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Biomedical subjects

C R Kennedy

Publications and source records attributed to C R Kennedy.

At least 55 records · Page 3Linked to original sources
PubMed2000

Knockout of the murine prostaglandin EP2 receptor impairs osteoclastogenesis in vitro.

Prostaglandin E2 (PGE2) stimulates the formation of osteoclast-like tartrate-resistant acid phosphatase-positive multinucleated cells (TRAP + MNC) in vitro. This effect likely results from stimulation of adenylyl cyclase, which is mediated by two PGE2 receptors, designated EP2 and EP4. We used cells from mice in which the EP2 receptor had been disrupted to test its role in the formation of TRAP + MNC. EP2 heterozygous (+/-) mice in a C57BL/6 x 129/SvEv background were bred to produce homozygous null (EP2 -/-) and wild-type (EP2 +/+) mice. PGE2, PTH, or 1,25 dihydroxyvitamin D increased TRAP+ MNC in 7-day cultures of bone marrow cells from EP2 +/+ mice. In cultures from EP2 -/- animals, responses to PGE2, PTH, and 1,25 dihydroxyvitamin D were reduced by 86%, 58%, and 50%, respectively. A selective EP4 receptor antagonist (EP4RA) further inhibited TRAP+ MNC formation in both EP2 +/+ and EP2 -/- cultures. In cocultures of spleen and calvarial osteoblastic cells, the response to PGE2 or PTH was reduced by 92% or 85% when both osteoblastic cells and spleen cells were from EP2 -/- mice, by 88% or 68% when only osteoblastic cells were from EP2 -/- mice and by 58% or 35% when only spleen cells were from EP2 -/- mice. PGE2 increased receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) messenger RNA expression in osteoblastic and bone marrow cell cultures from EP2 +/+ mice 2-fold but had little effect on cells from EP2 -/- mice. Spleen cells cultured with RANKL and macrophage colony stimulating factor produced TRAP+ MNC. PGE2 increased the number of TRAP+ MNC in spleen cell cultures from EP2 +/+ mice but not in cultures from EP2 -/- mice. EP4RA had no effect on the PGE2 response in spleen cell cultures. PGE2 decreased the expression of messenger RNA for granulocyte-macrophage colony stimulating factor in spleen cell cultures from EP2 +/+ mice but had little effect on cells from EP2 -/- mice. These data demonstrate that the prostaglandin EP2 receptor plays a role in the formation of osteoclast-like cells in vitro. A major defect in EP2 -/- mice appears to be in the capacity of osteoblastic cells to stimulate osteoclast formation. In addition, there appears to be a defect in the response of cells of the osteoclastic lineage to PGE2 in EP2 -/- mice.

Acid Phosphatase↗
PubMed2000

Potential interactions between the intestinal helminths of the cichlid fish Cichlasoma synspilum from southeastern Mexico.

This study presents and analyzes positional data on 18 helminth species forming the intestinal infracommunities of 59 Cichlasoma synspilum from southeastern Mexico. Interspecific interactions were found between 4 pairs of host specialists: Crassicutis cichlasomae (Digenea) with Neoechinorhynchus golvani (Acanthocephala), Spirocamallanus rebecae (Nematoda) with N. golvani, and Raillietnema kritscheri (Nematoda) with N. golvani. The interactions were expressed as negative correlations, positional shifts, and reductions in realized distribution. It is suggested that N. golvani produces unsuitable habitats for C. cichlasomae, S. rebecae, and R. kristscheri. All interactions were found among phylogenetically unrelated helminth specialists of cichlids.

Animals↗
PubMed1999

Comparison of screening instruments for disability and emotional/behavioral disorders with a generic measure of health-related quality of life in survivors of childhood brain tumors.

The sensory, motor, educational and emotional/behavioral outcomes in 32 survivors of childhood brain tumors were evaluated by examination, interview, questionnaires on emotion/behavior and the Health Utilities Index Mark 2 (HUI 2). Thirty-eight percent had moderate/severe disability, and this was associated closely with special educational provision. Pre- and peri-operative factors were the commonest determinants of disability. Fifty percent had a high score on the emotion/behavior questionnaires, suggesting a high risk of an emotional or behavioral problem. The HUI 2 discriminated well between those survivors who had and those who had not had special provision made for their education but poorly between those with high and those with low scores on the emotion/behavior questionnaires. Previous studies have found self-reported health-related quality of life to be related more closely to emotional/behavioral sequelae than to disability. Possible uses and limitations of the HUI 2 in this clinical context are discussed.

