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Biomedical subjects

R B Donoff

Publications and source records attributed to R B Donoff.

At least 19 recordsLinked to original sources
PubMed2000

Taste perception after lingual nerve repair.

PURPOSE: This retrospective study evaluates patients' perception of taste after lingual nerve injury and repair. It is hypothesized that return of taste is a distinct neurophysiologic phenomenon related to specialized taste physiology and it does not correlate with specific, objective sensory return. PATIENTS AND METHODS: During 1995 to 1996, 30 patients underwent microsurgical repair of lingual nerve injuries. Of these, 22 patients met the inclusion criteria for this study. Chart review documented the date and cause of injury, sensory examination, injury classification, procedures, operative findings, and postoperative sensory examination. A telephone questionnaire addressed whole mouth taste perception with normal daily eating. The questions asked were: 1) Was your sense of taste changed or abnormal after your nerve injury? and 2) Did your sense of taste recover after nerve repair? RESULTS: All patients had a postinjury, prerepair sensory deficit on levels A, B, and C testing: neurotmesis (n = 14); and axonotmesis (n = 8). The mean time from injury to repair was 16 weeks (range, 3 to 41 weeks). Operative findings confirmed 12 Sunderland Class IV (partial transection) injuries and 10 Class V (complete transection) injuries. All patients had primary microsurgical repair without a nerve graft or entubulization. Postoperatively, 18 patients showed marked improvement in sensory testing at levels A, B and C, and 4 patients showed no significant change. A telephone interview regarding whole mouth taste perception indicated that 20 of 22 patients perceived changed, abnormal taste postinjury and pre-repair. Two patients reported normal taste perception. Postrepair, only 7 of 20 patients reported an increase or return of taste perception to a more normal level. The mean follow-up time was 80 weeks. CONCLUSION: Most patients (20 of 22) with lingual nerve injuries in this study perceived whole mouth taste as abnormal. After nerve repair, although 82% (18 of 22) of patients had improvement in somatosensory function, whole mouth taste was perceived as improved by only 35% (7 of 20). It is proposed that the perception of whole mouth taste may not be related to the ability to perceive multiple sensory modalities, but rather to special sensory (taste) modality perception. Also, central changes may occur in the special sensory fibers that impact on the brainstem nucleus for taste (nucleus solitarius) and therefore the patient's perception of taste.

Cranial Nerve Injuries↗
PubMed1999

Intragenic mutation analysis of the human epidermal growth factor receptor (EGFR) gene in malignant human oral keratinocytes.

Alteration in epidermal growth factor receptor (EGFR) expression is frequently associated with malignant transformation of epithelial tissues, including oral mucosa. This study examines the mutations in the coding region of the human EGFR gene in normal and malignant human oral keratinocytes. To examine the intragenic mutations in the human EGFR gene, a panel of normal and malignant human oral keratinocytes were examined by a nonisotopic RNase cleavage assay. Two consistent alterations were detected. First, a polymorphism, which generates a unique BsrI restriction site, was detected at position 2073. This BsrI polymorphism was present only in malignant keratinocytes. Second, Southern blot hybridization of PCR products revealed that there is a truncated EGFR mRNA (approximately 1.5-kb) in oral squamous cell carcinoma cell lines. Similar analysis in normal cell lines revealed that this truncated EGFR transcript is also present. Immunoblotting revealed the presence of this truncated form of EGFR in all keratinocyte cell lines. These data permit us to conclude that there exists a novel truncated form of EGFR in human oral keratinocytes. Furthermore, there exists a tumor-associated BsrI polymorphic site at position 2073. The potential biological relevance of the truncated receptor and the utility of the BsrI polymorphic site for diagnostic applications are currently being explored.

Carcinoma, Squamous Cell↗
PubMed1998

Reduction of ornithine decarboxylase antizyme (ODC-Az) level in the 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis model.

Ornithine decarboxylase (ODC) activity is elevated in and necessary for oral carcinogenesis, but the mechanism for its deregulation is unclear. Using subtractive hybridization, a 1029 bp full-length cDNA encoding a 222 amino acid open reading frame has been isolated from normal hamster oral keratinocytes. The hamster cDNA is homologous to the human, mouse and rat ornithine decarboxylase antizyme gene (ODC-Az). The hamster ODC-Az gene demonstrated a restriction fragment length polymorphism (RFLP) upon Southern blot analysis comparing normal and tumor hamster genomic DNA. Northern blot analysis revealed that normal hamster oral keratinocytes express readily detectable level of ODC-Az mRNA. Malignant oral keratinocytes demonstrate reduced expression of the ODC-Az mRNA. In contrast, malignant hamster oral keratinocytes have elevated ODC mRNA levels and lengthened ODC protein half-life when compared to the normal counterparts. This was corroborated by direct measurement of ODC enzymatic activity. These data support the hypothesis that the reduced and/or loss of expression and function of the ODC-Az gene is an important event for the early de-regulation of cellular proliferation during oral tumor development.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Prediction of human oral cancer radiation responsiveness by histone (H3) mRNA in situ hybridization: a preliminary report.

