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Biomedical subjects

C Hine

Publications and source records attributed to C Hine.

13 recordsLinked to original sources
PubMed2006

Cochlear implants: informing commissioning decisions, based on need.

Cochlear implantation is a high cost, low volume intervention which is provided to adults and children with profound hearing impairment. Demand is increasing in the UK as a result of improved technology, changes in intervention criteria and the national newborn hearing screening programme. In order to inform commissioning policy for cochlear implantation in five English primary care trusts, we reviewed the evidence and assessed the complexities of developing needs and of service provision assessment and planning. Our results indicated that the current level of provision was well below what would be expected if the majority of people meeting current criteria were given a cochlear implant. Gaps between the clinical intervention thresholds and the level of service commissioned have widened. Long-term cost effectiveness and incidence studies are needed to assess cochlear implantation in the light of these lower clinical intervention thresholds.

Child↗
PubMed2001

Hypocoagulable state of human preovulatory ovarian follicular fluid: role of sulfated proteoglycan and tissue factor pathway inhibitor in the fluid.

Ovulation accompanied by tissue damage can cause an increase in the level of tissue factor (TF) in the follicular fluid, triggering the extrinsic coagulation pathway. However, follicular fluid must block fibrin formation and maintain fluidity until the release of the oocyte at ovulation. The combination of sulfated proteoglycan, antithrombin, and TF pathway inhibitor (TFPI) appears to play a critical role in the hypocoagulability of human follicular fluid. When compared with plasma, folicular fluid differs markedly in the levels of a number of important coagulation proteins. Principal among these are 15-fold, 13-fold, and 3.7-fold increases in free TFPI, thrombin-antithrombin complex, and TF, respectively. The excessively prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT) of human ovarian follicular fluid appear to be primarily due to high concentrations of sulfated proteoglycans, which accelerate the inactivation of thrombin and the anti-Xa activity of TFPI. Thus, heparitinase treatment shortened the clotting times of follicular fluid and reduced the inhibition of thrombin by the proteoglycan fraction combined with a fraction containing antithrombin. The remaining prolongation of APTT and PT may be caused by high levels of free TFPI in follicular fluid, which were confirmed by Northern blotting analysis, demonstrating TFPI mRNA expression by granulosa cells.

Antithrombin III↗
PubMed2000

A randomised controlled trial and economic evaluation of a referrals facilitator between primary care and the voluntary sector.

OBJECTIVES: To compare outcome and resource utilisation among patients referred to the Amalthea Project, a liaison organisation that facilitates contact between voluntary organisations and patients in primary care, with patients receiving routine general practitioner care. DESIGN: Randomised controlled trial with follow up at one and four months. SETTING: 26 general practices in Avon. PARTICIPANTS: 161 patients identified by their general practitioner as having psychosocial problems. MAIN OUTCOME MEASURES: Primary outcomes were psychological wellbeing (assessed with the hospital anxiety and depression scale) and social support (assessed using the Duke-UNC functional social support questionnaire). Secondary outcomes were quality of life measures (the Dartmouth COOP/WONCA functional health assessment charts and the delighted-terrible faces scale), cost of contacts with the primary healthcare team and Amalthea Project, cost of prescribing in primary care, and cost of referrals to other agencies, over four months. RESULTS: The Amalthea group showed significantly greater improvements in anxiety (average difference between groups after adjustment for baseline -1.9, 95% confidence interval -3.0 to -0.7), other emotional feelings (average adjusted difference -0.5, -0.8 to -0.2), ability to carry out everyday activities (-0.5, -0.8 to -0.2), feelings about general health (-0.4, -0.7 to -0.1), and quality of life (-0.5, -0.9 to -0.1). No difference was detected in depression or perceived social support. The mean cost was significantly greater in the Amalthea arm than the general practitioner care arm ( pound153 v pound133, P=0. 025). CONCLUSION: Referral to the Amalthea Project and subsequent contact with the voluntary sector results in clinically important benefits compared with usual general practitioner care in managing psychosocial problems, but at a higher cost.

Adolescent↗
PubMed1999

Monkey hepatocytes efficiently express tissue factor pathway inhibitor (TFPI), in contrast with human and rat hepatocytes.

It has been reported that tissue factor pathway inhibitor (TFPI), a Kunitz-type protease inhibitor that regulates the extrinsic blood coagulation pathway, is not expressed in human, bovine, rabbit, or rat liver. Here, we found that TFPI is efficiently expressed in Macaque monkey liver. Monkey hepatocytes were identified as the expression cells by Northern blot analysis. The hepatocytes were stained with anti-human TFPI antibody, as were endothelial cells of the small vessels. We isolated and sequenced the 5'-flanking 1.4 kb regions of monkey and human TFPI genes, and found them to show 92.6% identity in their nucleotide sequences. We measured their transcriptional activities using a luciferase reporter gene and showed that the activity of the monkey TFPI gene is higher than that of the human gene in monkey primary hepatocytes. Although the binding motif of hepatocyte nuclear factor-1 is present only in the monkey gene, the site does not seem to be involved in the transcriptional activity. Mutagenetic analyses revealed that the region from -138 to +28 in the monkey gene is important for the expression of TFPI in hepatocytes. The present study indicates that the expression of the monkey TFPI gene is regulated by different mechanisms from the human TFPI gene.

Animals↗
PubMed1997

Genomic organization and alternative splicing of human PACE4 (SPC4), kexin-like processing endoprotease.

