Distal esophageal perforation caused by tuberculosis.
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Adult↗
Biomedical subjects
R P McCabe
Publications and source records attributed to R P McCabe.
Transient and cyclic responses of strain-generated potential in rabbit patellar tendon are frequency and pH dependent.
The goal of this study was to expand understanding of strain-generated potential (SGP) in ligamentous or tendinous tissues. Most SGP studies in the past have focused on cartilage or bone. Herein, rabbit patellar tendon (PT) was used as a model. Each patellar tendon had two Ag/AgCl electrodes inserted at axial positions of 1/4 and 1/2 from patellar to tibial insertions. Each specimen was electrically isolated, gripped in a servohydraulic test system, and then subjected to a short session of uniaxial haversine tension (2.5 percent maximum strain) at a frequency of 0.5, 1.0, 2.0, or 5.0 Hz. A cyclic (sinusoidal) electrical potential superimposed upon a larger transient (exponentially asymptotic) potential was consistently observed. Upon termination of loading, the cyclic SGP ended, and the shifted baseline of the SGP exponentially decayed and asymptotically returned to a residual potential which over all specimens was not different than the original potential. The transient and cyclic SGPs were frequency dependent (P < 0.001, P = 0.06, respectively). To our knowledge, this transient portion of the SGP, although theoretically predicted by Suh (1996, Biorheology, 33, pp. 289-304) and Chen (1996, Ph.D. thesis, University of Wisconsin-Madison) has not been observed in other experiments using different protocols. Additional PTs were dehydrated and the rehydrated in solution at different pH levels. The magnitude of SGPs increased in basic solution (pH 9.5) but diminished in pH 4.7 buffer. This pH dependency suggests that electrokinetics is the dominant mechanism for the transient and cyclic responses of the SGPs, although this study does not provide direct evidence.
Animals↗
Experimental models to study molecular mechanisms underlying intestinal inflammation.
Experimental animal models, particularly the newer mouse models, have convincingly demonstrated that CD+ T cells play a central role in chronic intestinal inflammation. Such CD4+ effector T cells are induced by the bacterial flora. In at least one model, it is conventional protein antigens that are stimulating these pathogenic T cells. The antigens driving disease seem to be a selective subset of immunodominant proteins, likely derived from a subset of organisms. Multiple genes contribute to colitis susceptibility and a number of these genes are being localized.
Animals↗
CD4+ T cells reactive to enteric bacterial antigens in spontaneously colitic C3H/HeJBir mice: increased T helper cell type 1 response and ability to transfer disease.
C3H/HeJBir mice are a new substrain that spontaneously develop colitis early in life. This study was done to determine the T cell reactivity of C3H/HeJBir mice to candidate antigens that might be involved in their disease. C3H/HeJBir CD4+ T cells were strongly reactive to antigens of the enteric bacterial flora, but not to epithelial or food antigens. The stimulatory material in the enteric bacteria was trypsin sensitive and restricted by class II major histocompatibility complex molecules, but did not have the properties of a superantigen. The precursor frequency of interleuken (IL)-2-producing, bacterial-reactive CD4+ T cells in colitic mice was 1 out of 2,000 compared to 1 out of 20,000-25,000 in noncolitic control mice. These T cells produced predominately IL-2 and interferon gamma, consistent with a T helper type 1 cell response and were present at 3-4 wk, the age of onset of the colitis. Adoptive transfer of bacterial-antigen-activated CD4+ T cells from colitic C3H/HeJBir but not from control C3H/HeJ mice into C3H/HeSnJ scid/scid recipients induced colitis. These data represent a direct demonstration that T cells reactive with conventional antigens of the enteric bacterial flora can mediate chronic inflammatory bowel disease.
Adoptive Transfer↗
Regional differences in L-selectin expression in murine intestinal lymphocytes.
