Biomedical subjects

F P Reinholt

Publications and source records attributed to F P Reinholt.

At least 19 recordsLinked to original sources

PubMed2004

Vascularisation and osteochondrosis of the epiphyseal growth cartilage of the distal femur in pigs--development with age, growth rate, weight and joint shape.

Until recently, the cartilage canals of the epiphyseal growth cartilage have not been associated with any specific disease. However, data support the hypothesis that osteochondrosis could be related to inadequate blood supply from vessels in these channels. We have done a study to investigate the relationship between the regression of cartilage canals and the formation of osteochondrosis latens in the epiphyseal growth cartilage of the distal femur in pigs, and the relationship between these events and age, growth rate, weight and femoral shape of the individual animals. This involved, in part, a comprehensive study of the distribution and pattern of regression of the cartilage canals. We found that the regression is a highly predictable process that follows an age-dependent pattern. However, we failed to prove any association between overall vascular regression and osteochondrosis, between vascular regression and weight, growth rate or femoral shape or between osteochondrosis and weight, growth rate or femoral shape. This may indicate that osteochondrosis latens is not caused by a general failure of vascular supply or general factors such as growth rate, but rather a consequence of local conditions affecting a limited number of vessels. A factor fitting this description is local compression.

Animals↗

PubMed2004

Surgical treatment of osteochondroma of the mandibular condyle in the adult. A 5-year follow-up.

Five adult patients with temporomandibular joint (TMJ) pain and impaired mandibular function and with clinical and radiographic features of unilateral osteochondroma of the mandibular condyle was included in a 5-year prospective follow-up study. All patients were surgically treated with condylectomy and reshaping of the condylar neck which was then positioned underneath the preserved TMJ disk. The yearly follow-up evaluations comprised measurements of maximum interincisal opening and protrusive movements, assessments of occlusion and TMJ pain as well as tomographic interpretation of recurrent growth. No patient showed recurrence of growth at the 5-year follow-up and mandibular function and occlusion was normalized in all patients. The results indicate that this conservative surgical approach can be recommended for treatment of osteochondroma of the mandibular condyle.

Adult↗

PubMed2003

Synovial chondromatosis of the temporomandibular joint: clinical, surgical and histological aspects.

Nine patients with histologically confirmed unilateral synovial chondromatosis of the temporomandibular joint were treated surgically with extirpation of loose bodies and partial synovectomy. In six of them the histological material was available for a systematic examination. The results of treatment were evaluated clinically and with MRI after a follow-up ranging between 1 and 17 years. Our findings suggest that synovial chondromatosis of the temporomandibular affects only the synovial lining of the upper compartment. The histological appearance is that of a benign chronic inflammation varying in severity and with metaplastic activity. The most specific clinical sign of synovial chondromatosis is swelling over the joint. Distension of the lateral capsule and fluid in the joint on the MRI are very suggestive of this diagnosis. Loose bodies also indicate synovial chondromatosis, but they are not always detected on the preoperative MRI. The surgical treatment should be conservative and include thorough removal of the loose bodies and partial synovectomy in areas with marked inflammation.

Adult↗

PubMed2003

Inflammatory cell and cytokine patterns in patients with painful clicking and osteoarthritis in the temporomandibular joint.

The occurrence of a subset of cytokines and leukocytes in the posterior disc attachment area of the temporomandibular joint (TMJ) was investigated in two patient groups, i.e, one group with painful clicking and one with osteoarthritis. Synovial biopsies were taken during discectomy in 19 patients with painful clicking and 20 with osteoarthritis. One set of specimens was examined with immunohistochemistry, using frozen sections postfixed by para-formaldehyde and with the cell membranes permeablized in saponin. These sections were incubated with antibodies against cytokines IL-1alpha, IL-1beta, IL-1ra, TNFalpha, IFNgamma, IL2 in all patients and TGFbeta1,2,3 in 16. The other set of specimens was used to characterize cell infiltrates using immunohistochemistry with monoclonal antibodies against antigens CD68 and CD45RO, respectively. Moreover, PCNA was included as a marker for cell proliferation. The cytokine staining was most frequently positive for IL-1alpha and IL-1beta in both patient groups. However, joints with OA showed a more complex cytokine pattern, also involving IFN-gamma (P = 0.019), IL-ra (P = 0.047), and apparently but without reaching the chosen level of significance, IL-2, TNF-alpha and TGF-beta1,2,3. Positive staining for CD45RO was frequent in both groups. OA patients showed more frequently positive staining for CD68 (P = 0.025) and apparently for PCNA.

