Expression of β2m-Free HLA Class I Heavy Chains in Neuroblastoma Cell Lines

Flow cytometry with the specific monoclonal antibody (MoAb) L31 was used to analyse the expression of HLA class I heavy chains not bound with β₂-microglobulin (β₂m) by neuroblastoma (NB) cell lines IMR-32 and LA-N-1. The cells, which express barely detectable amounts of β₂m-free (L31-positive molecules) and β₂m-complexed HLA class I antigens (W6.32- and BBM. I-reactive molecules), expressed MHC class I molecules not bound to light chains upon differentiation with either retinoic acid or serum starvation. The expression was not accompanied by an increase of surface heterodimers. Conversely, recombinant interferon-γ (rIFN-γ) treatment led IMR-32 and LA-N-1 cells to almost exclusively express β₂m-complexed HLA class I heavy chains. Surface β₂m-free MHC class I molecules displayed a molecular mass of ~45 kDa and did not bind exogenously added β₂m. No changes in the synthesis of either HLA class I and β₂m mRNAs or of L31 proteins were observed in differentiated NB cells, thus suggesting that the surface exposure of unusual HLA class I antigens is regulated post-translationally. These findings indicate that, in addition to activated lymphocytes, the surface expression of β₂m-free class I heavy chains is a feature of other cell types, such as NB cells.     

Morphological and biochemical characteristics of trichothiodystrophy-variant hair are maintained after grafting of scalp specimens on to nude mice

Trichothiodystrophy (TTD) is a hair defect associated with abnormal composition of the high-sulphur proteins (HSP). HSP can be modified quantitatively (reduced amount of qualitatively normal HSP: TTD-variant) and qualitatively (TTD). In this study we show that the amino acid composition of hairs collected from the scalp of a patient with TTD-variant (donor) was preserved in hairs produced by donor scalp follicles maintained up to 6 months as grafts on to nude mice. It is the first time that an exceptionally rare, clinically and biochemically well-characterized hair dysplasia has been maintained under laboratory conditions for a long period of time. The linear growth rate of TTD-variant hairs was similar to that of control hairs grown under comparable conditions. The persistence of disease-specific abnormalities in the hair shaft indicates that the TTD-variant mutation is expressed without significant quantitative modifications, and appears independent of systemic host-related factors. This model may serve as a clinically relevant working platform for evaluating regulation of abnormal gene expression in the hair follicle under well-controlled experimental conditions.     

Keratinocytes resident in normal human skin constitutively express, at low levels, the intercellular adhesion molecule-1. An in situ immunoelectronmicroscopy study

Summary The expression of intercellular adhesion molecule-1 (ICAM-1) on keratinocytes (KC) was previously demonstrated in biopsies from various inflammatory skin lesions. KC were, however, found virtually ICAM-1 negative, in normal skin, when the same immunocytochemical techniques were employed. By contrast, epithelial cells resident in different organs constitutively express ICAM-1, albeit weakly. The aim of the present study was to use an immunostaining system more sensitive than the conventional immunocytochemistry, namely the in situ immunogold labelling of ultracryosections, to investigate the constitutive ICAM-1 expression by resting KC in normal skin, in vivo. The semiquantitative analysis performed on 500 resident KC, visualized within tissue ultracryosections of normal human skin, revealed that gold granules were present along the cell membrane in a small percentage (14·6%) of resident KC. The density of gold particles (10 nm sized) observed on the cell surface per KC section was as scarce as 13·72 ± 4·6 (mean ± standard deviation), although highly significant when compared with controls ( P < 0·005). This indicates the presumably low expression of ICAM-1 moieties on the plasma membrane of this KC subset. This ICAM-1 expression could be important in modulating the trafficking to and from normal epidermis of migrating Langerhans cells and occasional leucocytes. The fact that the ICAM-1 expression on KC in normal skin is limited can be considered favourable, because it can account for the prevention of inappropriate KC/leucocyte interactions in the resting cutaneous environment.     

A linkage between hereditary hyperferritinaemia not related to iron overload and autosomal dominant congenital cataract

Summary. The only genetic disorder with elevated serum ferritin levels so far described is hereditary HLA-related haemochromatosis. On the other hand, hereditary cataract is both genotypically as well as phenotypically heterogenous, and no specific locus or any useful marker has been yet identified. We studied two Italian families in whom a combination of elevated serum ferritin not related to iron overload and congenital nuclear cataract is transmitted as an autosomal dominant trait. Affected individuals have normal serum iron and transferrin saturation, but high serum ferritin. Red cell counts are normal and venesection therapy rapidly produces iron-deficiency anaemia.
This genetic disorder, which is characterized by hyperferritinaemia, differs from hereditary HLA-related haemochromatosis mostly for the absence of iron overload. A gene responsible for the congenital nuclear cataract likely maps on chromosome 19q close to the ferritin L-subunit gene. Within families with autosomal dominant congenital cataract, serum ferritin might be an early marker of disease.     

