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Biomedical subjects

R P McCabe

Publications and source records attributed to R P McCabe.

At least 19 recordsLinked to original sources
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1991

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↗
PubMed1988

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↗
PubMed1985

Leukoregulin, a direct-acting anticancer immunological hormone that is distinct from lymphotoxin and interferon.

Human lymphokine preparations can directly lyse or suppress proliferation of human tumor cells or can enhance the susceptibility of human tumor cells to lysis mediated by natural killer lymphocytes. In the past, these antitumor activities were attributed to lymphotoxin. This study demonstrates, however, that these human lymphokine antitumor cell activities are biochemically separable from lymphotoxin and are properties of a lymphokine which was named leukoregulin because it is produced by lymphocytes and it regulates target cell physiology and growth. Leukoregulin obtained by high-performance liquid chromatography and isoelectric focusing was free of detectable lymphotoxin, interferon, interleukins 1 and 2, and macrophage-activating factor activities. Leukoregulin has an apparent molecular weight of 135,000 as measured by linear gradient polyacrylamide gel electrophoresis and gel filtration chromatography and has isoelectric pHs of approximately 5.3 and 7.5. The molecular weight of leukoregulin, determined in the dissociating conditions of sodium dodecyl sulfate polyacrylamide gel electrophoresis, was 32,000. Flow cytometric analysis showed that tumor cell lysis, growth inhibition, and enhancement of susceptibility to natural killer cell-mediated cytotoxicity by leukoregulin were accompanied by rapid alterations in tumor cell membrane permeability. Lymphotoxin from human peripheral blood leukocytes and highly purified lymphotoxin from RPMI 1788 human lymphoblastoid cells lysed murine alpha-L929 tumor cells but did not possess any of the direct acting antihuman tumor cell cytostatic, cytolytic, or natural killer cell enhancing activities that leukoregulin exhibited against a broad spectrum of human tumor cell lines. The dual modes of the anticancer actions of leukoregulin, direct cytotoxicity and indirect enhancement of natural killer cell cytotoxicity, make leukoregulin a unique-acting lymphokine and suggest several ways in which leukoregulin may be used as a therapeutic agent against cancer.

Cell Line↗
PubMed1985

Generation of tumor cell-reactive human monoclonal antibodies using peripheral blood lymphocytes from actively immunized colorectal carcinoma patients.

The use of human monoclonal antibodies (MCA) in the detection and treatment of human cancer has been limited by the apparent scarcity of MCA to tumor cell surface antigens. Using peripheral blood lymphocytes from autologous tumor-immunized patients, we isolated 36 MCA that react to sections of colorectal carcinoma. Twenty of these human MCA appear to be directed against cell surface antigens. Two-thirds of the human MCA-producing cell lines were diploid human B-cells rather than human-mouse heterohybridomas. Direct antibody-binding assays performed with the MCA indicated that they recognized antigenic determinants preferentially expressed on tumor cells. Experiments with paired specimens of air-dried, dissociated colon tumor cells and normal colonic mucosa cells suggested that the MCA bound significantly more to the cell surfaces of tumor cells than to the surfaces of normal colonic mucosa cells. Similarly, tests with a panel of cryostat sections of paired colon tumor and normal colonic mucosa showed that MCA bound to the tumor cells and not to the normal colonic mucosa. None of the MCA bound to cells from frozen sections of normal breast, stomach, liver, skeletal muscle, or skin. Furthermore, the human MCA did not react with carcinoembryonic antigen and human erythrocyte antigens as measured by various techniques. Our data also demonstrated that these transformed B-cells and hybridomas were stable producers of human MCA. Thus, our studies show that these tumor-specific human MCA may have the specificity and stability necessary for in vivo evaluation of their use in the detection and treatment of cancer.

Animals↗
PubMed1984

Mechanism of natural delayed-type hypersensitivity reactions to tumor cells in nonimmunized syngeneic guinea pigs.

