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Biomedical subjects

Michael Benjamin

Publications and source records attributed to Michael Benjamin.

12 recordsLinked to original sources
PubMed2006

Connexin 32 and 43 gap junctions differentially modulate tenocyte response to cyclic mechanical load.

Gap junctions allow rapid exchange of ions and small metabolites between cells. They can occur between connective tissue cells, and in tendons there are two prominent types, composed of connexin 32 or 43. These form distinct networks - tenocyte rows are linked by both longitudinally, but only by connexin 43 laterally. We hypothesised that the junctions had different roles in cell response to mechanical loading, and measured the effects of inhibitors of gap junction function on secretion of collagen by tenocyte cultures exposed to mechanical strain. Chicken tendon fibroblasts were exposed to cyclic tensile loading in the presence or absence of general gap junction inhibitors (halothane or the biomimetic peptide gap27), or antisense oligonucleotides to chicken connexin 32 or 43. Untreated cultures increased collagen secretion by around 25% under load. Halothane eliminated this response but caused cell damage. Gap27 peptide reduced secretion but maintained loading effects - strained cultures secreting more collagen than unstrained. Antisense downregulation showed major differences between connexins: antisense 32 reduced, and antisense 43 increased, collagen secretion. In both cases loading effects were maintained. This shows that (i) gap junctional integration of signals is important in load response of tenocyte populations - mechanotransduction occurs in individual cells but integration of signals markedly enhances it and (ii) communication via connexin 32 and 43 have differential effects on the load response, with connexin 32 being stimulatory and connexin 43 being inhibitory. Cells coordinate and control their response to mechanical signals at least in part by differential actions of these two types of gap junction.

Anesthetics, Inhalation↗
PubMed2005

An immunohistochemical study of the tissue bridging adult spondylolytic defects--the presence and significance of fibrocartilaginous entheses.

UNLABELLED: Introduction Spondylolytic spondylolisthesis is an osseous discontinuity of the vertebral arch that predominantly affects the fifth lumbar vertebra. Biomechanical factors are closely related to the condition. An immunohistochemical investigation of lysis-zone tissue obtained from patients with isthmic spondylolisthesis was performed to determine the molecular composition of the lysis-zone tissue and enable interpretation of the mechanical demands to which the tissue is subject. METHODS: During surgery, the tissue filling the spondylytic defects was removed from 13 patients. Twelve spondylolistheses were at the L5/S1 level with slippage being less than Meyerding grade II. Samples were methanol fixed, decalcified and cryosectioned. Sections were labelled with a panel of monoclonal antibodies directed against collagens, glycosaminoglycans and proteoglycans. RESULTS: The lysis-zone tissue had an ordered collagenous structure with distinct fibrocartilaginous entheses at both ends. Typically, these had zones of calcified and uncalcified fibrocartilage labelling strongly for type II collagen and aggrecan. Labelling was also detected around bony spurs that extended from the enthesis into the lysis-zone. The entheses also labelled for types I, III and VI collagens, chondroitin four and six sulfate, keratan and dermatan sulfate, link protein, versican and tenascin. CONCLUSIONS: Although the gap filled by the lysis tissue is a pathological feature, the tissue itself has hallmarks of a normal ligament-i.e. fibrocartilaginous entheses at either end of an ordered collagenous fibre structure. The fibrocartilage is believed to dissipate stress concentration at the hard/soft tissue boundary. The widespread occurrence of molecules typical of cartilage in the attachment of the lysis tissue, suggests that compressive and shear forces are present to which the enthesis is adapted, in addition to the expected tensile forces across the spondylolysis. Such a combination of tensile, shear and compressive forces must operate whenever there is any opening or closing of the spondylolytic gap.

Adult↗
PubMed2005

An immunohistochemical study of the extracellular matrix of the tarsal plate in the upper eyelid in human beings.

The superior tarsus is a plate of tissue that stiffens the upper eyelid, gives it support and determines its form. The purpose of the present study was to relate the composition of its extracellular matrix to its function and to report regional differences that may influence the activity of its Meibomian glands. Fourteen methanol-fixed specimens were cryosectioned for immunohistochemistry and labelled with a panel of monoclonal antibodies against a wide range of collagens, glycosaminoglycans and proteoglycans. Labelling was detected with avidin-biotin-peroxidase. A further six specimens were formalin-fixed for routine histology. The tarsal plate immunolabelled strongly for types I, III and VI collagen and for aggrecan, versican, tenascin, cartilage oligomeric matrix protein (COMP) together with a variety of glycosaminoglycans (notably chondroitin 6 sulphate). A region of strong labelling for aggrecan, dermatan sulphate and chondroitin 6 sulphate immediately surrounded the Meibomian glands. The site of labelling corresponded to a layer of acellular and amorphous matrix seen histologically that we have termed the 'territorial matrix'. The results suggested that the tarsal plate is a specialized connective tissue that is neither purely fibrous nor cartilaginous, yet has an aggrecan content that probably contributes to its stiffness. Its unique character highlights the challenge in choosing an ideal mechanical substitute. As patients with rheumatoid arthritis often have problems relating to tear film deficiency, the ability of aggrecan or COMP to act as autoantigens may be significant. An immune reaction directed against these molecules could alter tarsal gland function by interfering with the interaction between the glands and their territorial matrix.

