Biomedical subjects

A M Rich

Publications and source records attributed to A M Rich.

At least 19 recordsLinked to original sources

PubMed2001

Determination of the structures of antiinflammatory copper(II) dimers of indomethacin by multiple-scattering analyses of X-ray absorption fine structure data.

Copper K-edge X-ray absorption spectroscopic (XAS) measurements were recorded for the veterinary antiinflammatory Cu(II) complexes of indomethacin (1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid = IndoH), of the general formula [Cu(2)(Indo)(4)L(2)] (L = N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), N-methylpyrrolidone (NMP), and water), and [Cu(2)(OAc)(4)(OH(2))(2)] at room temperature and 10 K. The bond lengths and bridging O-C-O angles of the dimeric Cu(II) cage (Cu(2)O(10)C(8)) obtained from the multiple-scattering (MS) fitting of the X-ray absorption fine structure (XAFS) using a centrosymmetric model of [Cu(2)(Indo)(4)(DMF)(2)] gave Cu.Cu = 2.62(2) A, mean Cu-O(Ac) = 1.95(2) A, Cu-O(L) = 2.15(2) A, bridging O-C-O = 125(1) degrees, Cu displacement from plane 0.19 A compared with the XRD data Cu.Cu = 2.630(1) A, mean Cu-O(Ac) = 1.959 A, Cu-O(L) = 2.143(5) A, bridging O-C-O angles = 123.2(5) degrees, Cu displacement from plane 0.20 A. The excellent agreement between the XAFS- and XRD-derived data allowed the structures of related [Cu(2)(Indo)(4)L(2)] (L = DMA, NMP) complexes to be determined. All display a similar Cu(2)O(10)C(8) coordination geometry, which is independent of the nature of the axial ligand. While XAFS analysis of [Cu(2)(Indo)(4)(OH(2))(2)] and [Cu(2)(OAc)(4)(OH(2))(2)] indicates a coordination geometry similar to that of [Cu(2)(Indo)(4)L(2)] (L = DMF, DMA, NMP), removal of symmetry restraints in the MS model is required to obtain axial bond lengths comparable to those derived in the XRD structures of the acetate complex. For the Indo complex, the fitted bond lengths with the lower symmetry model give a mean Cu-L(OH2) bond distance within experimental errors of the value for [Cu(2)(Indo)(4)(DMSO)(2)] (2.16(2) A) (XRD). The difficulty in refining the Cu-O(OH2) distance of [Cu(2)(OAc)(4)(OH(2))(2)] and [Cu(2)(Indo)(4)(OH(2))(2)] using a centrosymmetric MS model is attributed to a symmetry reduction due to hydrogen-bonding effects characteristic of the aqua adducts, as is observed in the XRD structure of the acetate complex.

Absorptiometry, Photon↗

PubMed2001

Photosynthetic water oxidation: towards a mechanism.

This mini-review outlines the current theories on the mechanism of electron transfer from water to P680, the location and structure of the water oxidising complex and the role of the manganese cluster. We discuss how our data fit in with current theories and put forward our ideas on the location and mechanism of water oxidation.

Chlorophyll↗

PubMed2001

Epithelial-mesenchymal interactions in experimental oral mucosal carcinogenesis.

In an effort to come to a better understanding of human oral mucosal carcinogenesis, an animal model was used in which the carcinogen 4-nitroquinoline-1-oxide was applied to rat palatal mucosa for varying periods of time. Histological and histometric analyses showed that there were quantifiable differences in the palatal epithelium to which carcinogen had been applied in comparison with control tissue. Tissue recombination experiments, using various combinations of the palatal mucosa and analysed after recovery from transplantation to hypothymic BALB/c mice, showed that control epithelium recombined with connective tissue from carcinogen-treated mucosa was altered, indicating that the underlying connective tissue modified histomorphological aspects of the epithelium in the later stages of carcinogenesis.

