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Tissue-specific determinants of human atrial natriuretic factor gene expression in cardiac tissue.

Elements controlling tissue-specific expression of the human atrial natriuretic factor gene have been examined in primary cultures of neonatal rat cardiocytes. When a 68-base pair fragment from human atrial natriuretic factor (hANF) 5'-flanking sequence (positions -400 to -333) was placed upstream from the herpes simplex thymidine kinase promoter linked to a bacterial reporter gene (chloramphenicol acetyltransferase), a tissue-specific positive regulatory effect was observed in atrial as well as ventricular cardiocytes but not in nonmyocardial cells. The cis-acting element in this fragment was orientation- and position-dependent. Examination of nuclear protein extracts for the presence of factors capable of interacting with the 5'-flanking sequence of the hANF gene revealed a cardiocyte-specific factor which bound to the 68-base pair fragment. This association was both tissue- and sequence-specific. These findings indicate that a cis-acting element present in the proximal 5'-flanking sequence confers tissue-specific expression upon the hANF gene, possibly through association with a cardiac-specific nuclear protein.

Atrial Natriuretic Factor↗

[Components of the extracellular tissue matrix as potential "markers" of connective tissue, cartilage and bone metabolism in diseases of the locomotor system].

Inflammatory and degenerative joint diseases are characterized by active degradation of the extracellular matrix of articular cartilage, bone and connective tissue. At the same time, specific changes in the neosynthesis of extracellular matrix components are seen. Thus, quantitative measurement of matrix related compounds and their metabolites in body fluids might provide a specific and sensitive tool for evaluating connective tissue involvement in rheumatic joint disease. The different components are linked to and may as such reflect different pathways of the pathological process, e.g.: Serum hyaluronan and serum procollagen type III peptides: fibroblast activation, early and late stage, respectively fibroproliferative tissue reaction. Synovial proteoglycans and glycosaminoglycans: degradation of proteoglycans derived from the extracellular matrix of cartilage; degree and activity of articular cartilage destruction. Serum keratan sulphate: proteoglycan metabolism (?). Urinary hydroxy pyridinium crosslinks (pyridinoline and deoxypyridinoline): degradation of mature cartilage and bone collagens; cartilage and bone catabolism. Cross-sectional and longitudinal clinical studies have shown that the quantitative measurement of some of these components may be of relevance in monitoring connective tissue disease. Further prospective studies are needed to prove the definite value of extracellular matrix-related components in early diagnosis and follow up of rheumatic joint and bone disease.

Arthritis↗

[Composition and degree of sulfation of glycosaminoglycans from tissues of different animal species: heterogeneity and tissue specificity of heparan sulfates].

The composition and degree of sulfation of glycosaminoglycans (GAG) in proteoglycans from various animal tissues were studied. It was shown that sulfated GAG contain chondroitin sulfates AC and B as well as heparan sulfates. The bulk of GAG in the majority of tissues under study is represented by 2-3 types of heparan sulfate molecules differing in the degree of sulfation. According to the degree of sulfation heparan sulfates from all tissues studied can be classified into three groups. Homologous tissues of various animal species are characterized by a similar composition and the degree of sulfation The data obtained are discussed in terms of the feasible role of proteoheparan sulfates in specific cell-to-cell interactions.

Animals↗

[Radiation-induced free radicals in DNA, DNA level in tissues and tissue radiosensitivity].

Radiochemical yields (G-values) of H-adducts of thymine bases of DNA (TH) in frozen (77 K) gamma-irradiated mouse and rat tissues were measured. The content of DNA and the number of TH radicals formed in DNA mass of 10(12)D at a dose of 1 Gy (beta parameter) were determined for each of the studied tissue. It was shown that beta parameter, which indicated DNA in situ radiosensitivity, was different for different tissues: it was higher for radiosensitive tissues. The possible causes of the effect observed are discussed.

Animals↗

Interaction of thyroid hormones with human muscular tissue, leucocytes and adipose tissue in vitro.

