Relationship of resting EMG level to total body metabolism with reference to the origin of "tissue noise".
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PURPOSE: To describe the cell of origin, tumor progression, light and electron microscopic appearance, immunohistochemical properties, and response to frequently used anticancer therapies in two transgenic models of intraocular melanoma. METHODS: Two lines of transgenic mice that develop pigmented intraocular tumors were produced with the SV40 T and t antigens under the control of the mouse tyrosinase gene. Tumors were sequentially studied and characterized by light microscopy, electron microscopy, and immunohistochemistry stains. Tumor response to two cycles of dacarbazine was assessed on the basis of tumor size in one group of animals. Response to external beam irradiation was measured by survival time in other animals. RESULTS: Two lines of transgenic mice developed bilateral intraocular tumors with complete penetrance and without primary cutaneous melanomas. Tumors developed first in the retinal pigment epithelial layer, with subsequent retinal and choroidal invasion, extraocular extension, and metastasis. Tumors stained positive for S-100, HMB-45, and Fas-ligand. Electron microscopy revealed polarization of tumor cells with basement membrane formation, microvilli, immature melanosomes, and abundant endoplasmic reticulum. Dacarbazine significantly reduced tumor size in these mice, and a trend toward dose-dependent decrease in survival was found with external beam irradiation. CONCLUSIONS: Tumors developed from the retinal pigment epithelium. Their histology and growth, however, closely resembled that of human choroidal melanoma. This model may be a useful tool for future studies of endogenous primary pigmented tumors limited to the eye. Response to standard therapies suggests it can serve as a model with which to evaluate therapeutic modalities.
The distribution of collagen type IV, one of the major constituents of basement membrane, was studied immunohistologically in a series of 103 soft tissue tumors including those of peripheral nerve origin, smooth muscle origin, striated muscle origin, fibrous tissue origin, fibrohistiocytic origin, adipose tissue origin, synovial tissue origin, and blood vessel origin, paragangliomas, alveolar soft part sarcomas, granular cell tumors, and epithelioid sarcomas. Intensely positive staining for collagen type IV was observed in neurilemomas, neurofibromas, malignant schwannomas, and blood vessel tumors. Weakly to moderately positive staining was seen in leiomyomas, angiomyomas, and leiomyosarcomas. In contrast, synovial, fibroblastic and fibrohistiocytic tumors, benign or malignant, were negative. In paragangliomas, granular cell tumors, and alveolar soft part sarcomas, positive staining was evident surrounding nests or clusters of tumor cells. In all tumors, staining for collagen type IV clearly illustrated the vascular pattern.
Subretinal strands in proliferative vitreoretinopathy removed during vitreous surgery in ten cases were studied histologically; tissue culture was taken from five of the ten cases to obtain more material for investigation. Tissue culture was successful in all five cases. The cultured tissue just next to the original strand preserved the characteristics of the original tissue, whereas the portion distal from the original strand did not. Definite and/or suspected retinal pigment epithelial cells (RPE) were found in seven of ten original strands and four of five samples of cultured material. RPE were considered to be a predominant component of subretinal strands.
Primary tumors and cysts of the mesentery are quite rare. The cysts are said to be from embryonic, traumatic, or neoplastic origin. Mesenteric cysts of ovarian tissue origin, which, to our knowledge, have been reported only three times, appear under the term ovarian remnant syndrome, and involved patients with previous oophorectomies. It appears that the incidental implantation and growth of the minute portions of the ovarian tissue in the pelvis or lower abdomen is the origin of the syndrome. We describe two cases of the mesenteric cyst-ovarian implant syndrome with a brief review of the literature.
PIBF was previously identified as a 34 kDa immunomodulatory molecule secreted by pregnancy lymphocytes and is thought to play a crucial role in preventing rejection of the embryo by the maternal immune response. Recent data suggested that PIBF protein was also expressed by the progesterone receptor (PR) positive MCF-7 breast tumor cell line. Therefore our study was designed to analyze the expression of PIBF in malignant cell lines and primary tumors both at the mRNA and protein levels. RNA expression analyses of several human cell lines with different tissue origin and paired human tumor/normal tissues, as well as of several PR+ and PR- breast tumors revealed that PIBF mRNA was overexpressed in highly proliferating cells independent of the presence of PR. In addition to the full-length PIBF mRNA encoding for a 90 kDa protein, several alternatively spliced species were detected, all resulting from perfect exon skipping. The most frequently identified splice variant is predicted to encode for an approximately 35 kDa protein. Immunofluorescence microscopy revealed a centrosomal localization for the full-length PIBF, while the 35 kDa form showed a diffuse cytoplasmic staining. These data, together with the identification of the PIBF gene in the chromosomal region associated with breast cancer susceptibility, reveal a strong parallel with known tumor suppressor proteins, such as BRCA1 and p53 having the same centrosomal localization. Given the notion that a number of proteins shown to be involved in tumorigenesis are associated with the centrosome and disturbed centrosome function causes unequal segregation of chromosomes, studies to evaluate whether or not PIBF that is highly expressed in tumors is directly involved in tumorigenesis are thus warranted.