Antigens, CD↗

PubMed2003

Recurrent angiolymphoid hyperplasia with eosinophilia mimicking temporal arteritis associated with nephrotic syndrome.

We report on a middle-aged Caucasian male who presented with nephrotic syndrome that on 2 consecutive recurrences was accompanied by a pulsating tumor suggesting temporal arteritis. Renal biopsies showed features of a low-grade mesangial-proliferative glomerulonephritis. The resected tumor in the temporal region revealed a lesion consistent with angiolymphoid hyperplasia with eosinophilia (ALHE), with moderate inflammatory involvement of the temporal artery. The patient was successfully treated with oral prednisolone in addition to removal of the tumor, but has remained steroid-dependent. To our knowledge, only 2 cases of ALHE and nephrotic syndrome have been reported so far in non-Japanese individuals [Altman et al. 1995, Sonkodi et al. 1987], and we are not aware of any previous case combining these features while simultaneuosly mimicking temporal arteritis.

Adult↗

PubMed2002

Ultrastructural distribution of osteoadherin in rat bone shows a pattern similar to that of bone sialoprotein.

Osteoadherin (OSAD) is a keratan sulfate proteoglycan recently isolated from bovine and rat bone. Based on results obtained from in vitro experiments, the protein was shown to bind osteoblasts via the integrin receptor alpha v beta 3. Due to OSAD's capacity to bind hydroxyapatite crystals, a role for the protein in the mineralization process has also been suggested. To test these hypotheses in an in vivo model, the ultrastructural localization of OSAD in bone, tibial (metaphyses and diaphyses), and calvarial samples from normal 10 to 12-day-old rats were examined by immunohistochemical techniques at the ultrastructural level. In addition to the qualitative studies, quantitative measurements of OSAD marker density were performed in relevant compartments. Immunolabeling for OSAD was located to the mineralized bone matrix, with highest concentration of marker at the border between bone and cartilage remnants in the metaphyseal trabeculi. Intracellular labeling was low and no systemic accumulation of OSAD markers was observed at the cell-matrix interface. The observed distribution pattern of OSAD is strikingly similar to that of bone sialoprotein (BSP), confirmed by double labeling. The results of the current study support a role for OSAD in the mineralization process. In this process BSP is assumed to be a nucleator of hydroxyapatite crystals, and OSAD could work in concert with BSP to regulate nucleation. However, the mechanisms involved remain to be elucidated.

Animals↗

PubMed2002

Fibromodulin-null murine knee joints display increased incidences of osteoarthritis and alterations in tissue biochemistry.

OBJECTIVE: To elucidate variations in tissue ultrastructure and incidence of pathology between fibromodulin (FM)-null mice and wild-type (WT) animals. DESIGN: FM-null and WT siblings from different age groups were compared. Serial sections were made through paraffin-embedded whole knees and investigated histologically. Additionally, medial femoral condyle peaks from sibling pairs were investigated ultrastructurally using transmission electron microscopy. RESULTS: Histological findings demonstrated a clear and increasing disparity between tissue degeneration in WT and FM-null animal knees with progressing age. Distinct differences were apparent by 36 weeks. Around the 80 week period and onward these differences became profound. However, qualitative ultrastructural investigation did not indicate either any aberrant tissue ultrastructure or any abnormal collagen fibril forms in FM-null articular cartilage compared with WT. Biochemical and immunohistochemical investigation of FM-null articular cartilage showed a significant increase in tissue levels of lumican (LUM). Conversely, the cruciate ligaments of the knee showed both an increase in LUM content and considerable structural abnormalities including the tendency towards rupture. CONCLUSION: This report indicates for the first time that FM-null mice have a higher propensity towards degenerative changes in their knee joints than comparable WT animals. Interestingly, no underlying ultrastructural or fibril abnormalities within the articular cartilage could be identified to explain why FM-null cartilage is more prone to pathological changes than wild-type tissue. We conclude that alterations in ligaments, and possibly other tissues within the knee, are of considerable importance in the pathogenesis of the observed articular cartilage degeneration.