Adolescent↗
PubMed1999

Density-dependent effects on Anguillicola crassus (Nematoda) within its European eel definitive host.

Density-dependent effects on adult and larval stages of the introduced nematode parasite Anguillicola crassus in the European eel definitive host were examined in the laboratory in naturally infected fish, and in field samples. The effect of adult nematode subpopulations on larval development over time and the effect of increasing adult intensity on the gravid female subpopulations were investigated. At high adult subpopulations the movement of larvae from the swimbladder wall into the swimbladder lumen appears to be inhibited, and A. crassus larvae to be arrested in development in a density-dependent manner. The number of gravid females per host reaches a constant level, and so the proportion of gravid female nematodes per adult subpopulation decreases relative to further increasing total adult nematode numbers. Both these mechanisms have the potential to regulate infrapopulations of A. crassus within the eel definitive host and thus the parasite suprapopulation.

Anguilla↗
PubMed1999

Salt-sensitive hypertension and reduced fertility in mice lacking the prostaglandin EP2 receptor.

Prostaglandins (PGs) are ubiquitous lipid mediators derived from cyclooxygenase metabolism of arachidonic acid that exert a broad range of physiologic activities, including modulation of inflammation, ovulation and arterial blood pressure. PGE2, a chief cyclooxygenase product, modulates blood pressure and fertility, although the specific G protein-coupled receptors mediating these effects remain poorly defined. To evaluate the physiologic role of the PGE2 EP2 receptor subtype, we created mice with targeted disruption of this gene (EP2-/-). EP2-/- mice develop normally but produce small litters and have slightly elevated baseline systolic blood pressure. In EP2-/- mice, the characteristic hypotensive effect of intravenous PGE2 infusion was absent; PGE2 infusion instead produced hypertension. When fed a diet high in salt, the EP2-/- mice developed profound systolic hypertension, whereas wild-type mice showed no change in systolic blood pressure. Analysis of wild-type and EP2-/- mice on day 5 of pregnancy indicated that the reduced litter size of EP2-/- mice is due to a pre-implantation defect. This reduction of implanted embryos could be accounted for by impaired ovulation and dramatic reductions in fertilization observed on day 2 of pregnancy. These data demonstrate that the EP2 receptor mediates arterial dilatation, salt-sensitive hypertension, and also plays an essential part in female fertility.

Animals↗
PubMed1999

Pronuclear orientation, polar body placement, and embryo quality after intracytoplasmic sperm injection and in-vitro fertilization: further evidence for polarity in human oocytes?

Three hypotheses were tested: (i) the distance between first and second polar bodies (PB) may relate to embryo morphology, (ii) that the orientation of pronuclei (PN) relative to PB may relate to embryo morphology, (iii) that the placement of a spermatozoon in a fixed plane relative to the first PB [intracytoplasmic sperm injection (ICSI)] may alter PN/PB orientation relative to in-vitro fertilization (IVF). A total of 251 two pronuclear (2PN) embryos (124 ICSI, 127 IVF) from 64 patients was studied. Angles were measured between the PN axis and the nearest PB (alpha), the furthest PB (beta), and between the two PB (gamma). On day 2, the morphological grades of embryos were recorded. gamma ranged from 0 to 150 degrees and was not significantly different for ICSI or IVF embryos of different grades; however, an unusual distribution of gamma suggested different populations of oocytes. The first hypothesis was rejected. alpha and beta ranged from 0 to 90 degrees : alpha did not relate significantly to embryo grade, but beta increased significantly with decreasing quality of ICSI embryos (P < 0.05) and the total group (P < 0.01), supporting hypothesis (ii). The difference in beta between ICSI and IVF embryos was not significant, so hypothesis (iii) was unproven. Significant differences between ICSI and IVF embryos in PN positions, irregular cleavage, and cleavage failure were noted.

Cell Nucleus↗
PubMed1999

Controlled trial of universal neonatal screening for early identification of permanent childhood hearing impairment: coverage, positive predictive value, effect on mothers and incremental yield. Wessex Universal Neonatal Screening Trial Group.