BACKGROUND & AIMS: The expression of the lymphocyte homing receptor and activation marker L-selectin is different in colon and small intestinal intraepithelial lymphocytes (IELs). In this study, the mechanism of this difference in L-selectin expression was investigated. METHODS: L-selectin expression on lymphocytes was measured by flow cytometry. L-selectin messenger RNA (mRNA) was detected by reverse-transcription polymerase chain reaction. L-Selectin expression on peripheral lymphocytes was analyzed after incubation with cytokines, food and bacterial antigens, and homogenates of small and large bowel. RESULTS: L-selectin was expressed by none of the small intestinal IELs but by 30% of those in the colon and by 60% of splenocytes. mRNA for L-selectin was detectable in isolated lymphocytes of all three sites. L-Selectin was down-regulated in colon IELs during colitis and up-regulated in small intestinal IELs after in vitro culture for 48 hours. Incubation of splenocytes with small intestinal homogenates led to a rapid down-regulation of L-selectin (1% vs. 60% untreated). Preincubation with a metalloproteinase inhibitor prevented L-selectin loss. CONCLUSIONS: The mechanism of the differential expression of L-selectin in mouse small intestine and colon appears to be an increased functional activity of a metalloproteinase (sheddase) in the small intestine compared with the colon.
Alanine↗
Evaluation of a new method to create a standardized muscle stretch injury.
Herein we describe a new test system to produce a standardized partial muscle-tendon junction (MTJ) stretch injury. In anesthetized rabbits the tibialis anterior (TA) muscle-tendon unit is unilaterally shortened using a custom designed clamp roller system. An angular displacement (average velocity of 450 degrees x s[-1]) is applied about the foot to plantarflex the ankle 90 degrees while the lower extremity is fixed. During ankle rotation the TA muscle is tetanically stimulated to generate an eccentric stretch injury at the MTJ. Forty-eight hours after injury, isometric torque deficit (injured/sham) was measured. Two groups of animals (N = 6 in each group) were tested with the only difference between the two groups being the initial tendon shortening. In Group 1 (tendon shortening = 1.2 cm. N = 6) the torque deficit was 36.7+/-5.9% (mean+/-SD). In Group 2 (tendon shortening = 1.5 cm. N = 6) the torque deficit was 58.7+/-7.4% (mean+/-SD). No order effect was suggested by the data (P = 0.6062), but the difference in torque deficit between the two groups was highly significant (P = 0.0001). For all tests in which the tendon was temporarily shortened before muscle stimulation and stretch (N = 12) there was a visible hematoma at the MTJ similar to the injury that is common in athletic injuries. Histological evaluation 48 h after injury revealed both fiber tearing and inflammation at the MTJ. In addition, there was focal fiber damage in the muscle belly for both groups. The damage and inflammatory process, however, were more severe in the group with greater initial tendon shortening.
Analysis of Variance↗
A device for measuring relative angular displacement.
A simple, inexpensive, and accurate way to measure relative segmental rotations resulting from torsional loadings locally is described. To measure these rotations, we fabricated a planar spatial linkage (open-loop kinematic chain) requiring only one rotational displacement transducer. This paper describes this device, defines its kinematics, and examines its accuracy.
Biophysics↗
Spontaneously colitic C3H/HeJBir mice demonstrate selective antibody reactivity to antigens of the enteric bacterial flora.
The idiopathic inflammatory bowel diseases, ulcerative colitis and Crohn's disease, are chronic disorders that appear to arise from an aberrant interaction of environmental, genetic, and immunologic factors. The aim of this study was to examine the immune reactivity of a spontaneously colitic mouse strain, C3H/HeJBir, to epithelial, food, and enteric bacterial Ags. Serum Ab responses of colitic C3H/HeJBir and noncolitic parental C3H/HeJ mice were measured by enhanced chemiluminescence Western blotting. No reactivity to epithelial or food Ags was detected. However, the sera from C3H/HeJBir mice had a reproducible banding pattern on Western blot to bacterial Ags, whereas sera from C3H/HeJ mice did not. Only a small, highly selected number of enteric bacterial Ags were recognized. There were major differences in the degree of recognition of different bacterial strains, marked by remarkably few Abs to Ags of the major anaerobes of the bacterial flora. The serum Abs detected on immunoblot were primarily IgG2a, suggesting a Th1 response. Comparison of sera reactivity to histopathologic severity showed an inverse relationship: one third of young C3H/HeJBir mice during the peak of colitis produced Abs to bacterial Ags, while later in life, when the colitis had resolved, 96% produced Abs. These data are consistent with an abnormal immune reactivity to enteric bacterial flora in C3H/HeJBir mice, a reactivity that is highly selective considering the abundant bacterial Ags present in the colon lumen. We postulate that this reactivity plays a role in the pathogenesis of colitis in these mice.
