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PubMed1984

Distribution of human Class I (HLA-A,B,C) histocompatibility antigens in normal and malignant tissues of nonlymphoid origin.

Indirect immunofluorescence and immunoperoxidase staining of surgically removed tissues of nonlymphoid origin with monoclonal antibodies to the heavy and light chain of HLA-A,B,C antigens have shown that they have a more restricted tissue distribution than previously assumed. HLA-A,B,C antigens were not detected in brain cortex, cerebellum, sympathetic ganglia, hypophysis, parathyroid gland, thyroid, exocrine pancreas, hepatocytes, sperm, seminiferous tubules, or skeletal or smooth muscle. Malignant transformation of cells may be associated with appearance, changes in cellular distribution of HLA-A,B,C antigens, and/or dissociation in the expression of the two subunits. Analysis of primary tumors and of autologous metastases showed heterogeneity in the expression of HLA-A,B,C antigens among lesions removed from different sites. The degree of heterogeneity did not correlate with the site of origin of metastases.

Female↗
PubMed2026

Exploring the transcriptional crosstalk between adipose tissue and locoregional recurrence in breast cancer using independent component analysis.

Locoregional recurrence (LRR) poses a persistent clinical challenge in breast cancer, with emerging evidence implicating the tumor-associated adipose tissue in modulating recurrence risk. This study investigates shared transcriptional programs between adipose tissue and breast tumors and examines their association with disease-free survival (DFS), particularly in the context of reconstructive surgery where adipose tissue from different body compartments are commonly used. We analyzed bulk gene expression data from 5,691 breast tumors and 978 human adipose tissue samples from different body compartments using consensus-independent component analysis (c-ICA) to identify transcriptional components (TCs). Gene set enrichment analysis (GSEA) and copy number alteration profiling were used for biological annotation. Associations between TCs and DFS were evaluated through univariate Cox regression. Key findings were validated using spatial transcriptomic and single-cell RNA sequencing datasets. Among the 411 TCs identified, 332 showed biological enrichment, and 35 were significantly associated with DFS. Four DFS-associated TCs (TC257, TC350, TC371, TC400) were enriched for adipogenesis-related genes and exhibited heightened activity in high-grade, triple-negative tumors and in patients with elevated BMI. Notably, TC350 was highly active in adipose tissue from common reconstructive donor sites (abdomen, omentum, subcutis) but not in native breast adipose tissue. Spatial transcriptomic and single-cell analyses confirmed the increased activity of these adipogenesis-related TCs in tumor regions and adipose cells. TC350 included FABP4, a gene previously linked to poor prognosis in breast cancer and considered as a potential new therapeutic target. Adipose tissue-derived transcriptional programs influence breast cancer prognosis and this seems to differ by tissue origin. These findings generate a hypothesis that donor site selection for adipose tissue in reconstructive surgery may impact LRR risk through adipogenesis-associated mechanisms. Further research is warranted to elucidate the biological and clinical implications of adipose-tumor transcriptional interactions.

Humans↗
PubMed2005

Prognostic factors for nosocomial bacteraemia outcome: a prospective study in a Greek teaching hospital.

Epidemiological and clinical features were studied as potential prognostic factors for outcomes of bacteraemic patients in a tertiary care teaching hospital in Greece. The prospective study was conducted over 12 months and enrolled 153 consecutive hospital-acquired bacteraemic episodes in 137 patients. The crude in-hospital mortality rate was 27% (37/137). The mean lengths of stay and of antimicrobial treatment were significantly longer for patients with a fatal outcome than for survivors (P<0.0001 and P=0.001, respectively). Needs for mechanical ventilation, urinary catheters and parenteral nutrition before or during the onset of episodes were significantly associated with fatalities [odds ratio (OR)=5.54, 95% confidence intervals (CI) 2.22-14.0, P<0.0001; OR=0.70, 95% CI 0.63-0.79, P=0.021; OR=5.03, 95% CI 1.88-13.95, P<0.0001, respectively]. Also, in logistic regression analysis, mechanical ventilation (OR=5.5, 95% CI 1.2-7.9, P=0.02) and parenteral nutrition (OR=8.8, 95% CI 3.8-11.4, P=0.003) were independent predictors of mortality. No differences between fatalities and survivors were found in sex, age, smoking habit, intensive care unit hospitalization, need for a nasogastric catheter and previous surgery. Neutropenia was associated with a fatal outcome (OR=3.65, 95% CI 1.24-10.91, P=0.006). None of the bacterial pathogens were significantly associated with an adverse outcome, whereas Staphylococcus aureus was recovered more frequently from survivors (P=0.02). Fatalities were more often associated with an intravascular catheter origin (P=0.002), whereas bacteraemias in survivors were associated with a skin/soft tissue origin (P=0.02). Various prognostic factors were associated with outcome in our bacteraemic population, and can be employed to identify bacteraemic patients at risk of death and to develop local strategies for its prevention.

