Results of two-dimensional electrophoresis (2-DE) analyses of human breast carcinoma are described. Tumor cells were extracted and purified from breast carcinomas with different proliferative indeces and degrees of genomic stability. Cells purified from fibroadenoma tissue served as controls for benign cells. The following results were observed: (i) Analysis of samples from different areas of the same tumor showed a high degree of similarity in the pattern of polypeptide expression. Similarly, analysis of two tumors and their metastases revealed similar 2-DE profiles. (ii) In contrast, large variations were observed between different lesions with comparable histological characteristics. Larger differences in polypeptide expression were observed between potentially highly malignant carcinomas compared to comparisons of less malignant lesions. These differences were in the same order of magnitude as those observed comparing a breast carcinoma to a lung carcinoma. (iii) The levels of all cytokeratin forms resolved (CK7, CK8, CK15, and CK18) were significantly lower in carcinomas compared to fibroadenomas. (iv) The levels of high molecular weight tropomyosins (1-3) were lower in carcinomas compared to fibroadenomas. The expression of tropomyosin-1 was found to be 1.7-fold higher in primary tumors with metastatic spread to axillar lymph nodes compared to primary tumors with no evidence of metastasis (p < 0.05). (v) The expression of proliferating cell nuclear antigen (PCNA) and some members of the stress protein family (pHSP60, HSP90, and calreticulin) were higher in carcinomas. We conclude that malignant progression of breast carcinomas results in large heterogeneity in polypeptide expression between different tumors, but that some common themes such as decreased expression of cytokeratin and tropomyosin polypeptides can be discerned.

Animals↗

PubMedDate not supplied

Clinical judgement and information seeking by nurses and physicians working with cancer patients.

This study examined and compared the processes of information collection and clinical judgement by nurses (n=107) and physicians (n=27) working with cancer patients. The data was collected in two university hospitals by means of a computer-simulated case description and the thinking-aloud method. Data interpretation was based on SPSS statistical software and the method of content analysis. Statistical differences between the two groups were tested with non-parametric Kruskal-Wallis Anova or the Mann-Whitney U-test. The Wilcoxon test was applied in pairwise comparisons. Independent questions were analysed by cross-tabulation and Pearson's chi(2). According to the results nurses and physicians apply different approaches to clinical judgement and problem-solving. On the basis of the status statement they received in the program both groups pointed to similar problems and sought a great deal of additional information. However the type of information required was different in the two groups. There were also significant differences in the knowledge base applied for purposes of clinical judgement: nurses tended to rely on personal knowledge, physicians on theory. Physicians were able to identify their patient's major clinical problems, but nurses had more difficulty doing this. On the other hand, nurses took a broader view on the general well-being of patients than physicians did.

Decision Making↗

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Serum levels of androgens are higher in women with premenstrual irritability and dysphoria than in controls.

Serum levels of progesterone, total testosterone, free testosterone, androstenedione (A2), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), 17-OH-progesterone (17-OHP), and sex hormone binding globulin (SHBG) were measured in the follicular phase, around ovulation, and in the luteal phase of 11 women with severe premenstrual irritability and dysphoria and in 11 age-matched controls with no premenstrual complaints. Serum levels of free testosterone were significantly higher in the subjects with premenstrual syndrome (PMS) than in the controls in the luteal phase (p < 0.01), the follicular phase (p < 0.05), and around ovulation (p < 0.01). DHEA levels were significantly higher in the PMS subjects, as compared to controls, around ovulation (p < 0.05), while 17-OHP levels were higher in the PMS women in the luteal phase (p < 0.05). With respect to the other steroids measured, as well as SHBG, no differences between PMS subjects and controls were found. These results indicate a possible involvement of androgens in the pathophysiology of premenstrual irritability and dysphoria.

Adult↗

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Gene expression of tenascin is altered in normal scars and keloids.

Tenascin is an extracellular matrix molecule with structural similarity to fibronectin. An increase in extracellular matrix content of both tenascin and fibronectin is associated with early wound healing and with various skin fibroses. However, the relationship of tenascin and fibronectin expression during scar remodeling and the formation of pathologic scars such as keloids is unknown. Expression of tenascin in normal and abnormal human scars was examined and compared with that of fibronectin by immunohistochemistry and in situ hybridization. Tenascin and fibronectin protein and messenger RNA contents were elevated in normal, mature scars relative to quiescent skin, similar to the situation during earlier stages of healing. Tenascin and fibronectin expression was further enhanced in keloids relative to normal skin and scar, and, as has been shown for fibronectin, tenascin expression in uninjured skin adjacent to keloids was indistinguishable from that in quiescent skin from unaffected individuals. These data suggest that tenascin and fibronectin gene expression are coordinated during later stages of normal wound healing and that a defect involving common regulatory elements for these genes is associated with the formation of keloids.