The uptake of triiodothyronine (T3) and thyroxine (T4) by human leucocytes as well as by adipose and muscular tissues in vitro was markedly dependent on the extracellular protein concentration. The presence of extracellular protein was responsible for the difference in the uptake of T3 and T4 by leucocytes (the incorporation of T4 was significantly lower than that of T3), whereas its presence in the medium containing adipocytes did nto influence the incorporation values. In a protein-free medium, the muscular tissue uptake of T3 exceeded that of T4. In this tissue the deiodination of both hormones was likewise significantly different, that of T4 being higher. The conversion of T4 to T3 was also higher in the muscle cells, but represented only about 75% of the total deiodinated fraction. In the remaining tissues, no differences were observed in the uptake and deiodination of T3 and T4. The deiodination of T4 in human leucocytes was found to be considerably dependent of pH of the incubation medium (two deiodination optima, a higher one in acid region) whereas the deiodination of T3 was fairly indifferent to variations of pH (one flat deiodination optimum in the weakly alkaline region).

Adipose Tissue↗

Immunohistochemical localization of gamma-enolase in normal human tissues other than nervous and neuroendocrine tissues.

The neuron-specific enolase, gamma-enolase, is present at high concentrations in tissues of the nervous and neuroendocrine systems and at significant levels in other human tissues as detected by enzyme immunoassay. Its precise localization, however, has remained unclear. We report here the immunohistochemical localization of gamma-enolase in normal adult human tissues other than those of the nervous and neuroendocrine systems using direct and indirect enzyme-labeled antibody methods. The gamma-enolase was found in such smooth muscle cells as the media of aorta, fibromuscular tissue of the prostate, and the myometrium of the uterus, myoepithelial cells, the conducting system of heart, epithelial cells of loops of Henle, and macula densa cells of the kidney. It was also demonstrated in spermatogonia, lymphocytes, plasma cells, platelets, and megakaryocytes and in lesser amounts in bronchial epithelial cells and type II alveolar epithelial cells of the lung, and in secretory cells of the fallopian tube. The significance of its presence in these cells and the application of the gamma-enolase detection for diagnostic purposes in pathology are discussed.

Histocytochemistry↗

[Primary soft tissue tumors of the epididymis, paratesticular tissue and spermatic cord].

The present study comprises 23 primary soft tissue tumors of the epididymis, paratesticular tissue and of the spermatic cord. These tumors were reclassified according to the diagnostic criteria of the WHO. The most common tumor of the paratesticular tissue is the adenomatoid tumor (65%), followed by the leiomyoma (17%). Other recognized tumors are: two typical lipomas, one lipo- and one leiomyosarcoma. Because of its relatively high frequency the adenomatoid tumor is reviewed more in detail with regard to its morphology and histogenesis. Some problems of the clinical pathology of paratesticular soft tissue tumors are briefly discussed.

Adult↗

Repair in arterial tissue. 2. Connective tissue changes following an embolectomy catheter lesion. The importance of the endothelial cells to repair and regeneration.

The neointimal hyperplasia following a severe mechanical lesion of the rabbit thoracic aorta was studied by vital staining with Evans blue and transmission electron microscopy. Neointimal tissue covered with endothelium contained organized laminated elastin-rich commective tissue. On the contrary neointimal connective tissue covered with pseudoendothelium was disorganized, with a tendency to fibrosis. Reendothelialization, re-establishment of intimal barrier function and formation of lamellated neointimal connective were parallel events. The importance of a intact subendothelial zone controlling healing processes is discussed. Interaction of endothelium and smooth muscle cells seems to be essential in the regulation of neointimal tissue formation and is probably implicated in a general vascular reactive pattern.

Animals↗

Subcutaneous adipose tissue cellularity of swine with different propensities for adipose tissue growth.

