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PubMed1979

A fine structural study of the tissue channels' numbers and dimensions in normal and lymphoedematous tissues.

The numbers and effective radii were estimated for the tissue channels in the intersitial tissue of rats in the cerebral cortex and the facial subcutaneous tissue. Normal animals and some with acute (3 days) abd chronic (12 months) lymphoedema were used. It was found that the numbers and sizes of the channels corresponded well to those obtained by other techniques, however it was possible that in the oedematous animals the largest channels may have been artefactually counted as a number of smaller ones, thus reducing the hydraulic conductivity calculated. It is unlikely that this error was important for the normal tissue. In acute lymphoedema the numbers of both the small and the larger channels increased markedly, as did the radii of the largest channels. In chronic lymphoedema the numbers of the smaller channels fell to some extent. It was noted that, especially in lymphoedema and especially in the brain, there were many extra channels in the basement membrane regions of the capillaries. It is concluded that this new technique will be of considerable use in investigating the tissue channels in human patients since it can be applied to biopsy specimens.

Animals↗

PubMed1984

[Distribution of lymphocyte subpopulation and natural killer activity in gastric cancer tissue, normal stomach and various tissues of gastric cancer patients].

Natural killer activity of lymphocyte against M-HeLa or MKN-28 cells was measured in the gastric cancer tissue, regional lymph nodes, spleen and peripheral blood, and also the influences of injection of Nocardia CWS into the tumor was studied. Tumor infiltrating lymphocyte showed higher rates of T and T gamma cells than the lymphocyte of normal gastric tissue, nearly the same value as the lymphocyte in peripheral blood. NK activity of the lymphocyte in the peripheral blood of the gastric cancer patient showed a significant decrease compared to that of the normal subject. NK activity of the tumor infiltrating lymphocyte was markedly lower than that of the lymphocyte in peripheral blood, and was at the same level as that of the normal stomach and the lymph node. Endoscopic injection of N-CWS into the gastric cancer tissue intensified the cytotoxicity of lymphocytes in the cancer tissue and regional lymph nodes to MKN-28 cells derived from gastric cancer 5 to 17 days later, however, the activity against M-HeLa did not augment. Human fibroblast interferon (interferon beta) increased NK activity of lymphocytes in peripheral blood and spleen, but showed no influence on the activity of lymphocytes in the gastric cancer tissue and the regional lymph nodes.

Adult↗

PubMed1983

The mediation of tissue eosinophilia in hypersensitivity reactions. V. Comparative study of tissue eosinophilia in the skin lesions of local and systemic passive cutaneous anaphylactic reactions.

Tissue eosinophilia in active cutaneous anaphylaxis reactions is biphasic: the early phase (6 hr) is induced by a low molecular (mol. wt. 300) factor (early ECF), and the delayed phase (24 hr) is mediated by synergy of two different factors (delayed ECF-a and -b). In this study, we report the mediation of tissue eosinophilia in passive cutaneous anaphylactic (PCA) reaction sites. Tissue eosinophilia in systemic PCA showed two phases with peaks at 6 hr and 24 hr, while that in local PCA was monophasic and peaked at 12 hr. A dialysable eosinophil chemotactic factor was isolated from the early stage (0-6 hr) of local PCA skin sites, and another chemotactic factor (mol. wt. 15,000), sharing a common antigenicity with guinea-pig serum C5, from 12-hr-old local PCA skin sites. On the other hand, a different chemotactic factor with a mol. wt. of about 70,000, sharing a common antigenicity with delayed ECF-b isolated from active cutaneous anaphylactic skin lesions, was isolated from 24-hr-old systemic PCA skin lesions. Although the dialysable factor was also isolated from systemic PCA skin sites, the factor from systemic PCA delayed skin sites may not contribute to delayed tissue eosinophilia, since the activity paralleled the intensity of basophil accumulation but not to that of eosinophils. It is thus suggested that tissue eosinophilia in systemic and local PCA reactions is mediated by different chemotactic factors.