AIMS: Tumour tissue microarray allows the analysis of hundreds of tumour samples simultaneously on a single microscope slide. However, the extremely small tissue samples taken from the original tissue may not always be representative of the entire tumour. METHODS: The reliability of this new technology was investigated by analysing HER-2 oncogene amplification by fluorescence in situ hybridisation (FISH) from representative slides of the whole tumour and small tissue core biopsies from 29 invasive breast tumours. RESULTS: The tissue microarray method had high accuracy; in only one of 29 cases (3.4%; 95% confidence interval, 0% to 10%) were the results discordant with whole tumour analysis. CONCLUSION: Tumour microarray is a highly reliable method for analysing HER-2 oncogene amplification by FISH in human breast tumours.
Porcine-derived xenogeneic extracellular matrix (ECM) has been successfully used as a scaffold for tissue repair and reconstruction in numerous preclinical animal studies and human applications. These scaffolds are completely and rapidly degraded and replaced by host-derived tissues that frequently mimic the original tissue composition and architecture. The purpose of the present study was to examine the morphology of ECM scaffolds after their use for laryngeal reconstruction. Thirty adult female dogs were subjected to a partial hemilaryngectomy. The right thyroid cartilage and vocal fold were replaced with ECM scaffold, and the dogs were painlessly sacrificed from 1 week to 12 months after surgery. Histologic examination of the reconstructed tissue showed the presence of a simple squamous epithelial lining, organized glandular structures within the submucosa, reconstructed thyroid cartilage, and bundles of skeletal muscle by 3 months after surgery. We conclude that ECM scaffolds are promising templates for constructive remodeling of laryngeal tissue.
A functional test was developed to measure different adhesive properties of various Escherichia coli strains on the urinary tract epithelium. The test is based on initial incubation of everted canine ureteral segments in 2-hr cultures of E. coli (adsorption period), followed by sequential elutions in phosphate buffered saline. The release of bacteria (desorption rate) was measured from each elution by quantitative bacteriology. The function of the desorption assay was tested by showing different adhesive properties of various strains of E. coli. The strains isolated from infected canine urinary tracts showed high adhesion capacities superior to other strains of E. coli from different animal and/or tissue origin. This indicates a selective tissue and animal trophism determined by the strength of mucosal attachment. The test is also a valuable tool for measuring adhesion inhibiting substances in urine. The bulk of the adhesion inhibiting effect was localized in the urine ultrafiltrate.
Minor salivary glands (MSG) play a substantial role in the secretory immunoglobulin A (sIgA)-mediated immunity of the oral cavity. There are two possibilities for the induction of this immunity: (i) an explicitly local antigenic stimulus, or (ii) a remote stimulus as part of the so-called 'common mucosal immune system'. This communication is an attempt to consolidate available evidence in support of both possibilities and to address the former in detail. Although there is strong circumstantial evidence supporting the feasibility of MSG functioning as a part of the common mucosal immune system, direct experimental evidence is yet to emerge. On the other hand, there is increasing structural and physiological evidence in support of MSG serving as a local immunological organ. The purely local response is attributed to the presence of MSG duct-associated lymphoid tissue (DALT), which is comparable to gut- or bronchial-associated lymphoid tissue (GALT or BALT) in origin, tissue organization and function. DALT is accessible to oral antigens by retrograde passage through MSG ducts. Repeated topical antigenic challenging via the oral mucosa may result in the appearance of interacinar plasma cells carrying specific homologous antibodies in MSG. Gut or enteric priming of the same antigen, by passing the oral mucosa by gastric intubation, need not evoke a remote immune response in MSG. Since DALT is more likely to occur in healthy, young growing individuals, who are less likely to undergo bioptic examination of MSG, it has not yet been documented in humans. The physiologically induced DALT is apt to be confused with focal accumulations of lymphoid tissue in pathologically altered MSG, as a consequence of local and some systemic autoimmune diseases. An attempt is made to demarcaate healthy and pathological MSG on the basis of currently available clinical, serological, immunological and genetic evidence.
