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M H Jones

Publications and source records attributed to M H Jones.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1997

Chromosomal assignment of 311 sequences transcribed in human adult testis.

A total of 311 expressed sequence tags (ESTs) derived from human adult testis have been assigned to human chromosomes by Southern analysis of a monochromosome somatic cell hybrid panel. Over 70% of the ESTs show conservation to hamster and mouse DNA, and the overall distribution of transcripts correlates well with physical chromosome size and to a greater extent with male meiotic chromosome length. The notable exception is the X chromosome, for which the number of testis-derived ESTs is greatly underrepresented. This finding may reflect inactivation of the X chromosome during the meiotic phase of spermatogenesis and a consequent selection against large numbers of X-linked germ cell transcripts. Further analysis of the distribution of testis ESTs showed that the EST density remains significantly correlated with the recombination density of each autosome. Analysis of a comparable number (320) of brain EST autosome assignments showed no similar correlation. These data suggest a specific association between transcription in testis tissue and male meiotic recombination.

Adult↗
PubMed1996

Characterization of a novel human dynein-related gene that is specifically expressed in testis.

A novel dynein-related transcript (designated DNEL1) from human adult testis has been identified that can encode a protein with a size of 91087 Da. The complete nucleotide sequence of the open reading frame is the first to be described for a human dynein-related gene. Northern blot analysis of mRNA from 16 different tissues has shown that DNEL1 is expressed specifically in testis. Analysis of somatic cell hybrids has mapped DNEL1 to Chromosome (Chr) 17. Analysis of a panel of 129 whole genome radiaton hybrid clones including 17q22-q25.3 has placed DNEL1 in 17q distal to the ERBA2L locus. DNEL1 shares a high degree of sequence identity and amino acid similarity with the C-terminal region of the outer arm axonemal dynein beta-heavy chains derived from sea urchin and other species, but not to any gene encoding dynein intermediate or light chains described to date. The close similarity of DNEL1 to the C-terminal part of the axonemal beta-heavy chain may suggest an origin from a common progenitor gene and the testis-specific pattern of expression a possible role in sperm development or motility.

Adult↗
PubMed1996

Regular audit of colposcopic biopsies from women with a mildly dyskaryotic or borderline cervical smear results in fewer cases of CINIII.

Two years after introducing mandatory review of cases in which the cervical smear was discrepant with subsequent colposcopic or histological finding, the predictive accuracy of a first abnormal smear and the need for treatment were analysed. The results were compared with performance figures prior to this form of audit policy. Over 12 months 415 women referred for colposcopy were studied. Three per cent of patients with a single borderline smear and 6% with mild dyskaryosis had cervical intraepithelial neoplasia grade III (CINIII) revealed in histopathological examinations after colposcopy. Only 25% with a borderline smear and 33% with mild dyskaryosis required treatment. Of women with moderate dyskaryosis, 18% had a biopsy showing CINIII and 46% were treated. Of women with severe dyskaryosis in their cervical smear, 61% were shown to have CINIII or invasive cancer on biopsy and 90% were treated. Regular audit improved cytological prediction of grade of epithelial abnormality found on biopsy, allowing accurate, safe surveillance for minor smear abnormalities.

Adult↗
PubMed1996

The Drosophila developmental gene fat facets has a human homologue in Xp11.4 which escapes X-inactivation and has related sequences on Yq11.2.

EST 221 derived from human adult testis detects homology to the Drosophila fat facets gene (fat) and has related sequences on both the X and Y chromosomes mapping to Xp11.4 and Yq11.2 respectively. These two loci have been termed DFFRX and DFFRY for Drosophila fat facets related X and Y. The major transcript detected by EST 221 is-8 kb in size and is expressed widely in a range of 16 human adult tissues. RT-PCR analysis of 13 different human embryonic tissues with primers specific for the X and Y sequences demonstrates that both loci are expressed in developing tissues and quantitative RT-PCR of lymphoblastoid cell lines carrying different numbers of X chromosomes reveals that the X-linked gene escapes X-inactivation. The amino acid sequence (2547 residues) of the complete open reading frame of the X gene has 44% identity and 88% similarity to the Drosophila sequence and contains the conserved Cys and His domains characteristic of deubiquitinating enzymes, suggesting its biochemical function may be the hydrolysis of ubiquitin from protein-ubiquitin conjugates. The requirement of faf for normal oocyte development in Drosophila combined with the map location and escape from X-inactivation of DFFRX raises the possibility that the human homologue plays a role in the defects of oocyte proliferation and subsequent gonadal degeneration found in Turner syndrome.