Animals↗

PubMed1981

[Studies on steroidogenesis of isolated granulosa cells and thecal tissue in tissue culture--with special reference to polycystic ovary syndrome (author's transl)].

The purpose of this study is to determine the steroidogenesis of polycystic ovary syndrome (PCO), through the comparison of steroidogenic potential between polycystic and normal ovarian cells harvested from follicles under 6 mm in diameter in vitro. 1) The granulosa cells were cultured by monolayer culture method, while the thecal tissue by explant culture method, at 37 degrees C using 5% CO2 in air for 18 days. 2) The cultured granulosa cells and thecal tissue grew successfully under 20% fetal calf serum with 80% medium 199. 3) The major product secreted by the cultured granulosa cells was progesterone, and the difference of steroidogenic potential between normal ovary and PCO was not significant. 4) The major products of isolated thecal tissue were delta 4-androstenedione and testosterone. Particularly, the cultured thecal tissue from PCO accumulated more androgens, in comparison with that from normal ovary. 5) The secretion of estradiol by the cultured granulosa cells was low in the absence of estrogen substrate and FSH. There was not appreciable difference in the capacity of granulosa cells from normal ovary and PCO to secrete estradiol. These results suggest that steroidogenic potential of isolated granulosa cells from PCO is comparable to that from normal ovary, whereas thecal tissue from PCO has more androgenic capacity than that from normal ovary.

Adult↗

PubMed1995

Integration of hepatitis B virus and alteration of the 1p36 region found in cancerous tissue of primary hepatocellular carcinoma with viral replication evidenced only in noncancerous, cirrhotic tissue.

We have studied the genetic profile of the host genome and hepatitis B virus (HBV) in HBV-associated primary hepatocellular carcinoma (HCC). Comparative analyses of HCC cell line Hep 40 and the original biopsy specimens showed the episomal and replicating form of HBV only in the biopsy specimen from nontumor (NT) cirrhotic liver tissue, where a molecular change in the 1p36 region was detected (NT tissue showed a normal 46XY karyotype). In contrast, only integrated HBV was detected in HCC tumor (T) tissue and Hep 40 cells. Two HBV integration sites were identical in HCC tissue and the hyperdiploid Hep 40 cell line, where genetic alteration in the 1p36 region was identified. These data indicate that viral replication is ongoing only in NT cirrhotic-hyperplastic, chromosomally normal tissue with evidence for genetic instability. Only the tumor cell with altered genotype has virus integrated

Carcinoma, Hepatocellular↗

PubMed1993

[Follow-up of tissue acidosis, lactic acid production and morphologic changes in testicular tissue in ischemia and the effect of cooling].

More than 90% of the patients with a testicular torsion are loosing their testis by orchiectomy or by following ischemic atrophy. The critical time of irreversible changes of the testis is according to literature 4-6 hours. The aim of our study was to measure the tissue acidification (pH) in the testis at different temperatures and to estimate the cooling effect on pH, lactate accumulation and morphological changes. We have measured in 36 human testis (orchiectomy in patients with metastatic prostate cancer) the tissue acidification (pH), the tissue lactate level and the morphology changes at a temperature of 35, 25, 15 and 5 C. In 12 testis of young dogs we have measured the same parameters. Starting with a normal testis temperature of 35 C the pH is falling to 6.0 within 1 hour of ischemia. By colling to 15 C this time can be prolonged to 6 hours. The tissue lactate level rises from 25 mumol/gdw to nearly 200 mumol/gdw at 35 C. The morphology of semi-thick slices of the testis shows a swelling of the intratubular tissue (spermatogenesis) by loss of the interstitial space. By reducing temperature also a slowdown of the changes can be observed. The critical pH value of the testis for irreversible changes is not known. A ph of less than 6.0 is probably a value, which may result in such changes.

Acid-Base Equilibrium↗

PubMed1993

Distribution of tissue factor pathway inhibitor in normal and malignant human tissues.

