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M H Jones

Publications and source records attributed to M H Jones.

At least 55 records · Page 3Linked to original sources
PubMed1994

Spermophagy in semen in the red wolf, Canis rufus.

The red wolf (Canis rufus) is an endangered species with 194 individuals remaining in the wild and in various captive facilities. Breeding efforts at the Graham, WA site (Point Defiance Zoo and Aquarium) have involved artificial insemination with fresh or frozen semen in an effort to increase population and maximize the genetic potential of the stock. Electron microscopic observations were made in semen specimens obtained by electro-ejaculation from mature males prior to their use in an effort to determine semen parameters that might be useful in guiding breeding procedures. Sperm samples were either fixed immediately or treated with capacitating media and fixed after 4 to 7 hr of incubation. Many of the specimens examined were pyospermic (white cell in semen) and showed evidence of spermophagy, primarily by neutrophils. Of the six animals surveyed, only one showed little evidence of spermophagy, and three had extensive pyospermia and spermophagy but this finding was not correlated with fertility. Samples fixed immediately as well as those incubated for several hours showed evidence of spermophagy, indicating that the phagocytosis was not the result of culture. Gene pool restriction and/or captive stress may be contributing factors of reduced semen quality.

Animals↗
PubMed1994

Molecular genetic investigations of the mechanism of tumourigenesis in von Hippel-Lindau disease: analysis of allele loss in VHL tumours.

Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome characterised by the development of retinal and central nervous system haemangioblastomas, renal cell carcinoma (RCC), phaeochromocytoma and pancreatic tumours. The VHL disease gene maps to chromosome 3p25-p26. To investigate the mechanism of tumourigenesis in VHL disease, we analysed 24 paired blood/tumour DNA samples from 20 VHL patients for allele loss on chromosome 3p and in the region of tumour suppressor genes on chromosomes 5, 11, 13, 17 and 22. Nine out of 24 tumours showed loss of heterozygosity (LOH) at at least one locus on chromosome 3p and in each case the LOH included the region to which the VHL gene has been mapped. Chromosome 3p allele loss was found in four tumour types (RCC, haemangioblastoma, phaeochromocytoma and pancreatic tumour) suggesting a common mechanism of tumourigenesis in all types of tumour in VHL disease. The smallest region of overlap was between D3S1038 and D3S18, a region that corresponds to the target region for the VHL gene from genetic linkage studies. The parental origin of the chromosome 3p25-p26 allele loss could be determined in seven tumours from seven familial cases; in each tumour, the allele lost had been inherited from the unaffected parent. Our results suggest that the VHL disease gene functions as a recessive tumour suppressor gene and that inactivation of both alleles of the VHL gene is the critical event in the pathogenesis of VHL neoplasms. Four VHL tumours showed LOH on other chromosomes (5q21, 13q, 17q) indicating that homozygous VHL gene mutations may be required but may not be sufficient for tumourigenesis in VHL disease.

Alleles↗
PubMed1994

Molecular genetic investigation of sporadic renal cell carcinoma: analysis of allele loss on chromosomes 3p, 5q, 11p, 17 and 22.

To investigate the role of tumour-suppressor genes on the short arm of chromosome 3 in the mechanism of tumorigenesis in non-familial renal cell carcinoma, we analysed 55 paired blood-tumour DNA samples for allele loss on chromosome 3p and in the region of known or putative tumour-suppressor genes on chromosomes 5, 11, 17 and 22. Sixty-four per cent (35/55) of informative tumours showed loss of heterozygosity (LOH) of at least one locus on the short arm of chromosome 3, compared with only 13% at the p53 tumour-suppressor gene and 6% at 17q21. LOH at chromosome 5q21 and 22q was uncommon (2-3%). Detailed analysis of the regions of LOH on chromosome 3p suggested that, in addition to the VHL gene in chromosome 3p25-p26, mutations in one or more tumour-suppressor genes in chromosome 3p13-p24 may be involved in the pathogenesis of sporadic renal cell carcinoma (RCC). We also confirmed previous suggestions that chromosome 3p allele loss is not a feature of papillary RCC (P < 0.05).

