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Biomedical subjects

C G Kelly

Publications and source records attributed to C G Kelly.

At least 37 records · Page 2Linked to original sources
PubMed1998

Malignant tumours of the maxillary complex: an 18-year review.

Over an 18-year period, 147 patients with malignant tumours involving the maxillary complex were treated in a combined head and neck clinic, of whom 50 underwent surgery. There were 33 males and 17 females, the mean age was 57 years (range 11-87 years). The most common clinical presentations were either painful facial swelling, infraorbital anaesthesia, palatal ulceration or nasal obstruction. Preoperative investigations included EUA, biopsy and either CT or MRI scans. Of the 50 tumours, 62% were squamous cell carcinomas. Surgery consisted of either partial or total maxillectomy including craniofacial resection in nine patients. Reconstruction was by either split skin grafting or by free tissue transfer when the cranial contents had been exposed. Adjuvant radiotherapy was given in 82% of the patients. The mean follow-up was 5 years and 59% of patients are alive and disease free. The 5-year local control rate was 67%; it was greatly influenced by histological evidence of nerve invasion, local recurrence being the major cause of death. It was concluded that adequate surgical clearance, followed by planned postoperative radiotherapy, is the most effective treatment for malignant disease of the maxillary complex.

Adolescent↗
PubMed1997

Malignant tumours of the parotid gland: a 12-year review.

Malignant parotid tumours are uncommon and present a significant management challenge. Fifty-one such patients (25 male, 26 female, median age 64 years) operated on in the Newcastle Plastic Surgery Unit between 1983 and 1994 were retrospectively evaluated. Preoperative investigations included FNA cytology (n = 20), and for staging CT and/or MRI scans (n = 21). Of the 35 primary tumours 32 were epithelial and three lymphomatous. Metastatic tumours were squamous cell carcinoma (7), melanoma (6), renal cell carcinoma (2) and sebaceous carcinoma (1). FNA cytology correctly diagnosed malignancy with an 88% sensitivity (false negatives = 2). A total or radical parotidectomy was required in 60% of patients, the rest undergoing superficial parotidectomy. In continuity neck dissection was undertaken in 23 (45%) cases. Postparotidectomy reconstruction included 10 free, 3 myocutaneous, and 4 local transposition/rotation flaps. Thirty-seven patients (73%) received postoperative radiotherapy. Seventy-two per cent of patients are alive after a mean follow-up of 42 months. The crude 5- and 10-year survival rates were 68% and 49% respectively while the loco-regional control rate (Kaplan-Meier method) at 10 years was 79%. Fifteen patients (30%) have permanent facial palsy. It is concluded that radical surgery with appropriate reconstruction followed by planned postoperative adjuvant radiotherapy gives effective control of malignant parotid tumours.

Adolescent↗
PubMed1997

Pain relief and quality of life following radiotherapy for bone metastases: a randomised trial of two fractionation schedules.

BACKGROUND: The optimum dose and fractionation schedule for the palliative irradiation of painful bone metastases is controversial. PURPOSE: To compare the efficacy, side-effects and effect on quality of life of two commonly used radiotherapy schedules in the management of painful bone metastases. MATERIALS AND METHODS: In a prospective trial, 280 patients were randomised to receive either a single 10 Gy treatment or a course of 22.5 Gy in five daily fractions for the relief of localised metastatic bone pain. RESULTS: Response rates have been calculated from 240 assessable treated sites of pain. The overall response rates were 83.7% (single treatment) and 89.2% (five fractions). The complete response rates were 38.8% (single treatment) and 42.3% (five fractions). The median duration of pain control was 13.5 weeks (single treatment) and 14.0 weeks (five fractions). None of these differences was statistically significant. There were no differences between the groups in the effect of treatment on a variety of quality of life parameters. CONCLUSIONS: It is concluded that a single 10 Gy treatment is as effective as a course of 22.5 Gy in five fractions in the management of painful bone metastases.

Bone Neoplasms↗
PubMed1997

The relationship between colonization and haemagglutination inhibiting and B cell epitopes of Porphyromonas gingivalis.

