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Biomedical subjects

R A Walker

Publications and source records attributed to R A Walker.

At least 163 records · Page 9Linked to original sources

Human cerebral hemispheres develop at different rates and ages.

The development of the cerebral hemispheres was assessed by using measures of electroencephalographic coherence and phase in 577 children ranging in age from 2 months to early adulthood. Two categories of age-dependent change in electroencephalographic coherence and phase were noted: continuous growth processes that were described best by an exponential growth function, and discrete growth spurts that appeared in specific anatomical locations at specific postnatal periods. The left and right hemispheres developed at different rates and with different postnatal onset times with the timing of growth spurts overlapping the timing of the major developmental stages described by Piaget.

Adolescent↗

Immunohistochemical analysis of HLA antigens and mononuclear infiltrates of benign and malignant breast.

Using immunohistochemistry, the epithelial expression of HLA Class I and II antigens (and beta 2 microglobulin) was compared in benign and malignant breast, and the stromal lympho-histiocytic infiltrate of these tissues quantified. The findings were compared with certain characteristics of the carcinomas. In contrast to other studies, malignancy was found to be associated with a far greater infiltrate of both lymphocytes and macrophages. In carcinomas, lymphocyte but not macrophage numbers showed a positive correlation with epithelial HLA ABC and HLA DR expression. This was particularly striking for T lymphocytes, and especially for the T4 subset. The histological grade of carcinoma is closely related to the degree of HLA ABC and beta 2 microglobulin expression, but no such relationship was found for HLA DR. There were greater numbers of mononuclear cells in the poorer differentiated tumours compared with other grades. Those carcinomas with evidence of lymph node metastasis contained greater numbers of macrophages identified by the antibody Y1/82A, but none of the other parameters studied was found to be associated with local lymph node status. The use of a large panel of monoclonal antibodies against various cellular subtypes has allowed a more detailed analysis of the interaction between breast epithelium and the host response.

Breast Neoplasms↗

The assessment of in vitro modulation of milk fat globule membrane expression by human breast carcinomas.

Although knowledge of functional differentiation and tumour-associated changes of breast carcinomas can be gained by the application of antibodies directed against the milk fat globule membrane, more significant information may be obtained by assessment of the potential of breast carcinomas to modulate their antigenic phenotype. In this study, the extend to which primary tumours can undergo modulation in vitro has been investigated, with consideration of the suitability of organ culture in combination with the immunohistochemical detection of two milk fat globule membrane epitopes, HMFG1 and HMFG2, as methods for detecting this. The preservation of three of the 30 carcinomas assessed, all poorly differentiated, was poor after 3 days of culture. The viability of the other 27 was variable, and was greater in the better differentiated tumours and with the addition of insulin. Expression of the milk fat globule membrane epitopes was generally well maintained. Six of the carcinomas showed a significant change in antigen expression, with this being more frequent in tissues incubated with insulin. Hence, a small group of carcinomas have been identified which appear to have a greater capacity to undergo functional differentiation. Organ culture is considered to be a suitable method for maintaining the tissues in vitro for such evaluation, but the problems encountered in quantifying the immunohistochemical staining, because of antigenic heterogeneity, were such that it is suggested that other approaches be employed.

Adenocarcinoma, Mucinous↗

The significance of argyrophilia in human breast carcinomas.

The significance of demonstrating argyrophilia in human breast carcinomas is a complex issue, although there is general agreement that "true" carcinoid tumours of the breast are rare. A predominantly unselected series of breast carcinomas has been investigated for evidence of argyrophilia using the Churukian Schenk method (Churukian and Schenk 1979), alpha lactalbumin and prealbumin, a marker of neuroendocrine cells. Argyrophilia has been detected in 25% of carcinomas, including all of mucinous types. However, only 4 of 68 tumours had a diffuse cytoplasmic reaction typical of that seen in neuroendocrine cells. The others showed a focal or subluminal/peripheral reaction. Those argyrophilic carcinomas with demonstrable alpha lactalbumin had this latter pattern of reactivity, although the milk protein was always detected in lesser amounts by comparison. Prealbumin was only found to varying degrees in eight tumours and the majority of these had a diffuse or focal cytoplasmic argyrophilic reaction. It would appear that in only a small number of breast carcinomas, approximately six percent, does the presence of argyrophilia probably represent neuroendocrine differentiation, whilst in others it is related to the secretory nature of the tumour cells.