Adult↗
PubMed2006

Developments in reconstruction of midface and maxilla.

Loss of the maxilla and midfacial structures after tumour removal has substantial functional and aesthetic consequences. The variable loss of soft tissue, bone, or both, leading to collapse of the lip, cheek, periorbital soft tissues, and palatal competence present a challenging dilemma for reconstructive surgeons. Efforts have been made to classify these midfacial defects and provide appropriate algorithms for optimum reconstruction. Not only does the cavity need to be obliterated and midfacial contours recreated, but swallowing function, phonation, and mastication need to be restored for an ideal result. Traditionally, these defects would have been repaired by a maxillofacial prosthesis but advances in tissue transfers, particularly of microvascular free flaps, have greatly increased reconstructive options. The wide variety of free flaps that contain both soft tissue and bone offer unique properties that could be applicable depending on the defect. Combinations of free tissue transfer, local flaps, and maxillofacial prostheses might achieve a more ideal result than one technique alone. Advances in osseointegration have also enhanced the ability to achieve the best function and form. No one flap or technique is sufficient to reconstruct midface defects in all patients. The choices should be tailored to the bony and soft-tissue needs of each specific defect, denture-bearing potential of the original tissues, and available prosthodontic support. Use of a multidisciplinary approach to reconstruct these defects can yield excellent results. The complexity of the techniques should match the desired goals and needs of each individual patient.

Algorithms↗
PubMed2004

Wound-healing studies in transgenic and knockout mice.

Injury to the skin initiates a cascade of events including inflammation, new tissue formation, and tissue remodeling, that finally lead to at least partial reconstruction of the original tissue. Historically, animal models of repair have taught us much about how this repair process is orchestrated and, over recent years, the use of genetically modified mice has helped define the roles of many key molecules. Aside from conventional knockout technology, many ingenious approaches have been adopted, allowing researchers to circumvent such problems as embryonic lethality, or to affect gene function in a tissue- or temporal-specific manner. Together, these studies provide us with a growing source of information describing, to date, the in vivo function of nearly 100 proteins in the context of wound repair. This article focuses on the studies in which genetically modified mouse models have helped elucidate the roles that many soluble mediators play during wound repair, encompassing the fibroblast growth factor (FGF) and transforming growth factor-beta (TGF-beta) families and also data on cytokines and chemokines. Finally, we include a table summarizing all of the currently published data in this rapidly growing field. For a regularly updated web archive of studies, we have constructed a Compendium of Published Wound Healing Studies on Genetically Modified Mice which is avaialble at http://icbxs.ethz.ch/members/grose/woundtransgenic/home.html.

Animals↗
PubMed2002

Interobserver variation among histopathologic evaluations of intestinal tissues from dogs and cats.