Nonimmunized 2/N guinea pigs respond to the presence of chemical carcinogen-transformed syngeneic tumorigenic cells with a sustained (delayed-hypersensitivity-type) 4-day intradermal induration consisting of predominantly polymorphonuclear leukocytes on day 1 and mononuclear cells by day 4, which is independent of the presence of tumor-specific antigens on the tumorigenic cells. Chemical carcinogen-induced morphologically transformed but nontumorigenic cells also induce a polymorphonuclear response by day 1, but neither induration nor a mononuclear response is present on day 4, demonstrating the specificity of the 4-day sustained indurative response for tumorigenic cells. Induration and cellular infiltrates are unaltered if tumor cells are treated prior to injection with the cytostatic lymphokine lymphotoxin or with x-irradiation to inhibit cell proliferation. The intradermal polymorphonuclear leukocyte host response on day 1, but not the mononuclear response on day 4, is also induced by mitomycin C-treated cells or a cytokine culture medium from the cells. No response is present on day 1 or day 4 when cell membranes or lyophilized cells are injected. Thus natural delayed-hypersensitivity-type skin reactivity is a mononuclear leukocyte response specifically directed against intact and metabolically active but not necessarily proliferating tumor cells.

Animals↗
PubMed1984

Secretion of proteinase inhibitors by tumorigenic and nontumorigenic guinea pig and Syrian hamster fibroblasts: evidence for autocrine regulation of local proteolysis.

A cytokine that inhibits fibrinolysis has been detected in the serum-free culture medium of guinea pig and hamster fibroblasts. This proteinase inhibitor was also present in Triton X-100 extracts of guinea pig cells. It was stable at pH 3.0 for 2 hr and was produced by cells rather than assimilated from serum in the culture medium as evidenced by: (a) an apparent molecular size (less than 45 kilodaltons) less than that of the principal serum-derived proteinase inhibitors; (b) its continued secretion after several passages of the cells in serum-free medium; and (c) the lack of inhibitory activity in the medium of mitomycin C-treated cells. The cytokine inhibited the proteinase activity of human urokinase, soluble TPA-stimulated guinea pig plasminogen activator, and the cell-associated plasminogen activator of tumorigenic guinea pig cells. Soluble plasminogen activator appeared to be inhibited to a greater degree than the cell-associated enzyme. The fluorogenic substrate (7-(N-carbobenzoxyglycylglycylargininamido)-4-methylcoumarin was used in a direct assay of proteinase activity and demonstrated that the cytokine inhibited both plasminogen activator and plasmin, the two proteinases of the fibrinolytic cascade. Tumorigenic guinea pig and hamster fibroblasts as well as nontransformed guinea pig fibroblasts were found to produce the inhibitory cytokine, and the amount of inhibitor secreted was independent of the tumorigenic potential of the cells. Production of the inhibitor by normal cells may be related to contact inhibition of growth, and this cytokine may contribute to the fine regulation of local proteolysis within tissues.

Animals↗
PubMed1984

A diagnostic-prognostic test for bladder cancer using a monoclonal antibody-based enzyme-linked immunoassay for detection of urinary fibrin(ogen) degradation products.

An enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody was developed to determine the clinical value of urinary fibrinogen/fibrin degradation product levels for the identification and management of patients with bladder cancer. Assays were performed on 286 serial urine specimens from 56 bladder carcinoma patients. Specimens were grouped according to whether the patient had an evident tumor at the time of specimen collection (134 specimens, 41 patients) or was clinically disease-free following treatment (152 specimens, 38 patients). Many patients contributed specimens to both groups as determined by their clinical status at the time of collection. In addition, 45 specimens from 33 patients with inflammation of the urogenital tract and 81 specimens from 19 patients with renal or prostatic cancer were assayed for urinary fibrin degradation products. The ELISA, using a high-sensitivity procedure, identified 83% of the specimens from bladder cancer-positive patients with an overall accuracy with all specimens of 78% and a false-negative rate of 5% for all specimens tested. The high-sensitivity ELISA appeared most appropriate for monitoring bladder cancer patients for recurrence of tumor after surgery. The ELISA using a high-specificity procedure appeared most appropriate for screening. The high-specificity ELISA accurately identified 96% of urine specimens from non-bladder cancer patients with a false-positive rate of only 5%. These results demonstrate that the ELISA is an efficient, reliable, quantitative, and noninvasive immunoassay that can be useful both for the identification of bladder cancer patients and for monitoring the course of the disease.

Aged↗
PubMed1983

Relationship of neoantigens induced by 3-methyl-cholanthrene treatment of Syrian hamster embryo cells to antigens expressed on fetal and 3-methyl-cholanthrene-transformed neoplastic cells.