Adult↗
PubMed1996

The mildly abnormal cervical smear: patient anxiety and choice of management.

Argument continues over the best management of women with a first mildly dyskaryotic cervical smear: should they be referred for prompt colposcopy, or should they be kept under cytological review, with recourse to colposcopy if the abnormality persists? One consideration is the amount of anxiety generated. We measured anxiety, retrospectively, in two groups of women who had been managed by one or other method. Colposcopy caused more anxiety than cytological surveillance. When told that their smear was mildly abnormal, 47% of the immediate-colposcopy group (n = 182), compared with 33% of the surveillance group (n = 163), thought they had cancer. None the less, there was a general preference for immediate colposcopy. Whatever the relative merits of these two strategies for clinical management, it is clear that both forms of screening, and especially colposcopy, demand better information for patients.

Adult↗
PubMed1995

Expression analysis, genomic structure, and mapping to 7q31 of the human sperm adhesion molecule gene SPAM1.

During the course of systematic sequence tag analysis of clones isolated from an adult testis cDNA library, clones 296 and 576 were found to detect 71-74% sequence identity to the guinea pig sperm surface protein PH-20. This surface protein is involved in sperm-egg adhesion in the guinea pig. Nucleotide sequence for 1919 bp of human DNA from a series of overlapping cDNA clones isolated from a testis cDNA library confirmed the sequence identity within a 1527-bp open reading frame to be 71-74% to the guinea pig gene and the similarity to be 60% for the predicted protein of 509 amino acids. Southern blot analysis of human genomic DNA and DNA from somatic cell hybrids indicates that the gene (SPAM1) is unique and does not form part of a larger family and that it maps to chromosome 7. Fluorescence in situ hybridization with yeast artificial chromosome (YAC) clones isolated from the CEPH megaYAC library has refined this localization to 7q31. PCR analysis of genomic DNA and YAC clone DNA has shown that the 1919 bp of the gene that has been cloned covers approximately 11 kb of genomic DNA and is encoded by at least 4 exons. Northern analysis of poly(A)+ mRNA from a range of 16 human tissues has demonstrated that expression of the gene as a single 2.4-kb transcript is strictly limited to the testis.

Adult↗
PubMed1995

Characterization and functional ordering of Slu7p and Prp17p during the second step of pre-mRNA splicing in yeast.

Temperature-sensitive alleles in four genes (slu7-1, prp16-2, prp17-1, and prp18-1) are known to confer a specific block to the second chemical step of pre-mRNA splicing in vivo in the yeast Saccharomyces cerevisiae. Previous studies showed that Prp16p and Prp18p are required solely for the second step in vitro. The RNA-dependent ATPase, Prp16p, functions at a stage in splicing when ATP is required, whereas Prp18p functions at an ATP-independent stage. Here we use immunodepletion to show that the roles of Slu7p and Prp17p are also confined to the second step of splicing. We find that extracts depleted of Prp17p require both Prp17p and ATP for slicing complementation, whereas extracts depleted of Slu7p require only the addition of Slu7p. These different ATP requirements suggest that Prp16p and Prp17p function before Prp18p and Slu7p. Although SLU7 encodes an essential gene product, we find that a null allele of prp17 is temperature-sensitive for growth and has a partial splicing defect in vitro. Finally, high-copy suppression experiments indicate functional interactions between PRP16 and PRP17, PRP16 and SLU7, and SLU7 and PRP18. Taken together, the results suggest that these four factors may function within a multi-component complex that has both an ATP-dependent and an ATP-independent role in the second step of pre-mRNA splicing.

Adenosine Triphosphate↗
PubMed1995

Outpatient oral sulindac to prevent recurrence of preterm labor.