Adult↗
PubMed1994

Cytological screening and management of abnormalities in prevention of cervical cancer: an overview with stochastic modelling.

AIMS: To develop a mathematical model of the histological changes of precancer and the development of invasive cancer and how these are related to cytological findings. To use this to investigate the effects on incidence of cervical cancer, number of smear tests and colposcopies, of different schedules for cervical screening, and the clinical management policies for dyskaryosis. METHODS: A stochastic model was developed relating the available data on tissue progression to the cytological findings. Two strategies, A and B, were compared: under A, women with any abnormal smear receive immediate colposcopy and treatment; under B, women with mild or borderline dyskaryosis have repeated smears at six monthly intervals with colposcopy only for persistent abnormalities. RESULTS: The model predicted an incidence of invasive cervical cancer in an unscreened population of women aged over 18 years of 5.9 per 10,000 per year. With 70% coverage and three yearly screening under strategy A, the incidence fell to 2.00 and under B to 2.10. The number of smears required was similar but A required two to three times as many colposcopies as B. Raising the coverage to 90% reduced the incidence to around 1 per 10,000 per year but changing the screening interval, the specificity or sensitivity of cytology had much less effect. CONCLUSION: The model has been tested under a wide range of possible variations in natural history, specificity and sensitivity of cytology. For low grade smear abnormalities, open colposcopic referral is predicted to reduce invasive cancer only slightly more than repeat cytology, at the expense of much additional colposcopy. Improving cytological coverage is suggested as more effective in reducing invasive cancer than increased use of colposcopy or more frequent screening.

Colposcopy↗
PubMed1993

Genetic linkage between von Hippel-Lindau disease and three microsatellite polymorphisms refines the localisation of the VHL locus.

Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome characterised by the development of retinal and central nervous system haemangioblastomas, renal cell carcinoma and phaeochromocytoma. The gene for VHL disease has been mapped to chromosome 3p25-p26 and presymptomatic diagnosis using linked DNA markers is available. We have previously mapped the VHL disease gene to a 4 cM interval between D3S1250 and D3S18. To increase access to presymptomatic diagnosis and to accelerate progress towards isolating the VHL disease gene we attempted to identify microsatellite DNA markers linked to the disease gene by genetic linkage analysis in 29 families. We found significant linkage between the VHL disease gene and dinucleotide (CA) repeat polymorphisms at D3S1038 (Zmax = 22.24 at theta = 0.01, CI 0.0001-0.06), D3S1110 (Zmax = 11.32 at theta = 0.07, CI 0.03-0.14) and D3S651 (Zmax = 7.73 at theta = 0.04, CI 0.008-0.13). We localised D3S1038 between D3S1250 and D3S601, and mapped D3S1110 and D3S651 centromeric to D3S1250. Multipoint linkage analysis mapped the VHL disease locus between D3S1038 and D3S18 with the maximum likelihood at D3S601. There was no evidence of locus heterogeneity. This study has (i) identified three microsatellite DNA markers in chromosome 3p25 linked to the VHL disease gene and (ii) narrowed the target region for the isolation of the VHL disease gene by positional cloning techniques. These findings will improve the management of families with VHL disease by improving the accuracy and availability of presymptomatic diagnosis using linked DNA markers, and will accelerate progress towards isolating the VHL disease gene.

Chromosome Mapping↗
PubMed1993

Evaluation of molecular genetic diagnosis in the management of familial adenomatous polyposis coli: a population based study.

