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Biomedical subjects

M W Lee

Publications and source records attributed to M W Lee.

At least 55 records · Page 3Linked to original sources

Vasoactive intestinal polypeptide stimulates the proliferation of HaCaT cell via TGF-alpha.

It is well known that psoriasis, an immunogenetic cutaneous disorder whose major pathogenic findings are epidermal hyperplasia and T-cell infiltration, is aggravated by psychological stresses. Although the exact mechanism is not yet clarified, antidromic secretion of neuropeptides by cutaneous nerve fibers is thought to be involved. In this study, we examined the effect and mechanism of vasoactive intestinal polypeptide (VIP), one of the major neuropeptides, on the proliferation of HaCaT cell which is a spontaneous, immortalized, human keratinocyte cell line. Twenty-four and 48 h after its addition, 1 pM to 100 nM of VIP increased the number of cells cultured with/without serum. We indirectly verified VIP(1)R on the surface of HaCaT cell based on the proliferative ability of various VIP families such as VIP, PACAP and secretin, and increased PKA level 30 min after stimulation. However, because H-89, a PKA inhibitor, did not inhibit the proliferative potential of VIP, its mitogenicity is not medicated through VIP(1)R. One nM VIP produced the TGF-alpha protein which is a strong mitogen of keratinocytes and increased in the psoriatic lesion 2.25 times more compared with the control. Genistein, a tyrosine kinase inhibitor, abrogated the mitogenic activity of VIP. Like VIP, VIP fragments, VIP(1-12) and VIP(10-28) also acted as a mitogen for HaCaT cells through the same mechanism. Collectively, our studies clearly show that VIP and its fragments stimulate keratinocyte growth, not through increased cAMP level, but through increased TGF-alpha protein production.

Cell Division↗

Congenital CD34-positive granular cell dendrocytosis.

Granular cell tumors involving the skin are mostly acquired lesions. The Schwann cell origin of these lesions is supported by positive immunostaining for S-100 protein and myelin basic protein. S-100- granular cell lesions rarely have been described in association with fibrous papules or dermatofibromas. The congenital variety of S-100- granular cell tumors occurs almost exclusively in the gingiva. The cell origin of these lesions is not well delineated. We report a hitherto undescribed case of a congenital cutaneous lesion which is histologically characterized by diffuse dermal infiltrates of S-100- but CD34+ granular dermal dendrocytes. The granular appearance of these CD34+ dendrocytes is attributed to an abundance of phagolysosomes. The pathogenetic mechanism of this unusual lesion remains to be elucidated.

Antigens, CD34↗

Assessment of body composition using dual energy x-ray absorptiometry in patients with liver cirrhosis: comparison with anthropometry.

OBJECTIVES: The aim of this study was to evaluate changes of body composition in cirrhotic patients. Dual energy x-ray absorptiometry (DEXA) and anthropometry were used, and the values obtained were compared. METHODS: Mid-arm fat and muscle areas were calculated by anthropometry in 66 cirrhotic patients and 94 healthy controls. In 37 of the cirrhotic patients and 39 of the controls, fat mass, lean soft tissue mass and bone mineral contents were measured with DEXA. RESULTS: The number of cirrhotic patients with measured values below the fifth percentile of normal controls was 21 (31.8%) by mid-arm fat area, six (9.1%) by mid-arm muscle area, 15 (40.5%) by fat mass and 0 (0%) by lean soft tissue mass. The fat mass in cirrhotic patients was less than in controls, whereas lean soft tissue mass and bone mineral content were not different. Fat depletion was severe in Child-class C patients and with severe ascites. Mid-arm fat area and fat mass showed close correlation (r = 0.85, p < 0.01), but mid-arm muscle area and lean soft tissue mass showed poor correlation (r = 0.32, p < 0.05). CONCLUSION: Cirrhotic patients showed lower fat component, with preserved lean soft tissue mass and bone mineral content. In clinical practice, the measurement of mid-arm fat area was useful for the assessment of fat mass.

Absorptiometry, Photon↗

Immunohistochemical profile of myogenin and MyoD1 does not support skeletal muscle lineage in alveolar soft part sarcoma.