Specific antibodies to tissue factor pathway inhibitor (TFPI) were used in immunohistochemical procedures to determine the distribution of TFPI in normal and neoplastic human tissues. TFPI was restricted to megakaryocytes and the endothelium of the microvasculature in normal and abnormal tissues, but was not found in the endothelium of larger vessels or in hepatocytes. TFPI was also detected in macrophages in the villi of term placenta. Tumor-associated macrophages in several types of malignancy that we have shown previously to express a complete tissue factor-initiated pathway of coagulation and thrombin generation also manifested TFPI. By contrast, malignant cells in small cell carcinoma of the lung, renal cell carcinoma, and malignant melanoma that we have shown previously to express coagulation factors together with tumor cell-associated fibrin formation failed to stain for TFPI. We postulate that TFPI may be lacking from the latter malignancies because of the absence of the appropriately configured tissue factor-factor VIIa-factor Xa complex required for TFPI binding.

Capillaries↗

PubMedDate not supplied

Significance of tissue specific and tissue non specific autoimmune reactions of Graves' disease.

The relationship between the many immunologic abnormalities demonstrated in the peripheral blood of patients with Graves' disease (GD) and the broad spectrum of clinical features with which patients may present has not yet been addressed in detail. In this review we examine the evidence to support the notion that GD could be considered a multi-system autoimmune disorder in which tissue damage is restricted to the thyroid gland, connective tissue of the skin and orbit, extra-ocular and other skeletal muscles and, possibly, the lacrimal glands. Apart from the well recognized reactions of autoantibodies and sensitized T lymphocytes with epitopes on the thyroid specific TSH receptor, thyroid peroxidase and thyroglobulin, in patients with hyperthyroidism, there is also good evidence for autoantibody and, to a lesser extent, T lymphocyte reactivity with several eye muscle, other skeletal muscle and connective tissue, antigens in patients with ophthalmopathy, systemic myopathy, dermopathy and acropachy. There is also some evidence for immunoreactivity against lacrimal gland antigens in patients with ophthalmopathy associated with other features of GD. There are, in addition, a variety of organ non-specific reactions in GD; antinuclear antibodies are detected in serum from about one-third of patients with hyperthyroidism and ophthalmopathy, while from 5% to 10% have antibodies reactive with several other ubiquitous tissue proteins. Cloned proteins which are autoantigenic in some patients with hyperthyroidism or Hashimoto's thyroiditis and ophthalmopathy include collagen XIII, nebulin, the calcium binding protein calmitine, and the Mac-II antigen. All antibodies reactive with eye muscle antigens, except the 64 kDa protein which is also expressed in the thyroid, cross react with the same, or a related, protein in other skeletal muscle. Future research should focus on the underlying mechanisms for this broad loss of tolerance to self antigens and the effect of environmental factors such as stress, radioiodine and viral infection of the thyroid gland and other target tissues, in precipitating disease.

Animals↗

PubMed1997

Detection and tissue distribution of potato spindle tuber viroid in infected tomato plants by tissue print hybridization.

Potato spindle tuber viroid (PSTVd) was detected in two cultivars of tomato (Lycopersicon esculentum Mill.) by tissue print hybridization of cross-sections of stem and rhachis, using a 35S-labeled PSTVd RNA probe. PSTVd was detectable in the viroid-sensitive and symptom-developing cv "Rutgers" 2 weeks p.i., and in the viroid-tolerant and practically symptomless cv "Goldkugel" 3 weeks p.i. In both tomato cultivars, PSTVd accumulated in the upper parts of the plants newly grown after inoculation. It was predominantly found in association with the ring formed by the vascular tissue. The final accumulation of PSTVd as well as its spatial distribution were similar in the sensitive and in the tolerant tomato cultivar, as estimated from the tissue print autoradiographs. Thus, tissue print hybridization provides a rapid and sensitive means for viroid diagnosis and for the assessment of tissue-specific localization of the viroid RNA.

