Search PubMed⌕ Search

Biomedical subjects

R B Donoff

Publications and source records attributed to R B Donoff.

At least 19 recordsLinked to original sources
PubMed1995

Deleted in oral cancer-1 (doc-1), a novel oral tumor suppressor gene.

We have identified, isolated, and partially characterized doc-1, a novel cDNA sequence whose activity is consistent with a suppressor of hamster oral carcinogenesis. Doc-1 is an evolutionarily conserved gene exhibiting loss of heterozygosity and marked reduction in expression in malignant hamster oral keratinocytes. The full-length doc-1 cDNA encodes an 87 amino acid product that shows a significant homology to one of the seven novel genes induced in mouse fibroblasts by TNF-alpha. Transfection of the full-length doc-1 cDNA into malignant hamster oral keratinocytes alters the behavior of the recipients in terms of morphology, growth rate, and anchorage-independent growth, suggesting reversion of transformation phenotypes. We propose that doc-1 is a novel tumor suppressor gene in oral cancer development.

Amino Acid Sequence↗
PubMed1995

Nerve regeneration: basic and applied aspects.

Increased knowledge is shedding new light on our understanding of central and peripheral nerve anatomy and molecular biology and function. New tools and methods provide important methods for the study of the behavior of cells, axons, and receptors. This review discusses the current state of that knowledge, with particular regard to the efficacy of the Seddon classification of nerve injury. The correlation of that new information to damage and repair of the peripheral sensory nerve, especially the inferior alveolar and lingual nerves, serves to highlight the progress and problems that exist.

Animals↗
PubMed1993

Identification of rabbit eosinophils and heterophils in cutaneous healing wounds.

The study of wound healing has traditionally used the rabbit as an experimental model. We have recently localized the production of the multifunctional cytokine, TGF-alpha, to eosinophils in rabbit skin wounds. It was evident that during the process of TGF-alpha localization, the distinction between the two granulocytic cell types, eosinophils and heterophils, was impossible by conventional histochemical techniques. This paper describes a rapid method to distinguish these two granulocytes by virtue of their endogenous peroxidases and differential resistance to blockade by inhibitors. In sections that have been blocked by hydrogen peroxide, the peroxidase substrate 3,3'-diaminobenzidine, together with nickel chloride (DAB-Ni), preferentially stained the cytoplasm of rabbit eosinophils while sparing those of heterophils. This selective DAB staining of rabbit eosinophil peroxidase in H2O2-blocked rabbit wounds was verified at the ultrastructural level by electron microscopy. We applied this technique to quantify eosinophil and heterophil infiltration into the 21-day rabbit cutaneous healing wound model. Heterophils were found infiltrated into all three layers of the wound (clot > granulation > base), but eventually all disappeared by day 21. As with the heterophils, eosinophils which had infiltrated into the clot and base of the wound had disappeared by day 21. Unlike the heterophils, eosinophils in the granulation layer of the wound continued to increase up to day 21. The continually increased and sustained presence of the eosinophils together with their demonstrated production of TGF-alpha, in the granulation layer of the healing would suggests that these cells play an important role in the organizational aspects of healing wounds.

3,3'-Diaminobenzidine↗
PubMed1993

Sequential expression of transforming growth factors alpha and beta 1 by eosinophils during cutaneous wound healing in the hamster.

Transforming growth factor-alpha (TGF-alpha) and TGF-beta 1 have been proposed as important regulators of processes critical to successful wound healing. Although various cells present in wounds represent potential sources of either TGF-alpha and/or TGF-beta, including macrophages, neutrophils, keratinocytes, fibroblasts, and endothelial cells, we recently identified eosinophils as an additional potential source of these cytokines. We therefore used in situ hybridization and immunohistochemistry to determine whether eosinophils represent significant sources of TGF-alpha and/or TGF-beta 1 in skin wounds in the hamster. We found that these wounds developed a prominent infiltration of eosinophils, and that eosinophils were a cellular source of both TGF-alpha and TGF-beta 1 mRNAs. TGF-alpha and TGF-beta 1 proteins were detectable both within eosinophils and extracellularly. Moreover, there was a sequential pattern of TGF-alpha and TGF-beta 1 expression by infiltrating eosinophils, with the onset of eosinophil-associated TGF-alpha expression preceding that of TGF-beta 1. This sequential pattern of TGF expression suggests that eosinophils may help to regulate critical biological processes during wound healing.

Amino Acid Sequence↗
PubMed1992

Critical analysis of mandibular reconstruction using AO reconstruction plates.

