Biomedical subjects

J M Greve

Publications and source records attributed to J M Greve.

At least 19 recordsLinked to original sources

PubMed2006

Articular cartilage MR imaging and thickness mapping of a loaded knee joint before and after meniscectomy.

OBJECTIVE: We describe a technique to axially compress a sheep knee joint in an MRI scanner and measure articular cartilage deformation. As an initial application, tibial articular cartilage deformation patterns after 2 h of static loading before and after medial meniscectomy are compared. METHODS: Precision was established for repeated scans and repeated segmentations. Accuracy was established by comparing to micro-CT measurements. Four sheep knees were then imaged unloaded, and while statically loaded for 2 h at 1.5 times body weight before and after medial meniscectomy. Images were obtained using a 3D gradient echo sequence in a 4.7 T MRI. Corresponding 3D cartilage thickness models were created. Nominal strain patterns for the intact and meniscectomized conditions were compared. RESULTS: Coefficients of variation were all 2% or less. Root mean squared errors of MR cartilage thickness measurements averaged less than 0.09 mm. Meniscectomy resulted in a 60% decrease in the contact area (P=0.001) and a 13% increase in maximum cartilage deformation (P=0.01). Following meniscectomy, there were greater areas of articular cartilage experiencing abnormally high and low nominal strains. Areas of moderate nominal strain were reduced. CONCLUSIONS: Medial meniscectomy resulted in increased medial tibial cartilage nominal strains centrally and decreased strains peripherally. Areas of abnormally high nominal strain following meniscectomy correlated with areas that are known to develop fibrillation and softening 16 weeks after medial meniscectomy. Areas of abnormally low nominal strain correlated with areas of osteophyte formation. Studies of articular cartilage deformation may prove useful in elucidating the mechanical etiology of osteoarthritis.

Animals↗

PubMed2000

Effects of changes in cadence, prosthetic componentry, and time on interface pressures and shear stresses of three trans-tibial amputees.

OBJECTIVE: To evaluate the effects of changes in cadence, prosthetic componentry, and time on interface pressures and resultant shear stresses in trans-tibial amputee case studies. DESIGN: Interface stresses were monitored using custom-designed instrumentation at 13 sites on three subjects with unilateral trans-tibial amputation walking with patellar-tendon-bearing prosthetic limbs. BACKGROUND: Previous studies suggested that week-to-week residual limb changes altered interface stresses more than did alterations in prosthetic alignment. No studies investigating effects of changes in cadence or componentry on interface stress distributions nor comparing their influence with week-to-week changes have been conducted previously. METHODS: Five different prosthetic componentry configurations were tested at each of three cadences in four sessions. Data were analysed for the magnitudes and timings of peak pressures and resultant shear stresses as well as corresponding resultant shear angles. RESULTS: None of the three cadences or five componentry configurations consistently induced significantly (P<0.05) higher or lower interface stress magnitudes for all subjects. However, an Aluminium Pylon/SACH Foot combination compared with an AirStance (pneumatic shank)/Seattle LightFoot unit induced later peak interface stress timings as a percentage of stance phase. Higher and more frequent interface stress changes were seen between the weekly sessions than between different cadences or between different componentry configurations. CONCLUSION: The amputees' capabilities to compensate for week-to-week residual limb changes were less than those for intra-session cadence or componentry alterations. RELEVANCE: Results suggest that effective techniques to accommodate week-to-week residual limb fluctuations could have a greater impact on maintaining consistent interface stress distributions than do adjustments in cadence or componentry.

Adult↗

PubMed2000

A T-cell-selective interleukin 2 mutein exhibits potent antitumor activity and is well tolerated in vivo.