OBJECTIVE: To determine whether substantial interobserver variation exists among diagnostic pathologists for descriptions of intestinal mucosal cell populations and whether histopathologic descriptions accurately predict when a patient does not have clinically evident intestinal disease. DESIGN: Comparative survey. Sample Population-14 histologic slides of duodenal, ileal, or colonic tissue from 10 dogs and 3 cats. PROCEDURE: Each histologic slide was evaluated independently by 5 pathologists at 4 institutions. Pathologists, who had no knowledge of the tissues' origin, indicated whether slides were adequate for histologic evaluation and whether the tissue was normal or abnormal. They also identified the main infiltrating cell type in specimens that were considered abnormal, and whether infiltrates were mild, moderate, severe, or neoplastic. RESULTS: Quality of all slides was considered adequate or superior by at least 4 of the 5 pathologists. For intensity of mucosal cellular infiltrates, there was uniformity of opinion for 1 slide, near-uniformity for 6 slides, and nonuniformity for 7 slides. Five dogs did not have clinical evidence of intestinal disease, yet the pathologists' descriptions indicated that their intestinal tissue specimens were abnormal. CONCLUSIONS AND CLINICAL RELEVANCE: Substantial interobserver variation was detected. Standardization of pathologic descriptions of intestinal tissue is necessary for meaningful comparisons with published articles. Clinicians must be cautious about correlating clinical signs and histopathologic descriptions of intestinal biopsy specimens.

Animals↗
PubMed1987

[Endogenous digitalis compounds and adrenal gland activity].

Endogenous inhibitors of the Na+,K+-pump have been postulated to participate in Na+ and water homeostasis. When present in high amounts, they have been proposed to induce a rise in blood pressure. There is no general agreement concerning their chemical structure and their possible tissue origin has not been well defined. In an attempt to identify a tissue source, (i) the digitalis-like contents of various organs (cross reactivity with digoxin antibodies and inhibition of ouabain binding to the Na+ pump) were determined and (ii) the circulating digitalis-like activity was analyzed under various conditions known to alter the activity of the putative source organs. High levels of digitalis-like compounds were present in the adrenal and pituitary glands (4.1 +/- 0.1, n = 15 and 3.7 +/- 0.4, n = 13 ng digoxin equivalents/g) or 328 +/- 66, n = 6 and 460 +/- 76, n = 6 ng ouabain equivalents/g) respectively. Much lower levels were found in heart, kidney, brain and hypothalamus. Plasma digitalis-like activity was measured in 5 groups of rats: control, ACTH treated, hypophysectomised, and in DOCA-salt treated animals with and without bilateral adrenalectomy. Changes in the plasma digitalis-like activity measured by the crossreactivity with anti-digoxin antibodies or by the inhibition of ouabain binding followed the same pattern. When compared to the control values, the plasma digitalis-like activity was partially decreased after hypophysectomy, markedly decreased after adrenalectomy and enhanced in ACTH-treated animals. These results suggest that the pituitary-adrenal axis plays a major role in the control of the circulating "digitalis-like" activity.

Adrenal Glands↗
PubMed1994

c-fes expression in ontogenetic development and hematopoietic differentiation.

The c-fes protein (NCP92) is a tyrosine-specific protein kinase, capable of both autophosphorylation and phosphorylation of other substrates. We have analysed c-fes RNA expression in human/murine ontogenetic development and in homogeneous populations of embryonic and adult human hematopoietic cells. c-fes expression has been observed in rapidly proliferating embryonic-fetal tissues originating from different germinal layers, but not in adult non-hematopoietic tissues. In particular, a spatially and temporally regulated transcription was observed in the central nervous system and in developing cartilage. Expression in hematopoietic cells was evaluated in progenitors purified from embryonic-fetal liver and adult peripheral blood differentiating gradually and specifically along the erythroid or granulomonocytic lineage. In both embryonic and adult hematopoietic cells c-fes was abundantly expressed in undifferentiated progenitors of both lineages, as well as in differentiated granulomonocytic precursors, but not in erythroblasts. This expression pattern correlates with that of GM-CSF and in part IL-3 receptors (Testa et al., 1993 and our unpublished results). Altogether, these results suggest a possible role for c-fes in signal transduction, in both embryonic non-hematopoietic tissues and embryonic/adult hematopoietic cells, following interaction of growth factors with their tyrosine-kinase negative receptors (i.e., GM-CSF and IL-3 receptors in adult hematopoietic cells and other hypothetical growth factor(s) receptors during embryonic development.

Adult↗
PubMed1981

Identification of prekeratin by immunofluorescence staining in the differential diagnosis of tumors.