BACKGROUND: The histogenesis of alveolar soft part sarcoma remains elusive. Myogenic origin is favored, although conflicting data on immunohistochemical demonstration of muscle-associated markers exist. Myogenin and MyoD1, transcription factors of the myogenic determination family, have crucial roles in commitment and differentiation of mesenchymal progenitor cells to myogenic lineage and in maintenance of skeletal muscle phenotype. Their immunohistochemical detection is specific in characterization of rhabdomyosarcoma. METHODS: Antibodies for myogenin, MyoD1, desmin, and muscle-specific actin were employed on a large series of cases (n = 19) of formalin-fixed, paraffin-embedded alveolar soft part sarcoma. RESULTS: Minimal scattered nuclear staining was seen with myogenin. All cases had pronounced, nonspecific granular cytoplasmic immunostaining with MyoD1; nuclei were negative. All tumors were negative for desmin and muscle-specific actin. Ultrastructural study in 10 cases failed to reveal features of skeletal muscle differentiation. CONCLUSIONS: Cytoplasmic staining with MyoD1 in alveolar soft part sarcoma may correspond to cross-reactivity with an undetermined cytoplasmic antigen. The lack of immunostaining with myogenin, MyoD1, desmin, and muscle-specific actin provides evidence against a myogenic origin for alveolar soft part sarcoma.

Actins↗

Spores and mycelia in cutaneous chromomycosis.

In 2 cases of cutaneous chromomycosis, potassium hydroxide preparations of lesional crust/scale easily revealed characteristic Medlar bodies. However, in both instances mycelia were also demonstrated. This contradicts the prevailing belief that concomitant spores and mycelia are found only in cerebral chromomycosis.

Biopsy↗

Cutaneous verruciform xanthoma: a report of five cases investigating the etiology and nature of xanthomatous cells.

Verruciform xanthoma is a rare clinicopathologic entity of uncertain etiology that occurs primarily in the oral mucosa. Aggregates of foam cells in the submucosal stroma or papillary dermis in association with verrucous epithelial hyperplasia are the hallmark of this lesion. Extraoral (cutaneous) occurrence of verruciform xanthoma is much rarer and has been reported mostly in the genital skin. Five cases of extraoral cutaneous verruciform xanthoma (three from the scrotum, one from the penis, and one from the nose) and one histologic "simulant" (from skin of the nose) were studied. The lesions were solitary, raised, or polypoid with cup-shaped craters filled with parakeratotic cells that blended into keratinocytes of an acanthotic and papillomatous epidermis. There was a neutrophilic infiltrate of varying intensity between plump parakeratotic cells and keratinocytes, near the surface of the epidermis. Aggregates of foam cells were present in the papillary dermis, which was highly vascular. A plasma cell predominant infiltrate was seen at the base in a bandlike fashion. Despite the architectural resemblance of verruciform xanthoma to verrucous mucocutaneous lesions related to human papillomavirus infection, it was not detected by either immunohistochemistry, in situ hybridization, polymerase chain reaction, or Southern blot analysis in any case. The foam cells were weakly positive for cytokeratin and for Factor XIIIa but negative for S-100 protein. The KP1 and Mac 387 immunostain showed focal weak staining in foam cells. We postulate that a cascade of events pursue after initial keratinocytic damage attracting neutrophils, with subsequent phagocytosis of necrotic keratinocytic debris by dermal dendrocytes, eventually leading to the ultimate manifestation of the lesion as verruciform xanthoma. The etiologic agent remains elusive, but based on our findings, we conclude that verruciform xanthoma is most likely not a human papillomavirus-associated squamoproliferative lesion and that the foam cells, a histologic hallmark of the lesion, are most likely derived from dermal dendritic cells.

Adult↗

Mycobacterium marinum: chronic and extensive infections of the lower limbs in south Pacific islanders.

We report three adult cases of very chronic, extensive infection of the lower limbs due to Mycobacterium marinum. The patients were from South Pacific islands and, clinically, the widespread warty plaques resembled chromomycosis. One was associated with severe lymphoedema. All three patients gave a history of at least 20 years duration. The patients were otherwise well and not immunologically compromised. In all cases, the organism was identified on tissue cultures and was not seen on histopathology. The mycobacteria were sensitive to most antibiotics tested in vitro. The patients were treated with a combination of rifampicin and cotrimoxazole with good results.

Adult↗

Effect of rebamipide on the glycosaminoglycan content of the ulcerated rat stomach.

To elucidate the mechanism of the anti-ulcer effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2-(1H)-quinolinon-4-yl] propionic acid), changes in glycosaminoglycan (GAG), uronic acid and hexosamine contents of stomach tissue were examined in rats treated with the ulcer-inducing agents and/or rebamipide. Uronic acid and hexosamine contents in acid hydrolysates of stomach tissue were increased after diethyldithiocarbamate (DDC, 800 mg/kg, s.c.) or histamine (300 mg/kg, i.p.) treatment, and similar changes in the GAG, uronic acid, and hexosamine levels were observed in stomach tissue extracts. Pretreatment with rebamipide (60 mg/kg, i.p.) resulted in an additional increase in the contents of the above components after DDC or histamine treatment. However, rebamipide treatment alone did not increase the gastric contents of GAG and GAG components in normal rats. Gel filtration chromatography of extracted GAGs suggested that DDC, histamine and rebamipide treatments do not cause a change in the aggregated forms of gastric GAGs. These results suggest that rebamipide stimulates the GAG synthesis in the ulcerated stomach and that this effect may contribute to the healing process of gastric ulcer.