Animals↗

PubMed2001

The CCR7 ligand elc (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment.

Lymphocyte homing to secondary lymphoid tissue is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial selectin-mediated tethering and rolling, firm adhesion of lymphocytes requires rapid upregulation of lymphocyte integrin adhesiveness. This step is mediated in part by the HEV-derived chemokine SLC (secondary lymphoid-tissue chemokine, or CCL21) that binds to the CC chemokine receptor (CCR)7 on lymphocytes. However, the CC chemokine ELC (Epstein-Barr virus-induced molecule 1 ligand chemokine, or CCL19) shares the same receptor, and ELC transcripts have been observed in the T cell areas of lymphoid organs. Here, we show that perivascular ELC is transcytosed to the luminal surfaces of HEVs and enables efficient T cell homing to lymph nodes. In situ hybridization on sections of human tonsil showed no ELC mRNA in HEVs, but immunostaining revealed ELC protein in cytoplasmic vesicles of HEV cells. Furthermore, ELC injected into the footpads of mice entered the draining lymph nodes and was presented by HEVs. Finally, intracutaneous injections of ELC in mice lacking functionally relevant ELC and SLC (plt/plt mice) restored T cell trafficking to draining lymph nodes as efficiently as SLC. We conclude that perivascular ELC is transcytosed to the luminal surfaces of HEVs and participates in CCR7-mediated triggering of lymphocyte arrest.

Animals↗

PubMed2001

[Diagnostic transmission electron microscopy].

BACKGROUND: Transmission electron microscopy (TEM) is an important diagnostic tool in surgical pathology. MATERIAL AND METHODS: We give an overview, based on our own experience, of the application of TEM in diagnostic pathology. RESULTS: In spite of its potential for high-grade resolution, the actual use of TEM in diagnostic pathology is rather limited. TEM is mandatory in the examination of kidney and muscle biopsies and is often indicated when a metabolic disease is suspected. However, in many centres its importance in tumour pathology has declined because of the advances in the field of immunohistochemistry. TEM requires a great deal of resources and high levels of skills in tissue processing and diagnostic interpretation. INTERPRETATION: The TEM diagnosis must be integrated with light microscopical and, often, immunohistopathological findings, as well as with the clinical data. We therefore recommend close collaboration between the clinician and the laboratory with regard to biopsy indication, handling of samples, and the final diagnosis.

Humans↗

PubMed2001

Ultrasound for diagnosis of infection in revision total hip arthroplasty.

Eighty consecutive patients (85 hips; 43 women; median age, 74 years [range, 33-90 years]) underwent a revision total hip arthroplasty. Preoperatively and guided by ultrasound, biopsy specimens of the joint pseudocapsule were taken, and joint fluid was aspirated for culture. Capsule morphology was investigated with light microscopy. When septic loosening was defined as 2 intraoperative cultures yielding the same microorganism, the prevalence was 12%. Sensitivity of the capsule biopsy cultures was 67%; specificity, 68%; positive predictive value, 22%; and negative predictive value, 94%. Joint fluid was often sparse and always falsely sterile. One specimen from a hip with septic loosening showed histologic changes (> or =3 foci, each with > or =3 plasma cells/high-power field) consistent with chronic infection. The remaining 8 septic loosenings eluded histologic detection, yielding 11% sensitivity. All aseptic loosenings were classified correctly (specificity 100%). Positive and negative predictive values were 100% and 89%. Ultrasound-guided aspiration and capsule biopsy with cultures and histology does not seem to be sufficiently accurate in the preoperative diagnosis of infected total hip arthroplasty.

Adult↗

PubMed2000

Area under the serum creatinine time-curve is a strong predictor of chronic renal allograft rejection.