Fibrillar proteins with a role in cellular shape and motility are present in the cytoplasm of most animal cells. They vary greatly in size, organization, and reactivity according to cell type and can be separately identified by the use of recently developed monospecific antisera and indirect immunofluorescence staining. Prekeratin, a structural protein in the form of intermediate sized filaments is present exclusively in cells of epithelial origin. In the present study 41 human tumors of various organs and their normal tissue counterparts were reacted with prekeratin antiserum and examined by immunofluorescence staining in paraffin embedded sections. Prekeratin was identified in all epithelial cells of the squamous type, which gave the strongest staining reaction, and in smaller amounts in epithelial cells of other histologic types. Cells of lymphoid, melanic, neural, and connective tissue origin were not stained. Thus, combining the specificity of antiprekeratin sera with the selectivity of immunofluorescence staining resulted in a new method of identifying tissues that is applicable to the differential diagnosis of tumors.

Diagnosis, Differential↗
PubMed1995

[Lactate dehydrogenase (LDH)].

The quantitative distribution of the lactate dehydrogenase (LDH) isozymes is different and characteristic. Therefore, when the LDH isozymes are released from tissue to serum, as on cell injury, the serum LDH isozyme pattern changes and in a sense resembling the profile of the affected tissue. However, the serum LDH isozyme pattern often differs from the isozyme pattern in the original tissues because of differing individual isozyme elimination rates. On the contrary, we should be able to determine the origin of enzyme release, disease stage and prognosis. The LDH isozyme pattern is sometimes modified by various factors, such as LDH-immunoglobulin complex or genetic variants. Results of isozyme determinations must therefore be carefully interpreted with a knowledge of biochemistry, physiology and limitation.

Clinical Enzyme Tests↗
PubMed2004

Adipocytes release a soluble form of VAP-1/SSAO by a metalloprotease-dependent process and in a regulated manner.

AIMS/HYPOTHESIS: Vascular adhesion protein-1 (VAP-1), which is identical to semicarbazide-sensitive amine oxidase (SSAO), is a dual-function membrane protein with adhesion properties and amine oxidase activity. A soluble form of VAP-1 is found in serum, where concentrations are enhanced in diabetes and obesity. In vitro, soluble VAP-1 enhances lymphocyte adhesion to endothelial cells, thus possibly participating in the enhanced lymphocyte adhesion capacity that is implicated in the cardiovascular complications associated with diabetes or obesity. In both, the tissue origin of the soluble VAP-1/SSAO is unknown. We examined whether adipose tissue, which has abundant expression of VAP-1/SSAO, is a source of soluble VAP-1. METHODS: We detected VAP-1/SSAO in plasma of diabetic animals, with or without VAP-1 immunoprecipitation, and in culture medium from 3T3-L1 adipocytes and human adipose tissue explants. VAP-1 protein glycosylation was measured. RESULTS: Diabetic and obese animals have increased plasma SSAO activity associated with VAP-1 protein. We also found that 3T3-L1 adipocytes and human adipose tissue explants release a soluble form of VAP-1/SSAO, which derives from the membrane. The release of soluble VAP-1 was enhanced by exposure of murine and human adipocytes to TNF-alpha and blocked by batimastat, a metalloprotease inhibitor. Partial ablation of adipose tissue reduced plasma SSAO activity in normal and diabetic rats. CONCLUSIONS/INTERPRETATION: Adipose cells are a source of soluble VAP-1/SSAO released by shedding of the membrane form. The release of SSAO is regulated by TNF-alpha and insulin. By releasing VAP-1/SSAO, adipose cells could contribute to the atherogenesis and vascular dysfunction associated with diabetes and obesity.

3T3 Cells↗
PubMed2005

Adipose tissue engineering using mesenchymal stem cells attached to injectable PLGA spheres.

The reconstruction of soft tissue defects remains a challenge in plastic and reconstructive surgery, and a real clinical need exists for an adequate solution. This study was undertaken in order to differentiate mesenchymal stem cells (MSCs) into adipocytes, and to then assess the possibility of constructing adipose tissue via the attachment of MSCs to injectable PLGA spheres. We also designed injectable PLGA spheres for scar-free transplantation. In this study, MSCs and adipo-MSCs (MSCs cultured in adipogenic medium for 7 days) were attached to PLGA spheres and cultured for 7 days, followed by injection into nude mice for 2 weeks. As a result, the difference between lipid accumulation in adipo-MSCs at 1 and 7 days was much higher in vitro than in the MSCs. Two weeks after injection, a massive amount of new tissue was formed in the APLGA group, whereas only a small amount was formed in the MPLGA group. We verified that the newly formed tissue originated from the injected MSCs via GFP testing, and confirmed that the created tissue was actual adipose tissue by oil red O staining and Western blot (PPAR(gamma) and C/EBP(alpha) were expressed only in APLGA groups). Therefore, this study presents an efficient model of adipose tissue engineering using MSCs and injectable PLGA spheres.

