Biomedical subjects

J Antoniou

Publications and source records attributed to J Antoniou.

At least 37 records · Page 2Linked to original sources

PubMed1997

A new technique for measuring lumbar segmental motion in vivo. Method, accuracy, and preliminary results.

STUDY DESIGN: A direct method for three-dimensional in vivo spine kinematic studies was developed and used to measure segmental motion patterns in healthy subjects. OBJECTIVES: To validate the new method, and to study the L3-L4 segmental motion patterns for complex dynamic movements. SUMMARY OF BACKGROUND DATA: Conventional two-dimensional and three-dimensional radiographic methods have been used in the past to study spine kinematics. Few studies provided a direct approach to study segmental kinematics. No dynamic recordings of three-dimensional segmental motion patterns have been reported previously. METHODS: In 16 healthy men, Kirschner wires were inserted in the spinous processes of L3 and L4. Electromagnetic tracking sensors were attached to the pins. Motion data recorded during ranging exercises were used with biplanar radiographs to calculate L3-L4 segmental motion patterns. Errors resulting from pin deformation and the dynamic accuracy of the tracking system were investigated thoroughly. RESULTS: The average range of motion for flexion-extension was 16.9 degrees, for one side lateral bending 6.3 degrees and for one side axial rotation 1.1 degrees. Large intersubject variation was found in flexion-extension with values ranging from 7.1 to 29.9 degrees. Coupled motion patterns were found to be consistent among subjects in active lateral bending and inconsistent for active axial rotation. CONCLUSIONS: This new method offers dynamic recording capabilities and a measurement error comparable with stereo radiographic methods. Repetitive ranging experiments are highly reproducible. The range of motion for axial rotation seems overestimated in previous cadaveric studies. Coupling patterns show large variations between individuals.

Electromagnetic Phenomena↗

PubMed1997

Sooty foot, a novel mouse mutation that affects the pigmentation of exposed skin, but not hair, maps to chromosome 2.

We have characterized a novel recessive mouse mutation, named sooty foot, that increases the pigmentation of the exposed skin on the foot pads, the genital region, around the snout and muzzle, the ears, and the tail. By contrast, the pigmentation of the hair is unaffected. We have localized the mutation to Chromosome 2 by polymerase chain reaction (PCR) amplification of simple sequence repeats from pooled DNA from backcross progeny. In an extended backcross we have generated a detailed map of the region around sooty foot.

Agouti Signaling Protein↗

PubMed1997

HLA-G functions as a restriction element and a transplantation antigen in mice.

HLA-G, a human MHC class I molecule expressed on the trophoblast during pregnancy, was expressed in transgenic mice by recombining the HLA-G gene with a transcriptional promoter from a murine H-2 MHC class I gene. Skin grafts from HLA-G transgenic mice were rejected by non-transgenic mice showing that HLA-G behaves as a xenotransplantation antigen in mice. Further investigation revealed that murine T cells recognize native HLA-G directly as a xenoantigen or they recognize processed peptides derived from HLA-G presented in the context of murine MHC molecules. HLA-G molecules also function as restriction elements capable of presenting peptides to murine T cells since immunization of HLA-G transgenic mice with peptide that binds specifically to HLA-G molecules elicited HLA-G-restricted, cytotoxic T cell responses. In addition, murine T cell responses to human xenoantigens are enhanced when responder cells originated from HLA-G transgenic mice. Based on these observations, we conclude that expression of HLA-G molecules influences selection of the murine T cell repertoire and that HLA-G exhibits immunological properties that are indistinguishable from classical HLA class I molecules when expressed in transgenic mice. Thus, any unique immunological functions mediated by HLA-G must arise from the distinctive, trophoblast-specific pattern of HLA-G expression in humans and not from structural peculiarities of HLA-G molecules.

Animals↗

PubMed1996

The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration.

Very little is known about the turnover of extracellular matrix in the human intervertebral disc. We measured concentrations of specific molecules reflecting matrix synthesis and degradation in predetermined regions of 121 human lumbar intervertebral discs and correlated them with ageing and Thompson grade of degeneration. Synthesis in intervertebral discs, measured by immunoassay of the content of a putative aggrecan biosynthesis marker (846) and the content of types I and II procollagen markers, is highest in the neonatal and 2-5-yr age groups. The contents of these epitopes/molecules progressively diminished with increasing age. However, in the oldest age group (60-80 yr) and in highly degenerated discs, the type I procollagen epitope level increased significantly. The percentage of denatured type II collagen, assessed by the presence of an epitope that is exposed with cleavage of type II collagen, increased twofold from the neonatal discs to the young 2-5-yr age group. Thereafter, the percentage progressively decreased with increasing age; however, it increased significantly in the oldest group and in highly degenerate discs. We identified three matrix turnover phases. Phase I (growth) is characterized by active synthesis of matrix molecules and active denaturation of type II collagen. Phase II (maturation and ageing) is distinguished by a progressive drop in synthetic activity and a progressive reduction in denaturation of type 11 collagen. Phase III (degeneration and fibrotic) is illustrated by evidence for a lack of increased synthesis of aggrecan and type II procollagen, but also by an increase in collagen type II denaturation and type I procollagen synthesis, both dependent on age and grade of tissue degeneration.