Forty-one cases (37 patients) of mandibular reconstruction using AO plates were reviewed. The patients' ages ranged from 27 to 83 years (mean, 52.3 +/- 18.1 years) and their cases were followed for 6 to 42 months (mean, 12.7 +/- 8.3 months). Cases were grouped by the location of reconstruction: anterior mandible crossing midline as group A (12 cases), body segment of the mandible as group B (16 cases), condyle and ramus of the mandible as group C (13 cases). The incidence of revision as a measure of outcome was calculated by actuarial methods accounting for loss to follow-up or death. Revision or plate removal occurred in 22.2% (9 of 41 cases), with an incidence of 52.2% (6 of 12 cases) in group A, 12.5% (2 of 16 cases) in group B, and 7.7% (1 of 13 cases) in group C. Combined use of an AO plate and bone graft had a revision rate of 33.3% (4 of 12 cases), whereas the reconstructions with only a plate had a revision rate of 17.2% (5 of 29 cases). The difference between the immediate reconstructions (19.2%; 5 of 26 cases) and delayed reconstructions (26.7%; 4 of 15 cases) was not significant, but delayed reconstruction of the anterior mandible resulted in the highest failure rate (57.1%; 4 of 7 cases). The revision incidence was significantly higher when the area had been radiated (33.3% of 24 radiated cases and 5.7% of nonradiated cases required revision). In particular, the radiated group A had a remarkably higher failure rate (63.2% of 10 cases).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Healing of bony defects in the irradiated and unirradiated rat mandible.

A model system of the irradiated rat mandible has been developed and used in conjunction with a non-spontaneously healing mandibular defect. The contribution of the tissue components in the healing of bony defects was studied using demineralized bone powder (DBP) prepared from unirradiated or in vivo irradiated rat long bones. Better bony fill of the defects occurred in the irradiated beds filled with unirradiated DBP than in the unirradiated beds containing irradiated DBP. This suggests that, at least in the early postirradiation period, the bed is not the limiting factor in healing of bony defects and the osteogenic components of bone in the DBP may be most affected by irradiation. In the irradiated bed, the defects grafted 2 weeks after irradiation healed better than those grafted at 4 weeks. Thus, the timing of surgery after irradiation also plays a role in the healing process, with early surgery producing better results.

Animals↗
PubMed1991

Cellular sources of transforming growth factor-alpha in human oral cancer.

Aberrant expression of TGF-alpha is associated with human malignant oral epithelium. Experiments were initiated to determine the cellular sources of transforming growth factor-alpha (TGF-alpha) in human oral cancer. Ten freshly resected human oral cancers and four specimens of normal human oral epithelium were studied by in situ hybridization and immunohistochemistry. Tissues were probed with 35S-labeled sense and antisense riboprobes to (i) human TGF-alpha (hTGF-alpha), (ii) human epidermal growth factor receptor (EGFR) to determine the distribution of TGF-alpha responsive cells, and (iii) histone H3 to examine TGF-alpha and/or EGFR's possible contribution to altered proliferation in transformed epithelium. Results of our experiments showed that TGF-alpha mRNA could be detected in normal and transformed human oral epithelium. More surprising, we have identified the major source of TGF-alpha mRNA to be the infiltrating eosinophils. A monoclonal antibody to the mature human TGF-alpha peptide stained similar areas in normal and malignant specimens. Eosinophils associated with tumors exhibited positive cytoplasmic immunostaining for TGF-alpha protein. Labeling of EGFR mRNA in human oral epithelium demonstrated uniform labeling of basal layers in normal, hyperplastic, and mildly dysplastic epithelium. In severely dysplastic epithelium and carcinomas (particularly moderate to poorly differentiated types), cellular levels of EGFR mRNA were significantly higher. The profile of altered cellular levels of EGFR mRNA correlated well with the profile of altered proliferation as indicated by H3 mRNA labeling. We hypothesize that the overproduction of EGFR mRNA in tumor epithelium--together with the localized delivery of high amounts of TGF-alpha by eosinophils at tumor-developing sites--is responsible for the increased proliferation of the tumor epithelium.

Antibodies, Monoclonal↗
PubMed1990

Electrodiagnostic evaluation of the uninjured rabbit inferior alveolar nerve.

This investigation describes the electrophysiology of the uninjured rabbit inferior alveolar nerve. There were no differences in the measured waveform parameters between animals nor between the two sides of each animal. The model is reliable and could be applied to basic studies of inferior alveolar nerve regeneration and the effects of pharmacologic or surgical intervention.

Animals↗
PubMed1990

Production of transforming growth factor alpha by hamster eosinophils.

