopathologic study of 6 cases.

BACKGROUND: Few case series describing Dowling-Degos disease (DDD) have been reported. OBJECTIVE: Our purpose was to review the clinical and histopathologic findings in DDD. METHODS: We reviewed the clinical and histopathologic findings in 6 patients with DDD who were evaluated at the Mayo Clinic. RESULTS: In addition to the typical flexural pigmented reticulate macules, comedo-like lesions on the back or neck or both were present in all 6 patients; 3 patients had pitted perioral scars, and 3 patients reported pruritus of affected flexural areas. Five patients were female, 5 patients had onset of pigmentation before age 24 years, and 3 patients had a family history of DDD. One patient had additional pigmentation involving the dorsum of the hands and proximal nailfolds and fingernail dystrophy. Histopathologically, pigmented rete ridge elongation with thinning of suprapapillary epithelium, dermal melanosis, and perivascular lymphohistiocytic infiltration were consistently observed. CONCLUSION: Comedo-like lesions, pruritus, and pitted perioral scars are common features in association with the reticulate flexural pigmentation. Histopathologically, pigmented rete ridge elongation and dermal melanosis of biopsy specimens from flexural areas are seen.

Adolescent↗

Possible involvement of DNA methylation in 5-azacytidine-induced neuronal cell apoptosis.

Eight chemicals that are cytidine analogues or nucleosides (5-azacytidine (5AzC), 5-azadeoxycytidine, 6-azacytidine, 5-azacytosin, cytidine, 3-deazaadenine, 3-deazauridine and 6-azauridine) were examined for the ability to induce neuronal apoptosis. 5AzC and 5-azadeoxycytidine induced apoptosis in the brain and spinal cord of the fetuses at 24 hr after the injection to dams, while the other chemicals tested failed to induce apoptosis. In the system of PC12 cells, only 5AzC induced apoptosis, and other chemicals failed to provoke morphological and biochemical changes characteristic of apoptosis. 5AzC, 5-azadeoxycytidine and 6-azacytidine failed to induce apoptosis in C6 cells. Gel electrophoresis after MspI or HapII digestions revealed no apparent evidence of DNA demethylation after 5AzC-treatment in either fetal brains or PC12 cells. These results indicate that DNA demethylation is possibly involved in 5AzC-induced neuronal apoptosis although no direct evidence of DNA demethylation was obtained.

Animals↗

Scleromyxedema: a complete response to prednisone.

Scleromyxedema is a disorder characterized by a typical rash due to the accumulation of mucin in the dermis. It is always associated with a monoclonal protein in the serum and can have a wide variety of systemic manifestations. We describe a 40-year-old woman who had scleromyxedema associated with a monoclonal G lambda protein. Severe systemic symptoms included fatigue, esophageal dysmotility, and myopathy. Symptoms resolved completely with oral prednisone therapy, and she remained in clinical remission 24 months after use of prednisone was discontinued. Scleromyxedema is commonly treated with alkylating agents, which have been associated with pronounced morbidity and mortality. We suggest that oral corticosteroid therapy may be a reasonable initial choice for treating this disease and that alkylating agents be reserved for corticosteroid-refractory disease.

Adult↗

Cutaneous manifestations of Churg-Strauss syndrome: a clinicopathologic correlation.

BACKGROUND: Allergic granulomatosis of Churg-Strauss (Churg-Strauss syndrome) is a distinct clinical disease of multisystem vasculitis. OBJECTIVE: We characterize the clinical and histologic features of cutaneous findings in Churg-Strauss syndrome. METHODS: All patients with Churg-Strauss syndrome seen between 1976 and 1995 were retrospectively reviewed. RESULTS: Ninety patients with the diagnosis of Churg-Strauss syndrome were identified; 36 (40%) had cutaneous findings. Five patients (6%) had skin lesions as the initial manifestation. The most frequent cutaneous findings were purpura and petechiae on the lower extremities and cutaneous nodules and papules on the elbows. In 37 biopsy specimens from 29 patients, the most common findings were extravascular necrotizing granuloma (15 specimens) and leukocytoclastic vasculitis (16 specimens). CONCLUSION: Cutaneous lesions in Churg-Strauss syndrome are common. Their characteristic clinical and histologic pattern may help establish the diagnosis.

