Tenascin expression in nephrogenesis and in normal or pathologic glomerulus morphologic features and functional implications.
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Animals↗
Biomedical subjects
J Pindur
Publications and source records attributed to J Pindur.
Tenascin is an important component of the glomerular extracellular matrix in normal and pathologic conditions.
Tenascin (TN), a large oligomeric glycoprotein, is a recently described component of the extracellular matrix (ECM). Previous reports focusing largely on the role of TN in nephrogenesis have documented the strong expression of TN in embryonic kidney tissue and implied an important role for TN in nephrogenesis. However, the expression of TN in normal and pathologic kidneys in adults has not been systematically evaluated. In this study immunohistochemical staining for TN was applied to 184 renal specimens diagnosed as: normal kidney (23 cases); minimal change disease and its variants (8); mesangial proliferative glomerulonephritis (GN) including IgA nephropathy and mesangial proliferative lupus nephritis (9); endocapillary proliferative GN including membranoproliferative GN, lupus nephritis, and post-infectious GN (25); crescentic GN (11); membranous GN (19); focal segmental sclerosis (15); thrombotic microangiopathy (8); amyloidosis (5); diabetic nephropathy (9); primary tubulointerstitial nephritis (14); transplant rejection (14); and ischemia (24). It was found that: (a) there was unequivocal global diffuse staining limited to the mesangium in normal kidney; (b) regardless of the etiologies and the morphologic types of glomerular disease, whenever there was expansion of the ECM, whether in the mesangial, endocapillary, or extracapillary spaces, there was a concomitant and proportional in situ increase in the TN staining; (c) globally sclerotic glomeruli, regardless of causes, showed diffuse, strong staining, especially in the subcapsular fibrous deposition seen in ischemic sclerosis; (d) non-sclerotic glomeruli showing early ischemic change uniformly displayed a marked decrease or complete loss of staining; (e) in cases of thrombotic microangiopathy, there was segmental or global staining of the capillary wall, probably corresponding to the enlarged lamina rara interna; (f) all nodular lesions in diabetic glomerulosclerosis showed strong staining, but in several of them this staining was much more pronounced in the periphery than in the center of the lesion. Our study proves that TN is probably a component of the normal mesangial matrix, that TN is an ubiquitous component of the expanded glomerular ECM in pathologic conditions regardless of morphologic subtypes, and that further studies on the cell types and mechanisms responsible for TN synthesis may provide a new venue for the understanding of the process of glomerular sclerosis.
Absorption↗
Tenascin is synthesized and secreted by rat mesangial cells in culture and is present in extracellular matrix in human glomerular diseases.
Tenascin (TN) is a large oligomeric protein recently described as a component of the extracellular matrix. The distribution of TN in adult kidney tissue has not been adequately evaluated, but preliminary data have suggested that TN is variably seen in rare mesangial areas and in stroma surrounding some tubules. The enlargement of the mesangial matrix (mesangial sclerosis) is a common feature of many renal diseases and is thought to be partially related to oversynthesis of the normal components of the mesangial matrix (collagen type IV, laminin, fibronectin, and heparan sulfate proteoglycans) by mesangial cells. However, the possibility that mesangial cells are also the source of other extracellular matrix proteins that participate in the process of mesangial sclerosis has not been explored. In this study, the synthesis of TN by cultured rat mesangial cells was documented by the following observations: (1) Northern hybridization of total RNA extracted from mesangial cells showed two distinct species of TN mRNA; (2) immunoblotting of the protein extracted from the conditioned medium demonstrated four TN protein bands; (3) immunoblotting of the protein extracted from the mesangial cell lysate demonstrated at least four TN protein bands; and (4) immunohistochemical techniques identified TN within the cytoplasm of mesangial cells and in the surrounding extracellular matrix.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Concurrence of de novo membranous glomerulonephritis and recurrent IgA nephropathy in a renal allograft.
Recurrent IgA nephropathy is commonly reported in renal transplant. De novo membranous glomerulonephritis is the most frequent type of glomerulonephritis seen in renal transplant. Nevertheless, to the best of our knowledge, the association of these two conditions in a single patient has never been documented. We wish to report one such case.
Adult↗
Cystic brain stem necrosis in a premature infant after prolonged bradycardia.
A case is described of symmetrical cavitating brain stem necrosis produced by cardiac arrest in a premature infant. Two months after birth this 25-week gestational age infant suffered a prolonged episode of bradycardia. She was resuscitated and then died 3 weeks later. The autopsy revealed striking bilateral cavitation of the brain stem tegmentum extending in a columnar fashion from the upper portion of the spinal cord to the hypothalamus. The findings in this case are identical to the brain stem injury experimentally produced by complete cardiac arrest in the rhesus monkey.
Bradycardia↗
Implants of keloid and hypertrophic scars into the athymic nude mouse: changes in the glycosaminoglycans of the implants.
