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Biomedical subjects

Robert J Moore

Publications and source records attributed to Robert J Moore.

25 records · Page 2Linked to original sources
PubMed2003

The bacteriocin piscicolin 126 retains antilisterial activity in vivo.

OBJECTIVE: We have conducted a series of experiments to show that the bacteriocin piscicolin 126 (P126) retains antilisterial activity after injection into a mouse. METHODS: Groups of mice were challenged intravenously with Listeria monocytogenes and treated with purified P126 at varying times before and after challenge to determine whether administration of this peptide reduced numbers of colonizing L. monocytogenes and the symptoms of listeriosis. RESULTS: The bacteriocin P126 retained antilisterial activity after injection into the mouse. During the early time-points of listerial infection, the purified P126 was found to significantly reduce the listerial load in the liver and spleen and, further, that this reduction translated to reduced clinical signs of disease. CONCLUSIONS: This is the first report of a Class IIA bacteriocin displaying in vivo antimicrobial activity. Such a result provides preliminary evidence that this class of molecules may be useful in controlling systemic bacterial infections.

Animals↗
PubMed2003

An anti-tumor necrosis factor-alpha antibody inhibits the development of experimental skin tumors.

The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) was originally considered to have activity against malignant disease. However, recent studies suggest TNF-alpha may also act as an endogenous tumor promoter. In the present work, mice deficient in TNF-alpha either genetically (TNF-alpha(-/-)) or after blockade with a neutralizing antibody (cV1q) were used to investigate the role of TNF-alpha in skin tumor development. Papillomas were induced in wild-type (wt) mice after treatment of skin with the initiating agent 9,10-dimethyl-1,2-benzanthracene followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 15 weeks. TNF-alpha(-/-) mice were resistant to papilloma development when compared with wt mice on C57Bl/6J, 129/SvEv, and BALB/c genetic backgrounds. Primary murine keratinocytes (newborn keratinocytes) and skin homogenates were used to characterize TPA-stimulated TNF-alpha expression. TPA induced TNF-alpha protein in newborn keratinocytes in vitro and epidermis in vivo. Neutralization of TNF-alpha protein with cV1q in vivo for 0-15 weeks of promotion significantly decreased skin tumor development after 9,10-dimethyl-1,2-benzanthracene/TPA treatment. cV1q treatment during the early stages of tumor promotion (0-6 weeks) was equally effective. These data suggest that early induction of TNF-alpha is critical for skin tumor promotion. cV1q also reduced TPA-stimulated expression of matrix metalloproteinase 9 and granulocyte macrophage colony-stimulating factor, proteins that are differentially regulated in wt and TNF-alpha(-/-) epidermis. Treatment of the 410.4 transplantable breast carcinoma with cV1q reduced tumor growth in vivo, illustrating that inhibition of tumor growth through neutralization of TNF-alpha is not limited to skin carcinogenesis. These results provide further evidence for procancer actions of TNF-alpha and give some rationale for use of TNF-alpha antagonists in cancer prevention and treatment.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2002

The biologic response to particles from a lumbar disc prosthesis.

STUDY DESIGN: Particles of a proprietary polyolefin rubber compound used in a lumbar disc prosthesis were generated in vitro and tested for biocompatibility in two animal models. OBJECTIVE To characterize any tissue response to polyolefin rubber particles. SUMMARY OF BACKGROUND DATA: Intervertebral disc prostheses are emerging as alternatives to fusion techniques for the treatment of symptomatic disc degeneration. The biocompatibility of all novel components used in the construction of these devices must be verified before they can be considered for general use. METHODS: Laboratory-generated polyolefin rubber particles were either injected into dorsal subcutaneous air pouches of 30 rats or placed directly onto the lumbosacral dura and nerve roots of 9 sheep. Histologic sections of tissues from, and remote from, the site of implantation were examined for evidence of inflammation and wound-healing responses. RESULTS: Polyolefin rubber particle debris induced a tissue response that was consistent with a normal foreign body reaction to large particles. The response was not significantly greater than that seen with similar size particles of ultrahigh molecular weight polyethylene. There was no evidence of particle migration from the site of implantation, and there was no evidence of local or systemic toxic effects. CONCLUSION: Polyolefin rubber particles induce only localized tissue response that is consistent with a normal foreign body reaction to large nontoxic particles.

Animals↗
PubMed2002

Tumour necrosis factor-alpha mediates tumour promotion via a PKC alpha- and AP-1-dependent pathway.