Adolescent↗

Antiphospholipid syndrome and the skin.

The antiphospholipid syndrome is an acquired multisystem disorder of hypercoagulation, which may be primary or secondary to underlying diseases. Serologic markers for the syndrome are the lupus anticoagulant and anticardiolipin antibodies. Clinical features include recurrent thrombotic events (arterial or venous), repeated fetal loss, and thrombocytopenia. Cutaneous manifestations may occur as the first sign of antiphospholipid syndrome. These include livedo reticularis, necrotizing vasculitis, livedoid vasculitis, thrombophlebitis, cutaneous ulceration and necrosis, erythematous macules, purpura, ecchymoses, painful skin nodules, and subungual splinter hemorrhages. Antiphospholipid syndrome may also be associated rarely with anetoderma, discoid lupus erythematosus, cutaneous T-cell lymphoma, or disorders that closely resemble Sneddon or Degos syndromes. Noninflammatory vascular thrombosis is the most frequent histopathologic feature observed. Prophylaxis and treatment of thrombosis in patients with antiphospholipid syndrome relies principally on anticoagulant and antiplatelet agents.

Antiphospholipid Syndrome↗

Microcystic adnexal carcinoma with extensive sebaceous differentiation.

We report two cases of microcystic adnexal carcinoma showing extensive sebaceous differentiation. Multiple cellular nests and strands within a moderately sclerotic stroma involving the full thickness of the dermis were observed. Clusters of basaloid cells with extensive sebaceous differentiation were present. Foci of sebaceous ductal differentiation were observed in the more superficial areas. Neither strikingly atypical cells nor mitotic figures were present. Perineural invasion was present in the deep areas of both tumors. Clinically, the lesions were solitary whitish-pink papules with a central dell on the faces of 2 men (aged 78 and 73 years old). We propose a relationship between these tumors and other cytologically bland but locally aggressive adnexal carcinomas. Sebaceous differentiation itself in a poorly circumscribed neoplasm does not indicate conventional extraocular sebaceous carcinoma. We propose a simple classification of locally aggressive adnexal carcinomas that takes into account the full range of adnexal differentiation that can occur in such lesions.

Aged↗

Malignant melanoma: basic approach to clinicopathologic correlation.

To provide an overview of the clinicopathologic correlation of the various types of malignant melanoma, we describe and illustrate the four major types of these tumors and discuss the concept of microstaging for the prognostic evaluation of melanoma. The four major types of malignant melanoma are lentigo maligna melanoma, acral lentiginous melanoma, superficial spreading melanoma, and nodular melanoma. Lentigo maligna melanoma has irregular margins and usually occurs on sunlight-exposed skin in elderly patients. Acral lentiginous melanoma occurs on the hands and feet; it often demonstrates massive invasion when the vertical growth phase occurs. Among Caucasians, superficial spreading melanoma, which affects the trunk and extremities, is the most common malignant melanoma. These lesions are often variegated in color. Nodular melanomas are deeply pigmented and enlarge rapidly. For microstaging of malignant melanoma, determining Clark's level of tumor invasion or Breslow's thickness (from the top of the granular cell layer of the epidermis to the deepest extension of the tumor) is useful for assessment of prognosis. Establishing a definite diagnosis of malignant melanoma is feasible through clinicopathologic correlation. Microscopic measurement of the deepest levels of melanoma involvement in the skin provides a useful indication of the associated prognosis.

Humans↗

The epidemiology of morphea (localized scleroderma) in Olmsted County 1960-1993.

