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Biomedical subjects

J H Bennett

Publications and source records attributed to J H Bennett.

At least 19 recordsLinked to original sources
PubMed2001

Patterns of integrin expression in a human mandibular explant model of osteoblast differentiation.

Cell-matrix interaction is crucial in regulating osteoblast differentiation and function. These interactions are themselves regulated, at least in part, by integrins. Although there are some data from mammalian models, few studies have compared integrin expression at different stages of the osteoblast lineage. Here, primary human mandibular osteoblast cultures were grown in the presence of epidermal growth factor (EGF), giving a proliferative, less differentiated phenotype, or of vitamin D(3) and hydrocortisone (D+Hc), giving a more differentiated phenotype. These cultures were compared with those of cells prepared in the absence of EGF or D+Hc by fluorescence-activated cell sorter using a panel of monoclonal antibodies to specific integrin heterodimers. To provide in vivo correlation, the same panel of antibodies was used to stain fresh-frozen, undemineralised sections of human mandibular bone. Under baseline conditions the alpha(3), alpha(5), alpha(v), alpha(v)beta(3), beta(3) and beta(1) integrin subunits were expressed strongly by the cells, with low-level expression of the alpha(1), alpha(2) and alpha(4) subunits. In the presence of EGF there was increased alpha(2) expression. With D+Hc, alpha(3) and alpha(5) expression was elevated. Immunohistochemical analysis demonstrated alpha(2), alpha(3), alpha(5), alpha(v)beta(3), beta(1) and beta(3) subunits in cells of the osteoblast lineage; alpha(2) staining was restricted to cells close to the bone surface whilst alpha(v)beta(3) and beta(3) were most frequently localised in the osteocytes. The results provide evidence that cells at successive stages of the osteoblast lineage show different patterns of integrin expression. These integrins may be important in cell-matrix interactions leading to osteoblast differentiation.

Antibodies, Monoclonal↗
PubMed2001

Cell adhesion molecules in human osteoblasts: structure and function.

Osteoblasts and bone lining cells form a near continuous layer covering the bone surface and interactions between these cells and the organic matrix of bone are important determinants of osteoblast proliferation and differentiation. In addition, cells of the osteoblast-lineage form functional communications with each other, with the extra-cellular matrix and with osteocytes through cytoplasmic processes extending through canaliculi in the bone. Together, these cells form a network of putative importance in the regulation of skeletal homeostasis. Cell-cell and cell-matrix interactions are mediated by members of several families of cell adhesion molecules, and knowledge of their interactions will be of fundamental importance in understanding the role of osteoblast in skeletal turnover. Here, the expression pattern of members of the major families of cell adhesion molecules by cells of the osteoblast lineage is reviewed. Special emphasis has been placed on human tissues. In addition, the possibility that cells at progressive stages of the osteoblast lineage have different profiles of cell adhesion molecule expression is explored, and the putative significance of cell-matrix interactions in human skeletal disease briefly discussed.

Cadherins↗
PubMed2000

Inhibition of mitosis and induction of apoptosis in MG63 human osteosarcoma-derived cells in vitro by surface proteins from Actinobacillus actinomycetemcomintans.

Gentle saline extraction releases a heterogeneous mixture of proteins associated with the cell surface of Actinobacillus actinomycetemcomintans, termed the surface protein fraction (SF). Some SF components are biologically active and may modulate cell behaviour in a manner of putative importance in the aetiology of periodontitis. To further characterize this activity, the ability of the SF to induce mitosis and apoptosis in MG63 cells was investigated. Cells were plated at 10(3)-10(4) cells/cm(2) and allowed to attach before culture in the serum-free medium in the presence of 25 microg/ml SF for 2-24 h. The apoptotic and mitotic figures present were counted and the results expressed as an apoptotic or mitotic index. The apoptotic and mitotic compartments were very small, but there was an inverse correlation between mitosis and apoptosis. In control experiments the mitotic was higher than the apoptotic index, whilst in the presence of SF this was reversed. These results were confirmed using in situ end-labelling. SF, therefore, may stimulate apoptotic, but inhibit mitotic, activity in MG63 cells. This raises the possibility that components of SF might induce subtle changes in the balance between apoptosis and mitosis, which, in turn, could contribute to the progression of periodontitis.