Journal Article↗

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Gene therapy in wound repair and regeneration.

The potential use of gene therapy to treat human disease increases with the development of various physical, chemical, and biological methods to deliver genes to mammalian cells, and with our rapidly expanding knowledge of the human genome. One area of therapeutic interest for gene therapy is the treatment of wound healing disorders. Most recently, recombinant human growth factor therapy has been examined as a means to treat problem wounds. However, this approach suffers from the difficulty in providing an accurate dose of growth factor and the expense of the recombinant proteins. Delivery of a gene that could be expressed within the wound is an attractive alternative to application of the protein. This review discusses several methods that have been used to deliver genes encoding growth factor proteins into wounds and the advantages/disadvantages of each approach. Novel methods to regulate the expression of the transgene are also presented, highlighting the ability of these unique vector systems to adjust gene dose as the wound heals. We expect that gene therapy will become a significant treatment modality for those wound healing pathologies refractory to other wound management approaches in the years ahead.

Genetic Therapy↗

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Age and growth factors in porcine full-thickness wound healing.

It has been recognized that the rate of cutaneous wound healing declines with age, yet the molecular processes that affect this decline remain poorly understood. The purpose of this study was to compare reepithelialization and contraction rates, and growth factor profiles in full-thickness wounds in swine of various ages. Multiple full-thickness excisional wounds were created on the dorsum of 24-month-old (n=2), 4-month-old (n=2), and 2-month-old (n=2) Yucatan Minipigs. The extent of reepithelialization was shown to decrease with increasing age in a manner that was statistically significant among the 2-month-old (79%), 4-month-old (48%), and 24-month-old pigs (22%). Enzyme-linked immunosorbent assay results showed that endogenous vascular endothelial growth factor concentrations in the 2- and 4-month-old animals peaked on day 4, reaching levels of 482 pg/ml and 420 pg/ml, respectively. In the 24-month-old pigs the vascular endothelial growth factor concentration peaked later (day 6), and was present at a lower level (229 pg/ml). On day 4 the vascular endothelial growth factor levels in the older pigs reached only 120 pg/ml, representing a four-fold decrease in concentration compared to the younger pigs. A comparison of platelet-derived growth factor-BB concentrations across the age groups showed similar patterns in the 2- and 4-month-old pigs (peaks of 77 and 91 pg/ml on days 2 and 3, respectively), and levels in the 24-month-old were below the sensitivity level (31.5 pg/ml) of the assay. Transforming growth factor-beta1 levels across the age groups did not differ in a manner that was statistically significant, and all age groups peaked on day 9. Wound contraction showed no statistical differences among the age groups from days 3 to 9. On day 11, however, wound contraction in 2-month-old pigs was about 10% faster than in 24-month-old pigs (p < 0.05). These data suggest a possible new algorithm for treating wounds in aged skin, by which exogenous growth factors can be added to the wound microenvironment in doses and at times that match the growth factor profiles observed in wounds made in younger skin.

Age Factors↗

PubMedDate not supplied

Hepatitis B immune serum globulin and standard gamma globulin in prevention of hepatitis B infection among hospital staff: a preliminary report.

In May 1973 a controlled double-blind clinical trail with prophylactic injects of hepatitis B immune serum globulin (antibody titer by passive hemagglutination 1:355,000) and standard gamma globulin (1:100) was started in Sahlgren's Hospital, Göteborg, Sweden. The annual attack rate of clinical hepatitis B in the three departments studied had been 5 to 8 per cent during recent years. A total of 118 members of the hospital staff were prophylactically treated while 125 staff members were unwilling to participate and received no prophylactic treatment. During the first 20 months of study nine cases of clinical hepatitis B with jaundice occurred within the untreated group (7.2 per cent) while three cases (2.5 per cent) were observed in prophylactically treated individuals. After decoding it was found that 60 individuals had received specific hepatitis B immune serum globulin while 58 had received standard gamma globulin. Two of the three clinical cases of hepatitis B occurred within the standard gamma globulin group. Both groups included two individuals with transient antigenemia only and the standard gamma globulin group also included four individuals with antibody seroconversion.

Antibody Formation↗