OBJECTIVE: To determine the incidence, prevalence, survival rates, clinical manifestations, and longterm outcome of patients with morphea (localized scleroderma) and its subtypes over a 33 year period in Olmsted County, Minnesota. METHODS: We used the unique data resources of the Rochester Epidemiology Project to review all Olmsted County medical records with any potential diagnosis consistent with morphea (including plaque, generalized, bullous, linear, and deep entities) from 1960 through 1993. RESULTS: We screened 1030 medical records and identified 82 (59 female; 23 male) cases of morphea first diagnosed between 1960 and 1993. All cases were followed until death or migration from Olmsted County, a total of 754 person-years of observation. The annual age and sex adjusted incidence rate per 100,000 population was 2.7 (95% confidence interval 2.1, 3.3). The incidence rate increased significantly over the 33 years (p = 0.0037) on an average of 3.6% per year. The prevalence (estimated using cumulative incidence) at 80 years of age was about 2/1000. 50% of the patients had a cutaneous softening or evidence of disease resolution by 3.8 years' duration. The shortest active disease duration was found in the plaque group (50% resolution or skin softening by 2.7 years) compared to 5.5 years in the deep group. Arthralgias, synovitis, uveitis, and joint contractures were more frequent in the linear and deep categories. Although 9 patients (11%) developed some disease related disability over the followup period, this was common (44%) in the deep group. No case of morphea developed severe internal organ involvement and none progressed to systemic sclerosis. The survival rate was not significantly different from the general population (p = 0.409). CONCLUSION: Morphea, and its subtypes, are more common than previously recognized, and can lead to important disability.

Adolescent↗

Trends in the population-based incidence of squamous cell carcinoma of the skin first diagnosed between 1984 and 1992.

OBJECTIVE: To examine the incidence of first diagnosis of invasive squamous cell carcinoma (SCC) of the skin over time. DESIGN: Retrospective, population-based incidence study. SETTING: Enumerated, geographically isolated, semiurban population served by the Mayo Clinic and its affiliated hospitals and the Olmsted Medical Center, including its affiliated hospital in Rochester, Minn. METHODS: Using the Rochester Epidemiology Project databases that capture virtually all medical care provided to the residents of Rochester, we identified and reviewed records of all documented residents in whom histologically proven, invasive SCC of the skin was first diagnosed between 1984 and 1992. Age and sex stratum-specific rates were calculated, and age-adjusted rates observed over time for individuals aged 35 years or older were analyzed using Poisson regression. Adjusted rates were compared with the results of other studies. RESULTS: Review of 1630 records identified 511 incidence cases of SCC. Tumors located on the head and neck accounted for 66.4% of tumors in females and 72.9% in males. The annual age- and sex-specific incidence rates per 100,000 increased from 0 cases among males aged 0 to 14 years to 1286.0 cases among males aged 85 years or older. Over time, the annual age-adjusted incidence rates per 100,000 females rose from 46.5 (95% confidence interval [CI], 32.4-60.6) for the 1984 to 1986 period to 99.6 (95% CI, 80.4-118.7) for the 1990 to 1992 period and were 71.2 (95% CI, 61.7-80.8) overall. The corresponding rates for males were 125.9 (95% CI, 95.3-156.4), 191.0 (95% CI, 156.9-225.0), and 155.5 (95% CI, 137.0-174.0). The age- and sex-adjusted SCC incidence rates for the period from 1987 to 1989 and 1990 to 1992 exceeded those for the period from 1984 to 1986 (P = .03 and P < .001, respectively). Our age-adjusted rates for SCC were within the ranges seen in other white populations from temperate climates. CONCLUSION: The frequencies of first diagnosis of SCC are increasing at rates beyond those explainable by demographic shifts alone.

Adolescent↗

Eosinophilic vasculitis in connective tissue disease.

BACKGROUND: Neutrophilic and lymphocytic vascular inflammation is common in vasculitis associated with connective tissue disease (CTD). We recently identified eight patients with CTD and eosinophilic vasculitis. OBJECTIVE: The purpose of this study was to characterize a variant form of vasculitis in CTD with eosinophilic infiltration. METHODS: Of 98 CTD patients with cutaneous necrotizing vasculitis, eight were found with predominantly eosinophilic vascular infiltration. Nine CTD patients with cutaneous neutrophilic vasculitis were identified for comparison. Clinical and laboratory findings were reviewed and compared. Indirect immunofluorescence for eosinophil granule major basic protein (MBP), neutrophil elastase, and mast cell tryptase was performed on lesional tissue. MBP levels and eosinophil survival enhancing activity were assayed in sera from three patients. RESULTS: The patients with eosinophilic vasculitis had depressed serum complement levels and peripheral blood eosinophilia; MBP levels were elevated in serum and eosinophil survival was prolonged. Immunofluorescence of tissue showed marked angiocentric eosinophil MBP staining with peripheral neutrophil elastase staining; mast cell tryptase staining was notably absent. The patients with neutrophilic vasculitis were variably hypocomplementemic and did not have peripheral blood eosinophilia. Immunofluorescence showed marked angiocentric neutrophil elastase staining with scattered eosinophil MBP staining; mast cell tryptase staining showed normal mast cell numbers. CONCLUSION: Patients with eosinophilic vasculitis, CTD, and hypocomplementemia show vessel wall destruction in association with vessel wall deposition of cytotoxic eosinophil granule MBP, which suggests that eosinophils mediate vascular damage in this disease process. In addition, perivascular mast cells appear diminished, thereby suggesting that mast cell degranulation occurs.