Animals↗
An evaluation of instrumented tank rowing for objective assessment of rowing performance.
The aim of this study was to evaluate instrumented tank rowing for its ability to measure objectively the individual performance components of power output and rowing skill in a sample of collegiate rowers. The measuring system utilized strain gauges and a potentiometer to measure force on the oar and its angular position at each sampling interval. Power outputs were calculated for 13 collegiate rowers tested individually during a 30-s bout of maximal work. Results from this 'tank test' were compared with power measurements from both Concept II (CII) and Stanford rowing ergometers and from a Wingate test, using similar 30-s bouts of maximal work. Significant differences (P < 0.05) were found between the tank test and all other modes of testing except the Wingate test for average power. These differences can probably be attributed to the different methods of power measurement and to the different skill-dependence associated with the tests. For each subject, peak power and average power per stroke were measured from the rowing tests. The CII and Stanford test data for all subjects were correlated with their tank test data. Similar correlations were made between tank data and the peak and mean power from the Wingate test. The strongest correlation was in peak power measurements with the Wingate test (r = 0.92, P = 0.0001). Instrumented tank rowing provided objective information on individual power output unique from rowing and cycling ergometry. Of the various tests, the tank test appeared to provide better and more complete power data specific to rowing. This method also provided objective data for interpreting various aspects of rowing skill, including oar handling, technical efficiency, consistency, stroke frequency, stroke recovery ratio and stroke length. Instrumented tank rowing has substantial potential as a coaching tool or as a self-training device for improving rowing ability.
Adult↗
Anterior cervical discectomy and fusion using a porous hydroxyapatite bone graft substitute.
OBJECTIVES: This study analyzed the use of a coral hydroxyapatite bone substitute for use in ACDF both with and without an anterior cervical plate. STUDY DESIGN: The healing of multilevel anterior cervical fusions was tested using a goat model. Comparisons were drawn with histologic, radiographic, and biomechanical test data. METHODS: Forty-nine mature alpine goats had three-level anterior discectomies performed. Seven treatment groups of seven goats each were used; Group I with no fusion, Group IIa having tricortical iliac crest autograft, Group IIb having autograft plus an anterior plate, Group IIIa having tricortical iliac crest fresh-frozen allograft, Group IIIb having allograft plus an anterior plate, Group IVa having rectangular-shaped implants of porous hydroxyapatite, and Group IVb having ProOsteon 500 implants with an anterior cervical plate. RESULTS: Histologically, at 12 weeks 48% of the ProOsteon (Interpore, Irvine, CA) implants were rated as incorporated, 10% as possessing a fibrous gap, 29% as collapsed, and 14% as extruded. Anterior cervical plating improved the results with 71% of the implants showing good incorporation, 24% with collapse, and 5% with a fibrous gap. These histologic results compare favorably with autogenous bone and are improved over allograft bone. Fluorochrome analysis showed that none of the implants had complete turnover with host bone, but that all possessed peripheral creeping substitution with cutting cones of new bone formation at 12 weeks. Biomechanically, the spines using the ProOsteon implant were less stiff in torsion than autograft, but equal in stiffness to allograft. Flexion-extension neutral zone stiffness was lower in the ProOsteon implant group than either allograft or autograft. CONCLUSIONS: The use of a coral-based hydroxyapatite bone graft substitute for anterior cervical fusions led to significant rates of implant collapse at 12 weeks but showed excellent biologic compatibility with good early creeping substitution of the implant by host bone. The concomitant use of an anterior cervical plate with the implant prevents extrusion.
Animals↗
Immunoglobulin variable region usage in human intestinal B lymphocytes.