Passive immunization with the monoclonal antibody 61BG1.3 selectively prevents colonization by Porphyromonas gingivalis in humans (Booth V, Ashley FP, Lehner T. Infect Immun 1996; 64:422-7). The protective MoAb recognizes the beta component of the RI protease of P. gingivalis which is formed by proteolytic processing of a polyprotein precursor termed PrpR1. This subunit is both a haemagglutinin and an antigen which is recognized by sera from patients with periodontitis. In this study the relationship was investigated between a colonization epitope which is recognized by the MoAb 61BG1.3, a haemagglutinating and B cell epitope which are recognized by sera from patients with periodontitis. B cell epitopes were mapped by Western blotting with a series of truncated recombinant polypeptides spanning the adhesion domain within residues 784-1130 of PrpR1 and by ELISA using a panel of synthetic peptides spanning the same sequence. The epitope which is recognized by the protective MoAb was mapped within residues 907-931 of PrpR1, while serum responses of patients were directed predominantly to the adjacent carboxy-terminal sequence within residues 934-1042. The haemagglutinating epitope was mapped to residues 1073-1112. In view of our previous findings that the MoAb 61BG1.3 prevents colonization of P. gingivalis in vivo and inhibits haemagglutination, these two epitopes may be in proximity in the native protein. Active or passive immunization strategies which target the protective or haemagglutinating epitopes of the adhesion domain of PrpR1 may provide a means of preventing infection with P. gingivalis.

Adult↗
PubMed1996

Induction of immune responses to functional determinants of a cell surface streptococcal antigen.

Antibodies directed against the cell surface adhesin, termed streptococcal antigen I/II of Streptococcus mutans can protect against dental caries. Streptococcal antigen I/II (SA I/II) interacts with salivary glycoproteins and promotes adhesion to the tooth surface. Topical application of monoclonal antibodies which recognize a domain within residues 816-1213 (fragment 3) prevents colonization by S. mutans in primates. In this study the immunogenicity and antigenicity of fragment 3 was investigated in five strains of mice. Fragment 3 induced an immune response following immunization with whole cells of S. mutans in all strains of mice. Immunization with recombinant fragment 3 also induced T-cell proliferative and antibody responses both to fragment 3 and to the SA I/II. Antibody responses to the previously defined adhesion determinants (residues 1005-1044) were weak or undetectable. Immunization of three representative strains of mice with a recombinant polypeptide (residues 975-1044) comprising this adhesion epitope and an adjacent T-cell epitope (residues 975-1004) elicited both T- and B-cell responses to the polypeptide and to native SA I/II. The B-cell epitopes overlapped with the adhesion determinant. These findings provide a means of directing immune responses to functional determinants of SA I/II.

Animals↗
PubMed1995

Investigation of the complement receptor 3 (CD11b/CD18) in human rectal epithelium.

Rectal and cervicovaginal mucosa are common routes of transmission of HIV, although the mechanism of transmission is unknown. We have investigated human rectal and cervicovaginal epithelia for the expression of complement receptors (CR) and cell adhesion molecules which may be involved in HIV and other infections. In rectal mucosa, CR3 was detected in the surface and crypt epithelial cells by immunohistology, using MoAbs to CD18 and CD11b in 10 out of 15 specimens. RNA transcripts encoding both CD11b and CD18 were also demonstrated in surface and crypt epithelial cells by in situ hybridization. Although CD11b was detected in the epithelial cells in three out of the 14 cervicovaginal specimens, we were unable to detect CD18. We suggest that expression of the CD11b/CD18 heterodimer might facilitate transmission of HIV by enhancing binding of HIV-antibody complexes in seminal fluid to epithelial cells. Alternatively, since intercellular adhesion molecule-1 (ICAM-1) is a receptor for CD11b/CD18, this may promote adhesion between epithelial cells and HIV-infected mononuclear cells in seminal fluid.

CD18 Antigens↗
PubMed1995

T-cell, adhesion, and B-cell epitopes of the cell surface Streptococcus mutans protein antigen I/II.