BACKGROUND: A number of risk factors for chronic renal allograft rejection have been identified; in particular the number and severity of acute rejections, hypertension, hyperlipidemia, and insufficient immunosuppression. METHODS: In a retrospective case control study, all histologically confirmed cases of chronic rejection (n=45) that occurred between 1985 and 1993 among patients transplanted at Huddinge Hospital were compared with twice as many controls. Determinants such as donor age and sex, HLA-mismatch, cold ischemia time, recipient age and sex, body mass index, cause of renal disease, time undergoing dialysis, condition of blood vessels at surgery, time of onset, number of acute rejection episodes during the first 3 months, area under the serum creatinine versus time curve (AUC(Creatinine)), blood pressure, blood lipids, and cyclosporine concentrations at various times after the transplantation were also compared. Additional data were obtained from a questionnaire, concerning 79% of the cases and controls. RESULTS: Cases and controls were similar with regard to most determinants, that is, blood pressure, blood lipids, and average cyclosporine concentrations. The main outstanding risk factor for chronic rejection was the time-averaged creatinine (AUC(Creatinine)) value between day 22 and 3 months after transplantation. The adjusted odds ratio for chronic rejection increased stepwise from 1.1 to 9.2, when AUC(Creatinine) increased from < 150 to >300 micromol/l. The number of acute rejection episodes and number of HLA-mismatches also had a significant effect on the risk of chronic rejection. CONCLUSIONS: To reduce the risk of developing chronic rejection after renal transplantation acute rejection episodes during the first 3 months should be avoided as much as possible.

Adult↗

PubMed2000

Morphological and functional features of clasts in low phosphate, vitamin D-deficiency rickets.

Focusing on resorption processes, we have extended our previous studies on chondroclasts and osteoclasts in normally developing tissues, using a model of nutritionally induced vitamin D-deficiency rickets. To analyze the resorption process, we investigated the matrix-resorbing cells in this modified and poorly mineralized tissue regarding morphological features and expression of tartrate-resistant acid phosphatase (TRAP) at the subcellular level. Our goal was to test the hypotheses that initiation of resorption is impaired with unmineralized matrix, and that such alterations involve changes in the subcellullar distribution of TRAP, implicating a role for this enzyme in the resorption process. Our results reveal distinctly different morphological appearances of clast-like cells in rickets compared with normal osteoclasts and chondroclasts. Ordinary resorption structures of osteoclasts and chondroclasts at the cell-matrix border, i.e., ruffled borders and clear zones, are profoundly altered in favor of a less well-defined intermediate zone. TRAP distribution at the subcellullar level is also clearly different from that in osteoclasts and chondroclasts from normal rodents, with impaired secretion; consequently, the enzyme is unable to function in the matrix outside the ruffled border. Our ultrastructural observations demonstrate that in rickets, the clasts are incapable of degrading the poorly mineralized cartilage and bone efficiently. Rachitic clasts seem to be recruited to the matrix surface and interaction between cell and matrix is also initiated, but definitive resorption structures at the cell-matrix border are not normally developed. Whether resorption is inhibited by the mere lack of mineral or mineral-associated proteins, or by other mechanisms remains to be settled.

Acid Phosphatase↗

PubMed1999

Extensive clear zone and defective ruffled border formation in osteoclasts of osteopetrotic (ia/ia) rats: implications for secretory function.

The cellular distribution of osteoclast integrin subunits alpha(v) and beta(3), the tissue distribution, and level of the apparent ligand osteopontin (OPN) as well as of the putative regulatory enzyme tartrate-resistant acid phosphatase (TRAP) were studied along with the intracellular distribution of the activation marker c-src in osteopetrotic ia/ia (incisors-absent) mutant rats and their normal littermates. In ia/ia rats, the osteoclasts are incapable of bone matrix resorption. Ultrastructurally the cells exhibit extended clear zones at the expense of ordinary ruffled borders. A secretory dysfunction in the mutant is strongly suggested by the absence of detectable extracellular TRAP, concomitant with an accumulation of the enzyme in abundant small cytoplasmic vesicles. Moreover, TRAP mRNA, protein content, as well as enzymatic activity were elevated. Furthermore, increased levels of integrin subunits alpha(v) and beta(3) were detected at the clear zone of mutant osteoclasts. OPN mRNA levels were elevated in long bones from mutants. In ia/ia rats, immunolabeling for OPN was homogeneously distributed at the surface facing osteoclasts, while in normal littermates it was concentrated at the clear zone area and barely detectable at ruffled borders. The absence of OPN labeling in the abundant, putative intracellular secretory vesicles in mutant osteoclasts suggests that these cells do not produce OPN. The osteoclasts of ia/ia rats appeared to produce and translocate the c-src protein to the cell membrane. In ia/ia a defect ruffled border-formation is observed along with extensive clear zone formation and decreased secretory function. The lesion may be due to a signaling defect, but in that case the defect seems to be located downstream to or not involving the c-src pathway. Our results illustrate the close relationship between secretory function and ruffled border formation in osteoclasts, a relationship that appears to be necessary for proper resorptive function.