Tumour necrosis factor-alpha (TNF-alpha) deficient mice (TNF-alpha(-/-) mice) are resistant to skin carcinogenesis. Cellular signalling via the transcription factor complex AP-1 is thought to play a key role in tumour promotion. The induction of a specific subset of AP-1 responsive genes thought to be important for tumour development, namely GM-CSF, MMP-9 and MMP-3, was suppressed in TNF-alpha(-/-) compared to wild-type mouse skin in response to the tumour promotor TPA. The differential induction of these genes correlated with a temporal shift in AP-1 activation and c-Jun expression in TNF-alpha(-/-) compared to wild-type epidermis. The major receptor for TPA-induced signalling in basal keratinocytes, PKC alpha, was also differentially regulated in wild-type compared with TNF-alpha(-/-) epidermis. A marked delay in TPA-induced intracellular translocation and downregulation of PKC alpha was observed in TNF-alpha(-/-) epidermis, which correlated with the deregulated TPA-induced AP-1 activation and c-Jun expression. The frequency of DNA adduct formation and c-Ha-ras mutations was the same in wild-type and TNF-alpha(-/-) epidermis after DMBA treatment, suggesting that TNF-alpha was not involved in tumour initiation. These data suggest that the pro-inflammatory cytokine TNF-alpha is a critical mediator of tumour promotion, acting via a PKC alpha- and AP-1-dependent pathway. This may be one mechanism by which chronic inflammation increases susceptibility to cancer.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2002

Degeneration of the atlanto-axial joints: a histological study of 9 cases.

Degeneration of the lateral atlanto-axial joints (AAJ) has been described as a potential cause of severe neck pain. However, hardly any data are available on its incidence, especially in comparison to the lower cervical spine. In this histological study, we examined the AAJs in 9 specimens from elderly patients, graded the findings and compared them to those in the facet joints of the lower cervical spine. Most histological changes in the AAJs were mild, but the changes in the lower cervical spine were severer. Previous mechanical studies have described the AAJ as a very mobile joint with large neutral zones, which may explain the mild degree of osteoarthrosis found in these specimens.

Aged↗
PubMedDate not supplied

Three-dimensional vertebral motions produced by mechanical force spinal manipulation.

OBJECTIVE: The aim of this study was to quantify and compare the 3-dimensional intersegmental motion responses produced by 3 commonly used chiropractic adjusting instruments. METHODS: Six adolescent Merino sheep were examined at the Institute for Medical and Veterinary Science, Adelaide, Australia. In all animals, triaxial accelerometers were attached to intraosseous pins rigidly fixed to the L1 and L2 spinous processes under fluoroscopic guidance. Three handheld mechanical force chiropractic adjusting instruments (Chiropractic Adjusting Tool [CAT], Activator Adjusting Instrument IV [Activator IV], and the Impulse Adjusting Instrument [Impulse]) were used to randomly apply posteroanterior (PA) spinal manipulative thrusts to the spinous process of T12. Three force settings (low, medium, and high) and a fourth setting (Activator IV only) were applied in a randomized repeated measures design. Acceleration responses in adjacent segments (L1 and L2) were recorded at 5 kHz. The multiaxial intersegmental (L1-L2) acceleration and displacement response at each force setting was computed and compared among the 3 devices using a repeated measures analysis of variance (alpha = .05). RESULTS: For all devices, intersegmental motion responses were greatest for axial, followed by PA and medial-lateral (ML) measurement axes for the data examined. Displacements ranged from 0.11 mm (ML axis, Activator IV low setting) to 1.76 mm (PA axis, Impulse high setting). Compared with the mechanical (spring) adjusting instruments (CAT, Activator IV), the electromechanical Impulse produced the most linear increase in both force and intersegmental motion response and resulted in the greatest acceleration and displacement responses (high setting). Significantly larger magnitude intersegmental motion responses were observed for Activator IV vs CAT at the medium and high settings (P < .05). Significantly larger-magnitude PA intersegmental acceleration and displacement responses were consistently observed for Impulse compared with Activator IV and CAT for the high force setting (P < .05). CONCLUSIONS: Larger-magnitude, 3D intersegmental displacement and acceleration responses were observed for spinal manipulative thrusts delivered with Impulse at most force settings and always at the high force setting. Our results indicate that the force-time characteristics of impulsive-type adjusting instruments significantly affects spinal motion and suggests that instruments can and should be tuned to provide optimal force delivery.

Acceleration↗