Aggregatibacter actinomycetemcomitans↗
PubMed2000

Metalloproteinase expression in normal and malignant oral keratinocytes: stimulation of MMP-2 and -9 by scatter factor.

Matrix metalloproteinases (MMPs) are Zn2+ dependent proteases produced by a variety of cell types. They have a fundamental role in tissue remodelling, tumour invasion and metastasis. Scatter factor (SF), secreted by fibroblasts, has a paracrine action on epithelial cells and binds the trans-membrane c-met receptor inducing loss of adhesion, cell motility and invasiveness in vitro. The purpose of this study was to test if SF can regulate the production of MMPs by epithelial cells. Supernatants from oral squamous cell carcinoma-derived cells (H375 and H376), a human keratinocyte line (UP), and primary cultures of oral mucosal keratinocytes, grown in the presence or absence of SF, were analysed using 0.1% gelatin zymography. MMPs were characterised by comparison with human recombinant enzymes and by the use of specific inhibitors. Oral mucosal keratinocytes, UP, and H357 cells expressed MMP-2 and MMP-9, whilst H376 cells only expressed MMP-2. SF increased the expression of MMP-9 in UP and MMP-2 in H376 supernatants. Both MMP-2 and MMP-9 activity were increased in H357 and normal keratinocyte supernatants. This could be blocked using a human recombinant anti-SF antibody. In all epithelial lines tested, c-Met, the cell surface receptor for SF, could be detected. The results indicate that SF stimulates MMP expression in UP, H376, H357, and normal oral mucosal cells and points to a role for SF in the regulation of oral keratinocyte behaviour in wound healing and neoplasia.

Analysis of Variance↗
PubMed2000

Osteosarcoma of the jaws: a 30-year retrospective review.

OBJECTIVE: This article reviews osteosarcomas of the jaws referred to the Department of Oral Pathology, Eastman Dental Institute, for histologic diagnosis during the 30 years from 1968 to 1998, to compare the clinical behavior of the tumors, to assess how they differ from the reported characteristics of tumors from other sites, and to report on observations of clinical and diagnostic significance. STUDY DESIGN: The clinical, radiographic, and histopathologic records of 25 patients were obtained for retrospective review. Supportive and follow-up clinical and histopathologic material was obtained from the referring clinicians. RESULTS: The mean age of presentation of the primary lesions was 36. 9 years (range, 10-87 years) with a slight female predilection. The most common presenting features were swelling, pain, ulceration, or a neurologic deficit. The radiographic appearance of the lesions was mixed with areas of radiopacity and radiolucency. Histologically, the lesions ranged from those dominated by immature bony trabeculae separated by a cytologically bland stroma to high-grade, cellular lesions with regions of marked atypia and mitotic activity. Most had areas of chondroid formation, in addition to neoplastic osteoid. The main complication was local recurrence. Metastasis was rare and occurred as a solitary process or at a late stage in the disease progression. This was in contrast to lesions metastatic to the jaws, which were higher grade in appearance and had metastasized widely, early in the disease process. Primary osteosarcoma occurring in patients with a history of radiotherapy was typically more aggressive. CONCLUSION: Primary osteosarcomas of the jaws are a group of lesions distinct from those occurring in the long bones. Osteosarcomas of the jaw arising in a former radiation field may be a discrete group of lesions with a more aggressive behavior pattern.

Adolescent↗
PubMed1998

Induction of apoptotic cell death by photodynamic therapy in human keratinocytes.