Middle subcutaneous adipose tissue samples were excised dorsal to the first rib, lat rib, and last lumbar vertebrae of lean and obese swine (Yorkshire and Ossabaw gilts) one year of age. Average backfat thickness per 100 kg body weight was approximately five fold greater for obese swine (6.8 versus 1.5 cm, respectively). Adipocyte diameter and volume distributions were determined after fixation with OsO4 with a Coulter Counter. To preclude connective tissue debris contribution to adipocyte number determinations, 8 M urea was used to solubilize connective tissue. Within a breed among tissue sites no differences in adipocyte size distributions were observed. Adipocyte diameter distributions for first rib, last rib, and last lumbar were significantly biphasic for lean and obese swine. However, the diameter distributions were markedly different between lean and obese swine. Twice as many small cells (20-30 micrometer diameter) were present in distributions from obese swine. Maximum cell diameter for lean and obese swine was 140 and 190 micrometer, respectively. The appearance of biphasic diameter distributions in lean and obese swine one year old suggests that adipocyte hyperplasia is continuing long after the time earlier work had suggested that hyperplasia had ceased.

Adipose Tissue↗

Investigations on the flucloxacillin levels in human serum, lung tissue, pericardial fluid and heart tissue.

Following intramuscular administration of 500 mg flucloxacillin, the levels of this antibiotic were measured in the serum, lung, and heart tissue as well as pericardial fluid obtained during 24 lung and 19 heart operations. Between 55 and 160 min following administration, the intact, inflamed, and tumorous lung tissue pieces contained 3.3-4.0, 2.0-2.7, and 1.5-2.4 mcg/g flucloxacillin, respectively, representing 16-36, 13-16, and 10-18% of the actual serum levels. Pericardial fluid contained practically no flucloxacillin. The cardiac auricle contained 2.3-3.5 mcg/g between 35 and 130 min after administration; the mitral valve showed 1.1-2.5 mcg/g between 90 and 170 min afterward, whereas in the aortic valve 1.6 mcg/g was found between 105-220 min later. These concentrations represented 16-20, 7-22, and 12% of the actual serum levels. Both the serum and tissue levels proved to be higher than those of oxacillin at the same dosage. The flucloxacillin levels of the serum and tissues studied were much higher than the minimum inhibiting concentrations for the sensitive bacteria. Therefore, flucloxacillin is considered an excellent antibiotic for the treatment of respiratory infections and endocarditis, whereas its levels in the pericardial fluid show it insufficient for treatment of pericarditis.

Adult↗

[Consensus soft tissue tumors. Dutch Workgroup Soft-Tissue Tumors].

Soft-tissue sarcomas constitute a rare group of malignant tumours with histopathological features of connective, muscular, fatty or peripheral nervous tissue. The prognosis at manifestation depends on only two factors: the spread, both local and remote, and the biological behaviour of the tumour. The latter factor cannot be influenced but the former can: by inexpert manipulation. Consequently, tumours suspected of being soft-tissue sarcomas require multidisciplinary management from the beginning, with the team members familiar with each other's diagnostic and therapeutic skills. Imaging diagnostic methods should precede invasive methods for collection of material for pathological examination. The number of mitotic figures observed at microscopical examination of the tissue is an important prognostic feature. Surgical resection is the treatment of first choice. Radiotherapy is indicated in grade 3 tumours, after recurrence surgery, and when radical resection would involve too much mutilation. Chemotherapy is only given in the context of clinical trials. Surgical treatment of lung metastases may be indicated in selected patients. Regional isolated perfusion with tumour necrosis factor may be an alternative for limb amputation.

Biopsy↗

Developmental and tissue-specific expression of prosaposin mRNA in murine tissues.

Prosaposin is a multifunctional locus in humans and mice that encodes in tandem and in the same reading frame four glycoprotein activators, or saposins, of lysosomal hydrolases. These ubiquitously expressed glycoproteins and the precursor, prosaposin, have been proposed to function in glycosphingolipid catabolic pathways and glycolipid transport. To characterize the temporal and spatial expression of the prosaposin locus, prenatal and postnatal mouse tissues were screened by in situ hybridization with a mouse antisense riboprobe for prosaposin. Prenatally, prosaposin mRNA was expressed differentially in the placenta and prominently in the decidua basalis and capsularis where expression was gestational age dependent. No other region of high-level expression was detectable in the prenatal mouse. In comparison, high-level differential expression of prosaposin was clearly evident postnatally in a variety of organs, including secretory epithelial cells of the choroid plexus, ependymal lining, upper trachea, esophagus, cortical tubules of the kidney, sertoli cells of the testes and epididymis. Discrete localization of prosaposin mRNA expression was also found in neurons of the cerebral cortex, cerebellar cortex, and lateral columns of the spinal cord as well as in hepatocytes of the mature liver. Very high levels of expression were found in specialized tissues including the Harderian glands and macrophages of lymph nodes, lungs, splenic tissue, and thymus. These studies indicate that the expression of the prosaposin locus, a presumed "housekeeping" gene, is under tissue- and cell-specific differential control. The spatial organization of expression suggests a role for this locus in the expression of glycosphingolipid-storage diseases.

