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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
PubMed2002

The decision-to-delivery interval for emergency caesarean section: is 30 minutes a realistic target?

OBJECTIVE: To evaluate whether a 30-minute decision-to-delivery interval is a realistic target for emergency caesarean section. DESIGN: An audit of all emergency caesarean sections over five separate periods. SETTING: A district general hospital. PARTICIPANTS: Five groups of women (343 women) with an indication for emergency caesarean section. METHODS: Following an initial survey, a structured time sheet was introduced, followed by four other surveys to complete the audit cycle. MAIN OUTCOME MEASURE: The proportion of caesarean sections where the decision-to-delivery interval was achieved within 30 minutes. The reasons for delay. RESULTS: In the first survey of 73 emergency caesarean sections, the time to deliver the infant exceeded 30 minutes in 47 women (64%). The main sources of delay were transferring the women to the operating theatre and starting the anaesthetic. After the introduction of a structured time sheet, there was an improvement with each survey, but the target of 30 minutes was reached in only 71% of caesarean sections in the final survey. CONCLUSIONS: The introduction of a time sheet can improve the decision-to-delivery interval for emergency caesarean section; however, a universal standard of 100% in 30 minutes is unrealistic.

Cesarean Section↗
PubMed2001

Yeast Dam1p has a role at the kinetochore in assembly of the mitotic spindle.

During mitosis, replicated chromosomes are separated to daughter cells by the microtubule-based mitotic spindle. Chromosomes attach to the mitotic spindle through specialized DNA/protein structures called kinetochores, but the mechanism of attachment is not well understood. We show here that the yeast microtubule-binding protein, Dam1p, associates physically and functionally with kinetochores, suggesting a role in kinetochore attachment to the spindle. An epitope-tagged version of Dam1p colocalizes with the integral kinetochore component Ndc10p/Cbf2p in immunofluorescence analysis of chromosome spreads. In addition, Dam1p is associated preferentially with centromeric DNA as shown by chromatin immunoprecipitation experiments, and this association depends on Ndc10p/Cbf2p. We also demonstrate genetic interactions between DAM1 and CTF19 or SLK19 genes encoding kinetochore proteins. Although the defect caused by the dam1-1 mutation leads to activation of the spindle checkpoint surveillance system and consequent persistence of sister chromatid cohesion, the metaphase arrest spindle abnormally elongates, resulting in virtually complete chromosome missegregation. Execution point experiments indicate that Dam1p has a role in formation of a metaphase spindle and in anaphase spindle elongation. Finally, we have observed that the protein encoded by the dam1-1 allele becomes delocalized at the nonpermissive temperature, correlating with the subsequent onset of the mutant phenotype. Our studies are consistent with a role for Dam1p in attachment of sister chromatids through the kinetochore to the mitotic spindle before chromosome segregation.

Cell Cycle Proteins↗
PubMed2000

Identification and characterization of BPTF, a novel bromodomain transcription factor.

The bromodomain is a 110-amino-acid conserved structural region associated with proteins that regulate signal-dependent, nonbasal transcription. The bromodomain can regulate histone acetyl transferase activity and interacts specifically with acetylated lysine residues. A key role for bromodomain proteins in maintaining normal proliferation is indicated by the implication of several bromodomain proteins in cancer, with four of these identified at translocation breakpoints. We searched EST databases for novel bromodomain genes. The sequence from one EST was used to initiate generation of a full-length clone from a testis cDNA library. The completed sequence encodes a predicted protein of 2781 amino acids, which, in addition to the bromodomain, harbors further motifs characteristic of a transcriptional coactivator: two PHD fingers and an extensive glutamine-rich acidic domain. There are several other regions that are conserved with the Caenorhabditis elegans putative protein F26H11, which may be functionally homologous. The novel gene, called BPTF, is expressed in all tissues examined as a 10.5-kb transcript. The protein has extensive identity with the smaller FAC1 protein, suggesting that the two either are derived from the same locus or are synonymous. BPTF has been mapped to 17q23. Functional domains found within BPTF are consistent with a role for this protein in hormonally regulated, chromatin-mediated regulation of transcription.

Amino Acid Sequence↗
PubMed2000

A novel family of bromodomain genes.

