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Biomedical subjects

M H Jones

Publications and source records attributed to M H Jones.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Isolation and characterization of 19 dinucleotide repeat polymorphisms on chromosome 3p.

We have screened cosmids on chromosome 3p for (dC-dA)n.(dG-dT)n dinucleotide-repeat sequences. Eighty-nine of 155 cosmids (58%) contained (dC-dA)n.(dG-dT(n repeats as determined by colony hybridization with a (dG-dT)10 oligonucleotide probe; 29 of these were subcloned and the sequences flanking the dinucleotide repeats were determined. Nineteen of the 24 loci examined for polymorphisms by PCR were found to be polymorphic with heterozygosities ranging from 3% to 86%. These dinucleotide repeat polymorphisms will be useful markers for high-resolution mapping of genes that have been localized to 3p, including tumour suppressor genes associated with several types of cancer and genes responsible for various hereditary disorders, such as von Hippel-Lindau disease.

Animals↗
PubMed1992

Deletion mapping of chromosome 3p in female genital tract malignancies using microsatellite polymorphisms.

We have constructed deletion maps of chromosome 3p for cancers of the female genital tract (uterine endometrium, uterine cervix and ovary). The tumours were tested for loss of heterozygosity using CA-repeat polymorphisms. The high degree of informativeness of these markers allowed the construction of detailed deletion maps from a relatively small number of samples. A common region of deletion was identified at chromosome 3p13-21.1 in endometrial cancer and at 3p13-14.3 in cervical cancer; 5 out of 13 (38%) endometrial cancers and six out of eight (75%) cervical cancers showed loss of heterozygosity at these regions. In ovarian cancer a separate common region of deletion was identified at 3p21.1-22; two out of four (50%) ovarian cancers had alleles deleted at this region. These data suggest the presence of a tumour-suppressor gene(s) for endometrial and cervical cancer at 3p13-21.3 and a separate gene at 3p21.1-22 that is involved in the carcinogenesis of ovarian cancer.

Adenocarcinoma↗
PubMed1990

Unexpected flexibility in an evolutionarily conserved protein-RNA interaction: genetic analysis of the Sm binding site.

Human autoantibodies of the Sm specificity recognize a conserved set of proteins found in the U class small nuclear ribonucleoproteins (U snRNPs), key trans-acting factors involved in the splicing of mRNA precursors. The Sm protein binding site in U snRNAs is unusual because of its single-stranded nature and its simple sequence motif (AU5-6GPu). Here we use genetics to probe this specific protein-RNA interaction by saturation mutagenesis of the Sm binding site of the Saccharomyces cerevisiae U5 snRNA. The assay system used to analyze these mutations takes advantage of a conditionally expressed U5 gene which does not support growth under non-permissive conditions; U5 genes containing Sm site mutations were tested for their ability to complement this lethal phenotype. Our results indicate that the Sm binding site is remarkably tolerant to mutation despite its high degree of conservation, suggesting that relatively few or redundant specific contacts can determine recognition of single-stranded RNA by protein. A complementary biochemical analysis of these mutants demonstrates that integrity of the Sm site is necessary for snRNP stability in vivo and in vitro.

Autoantigens↗
PubMed1988

Analysis of clustered point mutations in the human ribosomal RNA gene promoter by transient expression in vivo.

We have mapped the cis regulatory elements required in vivo for initiation at the human rRNA promoter by RNA polymerase I. Transient expression in COS-7 cells was used to evaluate the transcription phenotype of clustered base substitution mutations in the human rRNA promoter. The promoter consists of two major elements: a large upstream region, composed of several domains, that lies between nucleotides -234 and -107 relative to the transcription initiation site and affects transcription up to 100-fold and a core element that lies between nucleotides -45 and +20 and affects transcription up to 1000-fold. The upstream region is able to retain partial function when positioned within 100-160 nucleotides of the transcription initiation site, but it cannot stimulate transcription from distances of greater than or equal to 600 nucleotides. In addition, we demonstrate, using mouse-human hybrid rRNA promoters, that the sequences responsible for human species-specific transcription in vivo appear to reside in both the core and upstream elements, and sequences from the mouse rRNA promoter cannot be substituted for them.

Animals↗
PubMed1988

A method for measuring skin tension.

A simple device for measuring skin tension across a surgical incision was developed and tested. The device consists of a semicircular stainless steel stress member fitted with strain gauges in a wheatstone bridge configuration. The stress member transforms the external strain to a level that allows the strain gauges to function within their full dynamic range of five percent. A strain gauge reader was used to digitize the strain. Forces ranging from 0.5 grams to 500 grams were reliably measured with the device. A calibration curve was constructed, relating force to strain. The data acquired from three surgical tests of the device indicate that it is extremely easy to use, takes very little time to operate, and is compact. The tensiometer may aid in the development of a more quantitative description of in vivo skin tension. It is also possible to indicate suture strength required for a particular incision or the direction of the incision to minimize scarring.

Electric Conductivity↗
PubMed1987

Saccharomyces cerevisiae has a U1-like small nuclear RNA with unexpected properties.