Autoradiography↗

PubMed1997

Loss of retinoic acid receptor beta expression in breast cancer and morphologically normal adjacent tissue but not in the normal breast tissue distant from the cancer.

Retinoids and their receptors [retinoic acid receptors (RARs) and retinoid X receptors] play an important role in maintaining the balance between proliferation and apoptosis. Recently, Deng et al. [Science (Washington DC), 274: 2057-2059, 1996] reported a loss of heterozygosity on chromosome 3p24 in breast cancer specimens and the morphologically normal appearing adjacent tissue. The 3p24 locus includes, among other genes, the region coding for RAR-beta. This study was designed to determine whether there are abnormalities in the expression of retinoid receptors in surgical specimens of patients with breast cancer. In 14 patients, transcripts of nuclear retinoid receptors were detected by in situ hybridization in formalin-fixed, paraffin-embedded specimens by means of digoxigenin-labeled riboprobes specific for RAR-alpha, -beta and -gamma. We found RAR-alpha expressed in all specimens, whereas RAR-gamma was expressed in 100% of normal breast tissue but in only 11 of 14 tumorous lesions. RAR-beta was found in all cases of normal breast tissue localized distant from the tumor, but in 13 of 14 cases it was completely absent in the tumor and the morphologically normal appearing tissue adjacent to the tumor. One possibility to explain the suppression of RAR-beta is a mutation in the promoter region. Sequencing the DNA extracted from paraffin-embedded tumor tissue of the corresponding breast cancer specimens, we were not able to detect any mutation in the retinoic acid-responsive element. Our results clearly indicate a crucial role of RAR-beta in the carcinogenesis of breast cancer.

Breast↗

PubMedDate not supplied

[The determination of the optimal irradiation dose in the tumor tissue-normal body tissues system].

To estimate the optimal cancerocidal dose, it is necessary to construct the mathematical models describing the probability of radiation sterilization of tumor tissue and that of a radiation-induced complication in the selected system of normal tissues or in the particular normal tissue if its radiosensitivity is higher than that of other tissues. The optimal cancerocidal dose may be estimated while solving a special emergency problem from the proposed criterion by taking into account the limited probabilities of radiation-induced complications in normal organs and tissues if they are damaged.

Dose-Response Relationship, Radiation↗

PubMed1996

[An investigation of immunoreactive substances in normal gingival tissue and periodontitis tissue].

In order to study the effects of NO, endothelin (ET), substancep (SP) and caleiton gene-related paptide (CGRP) immunoreactive substances in chronic periodontitis tissue and the relationship with periodontitis, immunohistochemical and histochemical staining methods were used respectively to detect the expression of the above immunoreactive substances in 20 patients with chronic periodontitis. Quantitative analysis showed that NO and ET in periodontitis tissues were increased significantly (P < 0.01), particularly the content of ET, in comparison to normal tissue. Due to the increase of ET content, the bolld supply was diminished and influenced the periodontal tissue by causing tissue damage. This study suggests that NO and ET immunoreactive substances are closely associated with periodontitis and may play an important role in the disease. There were no marked changes on SP and CGRP.

Calcitonin Gene-Related Peptide↗

PubMed1998

A novel monospecific IgG2/lambda-autoantibody with specificity for a mitochondrial antigen: evidence for an antigen-driven pathogenetic B-cell response in rheumatoid synovial tissue, induced by tissue alteration.