4-Nitroquinoline-1-oxide↗

PubMed2000

Evidence for the presence of a component of the Mn complex of the photosystem II reaction centre which is exposed to water in the S(2) state of the water oxidation complex.

The interaction of water oxidising photosystem II preparations with the aqueous environment has been investigated using electron spin echo envelope modulation spectroscopy in the presence of 2H(2)O. The spectra show interaction of 2H of 2H(2)O with the preparation in the S(2) state. The component interacting with water decays during 1-4 weeks storage at 77 K. No interaction of water with the classical multiline S(2) Mn signal, which is more stable on storage at 77 K, was detected. The results show that a component of the water oxidation complex, possibly involving the Mn centre, is accessible to water and may be the water binding site for photosynthetic water oxidation.

Binding Sites↗

PubMed2000

Tongue lesions: what can it be?

In the course of the examination of a patient their tongue is easily visualized and with the use of gauze can be gently dried, held with gauze and stretched for inspection of all aspects. This can be followed by palpation of both the tongue and the floor of mouth. In this manner, any altered tissue is likely to be detected and, with or without further investigations, a diagnosis established. Appropriate management can then be undertaken. A wide range of conditions may involve the tongue and this article outlines some of these using a classification based on aetiology.

Diagnosis, Differential↗

PubMed1999

Determination of Fe-ligand bond lengths and the Fe-N-O bond angles in soybean ferrous and ferric nitrosylleghemoglobin a using multiple-scattering XAFS analyses.

The NO adducts of leghemoglobin (Lb) are implicated in biological processes, but only the adduct with ferrous Lb (Lb(II)NO) has been characterized previously. We report the first characterization of ferric nitrosylleghemoglobin (Lb(III)NO) and XAS experiments performed on frozen aqueous solutions of Lb(II)NO and Lb(III)NO at 10 K. The XANES and electronic spectra of the NO adducts are similar in shape and energies to the myoglobin (Mb) analogues. The environment of the Fe atom has been refined using multiple-scattering (MS) analyses of the XAFS data. For Lb(II)NO, the MS analysis resulted in an averaged Fe-N(p)(pyrrole) distance of 2.02 A, an Fe-N(epsilon)(imidazole) distance of 1.98 A, an Fe-N(NO) distance of 1.77 A, and an Fe-N-O angle of 147 degrees. The Fe-N(NO) distance and Fe-N-O angle obtained from the analysis of Lb(II)NO are in good agreement with those determined crystallographically for [Fe(TPP)(NO)] (TPP, tetraphenylporphyrinato), with and without 1-methylimidazole (1-MeIm) as the sixth ligand, and the MS XAFS structures reported previously for the myoglobin (Mb(II)NO) analogue and [Fe(TPP)(NO)]. The MS analysis of Lb(III)NO yielded an average Fe-N(p) distance of 2.00 A, an Fe-N(epsilon) distance of 1.89 A, an Fe-N(NO) distance of 1.68 A, and an Fe-N-O angle of 173 degrees. These bond lengths and angles are consistent with those determined previously for the myoglobin analogue (Mb(III)NO) and the crystal structures of the model complexes, [Fe(III)(TPP)(NO)(OH(2))](+) and [Fe(OEP)(NO)](+) (OEP, octaethylporphyrinato). The final XAFS R values were 16.1 and 18.2% for Lb(II)NO and Lb(III)NO, respectively.

Data Interpretation, Statistical↗

PubMed1999

p53 expression in oral precancer and cancer.

Expression of the p53 tumour suppressor gene is a frequent finding in human malignancies, including oral cancer, and it has been detected in some potentially malignant lesions. The results of the present project showed that 35 of the 41 (85 per cent) oral mucosal lesions with histological evidence of epithelial dysplasia expressed p53, but the presence or absence of p53 staining could not be used to predict the outcome of potentially malignant oral mucosal lesions.

Carcinoma, Squamous Cell↗

PubMed1999

Verruciform xanthoma and concomitant lichen planus of the oral mucosa. A report of three cases.