Breast Neoplasms↗

An immunohistochemical study of the tissue distribution of the breast cyst fluid protein, zinc alpha 2 glycoprotein.

Zinc alpha 2 glycoprotein is one of the proteins present in breast cyst fluids, being found at levels 30-50 times its plasma concentration. Using an immunoperoxidase technique the distribution of this glycoprotein has been studied in a range of non-mammary tissues and carcinomas, as well as in normal, benign and malignant breast specimens. The breast cyst fluid protein was detected in all apocrine cells of skin and in the apocrine metaplastic epithelium lining of breast cysts. A progression was apparent from normal to hyperplastic breast in the number of cells reacting, particularly of cystically dilated acini, to a final consistent staining of apocrine-lined cysts. Zinc alpha 2 glycoprotein was demonstrated in 16 of 33 invasive carcinomas, 15 of which were eosinophilic on haematoxylin and eosin staining, and in one of three non-invasive carcinomas. No staining was apparent in other non-mammary tissues and carcinomas apart from weak reactivity of serous cells of the parotid gland. Zinc alpha 2 glycoprotein is, therefore, a reliable immunohistochemical marker of apocrine cell differentiation.

Apocrine Glands↗

Alterations to either c-erbB-2(neu) or c-myc proto-oncogenes in breast carcinomas correlate with poor short-term prognosis.

We have examined the genomic organisation of c-myc, N-myc, L-myc, neu and N-ras in tissue from 41 breast carcinomas, lymph node metastases from 10 of these carcinomas, one fibrosarcoma, 10 cases of benign fibrocystic breast and six fibroadenomas. We have not observed an alteration in either N-myc or N-ras in any of the samples studied. We have seen a 2-fold amplification of L=myc in DNA from one infiltrating ductal (ID) carcinoma, but otherwise we have seen no alterations to this gene. Amplification of c-myc was seen in 22% of ID breast carcinoma sample. Levels of amplification ranged from 2- to 10-fold. We have found a significant (p less than 0.02) correlation between an altered c-myc gene and a very poor short-term prognosis. Amplification of neu was seen in 19% of ID breast carcinomas, but the levels of amplification were higher than those seen for c-myc. Alterations to neu also correlated well with poor short-term prognosis (p less than 0.0002). Finally, we have observed a low level of amplification of c-myc in DNA from a benign fibrocystic breast lesion. This lesion exhibited some features characteristic of those thought to be associated with an increased risk of developing breast cancer.

Breast Neoplasms↗

Helicopter cooling of heatstroke victims.

Theoretical and clinical evidence suggests that traditional ice water immersion is not the best therapy for heatstroke. We treated three patients with serious heatstroke using the downdraft from a light utility helicopter to dissipate heat primarily by evaporation and convection. The speed of cooling was substantially better than that reported in prior clinical series.

Adolescent↗

Differential expression of cellular oncogenes in benign and malignant human breast tissue.

We have examined 62 specimens of benign fibrocystic breast tissue, fibroadenomas, carcinomas and surrounding non-malignant tissue excised from 50 patients to determine the level of expression of 4 cellular oncogenes, c-myc, c-H-ras, c-K-ras, and c-N-ras. Our results demonstrate that in breast carcinoma the frequency and relative level of expression of these oncogenes are significantly greater than those found for benign breast tissue. However, some fibrocystic specimens having prominent hyperplastic features also exhibited enhanced oncogene expression. In view of the association between the increased frequency of carcinoma of the breast in women with a previous history of benign breast disease, it will be interesting to follow up donors of benign specimens to see if there is any relationship between the expression of oncogenes in such lesions and the development of carcinomas.

Adenofibroma↗

Transferrin receptor expression in non-malignant and malignant human breast tissue.

The expression of transferrin receptor by normal, pregnant and benign hyperplastic breast lesions and by breast carcinomas has been investigated immunohistochemically using two monoclonal antibodies directed against the receptor. Unlike a previous immunohistological study in which staining was confined to malignant breast, transferrin receptor has been detected in pregnant breast and in benign lesions as well as in all carcinomas examined. The latter showed variable reactivity but with staining of most cells in 70 per cent of cases. Although the expression of transferrin receptor in non-malignant conditions may be related to cell proliferation, as has been suggested from studies of activated cells, the extent of reactivity of carcinomas has shown no correlation with tumour characteristics such as differentiation and local tumour spread. It is therefore suggested that the immunologically active transferrin receptor of breast carcinomas may have significance other than that relating to proliferation. The finding that with some carcinomas differences in staining occurred between the two antibodies is a further illustration of the complexities of the nature of transferrin receptor.