Human interleukin 2 (IL-2; Proleukin) is an approved therapeutic for advanced-stage metastatic cancer; however, its use is restricted because of severe systemic toxicity. Its function as a central mediator of T-cell activation may contribute to its efficacy for cancer therapy. However, activation of natural killer (NK) cells by therapeutically administered IL-2 may mediate toxicity. Here we have used targeted mutagenesis of human IL-2 to generate a mutein with approximately 3,000-fold in vitro selectivity for T cells over NK cells relative to wild-type IL-2. We compared the variant, termed BAY 50-4798, with human IL-2 (Proleukin) in a therapeutic dosing regimen in chimpanzees, and found that although the T-cell mobilization and activation properties of BAY 50-4798 were comparable to human IL-2, BAY 50-4798 was better tolerated in the chimpanzee. BAY 50-4798 was also shown to inhibit metastasis in a mouse tumor model. These results indicate that BAY 50-4798 may exhibit a greater therapeutic index than IL-2 in humans in the treatment of cancer and AIDS.

Animals↗

PubMed2000

Energy, substrate and protein metabolism in morbid obesity before, during and after massive weight loss.

OBJECTIVE: To investigate the effect of surgically induced weight loss on energy, substrate and protein metabolism of morbidly obese patients. DESIGN: A prospective, clinical intervention study of morbidly obese patients before and after surgical treatment. SUBJECTS: Eight morbidly obese patients (BMI 47.88+/-7.03). METHODS: Total energy expenditure (TEE; doubly labeled water method), sleeping metabolic rate (SMR; respiration chamber), body composition (deuterium oxide component of doubly labeled water), substrate metabolism (48 h dietary records, 48 h urine collection and gaseous exchange in the respiration chamber) and whole body protein turnover (primed-continuous infusion of L-[1-13C]-leucine) were measured before, 3 and 12 months after vertical banded gastroplasty (VBG). RESULTS: The TEE decreased as a result of a decreased SMR (64%) and non-SMR (36%; P=0.001). SMR as a function of fat-free mass (FFM) decreased after weight loss (P<0.05). The physical activity index (PAI), defined as TEE/SMR, was low and was not influenced by weight loss. Protein and carbohydrate oxidation decreased significantly after VBG (P<0.05), although 3 months after VBG protein oxidation did not decrease enough to prevent loss of FFM. The energy used for protein turnover was approximately 24% of SMR and did not change after weight loss. CONCLUSIONS: Compensatory processes that oppose weight loss of morbidly obese patients exist, as demonstrated by the disproportional reduction of SMR, and a low PAI. Protein turnover is not a major contributor to the disproportional reduction of SMR.

Adenosine Triphosphate↗

PubMed2000

Changes in interface pressure and stump shape over time: preliminary results from a trans-tibial amputee subject.

Interface stresses and stump shape were measured during sessions over a two-month interval on a trans-tibial amputee subject. Results from thirteen transducer sites monitored during four sessions showed greater interface pressure changes over time at anterior sites than at lateral or posterior locations. There was a trend of decreased pressure with stump swelling and increased pressure for stump atrophy. During one session in which stump shape was monitored over a 23.1 min interval after ambulation, stump swelling was localised. Swelling tended to increase in the regions of initial enlargement, as opposed to redistributing through different areas over time. Regions of swelling were anterior lateral and posterior proximal, areas of thick underlying soft tissue. Identification of localised areas of swelling and atrophy and understanding of their effects on interface pressures could be used to improve individual socket design.

Adult↗

PubMed1999

The structure of the two amino-terminal domains of human intercellular adhesion molecule-1 suggests how it functions as a rhinovirus receptor.