Adult↗

Pyoderma gangrenosum: classification and management.

Pyoderma gangrenosum (PG) has four distinctive clinical and histologic variants. Some have morphologic and histologic overlapping features with other reactive neutrophilic skin conditions. PG often occurs in association with a systemic disease, and the specific clinical features of the skin lesion may provide a clue to the associated disease. Management of PG depends on its type and severity and usually requires aggressive local and systemic treatment.

Humans↗

Lipomembranous (membranocystic) fat necrosis. Clinicopathologic correlation of 38 cases.

Clinicopathologic correlation of cutaneous biopsy specimens demonstrating typical lipomembranous fat necrosis was performed. Material from 732 biopsies of various subcutaneous inflammatory disorders seen at our institution in the past 5 years was screened for typical lipomembranous (membranocystic) changes in the panniculus, and 39 specimens from 38 patients with these changes were identified. The most common clinical context in which this condition was observed was in chronic sclerotic plaques of the lower legs associated with venous insufficiency (37% of the total cases). All patients were women, and the majority were obese. Typical lipomembranous fat necrosis was also observed in eight cases (21%) of erythema nodosum, three (8%) of morphea or subcutaneous morphea (or both), two (5%) of lupus panniculitis, two (5%) of necrobiosis lipoidica, and in single cases of polyarteritis nodosa, necrotizing vasculitis, and erysipelas. Six cases (16%) had no definite underlying disease. The mean age of all patients was 57 years (range 32-86 years), and 34 patients (89%) were women. Of the five major categories identified, lipomembranes lining macrocysts and microcysts were most prominent in the venous insufficiency- and morphea-related cases and were much less prominent in erythema nodosum, lupus panniculitis, and necrobiosis lipoidica, which generally showed histopathologic findings typical of these disorders. In addition to lining the macrocystic and microcystic cavities formed in the fat lobules, lipomembranes were prominent in areas of septal fibrosis in all cases associated with morphea and necrobiosis lipoidica and in 35% and 25% of venous insufficiency- and erythema nodosum-related cases, respectively. In lupus panniculitis, lipomembranes were most prominent in areas of hyaline necrosis. We conclude that lipomembranous fat necrosis is most likely a nonspecific form of ischemic fat degeneration that may be induced by various clinical entities. This change is most often seen in venous insufficiency-associated chronic sclerotic plaques typically observed in middle-aged obese women, and we propose the term stasis-associated lipomembranous panniculitis (SALP) to describe this most common form of lipomembranous fat necrosis.

Adipose Tissue↗

Solitary sclerotic fibroma of the skin: a sclerotic dermatofibroma?

Two cases of solitary tumors showing well-demarcated hypocellular, dermal fibrocollagenous proliferations are reported. The lesions were composed of hyalinized eosinophilic collagen bundles arranged in the characteristic interwoven pattern with prominent clefts, as described in sclerotic fibroma of the skin. This pattern, although predominant, was not uniform. Some areas showed a more cellular pattern with histopathologic features suggestive of dermatofibroma. In those areas, multiple spindle-shaped cells and occasional multinucleated cells were observed. The collagen bundles did not adopt a whorled pattern, and the overlying epidermis showed mild acanthosis and elongation of the rete ridges. The sclerotic changes were present mainly at the periphery and in the deep areas of the tumor. Our observations confirm the possibility that solitary sclerotic fibroma of the skin may represent, at least in some instances, the later and sclerotic stage of other more cellular neoplasms (specifically dermatofibromas) rather than an individualized neoplasm, as has been recently proposed.

Adult↗