Cytokeratin expression in a congenital multipotential primitive neuroectodermal tumor

A case of an uncommon congenital primitive neuroectodermal cerebellar tumor (PNET) in a 5-month-old child is reported. After subtotal surgical resection, the residual tumor did not respond to radiation and chemotherapy. Histologically, the tumor was composed of small, round, undifferentiated cells and several other patterns like astrocytomatous, oligodendrogliomatous, and ependymomatous structures. Immunostaining was positive for most of the cells for vimentin and S 100, fewer were positive for glial fibrillary acid protein (GFAP) and neuron-specific enolase, and only a few for synaptophysin. Surprisingly, the tumor showed strong expression of several monoclonal cytokeratins (CK) with different molecular weights, together with epithelial membrane antigen. Furthermore, we found a coexpression of the tumor cells for CK and vimentin, while CK-GFAP and CK-S 100 were negative. Ultrastructurally, intracyto-plasmic intermediate filaments could be observed corresponding to immunohistochemical CK expression. The very strong CK and vimentin expression in this case was interpreted as a sign of the embryonic nature of the tumor.     

Protein kinase C agonist and antagonist effects in normal human epidermal keratinocytes

Abstract Several lines of evidence implicate protein kinase C (PKC) in the development of basal cell and squamous cell carcinomas, tumors which originate from epidermal keratinocytes. To examine PKC in a model relevant to human skin, we exposed normal human epidermal keratinocytes (NHEK) in serum-free media to a variety of PKC agonists and antagonists. NHEK PKC activity increased up to 10-fold within the 1st hour of exposure to tetradecanoyl phorbol acetate (TPA), and gradually returned to control values within 72 h. TPA-induced PKC activity was enhanced by pretreatment of cultures with protein and RNA synthesis inhibitors. TPA-induced growth arrest and differentiation was antagonized by staurosporine. Down-regulation by bryostatin pretreatment blocked TPA-stimulated differentiation. Our overall conclusion is that activation of PKC in cultured human keratinocytes is required for differentiation. These results are crucial to the analysis of compounds suspected of promoting or inhibiting epidermal tumors.     

25-Hydroxyvitamin D3 metabolism in a human leukemia cell line

Summary 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) is a potent inducer of monocytic differentiation of the human promyelocytic leukemia cell line, HL-60. We have noted that 25-hydroxyvitamin D₃ (25(OH)D₃) in high doses is also capable of promoting monocytic differentiation of this cell line. To test the possibility that the latter activity is due to conversion of 25OHD₃ to 1,25(OH)₂D₃ by HL-60, we exposed HL-60 cells to 25OHD₃ and analyzed the products by HPLC and radioreceptor assay. When chromatographed in the traditional solvent system (isopropanol-hexane), a new peak appears which migrates with authentic 1,25(OH)₂D₃. However, in a solvent system containing dichloromethane, 90% of the peak migrates with another metabolite, 19-Nor-10-Keto-25OHD₃ (19-Nor-25OHD₃). Production of this metabolite is enhanced by living cells and is synthesized by both virgin HL-60 and those which have undergone differentiation. We next determined if authentic 19-Nor-25OHD₃ also promotes differentiation of this cell. As assessed by appearance of the monocyte-specific surface antigen (63D3) and macrophage-specific esterase activity, we find that this metabolite does, in fact, induce monocytic differentiation of HL-60 with a potency of approximately 1/200 that of 1,25(OH)₂D₃ and similar to that of 25OHD₃. In agreement with the effect upon cell maturation, 19-Nor-25OHD₃ displaces³H-1,25(OH)₂D₃ from its HL-60 receptor with an efficiency comparable to 25OHD₃. Hence, HL-60 cells convert 25OHD₃ to 19-Nor-25OHD₃, and 19-Nor-25OHD₃ induces monocytic differentiation of HL-60 with comparable efficiency to its precursor, 25OHD₃.     

Mucinous adenocarcinoma with neuroendocrine differentiation of the mandibular ramus: report of a case

A rare case of mucinous adenocarcinoma with neuroendocrine differentiation of the mandibular ramus is presented. The patient, an 80-year-old man, was referred to our hospital with chief complaint of swelling and pain in the left buccal mucosa. CT and MRI examination showed an osteolytic tumor mass occupying the upper region of the left mandibular ramus. Macroscopically, the excised tumor was a relatively well-defined, solid mass with diffuse bone resorption, measuring 3 cm x 3.2 cm x 3 cm. Microscopical examination showed that the tumor forming glandular structures with abundant mucous production and high cellular atypia. Immunohistochemical studies demonstrated the positive reactivities for pan-keratin, cytokeratin 7, vimentin,alpha-amylase, alpha-smooth muscle actin, neuron-specific enolase, glial fibrillary acid protein, calcitonin, and somatostatin in tumor cells. These findings suggested that the tumor was originated from heterotopic or misplaced salivary gland in the mandible.     

Evaluation of neural fold fusion and coincident initiation of spinal cord occlusion in the chick embryo.

Although it is known that rapid expansion of the vertebrate brain begins near the time that the spinal neurocoel is occluded, it still remains unknown when occlusion occurs in relation to neurulation. Since both morphogenetic events are critical for normal brain growth, it is important to decipher the temporal relationship between the two processes. This study assessed the temporal relationship of the two events with the rationale that if it could be demonstrated that occlusion occurs coincident with the completion of neurulation, then it could be argued that factors shown to direct neurulation could also initiate occlusion. Nearly 600 chick embryos (stages 9- through 12+) were cultured atop egg-agar, the caudal extent of neurulation determined, the cranial five pairs of somites removed and the neurocoels assessed for occlusion. In stage 9- through 10- chicks, neurulation of the spinal cord is incomplete. Stages 10 through 12+ exhibit neurulation and occlusion from the 8th to 19th somites. When lateral tissues were removed in embryos 8 through 10-, the neural folds became dysraphic whereas in embryos stage 10 and older, the folds remained fused dorsomedially and occluded. The only surgical manipulation that was found to prevent occlusion was elimination of the lateral tissues responsible for elevation and closure of the neural folds. Analysis of particular components of the lateral tissues essential for convergence, by treating embryos (n = 75) with chemicals known to degrade tissue-tissue bonds or specific components of the perineural matrix, indicated that more than 75% of the embryos treated with EDTA, EDTA plus Ca2+, trypsin, collagenase, or hyaluronidase exhibited little or no effect on convergence, dorsomedial fusion, and concomitant occlusion.     

A Hemodynamically Responsive Antitachycardia System: Theoretical Bases for Design

Current antitachycardia systems such as the automatic implantable cardioverter/defibrillator (AICD), detect tachyarrhythmias primarily by sensing rate and thereby perform inadequately in differentiating hemodynamically stable from unstable arrhythmias. As a result, these devices may discharge during stable tachycardias (such as sinus tachycardia), causing discomfort to the patient and depleting the device's limited energy supply. If a parameter which could reflect the particular hemodynamic state of a tachycardia were incorporated into the sensing algorithm of these systems, function may be more hemodynamically precise and discharge specificity may be improved.