Acid Phosphatase↗

PubMed1999

Fibromodulin-null mice have abnormal collagen fibrils, tissue organization, and altered lumican deposition in tendon.

Fibromodulin is a member of a family of connective tissue glycoproteins/proteoglycans containing leucine-rich repeat motifs. Several members of this gene family bind to fibrillar collagens and are believed to function in the assembly of the collagen network in connective tissues. Here we show that mice lacking a functional fibromodulin gene exhibit an altered morphological phenotype in tail tendon with fewer and abnormal collagen fiber bundles. In fibromodulin-null animals virtually all collagen fiber bundles are disorganized and have an abnormal morphology. Also 10-20% of the bundles in heterozygous mice are similar to the abnormal bundles in fibromodulin-null tail tendon. Ultrastructural analysis of Achilles tendon from fibromodulin-null mice show collagen fibrils with irregular and rough outlines in cross-section. Morphometric analysis show that fibromodulin-null mice have on the average thinner fibrils than wild type animals as a result of a larger preponderance of very thin fibrils in an overall similar range of fibril diameters. Protein and RNA analyses show an approximately 4-fold increase in the content of lumican in fibromodulin-null as compared with wild type tail tendon, despite a decrease in lumican mRNA. These results demonstrate a role for fibromodulin in collagen fibrillogenesis and suggest that the orchestrated action of several leucine-rich repeat glycoproteins/proteoglycans influence the architecture of collagen matrices.

Animals↗

PubMed1999

Association of the aggrecan keratan sulfate-rich region with collagen in bovine articular cartilage.

Aggrecan, the predominant large proteoglycan of cartilage, is a multidomain macromolecule with each domain contributing specific functional properties. One of the domains contains the majority of the keratan sulfate (KS) chain substituents and a protein segment with a proline-rich hexapeptide repeat sequence. The function of this domain is unknown but the primary structure suggests a potential for binding to collagen fibrils. We have examined binding of aggrecan fragments encompassing the KS-rich region in a solid-phase assay. A moderate affinity (apparent Kd = 1.1 microM) for isolated collagen II, as well as collagen I, was demonstrated. Enzymatic digestion of the KS chains did not alter the capacity of the peptide to bind to collagen, whereas cleavage of the protein core abolished the interaction. The distribution of the aggrecan KS-rich region in bovine tarsometatarsal joint cartilage was investigated using immunoelectron microscopy. Immunoreactivity was relatively low in the superficial zone and higher in the intermediate and deep zones of the uncalcified cartilage. Within the pericellular and territorial matrix compartments the epitopes representing the aggrecan KS-rich region were detected preferentially near or at collagen fibrils. Along the fibrils, epitope reactivity was non-randomly distributed, showing preference for the gap region within the D-period. Our data suggest that collagen fibrils interact with the KS-rich regions of several aggrecan monomers aligned within a proteoglycan aggregate. The fibril could therefore serve as a backbone in at least some of the aggrecan complexes.

Aggrecans↗

PubMed1999

The long-term effect of a short course of transforming growth factor-beta1 on rat articular cartilage.