OBJECT: Congenital bilateral permanent childhood hearing impairment (PCHI) impairs communication skills and, in some cases, mental health and employment prospects. Management of PCHI within the first year of life can alleviate most of its adverse effects. We investigated whether neonatal screening of all babies born in hospital, in addition to the standard Health Visitor Distraction Test (HVDT), would increase the rates of early diagnosis. METHODS: Between 1993 and 1996, two teams of four part-time testers and equipment moved between two pairs of hospitals to achieve four periods with neonatal screening and four without neonatal screening, each of 4-6 mo duration in each hospital. Babies did or did not undergo neonatal screening dependent on the periods during which they were born. We used a transient evoked oto-acoustic emissions (TEOAE) test followed, in infants who failed this test, by an automated auditory brainstem response (AABR) test on the same day. We referred babies with positive results for audiological assessment. RESULTS: 53,781 infants were included in the trial, including 25,609 born during periods of neonatal screening. The neonatal screen achieved 87% coverage of inborn births, with a false alarm rate of 1.5%, and an overall yield from the screen of 90 cases of bilateral PCHI > or = 40dB HTL per 100,000 target population, equivalent to 80% of the expected prevalence of the condition in the population. Seventy-one more babies with moderate or severe PCHI per 100,000 target population were referred before age 6 mo during periods with neonatal screening than during periods without. Early confirmation and management of PCHI were significantly increased. The false-negative rate of neonatal screening was significantly lower than that of HVDT screening (4% vs 27%). CONCLUSIONS: Neonatal screening is effective in identification of congenital PCHI and may be particularly useful for babies with moderate and severe PCHI for whom early management may have the most benefit.

Audiometry, Evoked Response↗
PubMed1999

Patterns in metazoan parasite communities of some oyster species.

Metazoan parasite communities of Crassostrea gigas and Ostrea edulis from Great Britain, Crassostrea virginica from Mexico, and Saccostrea commercialis from Australia are described and summarized in terms of species composition, species richness, total number of individuals and dominance. Metazoan parasite communities in all host species were composed of turbellarians and the metacercarial stage of digeneans, with the exception of S. commercialis where only metacercariae were found. Arthropods, including one copepod and one mite species, were present only in British oyster species. All metazoan parasite communities of oysters had few species and low density of individuals. Richest communities were found in C. virginica at both component and infracommunity level. The least diverse component community occurred in S. commercialis. Infracommunities in O. edulis and S. commercialis never exceeded one species per host. The host response against parasites is suggested as the principal factor responsible for depauperate parasite communities of oysters. Environmental factors characteristic of tropical latitudes are likely to have enhanced both the number of species and the densities of parasites per host in the infracommunities of C. virginica.

Animals↗
PubMed1998

An audit of paediatric epilepsy care.

Basic standards for the process of paediatric epilepsy care were identified and applied in a clinical audit; findings were presented and the audit repeated. Standards agreed related to quality of correspondence, prescribing practice, appropriateness of drug monitoring, use of neuroimaging, and quality of requests for electroencephalography (EEG). Parent satisfaction with staff courtesy, doctor communication, and clinic visits were also assessed. In the second audit prescribing practice and appropriateness of drug monitoring had improved, but quality of patient correspondence and requests for EEG were unchanged. In both periods of care many parents were dissatisfied with the quality and amount of information provided about epilepsy. Standards of care for the medical management of children with epilepsy can be agreed and used to identify achievable improvements in that care.

Appointments and Schedules↗
PubMed1998

Ataxia with isolated vitamin E deficiency presenting as mutation negative Friedreich's ataxia.

Ataxia with vitamin E deficiency is an autosomal recessive condition associated with a defect in the a-tocopherol transfer protein. Clinically it manifests as a progressive ataxia with a phenotype resembling that of Friedreich's ataxia. There is some evidence that progression of neurological symptoms is prevented by vitamin E therapy. A patient is described who was given a clinical diagnosis of Friedreich's ataxia. Molecular genetic analysis showed the absence of the frataxin gene expansion. Subsequent vitamin E assay showed deficiency and a diagnosis of ataxia with vitamin E deficiency was made. It is recommended that all patients with ataxia of unknown cause should have vitamin E deficiency excluded. When a diagnosis of Friedreich's ataxia is considered patients should have frataxin analysis in addition. Further, neurologists should be aware that ataxia with vitamin E deficiency may present as "mutation negative" Friedreich's ataxia.

Adolescent↗
PubMed1997

Establishment of human tubal epithelial cells for coculture in an IVF program.