Verruciform xanthomas are benign muco-cutaneous lesions of unknown aetiology. They have a papillated surface and histologically they are characterised by the presence of foam cells in connective tissue papillae between elongated parakeratinised epithelial rete ridges. Three cases are reported in which oral mucosal verruciform xanthoma and oral mucosal lichen planus occurred concomitantly.

Adult↗

PubMed1997

Expression of p53 in oral mucosal hyperplasia, dysplasia and squamous cell carcinoma.

OBJECTIVE: To assess p53 expression in a range of oral mucosal lesions and to relate the results to the clinical outcome in patients with dysplastic oral mucosal lesions and oral squamous cell carcinomas (OSCC). MATERIALS AND METHODS: Archival tissue was available for eight cases of normal oral mucosa, 50 cases of oral mucosal hyperplasia, 41 cases of oral mucosal dysplasia and 48 cases of OSCC. The monoclonal antibody DO-7, reactive to p53 protein, was applied to paraffin-embedded sections using microwave pretreatment and immunohistochemical techniques. RESULTS: The results showed that normal oral mucosa did not express p53. Positive nuclear staining was found in 18/50 (36%) cases of hyperplasia, 35/41 (85%) cases of dysplasia and 45/48 (94%) cases of OSCC. None of the p53 negative dysplasias progressed, while 19% of p53 positive cases of dysplasia recurred following excision and 11% of the cases underwent neoplastic transformation. Five out of 10 (50%) cases of severe dysplasia which were p53 positive resolved. CONCLUSION: The proportion of cases with positive p53 expression increased from hyperplasia to dysplasia to OSCC. These results may indicate an involvement of p53 in neoplastic transformation as well as in proliferative events although the presence or absence of p53 staining could not be used to predict the outcome of potentially malignant oral mucosal lesions.

Analysis of Variance↗

PubMed1996

Nuclear morphometry in experimental oral mucosal carcinogenesis.

The area, perimeter and diameter of basal cell nuclei of rat palatal epithelium were measured and the deviation of the basal cell nuclear profile from the form of a sphere was assessed after the application of the carcinogen 4-nitroquinoline-1-oxide (4NQO). After a 24-week treatment-free period, designed to eliminate the irritant effect of the carcinogen, the rats were killed, the palatal mucosa was recovered and processed and the nuclear histometry was assessed with image analysis techniques. The basal cell nuclear area increased as the epithelium became dysplastic and then decreased as carcinoma developed, but there were significant variations in this parameter in the control groups. Basal cell nuclei from moderately or severely dysplastic epithelium, and from epithelium adjacent to areas of invasive carcinoma, were significantly less regular in profile by comparison with control nuclei. Variations in nuclear profile, but not nuclear area, perimeter or diameter, might reflect fundamental nuclear alterations of significance during the process of carcinogenesis.

4-Nitroquinoline-1-oxide↗

PubMed1996

Induction by 4-nitroquinoline-1-oxide of oral epithelial dysplasia and neoplasia in scurvy-prone osteogenic disorder Shionogi (ODS) rats.

