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Biomedical subjects

G Robertson

Publications and source records attributed to G Robertson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Growth control by tumor suppressors in malignant melanoma.

The development of malignant melanoma is accompanied by an accumulation of genetic damage that is evident within tumor cells at both cytogenetic and molecular levels, and mutations at several gene loci are thought to contribute to malignant progression. Some of these loci are known oncogenes and tumor suppressor genes; others remain to be identified, although their chromosomal locations have been determined. Gene mapping studies indicate the presence of melanoma tumor suppressor genes on chromosomes 1, 6, and 9. The presence of a tumor suppressor gene on a particular chromosome can be demonstrated by transfer of an intact, normal copy of the chromosome into tumor cells. We have used this approach to investigate the mechanisms by which chromosome 6 suppresses the growth and tumorigenicity of human malignant melanoma cells.

Cell Division↗
PubMed1994

Thrombocytosis as a prognostic factor in women with cervical cancer.

BACKGROUND: Thrombocytosis (a platelet count > 400 x 10(9)/l) is found frequently in association with malignant disease and recently has been suggested to be a poor prognostic indicator in patients with cervical cancer. The authors decided to see if these findings could be verified. METHODS: The pretreatment platelet counts of 643 women treated for cervical cancer between 1983 and 1992 were reviewed and correlated to each patient's age, stage of disease, histologic type, node status (when available), and outcome. Differences between groups were analyzed using the chi 2 test, and survival was compared using the log rank test on Kaplan-Meier life tables. RESULTS: The 5-year survival rate for patients with thrombocytosis was 57.1%, which was significantly worse than the 76.5% for those with normal platelet counts (P < 0.01). When adjusted for stage of disease, however, thrombocytosis failed to have a significant effect on patient survival. There was also no relation between thrombocytosis and the incidence of positive lymph nodes. CONCLUSION: Thrombocytosis was not found to be an independent prognostic factor in patients with carcinoma of the cervix in this series of 643 patients.

Adult↗
PubMed1994

Distinct deletions of chromosome 9p associated with melanoma versus glioma, lung cancer, and leukemia.

Deletions of DNA on chromosome 9p21-22 are frequently observed in cells derived from melanomas, gliomas, non-small cell lung cancers, and acute lymphoblastic leukemia. The minimal deletion shared by the latter three cancers extends from the interferon-alpha locus towards the centromere; its centromeric end is flanked by the gene encoding methylthioadenosine phosphorylase. We have determined that the telomeric end of the minimal homozygous deletion shared by two melanoma cell lines does not include the methylthioadenosine phosphorylase locus. Thus, a distinct region of DNA is lost in melanoma. The physical size of this region remains to be defined precisely, but it may extend over several million base pairs.

Carcinoma, Non-Small-Cell Lung↗
PubMed1994

Maintenance of identical p53 mutations throughout progression of squamous cell carcinomas of the tongue.

The occurrence of mutations within the coding sequence of the p53 tumour suppressor gene is now well documented for squamous cell carcinomas of the head and neck region. However, evidence that these mutations are required for the maintenance and progression of squamous tumours is still formally lacking. To test this we have examined whether p53 mutations detected in primary squamous cell carcinomas of the tongue are also detected in the corresponding lymph node metastases. Three different p53 mutations were detected in each of three primary tongue squamous cell carcinomas (SCC), and in each case the same mutation was detected in a lymph node metastasis excised from the same patient. Although the sample number is small, the chance of obtaining the same p53 mutation independently in both the primary and metastatic tumour of each patient is at least 10(-4), therefore the results indicate that keratinocytes harbouring these p53 mutations possess a selective advantage throughout SCC progression.

Carcinoma, Squamous Cell↗
PubMed1994

Epidermal growth factor receptor expression by human squamous cell carcinomas of the head and neck, cell lines and xenografts.