The T-cell and antibody responses to a cell surface streptococcal antigen (SA I/II) were investigated in naturally sensitized humans. Serum antibody responses were directed predominantly to the N-terminal (residues 39 to 481) and central (residues 816 to 1213) regions of SA I/II which may be involved in bacterial adhesion to salivary receptors. T-cell responses were also directed predominantly towards the central region. The linear peptide relationship of the immunodominant and minor T- and B-cell as well as adhesion epitopes was mapped within residues 816 to 1213. Immunodominant T-cell and B-cell epitopes were identified within residues 803 to 853, which were separated in linear sequence from the adhesion epitopes (residues 1005 to 1044). Adhesion epitopes overlapped with minor B- and T-cell epitopes (residues 1005 to 1054 and 1085 to 1134). An immunodominant promiscuous T-cell epitope (residues 985 to 1004) was adjacent to an adhesion epitope (residues 1005 to 1024). The limited B-cell response to adhesion epitopes is consistent with the success of Streptococcus mutans in colonizing the oral cavity. The strategy of T-cell, adhesion, and B-cell epitope mapping has revealed a general approach for identifying components of subunit vaccines which may focus responses to critical functional determinants. Such epitopes of SA I/II may constitute the components of a subunit vaccine against dental caries.

Amino Acid Sequence↗
PubMed1993

A protein fragment of streptococcal cell surface antigen I/II which prevents adhesion of Streptococcus mutans.

Attachment of Streptococcus mutans to the tooth surface involves a cell surface protein with an M(r) of 185,000, termed streptococcal antigen (SA) I/II. Four overlapping fragments of the gene encoding SA I/II were amplified by polymerase chain reaction, cloned, and expressed in Escherichia coli. The recombinant polypeptides were assayed for adhesion-binding activity to salivary receptors and for recognition by a panel of monoclonal antibodies (MAbs) raised against SA I/II. Two of the MAbs which are known to prevent colonization of S. mutans in vivo bound the recombinant polypeptide comprising residues 816 to 1161. In vitro adhesion of S. mutans to saliva-coated hydroxyapatite beads was also inhibited specifically by a polypeptide (residues 816 to 1213) encompassing the same region. The evidence from the MAbs preventing colonization of S. mutans and the adherence inhibition assay suggests that an adhesion-binding activity resides within the portion of SA I/II comprising residues 816 to 1213, which is highly conserved among oral streptococcal species.

Animals↗
PubMed1992

A mechanism of passive immunization with monoclonal antibodies to a 185,000 M(r) streptococcal antigen.

The cell surface streptococcal antigen (SA) I/II of 185,000 M(r) is an immunodominant molecule that expresses one or more adhesion determinants. A series of 14 monoclonal antibodies (MAb) to defined parts of SA I/II were generated and some of these were used in passive immunization of macaques. Topical administration of selected MAb to the teeth of macaques prevented colonization of endogenous or implanted exogenous Streptococcus mutans for a period of 1 year. Significant reduction of both smooth surface and fissure caries was found in macaques who had MAb (Guy's 1) applied to their teeth, as compared with saline-treated animals. A series of in vivo passive immunization experiments was then carried out in 57 human subjects. Topical application of MAb to SA I/II prevented colonization of both artificially implanted exogenous strains of S. mutans, as well as natural recolonization by indigenous S. mutans. The properties of the protective MAb were then investigated and the epitope specificity within the SA I/II molecule was found to be essential but not the isotype specificity of the immunoglobulin (Ig). The requirement for complement activating and the phagocyte binding sites of the Fc fragment of MAb was not essential, as the F(ab')2 fragment of the MAb was as protective as the intact IgG, but the Fab fragment failed to prevent recolonization of S. mutans. Prevention of recolonization was specifically restricted to S. mutans, as the proportion of other organisms, such as S. sanguis, failed to show a significant change. The surprising feature of these experiments was that protection of re-colonization of S. mutans lasted up to 2 years, although MAb was applied for only 3 weeks and functional MAb was detected on the teeth only 3 days following application of the MAb. The long-term protection could therefore not be accounted for by a persistence of MAb on the teeth, but may be due to a shift in the microbial balance in which other bacteria occupy the ecological niche vacated by S. mutans, resulting in colonization resistance to S. mutans. Gene cloning and sequencing the SA from S. mutans, S. sobrinus and S. sanguis identified a conserved region (residues 955-1213) which on Southern hybridization and partial DNA sequence analysis was also found in 19 alpha-haemolytic oral streptococci. The results suggest that the SA molecule may constitute a family of adhesins in oral alpha haemolytic streptococci.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

An audit of survival in small cell lung cancer.