Adenofibroma↗

The expression of fucosylated type 2 blood group chains in human breast and their significance.

Monoclonal antibodies directed against O(H) blood group antigen and 3-fucosyl-N-acetyllactosamine have been used to investigate the incidence and significance of these type 2 blood group chains in non-malignant and malignant human breast tissue. The findings have been compared with those obtained with the fucose-binding lectins, Ulex europeus I and Lotus tetragonolobus. The expression of O(H) antigen in non-malignant breast is heterogeneous and shows no relationship to blood group status. Its expression in carcinomas shows no relationship to prognostic parameters such as differentiation and node status, whereas loss of Ulex europeus I binding is related to metastasis. The presence of 3-fucosyl-N-acetyllactosamine is limited in non-malignant breast, apart from pregnancy, but in carcinomas shows a relationship to differentiation, a feature not seen with fucose-binding lectins. It is apparent that to obtain the maximum amount of information about the modifications occurring in fuco-substances that appear to be of significance in breast malignancy, it is important to use monospecific probes as well as reagents with broader specificities, such as lectins.

ABO Blood-Group System↗

The utilization of [3H] sugars by non-malignant and malignant human breast.

The utilization of [3H] sugars and leucine by non-malignant and malignant human breast has been assessed using an organ culture technique with subsequent tissue autoradiography. The uptake of sugars by normal and hyperplastic breast was generally constant, with some differences observed in the utilization of galactose by acini of normal and hyperplastic tissues. After 24 h incubation localization was predominantly at the luminal cell periphery. The utilization of sugars by carcinomas was much more variable. Differences were observed between adjacent cells and cell groups of the same tumour. The uptake of individual sugars within a carcinoma was also varied being either similar to, or greater or lesser than normal breast. Variation between carcinomas was also present. No correlation between type and differentiation was noted in this respect, but there was between localization of sugars and differentiation. Better differentiated areas in tumours showed patterns similar to non-malignant breast whilst localization in poorly differentiated cell groups was cytoplasmic. The uptake of leucine was more constant and proved to be a useful indicator of viability. While this approach cannot give information with regard to differences in glycoprotein structure between non-malignant and malignant breast, it has been of value in determining the heterogeneity of tumour cells with regard to the enzymes involved in glycosylation. As such it would be of use in assessing the uniformity of response to agents modifying glycosylation.

Breast↗

DNA flow cytometry of human breast carcinomas and its relationship to transferrin and epidermal growth factor receptors.

The expression of transferrin and epidermal growth factor receptors in breast carcinomas, as detected by immunohistochemistry, has been compared with DNA ploidy and S-phase content of the same tumours as determined by DNA flow cytometry of fixed, paraffin embedded tissue, and with tumour differentiation. Good correlations have been found between DNA ploidy, S-phase content and differentiation. The expression of transferrin receptor appears to relate to DNA ploidy, but only to a limited extent to S-phase content, indicating that in breast carcinomas immunoreactive transferrin receptor may not be directly related to proliferation. The presence of epidermal growth factor receptor shows a close correlation with high S-phase content, but only a lesser association with DNA ploidy, and no correlation with tumour differentiation. DNA flow cytometry provides a more reliable method of assessing the relationship of such growth factor receptors in breast carcinomas to cell proliferation, than that obtained from more subjective tumour grading criteria.

Breast Neoplasms↗

Expression of the antigen detected by the monoclonal antibody Ca 19.9 in human breast tissues.

The incidence and significance of the expression of the antigen defined by the monoclonal antibody Ca 19.9 (Sialyl Lea) has been assessed in human breast tissue. Frozen and formalin-fixed, paraffin embedded specimens of normal, hyperplastic, pregnant breast and carcinomas were examined using an immunoperoxidase technique. Ductal and acinar epithelium of normal and hyperplastic tissues showed variable reactivity in frozen sections but there was a reduction in staining in comparable samples after fixation and processing, such that in many instances only focal ductal epithelium reacted. A distinctive feature in the pregnant breast was the absence of staining in acini showing differentiated secretory activity, despite a reaction in adjacent nonsecretory acini and ducts. The overall incidence of detection of the Ca 19.9 antigen in breast carcinomas was 62%, but in half of these only a small number of cells stained. A significant relationship between expression of Sialyl Lea and poor differentiation of carcinomas was identified, but there was no correlation with local lymph node status. In contrast to the non-malignant tissue fixation and processing had little effect on the reactivity of carcinomas. It is suggested that this difference may be quantitative in nature, with malignant breast showing much greater expression, or be related to organisation of the antigen. The observations concerning carcinomas and pregnant breast indicate that the synthesis of the Ca 19.9 antigen is related to the state of differentiation and functional activity of human breast.