Animals↗

[Forum on tissue expansion. Are tissue expansion and radiotherapy compatible? Apropos of a series of 50 consecutive breast reconstructions].

Tissue expansion has become a method of choice for immediate or delayed breast reconstruction. The compatibility of radiotherapy and tissue expansion is a growing problem. We analyse a series of 50 breast reconstructions by expansion, 24 without radiotherapy and 26 with radiotherapy. For the 24 patients without radiotherapy, very satisfactory cosmetic results were obtained in 71% of cases with 21% of stage III-IV capsular contractures and 8% of failures. For the 26 patients with a history of radiotherapy, very satisfactory cosmetic results were obtained in 65% of cases with 20% of capsular contractures and 10% of failure. 20% of cases also required a myocutaneous flap to complete the reconstruction. The complications related to radiotherapy are due to radiation lesions of endovasculitis and destruction of the network of elastin fibres. They result in the impossibility of filling the expander, deformation of the thoracic cage, expansion without projection, thinning of the tissues over the prosthesis and necrosis and exposure requiring the use of a myocutaneous flap. In conclusion, signs of radiation dermatitis constitute a contraindication to tissue expansion, which is nevertheless possible, but with a higher risk of complications. Irradiation to an expansion prosthesis is associated with an unacceptable complication rate.

Adult↗

Bacterial contamination of tissue allografts - experiences of the donor tissue bank of Victoria.

The aim of this study is to report the experience of the Donor Tissue Bank of Victoria with bacteria isolated from musculoskeletal, skin and cardiac allografts retrieved from cadaveric donors. The results of all quality control samples for bacterial culture, taken during retrieval and processing of allografts at the DTBV for a 12 month period, were extracted and analysed. It was found that 15.7% of skin, 15.1% of heart valves and 5.8% of musculoskeletal samples had positive culture results. The number and types of organisms isolated varied with tissue type. The most commonly isolated organisms were Staphylococcus species (including S. aureus). The identity of the isolate and the number of positive specimens from the same donor were considerations in the decision concerning the suitability of tissue for subsequent implantation.

Australia↗

Stimulation of growth of connective tissue by low-molecular-weight constituents from rapidly growing tissues.

The effect of low-molecular-weight cell constituents from regenerating liver and granulation tissue on the growth of the connective tissue during skin wound healing has been investigated. Repeated injections (intravenous or subcutaneous) of these compounds greatly accelerated the growth of connective tissue by stimulation of both fibroblast proliferation and collagen biogenesis and thus promoted wound healing. These results suggest that the low-molecular-weight cell constituents from dividing cells contain internal factor(s) capable of committing resting cells to D.N.A. synthesis and division or of accelerating D.N.A. synthesis in committed cells.

Animals↗

Matrix metalloproteinases, tissue inhibitors of metalloproteinases, aminoterminal propeptide of procollagen type III, and hyaluronan in sera and tissue of patients with capsular contracture after augmentation with Trilucent breast implants.