Adult↗

PubMed1996

The human lumbar endplate. Evidence of changes in biosynthesis and denaturation of the extracellular matrix with growth, maturation, aging, and degeneration.

STUDY DESIGN: The authors measured concentrations of specific molecules reflecting matrix synthesis and degradation in 121 human endplates and correlated them with aging and grade of degeneration. OBJECTIVES: Abnormal endplate development has been implicated in many spinal abnormalities, yet little is known about endplate matrix component turnover. SUMMARY OF BACKGROUND DATA: Techniques are available to perform an in situ investigation of matrix component turnover with aging and degeneration. METHODS: Newly synthesized aggrecan and Type I and Type II procollagens were measured with recently developed immunoassays. Percentage of denatured Type II collagen was assessed with a new enzyme-linked immunosorbent inhibition assay. RESULTS: Synthesis in endplates, measured by content of an aggrecan marker (846) and content of Types I and II procollagen markers (CPI and CPII), is highest in the neonatal and 2- to 5-year age groups and steadily diminishes with increasing age. However, in the oldest age group and in highly degenerated discs, the CPI epitope level increased significantly. Percentage of denatured Type II collagen, assessed by the presence of an epitope exposed with the cleavage of Type II collagen, increased from the neonatal to the 2- to 5-year age groups. The percentage progressively decreased with increasing age. However, it significantly increased in endplates from highly degenerated discs. CONCLUSIONS: The authors identified three matrix turnover phases, related to age and grade of degeneration. Phase I (growth) is characterized by active synthesis of matrix molecules and active denaturation of Type II collagen. Phase II (aging and maturation) is distinguished by a drop in synthetic activity and a reduction in denaturation of Type II collagen. Phase III (degenerative) is illustrated by an increase in Type II collagen denaturation and Type I procollagen synthesis, both related to grade of tissue degeneration.

Adolescent↗

PubMed1996

Unicompartmental knee arthroplasty with patelloplasty.

Patellofemoral arthritis is generally regarded as a contraindication to unicompartmental knee arthroplasty. A retrospective review of 52 patients (60 knees) who underwent this operation together with nonresurfacing excisional patelloplasty was carried out. The patellar facets were resected through subchondral bone retaining the triangular shape of the bone. There were 90% good and excellent results at an average follow-up of 6 years with no patellofemoral pain, despite marked to moderate patellofemoral crepitus in 98%. Patellofemoral arthroplasty can extend the indications for unicompartmental knee arthroplasty, providing an alternative to total knee replacement.

Arthritis↗

PubMed1996

Effects of different antigenic microenvironments on the course of CD8+ T cell responses in vivo.

The influence of microenvironment on the course of CD8 + T cell responses in vivo was investigated by injecting H-2Kb-specific T cells from donor TCR transgenic (TCR-Tg) mice into H-2kb-Tg mice. H-2Kb expression in recipients was either ubiquitous (CBK mice) or restricted to myeloid and erythroid cells (K beta mice). Donor T cells proliferated as extensively and acquired similar surface phenotypes in spleen of both recipient types. Thus, neither the restricted pattern of H-2Kb expression nor the significantly reduced level of H-2Kb expression by myeloid cells in Kbeta recipients affects the ability of the splenic microenvironment to prime T cell proliferation in vivo. However, an unsustained burst of cytolytic activity was generated rapidly in spleen of CBK recipients, whereas relatively little cytolytic activity was generated in K beta spleen. This indicates that effector T cells were not generated efficiently in spleen of Kbeta recipients even though extensive T cell proliferation was taking place in this microenvironment. Furthermore, activated donor T cells dispersed rapidly throughout primary and secondary lymphoid organs of Kbeta recipients, whereas few T cells migrated from spleen in CBK recipients. Consequently, the course of CD8+ T cell responses and the anatomical distribution of activated T cells are profoundly influenced by the nature of the antigenic microenvironment encountered in vivo. We conclude that T cells rapidly proliferate and acquire new tissue-homing characteristics but do not differentiate into cytolytic effector cells at the site of priming when they encounter myeloid cells expressing low levels of antigen in vivo.