Alanine↗

Pagetoid Merkel cell carcinoma: epidermal origin of the tumor.

We report a case of intraepidermal Merkel cell carcinoma which occurred on the face of a 76-year-old white male. This slow-growing tumor was mostly confined in the epidermis and pilosebaceous apparatus where tumor cells spread in a pagetoid fashion forming tumor cell nests. Histologically it resembled a superficial spreading melanoma. A heavy lymphocytic infiltration was seen beneath the epidermal lesion as is often seen in pagetoid melanomas. Histochemical and ultrastructural features such as the presence of cytokeratin 20, synaptophysin, neuron specific enolase, desmosomes, and dense cored granules confirmed the diagnosis of Merkel cell carcinoma. Occasional mitotic cells and many apoptotic cells were found in the tumor. Dylon positive, amyloid depositions were seen in the lower epidermis and papillary dermis; they were probably derived from apoptotic tumor cells. It was thought that apoptosis limited the speed of growth of this tumor. We believe that this is probably the most convincing case of intraepidermal Merkel cell carcinoma originating from epidermal Merkel cells or its precursors (stem cells).

Aged↗

Antimitochondrial antibody (113-1) in the differential diagnosis of granular renal cell tumors.

Abundant granular eosinophilic cytoplasm is a common feature of renal oncocytoma, chromophobe renal cell carcinoma, eosinophilic variant of papillary renal cell carcinoma, and the granular variant of clear cell renal cell carcinoma (RCC). Each of these entities has a unique architectural pattern and a distinctive molecular or cytogenetic profile. The chief reason for their distinction from one another is the difference in their biologic behavior. Careful and thorough light microscopic examination distinguishes most cases based on individual characteristic architectural and cytomorphologic features. However, precise characterization may be difficult in some cases because of overlapping morphologic features. We evaluated the antimitochondrial antibody 113-1 in an attempt to ascertain differences in immunostaining patterns in 57 cases of granular renal tumors, including 20 renal oncocytomas, 15 chromophobe RCCs, 13 granular variants of clear cell RCC, and nine eosinophilic variants of papillary RCC. Distinctive, and nearly exclusive, staining patterns were observed among the groups, with chromophobe RCC showing peripheral accentuation of coarse cytoplasmic granules (15 of 15), renal oncocytoma with diffuse and fine granularity (20 of 20), and granular variant of clear cell RCC with irregular cytoplasmic distribution of coarse granules (11 of 13). Staining was most intense in the eosinophilic variant of papillary RCC and was generally coarsely granular and diffuse. Staining patterns also differed in clear cell areas within chromophobe RCC and the granular variant of clear cell RCC. Although clear cells in the former group showed granular staining with peripheral accentuation, most of the clear cells in the latter lacked any staining. We conclude that, in addition to distinct cytoarchitectural features, immunostaining patterns with antimitochondrial antibody 113-1 appear to be a useful discriminatory adjunct in the complex differential diagnosis of granular renal cell tumors.

Adenoma, Oxyphilic↗

Testing the hypothalamic-pituitary-adrenal axis in survivors of childhood brain and skull-based tumors.

The objective of this study was to determine whether a low dose of ACTH (0.2 microg/kg) improves the sensitivity of ACTH testing in detecting hypothalamic-pituitary-adrenal (HPA) axis abnormalities in survivors of childhood brain and skull-based tumors. Twenty-two children who had undergone treatment for brain or skull-based tumors were enrolled in a prospective study to extensively evaluate the HPA axis. Five tests of the adrenal axis were evaluated in each patient, including determination of basal serum cortisol, a standard ACTH test (250-microg i.v. bolus), a low dose ACTH test (0.2 microg/kg i.v. bolus), an insulin tolerance test, and a single dose metyrapone test. Cortisol responses to both ACTH tests were nearly identical. Two patients (9%) failed the low dose ACTH test, whereas three (14%) failed the standard ACTH test; five of the children (23%) failed the insulin tolerance test, and five (23%) had abnormal responses to metyrapone. One child who initially passed the metyrapone test failed the test 19 months later after becoming symptomatic. All children with abnormal metyrapone test results had low levels of basal cortisol secretion. In this study, the low dose ACTH test did not improve the sensitivity of ACTH testing for evaluation of the HPA axis. We conclude that a single morning basal cortisol level is a good screen for testing the HPA axis in children. We recommend confirming HPA axis dysfunction with the single dose metyrapone test, although this test also has limitations.

Adrenocorticotropic Hormone↗