PACE4 (paired basic amino acid cleaving enzyme) is a member of a family of the mammalian kexin-like proprotein convertases containing a subtilisin-like catalytic domain. Previously we reported seven isoform mRNAs of PACE4 that vary in size and 3'-coding sequence [A. Tsuji et al. (1994) Biochem. Biophys. Res. Commun. 200, 943-950; K. Mori et al. (1997) J. Biochem. 121, 941-948]. To determine the origin of these isoforms, the entire human PACE4 gene has been isolated as a set of overlapping genomic DNA fragments, and analyzed by restriction enzyme digestion and nucleotide sequence determination. The human PACE4 gene spans at least 250 kb and is distributed over 25 exons that range in size from 39 to 1,422 base pairs. Human PACE4 gene is the largest kexin-like proprotein convertase gene reported to date. The most striking feature of its genomic structure is the size of the introns and the number of exons, although the general organization of signal peptide, propeptide, and catalytic domains, which are conserved in this family, is very similar to that reported for other kexin-like protease genes. The structural analysis of PACE4 genomic DNA indicates that multiple PACE4 transcripts are produced as a consequence of alternative RNA splicing events, including exon skipping, and differences in the usage of the inner 5'-splicing donor and polyadenylation sites. A major transcriptional start site was detected 314 bp upstream from the ATG translational start site by primer extension analysis. Sequence analysis of the 5'-flanking region revealed that PACE4 gene lacks TATA and CCAAT boxes in the proximal upstream region of the start site, although potential binding sites for several transcription factors including SP1, AP1, AP2, PEA3, Ets-1, GHF (growth hormone factor)-1, CREB (cyclic AMP response element binding protein), and basic helix-loop-helix proteins, were present. An unusual sequence of six tandem repeats of a nonadecamer (GGCCTGGGGGTTCACCTGC) containing an E box is found in the 5'-flanking region. These results suggest that PACE4 is not a constitutive gene product and its expression is regulated by various transcription factors.

Alternative Splicing↗
PubMed1996

Do community hospitals reduce the use of district general hospital inpatient beds?

Community hospitals have been supported by the general public and by professionals as one means of increasing choice between local, low technology, care and high technology care at the district general hospital. However, there is no information on the impact of community hospitals on district general hospital use subsequent to NHS and community care reforms. Examination of routinely gathered activity data in the Bath Health District revealed that availability of community hospital beds was associated with reduced use of central inpatient services in the city of Bath. The reduction was most apparent for medical and geriatric beds. Decrease in the use of surgical beds was small. However, total inpatient bed use (including central and community hospital beds) was higher in the population with access to community hospital beds. We conclude that community hospitals offer one option for accessible health care and, as such merit systematic evaluation of costs and benefits. This study presents some evidence that savings could be achieved through improved efficiency.

Adolescent↗
PubMed1994

The tissue distribution of mRNAs for the PACE4 isoforms, kexin-like processing protease: PACE4C and PACE4D mRNAs are major transcripts among PACE4 isoforms.

In the previous study [Biochem. Biophys. Res. Commun. (1994) 200, 943-950] we identified two novel cDNAs (PACE4C and PACE4D) encoding human Kexin-like protease, the PACE4 isoforms. In this study, we examined the expression of PACE4 isoform transcripts in various rat tissues. To detect very low levels and to distinguish among these isoforms, we used the reverse transcriptase-polymerase chain reaction (RT-PCR). PACE4C and PACE4D transcripts were detected in most tissues like PACE4A transcripts, however their tissue distribution profiles and the extent of expression differ. PACE4C and PACE4D transcripts are expressed at a much higher level than PACE4A transcript. These results indicate that PACE4C and PACE4D mRNAs are major transcripts of PACE4.

Animals↗
PubMed1994

A novel member, PC7, of the mammalian kexin-like protease family: homology to PACE4A, its brain-specific expression and identification of isoforms.

By polymerase chain reaction (PCR) with primers corresponding to the sequences of catalytic domain conserved among the mammalian kexin-like protease family, a cDNA fragment encoding a novel member of the family was obtained from rat pituitary. A cDNA for the novel protease was obtained from three overlapping clones isolated from a rat pituitary cDNA library using the PCR product as a screening probe. The protein, designated as PC7, encoded by this cDNA contained a putative activation site with the sequence RXKR, subtilisin-like catalytic domain and a homo B region which are typical of mammalian kexin-like proteases, and short cysteine-rich region at the carboxyl-terminal end. It exhibited surprising sequence similarity to PACE4A. The PC7 transcript was expressed at high levels in the brain. However it was undetectable in the liver, kidney, heart, and spleen. The presence of PC7 isoforms (PC7A and PC7B) was also shown.

Amino Acid Sequence↗
PubMed1994

Identification of novel cDNAs encoding human kexin-like protease, PACE4 isoforms.

PACE4 has been identified as a second human subtilisin-like protease by Keifer et al. [DNA and Cell Biology (1991) 10, 757-769]. In this study, we isolated two novel cDNAs coding for PACE4 isoforms (PACE4C and PACE4D) from a human placenta cDNA library. The deduced PACE4C protein sequence (652 amino acids) lacks the cysteine-rich region located at the carboxy terminus of PACE4. The DNA sequence of the 3'-untranslated region (1 kb) of PACE4C is not homologous to the PACE4 sequence. The protein (497 amino acids) encoded by PACE4D cDNA lacks a signal peptide, a propeptide and the cysteine-rich region. These isoform cDNAs were also isolated from rat pituitary cDNA library.

Amino Acid Sequence↗