To elucidate the pathogenic role of synovial B cells in rheumatoid arthritis (RA), nine human IgG/lambda-secreting B-cell hybridomas from rheumatoid synovial tissue of a patient with definite RA were screened by enzyme-linked immunosorbent assay and indirect immunofluorescence on tissue cryosections for detection of antibodies against autoantigens. One IgG2/lambda monoclonal antibody (mAb) from the B-cell hybridoma ELG211/15/63 (= hybr63) exhibited intense immunofluorescence reactivity in the cytoplasm of chondrocytes and epithelial cells of the gastrointestinal tract, especially in parietal cells of gastric mucosa (human and mouse tissue), representing a mitochondrial pattern. This result was confirmed by morphometric analysis of immunoelectron microscopy data, exhibiting a significantly higher labeling density in mitochondria (p < or = 0.001) than in the cytoplasmic background, with predominant staining in the inner mitochondrial membrane and mitochondrial matrix (p < or = 0.05). Immunoblotting experiments carried out with gastric mucosa, and a mitochondrial protein preparation revealed two major proteins of 38 and 50 kd under reducing conditions. The analysis of the IgV(H) genes from this B-cell hybridoma showed highest homology to the human germline gene DP53 (96%). The IgV(L) region gave highest homology to the human germline gene DP5 (93%). In the complementarity-determining regions, residues of the H- and L-chain variable regions replacement mutations only indicated that this B-cell clone had been antigen-selected for its affinity (ratio of replacement to silent mutations: > or = 7). To analyze the in vivo expansion of the B-cell clone, primers specific for the V(H) to D to J(H) rearrangement of this B-cell hybridoma were used. Specific amplifications could be detected within part of the synovial tissue but not within the cells of the synovial fluid and peripheral blood of the patient. The ability of the IgG2/lambda mAb to induce an inflammatory reaction was tested by intraperitoneal application in severe combined immunodeficiency (SCID) mice, which resulted in an inflammatory, predominantly granulocytic infiltration of the peritoneum. Consequently, intrasynovial cell death or cartilage destruction seems to be a possible source of liberation of mitochondrial antigens, inducing a local, antigen-driven IgG2/lambda B-cell response with the ability to induce an inflammatory reaction. These data suggest that tissue destruction may serve as a source of arthritogenic antigens that perpetuate and amplify the local pernicious inflammatory process in RA synovialitis.

Amino Acid Sequence↗

PubMed1998

Immunohistochemical evaluation of estrogen and progesterone receptors in paraffin-embedded, formalin-fixed endometrial tissues: comparison with enzyme immunoassay and immunohistochemical analysis of frozen tissue.

Monoclonal antibody (MoAb) 1D5 with specificity to the estrogen receptor (ER), MoAb 1A6, and a polyclonal antibody (PoAb) (the latter two with specificity to the progesterone receptor [PgR]) were used to stain microwave-pretreated sections of formalin-fixed, paraffin-embedded normal and malignant endometrial tissues (n = 60). The tissues were previously evaluated for ER and PgR by enzyme immunoassay (EIA) (n = 44) and immunohistochemical analysis of frozen tissue (ICAfroz, n = 59). With results of EIA as a reference, the ER-1D5 method yielded a better agreement on receptor status, i.e., positive versus negative (74 vs. 51%) and a higher sensitivity (71 vs. 45%) but a similar high specificity (100%) than the ER-ICA method. Compared with results of PgR-EIA, the immunohistochemical assays for PgR gave similar results as to agreement (86-95%) and sensitivity (95-97%). Quantitative agreement on the fraction of cells stained for ER and PgR by immunohistochemical analysis in frozen and formalin-fixed tissue was obtained in approximately 60% of the cases. The results of semiquantitation were correlated with the results of both ICA and EIA. The MoAbs 1D5 and 1A6, as well as the anti-PgR PoAb, thus seem to be valid for evaluation of ER and PgR status in formalin-fixed endometrial tissue. Differences in the specificity of the Abs and in the sensitivity of the methods used to demonstrate ER and PgR might explain some of the discordant findings.

Carcinoma↗

PubMed1998

How do tissues respond to damage at the cellular level? The role of cytokines in irradiated tissues.

