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Biomedical subjects

M Sarna

Publications and source records attributed to M Sarna.

7 recordsLinked to original sources

Evaluation of the expression levels of nm23-H1 mRNA in primary breast cancer, benign breast disease, axillary lymph nodes and normal breast tissue.

Expression levels of nm23-H1 were evaluated in a variety of normal benign and malignant breast tissues by Northern and slot blot. Tissues from 153 patients presenting with palpable breast lesions were studied: 132 primary infiltrating breast cancers, 9 pure duct carcinoma in situ lesions, a phyllodes tumor, 9 benign lesions and 2 local recurrences of carcinoma. In addition to lesional tissue, 49 samples of macroscopically normal breast tissue, 37 axillary lymph nodes and 9 samples from patients undergoing cosmetic reduction mammoplasty were studied. Sets of normal breast tissue, primary tumor and lymph node tissue from individual patients were available for comparison in 37 cases. A wide range of gene expression was detected in the various tissue types. The highest levels of expression were detected in malignant samples with in situ carcinomas being associated with the highest levels of gene expression. The expression levels of nm23-H1 in normal breast tissue were lower than the corresponding tumors from the same patients (p < 0.0005). Benign breast lesions (including 6 fibroadenomas) had levels of gene expression approximating those of the normal tissue samples. Normal axillary lymph nodes had significantly lower levels of nm23-H1 expression than nodes with metastatic deposits (p < 0.03). No significant association was observed between nm23-H1 expression levels and axillary node status in patients with infiltrating carcinoma, although there was a slight trend toward lower nm23-H1 mRNA levels in the node negative group.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern

What's new in breast cancer? Molecular perspectives of cancer development and the role of the oncogene c-erbB-2 in prognosis and disease.

The oncogene c-erbB-2 is frequently amplified in human breast carcinoma. The c-erbB-2 gene is present as a single copy in normal cells, and has been mapped to chromosome 17 in the region 17q 12-21.32. c-erbB-2 encodes a transmembrane glycoprotein known as p185. The intracellular component of p185 has tyrosine kinase activity; the extracellular domain has a structure resembling a growth factor receptor. c-erbB-2 amplification, p185 overexpression and levels of transcribed c-erbB-2 specific messenger RNA have been studied in a large number of breast carcinomas using a variety of techniques. In general, overexpression of p185 oncoprotein reflects various levels of DNA amplification, though in some cases amplification can be detected in the absence of overexpression of p185 and similarly overexpression of p185 can be present without detectable levels of c-erbB-2 amplification. This findings suggests that multiple mechanisms may be responsible for overexpression. c-erbB-2 amplification and/or overexpression occurs in almost all cases of high grade duct carcinoma in-situ, but has been reported in only 10%-40% of infiltrating duct carcinoma. c-erbB-2 amplification or overexpression occurs rarely in invasive lobular carcinoma, and has not been detected in ductal or lobular epithelial hyperplasia, or in atypical ductal or atypical lobular hyperplasia. It is generally believed that c-erbB-2 amplification/overexpression is an important independent prognostic indicator in breast carcinoma, identifying a subset of patients with poor prognosis tumours, particularly if axillary node metasases are present. However, many unanswered questions remain regarding c-erbB-2 and its role in breast cancer development and progression. The causes of c-erbB-2 amplification are unknown. There is no evidence of mutations in the human gene which might cause amplification or overexpression. The significance of the differences in levels of c-erbB-2 amplification/overexpression in in-situ duct carcinoma and associated invasive duct carcinoma has not been established. Amplification or overexpression have not been reported in atypical duct hyperplasia, a proposed precursor of duct carcinoma in-situ, yet overexpression occurs almost always in high grade duct carcinoma in-situ. c-erbB-2 may play a critical role in the development of a clonal in-situ, proliferation of high histological grade, yet does not obviously influence the acquisition of an invasive phenotype. We would postulated that this instability in amplification/overexpression is of biological significance, and if better understood may aid in the study of progression of human breast carcinoma.