The use of photodynamic therapy (PDT) for the treatment of skin and oral cancer has been the subject of several clinical studies but there has been little scientific evaluation of its mechanism of action. Evidence to date suggests that whilst epithelial cell death may be secondary to vascular damage, direct cell killing may occur and may involve an apoptosis-like mechanism. To investigate the mechanism of epithelial cell death following PDT, two cell lines, human epidermal keratinocytes (UP) and oral squamous cell carcinoma-derived cells (H376) were subjected to PDT with aluminium disulphonated phthalocyanine (AlS2Pc) as the photosensitizer and red laser light at 675 nm. Control groups received red laser light, photosensitizer or neither. The effects of PDT were assessed using an MTS cell-proliferation assay, which showed a significant reduction in viability (p < 0.01) for PDT-treated cells compared to controls. For morphological analysis, cells were stained with haemotoxylin and eosin and the numbers showing typical apoptotic features counted. The treated cultures showed significantly increased numbers of apoptotic cells. Moreover, the H376 control cultures showed a baseline level of apoptosis of approx. 15%. Apoptosis was confirmed by ultrastructural analysis and by in situ end-labeling of DNA fragments. The results show that PDT using AlS2Pc as a photosensitizer promotes apoptotic cell death in UP and H376 cells in vitro and suggest that direct killing of epithelial cells may contribute to tumour necrosis in vivo.

Aluminum↗
PubMed1998

Dental problems associated with hypophosphataemic vitamin D resistant rickets.

OBJECTIVE: To review a series of cases of hypophosphataemic vitamin D resistant rickets. SUBJECTS INCLUDED: Seventeen cases, aged between 2 years 1 month and 15 years 9 months at first referral, and with an established diagnosis of vitamin D resistant rickets from twelve families were included in the review. Information was drawn from patient records for follow-up periods between 9 months and 20 years 4 months. SETTING: All subjects had been referred to the Eastman Dental Hospital between 1973 and 1997. FINDINGS: Abscessed non-carious primary and/or permanent teeth were a presenting feature in eleven of the seventeen cases. Although attrition and exposure of the abnormally formed dentine accounted for the route of infection in primary teeth, the route for microbial invasion of pulpal tissues in permanent teeth remained unexplained in a number of patients. The possible part played by infractures of the enamel as a portal of entry for infection is discussed. Enamel defects were observed in only six patients, in three of whom these changes were limited to the primary dentition. Taurodontism of permanent molar teeth was confirmed as a feature of the condition in the more severely affected male subjects.

Abscess↗
PubMed1996

Oral Mycobacterium avium complex infection in a patient with HIV-related disease. A case report.

Mycobacterium avium complex infection is a common complication of the later stages of AIDS. Although a recognized cause of oral lesions, atypical mycobacteria are rarely detected in AIDS-related oral ulceration. Here we report a case of oral ulceration in a patient in the later stages of AIDS in which atypical mycobacteria were detected both histologically and microbiologically. The features of this case are similar to the one other case previously reported permitting some characterization and comparison of the clinical features of mycobacterium avium complex infection in AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1995

Bone morphogenetic protein-2 and -4 expression during murine orofacial development.

In the developing orofacial region, epithelial-mesenchymal interactions induce a differentiation cascade leading to bone and cartilage formation. Although the nature of this interaction is unknown, bone morphogenetic proteins (BMP)-2 and -4 have been suggested as putative signalling molecules. Using 35S-labelled cDNA probes, the expression patterns of BMP-2 and -4 mRNA were examined in murine perioral tissues preceding, during and following the time of the epithelial-mesenchymal interaction leading to mandibular formation. At embryonic age (e) 9.5 days, a restricted pattern of BMP-4 mRNA was expressed in the epithelium of the developing facial processes. This decreased rapidly, with little or no signal on E10.5 or E11.5. By E13.5, BMP-4 signal was restricted to the dental lamina, follicle and papilla. BMP-2 expression was not prominent in the developing face until E13.5. At this stage, signal was widespread throughout mesenchyme of neural-crest, but not somatic origin. Different domains of expression were present in the developing epithelium: for example, there was strong signal in the floor of the mouth and the ventral tongue, in contrast to that of the dorsum of the tongue and primary palate, which were negative. These results support the role of BMP-2 and -4 as regulators of orofacial development and demonstrates different fields of BMP-2 expression in developing oral mucosal epithelium.