Glucose-6-phosphatase is primarily a liver and kidney enzyme. This enzyme was studied in various tumors, however, glucose-6-phosphatase activity was found only in tumors of liver, kidney, or adrenal origin. Glucose-6-phosphatase activity was useful in identifying the tissue origin of extrarenal Wilms'. Metastatic tumors within the liver or kidney that originated from other tissues did not have glucose-6-phosphatase activity. Therefore, it is suggested that glucose-6-phosphatase can be used as a specific enzyme marker for tumors of liver and kidney origin.
Minimally Invasive Dentistry is the application of "a systematic respect for the original tissue." This implies that the dental profession recognizes that an artifact is of less biological value than the original healthy tissue. Minimally invasive dentistry is a concept that can embrace all aspects of the profession. The common delineator is tissue preservation, preferably by preventing disease from occurring and intercepting its progress, but also removing and replacing with as little tissue loss as possible. It does not suggest that we make small fillings to restore incipient lesions or surgically remove impacted third molars without symptoms as routine procedures. The introduction of predictable adhesive technologies has led to a giant leap in interest in minimally invasive dentistry. The concept bridges the traditional gap between prevention and surgical procedures, which is just what dentistry needs today. The evidence-base for survival of restorations clearly indicates that restoring teeth is a temporary palliative measure that is doomed to fail if the disease that caused the condition is not addressed properly. Today, the means, motives and opportunities for minimally invasive dentistry are at hand, but incentives are definitely lacking. Patients and third parties seem to be convinced that the only things that count are replacements. Namely, they are prepared to pay for a filling but not for a procedure that can help avoid having one.
PURPOSE: To report on an uncommon, previously unidentified, progressive silicone punctal plug extrusion. DESIGN: Small, retrospective case series. PARTICIPANTS: Five cases of punctal plug extrusion were identified among a series of 424 consecutive implantations. Histopathologic analysis was obtained in one case. One additional referred case was included in this report. RESULTS: The plugs were completely extruded from the punctal lumen 6 to 14 months after insertion after an otherwise uncomplicated postoperative course. All plugs were retained at the punctal margin by an encircling band of vascularized mucosal tissue originating from the canalicular lumen. The band consisted of connective tissue of canalicular mucosal origin, attached just below the junction of the punctal and canalicular epithelium. Mild mononuclear infiltration was present in the connective tissue component of the punctal region. There was no cytologic or architectural evidence of abnormal epithelium or connective tissue or of pyogenic granuloma. CONCLUSIONS: These observations suggest that progressive lacrimal punctal plug extrusion may relate to mucosal dissection by the plug edges. We speculate that mechanical stress induced by eyelid closure on an improperly sized or placed implant may result in plug tilt. Subsequent epithelial hyperplasia further enhances the tilt, and the sharper edge of the conical bulb promotes separation of the canalicular mucosa from its distal luminal aspect. At the completion of the extrusion, the mucosal surface is separated from its connective tissue base, at a proximal subpunctal level, causing formation of an encircling tissue band.
Histophysiologic gradient culture methods reconstitute important spatial relationships that occur in nature between a parenchyma and its supporting stroma. At the epithelial-stromal interface, epithelia are firmly attached to the stromal substrate, initiation of renewal takes place, and metabolites are exchanged by a process of diffusion between epithelium and substrate. Other spatial imperatives characteristic of stratified epithelium are high density of cells, gradients of maturation, and continuity of epithelia along the entire course of the stromal-parenchymal interface. In radial gradient culture these relationships of epithelial cells, and supporting substrates are reconstituted. The culture chamber consists of a thin-walled cylinder, 2 to 3 mm in diameter and 3 cm long. The wall is a transparent collagen membrane in whose substance is embedded a reinforcing nylon mesh. To prepare a culture, one end of the cylinder is ligated, 1 or 2 particulate inocula are inserted in the open end of the cylinder, guided toward the ligature, and the open end is ligated. Subsequently, during incubation in a container with medium, the explants attach and proliferate. Proliferation and migration result in the cylinder being completely lined by a complex organoid tissue with structural characteristics of the original tissue. The tissue patterns in radial gradient culture of two human cell lines, RT-4, a bladder cancer, and 87 x 50, an ovarian cancer, are illustrated.