Blotting, Southern

c-erbB-2 amplification and overexpression in breast cancer: evaluation and comparison of Southern blot, slot blot, ELISA and immunohistochemistry.

The oncogene c-erbB-2 has been shown to be amplified in 17-30% of breast cancers, with similar levels of overexpression of the oncogene product p185, a transmembrane growth factor receptor glycoprotein. Amplification of c-erbB-2 is now generally considered to be a significant prognostic indicator in patients with breast cancer. A series of 74 consecutive breast carcinomas were analysed for c-erbB-2 amplification and p185 overexpression. The procedures of Southern blotting and slot blot were used for the analysis of oncogene amplification, while immunoperoxidase (IPOX) staining and enzyme-linked immunosorbent assay (ELISA) were used for the analysis of p185 overexpression. Detection of c-erbB-2 oncogene amplification by both the conventional Southern blotting technique and by the slot blot technique showed complete accord, with the amplified c-erbB-2 oncogene being detected in 14 of the 74 patients (18.9%). The c-erbB-2 oncoprotein, as measured by IPOX and ELISA, was found to be overexpressed in 21% and 19% of patients, respectively. Comparison was made between the results attained by all four methods, and further comparison of the techniques was made from the point of view of ease of use, expense and ease of introduction into routine diagnostic laboratories. Immunocytochemistry in combination with slot blotting procedures were considered to be the most cost effective methods for evaluation of overexpression and amplification in routine pathology laboratories.

Blotting, Southern

Unsupervised waveform classification for multi-neuron recordings: a real-time, software-based system. I. Algorithms and implementation.

We describe a new, mostly software-based device for the sorting of waveforms in an extracellular multi-neuron recording situation. The sorting algorithm is largely unattended, and, after an initial 'learning' process, works in real time. Shape comparisons are based on up to 8 time points in the waveform; these points (the reduced feature set) are chosen automatically by analyzing the current incoming data stream. A feasibility version has been implemented on a LSI-11/2 system, using FORTRAN for set-up calculations and assembler for the real-time operations. Detailed comparisons with performance of other sorting devices are presented in the companion paper.

Algorithms

The influence exerted by Nembutal on reactivity of the superior colliculus neurons.

Effects of a Nembutal upon responses of the superior colliculus neurons were analyzed in pretrigeminal cats. Most cells were studied during the spindly barbiturate pattern in the EEG. In this condition collicular neurons lose their spontaneous activity, become sluggish in their reactivity to stimuli moving at high velocity, and less sensitive to direction of movement. After a further increase in the anesthesia down to the isoelectric EEG pattern the responses of neurons were gradually depressed and finally neurons became non-driveable by visual stimulation. A possible mechanism responsible for the reduction of the cells excitability is discussed.

Animals

Single-unit activity in cat's isolated midbrain.

The midbrain was isolated by two brainstem transections, pretrigeminal and premesencephalic. In the isolated midbrain, particularly within the reticular formation, EEG activity was greatly depressed. On the other hand, single-unit spike activity remained at a high level. The spatial density of active reticular units and the rate of their spontaneous activity were at least not smaller than those in the midbrain of the cat with only a pretrigeminal transection. Thus the flat EEG record is not necessarily a sign of the absence of neural activity.

Animals

Effects of binocular deprivation of pattern vision on single unit responses in the cat superior colliculus.

Single unit responses in the superior colliculus of cats deprived of pattern vision from birth and of normally reared cats were studied in unanesthetized pretrigeminal preparations. Collicular units of deprived cats showed a diminished direction-selectivity but a somewhat better speed-selectivity compared to normals; they also preferred lowspeed stimuli, and reacted less frequently to diffuse flash. The impairment of direction-selectivity of collicular neurons may be partly responsible for the impairment of the pursuit eye movements in visually deprived cats.

Animals