The long-term effect of 3 days' topical administration of TGF-beta1 on unloaded articular cartilage in growing rats was investigated. Three to five rats were sacrificed on days 15, 30, 45, 60 and 90 after the last injection and the patellas were subjected to light and electron microscopic evaluation. The patellas showed age-related changes when entering the maturation phase. Absence of a hypertrophic zone and formation of a subchondral bone plate were observed in both treated rats and controls from that time point. Reduction of total cell amount was observed between older and younger patellas in both treated rats and controls. TGF-beta1 treatment resulted in accelerated maturation and ageing. Furthermore, the administration of TGF-beta1 resulted in a higher unmineralized cartilage with an increased total amount of cells in the intermediate zone. Matrix areas showing ultrastructural features of disturbed matrix composition were seen in the deeper part of this zone at all time points, but in the treated patellas only. The present results indicate that TGF-beta1 treatment may induce changes in articular cartilage in some respects similar to those seen in the early stages of degenerative and inflammatory joint diseases.

Animals↗

PubMed1998

Polymerase chain reaction and in situ hybridization of Epstein-Barr virus in liver biopsy specimens facilitate the diagnosis of EBV hepatitis after liver transplantation.

A nested polymerase chain reaction (nPCR) for Epstein-Barr virus (EBV) DNA, RNA in situ hybridization (EBER-ISH), and immunostaining against the ZEBRA EBV protein for diagnosis of EBV hepatitis were performed on 43 liver biopsy specimens obtained from 18 patients in the 1st year after liver transplantation (LTX). The findings were related to liver histology and results of EBV-nPCR on concomitantly obtained serum samples. EBV DNA was detected in 30% and RNA in 34% of the liver biopsy specimens using nPCR and EBER-ISH, respectively, giving a significant correlation between the two methods (P = 0.003). All but one patient had detectable EBV DNA in serum samples obtained within 1 month of the biopsy. More than 90% of the nPCR and EBER-ISH-positive biopsy specimens were obtained 3 months or less post-LTX. There was no significant difference in EBV genome findings in biopsy specimens with or without lymphocytic-immunoblastic infiltrates, either in nPCR (P = 0.73) or in ISH (P = 0.73). Two of three biopsy specimens with these histological changes suggesting a viral genesis were positive in EBV-nPCR but negative in ISH. Histopathological changes in EBV hepatitis may be nonspecific and masked by other complications. The use of EBV-nPCR and EBER-ISH in liver graft biopsy specimens of heavily immunosuppressed patients may give an early indication of EBV-related disease and can be used to guide therapeutic intervention.

Adolescent↗

PubMed1998

Chondroclasts and osteoclasts in bones of young rats: comparison of ultrastructural and functional features.

The aim of the present study was to characterize cells involved in resorption during endochondral bone formation. We investigated whether the cells involved in cartilage breakdown at the epiphyseal/metaphyseal border, i.e., chondroclasts, share the characteristics of bone/cartilage-resorbing osteoclasts at the metaphyseal/diaphyseal border regarding ultrastructural features and functional activity. Morphometric evaluation showed that chondroclasts do not form ruffled borders and clear zones, i.e., well-known resorption characteristics, to the same extent as osteoclasts, present at the lower metaphysis. Instead, chondroclasts tend to express an undifferentiated surface adjacent to the matrix, not structurally different from the basolateral plasma membrane. Tartrate-resistant acid phosphatase (TRAP) was used as a marker for functional activity. Immunohistochemical staining by light microscopy was strong in both chondroclasts and in osteoclasts. Furthermore, in situ hybridization revealed large amounts of TRAP mRNA in chondroclasts as well as in osteoclasts. Ultrastructural immunohistochemistry suggests extensive secretion of the TRAP enzyme in the ruffled border area of both chondroclasts and osteoclasts. Intracellular accumulation was seen particularly in chondroclasts, possibly as a consequence of a relative disinclination to develop a ruffled border. Thus, semiquantitative estimation of TRAP distribution showed an inverse relationship between extracellular and intracellular TRAP in chondroclasts and osteoclasts. These results indicate that chondroclasts and osteoclasts differ, not only with respect to location but possibly also by mode of action. The observed differences may reflect the maturation sequence of these multinucleated cells when associated with different metaphyseal trabecular surfaces.

Acid Phosphatase↗