PURPOSE: Cell cycle kinetics are believed to be a key determinant in radiation responsiveness. However, histomorphologic analysis remains an unreliable method of identifying proliferating cells. In this study, the fraction of cells undergoing division within oral cancer biopsy samples was used to predict the responsiveness of the tumor to radiation therapy. PATIENTS AND METHODS: Eighteen cases of T1 or T2 squamous cell carcinoma of the floor of the mouth with known clinical outcomes were identified. All were treated at the Massachusetts General Hospital with external beam radiation therapy alone. The fraction of proliferating cells was determined using in situ hybridization of histone (H3) mRNA expression. Tissue viability and mRNA status was verified using in situ hybridization for beta-actin mRNA expression. RESULTS: Matching the fraction of oral tumor cells positively labeled for histone (H3) mRNA (histone labeling index or HLI) with the actual clinical outcome showed that the HLI of radioresponsive oral tumors (12 cases) was 0.336+/-0.185 (approximately 34%+/-19%), whereas that for radioresistant oral tumors (six cases) was 0.088+/-0.078 (approximately 9%+/-7.8%). Using t-test statistical analysis for unpaired samples showed that the difference in HLI between the two groups was significantly different (P=.0068). CONCLUSIONS: It is concluded that the use of in situ detection of histone (H3) mRNA may be a useful adjunctive criterion in the choice of treatment for human oral cancer.

Adult↗
PubMed1997

The molecular biology of oral carcinogenesis: toward a tumor progression model.

PURPOSE: An understanding of the molecular basis of oral carcinogenesis will alter our clinical approach to oral cancer. The nomenclature and major themes of molecular oral tumor biology are reviewed, beginning with the regulation events governing normal cellular physiology. In carcinogenesis, chromosomal or cytogenetic alterations lead to deregulation of tightly controlled stimulatory and inhibitory pathways, growth-promoting proto-oncogenes are mutated into overactive oncogenes, and growth-suppressing or tumor suppressor genes are inactivated. Recent advances in defining these fundamental mechanisms of tumor biology may allow prevention, diagnosis, and treatment of oral cancer to be approached at the molecular level.

Anticarcinogenic Agents↗
PubMed1997

Assessment of preclinical problem-based learning versus lecture-based learning.

Academic performance on a standardized oral comprehensive exam (OCE) was compared for students taught basic science in a problem-based learning (PBL) curriculum and a lecture-based learning (LBL) curriculum. The OCE was administered to the graduating classes of 1991-1994 (n approximately 20/class) six months after completion of their basic science courses. The OCE contained six components including: Organization and Thoroughness, Diagnosis, Primary Treatment Plan, Alternate Treatment Plan, Science and Medical Knowledge, and Dental Knowledge. Six to eight examiners graded each of the students by using a standardized scoring system and by subjective comments. The class of 1991 was taught by LBL, classes of 1993 and 1994 by PBL, and the class of 1992 by an incomplete PBL teaching method. Mean OCE scores were not significantly different between classes; however, the Science and Medical Knowledge component score was significantly better for the class of 1994 than for 1991 (p < 0.05). There was a non-significant 40 percent increase (p = 0.07) in honors and a 269 percent (p < 0.001) increase in cumulative positive examiner comments between 1991 and 1994.

Attitude↗
PubMed1997

Depletion of eosinophil infiltration by anti-IL-5 monoclonal antibody (TRFK-5) accelerates open skin wound epithelial closure.

Wound healing is critical to the survival of the species after injury. Using hamsters as an experimental model, we have shown that eosinophils infiltrate prominently into skin wounds and that they express transforming growth factor-alpha and -beta 1 mRNAs and proteins. We hypothesized that eosinophils are important in wound healing. As no animal model is genetically deficient in eosinophils, a suitable way to test the hypothesis is to selectively reduce and/or deplete the influx of eosinophils into the wound sites. In this study, we report that anti-interleukin-5 monoclonal antibody (TRFK-5) treatment can deplete eosinophils in cutaneous healing wounds. We found that wound closure by re-epithelialization in the experimental group was 4 days faster than in the control group (P < 0.01). The density of eosinophils in day-9 wounds was significantly lower in the experimental group (P < 0.01). Wound-associated eosinophils in each of the TRFK-5-treated hamsters were depleted to the level comparable to unwounded hamster skin. These results demonstrate that anti-interleukin-5 monoclonal antibody treatment can effectively decrease eosinophil infiltration into hamster cutaneous healing wounds and indicate a role for eosinophils in negatively affecting wound re-epithelialization.

Animals↗
PubMed1996

Salivary EGF regulates eosinophil-derived TGF-alpha expression in hamster oral wounds.

Using hamster as an oral wound healing model, we examined eosinophils and their expression of transforming growth factor-alpha (TGF-alpha) and transforming growth factor-beta 1 (TGF-beta 1). Oral wounds healed approximately two times faster than their cutaneous counterparts. Eosinophils infiltrated prominently into oral wounds; however, unlike the dual expression of TGF-alpha and TGF-beta 1 in skin wounds, oral wound-associated eosinophils expressed TGF-beta 1, but not TGF-alpha. Because saliva is present in oral environments and contains epidermal growth factor (EGF) and TGF-alpha, sialoadenectomy was performed in this model to determine whether the lack of TGF-alpha expression by eosinophils in oral wounds is due to the presence of salivary EGF and/or TGF-alpha. We found that eosinophils in sialoadenectomized hamsters did express TGF-alpha during oral wound healing but that such expression was suppressed when EGF was added to their drinking water. Taken together, our findings suggest that eosinophil-derived TGF-alpha and salivary TGF-alpha/ EGF may have complementary roles in contributing to TGF-alpha in oral wound healing.

Animals↗
PubMed1996

Molecular biology of human oral cancer.

The application of molecular biological tools to the study of cancer has significantly advanced the field of human cancer research. Such study has demonstrated the involvement of two classes of highly conserved cellular genes in the malignant transformation process: oncogenes and tumor suppressor genes. Despite these advances in the molecular biology of human cancers, our understanding of human oral cancer lags behind that of cancer of other body sites. This review attempts to assess the current status of the molecular biology of human oral cancer.

Cell Adhesion Molecules↗
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↗