Epidermal growth factor receptor (EGFR) overexpression has been associated frequently with squamous cell carcinomas (SCC) and SCC cell lines. In most cases the level of EGFR on the tumours from which the cell lines were derived has not been determined, nor have EGFR levels been determined for xenograft tumours from the cell lines. In this study we determined EGFR expression on a new series of head and neck SCC (SCCHN)-derived cell lines, which were obtained from tumours representing a spectrum of malignant progression, and two cell strains derived from erythroplakia premalignant lesions. The level of EGFR on cell lines was determined by [125I]EGF competitive binding assays. EGFR levels on some of the original tumours and xenografts of the cell lines were determined on cryosections by a competitive binding assay based on [125I]EGFR1, an EGFR-specific monoclonal antibody. EGFR expression on the tumour cryosections was compared with expression on cryosections of skin and buccal mucosa. Eight of the ten tumour cell lines had elevated EGFR. Two of the tumour-derived cell lines and the two erythroplakia-derived cell strains expressed EGFR at levels similar to that detected on normal keratinocytes in tissue culture. Only two of the tumours overexpressed EGFR when compared with normal tissue. The other tumours had levels similar to that detected on the basal layers of skin or buccal mucosa. The xenografts expressed EGFR, as did the original tumours, even though they were derived from cell lines that displayed significant overexpression of EGFR. This study suggests that most tumours have a latent potential to overexpress EGFR which is realised in tissue culture.

Animals↗
PubMed1994

Pelvic exenteration: a review of the Gateshead experience 1974-1992.

OBJECTIVE: To examine morbidity and survival among women treated by pelvic exenteration for gynaecological malignancy. DESIGN: Retrospective review by analysis of case records. SETTING: Department of Gynaecological Oncology, Queen Elizabeth Hospital, Gateshead, UK. SUBJECTS: Eighty-three consecutive patients referred from within the UK from 1974 to 1992 for initial treatment of advanced gynaecological malignancy or management of recurrent disease following unsuccessful initial therapy. RESULTS: Overall five year actuarial survival was 41%, falling to 36% at 10 years. Serious morbidity was low, and there were only three peri-operative deaths. CONCLUSIONS: For patients with limited options for treatment of advanced primary or recurrent cancer, exenteration offers a reasonable prospect of survival with good quality of life.

Actuarial Analysis↗
PubMed1994

A follow-up of remanded mentally ill offenders given court hospital orders.

A follow up study of 101 men who were remanded to Brixton prison and who were given hospital orders by courts is reported. In 93% of cases the hospitals who responded to our enquiries reported that the admission had been appropriate. Only 5 (11%) of the 46 men who had been discharged from hospital had absconded or discharged themselves without medical approval. The process of referral and admission to hospital resulted in these men having to spend, on average, between two and three times longer in custody when compared to men charged with similar offences. It is generally recognized that the acutely ill should not be imprisoned, and encouragement has been given to the diversion of such people from the Criminal Justice System. However, London presents particular problems in this respect and it is argued that, since such problems will always be present, there is a need for special psychiatric facilities to be opened in order to serve the needs of the Capital.

Adult↗
PubMed1994

Psychotic men remanded in custody to Brixton Prison.

All referrals to medical officers in Brixton Prison over a five-month period in 1989 were examined. This paper reports the progress through this remand prison of those men who were considered to be suffering from a major psychiatric disorder. Many men had been charged with relatively minor offences. The net effect of medical intervention was to delay release from custody. Because of the administrative delays inherent in the system of medical referral and hospital admission under section 37 of the Mental Health Act 1983, it was those prisoners who were most ill who tended to remain in prison for the longest periods. Judged in terms of its efficiency to ensure speedy treatment for mentally ill remanded offenders, the present system is regarded as cumbersome and extremely inefficient. It is suggested that greater use should be made of section 48 of the 1993 Act to divert mentally ill, remanded offenders from prison.

Adolescent↗
PubMed1994

The efficacy of cervical extension-compression traction combined with diversified manipulation and drop table adjustments in the rehabilitation of cervical lordosis: a pilot study.