Studies have been made of the glycosaminoglycan (GAG) composition of implants of keloid and hypertrophic scars in athymic nude mice in order to evaluate these implants as a model for studies of causation and therapy of these abnormal human scars. Changes in weight of implanted tissue were also recorded. Pieces of keloid, hypertrophic scar or normal human skin were placed in subcutaneous pockets of athymic nude mice and left for various times up to 246 days. The uronic acid content of the scar implants did not change significantly until after 80 days when the level decreased; the uronic acid level of normal skin increased slightly during the 110 days studied. The initially high percentage of chondroitin-4-sulfate of keloid and hypertrophic scar tissue decreased in the implants (averaging a 50% decrease at 164 days for keloids and at 176 days for hypertrophic scars). The average weight of the scar implants increased slightly after implantation and then decreased when expressed either as wet or dry weight. The regression lines of weight on time indicated an average loss of 50% dry weight at 66 days for keloid implants and 68 days for hypertrophic scars. Normal human skin increased in net weight until 20 days and dry weight until 40 days and then decreased, losing about 20% of weight (either wet or dry) at 110 days. On the basis of the glycosaminoglycan changes, the model should be useful for short term studies of therapy and causation.
Adolescent↗
Optimization of immunocytochemical P-glycoprotein assessment in multidrug-resistant plasma cell myeloma using three antibodies.
Seeking to optimize the immunocytochemical assay of P-glycoprotein, a 170-kilodalton (P-170) molecule associated with multidrug resistance, we experimented with a variety of antibodies (JSB-1, C219, and MRK-16), fixation conditions, and titers using both human myeloma cell lines and clinical myeloma specimens. Under optimized conditions, using all three antibodies and the cell lines as standards and controls, the ICC method proved sensitive, specific, reliable, rapid, and within the realm of everyday hospital laboratory expertise. The 3 anti-P-glycoprotein antibodies revealed different reactivities with P-170. Both C219 and JSB1 were optimized by fixation in cold acetone. With MRK-16 optimal results were obtained on unfixed or formalin fixed specimens. Under optimal fixation and titering conditions, low level (DOX 4) detection was possible. Given that the three antibodies differ in reactivity and recognize different P-170 epitopes, it follows that using the antibodies in a small panel is a useful strategy in increasing the likelihood of detecting true P-glycoprotein expression by the immunocytochemical method. In dilution experiments, the immunocytochemical method was as sensitive as RNase protection assay and more sensitive than Western blot detection. Immunocytochemistry coupled to computer-assisted single-cell densitometry, showed a strong correlation (R = 0.98) between cellular P-170 density and in vitro resistance to doxorubicin. Multidrug-resistant specific probes for RNA expression and Western blot assays confirmed the specificity of P-170 expression in both cell lines and clinical samples. Thus, a small panel of antibodies, under optimized immunocytochemical conditions, appears to have potential as a rapid, sensitive, clinically useful assay for multidrug resistance in myeloma.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Characteristics of granulation tissue which promote hypertrophic scarring.
Hypertrophic scars and keloids are characterized by nodules of collagen that originate in granulation tissue arising from full thickness or deep 2 degrees injuries to the skin. Fifty-six granulation tissues of varying ages post-injury were examined morphologically for evidences of how the nodules and, thus, the scar form. New microvessels grow in ascension towards the free surface in a milieu of inflammatory cells and fibroblasts. Collagen deposition increases with time from the base of the wound to the free surface and begins to concentrate between lateral branching of the new microvessels. Computer derived serial reconstructions of hypertrophic scar nodules indicate they are of varying shape and size probably due to fusion of adjacent microvascular collagen masses between lateral branches. This is accomplished by the gradual but persistent degeneration of microvascular endothelia and pericytes. Fifty-six pieces of granulation tissue taken from 5 cases of varying age post-injury were implanted into nude mice. Several proceeded to develop scar and some of those developed nodules. The latter developed only when the zero-time implant contained lateral microvascular branches. Hypertrophic scars and keloids are a product of granulation tissue elements, the most important of which are primed active fibroblasts and excessive microvascular regeneration, including lateral branching, which subsequently degenerates, in part, promoting nodule formation and remodeling.
Animals↗
Use of nude (athymic) mice for the study of hypertrophic scars and keloids: vascular continuity between mouse and implants.
Hypertrophic scars and keloids appear to be unique to humans since animals are not known to form these lesions. Therefore, in an effort to develop an experimental model for their study, implants of these human lesions were made in nude (athymic) mice (nu/nu) in suprascapular subcutaneous pockets. The implants were recovered from 2 to 246 days. By histological and fine structural parameters all implants remained viable and their morphological character was maintained. Selected mice were injected with barium to confirm by microangiography vascular flow between mouse and implant. Hoechst stain for DNA, used to distinguish mouse cells from human cells, confirmed vascular anastamosis between host and implant: barium-filled vessels in the interior of the implant demonstrated human endothelial cells. Peripheral vascularization of the implant with minimal ingrowth of mouse vessels occurs during the first 8 days. Anastamosis probably occurs sometime before 16 days postimplantation, or earlier, depending upon the availability of patent microvessels in the implanted tissue. The presence of the implant does not appear to prompt a continuing vascular growth into or throughout the implant. The time frame of 16 days postimplantation should be taken into account when developing schemata of experimental or therapeutic modalities.
