The developmentally regulated neural crest-associated glycotope HNK-1 predicts metastasis in cutaneous malignant melanoma

Aberrant glycosylation is a common feature of metastatic sub-clones of malignant tumours and in uveal melanoma in particular, the HNK-1 glycotope has been positively correlated with poor prognosis. So far, no such correlation has been investigated in cutaneous melanoma. In order to do so, HNK-1 expression was evaluated immunohistochemically in 100 primary cutaneous melanomas and correlated with metastasis after up to 10-years' follow-up. Furthermore, HNK-1 expression was analysed in metastatic deposits (19 distant cutaneous metastases and six sentinel lymph node metastases), as well as in benign nevi. Kaplan-Meier analysis revealed a positive association between HNK-1 expression and metastasis (p < 0.005) and multivariate Cox regression analysis adjusted for the standard prognostic markers ulceration and vertical tumour thickness confirmed HNK-1 expression as an independent prognostic marker. HNK-1 expression was preserved in 42% of the distant cutaneous metastases, but metastatic cells in lymph nodes were devoid of HNK-1 immunoreactivity. None of the benign pigmented lesions exhibited HNK-1 immunoreactivity. Expression of the HNK-1 glycotope in cutaneous malignant melanoma is an independent prognostic marker of metastasis. Differential HNK-1 expression at the metastatic sites implies that its expression is modulated by the surrounding environment. As HNK-1 is also transiently expressed during migration of melanocyte precursor cells derived from the neural crest, recapitulation of this transient expression might occur during metastatic spread of cutaneous malignant melanoma.     

Dissociated cells of foetal rat pallium grown in culture medium supplemented with noradrenaline: effects on the expression of neuron-specific enolase and cell adhesion molecule L1

The possible influence of noradrenaline (NA) upon cell differentiation has been studied by comparing NA-supplemented cultures of foetal pallial cells with control cultures grown in normal medium. Two days after plating, the cultures were processed for immunocytochemical detection of either an adhesion molecule and marker of early stages of neuronal differentiation (L1) or a marker expressed at relatively late stages (gamma-enolase). In both cases, the NA supplement reduced the expression of the antigen. The effects were more clear-cut for the late than for the early marker. In conclusion, the NA supplement to the culture medium, in our model, seemed to have a 'differentiation regulating' rather than a 'neurotrophic' function sensu stricto. It remains to be clarified, however, to which extent this finding can be generalized to in vivo situations.     

Antibody L1 ejected from a micropipette identifies neurons without altering electrical activity

Antibody L1 which reacts specifically with the cell surface of central nervous system neurons was pressure ejected from a micropipette into the vicinity of a cultured neuron, or applied to the bathing fluid during intracellular recording of activity. No alterations in membrane potential, shape of action potential, firing rates and postsynaptic activities were observed. Binding of antibody was observed by indirect immunofluorescence after injection of Lucifer Yellow. Bath application of antibody resulted in a uniform neuronal staining over the entire culture, whereas pressure ejected antibodies were limited to neuronal structures within about 200 micron of the cell recorded from. Live, L1 antigen-positive neurons could be identified by indirect immunofluorescence prior to recording.     

Photoreception and sensory transduction in Aneural Organisms,NATO advanced study institutes series A,Vol. 33: Edited by Francesco Lenci and Giuliano Colombetti Plenum Press,New York, 1980. $45.00 in U.S.A. and Canada and $54.00 outside U.S.A. and Canada (432 pp.) ISBN 0-306-404370-0

(?) 2-Amino-7-phosphonoheptanoate and (?) 2-amino-5-phosphonovalerate were shown to possess selective and powerful antagonistic activity vis-à-vis the neurotoxic effects of ibotenic acid in the rat hippocampal formation. The neurotoxicity of kainic acid was not blocked by either drug.     

Epidermal growth factor is not detectable in developing and adult rodent brain by a sensitive double-site enzyme immunoassay

A highly sensitive double-site enzyme immunoassay for epidermal growth factor (EGF) was used to quantify EGF concentrations in brain and cerebrospinal fluid of early postnatal and adult mice and rats. EGF was not detectable under any condition at sensitivity levels of 0.06 ng/g wet wt. These observations support the notion that EGF receptors on astrocytes are triggered by other growth factors than EGF.     

Tenascin-C expression by neurons and glial cells in the rat spinal cord: Changes during postnatal development and after dorsal root or sciatic nerve injury

Summary We have usedin situ hybridization with a digoxigenin-labelled probe for tenascin-C mRNA and immunocytochemistry with antibodies against tenascin-C, glial fibrillary acidic protein, OX-42 and the 200 kDa neurofilament protein to study the expression, distribution and cellular relationships of tenascin-C mRNA and protein in the developing (postnatal) and adult spinal cord of rat, and the effects thereon of dorsal root, ventral root and sciatic nerve injuries. The most interesting finding was that on postnatal day 7 (P7), P14 and in the adult, but not on P0 or P3, a group of neurons in the lumbar ventral horn expressed the tenascin-C mRNA gene. They represented about 5% of ventral horn neurons in the adult and were among the smaller such neurons. Since 40–60% of such cells were lost at P13 following sciatic nerve crush on P0, some were almost certainly motor neurons. In addition, we found that at P0 and P3, mRNA-containing glial cells were widespread in grey and white matter but sparse in the developing dorsal columns; tenascin-C immunofluorescence showed a similar distribution. By P7 there were fewer mRNA-containing cells in the ventral horns and in the area of the dorsal columns containing the developing corticospinal tract where immunofluorescence was also weak. At P14 there were no glial-like mRNA-containing cells in the grey matter; such cells were confined to the periphery of the lateral and ventral white columns but were present throughout the dorsal columns where tenascin-C immunofluorescence was also strong. No glial-like mRNA-containing cells were present in the adult lumbar spinal cord and tenascin-C immunofluorescence was confined to irregular patches in the ventral horn, especially around immunonegative cell bodies of small neurons, a zone around the central canal, and a thin zone adjacent to the glia limitans. Thus the expression of tenascin-C is differentially developmentally regulated in the grey matter and in different parts of the white matter. Three days after injury of dorsal roots L4–6, many cells containing tenascin-C mRNA, some identified as glial fibrillary acidic protein-positive astrocytes, were present in the ipsilateral dorsal column, but were rare after longer survivals. Immunoreactivity, however, was elevated in the ipsilateral dorsal column at 3 days, remained high for several months and disappeared at 6.5 months. Dorsal root injury had no effect on tenascin-C mRNA or protein in the grey matter. Sciatic nerve or ventral root injury had no effect on these molecules in any part of the spinal cord.     

Bronchial adenoma: surgical experience with long-term follow-up (4-17 years)

Of 16 patients with bronchial adenoma who were operated on at Beilinson Medical Center from 1967 to 1980, only three presented the "triad" of cough, hemoptysis, and recurrent pulmonary infections. In two patients the tumor was diagnosed incidentally and in five patients histological evidence of adenoma was made during bronchoscopy. One patient died of myocardial infarction following reoperation for bleeding, and one patient was lost to follow-up. The remaining 14 patients were followed for 4 to 17 years without evidence of local recurrence or distant metastases. We conclude that the long-term prognosis of patients with bronchial adenoma is excellent, and limited surgical procedure should be the treatment of choice whenever possible.