A total of 351 previously untreated patients presented to this department with limited small cell bronchogenic carcinoma between 1974 and 1985. They were treated with either radical or palliative radiotherapy (152), chemotherapy alone (63), or combined chemoradiotherapy (136). Their 5-year survival rates were 2.6%, 0%, and 5.1% with median survival being 25.7, 29.0 and 47.4 weeks, respectively. Forty-seven patients were given radical radiotherapy, 30 of these received chemotherapy as initial treatment (20), as adjuvant (3) or at relapse (7). Their 5-year survival rate was 12.8%, with a median of 58 weeks, compared with 2.1% and 31.5 weeks for 241 patients who had palliative radiotherapy (P < 0.001). Seventeen of the 47 patients (36%) and 135 of the 241 patients (56%) were given radiotherapy alone. Univariate analysis showed that gender and age had no significant influence on survival but lymph node status did. The median survival for patients who had no lymph node metastases was 37 weeks compared with 24.5 for those who had (P < 0.01). The median and long-term survival rates for patients in this report contradict previous reports that radiotherapy has no influence on survival. Only patients who received radiotherapy, either alone, or with chemotherapy, have survived 5 years.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Expression and gene transcript of Fc receptors for IgG, HLA class II antigens and Langerhans cells in human cervico-vaginal epithelium.

The mechanism of transmission of HIV from the male to the female genital tract or in the reverse order is not clear. CD4 glycoprotein is the receptor for HIV and Langerhans cells and the related dendritic cells could play a role in the initial transmission of HIV. Fc receptors (FcR) for IgG might be involved in antibody-mediated binding of HIV. We carried out an immunohistological study of normal human cervical and vaginal epithelia for the presence of CD4 glycoprotein, Langerhans cells and FcR to IgG. CD4+ glycoprotein was not found in the vaginal or cervical epithelium, with the exception of a few endocervical epithelial cells. A small number of CD4+ mononuclear cells were found in the endocervical epithelium of a third of the specimens but a large number of CD4+ cells was found in the submucosa of most of the cervical and vaginal specimens. Langerhans cells expressing CD4, HLA class II, Fc gamma R2 and Fc gamma R3 were detected in most vaginal, ectocervical and transformation zone epithelia and in 9/14 endocervical tissues. Fc gamma R3 was detected in about two-thirds of the columnar endocervical epithelium and the transformation zone. A smaller number of specimens expressed Fc gamma R2 in these epithelia, but Fc gamma R1 was not detected. We then demonstrated mRNA for Fc gamma R3 in the columnar endocervical epithelial cells and transformation zone by in situ hybridization, using a CD16-RNA probe. Fc gamma R3 and Fc gamma R2 gene transcripts were also found in fetal cervical tissue by applying the polymerase chain reaction to amplify portions of the Fc gamma R3 and Fc gamma R2 coding sequences in cDNA prepared from fetal RNA. HLA-DR was found in the endocervical cells, transformation zone and in Langerhans cells of all specimens. The presence of Langerhans cells, Fc gamma receptors and HLA class II antigen offers three potential mechanisms for cervico-vaginal HIV transmission: (i) direct HIV infection of Langerhans cells, (ii) binding of HIV antibody complexes to cervical epithelial Fc gamma receptors and (iii) binding of HIV infected CD4+ cells to cervical HLA class II antigen which may infect these or the adjacent CD4+ cells.

Adult↗
PubMed1992

Stage IB cervical carcinoma: a clinical audit.

All patients with FIGO Stage IB cervical cancer registered with the Department of Clinical Oncology at the Western General Hospital, Edinburgh, during the 6 years from 1979 to 1984 have been reviewed, as part of a continuing programme of clinical audit. Of the 140 patients with Stage IB disease, 68 (49%) were treated by primary surgery of whom 44 (31%) also received adjuvant radiotherapy. Radical radiotherapy was the definitive treatment for 69 patients (49%). Three patients (2%) were not treated with curative intent. The crude 5-year survival rate for all cases was 72% and the cause-specific 5-year survival rate was 78%. Local tumour control at 5 years was 72%. There was no significant difference in outcome between the surgically treated and irradiated groups of patients. Age, histology and nodal status did not influence outcome. Irradiated patients with bulky tumours fared significantly worse than the other patients who received radical radiotherapy. Multivariate analysis of all patients revealed no significant independent prognostic variables. Primary surgery appears to confer no benefit over radical radiotherapy in terms of either survival or local control. Treatment-related late bladder and bowel morbidity was, however, significantly worse in irradiated patients.