Neoantigen(s) induced on Syrian hamster cells during chemical carcinogenesis are also found on fetal and neoplastic hamster cells. 46 neoplastic cell lines independently isolated from colonies of 3-methylcholanthrene (3-MCA) in vitro-transformed hamster cells growing in semi-solid agar medium were assayed for expression of neoantigens recognized by hamster antisera to primary cultured late-term (15 days) hamster embryo cells treated for 18 h with 10 micrograms 3-MCA/ml. Ratios of the binding of this sera compared to solvent control sera ranged from 0.7 to 2.1 in terms of cpm bound. Only four of the 46 neoplastic cell lines exhibited significant (P less than 0.05) neoantigen expression. No correlation existed between the concentration of 3-MCA used to establish the neoplastic cell line and expression of the neoantigen(s). Absorption of the sera with these four highly reactive neoplastic cell lines and mid-term (10 days) embryo cells indicated that the neoantigen(s) recognized were common to the four reactive neoplastic cell lines and the mid-gestation fetal cells. The occurrence of early persistent immunogenic cell-surface alterations during in vitro carcinogenesis provides an approach to isolation of preneoplastic populations and provides potential target structures for the inhibition of carcinogenesis.

Animals↗
PubMed1982

Plasminogen activator, fibronectin, lymphotoxin sensitivity, and natural skin reactivity relationships to guinea pig cell tumorigenicity.

The quantitative expression of five properties of chemical carcinogen-induced, neoplastically transformed NIH strain 2 guinea pig fibroblasts was compared in cells possessing thousandfold differences in tumorigenicity. Plasminogen activator synthesis, sensitivity to lymphotoxin inhibition of cell proliferation, and the ability to induce a natural delayed tuberculin-type skin reaction in nonimmune syngeneic guinea pigs correlated directly with the number of cells required to produce a tumor. The most tumorigenic cells (10(2)-cell threshold dose) produced the most plasminogen activator, were most sensitive to lymphotoxin, and produced the greatest skin reactivity. Cells with a threshold tumor dose of 10(5)-10(7) cells exhibited the lowest expression of these properties. Fibronectin incorporation into an extracellular matrix was diminished in tumorigenic cells, as was anchorage-dependent growth; but neither diminished fibronectin incorporation nor the decreased anchorage requirement correlated quantitatively with the number of cells required to produce a tumor. The present investigation indicates that plasminogen activator synthesis, sensitivity to lymphotoxin, and the capacity of tumorigenic cells to induce natural delayed-type skin reactivity are among the factors that influence initial tumor growth. Plasminogen activator, an extracellular protease, may aid in the growth and spread of tumor cells in vivo by interfering with host fibrin deposition and by inactivating other host proteins such as lymphotoxin.

Animals↗
PubMed1981

Immunogenicity of guinea pig cells transformed in culture by chemical carcinogens.

The immunogenicity of inbred strain 2/N guinea pig fibroblasts transformed to the malignant state in vitro by chemical carcinogens was evaluated with the use of a variety of in vivo and in vitro methods including delayed-type hypersensitivity skin and tumor transplantation tests and analysis of antibody production by immunofluorescence, complement fixation, and staphylococcal protein A binding tests. Neoplastic transformation was induced by direct treatment of cells in culture with benzo[a]pyrene, 3-methylcholanthrene, or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or by the host-mediated method by which fetuses were exposed to diethylnitrosamine or MNNG in vivo prior to cell culture. Rabbits and syngeneic guinea pigs were inoculated with unirradiated and X-irradiated clonally derived cells. Delayed hypersensitivity skin reactions to immunizing or other cells were equivalent in immunized or control guinea pigs, and no protection to tumor outgrowth from a challenge inoculum of immunizing cells was observed. Antibody activity induced in the sera of immunized guinea pigs was cross-reactive and removed by absorption with nontumorigenic cells. Rabbit antisera after absorption with fetal guinea pig cells were nonreactive with the specific immunizing or other culture cells. Chemical carcinogen-induced neoplastic transformation of guinea pig cells can, therefore, occur without formation of detectable, individually distinct cell surface tumor-specific neoantigens.

Animals↗