OBJECTIVE: To experimentally investigate the effect of cervical extension-compression traction combined with diversified chiropractic manipulation and drop table adjusting in establishing or increasing cervical lordosis. DESIGN: Blinded, before and after trial with pre- and postlateral cervical radiographic measurement. SETTING: Primary care private chiropractic clinic in Saugus, MA. SUBJECTS: A) Control group--convenience sample who had no health care for 10-14 wk, 30 persons. B) Treatment group 1, nonrandomized control trial, 35 persons, whose pre- and postlateral cervical radiographs were taken 10-14 wk apart and whose radiographs clearly depicted C1 through C7. C) Treatment group 2, nonrandomized control trial, 30 persons, whose pre- and postlateral cervical radiographs were taken 10-14 wk apart and whose radiographs clearly depicted C1 through C7. INTERVENTIONS: Treatment group 1: diversified spinal manipulation, drop table adjustments and cervical extension-compression traction five times per week for 10-14 wk (12 wk +/- 2). Treatment group 2: diversified spinal manipulation and drop table adjustments five times per week for 10-14 wk (12 wk +/- 2). MAIN OUTCOME MEASURES: Anterior head translation millimeters, C2 to C7 absolute rotation angle, angle of C1 to horizontal (atlas plane angle), five relative rotation angles (C2-3, C3-4, C4-5, C5-6, C6-7) and qualitative classification of lordotic configuration. RESULTS: No statistically significant changes existed between the pre- and posttests for the control group except in the C6-7 relative rotation angle. In the treatment group 1, statistically significant differences were found in all X-ray markings. Twenty-nine of 35 members have a lordosis after treatment compared to 11 of 35 before treatment. The C2 to C7 angle changed an average 13.2 degrees, C1 to horizontal changed an average 9.8 degrees, the anterior head translation reduced an average of 6.8 mm, the average relative rotation angle changed: C2-3: 3.1, C3-4: 5.5, C4-5: 4.80, C5-6: 2.7 and C6-7: 1.1. In the treatment group 2, no statistically significant changes existed between the pre- and posttests except atlas angulation to horizontal which increased an average of 3.0 degrees. CONCLUSIONS: A transformation to a lordotic configuration or increase in lordotic configuration occurred and was measured in the majority of treatment group 1 subjects, while no change in the control group and essentially no change in treatment group 2 was measured. Extension-compression traction combined with diversified chiropractic manipulation and drop table adjusting procedures may improve or partially reestablish the cervical lordosis in 10-14 wk of daily care.

Adult↗
PubMed1994

Anal human papillomavirus infection and squamous neoplasia in patients with invasive vulvar cancer.

OBJECTIVE: To test the hypothesis that women with invasive vulvar cancer are at high risk of developing human papillomavirus (HPV)-associated anal squamous neoplasia. METHODS: Forty women (median age 54.5 years; range 25-86) who were being treated or had been treated for invasive vulvar cancer and who had not had radiotherapy to the pelvis or anogenital region underwent anal microendoscopy and biopsy. A second group of 80 women who were similar in age to the study group and had no history of anogenital HPV infection or neoplasia formed the control group. The polymerase chain reaction was used to detect HPV 16 DNA in the vulvar and anal tissue samples from 33 patients in the study group and in the anal biopsies of all controls. RESULTS: A histologic diagnosis of anal HPV infection or squamous neoplasia was made in 19 of 40 biopsies (47.5%) in the study group. These diagnoses consisted of one HPV, two anal squamous intraepithelial lesions (SIL) grade I, 15 and SIL grade III (four of which were associated with invasive anal cancers), and one invasive cancer in the absence of anal SIL. Human papillomavirus 16 DNA was detected in 16 of 33 (48.5%) of anal and 25 of 33 (75%) of vulvar biopsies. In addition, HPV 16 was detected in both the anal and vulvar samples in 13 of 16 cases (81%) of anal SIL III and invasive anal squamous cancer. No evidence of anal SIL was found in the controls, and HPV 16 DNA was identified in only 11 (13.7%) of the anal biopsies in this group. CONCLUSIONS: This study provides further evidence for the etiologic relation between genital and anal squamous neoplasia. Furthermore, it shows that women with vulvar cancer are at high risk of having or developing HPV-associated anal neoplasia, particularly in younger patients (P = .0006; 95% confidence interval 12-34). Routine anal examination should be performed in patients with invasive vulvar cancer.