Animals↗
PubMed1995

A clinicopathological and immunohistochemical analysis of primary oral mucosal melanoma.

Nine cases of primary oral mucosal melanoma in Caucasian patients were reviewed and the tumours analysed for expression of S100, HMB45, NKI/C3, HLA-DR, PCNA, cytokeratin and von Willebrand factor. The clinical, histopathological and immunohistochemical features were quite distinctive and our findings support previous suggestions that oral melanoma should be classified as a separate entity rather than as a sub-type of cutaneous melanoma.

Adult↗
PubMed1995

Immunohistochemical identification of tumours of adipocytic differentiation using an antibody to aP2 protein.

AIM: To determine whether aP2 expression is a useful diagnostic marker in soft tissue tumour pathology. METHODS: A polyclonal antibody to aP2 was used to investigate the immunohistochemical expression of this protein in benign and malignant tumours of adipocytic differentiation and a wide variety of other neoplasms. RESULTS: aP2 was only expressed by lipoblasts (in all types of liposarcoma and in lipoblastomatosis) and by brown fat cells (in both hibernomas and normal periadrenal fetal fat). Other benign adipose tissue tumours and malignant connective tissue or epithelial tumours were distinguished from liposarcoma by the absence of staining for aP2. CONCLUSION: Identification of lipoblasts using markers of aP2 expression is of value in the differential diagnosis of benign and malignant adipose tissue tumours and in distinguishing liposarcomas from other malignant mesenchymal and epithelial neoplasms, some of which contain cells that morphologically resemble lipoblasts.

Adipose Tissue, Brown↗
PubMed1995

Teaching information mastery: evaluating information provided by pharmaceutical representatives.

BACKGROUND: The pharmaceutical industry plays a large role in the lifelong learning of family physicians. Controversy exists over how to integrate this potential information source into residency curricula. METHODS: Based on a a faculty and resident needs assessment, a curriculum was designed to teach the evaluation of pharmaceutical representatives' (PRs) presentations. The Pharmaceutical Representative Evaluation Form is the keystone of the curriculum. This evaluation form guides discussion of pharmaceutical presentation to facilitate understanding of the sales process and help residents confirm or dispute the presentation's content, based on the sales methods used. A second goal of the evaluation program is to improve the content of the PRs' presentations. RESULTS: Residents rapidly acquire the ability to identify potential fallacies of logic and other misleading sales techniques in representatives' presentations. Compared with pretest results, residents' posttest scores demonstrate an understanding that PRs and the acceptance of promotional items can affect their prescribing behavior. Most PRs are pleased that their role is seen as educational. CONCLUSIONS: Physicians must function more as information managers than as information repositories, and it is important that residents be able to obtain useful information from PRs. Our curriculum has been effective in increasing residents' abilities to evaluate the pharmaceutical sales process and allowing them to separate the ¿wheat from the chaff¿ contained in this ubiquitous source of information.

Advertising↗
PubMed1994

Becoming an information master: a guidebook to the medical information jungle.

The medical information system is a "jungle" in which the unguided visitor can become lost or disoriented. This paper, the second in a series on becoming a medical information master, is a guidebook for traveling through this jungle. It focuses on techniques for efficiently obtaining patient-oriented evidence that matters (POEM). From original research to clinical experience, each source of medical information is valuable; the trick is to learn which source is best for the specific information being sought. Armed with this guide, clinicians can find the most appropriate source of information, evaluate it quickly, and apply it confidently in their efforts to provide the best care for their patients.

Education, Medical, Continuing↗
PubMed1994

Should all women with cervical atypia be referred for colposcopy: a HARNET study. Harrisburgh Area Research Network.