Carcinogenesis by 4-nitroquinoline-1-oxide (NQO) in the oral mucosa is a reliable method of obtaining oral mucosal squamous cell carcinoma (OMSCC) and allows examination of various stages of oral cancer development. In vivo and in vitro studies have indicated that L-ascorbic acid (AA) may have a role in cancer prevention. The Wistar "scurvy-prone" osteogenic disorder Shionogi (ODS) rat of the od/od substrain is unable to synthesize AA and requires supplementation for its survival. This study examined the effects of NQO on the oral mucosa of ODS and outbred Wistar rats. NQO (0.5%) was applied topically to the palatal mucosa of 72 male ODS and 36 outbred Wistar rats three times weekly for 4, 8, 12, 16, 20, and 24 wks. The ODS rats were divided so that 36 rats were given 2.5 g/l AA in the drinking water and 36 rats were given 0.33 g/l AA. Vehicle-treated and untreated control animals were included. The rats were killed two weeks after the final NQO application, and the tissues were examined. Epithelial dysplasia was assessed using a modified Smith and Pindborg (1969) index. The ordered categorical scores were analyzed appropriately. Plasma AA levels were checked in ODS and outbred rats at the start and end of the experiment. The results indicated that the oral mucosa of the ODS and outbred rats were susceptible to NQO but that the rate of dysplasia and OMSCC development differed between them, with more rapid changes being found in the ODS rats (p < or = 0.05). No significant difference was found in the dysplasia scores and in the rate of OMSCC development between ODS rats given 2.5 g/l of AA and ODS rats given 0.33 g/l of AA (p > 0.05). No epithelial changes were observed in the palatal mucosa of vehicle-treated and untreated controls. The plasma AA level mean (+/- SEM) was 56 +/- 6 microM for the outbred rats, 8 +/- 1 microM for the ODS rats given 0.33 g/l AA supplementation, and 29 +/- 2 microM for the ODS rats given 2.5 g/l AA. It was concluded that the chronic AA-deficient state in ODS rats played an insignificant role in oral carcinogenesis and that other factors, for example, genetic differences in susceptibility to NQO, contributed to the present findings.

4-Nitroquinoline-1-oxide↗

PubMed1996

Expression of c-erbB-2 protein in keratinocytes of oral mucosal lichen planus and subsequent squamous cell carcinoma.

Oral mucosal lichen planus (OMLP) is a well recognized mucosal disease with unknown etiology. Considerable controversy exists as to whether OMLP is intrinsically premalignant, or if the disorder facilitates the development of oral mucosal squamous cell carcinoma (OMSCC) by external factors. The aim of the present study was to investigate the expression of c-erbB-2 protein in the keratinocytes of initial biopsies or oral mucosal disorders diagnosed as OMLP with no evidence of epithelial dysplasia, and to compare the results with the expression of c-erbB-2 protein in subsequent biopsies obtained from the same patients. These results were compared with the findings from control groups (patients with dysplasia with no evidence of OMLP, patients with OMSCC with no evidence of OMLP and normal oral mucosa). The expression of the c-erbB-2 protein was evaluated by immunohistochemical staining of the gene product with the avidin-biotin-complex method using paraffin-embedded tissues sections. Five of the initial biopsies from patients with OMLP expressed the c-erbB-2 protein and one did not. None of the OMLP cases that subsequently showed evidence of dysplasia expressed the c-erbB-2 protein, and of the three OMSCC specimens from the patients with OMLP, two were negative and one expressed c-erbB-2 protein. The specimens from the control groups all expressed the c-erbB-2 protein. The results indicated the probability of the absence of c-erbB-2 staining being an indication of a potential for neoplastic transformation in OMLP with dysplastic changes.

Adult↗

PubMed1996

Studies of the inflammatory process and malignant potential of oral mucosal lichen planus.

Oral mucosal lichen planus (OMLP) is a well recognized mucosal disease with unknown aetiology. Considerable controversy exists as to whether OMLP is intrinsically premalignant, or if the disorder facilitates the development of oral mucosal squamous cell carcinoma (OMSCC) by external factors. The aim of the present studies was to investigate the expression of c-erbB-2 protein in the keratinocytes of the initial biopsies of oral mucosal disorders diagnosed as OMLP with no evidence of epithelial dysplasia and to compare the results with the expression of c-erbB-2 protein in subsequent biopsies obtained from the same patients. These results were compared with the findings from another 26 biopsies from patients with OMLP and control groups (patients with dysplasia with no evidence of OMLP, patients with OMSCC with no evidence of OMLP and normal oral mucosa). The expression of the c-erbB-2 protein was evaluated by immunohistochemical staining of the gene product with the avidin-biotin-complex method using both fresh frozen and paraffin-embedded tissue sections. Five of the initial biopsies from patients with OMLP expressed the c-erbB-2 protein and one did not. None of the OMLP cases that subsequently showed evidence of dysplasia expressed the c-erbB-2 protein and of the OMSCC specimens from the patients with OMLP, 2 were negative and 1 expressed c-erbB-2 protein. Within the other group of OMLP specimens 3 (3/26) were negative for c-erbB-2 staining. The specimens from the control groups all expressed the c-erbB-2 protein. The results indicated the probability of the absence of c-erbB-2 staining being an indication of a potential for neoplastic transformation in OMLP with dysplastic changes.