The bromodomain is a structural motif characteristic of proteins involved in chromatin-dependent regulation of transcription. Bromodomain proteins have been identified as integral components of chromatin remodeling complexes and frequently possess histone acetyltransferase activity. Their encoding genes have been identified at translocation breakpoints, and at least one, CBP, is a tumor suppressor gene. We have identified a series of novel bromodomain genes by EST database and cDNA library screening. Comparison of sequences for four clones indicated that they represent genes belonging to a novel bromodomain family. Full-length sequences for these genes, which are widely expressed, predict encoded proteins of between 1527 and 1972 amino acids. In addition to a carboxy-terminal bromodomain, an adjacent PHD finger, and a WACZ motif, at least four other conserved novel motifs are present in each protein. The genes contain regions conserved with Drosophila Acf1 and Caenorhabditis elegans ZK783.4. The novel genes, termed BAZ1A, BAZ1B, BAZ2A, and BAZ2B, localize to chromosomes 14q12-q13, 7q11-q21, 12q24.3-qter, and 2q23-q24, respectively. Conservation of multiple domains throughout these genes with Acf1 indicates that they are likely to be components of chromatin remodeling complexes.

Amino Acid Sequence↗
PubMed2000

An alternative approach to the management dilemma of the mildly dyskaryotic smear based on audit of outcome.

We describe a study which takes an alternative approach to the management dilemma of the mildly dyskaryotic cervical smear. Two hundred and fifty women with a smear showing mild dyskaryosis were studied by auditing the clinical outcome as well as the cost. The cost of providing the colposcopy services during the index year was approximately pounds sterling 70000 for an average size district general Hospital. The proportion of women managed by the current guidelines and avoiding colposcopy after a first mildly dyskaryotic smear was only 30%. The majority of patients will eventually have colposcopy despite a policy of cytological surveillance. The alternative approach, to offer colposcopy immediately after the first mildly dyskaryotic smear, would result in a small increase in cost for our unit, equivalent to one extra colposcopy patient per week.

Colposcopy↗
PubMed2000

The use of ultrasound in the diagnosis of injuries of the ulnar collateral ligament of the thumb.

We describe the use of a specialist referral clinic and ultrasound assessment for all injuries to the ulnar collateral ligament of the metacarpophalangeal joint of the thumb presenting to an Accident and Emergency (A&E) department. Senior House Officers in the A&E department were able to correctly diagnose only 45% of the ruptures of the ulnar collateral ligament. The overall agreement between specialist clinic examination and ultrasound for injury to the ulnar collateral ligament was 85% (kappa 0.647). When compared with the operative finding ultrasound had a positive predictive value for rupture of 94%. An algorithm is presented for the assessment of injuries to the ulnar collateral ligament in A&E departments.

Adolescent↗
PubMed2000

Flow limitation in infants assessed by negative expiratory pressure.

Forced expiratory flows by the rapid compression technique are often used to assess airway function in infants; however, it remains unclear as to whether flow limitation (FL) is achieved. Studies in adults have used negative expiratory pressure (NEP) at the airway opening as a noninvasive technique to assess whether FL is achieved. An increase in flow with NEP indicates that FL has not been achieved, whereas no increase in flow with NEP indicates FL has been achieved. In the adult studies, the change in flow was assessed by visual inspection of the flow-volume curve. We evaluated whether NEP could be used to assess FL during forced expiration in infants. In addition, we quantified the change in flow secondary to NEP. We applied -5 cm H(2)O NEP to four infants during forced expiratory maneuvers. The step increase in flow with NEP was always less than 5% at high jacket compression pressures and consistent with FL. For one subject, FL was also confirmed from isovolume pressure flow-curves measured with an esophageal catheter. We conclude that NEP can be used in infants to assess FL during forced expiratory maneuvers by the rapid compression technique.

Adult↗
PubMed1999

Yeast Dam1p is required to maintain spindle integrity during mitosis and interacts with the Mps1p kinase.

