Chromosomal duplication accompanies allelic loss in non-small cell lung carcinoma

Hemizygous deletion in the short (p) arm of chromosome 3 is a common finding in non-small cell lung carcinoma (NSCLC) and is postulated to be a crucial early change in lung tumorigenesis. Yet one of the most frequent nuclear abnormalities in both NSCLC and premalignant bronchial epithelium is increase in chromosomal copy number. Deletion and duplication have not been assessed in the same tumor set by both molecular and cytogenetic methods to determine whether allelic loss correlates with chromosomal duplication in the same tumor cell populations. It is also not established what biological mechanisms might lead to allelic deletion and chromosomal duplication. We have investigated changes in the copy number of chromosome 3 in touch preparations of 38 NSCLCs (19 adenocarcinomas and 19 squamous cell carcinomas) using dual-target, dual-color fluorescence in situ hybridization (FISH) assays. Chromosome 3 centromere probe was matched with a 3p14.2 probe [intron 4 of the fragile histidine triad (FHIT) gene] and a 3p21.31 probe (HSemaIV gene). We then correlated FISH results with results of molecular analyses for allelic losses at loci in the regions to which the FISH probes mapped in 20 of these cases. Although various combinations of FISH abnormalities were sometimes detected within the same specimens, individual cases could be classified according to the predominant FISH pattern, usually with one abnormality present in >60% of tumor cells. Chromosomal duplication, indicated by the presence of more than two centromeric signals, was the most frequent abnormality observed by FISH and was accompanied by loss of specific sequences on 3p in approximately one-half of the specimens in which it was observed. The most frequent abnormality observed by molecular analysis was loss of heterozygosity (LOH) in both of the chromosomal regions tested and was demonstrated in 83% of cases with chromosomal duplication. We conclude that LOH may occur in the presence of chromosomal duplication, suggesting that the duplicated chromosome is homozygous. Our findings imply that LOH occurs before chromosomal duplication during lung carcinogenesis.     

Choices: biomedical ethics and women''s health. Ethical issues and dilemmas

Distribution of markers of local cell-mediated immunity was examined in oral tumors exhibiting different histological stages of differentiation. Using a RT-PCR-based semiquantitative technique we determined levels of Langerhans cells, CD4- and CD8-positive T-cells, macrophages/NK cells, beta2-microglobulin and IFN-gamma mRNAs from tissue biopsies. A positive correlation was found between levels of these immunological markers and the tumor differentiation stage. Since tumor differentiation may correlate with the prognosis and response to various treatment modalities, our results may be useful clinically.     

The value of palpation as basis for decision on lymph node excision

The purpose of the study was to evaluate palpation of the regional lymph nodes in control examinations of patients with malignant disease. A retrospective review of the medical records of 188 cases in which the patients had had an extirpation of the regional lymph nodes was performed. We have compared the preoperative findings through palpation with the histological diagnosis. The patients were grouped according to the region in which the lymph node removal had been done. The specificity of palpation when the histological diagnosis was malignant was (with 95% confidence limits), in the axilla 0.65 (0.54-0.75), in the inguinal region 0.86 (0.75-0.94) on the neck 0.83 (0.52-0.98) and in the suprahyoid region 0.58 (0.28-0.85). In conclusion, palpation of regional lymph nodes is not a sufficient control examination in the estimation of the course of malignant disease. Supplementary examination methods are recommended.     

A new source of X-ray line broadening: inhomogeneous strains induced by uniform homogeneous temperature conditions in polyphase or non-cubic materials

Thermal strains may contribute to X-ray diffraction line broadening in both single-phase non-cubic and in polyphase cubic polycrystalline materials even under uniform temperature conditions. A method is developed for calculating the magnitude of these thermally induced strains directly from the measured diffraction peak profiles. Corrections for particle-size effects can be made readily if particle-size broadening is significant, and the thermal diffuse scattering (TDS) contribution to the diffracted intensity can be taken into account experimentally. By this method, the strains in a Mg-5 wt% Si alloy were found to be increased by as much as 35% by a 190° C temperature change. Even in the case of this relatively low melting point alloy, the TDS effect causes only a maximum of 15% error in these measured strain effects. The interpretation of these isothermally induced strains in terms of crystal anisotropy, grain morphology and orientation and the relative sizes of phases and grains is discussed.     

Experimental observations of chemical and thermal gradients in an experimental BOF

The objective of this investigation was to determine the chemical and thermal gradients during steel making in a pilot size basic oxygen furnace. It was postulated that if these gradients could be determined under different conditions, conflicting theories of operation could be tested and optimum operating conditions would be indicated. New sample probe techniques were developed in which the probes are inserted through the side of the vessel to desired locations. Shortly after reaching the desired locations, the tip of an evacuated tube inside the probe opens and delivers metal to the other end of the probe outside the vessel. Temperatures were determined throughout the bath by specially reinforced but sensitive thermocouple probes. Important differences in both chemical and thermal gradients were found. The gradients were greatest with shallow penetration of the jet-for example after 3 min in a heat with about 1 in. penetration, the P content varied from 0.05 to 0.17 pct, silicon from 0.05 to 0.20 pct and the temperature from 2500° to 2900° F. These variations were found in a bath only 6 in. deep and 15 in. diam. By contrast, with deeper jet penetration to the center of the bath, the gradients were greatly reduced. Regardless of the operating conditions employed, the data indicate a metal circulation pattern which is upward from the jet cavity and radially outward at the surface. Even more important, by inserting a spray collector above the bath, it was found that with hard blowing the jet pumps out a volume of droplets during a heat which is equal to the bath volume. These droplets are rapidly oxidized,e.g. from 3.6 to 0.4 pct C, in their flight above the bath and are an important consideration in refining.