Previously it was demonstrated that malignant transformation of the Syrian hamster cheek pouch mucosa is associated with the expression of TGF-alpha. Therefore in situ hybridization and immunohistochemistry was used to investigate the cellular sources of TGF-alpha production in this model system. Surprisingly one cell type in the inflammatory infiltrate present in the connective tissue adjacent to the transformed epithelium represented a major source of TGF-alpha mRNA. Detailed analysis of these cells revealed that they were eosinophils. In addition to TGF-alpha mRNA, about 40% of the eosinophils associated with the oral tumors exhibited TGF-alpha product reactive with a monoclonal antibody against the C terminus of the mature TGF-alpha peptide. Normal hamster bone marrow eosinophils also exhibited TGF-alpha mRNA and product by in situ hybridization and immunohistochemistry. These results suggest that the eosinophil represents a biologically significant source of TGF-alpha.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Fluorescent latex microspheres as a retrograde tracer in the peripheral nervous system.

Rhodamine labeled latex microspheres were used as a fluorescent retrograde tracer in the peripheral nervous system. Examination of rabbit trigeminal ganglia following application of microspheres to crushed or intact inferior alveolar nerve revealed that: (1) microspheres were taken up by only damaged axons; (2) microspheres remained in trigeminal cell bodies for up to 3 months without degradation or diffusion to extracellular structures; and (3) cells containing microspheres were capable of regenerating axons as evidenced by the return of evoked sensory action potentials and the retrograde axonal transport of True blue. Thus, fluorescent microspheres may be useful tools for in vivo survival studies of peripheral nervous system regeneration and development.

Action Potentials↗
PubMed1988

Healing of cutaneous and mucosal wounds grafted with collagen-glycosaminoglycan/silastic bilayer membranes: a preliminary report.

This report describes the healing of cutaneous wounds in experimental animals grafted with collagen-glycosaminoglycan (GAG) matrix/Silastic (Dow Corning Corp., Midland, MI) bilayers; assesses the feasibility of using collagen-GAG matrix as a vehicle for delivering culture-selected, autogenous fibroblasts to cutaneous wound sites; and evaluates the use of collagen-GAG/Silastic bilayers as mucosal substitutes. Cutaneous and mucosal wounds in New Zealand white rabbits were grafted with either acellular collagen-GAG/Silastic membrane or collagen-GAG/Silastic membrane previously seeded with cultured autogenous fibroblasts. Over 63 days, wound sites were analyzed at intervals based on wound contraction and histology. Cutaneous wound successfully incorporated grafted collagen-GAG matrix and were significantly inhibited in their rate and extent of wound contraction. Seeding membrane matrices with autogenous, cultured fibroblasts before grafting caused a marked increase in cellularity that persisted throughout the postgraft period. In mucosa, matrices were exteriorized rather than incorporated. This work suggests that collagen-GAG/Silastic bilayer may have value as a dermal substitute and, more significantly, may be appropriate as a vehicle for delivering culture-selected fibroblasts to cutaneous wound sites.

Animals↗
PubMed1987

The acoustical characteristics of the normal and abnormal temporomandibular joint.

This paper describes the results of a clinical study that recorded and analyzed sounds emitted from the temporomandibular joint (TMJ) during simple function as a means for differentially diagnosing disorders of the joint. The technique is based on the principle that each different disorder of the TMJ produces a different effect on the mechanical relationship between the articulating surfaces of the joint, and that these mechanical effects can be determined by analyzing joint sounds in relation to joint movement. A total of 79 patients (101 joints) were studied; 32 (46 joints) were diagnosed as having extracapsular disorders, (primarily MPD), 27 (32 joints) were diagnosed as having a displaced disc with reduction, nine (10 joints) were diagnosed as having a displaced disc without reduction, and 11 (13 joints) were diagnosed as degenerative disease (osteoarthritis/arthrosis). In addition, 25 adults (50 joints) with normal TMJs were included as controls. The results of this study demonstrated that each specific disease of the TMJ is characterized by a unique relationship between the sounds propagated by the joint and the movement of the joint. Essentially, an extracapsular disease was characterized by acoustic quiescence during natural (as opposed to maximal) jaw movement, an internal derangement by a usually symmetrical short duration click/reciprocal click, or random click complex, depending on the subcategory of the disorder, and a degenerative disease by a long duration noise during either or both jaw opening and closing. The data further suggest that the technique serves to reflect the mechanical events (and abnormalities) that are involved in function of the diseased joint and has potential for use as a clinical diagnostic tool.

Acoustics↗