Anastomosis, Surgical↗
Implants of hypertrophic scars and keloids into the nude (athymic) mouse: viability and morphology.
Pieces of hypertrophic scars and keloids were implanted into subcutaneous pockets of nude (athymic) mice and carried for varying times up to 246 days. No rejection phenomena were observed. Microvascular anastomosis occurred between host and implant within the first several days. Remodeling of the edges of the implant occurred very early. Multiple regression analysis of volume measurements suggests there was a size reduction of the implants with time. Yet virtually all implants retained their original histotypic character regardless of the length of implantation. The nodular character typical of all hypertrophic scars and keloids was retained in every case. Histologic analysis, confirmed by transmission electron microscopy, demonstrated a sustained cellular character. The degree and magnitude of microvascular occlusion was also sustained. Use of the nude mouse for implants of hypertrophic scar or keloid sustains true viability and morphology of the lesions. This procedure shows clear potential as an experimental model for the study of these lesions.
Animals↗
Increased fibronectin production by cell lines from hypertrophic scar and keloid.
Primary cell lines of fibroblasts from 8 tissues were established--three from hypertrophic scars (HS), one keloid (K) and four from the normal uninvolved dermis adjacent to each lesion. The objective was to quantify and compare all eight cell lines on the basis of fibronectin (FN) produced per cell and per total protein (PR). Two hypertrophic scars and their adjacent skin cell lines were evaluated by the ELISA method for FN and a micro Lowry assay for PR. The scar lines showed statistically significant increases in the amount of FN/cell compared to the cell lines from their adjacent normal dermis. The third hypertrophic scar and the keloid with their adjacent skin cell lines were assayed for FN and PR by radioimmunoprecipitation. Subconfluent cells were metabolically labeled with 35S-methionine for 20 hours. Harvested media and cell monolayers were assayed for radioactivity incorporated into FN and PR. The percentage of FN/PR was significantly higher in media for HS and K compared to the adjacent normal skin lines in the three passages tested. These results support our previous immunofluorescence studies and demonstrate that a fibroblast-type cell line from a hypertrophic scar or keloid produces more FN/PR over time than the normal fibroblast-type cell line from adjacent uninvolved dermis.
Cell Line↗
Characterization of implants from Dupuytren's contracture tissue into the nude (athymic) mouse.
Dupuytren's contracture tissues were obtained from six patients as excess surgical material. Pieces of these tissues (a total of 38 implants) were placed into subcutaneous pockets in the suprascapular area of nude (athymic) mice. The objective was to determine whether the implant tissues would be maintained in the mouse with the characteristics of Dupuytren's tissue. The implants were removed for study at 14-179 days after implantation. Microvascular anastomosis between implant and host skin was established within the first 14 days. Histologic character and electron microscopic structure of the implants did not change during the course of the study. The implants became reduced in size with time. However, neither the spatial pattern of collagen nor the appearance of fibroblast cells changed. The original high levels of chondroitin-4-sulfate were significantly decreased in the 66- to 179-day postimplantation group, but were not significantly different from the values for normal fascial bands. The hyaluronic acid of the implants increased significantly with time of implantation, but never reached the level found in the normal fascial bands. The use of implants into nude mice may be useful for further experimental studies of Dupuytren's contracture.
Animals↗
Proliferative activity in invasive breast carcinoma: a comprehensive comparison of MIB-1 immunocytochemical staining in aspiration biopsies to image analytic, flow cytometric and histologic parameters.
OBJECTIVE: To use MIB-1 antibody to assess proliferative activity in fine needle aspiration (FNA) samples of invasive breast carcinoma and compare these results to multiple other measures of proliferative activity. STUDY DESIGN: FNA slides from 62 patients with invasive breast carcinoma were subjected to staining with MIB-1. Quantitative MIB-1 values were compared to image analytic proliferative fractions (IPF) obtained from the same FNAs. MIB-1 values were also compared to flow cytometric S-phase fractions (SPF) and S + G2/M-phase fractions (FPF) and to histologic assessment of mitotic count (MC) in resected tumors. RESULTS: MIB-1 values, IPF, SPF, FPF and MC were suitable for evaluation in 55, 53, 50, 50 and 56 cases, respectively. MIB-1 values showed good correlation with IPF in FNAs (correlation coefficient = .57, P <.00001). MIB-1 values also showed correlation with SPF (correlation coefficient =.447, P = .003), FPF (correlation coefficient = .325, P = .023) and MC (correlation coefficient = .402, P = .01) in resected tumors. CONCLUSION: This study supports the use of MIB-1 values obtained from FNA samples for assessment of proliferative activity in invasive breast carcinoma, based on correlation of these values with multiple other parameters of proliferative activity. Assessment of these values can play a role in predicting prognosis and in selecting patients with invasive carcinoma of the breast for preoperative or adjuvant chemotherapy.
Adenocarcinoma↗