S-100 protein in human lung neuroendocrine neoplasms. Immunohistochemical study of 14 cases and review of the literature

A group of lung neuroendocrine (NE) neoplasms are investigated in view of the possible presence of S-100 protein immunoreactivity in their cells. The selected tumours were classified according to Gould et al. (1983a) and Mosca et al. (1985). They comprise 5 carcinoids, 3 neuroendocrine carcinomas of the well-differentiated type, or peripheral carcinoids, 5 neuroendocrine carcinomas of the intermediate cell type, or intermediate-cell, poorly differentiated carcinomas, 3 neuroendocrine carcinomas of the microcytoma type, or small cell carcinomas-SCC and a nodal metastasis of microcytoma. All but 2 tumours were immunoreactive for neuron specific enolase (NSE). Few S-100 immunoreactive cells were detected in 4 out of 5 carcinoids, in 1 out of 3 peripheral carcinoids, in 4 out of 5 poorly differentiated carcinomas and in the 3 microcytomas examined. No S-100 positive cells were found in the SCC's nodal metastasis. The S-100 immunolabelled cells can be interpreted as dendritic reticulum cells migrating through the tumours. However, in one case of typical carcinoid, abundant S-100 positive cells were detected: their stellate morphology and their intimate relation with neoplastic cells suggest that they are part of the neoplasia as a sort of satellite cell.     

Inhibition of human natural killer activity by monolayers of primary cell cultures

Some primary and continuous cell cultures were tested for their capacity to regulate human natural killer (NK) activity. Primary cultures of endothelial cells, fetal fibroblasts, adult fibroblasts, amnion epithelial cells, renal parenchymal cells, and ovarian carcinoma cells inhibited NK activity when peripheral blood lymphocytes were preincubated on target cell monolayers for 18 h before testing the cytotoxicity against K-562. The supernatants of the inhibiting cell cultures were not suppressive. Prostaglandins or suppressive lymphocytes were not involved in the phenomenon. The binding capacity of the effector cells was not changed, suggesting that the suppressive signal was targeted at the cytolytic machinery of NK cells. The down-regulating capacity of the cell cultures weakened significantly during subculturing in vitro, and continuous cell lines were not inhibitory. The inactivation of NK cells may be one of the mechanisms by which target cells are protected from NK activity.     

Evaluation of nucleolar organizer region-associated proteins in endometrial pathology.

In the current study the argyrophil staining technique for NOR proteins (Ag-NORs) has been performed on cases of different endometrial lesions, trying to find an aid in differentiating atypical hyperplasia from well differentiated carcinoma in biopsy specimens. We conclude that the Ag-NOR count, even though in endometrial carcinoma is significantly exceeding that of atypical hyperplastic endometrium, could be a misleading discriminator, because of a wide overlap of values in individual cases.     

Mass Spectrometric Analyses of Brain Synaptic Peptides Containing Taurine

The structure of a number of low-molecular-weight acidic peptides containing taurine prepared from calf brain synaptosomes and their subcellular vesicles was studied using electron impact mass spectrometry. At least seven sequences could be identified: N-acetylaspartyl-glutamyl-taurine, N-acetylaspartyl-taurine, N-acetylglutamyl-taurine, glutamyl-taurine, aspartyl-taurine, seryl-glutamyl-seryl-taurine, and seryl-taurine.     

Prognostic value of non-MHC-restricted killer cell activity in lung cancer

The prognostic value of peripheral blood non-MHC-restricted cytotoxicity against the myeloid leukaemic line K562 in lung cancer patients was studied. At the time of diagnosis and before operation, 57 patients with lung cancer were tested for cytotoxicity and subsequently followed for up to 4 years. In addition, 145 lung cancer patients, 30 patients with non-neoplastic lung diseases and 76 healthy donors were tested for cytotoxicity without the follow-up, in order to correlate the stage of lung cancer and the growth rate of tumours to the level of non-MHC-restricted cytotoxicity. On average, lung cancer patients had similar non-MHC-restricted cytotoxicity to the controls. However, patients with stage II–IV diseases showed an impaired activity, stages III and IV differing significantly from the controls. This result shows that the decline in natural killer (NK) activity is associated with tumour burden. Patients with slowly growing neoplasms had stronger cytotoxic activity than patients with fast or moderately progressing disease. In the follow-up study, the whole material of 57 patients showed only a slight correlation between cytotoxicity and survival: 42% of the patients with strong activity survived for more than 2.5 years, whereas 6% of the patients with weak activity did so. In stage I patients there was no correlation between cytotoxicity and survival, nor was there a correlation in patients with stages II–IV of the disease. Hence, in our group of patients the determination of cytotoxicity preoperatively yielded no prognostic information beyound that already available from staging. However, those stage II–IV patients that survived for 1 year or more after the diagnosis and cytotoxicity tests, showed a significant correlation between cytotoxicity and survival.     

Maternal origin of nucleated erythrocytes in peripheral venous blood of pregnant women

We studied the origin of nucleated red blood cells (NRBC) in peripheral venous blood samples from 40 pregnant women carrying a male fetus, using a technique that allows direct chromosomal analysis by in situ hybridisation on immunologically and morphologically classified cells. Samples from ten nulligravid women were studied as controls. NRBC were enriched by negative magnetic activated cell sorting (miniMACS) using anti-CD45 monoclonal antibody. NRBC were detected by alkaline phosphatase anti-alkaline phosphatase immunostaining using a monoclonal anti-glycophorin A antibody. The origin of the NRBC was determined by fluorescence in situ hybridisation using X and Y specific probes. NRBC were found in 37 of the 40 pregnant women at a range of 1 to 230 per 20 ml of venous blood and in 6 of the 10 controls at a range of 1 to 3 per 20 ml of venous blood. All NRBC detected in the pregnant women were evidently of maternal origin, and in the pregnant women the number of NRBC was significantly higher (P < 0.05) than in the controls. Pregnancy per se seems to induce the appearance of maternal NRBC in the circulation, and it cannot therefore be assumed that NRBC isolated from the maternal blood are of fetal origin on the basis of morphology alone. Discrimination of fetal NRBC must occur for prenatal diagnosis of fetal genetic disorders.     

Cultures of purified human natural killer cells: Growth in the presence of interleukin 2

We have isolated highly enriched populations of LGL, which are virtually devoid of mature typical lymphocytes (as enumerated by morphological and surface antigen analysis using monoclonal antibodies e.g., OKT3) in comparison to T cells which contain greater than 95% sheep erythrocyte-forming cells and are devoid of LGL and $\text{NK}\text{K}$ activities. Both types of cells grew in the presence of crude or partially purified IL-2. Cultures of LGL could be initiated consistently even in the absence of lectins and the cultured LGL retained their characteristic morphology and cytotoxic activity. However, within 7–10 days after initiation, the cultured LGL changed in surface phenotype to become antigenically indistinguishable from cultured T cells.     

Recognition of chromosome 6-associated target structures by human lymphokine-activated killer cells

Different populations of unstimulated and IL-2-activated PBL were used in binding and killing assays against somatic mouse/human lymphocyte cell hybrids containing different human chromosomes. Unstimulated PBL effector cells showed low binding and killing activity to both cell hybrids and mouse parental cell lines. However, IL-2-activated killer (LAK) cells bound strongly to, and effectively killed, cell hybrids carrying human chromosome 6, but were inefficient in both assays to mouse parental cells and to cell hybrids not carrying human chromosome 6. These results show that human LAK cells but not endogenous NK cells bind and kill mouse/human lymphocyte hybrids containing human chromosome 6. We thus suggest that LAK cells recognize ligands encoded by genes on chromosome 6.