PubMed HealthSearch

Biomedical subjects

J H Bennett

Publications and source records attributed to J H Bennett.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

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

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

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

Drug samples.

Explore the source record for details and available documents.

Drug Industry

Follow-up Papanicolaou smear for cervical atypia: are we missing significant disease? A HARNET Study.

BACKGROUND: The presence of cervical atypia on the Papanicolaou (Pap) smear may be an indicator of significant cervical disease. Many investigators recommend that colposcopy be performed in these women. We wished to determine the prevalence of undetected cervical intraepithelial neoplasia (CIN) among women identified as having cervical atypia by cytologic testing in a primary care setting. 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. Cytologic specimens were obtained using an endocervical Cytobrush and wooden spatula. Consenting subjects with cervical atypia underwent repeat Pap smear testing immediately before a colposcopic examination after a 4- to 6-month waiting period. RESULTS: One hundred fifty-nine women identified as having cervical atypia consented to having a colposcopic examination. Of these, 96 (60%) demonstrated abnormalities on biopsy, including 40 with condyloma, 41 with CIN I, and 15 with CIN II to III. The false-negative rate of the follow-up Pap smear for detecting these cases of condyloma and CIN was 57%. CONCLUSIONS: One third of the women with cervical atypia identified on an initial Pap smear in this primary care community setting had CIN after colposcopic biopsy. The single follow-up Pap smear obtained with the endocervical Cytobrush and wooden spatula failed to detect one half of the cases of biopsy-proven CIN. Further studies regarding the use of additional screening methods for follow-up are necessary.

Adolescent

Gonadotrophin-induced oestrus and ovulation in the polyovulatory marsupial Sminthopsis crassicaudata.

Sminthopsis crassicaudata is a small (approximately 16 g) polyovulatory dasyurid marsupial which has the potential to become an important model species. This study examined the use of exogenous hormone treatment to manipulate the breeding of S. crassicaudata and as a means to obtain timed developmental stages for further study. Two thirds (21/32) of the females treated with 1.0 or 5.0 I.U. of pregnant mare serum gonadotrophin (PMSG) had ovulated when the contents of their reproductive tracts were examined 5 or 6 days later. Only one of eight females treated with 0.2 I.U. PMSG had ovulated in the same period. Although a similar proportion of animals treated with 1.0 I.U. and 5.0 I.U. ovulated, the ovulation rate was significantly lower when the higher dose was administered (mean of 10.5 ovulations per female v. 3.8 ovulations per female). In addition, the ovaries of 6/8 of the animals treated with 5.0 I.U. PMSG had luteinized follicles with degenerating oocytes, evidence of over-stimulation. Follicular luteinization also occurred in 4/8 animals treated with 1 I.U. PMSG. Oocyte maturation and ovulation occurred following PMSG stimulation without injection of synthetic gonadotrophin releasing hormone (GnRH). Treatment with a 10-micrograms dose of GnRH following PMSG seemed to have no effect on the outcome. Of the females that had ovulated by Day 6, three quarters had mated and some had fertilized eggs and two-cell embryos in the oviducts and uteri. In a further series of experiments the subsequent development of embryos conceived after PMSG treatment was assessed. Two thirds of treated females mated within 7 days of treatment and 60% of these matings yielded embryos when examined 11 days after PMSG. However, full-term development was only achieved in one animal. Gonadotrophin treatment of S. crassicaudata thus may have application as a means to obtain mature or maturing oocytes, cleavage stage embryos and blastocysts, but at this stage it appears not to offer promise as a method to achieve full-term development.

Animal Husbandry

Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures.

The differentiation of adipocytic and osteogenic cells has been investigated in cultures of adult rat marrow stromal cells. Adipocytic differentiation was assessed using morphological criteria, changes in expression of procollagen mRNAs, consistent with a switch from the synthesis of predominantly fibrillar (types I and III) to basement membrane (type IV) collagen, and the induction of expression of aP2, a specific marker for differentiation of adipocytes. Osteogenic differentiation was assessed on the basis of changes in the abundance of the mRNAs for the bone/liver/kidney isozyme of alkaline phosphatase and the induction of mRNAs for bone sialoprotein and osteocalcin. In the presence of foetal calf serum and dexamethasone (10(-8) M) there was always differentiation of both adipocytic and osteogenic cells. When the steroid was present throughout primary and secondary culture the differentiation of osteogenic cells predominated. Conversely, when dexamethasone was present in secondary culture only, the differentiation of adipocytes predominated. When marrow stromal cells were cultured in the presence of dexamethasone in primary culture and dexamethasone and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3; 10(-8) M) in secondary culture, the differentiation of adipocytes was inhibited whereas the differentiation of osteogenic cells was enhanced, as assessed by an increase in expression of osteocalcin mRNA. The results, therefore, demonstrate an inverse relationship between the differentiation of adipocytic and osteogenic cells in this culture system and are consistent with the possibility that the regulation of adipogenesis and osteogenesis can occur at the level of a common precursor in vivo.

Adipose Tissue

Monoclonal antibody BRL 12 reacts with bone keratan sulphate proteoglycan.

Our previous studies suggest that a monoclonal antibody, BRL 12, reacts with a specific product of differentiated cells of the osteoblastic lineage. In the present study, the bone constituent recognized by this antibody has been characterized by gel filtration, ion exchange chromatography, protein blotting and immunolocalization. Our findings show that the antibody reacts with an epitope associated with the core protein of rabbit keratan sulfate proteoglycan (KSPG), a molecule which shares considerable homology with the sialoprotein present in the bone tissue of other mammalian species.

Animals