Animals↗

PubMed1994

Tolerance induction by elimination of subsets of self-reactive thymocytes.

Immature thymocytes expressing TCRs which confer reactivity to self-MHC molecules are subject to efficient elimination as a result of negative selection. Previously, we have identified a lineage of H-2Kb Tg mice, CD2Kb-3, which fails to reject skin grafts from mice expressing H-2Kb even though H-2Kb-specific cytotoxic T cells can be generated in vitro. We now show that bone marrow derived cells are responsible for tolerance induction and that tolerance is acquired, at least in part, by negative selection in CD2Kb-3 mice. Thymocytes expressing two different transgenic TCR (TCR-Tg) clonotypes conferring reactivity to H-2Kb are eliminated prior to the CD8+CD4+ stage of differentiation in double Tg (CD2Kb-3 x TCR-Tg)F1 mice. As in other cases where thymocytes from TCR-Tg mice develop in the presence of deleting ligands, large numbers of TCR+ CD8-CD4- T cells accumulate in double Tg mice. However, these T cells fail to respond to H-2Kb in vitro but can be activated with immobilized anti-clonotypic antibody. Consequently, thymocytes expressing these types of TCR molecules represent a fraction of H-2Kb-reactive thymocytes which are unable to mature into T cells capable of mounting H-2Kb-specific cytotoxic responses. Presumably, precursors of H-2Kb-specific cytotoxic T cells found in the periphery of CD2Kb-3 mice express a distinct repertoire of TCR molecules conferring reactivity to H-2Kb. We consider potential explanations to account for this discrepancy and their wider implications, including the possibility that the repertoire of thymocytes able to recognize self-H-2Kb molecules in CD2Kb-3 mice is divided into distinct subsets; those which are, and those which are not, subject to negative selection.

Animals↗

PubMed1994

Induction of tolerance to self MHC class I molecules expressed under the control of milk protein or beta-globin gene promoters.

We have studied tolerance induction in transgenic CBA mice expressing H-2Kb genes under the influence of guinea-pig alpha-lactalbumin (KAL) or human beta-globin gene promoter (K beta). KAL radio-resistant cells, but not bone marrow derived cells, induce tolerance to H-2Kb in chimeric mice. In contrast, bone marrow derived and radio-resistant cells of K beta mice induce tolerance. Although appropriate, tissue-specific, expression of H-2Kb molecules occurs in KAL and K beta mice, H-2Kb is expressed at low levels in thymus of transgenic mice. In addition, dendritic cells and macrophages express H-2Kb molecules when K beta, but not when KAL bone marrow is cultured in vitro. The mode of tolerance induction was examined in double transgenic mice by mating KAL or K beta mice to mice expressing TCR transgenes (Tg-TCR) derived from a H-2Kb specific, CD8-independent cytotoxic T cell clone. In both cases, a large number of Tg-TCR+ CD8+CD4+ thymocytes develop but mature CD8+CD4- thymocytes fail to appear suggesting that thymocytes are eliminated late in development. Some CD8-CD4- and CD8-CD4+ Tg-TCR+ T cells develop in double transgenic mice and respond to activation through their TCR-CD3 complex in vitro, although no responses to stimulation with H-2Kb expressing cells were detected. Thus, tolerance induction in KAL and K beta mice proceeds via a deletional mechanism that is inefficient due either to low numbers of H-2Kb expressing thymic cells or to the low levels of H-2Kb expressed by thymic cells, or to a combination of these factors.

Animals↗

PubMed1994

Separation of thymic education from antigen presenting functions of major histocompatibility complex class I molecules.

Participation of transmembrane (TM) and glycosyl-phosphatidylinositol (GPI) anchored H-2Db molecules in antigen presentation and thymic selection events was investigated using transgenic mice. Both GPI-Db and TM-Db can efficiently present H-Y antigen, influenza and lymphocytic choriomeningitis virus (LCMV) peptides to primed cytotoxic, H-2Db-restricted T cells. Transgenic mice expressing GPI-Db, although unable to reject TM-Db skin grafts, nevertheless generate secondary CTL responses which can lyse TM-Db-bearing targets, indicating that GPI-Db mice fail to delete all TM-Db-reactive T cells. Furthermore, double-transgenic mice bearing GPI-Db and a T-cell receptor (TcR) for H-2Db+LCMV do not positively select receptor positive, CD8+CD4- T cells. This paradoxical behaviour of GPI-Db molecules suggests that the structural requirements for antigen presentation and thymic selection by class I molecules are different and may explain why GPI-linked class I molecules, such as Qa-2, do not appear to function as restriction elements in vivo.