Adult↗
PubMed2004

Magnetic resonance imaging of periosteum with ultrashort TE pulse sequences.

PURPOSE: To assess the values of pulse sequences with ultrashort echo times (0.08 msec) for detecting and characterizing periosteum. MATERIALS AND METHODS: Two normal volunteers aged 33 and 58 years and 12 patients aged seven to 55 years were studied. A total of 10 of the patients had contrast enhancement with intravenous Gadodiamide. Two ovine tibias were examined before and after the periosteum was stripped from the bone. RESULTS: High signal regions were observed adjacent to cortical bone in all parts of the skeleton imaged. They were generally more conspicuous after fat suppression and contrast administration. In the ovine tibia there was a reduction in the high signal normally seen at the surface of the bone after periosteal stripping. The detached periosteum produced a high signal. Mean T(2)* values for adult human periosteum ranged from 5.3 to 11.4 msec. After enhancement the signal intensity increased. In two patients with tibial fractures, increased periosteal signal was seen and this showed marked enhancement. Signals from periosteum could be simulated by fat, contrast-enhanced blood and artifacts. CONCLUSION: The periosteum can be visualized with ultrashort echo time pulse sequences in health and disease.

Adult↗
PubMed2003

Myeloma and race: a review of the literature.

Multiple myeloma is an uncommon disease, with approximately 12,000 cases per year diagnosed in America. Blacks have had at least double the risk of being diagnosed with myeloma, and have had twice the mortality rate from the disease compared to whites. Research of the origins of this difference has yielded both insight and controversy. Obesity is likely a risk factor for myeloma, in both blacks and whites. Obesity is more prevalent in the black population, and this may help explain some of the increased incidence of myeloma. Also, genetic factors such as HLA antigens and family history seem to be important in explaining the differential risk of myeloma. Exposure to immunological challenges, especially urinary tract infections in black men, seems important in explaining some of the excess risk in blacks. Factors such as socioeconomic status, dietary preferences, vitamin intake, alcohol and tobacco use, either lack a consensus finding, or may not play a role in explaining the increased myeloma morbidity and mortality in blacks.

Black or African American↗
PubMed2003

Immunohistochemical analysis of the extracellular matrix in the posterior capsule of the zygapophysial joints in patients with degenerative L4-5 motion segment instability.

OBJECT: Although the hypertrophied shape of the zygapophysial joints in degenerative instability of the lumbar spine is well known, its underlying pathophysiological mechanism is unclear. The authors sought to provide evidence that there is increased fibrocartilaginous metaplasia in the posterior joint capsule resulting from greater mechanical loading; the authors suggest that these capsular changes are central to understanding the altered joint shape. METHODS: The LA-5 posterior articular complex was removed in 14 patients undergoing fusion for degenerative instability. After methanol-assisted fixation, cryosections were immunolabeled for a wide range of extracellular matrix molecules. These were collagens (Types I, II, III, V, and VI), glycosaminoglycans (chondroitin 4 and 6 sulfates; dermatan- and keratan-sulfate), and proteoglycans (versican, tenascin, aggrecan, and its associated link protein). The grade of degeneration of the articular complexes was assessed radiologically and histologically. CONCLUSIONS: The results of this study provide molecular evidence for an altered loading history on the joint capsule. The pronounced loss of intervertebral disc height that occurred in all patients with severe degeneration of the lumbar motion segment promotes an increased range of axial rotation that places the posterior capsule under greater mechanical load. Compared with normal joints studied previously, the posterior capsules involved in these degenerative joint complexes were hypertrophied and fibrocartilaginous throughout. Cartilaginous metaplasia was especially pronounced at the attachment sites (entheses) where the fibrocartilage now extended beyond the original level of the joint space, and capped the osseous spurs arising from these attachment sites.

Adult↗
PubMed2003

The structure and histopathology of the "enthesis organ" at the navicular insertion of the tendon of tibialis posterior.

OBJECTIVE: To investigate the structure, histopathology, and molecular composition of tissue specializations of the tibialis posterior enthesis. They collectively reduce stress concentration at the insertion site and are part of an "enthesis organ." This has implications for understanding the basis of enthesopathy. METHODS: Fifty-two specimens of tibialis posterior and the associated superomedial part of the calcaneonavicular ligament taken from cadavers were sectioned longitudinally and examined by routine histology (42 samples) or immunohistochemistry (10 samples). Serial sections of formalin fixed material were stained with Masson's trichrome, toluidine blue, or hematoxylin, eosin and alcian blue. A panel of antibodies against collagens, glycosaminoglycans, and proteoglycans was used to immunolabel methanol fixed material. RESULTS: The enthesis organ consists of the enthesis itself, the superomedial part of the calcaneonavicular ligament (which may fuse with the tendon), the tendon sheath, and associated accessory bones. The accessory bones lay in a region of fibrocartilage that was present even in specimens where the bones themselves were absent. Degenerative changes were seen at the enthesis, around the accessory bones, and in the walls of the tendon sheath. The navicular and accessory bone entheses, together with the calcaneonavicular ligament, were all rich in fibrocartilage. This immunolabeled for aggrecan, link protein, type II collagen, and versican. CONCLUSION: The complexity of the enthesis organ, and the diversity of sites showing histopathological changes, suggest that enthesopathy may not be located precisely at the osteotendinous junction. It could target a number of adjacent locations, in accord with what happens at other entheses; e.g., in patients with spondyloarthropathy. The prominence of fibrocartilage in the enthesis organ, and the degenerative changes to which it is subject, support the view that spondyloarthropathy has an underlying biomechanical basis.