The normal function of human intercellular adhesion molecule-1 (ICAM-1) is to provide adhesion between endothelial cells and leukocytes after injury or stress. ICAM-1 binds to leukocyte function-associated antigen (LFA-1) or macrophage-1 antigen (Mac-1). However, ICAM-1 is also utilized as a receptor by the major group of human rhinoviruses and is a catalyst for the subsequent viral uncoating during cell entry. The three-dimensional atomic structure of the two amino-terminal domains (D1 and D2) of ICAM-1 has been determined to 2.2 A resolution and fitted into a cryo-electron microscopy reconstruction of a rhinovirus-ICAM-1 complex. Rhinovirus attachment is confined to the BC, CD, DE and FG loops of the amino-terminal immunoglobulin-like domain (D1) at the end distal to the cellular membrane. The loops are considerably different in structure to those of human ICAM-2 or murine ICAM-1 which do not bind rhinoviruses. There are extensive charge interactions between ICAM-1 and human rhinoviruses, which are mostly conserved in both major and minor receptor groups of rhinoviruses. The interaction of ICAMs with LFA-1 is known to be mediated by a divalent cation bound to the I-(insertion) domain on the alpha chain of LFA-1 and the carboxy group of a conserved glutamic acid residue on ICAMs. Domain D1 has been docked with the known structure of the I-domain. The resultant model is consistent with mutational data and provides a structural framework for the adhesion between these molecules.

Amino Acid Sequence↗

PubMed1998

An immune cell-selective interleukin 4 agonist.

Interleukin 4 (IL-4) is a pleiotropic cytokine. Of the cell types responsive to IL-4, T cells express one IL-4 receptor (IL-4R) type, IL-4Ralpha/IL-2Rgamma (class I IL-4R), whereas endothelial cells express another type, IL-4Ralpha/IL-13Ralpha (class II IL-4R). It was hypothesized that IL-4 variants could be generated that would be selective for cell types expressing the different IL-4Rs. A series of IL-4 muteins were generated that were substituted in the region of IL-4 implicated in interactions with IL-2Rgamma. These muteins were evaluated in T cell and endothelial cell assays. One of these muteins, containing the mutation Arg-121 to Glu (IL-4/R121E), exhibited complete biological selectivity for T cells, B cells, and monocytes, but showed no activity on endothelial cells. Receptor binding studies indicated that IL-4/R121E retained physical interaction with IL-2Rgamma but not IL-13Ralpha; consistent with this observation, IL-4/R121E was an antagonist of IL-4-induced activity on endothelial cells. IL-4/R121E exhibits a spectrum of activities in vitro that suggest utility in the treatment of certain autoimmune diseases.

B-Lymphocytes↗

PubMed1998

The structure of the two amino-terminal domains of human ICAM-1 suggests how it functions as a rhinovirus receptor and as an LFA-1 integrin ligand.

The normal function of human intercellular adhesion molecule-1 (ICAM-1) is to provide adhesion between endothelial cells and leukocytes after injury or stress. ICAM-1 binds to leukocyte function-associated antigen (LFA-1) or macrophage-1 antigen (Mac-1). However, ICAM-1 is also used as a receptor by the major group of human rhinoviruses and is a catalyst for the subsequent viral uncoating during cell entry. The three-dimensional atomic structure of the two amino-terminal domains (D1 and D2) of ICAM-1 has been determined to 2.2-A resolution and fitted into a cryoelectron microscopy reconstruction of a rhinovirus-ICAM-1 complex. Rhinovirus attachment is confined to the BC, CD, DE, and FG loops of the amino-terminal Ig-like domain (D1) at the end distal to the cellular membrane. The loops are considerably different in structure to those of human ICAM-2 or murine ICAM-1, which do not bind rhinoviruses. There are extensive charge interactions between ICAM-1 and human rhinoviruses, which are mostly conserved in both major and minor receptor groups of rhinoviruses. The interaction of ICAMs with LFA-1 is known to be mediated by a divalent cation bound to the insertion (I)-domain on the alpha chain of LFA-1 and the carboxyl group of a conserved glutamic acid residue on ICAMs. Domain D1 has been docked with the known structure of the I-domain. The resultant model is consistent with mutational data and provides a structural framework for the adhesion between these molecules.

Amino Acid Sequence↗

PubMed1998

Material properties of commonly-used interface materials and their static coefficients of friction with skin and socks.