Antibodies, Monoclonal↗

A revised method of age determination using the os pubis, with a review and tests of accuracy of other current methods of pubic symphyseal aging.

All current standardized methods of age determination using the os pubis were tested by blind assessment of a skeletal sample with documented ages (from the Todd collection; N = 96). No demographic data (sex, age, race, age composition) were known to the assessors prior to completion of the test. Results showed the Todd method to be more reliable than more recent component techniques and that all systems tended to underage. Therefore, modifications were made of the Todd system to eliminate this and other deficiencies, and a second test using a new sample was conducted (N = 109). The age distribution determined by the revised Todd method did not significantly differ from the actual age distribution of the second sample. Error due to race was nonsignificant. Biological stages of pubic metamorphosis are described and possible evolutionary specializations of the hominid symphysis are discussed. Revised standards for age determination are presented.

Adult↗

Radiographic changes in the clavicle and proximal femur and their use in the determination of skeletal age at death.

Visually seriated radiographs of the proximal femur, proximal humerus, clavicle, and calcaneus from 130 individuals from the Hamann-Todd collection were examined as indicators of skeletal age at death. The clavicle demonstrated the most consistent relationship to age in both sexes. The same radiographs were also seriated by size-normalized optical density as a means of establishing relative radiolucency. In this context, visual seriation proved superior. The four sites studied showed strong divergence in response to age. Since each was sampling bone response from the same individual, it is concluded that bone loss is highly site specific. This demonstrates the individual character of specific skeletal sites. Visual inspection of clavicular radiographs, seriated on a populational basis, provides age estimates that are comparable to anatomical age indicators and provides independent estimates of skeletal age when included in the summary age method (1985: Am. J. Phys. Anthropol. 68:1-14).

Adolescent↗

The binding of peroxidase-labelled lectins to human breast epithelium. IV--The reactivity of breast carcinomas to peanut, soy bean and Dolichos biflorus agglutinins.

The binding of the lectins from peanut, soy bean and Dolichos biflorus (specific for galactose and/or N-acetyl-D-galactosamine), to human breast carcinomas has been investigated. In contrast to the consistent pattern found in normal breast the reactivity of carcinomas to peanut lectin is varied, the most striking differences being prominent binding without desialation in some tumours and virtual lack of reactivity in others. There tends to be a greater degree of binding of soy bean agglutinin to carcinomas than normal although this is not absolute, and the reverse applies to Dolichos biflorus agglutinin. Comparison of the binding of the three lectins has revealed a complex heterogeneity of the carbohydrate chains within individual tumours and between different carcinomas. A significant relationship between peanut lectin binding, with the use of neuraminidase, and tumour differentiation as been found, and to a lesser extent with soy bean agglutinin when desialation is performed. However, the pattern of reactivity of the carcinomas with these three lectins does not appear to be related to local lymph node metastasis.

Arachis↗

Ulex europeus I--peroxidase as a marker of vascular endothelium: its application in routine histopathology.

Peroxidase-labelled Ulex europeus I lectin has been applied to a series of routinely fixed and processed vascular lesions to assess its value in the identification of endothelium. A group of breast carcinomas previously examined for binding of the lectin to the tumour have been re-assessed for evaluation of the use of Ulex europeus I in the determination of vascular invasion. There was consistent binding to normal vascular endothelium but this could be variable, there being stronger reactivity in small vessels of some tissues. All benign lesions stained showed clear definition of vascular channels but angiosarcomas were much less consistent in their staining reaction and the peroxidase-labelled lectin was considered to be a less satisfactory marker. Lymphatic endothelium was always negative; this proved to be a useful feature in differentiating between blood vessel and lymphatic invasion by breast carcinoma. Ulex europeus I-peroxidase could certainly have a role in routine histopathology in this area.

Breast Neoplasms↗