Carcinoma, Squamous Cell↗

PubMed1995

The expression of c-erbB-2 protein in the keratinocytes of oral mucosal lichen planus.

The expression of the c-erbB-2 protein was studied in the keratinocytes from patients with: (i) oral mucosal lichen planus (OLP) (n = 26); (ii) oral mucosal squamous cell carcinoma (OMSCC) which had arisen in mucosa affected by OLP (n = 5); and (iii) normal oral mucosa (n = 5). C-erbB-2 protein was expressed on the cell membranes of the keratinocytes of nucleated epithelium in the stratum spinosum. The antigenic determinant recognized represents the cytoplasmic domain of a cell surface receptor which binds an as yet uncharacterized heparin binding ligand of unknown function. The specimens from the five normal subjects showed positive immunohistochemical staining with the monoclonal c-erbB-2 protein antibody, the OMSCC specimens were negative, and 23 of 26 of the OLP specimens were positive. The lack of c-erbB-2 expression in the three OLP and in the five OMSCC specimens may indicate a genetic alteration, or masking of the expression of c-erbB-2. The absence of expression in OLP specimens might be an indicator of the possibility of future neoplastic transformation.

Carcinoma, Squamous Cell↗

PubMed1994

Oral mucosal ulceration due to cytomegalovirus associated with human immunodeficiency virus infection. Case report and brief review.

Reports of oral lesions associated with cytomegalovirus (CMV) infection in human immunodeficiency virus (HIV) infected patients are uncommon. In this article a case of CMV infection associated with oral mucosal ulceration and a brief review of the subject is presented. Establishing the cause of ulceration is important in determining a definitive diagnosis and prescribing appropriate therapy. It is important to recognize that CMV associated oral mucosal ulceration may be the initial manifestation of human immunodeficiency virus (HIV) infection.

AIDS-Related Opportunistic Infections↗

PubMed1994

Giant cells in lesions of the oral region.

Multinucleated giant cells form by several different mechanisms in a variety of disease processes. They play a role in the host immune response to chronic infections, react to foreign materials and are an integral part of a number of bone disorders. A selection of lesions of the oral regions that contain giant cells will be presented.

Giant Cells↗

PubMed1992

Direct immunofluorescence of oral mucosal biopsies: a comparison of fresh-frozen tissue and formalin-fixed, paraffin-embedded tissue.

The diagnosis of some oral mucosal diseases can be facilitated by the use of direct immunofluorescence. Fresh frozen tissue is preferred when using this technique, however frequently the material received by the histopathology laboratory has been fixed in formalin. Enzyme digestion of tissue sections glued to glass slides prior to incubation with antibodies was shown in this study to give comparable results with direct immunofluorescence on fresh frozen tissue and can be used for diagnostic purposes when fresh frozen tissue is unavailable or not representative of the disease process.

Basement Membrane↗

PubMed1992

Epithelial-mesenchymal interactions in experimental oral mucosal carcinogenesis: establishing a technique.

The carcinogen 4-nitroquinoline-1-oxide was applied to the palatal mucosa of rats for varying periods of time. This tissue was separated into epithelial and connective components and then recombined in various combinations and implanted into hypothymic mice. Seventy-two per cent of the implants were recovered and were suitable for detailed histological analysis. The technique provides a suitable model for the assessment of epithelial-connective tissue interactions in experimental oral mucosal carcinogenesis.

4-Nitroquinoline-1-oxide↗