Previous experiments indicated that only a small subset of the approximately equal to 24 small nuclear RNAs (snRNAs) in Saccharomyces cerevisiae have binding sites for the Sm antigen, a hallmark of metazoan small nuclear ribonucleoproteins (snRNPs) involved in pre-messenger RNA splicing. Antibodies from human serum to Sm proteins were used to show that four snRNAs (snR7, snR14, snR19, and snR20) can be immunoprecipitated from yeast extracts. Three of these four, snR7, snR14, and snR20, have been shown to be analogs of mammalian U5, U4, and U2, respectively. Several regions of significant homology to U1 (164 nucleotides) have now been found in cloned and sequenced snR19 (568 nucleotides). These include ten out of ten matches to the 5' end of U1, the site known to interact with the 5' splice site of mammalian introns. Surprisingly, the precise conservation of this sequence precludes perfect complementarity between snR19 and the invariant yeast 5' junction (GTATGT), which differs from the mammalian consensus at the fourth position (GTPuAGT).

Animals↗
PubMed1983

The effect of chemical mutagens on purine and pyrimidine nucleotide biosynthesis.

Nucleotide biosynthesis in Novikoff hepatoma cells is markedly altered by a variety of chemical mutagens, whether the mechanism of mutagenesis is by base substitution, covalent binding (adduct formation), intercalation, or cross-linking of DNA. The compounds investigated (N-methyl-N'-nitro-N-nitrosoguanidine, 4-nitroquinoline 1-oxide, 9-aminoacridine, and mitomycin C), at concentrations that cause some inhibition of RNA and DNA synthesis, bring about a large increase in the pool levels of all four nucleoside triphosphates. At the same time, reactions leading to the synthesis of CTP from exogenous uridine and GTP and ATP from exogenous hypoxanthine are severely inhibited. The formation of UTP from uridine and ATP from adenosine, by more direct phosphorylation reactions, appears relatively unaffected. The increase in nucleotide pool size cannot be accounted for by a corresponding increase in de novo purine and pyrimidine nucleotide synthesis, as experiments with labeled formate and aspartate show similar inhibitions by the mutagens. With the salvage precursors, [3H]uridine and [3H]hypoxanthine, the mutagens can produce a widely divergent reduction in the labeling of RNA-CMP versus RNA-UMP and of RNA-GMP versus RNA-AMP, mostly a result of these agents causing large differences in the specific activities of the respective triphosphate precursors. These observations suggest that, in addition to the reactions with DNA, nucleotide biosynthesis could be another important biochemical target of chemical mutagens.

4-Nitroquinoline-1-oxide↗
PubMed1978

The relationship of some copper (II) complexes of facultative tetrathioethers to the coordination environment in the "blue" copper proteins.

The facultative potentially tetradentate thioether ligands 1,2-bis(methylthioethylthio)ethane (2,2,2), 1,3-bis(2-methylthioethylthio)propane (2,3,2) and 1,2-bis(3-methylthiopropylthio)ethane (3,2,3) react with copper(II) salts to form Cu2(2,2,2)Cl4, Cu3(ligand)X6 (ligand = 2,3,2 and 3,2,3 X = Cl; ligand = 2,2,2 2,3,2 and 3,2,3 X = Br), and Cu(ligand)(ClO4)2. The stoichiometry and structures of these complexes are discussed in terms of the steric demands of the ligand and the nature of the halide. The [Cu(2,3,2)(ClO4)] ClO4 and [Cu(3,2,3)(ClO4) [ClO4 complexes have electronic spectra which exhibit the intense 600 nm band characteristic of the "blue" copper proteins. In fact, the spectrum of [Cu(2,3,2)(ClO4)]ClO4 is very similar to that of pseudomonas aeroginosa azurin.

Chemical Phenomena↗
PubMed1975

Automatic operant response procedure ('play-test') for the study of auditory perception of neurologically impaired infants.

Ten babies with cerebral palsy of varying types and degrees (age-range 10 to 27 months) participated in an initial exploratory study designed to determine the effectiveness of an automated, two-choice audio feedback system (Playtest') for evaluation of the auditory perception and processing capabilities of neurologically impaired infants. The major components of the 'Playtest' are a master control unit and two toy-like switches which are attached to the baby's crib. By playing with the 'toys', the baby is able to listen to one of two pre-recorded audio stimuli, music or a monotone hum. Frequency and duration of the baby's self-selected listening responses are automatically recorded on meters inside the control unit and provide a precise numerical record over an extended period of time. In this study the handicapped infants were physically able to operate the apparatus and demonstrated highly significant preferential listening. Comparison of the recorded data from the study infants with those from normal infants showed no significant difference between the performances of the two groups. The findings suggest that the 'Playtest' technique could be successfully applied to the objective assessment of auditory perception and processing abilities of neurologically impaired infants, whose handicaps often prevent them from effectively participating in other standardised test procedures. The principal advantages of the technique are that testing is done in the child's most familiar environment--his own crib at home--without the intrusion of other people, and the evaluation of hearing competence is a function of the baby's spontaneous self-selected responses to sound variables, and hence of his auditory discrimination.

Audiometry↗