The capacity of ionizing radiation to affect tissue function, control tumor growth and elicit pathological sequelae has been attributed in great part to its effects on cellular DNA, which, as the transmitter of genetic information, can both register damage and perpetuate it. Nonetheless, multicellular organisms function as the result of the cooperation of many cell types. What then occurs when individual cells are damaged by ionizing radiation? Is tissue response a sum of cellular effects such as cell death and DNA damage? Or does the tissue respond as a coherent unit to the damage of its parts? In this paper, data in support of the latter model that indicate a role for cytokines, in particular transforming growth factor beta1, as critical components of extracellular signaling pathways that mediate tissue response to radiation will be reviewed. The key to manipulating the consequences of radiation exposure lies in understanding the complex interplay of events initiated at the cellular level, but acting on the tissue.

Animals↗

PubMed1998

Current perspectives on the molecular biology of the renal tissue kallikrein gene and the related tissue kallikrein gene family.

Renal tissue kallikrein is a member of the multigene family of serine proteases called the tissue kallikrein (KLK) gene family. This is a highly conserved family of genes, with a genomic structural organization that is identical for all these genes and other genes in the larger serine protease family, such as trypsin and chymotrypsin. These genes exhibit high sequence similarity both within and between species. However, there are clearly areas of sequence variability, which is most apparent in regions that form the substrate binding pocket of each enzyme and confers the substrate specificity of each individual enzyme. These genes are also often expressed in the same tissue, although each gene can have an individual tissue-specific pattern of expression. Similar patterns of diversity yet identity are also apparent in the regulation of kallikrein gene expression or enzyme activity. These similarities, and the fact that several of these gene families are located in tight clusters in the genome, support the notion that they have arisen by gene duplication. In this review, an overview of the molecular biology of the renal tissue kallikrein (KLK1) gene and the larger KLK gene family is given, highlighting the similarities yet diversity that is the hallmark of this family of genes, and how this knowledge has, and will, impact on our understanding of the role these enzymes play in normal physiological events and disease.

Animals↗

PubMed1989

The elastic tissue of Bruch's membrane. Connections to choroidal elastic tissue and the ciliary epithelium of the rabbit and human eyes.

Ultrastructural observations on the elastic lamina of Bruch's membrane of the rabbit and human eyes revealed connections to the ciliary epithelium and choroidal elastic tissue. The connections to the ciliary epithelium are in the form of bundles of microfibrils that peel off the anterior extension of Bruch's membrane beyond the ora serrata and insert into the basement membrane of the pigmented epithelium of the pars plana. The connections to the choroidal elastic tissue are in the form of bundles of microfibrils (in the rabbit) or elastin and microfibrils (in the human) that cross the tissue space between the choriocapillaris and join bundles of choroidal elastic tissue. These connections suggest that the elasticity of Bruch's membrane exerts its influence distant from the membrane itself. The connections onto the pars plana of the ciliary body implicate Bruch's membrane in disaccommodation when the ciliary muscle relaxes.

Animals↗

PubMed2007

Estrogen-dependent expression of the tissue kallikrein gene (Klk1) in the mouse uterus and its implications for endometrial tissue growth.

Tissue kallikrein mK1 is a serine protease involved in the generation of bioactive kinins for normal cardiac and arterial function in the mouse. In the present study, the tissue kallikrein gene Klk1, which codes for mK1, was shown to be one of the most prevalent of the Klk gene species in the uteri of adult mice, and its mRNA level was significantly higher at estrus than at diestrus. Klk1 mRNA expression was enhanced in the uteri of ovariectomized mice receiving estradiol-17beta treatment. Both endometrial epithelial and stromal cells isolated from the mice exhibited Klk1 expression at detectable levels when cultured in the presence of estradiol-17beta. mK1 was characterized using the recombinant active enzyme. mK1 had trypsin-like activity with a strong preference for Arg over Lys in the P1 position, and its activity was inhibited by typical serine protease inhibitors. Casein, gelatin, fibronectin, collagen type IV, and high-molecular-weight kininogen were degraded by mK1. The single-chain tissue-type plasminogen activator was converted to the two-chain form by mK1. In addition, mK1 degraded insulin-like growth factor binding protein-3. The present data suggest that mK1 may be implicated in the growth of uterine endometrial tissues during the proliferative phase.

Animals↗