Adipocytes↗
PubMed1994

Establishment of a human cell line from maxillary squamous cell carcinoma and its biological features as a stimulator for induction of cytotoxic T lymphocytes.

A cancer cell line named FS-1 was established from maxillary cancer of which histological diagnosis was well differentiated squamous cell carcinoma (SCC). The HLA class I typing showed that FS-1 expressed the same HLA class I antigens as those of the host lymphocytes. The chromosome analysis and nuclear DNA contents suggested that FS-1 was not a normal human cell. FS-1 is characteristic of SCC in that it grows adhesively on the surface of a culture flask. The structure of tumor tissue obtained from FS-1-transplanted nude mice is very much like the original tissue of SCC. The SCC-antigen was determined in the culture supernatant of FS-1. Autologous tumor killing activity was induced from peripheral blood lymphocytes of some patients suffering from head and neck SCC after mixed lymphocyte tumor culture with FS-1. Thus, FS-1 can serve as a useful allogeneic stimulator of SCC for induction of autologous tumor killing activity.

Aged↗
PubMed2001

Cryptic responses to tissue manipulations in avian embryos.

Experimental embryology performed on avian embryos combines tissue manipulations and cell-labeling methods with increasing opportunities and demands for critical assays of the results. These approaches continue to reveal unexpected complexities in the normal patterns of cell movement and tissue origins, documentation of which is critical to unraveling the intricacies of cell and tissue interactions during embryogenesis. Viktor Hamburger's many pioneering contributions helped launch and promote the philosophical as well as technical elements of avian experimental embryology. Furthermore, his scholarship and profoundly positive presence influenced not just those of us fortunate to have trained with him, but several generations of developmental biologists. The first part of this article presents examples of the opportunities and rewards that have occurred due to his influences. Surgical manipulation of avian embryonic tissues always introduces a greater number of variables than the experimenter can control for or, often, readily identify. We present the results of dorsal and ventral lesions of hindbrain segments, which include defects in structures within, beside, and also at a considerable distance from the site of lesion. Extramedullary loops of longitudinal tract axons exit and re-enter the neural tube, and intra-medullary proliferation of blood vessels is expanded. Peripherally, the coalescence of neural crest- and placode-derived neuroblasts is disrupted. As expected, motor neurons and their projections close to the sites of lesion are compromised. However, an unexpected finding is that the normal projections of cranial nerves located distant to the lesion site were also disrupted. Following brainstem lesions in the region of rhombomeres 3, 4 or 5, trigeminal or oculomotor axons penetrated the lateral rectus muscle. Surprisingly, the ability of VIth nerve axons to reach the lateral rectus muscle was not destroyed in most cases, even though the terrain through which they needed to pass was disrupted. These axons typically followed a more ventral course than normal, and usually, the axons emerging from individual roots failed to fasciculate into a common VIth nerve, which suggests that each rootlet contains pathfinder-competent axons. The lesson from these lesions is that surgical intervention in avian embryos may have substantial effects upon tissues within, adjacent to, and distant to those that are being manipulated.

Animals↗
PubMed2006

SwePep, a database designed for endogenous peptides and mass spectrometry.

A new database, SwePep, specifically designed for endogenous peptides, has been constructed to significantly speed up the identification process from complex tissue samples utilizing mass spectrometry. In the identification process the experimental peptide masses are compared with the peptide masses stored in the database both with and without possible post-translational modifications. This intermediate identification step is fast and singles out peptides that are potential endogenous peptides and can later be confirmed with tandem mass spectrometry data. Successful applications of this methodology are presented. The SwePep database is a relational database developed using MySql and Java. The database contains 4180 annotated endogenous peptides from different tissues originating from 394 different species as well as 50 novel peptides from brain tissue identified in our laboratory. Information about the peptides, including mass, isoelectric point, sequence, and precursor protein, is also stored in the database. This new approach holds great potential for removing the bottleneck that occurs during the identification process in the field of peptidomics. The SwePep database is available to the public.