To obtain accurate estimates of radiation doses within the head and neck, a phantom was constructed. The osseous structures were represented by a human skull and cervical vertebrae with Mix D simulating the soft tissues originally with the bone. The soft tissues of the head and neck were also represented by this mixture of wax, plastic, magnesium oxide, and titanium dioxide with the x-ray absorption and scattering properties nearly equal to water and soft tissue. Soft tissue thicknesses and facial contours were based on depths reported in the literature and supplemented by cadaver measurements. Air passages, air cells, sinuses, and the oral cavity were left open to accurately simulate the patient. The locations of 16 anatomic sites were based on cadaver dissection and measured relationships to osseous landmarks and the skin surface. To confirm the accuracy of the phantom, doses were measured with lithium fluoride thermoluminescent dosimeters and compared with the results of other investigations reported in the literature.
Metastatic spread of breast cancer begins with the dissociation of cancer cells from the primary tumour. The dissociated cancer cells either settle in or trespass through the tissues/organs that they encounter, thus leaving residual or micro-metastasis in the tissues or organs. Detection of the residual cells and micro-metastasis in tissues or organs other than the originating tissues and circulating cancer cells constitutes an important aspect in staging, predicting prognosis and design therapy. However, the size of micro-metastasis and number of tumour cells, particularly in the circulation and bone marrow have presented a challenge for reliably and sensitively detecting them. Recent development in technology, including quantitative DNA sequence detection has increased the prospect for detection in this area. Recent studies have shown that molecular detection of micro-metastasis disease from lymph nodes, bone marrow, and the blood circulation can provide very valuable information for the presence of micro-residual disease and its impact on tumour progression and clinical outcomes. The current article discusses recent developments, in the detection of micro-metastasis using molecular biology techniques.
Organotypic cocultures of keratinocytes and fibroblasts generate a normal epidermis irrespective of the species and tissue origin of fibroblasts. The use of mouse fibroblasts and human keratinocytes facilitates the identification of the origin of compounds involved in epidermal tissue reconstitution and growth regulation. Moreover, the functional significance for the keratinocyte phenotype of genetically modified fibroblasts from transgenic or knockout mice, even those exhibiting an embryonic lethal phenotype, can be studied in such heterologous in vitro tissue equivalents. Here we communicate results of such studies revealing the antagonistic function of mouse fibroblasts defective in the AP-1 constituents c-Jun and JunB, respectively, on human keratinocyte growth and differentiation. Furthermore, the hematopoietic growth factor granulocyte macrophage-colony stimulating factor has been identified as a novel regulator of keratinocyte growth and differentiation. As will be reported in detail elsewhere both granulocyte macrophage-colony stimulating factor and keratinocyte growth factor have been identified as major mediators of fibroblast-keratinocyte interactions and their expression is induced via AP-1 by interleukin-1 released by the epithelial cells. Thus, these heterologous cocultures provide a novel promising tool for elucidating molecular mechanisms of epithelial-mesenchymal interactions and their consequences on epithelial cell proliferation and differentiation.
Advances in the fields of biotechnology and biomaterials offer the orthopaedic surgeon the exciting possibility of repair or regeneration of tissue lost to injury, disease, or aging. The promising area of tissue engineering represents a multidisciplinary approach aimed at solving some of the most perplexing biologic problems, namely, the creation of new tissues and organs similar to the original tissues and organs. In addition, strategies using new synthetic polymer formulations can facilitate tissue replacement and represent alternatives to tissue regeneration in certain conditions. Although biotechnology has broad application over many medical specialties, orthopaedics is receiving a large focus of the research effort devoted to techniques for developing bone, articular cartilage, ligaments, and tendons. Because bioengineered tissue and/or techniques to stimulate tissue regeneration soon may be used clinically, orthopaedic surgeons should have a working knowledge of the basic concepts involved. Terms, such as biomaterial, biotechnology, matrices of synthetic or biologic polymers or both, adhesion, cohesion, porosity, induction, conduction, stem cell, progenitor cell, mesenchymal cell, tissue growth factor, bone morphogenetic protein, mitogenic and chemotactic factors, and numerous other terms will become part of the working language of clinicians of the twenty-first century.