We have identified a mutant allele of the DAM1 gene in a screen for mutations that are lethal in combination with the mps1-1 mutation. MPS1 encodes an essential protein kinase that is required for duplication of the spindle pole body and for the spindle assembly checkpoint. Mutations in six different genes were found to be lethal in combination with mps1-1, of which only DAM1 was novel. The remaining genes encode a checkpoint protein, Bub1p, and four chaperone proteins, Sti1p, Hsc82p, Cdc37p, and Ydj1p. DAM1 is an essential gene that encodes a protein recently described as a member of a microtubule binding complex. We report here that cells harboring the dam1-1 mutation fail to maintain spindle integrity during anaphase at the restrictive temperature. Consistent with this phenotype, DAM1 displays genetic interactions with STU1, CIN8, and KAR3, genes encoding proteins involved in spindle function. We have observed that a Dam1p-Myc fusion protein expressed at endogenous levels and localized by immunofluorescence microscopy, appears to be evenly distributed along short mitotic spindles but is found at the spindle poles at later times in mitosis.

Carrier Proteins↗
PubMed1999

Forced expiratory maneuvers in very young children. Assessment of flow limitation.

The application of negative expiratory pressure (NEP) to the airway opening during forced expiratory maneuvers has recently been described as a noninvasive method to assess whether flow limitation is achieved in adults. This methodology has great potential for extending the measurement of forced expiratory maneuvers to young children who may not produce maximal efforts as reproducibly as adults. We used NEP to assess flow limitation in 10 children between 3 and 5 yr of age. NEP was well tolerated by all subjects. With the application of NEP, there was not a step increase in flow, a finding consistent with flow limitation for the subjects. In addition to visual inspection, we proposed a method to quantify the change in flow during a short NEP. The flow-volume curves obtained with and without NEP were visually the same, other than the flow transients produced by NEP. The calculated values of FVC and FEF25-75 were not significantly different when measured from flow- volume curves with and without NEP. There was a statistically significant increase in FEV1 with NEP; however, the group mean increase in FEV1 was less than 2%. We conclude that NEP may be a useful technique to determine whether flow limitation has been achieved in young children performing forced expiratory maneuvers.

Child, Preschool↗
PubMed1998

Regional assignment and expression analysis of 29 expressed sequence tags mapped to chromosome 3.

Of 311 expressed sequenced tags (ESTs) mapped to single human chromosomes by analysis of a monochromosome somatic cell hybrid panel, 29 were localized to chromosome 3. Analysis of somatic cell hybrid lines containing different regions of chromosome 3 has enabled the regional assignment of these 29 ESTs to 13 of 23 intervals covering chromosome 3. Northern analysis of 25 of the EST clones has provided information on the pattern of expression of potential genes represented by these transcripts in 16 human tissue types. Nine of the clones hybridized solely to a transcript(s) in the testis, 12 hybridized to transcripts in testis and other tissues, and 4 hybridized with transcripts in testis and other tissues but in addition have testis-specific transcript sizes. These ESTs will provide useful markers throughout chromosome 3 for the development of physical and transcription maps. In addition, they provide candidate genes for disease loci mapping to the intervals defined by the chromosome 3 deletion panel.

Chromosome Mapping↗
PubMed1998

Characteristics of fresh and frozen-thawed red wolf (Canis rufus) spermatozoa.

Ejaculates of the red wolf (Canis rufus) were evaluated immediately after collection and freeze-thawing to initiate a reproductive database for this endangered species. Electroejaculates from 13 adult red wolves collected during the breeding season (February-March; n=25; 1-3 collections/male) had a mean volume of 4.7+/-0.7 ml, 146.5+/-25.7 x 10(6) spermatozoa/ml and 71.2% motile spermatozoa. The mean proportion of cells with normal morphology was 73.6+/-3.2% (range, 20.3-93.7%), with 64% of ejaculates (16/25) containing 70-90% normal spermatozoa. The four most predominant abnormalities were a coiled flagellum (8.1%), a bent flagellum (4.7%), a bent midpiece with no cytoplasmic droplet (3.3%;), and a detached head defect (6.4%). After cooling in glycerolated extender, semen was frozen using a pelleting method on dry ice before plunging into liquid nitrogen. Pellets were thawed in phosphate buffered saline and examined for % sperm motility, normal morphology, viability and intact acrosomes. There was a decline (P < 0.05) in sperm motility (approximately 40%) and percentage of normal sperm (11.9%) after freezing, but no change in the proportion of viable cells. After freezing, there was a marked decline (P < 0.05) in the proportion of intact acrosomes from 74.5% to 55.5% which was accompanied by an increased proportion (P < 0.05) of partial acrosomes from 11.9% to 35.8%. These data demonstrate that, although red wolf spermatozoa can survive freeze-thawing using a technique common for domestic dog sperm, the finding of significant acrosome damage reveals (1) likely species specificity in the Canis genus and (2) the need for refining sperm cryopreservation technology for the red wolf.