Animals↗

PubMed1993

[Chemonucleolysis. Its effectiveness in the treatment of lumbar diskopathies caused by compressive or rotational injuries].

One hundred patients who meet McCulloch's indicators for treatment of lumbar disc herniation by chemonucleolysis were entered in this study. Chemonucleolysis in the patients suffering from sciatica secondary to a compression injury, especially with clinical and radiographic evidence of nerve root compression at a single level, can be expected to attain good to excellent results. Chemonucleolysis is far less efficacious in patients suffering from either torsional injury or multiple level abnormality, especially in the absence of neurological deficit. Meticulous attention to patient selection will yield optimal results. The result was excellent or very good in 60% of patients, while in 40% the procedure failed. The rate of success at the L.5/S.1 level was 70%, at the L.4/5 level it was 63% and 37% were successful when multiple levels were treated.

Adult↗

PubMed1992

The effect of chymopapain on low back pain.

One hundred and fifteen patients underwent chymopapain treatment for acute disc protrusion between 1980 and 1988. Sixty-six patients who were treated with single-level injection were reviewed retrospectively with clinical follow-up from 2 to 10 years (mean, 4.6 years). All patients met modified McCulloch criteria (not all patients had leg pain greater than back pain). The presence of pre-existing chronic low back pain (LBP) was recorded in 33 patients and compared to their present low back symptomatology and functional limitations. Patients with pre-existing chronic LBP had a success rate of 52%, whereas patients meeting all the McCulloch criteria without chronic LBP had a success rate of 52%, whereas patients meeting all the McCulloch criteria without chronic LBP had a success rate of 85%. The overall effect of chemonucleolysis on LBP demonstrated no change in 18% and a mild increase in 45% of the patients (even though they had a successful outcome). The pre-existing disc space narrowing and the postoperative change of disc space height of 33 patients assessed on lateral roentgenograms showed no correlation to the clinical response. Temporal sequential computed tomography scan assessment of 56 patients following chemonucleolysis demonstrated little change of disc herniation in the first 3 months, with only a gradual and incomplete resolution in the ensuing 12 months.

Adult↗

PubMed1991

Expression and function of Qa-2 major histocompatibility complex class I molecules in transgenic mice.

Qa-2 molecules are weak transplantation antigens encoded by class I genes of the major histocompatibility complex. When expressed in transgenic CBA mice, Qa-2 molecules provoke rapid rejection of skin grafts and strong, Qa-2 specific, cytotoxic T-cell responses. Efficient rejection of skin grafts from Qa-2 transgenic mice takes place when Qa-2 molecules are attached to the cell membrane with a glycophosphatidyl anchor or by a transmembrane protein domain, except that rejection times are slightly longer in the former case. These results demonstrate that Qa-2 molecules can behave as major transplantation antigens, as do closely related H-2 molecules. Failure of Qa-2 molecules to provoke strong T-cell responses in non-transgenic mice is probably due to the very low level of expression of Qa-2 molecules in skin keratinocytes from such mice since these cells express increased levels of Qa-2 molecules in all Qa-2 transgenic mice.

Animals↗

PubMed1989

A glycophospholipid anchor is required for Qa-2-mediated T cell activation.

A number of lymphocyte surface proteins are anchored in the cell membrane by glycophosphatidyl inositol (known as GPI) linkages instead of hydrophobic protein domains. Treatment of mouse T lymphocytes with antibodies specific for two such proteins, Thy-1 and Ly-6, are known to induce proliferation. We have found that antibodies specific for Qa-2, a GPI-anchored class I histocompatibility antigen, can also activate mouse T cells. To determine whether the GPI-anchor is important for this pathway of cell activation, we produced transgenic mice expressing either normal GPI-anchored Qa-2, or Qa-2 molecules with a membrane-spanning protein domain derived from H-2. Our studies show that only lymphocytes from transgenic mice carrying GPI-anchored forms of Qa-2 can be activated in vitro by Qa-2-specific antibodies. We also show that transgenic mouse T cells expressing a GPI-anchored form of H-2Db can be activated by anti-H-2Db antibodies. These results strongly indicate that the GPI-anchor is critical for this pathway of T cell activation.

Animals↗

PubMed1985

Structure and expression of genes encoding murine Qa-2 class I antigens.