OBJECTIVE: To assess the efficacy and safety of oral sulindac in preventing the recurrence of preterm labor. METHODS: This was a randomized, double-blind, placebo-controlled study of patients between 24-34 weeks' gestation with preterm labor treated with intravenous magnesium sulfate. After successful tocolysis, patients were randomized by the pharmacy to receive either oral sulindac (200 mg) or placebo (once orally every 12 hours) for 7 days. RESULTS: Sixty-nine patients were enrolled (34 in the sulindac group, 35 controls). No significant differences were found with respect to time gained in utero (40 +/- 4.4 versus 31 +/- 3.4 days, P = .1), delivery at more than 35 weeks' gestation (20 versus 18, P = .70), recurrent preterm labor (11 versus 13, P = .88), birth weight (2528 +/- 646 versus 2459 +/- 707 g, P = .68), or time spent in the neonatal intensive care unit (4.2 +/- 12.9 versus 5.7 +/- 13.5 days, P = .63) for the sulindac and control groups, respectively. However, in women who failed therapy (ie, those who delivered before 37 weeks' gestation or required readmission for tocolysis), there was a significantly longer interval between the start of therapy and failure in the sulindac group (25.9 +/- 3.4 days, n = 26) than in the control group (15.2 +/- 2.8 days, n = 25; P < .05). CONCLUSION: The use of oral sulindac for 1 week after successful parenteral tocolysis failed to reduce the overall rate of preterm birth. In women who delivered prematurely or required readmission for tocolysis, oral sulindac significantly prolonged the interval from the start of therapy until delivery or readmission. Moreover, this benefit was achieved without observable adverse effects on the fetus.

Administration, Oral↗
PubMed1994

A set of ninety-seven overlapping yeast artificial chromosome clones spanning the human Y chromosome euchromatin.

Contiguous arrays of yeast artificial chromosomes (YACs) extending from proximal heterochromatic Yq into the pseudoautosomal portion of the Y chromosome and separated by a small interval at the centromere have been constructed. A total of 97 YACs have been aligned along the Y chromosome by STS content analysis using 222 sequence tagged sites (STSs) that detect 263 loci. Forty-five of the STSs used are novel. Their inclusion provides a significant improvement over previously available maps on the density of STS coverage along the Y chromosome, reducing the average spacing to 120 kb assuming a length of 30 Mb for the euchromatin. The average size of 61 YACs determined by pulsed-field gel electrophoresis analysis was at least 0.9 Mb. Minor differences noted between the ordering of STSs on this map compared with those previously reported may be attributed to inherent polymorphism between the Y chromosomes used to construct the YAC libraries.

Base Sequence↗
PubMed1994

The identification of novel gene sequences of the human adult testis.

To facilitate the characterization of genetic expression in human adult testis, expressed sequence tag analysis of cDNAs from this tissue has been undertaken. Over 180 kb of DNA sequence has been determined and used to search the GenBank database. The results from the first 359 cDNA clones analyzed indicate that the sequences could be sorted into several categories with a high proportion being novel. Twenty-five clones (7%) showed 100% identity with human genes, 11 (3%) with prokaryotic sequences, 21 (5%) with between 60 and 95% similarity to human genes, 27 (8%) with between 60 and 95% similarity to genes from other species, and 33 (9%) with matches to human repeat sequences. Two hundred forty-two (67%) showed no significant matches and thus are likely to represent novel transcripts. In comparison to similar studies on human brain tissue and a hepatoma cell line, the findings indicate that the matches in the testis transcript population appear to be identifying a different spectrum of gene sequences.

Adult↗
PubMed1994

Allelotype of uterine cancer by analysis of RFLP and microsatellite polymorphisms: frequent loss of heterozygosity on chromosome arms 3p, 9q, 10q, and 17p.

Cancers in which mutations have been identified in putative tumor suppressor genes, such as the TP53 gene, the retinoblastoma (RBI) gene, the adenomatous polyposis coli (APC) gene, and the Wilms tumor (WTI) gene, frequently show loss of the corresponding allele on the homologous chromosome. To identify locations of tumor suppressor genes involved in uterine cancer, we examined loss of heterozygosity (LOH) by using genomic probes detecting RFLPs in 35 uterine cancers at 29 loci throughout the genome, and with highly informative microsatellite markers in 21 uterine cancers at nine putative or known tumor suppressor gene loci. High frequencies of allelic loss found at loci on 3p (71%), 9q (38%), 10q (35%), and 17p (35%) suggest that tumor suppressor genes involved in uterine carcinogenesis exist in these regions. There were no significant differences in frequencies of LOH between cancers of the uterine cervix and cancers of the uterine endometrium at any of the loci tested.

Adenocarcinoma↗