The B cell repertoire was studied in intestinal mononuclear cells from normal individuals and patients with inflammatory bowel disease (IBD) by examining Ig heavy chain variable gene (VH) usage. Using reverse transcription of intestinal mucosal RNA followed by polymerase chain reaction with primers specific for each VH family and a housekeeping gene, a semiquantitative assay of VH family content in RNA samples was developed. While all VH family members were expressed, differences in VH usage in lamina propria intestinal B cells were noted between Crohn's disease, ulcerative colitis, and normal individuals. mRNA transcripts for VH4 were present at seemingly higher levels than their genomic representation and transcripts for VH1 and VH4 appeared to have higher levels in active, compared to inactive, IBD. Thus, within the massive polyclonal intestinal B cell response, there is a skewed VH usage which may be relevant to the antigenic and/or autoimmune response noted in IBD.
B-Lymphocytes↗
A multi-degree of freedom system for biomechanical testing.
A system is described that allows axial, torsional, and bending testing of biomechanical specimens. The system uses electric motors under closed loop control in its grips allowing application of pure bending moments. These grips attach to an axial/torsional testing system. Thus, it provides simultaneous closed loop control of all three degrees of freedom (D.O.F), so that under any given test condition either the loads or the displacements for each D.O.F. can be maintained at zero, selected constant values, or simultaneously controlled. This enables the expedient evaluation of the mechanical behavior of biological structures under complex loadings or simple loadings (one D.O.F.) with no artificially induced constraints in the other two D.O.F.'s due to specimen mounting.
Biomechanical Phenomena↗
Cervical stability after sequential capsule resection.
A portion of the cervical facet joint must be resected to expose and decompress cervical nerve roots from a posterior approach. When posterior fusion is performed, it is common to remove the facet capsule only for the joints being fused. This study was performed to examine the effect of resection of the facet capsule alone, without disruption of the bony facet to determine what degree of facet-capsule resection leads to acute instability. Seven human cervical cadaveric spines were used in the experiment. Nondestructive biomechanical testing was performed in axial load, flexion, extension, and torsion. Each specimen was tested intact and after sequential resection of 25%, 50%, 75%, and 100% of the C5-6 facet capsules. Axial stiffness changed very little during the experiment. In torsion, the displacement increased 1% after a 25% capsule resection, 19% after a 50% resection, and 25% after a 75% or 100% resection. No gross subluxation was seen during the torsional test. In the flexion test, posterior displacement increased 4% after a 25% resection, 5% after a 50% resection, 32% after a 75% resection, and 22% after a 100% resection. There was a statistically increased displacement seen during the flexion test after 75% or 100% of capsule resection. Thus, significant hypermobility did occur during both torsion and flexion testing with greater than 50% resection of the facet capsules. Great care should be taken when exposing an unfused facet to limit facet-capsule resection to less than 50%. With resection of greater than 50% of the capsule, postoperative hypermobility can occur and may require stabilization.
Biomechanical Phenomena↗
Delivery of radionuclides to pretargeted monoclonal antibodies using dihydrofolate reductase and methotrexate in an affinity system.
A novel affinity system for a two-phase delivery of radionuclides to tumor cells has been developed. In the first phase, a nontoxic bivalent monoclonal antibody conjugated to an enzyme is targeted to the tumor cells. In the second phase, a radionuclide-derivatized enzyme inhibitor, specific for the enzyme conjugated to the antibody, is administered. The model system selected for this study is the recombinant human enzyme dihydrofolate reductase (rhDHFR) and its high-affinity competitive inhibitor methotrexate (MTX). MTX was labeled with a radionuclide by covalent attachment of diethylenetriaminepentaacetic acid (DTPA) complexed with 111In. Using the gamma-carboxyl residue of MTX for the attachment of DTPA, binding of the inhibitor to rhDHFR was not affected. The inhibitory activities of nonderivatized MTX and DTPA-MTX were indistinguishable. Human K562 erythroleukemia cells were used to evaluate under in vitro conditions the DHFR-MTX affinity system for the delivery of 111In-labeled DTPA-MTX to pretargeted alpha-transferrin receptor antibody-rhDHFR conjugates (alpha-TFR-DHFR). The data demonstrate that the delivery of 111In is dose dependent and highly specific. Under saturating conditions, binding of 111In-DTPA-MTX to alpha-TFR-DHFR-treated cells was 14-fold higher than to cells treated with nonconjugated alpha-TFR antibody. Further experiments indicated that the low level of nonspecific binding of 111In-DTPA-MTX was comparable to that of 111In-DTPA, known for its complete extracellular distribution and rapid clearance through the kidneys. Based on the data of this study, antibody-conjugated rhDHFR and radionuclide-labeled DTPA-MTX complexes provide components for an alternative radioimmunotherapeutic approach that can be expected to result in improved tumor tissue ratios of both the targeting moiety and the radionuclide-labeled derivative as compared to current approaches.