Acrosome↗
PubMed1998

Characterisation of the coding sequence and fine mapping of the human DFFRY gene and comparative expression analysis and mapping to the Sxrb interval of the mouse Y chromosome of the Dffry gene.

DFFRY (the Y-linked homologue of the DFFRX Drosophila fat-facets related X gene) maps to proximal Yq11.2 within the interval defining the AZFa spermatogenic phenotype. The complete coding region of DFFRY has been sequenced and shows 89% identity to the X-linked gene at the nucleotide level. In common with DFFRX , the potential amino acid sequence contains the conserved Cys and His domains characteristic of ubiquitin C-terminal hydrolases. The human DFFRY mRNA is expressed in a wide range of adult and embryonic tissues, including testis, whereas the homologous mouse Dffry gene is expressed specifically in the testis. Analysis of three azoospermic male patients has shown that DFFRY is deleted from the Y chromosome in these individuals. Two patients have a testicular phenotype which resembles Sertoli cell-only syndrome, and the third diminished spermatogenesis. In all three patients, the deletions extend from close to the 3' end into the gene, removing the entire coding sequence of DFFRY. The mouse Dffry gene maps to the Sxrb deletion interval on the short arm of the mouse Y chromosome and its expression in mouse testis can first be detected between 7.5 and 10.5 days after birth when type A and B spermatogonia and pre-leptotene and leptotene spermatocytes are present.

Adult↗
PubMed1998

Mph1, a member of the Mps1-like family of dual specificity protein kinases, is required for the spindle checkpoint in S. pombe.

The spindle assembly checkpoint pathway is not essential for normal mitosis but ensures accurate nuclear division by blocking the metaphase to anaphase transition in response to a defective spindle. Here, we report the isolation of a new spindle checkpoint gene, mph1 (Mps1p-like pombe homolog), in the fission yeast Schizosaccharomyces pombe, that is required for checkpoint activation in response to spindle defects. mph1 functions upstream of mad2, a previously characterized component of the spindle checkpoint. Overexpression of mph1, like overexpression of mad2, mimics activation of the checkpoint and imposes a metaphase arrest. mph1 protein shares sequence similarity with Mps1p, a dual specificity kinase that functions in the spindle checkpoint of the budding yeast Saccharomyces cerevisiae. Complementation analysis demonstrates that mph1 and Mps1p are functionally related. They differ in that Mps1p, but not mph1, has an additional essential role in spindle pole body duplication. We propose that mph1 is the MPS1 equivalent in the spindle checkpoint pathway but not in the SPB duplication pathway. Overexpression of mad2 does not require mph1 to impose a metaphase arrest, which indicates a mechanism of spindle checkpoint activation other than mph1/Mps1p kinase-dependent phosphorylation. In the same screen which led to the isolation of mad2 and mph1, we also isolated dph1, a cDNA that encodes a protein 46% identical to an S. cerevisiae SPB duplication protein, Dsk2p. Our initial characterization indicates that S.p. dph1 and S.c. DSK2 are functionally similar. Together these results suggest that the budding and fission yeasts share common elements for SPB duplication, despite differences in SPB structure and the timing of SPB duplication relative to mitotic entry.

Amino Acid Sequence↗
PubMed1998

Semen parameters and electron microscope observations of spermatozoa of the red wolf, Canis rufus.