Animals↗
PubMed1997

The regenerative potential of oxytalan fibers. An experimental study in the monkey.

Although a number of studies have described the oxytalan fibers as being a natural component of the periodontal ligament, little information exists about the regenerative potential of these connective tissue fibers. The aim of the present study was to examine whether oxytalan fibers have the capacity to reform after regenerative periodontal therapy. Intrabony defects were produced surgically at the mesial aspects of teeth 37, 35, 45, 47 and at the distal aspects of teeth 11, 21, 31, 41 in one monkey (Macaca fascicularis). After 3 months, the defects were exposed using a full-thickness flap procedure. The root surfaces were debrided and subsequently PDGF-growth factors were placed in the defects. 4 of the 8 sites were covered with a bioresorbable membrane before closure of the wound. Post-surgically, antibiotics were given systemically for 1 week, and tooth cleaning was carried out 1x a week during the entire experimental period. After 5 months, the animal was sacrificed and the oral tissues were fixed by perfusion with 10% buffered formalin. Specimens containing the defects and surrounding tissues were dissected free and histological sections were cut in the mesio-distal direction, parallel to the long axes of the teeth. The sections were stained with hematoxylin and eosin or with the oxone-aldehyde-fuchsin-Halmi staining method and subsequently examined in the light and in the electron microscope. The results revealed that new oxytalan fibers oriented mainly in an apico-occlusal direction had developed in the regenerated periodontal ligament. Many of the newly-formed fibers were inserted into the new cementum, thus suggesting a strong relationship between this tissue and the oxytalan fibers. It is concluded that the regenerated periodontal ligament connective tissue formed after surgery contains oxytalan fibers similar to those present in the original tissue. These results demonstrate that oxytalan fibers develop de novo in the newly-formed periodontal ligament.

Alveolar Bone Loss↗
PubMed2006

Gene expression profiles of the fibroblasts from breast tumors and normal tissue compared with the tumor expression profiles.

OBJECTIVE: The study was designed to examine whether the gene expression profiles of fibroblast cell lines, established from the tumor and the normal tissue from the same breast, exhibit any similarities with the profiles of the original tissues. METHODS: Fibroblast cell lines were established from invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) of the breast and the adjacent normal tissues. Isolated total RNA from the cell lines and tissues were used to prepare labeled cDNA which was hybridized to Becton Dickinson Atlas microarrays for obtaining profiles of expressed genes. The profiles of tumors and cell lines were compared. This study was carried out at King Faisal specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia, during 2004 and 2005. RESULTS: Alterations of expression of most of the genes in the tissues were not detectable in the cell lines. The expression of a lower number of genes was altered in DCIS compared with that in IDC tumors. CONCLUSION: Although the fibroblasts discharge important functions, their gene expression profiles do not represent the breast tissue to the extent that any prognostic decisions could be made.

Adult↗
PubMed1994

Mediastinal teratoma: two case reports.

Teratomas in the mediastinum arise from pluripotent cells and are composed of a wide diversity of tissues originating from three germ layers ectoderm, mesoderm and endoderm. Hence we get all tissues represented in the mass, for example, epithelial and endodermal cysts lined by the squamous and collumnar cells respectively. It also has mesodermal elements, like tooth, bone muscle, etc. Benign teratomas are usually slow growing and give minimal symptoms and are often discovered when a routine chest x-ray is done. They are well circumscribed and usually removed without much difficulty. Malignant teratomas are fast growing, often cause pressure symptoms early and are diffuse. Diagnosis is done at thoracotomy and often only biopsy is possible. These tumours enlarge rapidly and fatal in six to twelve months after the diagnosis is established. Malignant teratomas of testes, seminoma, have better prognosis, compared to mediastinal lesions. Both types of teratomas also occur in ovaries. Two cases of benign mediastinal teratomas are presented. They were treated by thoracotomy with good results.

Adult↗