DNA structural analysis of the Qa region in two BALB/c mouse substrains with different Qa-2 phenotypes reveals that a deletion of DNA has occurred in BALB/cBy (Qa-2-) mice relative to BALB/c (Qa-2+) mice. We propose that this deletion arises from unequal crossing-over and recombination between adjacent BALB/c class I genes and results in the generation of a hybrid class I gene in BALB/cBy mice. Furthermore, we suggest that this is a direct cause of the change in Qa-2 phenotype. Further support for this model was obtained from transfection experiments in which cloned genes from the equivalent part of the Qa region in C57BL/10 mice were introduced into L cells. Four C57BL/10 genes, arranged in two almost identical pairs, encode polypeptides that are precipitated from lysates of transfectants with anti-Qa-2/3 antiserum. Although loss of one pair of these genes in BALB/c mice has no qualitative effect on Qa-2 phenotype, the loss of both pairs of genes via gene fusion leads to the loss of the Qa-2+ phenotype in BALB/cBy mice.

Animals↗

PubMed1982

A method for culturing chick melanocytes: the effect of BRL-3A cell conditioning and related additives.

A method for growing chick embryo melanocytes is described that utilizes medium conditioned by Buffalo Rat liver (BRL-3A) cells. The dissected trunk region of each 72 h (Stages 14 to 19) embryo produces approximately 200,000 melanocytes (purity, 80%) when processed and cultured for 8 d. Thus, a typical experiment involving 20 embryos would produce a total of 4 x 10(6) melanocytes. Choice of serum, serum concentration, and cell density were determined experimentally. Partially purified multiplication stimulating activity (MSA) from BRL-3A cells and insulin were also tested as medium additives. MSA was not stimulatory, whereas insulin gave a positive response in 2% but not 10 or 0% serum. The final protocol used a modified F12 medium with 10% bovine calf serum conditioned by BRL-3A cells. Cultures were fed every other day. Small colonies of cells became evident by culture Day 3 and increased rapidly to Day 5 when pigmentation became obvious. Colony size continued to increase but more slowly from Days 5 to 8, whereas pigmentation increased rapidly and maximized on Day 8. There is a factor, or factors, present in BRL-3A conditioned medium that stimulates embryonic chick melanocytes to divide preferentially over contaminating cell types. This results in cultures that can provide adequate numbers and purity for biochemical studies.

Animals↗

PubMedDate not supplied

A prospective, multipractice study of shoulder function and health status in patients with documented rotator cuff tears.

A total of 191 patients from 29 orthopedic practices are analyzed in this report. All had full-thickness tears documented by imaging tests and/or surgical observation; 190 had tears of the supraspinatus, 54 had tears of the infraspinatus, and 13 had tears of the subscapularis. The greatest functional deficits were in the ability to place 8 pounds on a shelf at the level of the head (93% unable), the ability to throw overhand (93% unable), and the ability to sleep on the affected side (86% unable). The SF-36 physical role function and comfort scores were 27% and 48%, respectively, of those of age- and sex-matched controls. Of the variables suggested by a review of the literature, only female sex, involvement of the infraspinatus in the cuff tear, and workers' compensation claims were significantly correlated with lower shoulder function in this series of patients.

Adult↗

PubMedDate not supplied

Correlates with comfort and function after total shoulder arthroplasty for degenerative joint disease.

Although most patients are improved after shoulder arthroplasty, the degree of improvement is variable. The factors contributing to this variability are not well understood. In particular, little information is available regarding the preoperative characteristics of the patient that may influence the quality of the result. This study correlated patient demographics, preoperative health status, and preoperative shoulder function with 3 outcome metrics: comfort, physical role function, and shoulder-specific function. One hundred thirty-four shoulders having total shoulder arthroplasty for degenerative glenohumeral joint disease had an average follow-up of 3.4 +/- 1.8 years. The SF-36 Comfort score improved from 39 to 61 (P < .0001). The SF-36 Physical Role Function score improved from 30 to 52 (P < .0001). The average number of Simple Shoulder Test functions performable (out of 12) improved from 4 to 9 (P < .0001). The strongest correlates with postoperative comfort included preoperative physical function (P < .0001), general health (P < .0001), and social function (P < .001). The strongest correlates with postoperative physical role function included preoperative physical function (P < .0001) and general health (P < .001). The strongest correlates with postoperative shoulder function included male gender (P < .0001), and preoperative physical function (P < .0001), social function (P < .0001), mental health (P < .0001) and shoulder function (P < .0001). These data indicate that the overall well-being of the patient before surgery is strongly correlated with the quality of the outcome from total shoulder arthroplasty for degenerative glenohumeral joint disease.

Adult↗