Intra- and inter-observer variation in the interpretation of histological features suggesting chromosomal abnormality in early abortion specimens

Early spontaneous abortion is a common phenomenon, with more than 50% of early cases showing chromosomal abnormalities. We have undertaken a study to evaluate intra- and inter-observer reproducibility of histological diagnoses of features associated with chromosomal abnormalities, such as chorionic villus size, shape, vascularity, trophoblastic proliferation and trophoblastic pseudo-inclusions. The intra-observer variation for most histological features was small. However, the agreement beyond chance between two or more observers in judging histomorphological features of early abortion placentae only reached clinically relevant values for size and shape of the chorionic villi and for the number of trophoblastic pseudo-inclusions.     

Occupational health promotion amongst cattle farmers in Zambia

One of the main activities of the Italian Animal Health Programme(IAHP) in the Republic of Zambia, a bilateral project betweenthe Ministry of Agriculture of the Zambian Government and theGeneral Directorate for Development Cooperation of the ItalianMinistry of Foreign Affairs, is the control of Malignant Theileriosisin Southern Province, through immersion of cattle in dip tankscontaining an acaricide. There are potentially important healthrisks to farm workers and the environment as a result of thisintervention and these are discussed. The control measures undertaken,with special reference to health education programmes, are described.     

Primary cutaneous medium and large cell lymphomas other than mycosis fungoides. An immunohistological and follow-up study on 54 cases

Summary Primary cutaneous medium and large cell lymphomas (MLCL) other than mycosis fungoides (MF) are rare, and their prognosis and treatment are controversial. The clinical, immunohistological and follow-up data of 54 well-documented cases of primary cutaneous MLCL other than MF, seen in our institutions over a 14-year period, were retrospectively reviewed, in order to determine the prognostic factors related to these lymphomas, and to analyse the results obtained with different treatment regimens. Forty-six patients presented with a solitary tumour or with localized lesions. and eight had disseminated cutaneous lesions. According to the updated Kiel classification, 45 cases (83%) corresponded to B-cell lymphomas: centroblastic lymphomas, 32 cases; centroblastic-centrocytic lymphomas, 11 cases; immunoblastic lymphomas, two cases. Nine cases (17%) were classified as T-cell lymphomas: pleomorphic medium and large cell lymphomas, eight cases; anaplastic large cell lymphoma. one case. Four of eight patients with disseminated skin lesions had a T-cell lymphoma. whereas 41 of 46 patients with a solitary tumour had a B-cell lymphoma. Patients with disseminated skin lesions and elevated serum lactate dehydrogenase (LDH) levels had a poor prognosis. Comparison of patients' overall survival, depending on immunohistological subtype, showed that the median survival of patients with pleomorphic T-cell lymphoma was 2·5 years, whereas it was not reached at 12 years for patients with centroblastic centrocytic and centroblastic lymphoma. The eight patients with disseminated skin lesions were treated with polychemotherapy. Most patients with a solitary tumour or with localized lesions of low tumour bulk were treated by surgical excision or radiotherapy alone, and nine other patients with localized lesions of high tumour bulk were treated with initial polychemotherapy. Clinical presentation (i.e. solitary or disseminated lesions), serum LDH levels, and the immunohistological subtype, are important prognostic factors in cutaneous MLCL. Patients with disseminated skin lesions have a poor prognosis, and should be treated with intensive polychemotherapy regimens, whereas those with a solitary tumour, or with localized lesions of low tumour bulk, are adequately treated by radiotherapy.     

Myomenukleation in der Therapie der weiblichen Infertilität

Zusammenfassung Die Myomnukleation scheint als prim?re therapeutische Ma?nahme in der Sterilit?tsbehandlung effektiv zu sein, falls zus?tzliche fertilit?tsmindernde Faktoren fehlen und die Dauer der Sterilit?t 4 Jahre nicht überschreitet. Ein Weiterbestehen der Sterilit?t über ein Jahr nach Myomnukleation macht ein neues Therapiekonzept erforderlich.