Anal Canal↗
PubMed1993

Gene mutations and increased levels of p53 protein in human squamous cell carcinomas and their cell lines.

Using immunocytochemical and Western blotting techniques we have demonstrated the presence of abnormally high levels of p53 protein in 8/24 (33%) of human squamous cell carcinomas (SCC) and 9/18 (50%) of SCC cell lines. There was a correlation between the immunocytochemical results obtained with eight SCC samples and their corresponding cell lines. Direct sequencing of PCR-amplified, reverse transcribed, p53 mRNA confirmed the expression of point mutations in six of the positive cell lines and detected in-frame deletions in two others. We also detected two stop mutations and three out-of-frame deletions in five lines which did not express elevated levels of p53 protein. Several of the mutations found in SCC of the tongue (3/7) were in a region (codons 144-166) previously identified as being a p53 mutational hot spot in non-small cell lung tumours (Mitsudomi et al., 1992). In 11/13 cases only the mutant alleles were expressed suggesting loss or reduced expression of the wild type alleles in these cases. Six of the mutations were also detected in the SCCs from which the lines were derived, strongly suggesting that the mutations occurred, and were selected, in vivo. The 12th mutation GTG-->GGG (valine-->glycine) at codon 216 was expressed in line SCC-12 clone B along with an apparently normal p53 allele and is to our knowledge a novel mutation. Line BICR-19 also expressed a normal p53 allele in addition to one where exon 10 was deleted. Additionally 15 of the SCC lines (including all of those which did not show elevated p53 protein levels) were screened for the presence of human papillomavirus types 16 and 18 and were found to be negative. These results are discussed in relation to the pathogenesis of SCC and the immortalisation of human keratinocytes in vitro.

Base Sequence↗
PubMed1993

The absence of Harvey ras mutations during development and progression of squamous cell carcinomas of the head and neck.

We have examined the incidence of Harvey ras mutations in human squamous cell carcinomas (SCC) of the upper aerodigestive tract using the polymerase chain reaction (PCR) followed by direct sequencing. No mutations were detected at codons 12, 13, 59 or 61 of this gene in any of six papillomas, five erythroplakias, 56 squamous cell carcinomas, and 16 SCC cell lines. Some of the SCC were lymph node metastases (three) or tumours which had recurred following radiotherapy (seven). We conclude that Harvey ras mutations are not a common event in the pathogenesis or recurrence of SCCs from Caucasian subjects, in contrast to the situation with Indian populations (Saranath et al., 1991).

Base Sequence↗
PubMed1993

Effects of exercise on total and segmental colon transit.

To investigate the effect of aerobic exercise on total gastrointestinal and segmental colon transit, 16 male health care workers with a sedentary life-style were studied during 1 week of rest and 1 week of exercise. The exercise phase consisted of walking 4.5 km on a level treadmill for 1 h on each of 3 days. Total gastrointestinal and segmental colon transit times were measured using radiopaque markers ingested on each of 3 consecutive days with an abdominal radiograph obtained on the fourth day. With exercise, total gastrointestinal transit time decreased in 5, increased in 6, and did not change in 5 subjects. Using a paired t test, total transit did not show a significant change from rest (24.5 +/- 21.8 h) to exercise (20.9 +/- 16.8 h), p = 0.50. These observations support our previous findings that physical activity to the extent that average people consider routine exercise does not necessarily improve gastrointestinal transit. Therefore, the role of such exercise in the management of chronic constipation can be seriously questioned.

Adult↗