Compressive stiffness (CS) of different supporting materials used in prosthetics and orthotics and their static coefficients of friction (COF) with skin and socks were characterized. Materials tested included Spenco, Poron, nylon-reinforced silicone, Soft Pelite, Medium Pelite, Firm Plastazote, Regular Plastazote, and Nickelplast. A displacement-controlled testing device was constructed to assess the CS of 11.1 mm diameter material specimens under cyclic loading (1 Hz) to 220 kPa over 10- and 60-min periods. Results demonstrated local CS ranging from 687 kPa (Poron) to 3,990 kPa (Soft Pelite). To fit the cyclic stress-strain (S-S) data within an error of 4.0 percent full-scale output, the minimum order of fit required for Spenco, Poron, and nylon-reinforced silicone was a third-order polynomial; for Soft Pelite, Medium Pelite, Firm Plastazote, and Regular Plastazote, a second-order polynomial; and for Nickelplast, a linear fit. For all materials, the nonrecovered strains were related to loading time using an exponential fit. A biaxial force-controlled load applicator device was used to assess COF at skin-material, sock-material, and skin-sock interfaces for shear forces of 1 to 4 N applied to a 10.2 x 7.8 mm loading pad. COFs ranged from 0.48 (+/- 0.05) to 0.89 (+/- 0.09). COFs at skin-material interfaces were significantly (p < 0.05) higher than those at skin-sock interfaces. There was a trend of a higher COF at sock-material interfaces than at skin-sock interfaces. These data are of potential utility in finite element modeling sensitivity analysis of residual limb-prosthetic socket systems or body-orthosis systems to characterize effects of material features on interface pressure and shear stress distributions.

Biocompatible Materials↗

PubMed1997

Identification and cloning of human placental bikunin, a novel serine protease inhibitor containing two Kunitz domains.

Interrogation of the public expressed sequence tag (EST) data base with the sequence of preproaprotinin identified ESTs encoding two potential new members of the Kunitz family of serine protease inhibitors. Through reiterative interrogation, an EST contig was obtained, the consensus sequence from which encoded both of the novel Kunitz domains in a single open reading frame. This consensus sequence was used to direct the isolation of a full-length cDNA clone from a placental library. The resulting cDNA sequence predicted a 252-residue protein containing a putative NH2-terminal signal peptide followed sequentially by each of the two Kunitz domains within a 170-residue ectodomain, a putative transmembrane domain, and a 31-residue hydrophilic COOH terminus. The gene for this putative novel protein was mapped by use of a radiation hybrid panel to chromosome 19q13, and Northern analysis showed that the corresponding mRNA was expressed at high levels in human placenta and pancreas and at lower levels in brain, lung, and kidney. An endogenous soluble form of this protein, which was designated as placental bikunin, was highly purified from human placenta by sequential kallikrein-Sepharose affinity, gel filtration, and C18 reverse-phase chromatography. The natural protein exhibited the same NH2 terminus as predicted from the cloned cDNA and inhibited trypsin, plasma kallikrein, and plasmin with IC50 values in the nanomolar range.

Amino Acid Sequence↗

PubMed1997

Surface expression of intercellular adhesion molecule 1 on epithelial cells in the human adenoid.

Human rhinoviruses enter the host by way of the nose and conjunctiva. Intercellular adhesion molecule 1 (ICAM-1) is the cellular receptor for the majority of rhinoviruses. ICAM-1 expression on the luminal surface of epithelial cells in the upper airway may be an important determinant of virus localization in the airway. Eighteen adenoids and 5 nasopharyngeal biopsies were evaluated by immunohistochemistry for surface expression of ICAM-1. Heavy immunoreactivity of ICAM-1 was found on the surface of a small number of single nonciliated cells in the lymphoepithelium. Squamous epithelial cells showed minimal to no staining, and ciliated epithelium had positive ICAM-1 staining of the basal cells but not on the ciliated border. The localization of ICAM-1 expression to specific, limited areas of the surface epithelium of the nasopharynx may have important implications in the pathogenesis of rhinovirus infections, especially initiation of the host response to rhinovirus.