Antibodies, Monoclonal↗
Cytokine mRNA expression in intestine from normal and inflammatory bowel disease patients.
Cytokines are involved in the regulation of normal immune events and may be important in the development or perpetuation of immune events in inflammatory bowel disease. We have previously shown that normal human mononuclear cells from tonsil, spleen, and peripheral blood exhibit tissue and stimulus-specific patterns of cytokine mRNA expression. The aim of this study was to determine if disease-dependent differences of cytokine mRNA expression could be found in the intestine. Total RNA was isolated from intestinal mucosa and lamina propria mononuclear cells from inflammatory bowel disease patients and controls. cDNA probes specific for interleukins (IL)-1, -4, -5, and -6 and transforming growth factor-beta were used. IL-1 beta mRNA and TGF-beta mRNA steady state expressions were higher in inflammatory bowel disease specimens than in normal intestine. In addition, mononuclear cell specimens had stronger cytokine mRNA expression than mucosal specimens. The steady state mRNA expression of proinflammatory cytokines is higher in inflammatory bowel disease, consistent with the ongoing inflammation seen.
Blotting, Northern↗
Invasion of bacteria in enamel carious lesions.
A review of recent findings concerning enamel carious lesions is presented. This lesion represents the initial phase of dental caries and is characterized by a demineralization of the subsurface enamel caused by acids of the plaque bacteria. Streptococcus mutans has been described as the etiologic agent of the dental caries and the most acidogenic plaque bacteria. Morphological studies have shown an invasion of microorganisms inside the enamel carious lesion. Unfortunately, several technical problems are associated with such studies. The identification of the invading bacteria has not yet been achieved. The future identification of bacteria inside the subsurface enamel lesions will represent an important step in the prevention of the carious progression.
Dental Caries↗
Preclinical studies on the pharmacokinetic properties of human monoclonal antibodies to colorectal cancer and their use for detection of tumors.
We studied the pharmacokinetic properties of two human monoclonal antibodies to colon carcinoma cells and their ability to detect tumors in nude mice bearing primary human colon carcinoma xenografts. The 16-88 and 28A32 monoclonal antibodies are immunoglobulin M class human antibodies produced by cell lines derived from peripheral blood lymphocytes from patients with colon carcinoma. The patients received an autologous tumor cell vaccine as part of an active specific immunotherapy protocol. The 125I-labeled antibodies were cleared from the circulation of non-tumor-bearing and tumor-bearing nude mice with a 6-8-h half-life. The half-life of the antibodies in tumor tissue was 48 to 72 h compared to 8 to 12 h for normal tissues. Tumor:normal tissue ratios were highest 4 to 7 days postinjection with tumor:blood ratios of 12:1 for 16-88 and 10:1 for 28A32 antibody. Experiments with a control human immunoglobulin M myeloma protein confirmed the specificity of the human monoclonal antibodies. Radioimmunoscintigraphic studies using nude mice bearing contralateral antibody-reactive and nonreactive colon tumor xenografts further confirmed that the antibodies specifically localized in tumor tissues. The antibody-reactive tumors were clearly visible by radioimmunoscintigraphy within 4 days of injection. These experiments, undertaken as a preliminary step to clinical trials, demonstrated for the first time that i.v. administered human immunoglobulin M monoclonal antibodies could be taken up by human colon tumor tissue and retained to a sufficient extent to easily permit tumor detection by external radioimmunoscintigraphy. These studies also demonstrated that the nude mouse human colon tumor xenograft model is a useful in vivo system for comparison studies of human monoclonal antibodies as part of a selection process for clinical trials and for evaluating immunoconjugates containing these antibodies for relative pharmacokinetic properties and potential diagnostic or therapeutic efficacy.
Animals↗
The mechanism of leukoregulin enhancement of target cell susceptibility to NK cell mediated cytotoxicity in humans.
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Cell Membrane Permeability↗