In various fibrotic diseases, matrix metalloproteinases (MMPs) and their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), play an important role. In our study, serum concentrations of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined by enzyme-linked immunosorbent assay in 17 female patients with Baker grade II (n =9), III (n =7), and IV (n =1) capsular contracture after bilateral cosmetic mamma augmentation with Trilucent implants (AEI, Inc., Caversham, United Kingdom). Samples of capsular tissue for standard histology and immunohistochemistry were obtained from all patients. Sera from 20 female patients who had plastic surgery for reduction mammaplasty were used as the control group. The aminoterminal propeptide of procollagen type III (PIIINP) and hyaluronan were analyzed as markers for fibrogenesis in both groups, too. Statistical analysis was performed using the Mann-Whitney test and Spearman rank correlation. Patients with capsular contracture presented significantly higher concentrations of TIMP-1 and TIMP-2 in their sera than did the control group (p < 0.05), which correlated with Baker grade (r = 0.7 versus r = 0.65; p < 0.05). The concentration of MMP-2 was significantly higher in the sera of patients with capsule fibrosis, whereas there were no significant differences in MMP-1, MMP-9, and PIIINP serum concentrations. Patients with capsule fibrosis had a significantly lower MMP-to-TIMP ratio (1.1 +/- 0.4, p <0.05) than the control group (1.5 +/- 0.4), which correlated with the Baker classification (r =0.7; p <0.05). The hyaluronan serum concentration of patients with capsular contracture was significantly higher (p < 0.05) and correlated with the Baker grade (r = 0.73; p < 0.05), whereas PIIINP showed no difference. In the histologic evaluation, there was a chronic inflammatory reaction in the capsules around the breast implants and refracting material within the substance. Immunohistochemically, TIMP-1 and TIMP-2 showed an intensive accumulation, and MMP-2 showed a local reaction. PIIINP could be detected, too, whereas there was no staining for MMP-1 and MMP-9. The elevated systemic MMP-2 concentration and the local positive staining in the tissue might be due to the chronic inflammatory reaction. Nevertheless, the balance between MMPs and their natural inhibitors is disturbed in patients with capsule contracture. The elevated systemic concentration of TIMPs might be a pathway in the pathogenesis of severe fibrosis after breast augmentation with alloplastic material. Hyaluronan might be a useful marker for early prediction of capsule fibrosis, whereas PIIINP is not useful as a predictor.

Adult↗

Limb salvage despite extensive tissue loss. Free tissue transfer combined with distal revascularization.

Extensive lower-extremity tissue loss may preclude limb salvage despite successful arterial reconstruction. We attempted to avoid limb loss in such patients by combining arterial bypass with microvascular free tissue transfer. Fourteen patient (12 diabetic), 33 to 74 years of age, presented with extensive tissue loss in 15 lower extremities, exposing bone or tendon on the heel, ankle, lower part of the leg, or hindfoot. Mean ulcer size was 5 X 8 cm. Four patients had had previous contralateral below-knee amputations. Femorodistal (seven), popliteal-distal (three), or femoropopliteal (four) bypass, or tibial angioplasty (one), was performed to provide sufficient inflow for free tissue transfer. Serratus anterior, scapular, latissimus dorsi, rectus abdominis, gracilis, ulnar, or temporalis free flaps were used. One free flap failed due to venous thrombosis and was corrected with a second flap. Limb salvage was achieved in 14 (93%) of 15 limbs during a mean follow-up of 24 months. The single amputation occurred due to severe foot ischemia in a patient whose femorodistal bypass remained patent only to the viable free flap. The remaining 13 patients (14 limbs) became ambulatory, including those with free flaps to weight-bearing regions.

Adult↗

Laser-tissue interaction with a high-power 2-microm fiber laser: preliminary studies with soft tissue.

BACKGROUND AND OBJECTIVE: Recent developments in fiber laser technology have introduced highly efficient, compact sources with high output beam quality. The first laser-tissue interaction studies with a high-power 2-microm fiber laser were conducted. STUDY DESIGN/MATERIALS AND METHODS: Chicken breast and porcine muscle tissue samples were subjected to continuous wave (cw) irradiation at 800-mW and 5-W output power levels, with spot sizes of approximately 150 microm. After laser irradiation, samples were inspected with an optical microscope and prepared for histologic processing. RESULTS: Evaluation of surface changes in tissue samples indicated an interaction similar in nature to those previously demonstrated with other cw lasers, but with photothermal ablation characteristics typical of strongly absorbed lasers operating in the infrared wavelength region. An ablation velocity of 0.27 mm.sec(-1) in porcine tissue was determined at 800-mW incident power. Histopathologic analysis demonstrated the formation of lesions with minimal damage at boundaries and no evidence of carbonization. CONCLUSIONS: Results indicate that this fiber laser has the potential to fulfill applications in the medical field.

Absorption↗