Adenoids↗

PubMed1997

Prevention of rhinovirus infection in chimpanzees by soluble intercellular adhesion molecule-1.

Intercellular adhesion molecule-1 (ICAM-1) is the cell surface receptor for the major class of human rhinoviruses, and tICAM453, a truncated, soluble form of ICAM-1, has been shown previously to be a potent in vitro inhibitor of rhinovirus. In this report, we have investigated the in vivo efficacy of tICAM453 for the prophylaxis of rhinovirus serotype 16 infection in the chimpanzee. Because chimpanzees do not show clinical symptoms of infection after rhinovirus challenge, infection was followed by measuring antirhinovirus serum antibody responses and detection of virus shedding. By both of these measures, intranasal application of tICAM453 was efficacious in preventing rhinovirus infection in chimpanzees subsequently challenged with infectious doses of virus. These results suggest that the use of soluble rhinovirus receptor to inhibit virus binding to host cells should be feasible in humans.

Administration, Intranasal↗

PubMed1994

Crystallographic and cryo EM analysis of virion-receptor interactions.

Cryoelectron microscopy has been used to determine the first structure of a virus when complexed with its glycoprotein cellular receptor. Human rhinovirus 16 (HRV16) complexed with the two amino-terminal, immunoglobulin-like domains of the intercellular adhesion molecule-1 (ICAM-1) shows that ICAM-1 binds into the 12 A deep "canyon" on the surface of the virus. This is consistent with the prediction that the viral receptor attachment site lies in a cavity inaccessible to the host's antibodies. The atomic structures of HRV14 and CD4, homologous to HRV16 and ICAM-1, showed excellent correspondence with observed density, thus establishing the virus-receptor interactions.

Cell Adhesion Molecules↗

PubMed1994

Spectrum of activity of soluble intercellular adhesion molecule-1 against rhinovirus reference strains and field isolates.

The antiviral potency of soluble intercellular adhesion molecule-1 (ICAM-1; the major receptor for human rhinoviruses) was determined for a subset of American Type Culture Collection reference serotypes and field isolates of rhinovirus. The results indicate that soluble ICAM-1 exhibits a broad spectrum of activity against rhinoviruses and that field isolates have a sensitivity indistinguishable from that of laboratory strains.

Cell Adhesion Molecules↗

PubMed1993

Structure of a human rhinovirus complexed with its receptor molecule.

Cryoelectron microscopy has been used to determine the structure of a virus when complexed with its glycoprotein cellular receptor. Human rhinovirus 16 complexed with the two amino-terminal, immunoglobulin-like domains of the intercellular adhesion molecule 1 shows that the intercellular adhesion molecule 1 binds into the 12-A deep "canyon" on the viral surface. This result confirms the prediction that the viral-receptor attachment site lies in a cavity inaccessible to the host's antibodies. The atomic structures of human rhinovirus 14 and CD4, homologous to human rhinovirus 16 and intercellular adhesion molecule 1, showed excellent correspondence with observed density, thus establishing the virus-receptor interactions.

Antigens, CD↗

PubMed1993

Cell contact between T cells and synovial fibroblasts causes induction of adhesion molecules and cytokines.