Aged↗
PubMed2003

Expression of a wide range of fibrocartilage molecules at the entheses of the alar ligaments - possible antigenic targets for rheumatoid arthritis?

OBJECTIVE: To provide evidence for the existence of a wide range of molecules characteristic of fibrocartilage at normal alar ligament entheses, that may have a bearing on the pathogenesis of rheumatoid arthritis. The alar ligaments provide the mechanical restraint for head rotation and their integrity can be compromised in patients with RA and occasionally in those with spondyloarthropathy. METHODS: Both alar ligaments from 6 cadavers were fixed in 90% methanol and cryosectioned longitudinally. Sections were immunolabelled with antibodies against collagens, glycosaminoglycans, and proteoglycans. The immunohistochemical data were related to estimates of insertional angle change at the entheses that were calculated from measurements of ligament length and dens diameter. RESULTS: Molecules typical of fibrocartilage (including type II collagen, link protein, and aggrecan) were found at both entheses, but labelling was more prominent at the odontoid end. This correlated with a 3-fold greater insertional angle change during 40 degrees of head rotation at the attachment of the ligament to the dens. At the odontoid enthesis, fibrocartilage differentiation was most conspicuous posteriorly. CONCLUSION: The changes in insertional angle mean that compressive forces are prominent at both entheses, but particularly at the odontoid end, where the ligament partly wraps around the dens during head rotation. Thus, mechanical conditions are created that lead to pronounced fibrocartilage development, hence the expression of type II collagen, link protein, and aggrecan. The prominence of these molecules at the entheses raises the possibility that they could be antigenic targets for an autoimmune response in rheumatic diseases.

Aged↗
PubMed2002

Advances in the understanding of entheseal inflammation.

The importance of enthesitis in the pathogenesis of spondyloarthropathy (SpA) is now well recognized. Several entheses comprise more than simply the insertion site, and they are part of a complex biomechanical organ to resist shear and compression. It is also evident that tendons that wrap around bony pulleys form an integral part of joint capsules, and share, along with imaging abnormalities and histopathologic changes, common anatomic, histologic, and biomechanical features with classically defined entheses. Researchers have called these regions of tendons functional entheses. Furthermore, certain synovial joints have much in common with classic entheses--most notably those lined with fibrocartilage rather than hyaline cartilage. These observations provide a unifying anatomic basis for SpA. Enthesitis is associated with underlying osteitis, whether mechanically induced or inflammatory-related--with the extent of osteitis determined by the human leukocyte antigen-B27 gene. Until recently, there was no effective therapy for resistant enthesitis, but it is now evident that enthesitis responds well to biologic blockade with anti-tumor necrosis factor. Unraveling the pathogenic basis of enthesitis will have important implications for understanding and defining therapies in SpA.

Antibodies, Monoclonal↗
PubMed2002

Expression of a wide range of extracellular matrix molecules in the tendon and trochlea of the human superior oblique muscle.

PURPOSE: To show that the molecular composition of the extracellular matrix of the trochlea and its associated tendon may explain the link between some cases of acquired Brown syndrome and rheumatoid arthritis. METHODS: One trochlea and its tendon from 11 dissecting-room cadavers were fixed in methanol, cryosectioned, and immunolabeled with a panel of monoclonal antibodies against types I, II, III, V, and VI collagens, chondroitin-4 and -6, keratan and dermatan sulfates, aggrecan, link protein, versican, and tenascin. Labeling was detected with an avidin-biotin-peroxidase detection kit. RESULTS: The trochlea had a central core of hyaline cartilage surrounded by a band of fibrocartilage, but the tendon had no cartilage cells. Significantly, however, both structures immunolabeled for aggrecan, link protein, and type II collagen-molecules typical of articular cartilage. CONCLUSIONS: The presence of aggrecan, link protein, and type II collagen may account for the coincidence between transient attacks of acquired Brown syndrome in patients with juvenile and adult forms of chronic rheumatoid arthritis. Cleavage of aggrecan by aggrecanase in articular cartilage characterizes cartilage degeneration in rheumatoid arthritis. Thus, it is possible that aggrecan cleavage also occurs in the trochlea and tendon and contributes to their degeneration or to a local inflammatory reaction that may swell and thicken the tendon. In this context, it is also significant that link protein and type II collagen are now regarded as relevant antigenic targets for autoimmune responses in rheumatoid arthritis.

Adolescent↗