BACKGROUND: Clinicians who manage women with Papanicolaou (Pap) smears showing atypical squamous cells of undetermined significance (ASCUS) may miss clinically significant cervical disease by repeating the cytology alone. We evaluated the ability of the human papillomavirus (HPV) screen and the naked-eye examination after a cervical acetic acid wash to enhance the follow-up Pap smear in predicting an abnormal colposcopic biopsy. METHODS: Pap smears were performed on all women (N = 7458) attending six family practice offices for a health maintenance examination from August 1989 through February 1991. Consenting subjects with ASCUS underwent repeat cytological testing, an HPV screen, and a cervical acetic acid wash examination immediately before colposcopy after a 4- to 6-month waiting period. RESULTS: Of the 122 consenting women identified with ASCUS, 67 (55%) demonstrated abnormalities on biopsy, including 26 with condyloma, 26 with cervical intraepithelial neoplasia I (CIN I), and 15 with CIN II to III. The false-negative rate, 58%, of the follow-up Pap smear alone for detecting these cases of condyloma and CIN was significantly decreased (false-negative rate, 27%) with the use of the cervical acetic acid wash as an adjunctive test. There was no additional reduction in the false-negative rate with the use of the HPV screen. Of the 15 subjects with high-grade cervical lesions (CIN II to III), 14 had either an abnormal follow-up Pap smear or an abnormal cervical acetic acid wash examination. CONCLUSIONS: Among women with cervical atypia, a single follow-up Pap smear alone failed to detect one third of the cases of high-grade disease. Ninety-three percent of these cases were detected, however, with a follow-up Pap smear and an acetic acid wash. Our one subject with a high-grade lesion missed with this combination of tests had an unsatisfactory Pap smear. Use of both tests together may reliably guide clinical decisions regarding the management of cervical atypia.

Acetates↗
PubMed1994

Becoming a medical information master: feeling good about not knowing everything.

The body of knowledge in medicine is growing at a phenomenal pace. Clinicians rely on many sources of medical information--journal articles and reviews, textbooks, colleagues, continuing medical education conferences, videotapes and audiotapes, and pharmaceutical representatives--although they probably have had little formal training in assessing the clinical usefulness of the information obtained from each source. Excellent reader guides on how to evaluate clinical trials and review articles have been published, but these techniques are time-consuming and are rarely employed by busy clinicians. In this paper, we present a "user-friendly" method of managing new information in a practical and time-efficient manner. This approach allows clinicians to disregard most of the available medical information and focus on patient-oriented evidence that truly matters.

Clinical Trials as Topic↗
PubMed1993

Single community research networks. The HARNET experience. Harrisburg Area Research Network.

Clinical research performed in family physicians' offices is critical for building an expanded knowledge base for modern health care. Practitioners do not usually have the time, funds, or research expertise to conduct clinical studies. Organized networks can accomplish this goal. Large-area networks, composed of many separate practice sites from a wide geographic area, are valuable sources of information for describing the natural history of disease. These observational studies usually consist of data collection during clinical practice. Experimental trials include evaluations of new protocols, diagnostic tests, or therapies, often in a randomized and blinded fashion. Because of the difficulties in adhering to a standardized protocol, experimental trials are rarely undertaken in the busy clinician's office. Similarly, it may be difficult to standardize these studies in large-area networks. Smaller networks, often in a single community, can feasibly perform more complex studies. Important strategies are required to avoid loss of interest, lack of continuity, and conflict of interest.

Family Practice↗
PubMed1993

Odontogenic squamous cell carcinoma with osseous metaplasia.

Intra-osseous carcinomas of the jaw are rare tumours, thought to arise from residual elements of the odontogenic epithelium. We report an additional case which, unusually, was characterised by marked osseous metaplasia. We propose that the new bone formed around the tumour is the result of an epithelial-mesenchymal interaction between malignant odontogenic epithelium and osteogenic precursor cells in the surrounding stroma.

Carcinoma, Squamous Cell↗