Human activated T cells adhere to synovial fibroblast-like cells in vitro. The present study was conducted to investigate the consequences of T cell-synovial fibroblast interactions with regard to induction of adhesion molecules and proinflammatory cytokines. A sensitive Western blot technique, polymerase chain reaction (PCR) amplification, and fluorescence-activated cell sorter (FACS) analysis were used to analyze the induction of VCAM-1 and ICAM-1 expression in T cell-synovial fibroblast cocultures. VCAM-1 and ICAM-1 expression could be induced in synovial fibroblast-like cells by 2 h. PCR amplification showed that both forms of VCAM-1 mRNA are found after the interaction of synovial fibroblasts with T cells. Up-regulation of VCAM-1 and ICAM-1 was confined to synovial fibroblasts; T cells did not express VCAM-1 or increased ICAM-1. In contrast to the T cell-synoviocyte interaction, the interaction between T cells and dermal fibroblasts resulted in the up-regulation of ICAM-1 but not VCAM-1, suggesting tissue-specific regulation of VCAM-1. The T cell-synovial fibroblast interaction also resulted in increased levels of tumor necrosis factor (TNF), interferon-gamma, and interleukin-6 in coculture supernatant. Of the neutralizing antibodies used against these cytokines, only anti-TNF could significantly inhibit VCAM-1 and ICAM-1 expression. When T cells were separated from synoviocytes by a chamber that allowed medium exchange but no cell contact, VCAM-1 and ICAM-1 failed to be up-regulated and cytokine accumulation in cocultures was drastically reduced. Our results demonstrate mutual cell activation of T cells and synoviocytes upon cell contact as shown by the release of T cell- and synoviocyte-specific cytokines and suggest a cell contact-mediated and T cell-initiated mechanism for the chronic accumulation and retention of mononuclear cells via VCAM-1/ICAM-1 by synovial fibroblasts in the rheumatoid synovium.

Arthritis, Rheumatoid↗

PubMed1993

Functional electrical stimulation (FES): muscle histochemical analysis.

Functional electrical stimulation (FES) has been used in Brazil since 1989 to obtain functional improvement in paraplegic patients' orthostasis and locomotion. The aim of this paper is to evaluate the histochemical changes observed in the quadriceps femoris muscle following the use of FES. We studied four patients with traumatic spinal cord lesions at T4-10 level, Frankel A, all within 12-24 months postlesion. They were all submitted to FES using the following criteria: square-wave, 20-30 Hz frequency, pulses of 0.003 seconds, time of stimulation 5 seconds, resting interval 10 seconds. The stimulation was applied during 90 consecutive days, 30 minutes each time, twice daily. The interval between the stimulations was 6 hours. Quadriceps muscle biopsies were performed before and after the use of FES. We used ATPase technique for the histochemical analysis, where three different dying patterns can be observed for the three types of muscular fibres (I, IIa and IIb). The two samples from each patient were analysed measuring the fibres' diameters and their index of atrophy, and counting the total number of each type of fibre in each sample. The mean total number of fibres in each sample was 256 +/- 12.3. The results showed that the sizes of the three types of fibres were not modified with the use of FES; the number of type IIa fibres increased in a significant fashion, after using of FES.

Adult↗

PubMed1993

Formation of rhinovirus-soluble ICAM-1 complexes and conformational changes in the virion.

Viral receptors serve both to target viruses to specific cell types and to actively promote the entry of bound virus into cells. Human rhinoviruses (HRVs) can form complexes in vitro with a truncated soluble form of the HRV cell surface receptor, ICAM-1. These complexes appear to be stoichiometric, with approximately 60 ICAM molecules bound per virion or 1 ICAM-1 molecule per icosahedral face of the capsid. The complex can have two fates, either dissociating to yield free virus and free ICAM-1 or uncoating to break down to an 80S empty capsid which has released VP4, viral RNA, and ICAM-1. This uncoating in vitro mimics the uncoating of virus during infection of cells. The stability of the virus-receptor complex is dependent on temperature and the rhinovirus serotype. HRV serotype 14 (HRV14)-ICAM-1 complexes rapidly uncoat, HRV16 forms a stable virus-ICAM complex which does not uncoat detectably at 34 degrees C, and HRV3 has an intermediate phenotype. Rhinovirus can also uncoat after exposure to mildly acidic pH. The sensitivities of individual rhinovirus serotypes to ICAM-1-mediated virus uncoating do not correlate with uncoating promoted by incubation at low pH, suggesting that these two means of virus destabilization occur by different mechanisms. Soluble ICAM-1 and low pH do not act synergistically to promote uncoating. The rate of uncoating does appear to be inversely related to virus affinity for its receptor.

Capsid↗