A population based clinical and molecular genetic study of familial adenomatous polyposis coli (FAPC) was performed to investigate the value of molecular genetic analysis and ophthalmological assessment in the presymptomatic diagnosis of FAPC. The point prevalence of affected patients was 2.62 x 10(-5) (1/38,000) and the minimum heterozygote prevalence was estimated at 3.8 x 10(-5) (1/26,000). Eight of 33 (24%) probands were new mutations. Forty-eight asymptomatic relatives at 50% prior risk aged between 10 and 40 years were assessed for risk modification with linked DNA markers: in nine subjects (18%) the family structure was unsuitable for linkage based analysis, but 32 subjects were informative with a panel of intragenic and closely linked markers (25 had a combined age/DNA related risk of < 1% (low risk group) and seven were at high risk (DNA predicted risk > 99%)). Ophthalmological assessment for CHRPEs showed that 27/43 (63%) affected patients and high risk relatives and 0/18 low risk relatives had more than three CHRPEs. Interfamilial variation in CHRPE expression was apparent. This study has shown that DNA based risk modification with intragenic and closely linked DNA markers is informative in most FAPC families. In addition to the clinical benefits of presymptomatic diagnosis for FAPC, the reduction in screening for low risk relatives (365 person years in the present study) means that molecular genetic diagnosis of FAPC is a cost effective procedure.

Adenomatous Polyposis Coli↗
PubMed1992

Mild cervical dyskaryosis: safety of cytological surveillance.

How best to manage women who are found on cervical screening to have mild dyskaryosis remains controversial. Cytological surveillance misses some lesions picked up by colposcopy, but colposcopy is emotionally traumatic for women, the majority of whom will have a normal result. To determine what proportion of lesions are missed by cytological surveillance, and whether any abnormalities persist after colposcopy, we studied, by means of colposcopy and biopsy, the prevalence of cervical intraepithelial neoplasia (CIN) and subclinical human papillomavirus infection (HPVI) in two groups of patients who had had a first smear showing mild dyskaryosis at least 24 months earlier. One group was recruited from a centre practising cytological surveillance, with colposcopy for patients showing persistent or progressive cytological abnormality. The other group all had early colposcopy and treatment. Of 214 patients recruited into the cytological surveillance group, 70 (33%) had been referred for colposcopy within 24 months. Colposcopy of the remaining 144 (after a mean interval of 27 months from presentation) revealed that 54 (38%) were disease free, 64 (44%) had HPVI/CIN1, 8 (6%) had CIN2, and 18 (12%) had CIN3. A smear at that time identified 12 of the 18 (67%) with CIN3 as needing close cytological follow-up (1 patient) or prompt referral for colposcopy (11 patients). 137 women in the early colposcopy group attended for the study colposcopy (after a mean interval of 32 months from presentation). 37% were found to have some abnormality persisting after an earlier colposcopy, but none had CIN3. Cytological surveillance of mild dyskaryosis resulted in a 12% risk of patients having a small CIN3 lesion after 2 years, but this risk was reduced to 4% by the addition of a third repeat smear 12 months after the second. With such a policy only about a third of women would require colposcopy, and the risk of missing serious underlying precancerous changes would be low.

Adult↗
PubMed1992

Detection of loss of heterozygosity at the human TP53 locus using a dinucleotide repeat polymorphism.

Loss of heterozygosity at the TP53 locus occurs frequently in many types of cancer and requires polymorphic markers for detection. Several polymorphisms at the TP53 locus have been described previously, and polymerase chain reaction (PCR)-based assays have been developed to detect these polymorphisms. However, these polymorphisms have relatively low levels of heterozygosity and are often uninformative. We report here the detection of loss of heterozygosity at the TP53 locus in various human cancers by using a highly informative dinucleotide repeat polymorphism.

Base Sequence↗
PubMed1992

Somatic mutations at CA-repeat loci.

We found somatic mutations, detected as novel PCR bands, at three separate polymorphic CA-repeat loci. At one of these loci, analyzed in a three-generation pedigree, a new band generated from the same paternal allele was observed in four of six offspring. The other two children inherited the alternative paternal allele unchanged. Somatic mutations at two additional loci were identified upon subsequent comparison of banding patterns among 25 cancers and their corresponding normal tissues at 15 CA-repeat loci. Since somatic mutations of CA-repeats seem to be quite frequent, individuals who are mosaic for CA-repeat alleles at a particular locus probably are not unusual. Hence, the possibility of somatic mutation generating new length alleles at CA-repeat loci should be considered when one compares DNA samples, whether in forensic and paternity testing, loss of heterozygosity studies, or linkage analyses.

Alleles↗