Semen parameters were evaluated on ejaculates of a captive population of red wolves (Canis rufus) sampled over two consecutive mating seasons. A total of 31 samples from 15 animals yielded mean sperm motility of 69.6 +/- 19.4%, mean sperm density of 131 +/- 124 x 10(6) ml-1, mean total number of spermatozoa of 470 +/- 465 x 10(6) and mean percentage morphologically abnormal spermatozoa of 35 +/- 11.8%. Restricting the data to animals sampled three times or more or limiting the samples to proven breeders resulted in statistically non-significant differences in these numbers (P < 0.05). When compared with data from other canines the seminal parameters of red wolves are at the lower extremes of the range. In particular the proportion of morphologically abnormal spermatozoa (35%) is approximately twice that seen in other canine species. Light microscopic analysis of abnormal forms revealed that almost half (45%) were bent defects, another 40% were secondary defects (coiled, detached and immature) and 15% were primary defects. Electron microscopy confirmed the presence of substantial numbers of morphologically abnormal forms including double-headed and double-flagellar cells, bent or kinked forms especially in the neck region, acrosomal abnormalities and bizarre spermatids. Approximately one-third of the samples also showed the presence of white blood cells, in some cases demonstrating sperm phagocytosis (spermophagy). These results are consistent with the concept of declining sperm parameters associated with restricted gene pools in numerically limited populations. However, alternative explanations are also explored.

Animals↗
PubMed1998

The management dilemma of the mildly abnormal smear: fact or fiction?

For at least 10 years, there has been much controversy regarding the management of women presenting with a first mildly dyskaryotic cervical smear. Argument has centred on many key issues, including the risk of progression to more serious disease, the anxiety caused to the patient, the risk of overtreating patients with minor disease and, more recently, the financial implications of prompt intervention and treatment. Essentially, it has been established for many years that only two main management options are appropriate. The first is a policy of referring all patients with mild dyskaryosis for prompt colposcopy and intervention. The second option is to keep such patients under cytological surveillance, with recourse to colposcopy only if the lesion persists or progresses on subsequent cytological screening. This review article aims at appraising the evidence that is currently available in an attempt to try and resolve the management dilemma posed by a mildly abnormal smear.

Colposcopy↗
PubMed1997

Identification and characterization of BRDT: A testis-specific gene related to the bromodomain genes RING3 and Drosophila fsh.

The RING3 gene encodes a 90-kDa mitogen-activated nuclear protein. In proliferating cells, including in leukemia, RING3 has serine-threonine kinase and autophosphorylation activities. The cloning of D26362, a gene closely related to RING3, suggests a gene family. RING3 and D26362 are also related to the Drosophila developmental gene fsh. A database search for further members of the RING3 family identified an EST derived from a testis-specific library. cDNA clones representing the full coding sequence of the gene were isolated. The gene encodes a protein of 947 amino acids with extensive homology to RING3, D26362, and fsh. Similar to these proteins, it possesses two bromodomain motifs and a PEST sequence. Northern analysis of 16 normal tissues and eight cancer cell lines shows transcripts of 3.5 and 4.0 kb expressed specifically in testis. The gene has been named BRDT (for bromodomain, testis specific). PCR analysis of a panel of monochromosomal human/rodent hybrid cell lines and the GeneBridge 4 panel of radiation hybrids localizes the gene to chromosome 1p between markers WI-7719 and WI-3099 (D1S2154).

Amino Acid Sequence↗
PubMed1997

Identification of two novel human putative serine/threonine kinases, VRK1 and VRK2, with structural similarity to vaccinia virus B1R kinase.

A cDNA library enriched for human fetal-specific liver genes was constructed by suppressive subtractive hybridization. EST fls223 generated from this library was found to represent a novel putative serine/threonine (Ser/Thr) kinase. A full-length clone isolated for this gene encodes a protein of 396 amino acids. The amino acid sequence has 40% identity over 305 amino acids with the B1R Ser/Thr protein kinase of vaccinia virus. This gene has therefore been named VRK1 (vaccinia virus B1R kinase related kinase). VRK1 was also found to have sequence identity (62.0% over 481 nucleotides) to a database EST. A full-length clone for this EST was isolated and sequenced. Conceptual translation predicts a protein of 508 amino acids that, like VRK1, has similarity to B1R kinase (38.7% identity over 300 amino acids). This gene has been named VRK2. Comparison of VRK1 with VRK2 indicates that they encode structurally related putative Ser/Thr protein kinases. Northern analysis shows that expression of both genes is widespread and elevated in highly proliferative cells, such as testis, thymus, and fetal liver. B1R kinase is reported to be essential for DNA replication of vaccinia virus. The similarity of VRK1 and VRK2 to B1R indicates that these genes may have similar functions.

Amino Acid Sequence↗