Adult↗
PubMed1991

The expression of Fc receptors for immunoglobulin G in human rectal epithelium.

The rectal mucosa is one of the routes of transmission of the HIV virus, although the mechanism of transmission is unknown. We carried out an immunohistological investigation of human rectal epithelium to detect CD4 glycoprotein and Fc receptors (FcR) for immunoglobulin G which may be involved in HIV infection. CD4 was not detected by monoclonal antibodies (MAb) in normal rectal epithelial cells, although CD4+ mononuclear cells were found in the lamina propria of the rectum. FcR3 and FcR2 were, however, detected in surface or crypt epithelial cells of rectal mucosa, using MAb to CD16 and CD32, respectively. In addition, CD16 messenger RNA (mRNA) was found in surface and crypt epithelial cells by in situ hybridization using an RNA probe. FcR3 and FcR2 were also detected in fetal recto-colonic tissue by immunohistology, suggesting that these are constitutive receptors. FcR3 and FcR2 gene transcripts were then demonstrated in fetal recto-colonic tissue using the polymerase chain reaction to amplify a portion of FcR3 and FcR2 coding sequences in complementary DNA (cDNA) prepared from fetal RNA. These findings suggest the possibility that rectal transmission of HIV-antibody complexes might be facilitated by the expression of FcR3 and FcR2 in rectal epithelial cells.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Sequence and structural analysis of surface protein antigen I/II (SpaA) of Streptococcus sobrinus.

Streptococcal antigen I/II or the surface protein antigen A (SpaA) of Streptococcus sobrinus is an adhesin which mediates binding of the organism to tooth surfaces. The complete sequence of the gene which encodes SpaA has been determined. The gene consists of 4,584 bp and encodes a protein of 1,528 amino acid residues. The deduced amino acid sequence shows extensive homology with those of the cell surface adhesins from Streptococcus mutans serotypes c and f and from Streptococcus sanguis. Structural analysis of the N-terminal region (residues 50 to 550), which is rich in alanine and includes four tandem repeats of an 82-residue sequence, suggests that it adopts an alpha-helical coiled-coil conformation. Cell surface hydrophobicity may be associated with this region. The C-terminal region is more conserved and includes two tandem repeats of a 39-residue proline-rich sequence. A further proline-rich sequence in this region is predicted to span the cell wall. Although a hydrophobic sequence is present in the C-terminal region, it appears to be too short to span the cell membrane. Anchoring of SpaA in the cell membrane may therefore require some form of posttranslational modification or association with another membrane protein.

Adhesins, Bacterial↗
PubMed1991

Conservation of the gene encoding streptococcal antigen I/II in oral streptococci.

The spaP gene of Streptococcus mutans serotype c encodes a major cell surface protein, streptococcal antigen (SA) I/II, with an Mr of 185,000, that is thought to be involved in bacterial adhesion to teeth. Proteins with significant amino acid sequence homology to SA I/II have also been found in S. sobrinus and S. sanguis. The objectives of this study were to investigate the conservation of the spaP gene in the mutans groups of streptococci and to determine whether homologous genes were present in other species of alpha-hemolytic streptococci. DNA extracted from representative strains of 19 streptococcal species was examined by Southern hybridization and partial DNA sequence analysis. A series of five overlapping DNA probes from the spaP gene were amplified by the polymerase chain reaction and used in the Southern hybridizations. The entire gene was found to be well conserved in all strains of S. mutans serotypes c, e, and f investigated. A probe from the 3' region of the gene, which encodes residues 857 to 1207 of the SA I/II protein, hybridized with DNA from a number of mutans streptococci, as well as with DNA from nonmutans alpha-hemolytic streptococci. Conservation within this region was further demonstrated by sequencing gene fragments of two strains of S. intermedius and S. oralis. The results show that some regions of the spaP gene are highly conserved not only in the mutans group of streptococci but also in other nonmutans alpha-hemolytic streptococci. This suggests that a family of cell surface proteins which, by analogy with the 185,000-Mr SA I/II of S. mutans, could be involved in bacterial adhesion might exist.

Amino Acid Sequence↗