OBJECTIVE: Our goal was to develop a coculture system from human tubal epithelial cells for use in a human IVF program. DESIGN: Fallopian tubes were obtained from women undergoing hysterectomy for benign disease. Ampullary epithelial cells were cultured, passaged, and frozen and the karyotype and epithelial characteristics of later passages examined. SETTING: The study took place at the Assisted Conception Clinic, Walsgrave Hospital, and the Department of Biological Sciences, University of Warwick. RESULTS: Ampullary epithelial cells can be successfully cultured and maintained as diploid epitheliod lines until the fifth passage. Freezing does not affect subsequent culture, the cytoskeleton, or the karyotype. In excess of 12 x 10(6) cells may be obtained from a pair of Fallopian tubes. CONCLUSIONS: The ease of establishing and maintaining human tubal epithelial cell cultures justified their use in clinical IVF for human embryo cocultures, and further investigations into their mode of action should be encouraged.

Cells, Cultured↗
PubMed1997

Human protamines and male infertility.

PURPOSE: Our purpose was to determine the ratio of protamine 1 to protamine 2 in human spermatozoa and relate it to in vitro fertilization rates (IVF) and standard semen parameters. METHODS: Couples who had been clinically diagnosed as having male-factor infertility and had undergone IVF treatment were grouped according to IVF rates and pregnancy outcome. Protamines were extracted and separated on acid urea polyacrylamide gels. The P1/P2 ratio correlation with semen parameters and IVF rates was investigated using nonparametric analysis. RESULTS: The P1/P2 ratio ranged from 0.55 to 1.29 in the control group of patients, who had fertilization rates > or = 50% and had achieved a pregnancy in one IVF cycle. Of the test patients with IVF < 50%, three (14%) had P1/P2 ratios outside the range exhibited by the control group and their sperm possessed large heads. CONCLUSIONS: P1/P2 ratios were statistically negatively correlated with IVF rates in the control group and with progressive motile sperm concentration in the test group. We do not think that altered P1/P2 ratios are the primary cause of reduced fertilization.

Female↗
PubMed1997

Composition and structure of helminth communities in eels Anguilla anguilla from Italian coastal lagoons.

The composition and diversity of total and intestinal helminth component and infracommunities were determined in eels Anguilla anguilla from four shallow coastal lagoons near Rome. The lagoons differed principally in respect of their salinity. Only Lake Burano still received an input of freshwater, and both freshwater and marine helminth species were found in eels. In the other three lagoons all helminth species were marine or euryhaline and communities were dominated by digeneans. At component community level these three lagoons were far more similar to each other than to Lake Burano, but this distinction almost disappeared at infracommunity level. Species richness and diversity declined with increasing salinity at component community level but not at infracommunity level. Despite the changes and differences in helminth community composition, intestinal helminth infracommunity structure was very similar in all four lagoons and to that in eels from freshwater localities in Britain. The findings thus provide further and unexpected support for the view that some factor(s) other than supply side ones must be operating to produce the fundamental structural similarity in helminth communities in eels.

Anguilla↗
PubMed1997

Bradykinin-stimulated arachidonic acid release from MDCK cells is not protein kinase C dependent.

Bradykinin (BK)-induced release of arachidonic acid (AA) from Madin-Darby canine kidney (MDCK) D1 cells was investigated. Phorbol 12-myristate 13-acetate (PMA) caused a synergistic increase in BK- and A-23187-induced release of AA but alone had no effect on this release. Inhibition of protein kinase C (PKC) with bisindolmaleimide I (BIS) abolished the synergistic effects of PMA but did not affect AA release caused by BK or A-23187 alone. Downregulation of PKC with 100 nM PMA resulted in a reduction of AA release induced by BK or A-23187 addition, which corresponded to a decrease in cytoplasmic phospholipase A2 (cPLA2) activity as measured in cell extracts. Although Western blotting revealed no differences in cPLA2 expression as a result of PMA treatment, phosphorylation of the enzyme, as assessed by phosphoserine content, was significantly reduced in PKC-depleted cells. These results imply that, with PKC downregulation, subsequent BK stimulation results in a Ca(2+)-dependent translocation of a less phosphorylated, less active form of cPLA2. Any stimulation of PKC by BK addition did not appear as a significant event in onset responses leading to AA release. On the other hand, inhibition of the mitogen-activated protein kinase (MAPK) cascade with the MAPK kinase inhibitor, PD-98059, significantly decreased BK-induced release of AA, a finding that, with our other results, points to the existence of a PKC-independent route for stimulation of MAPK and the propagation of onset responses.

Animals↗
PubMed1997

Bradykinin-stimulated cPLA2 phosphorylation is protein kinase C dependent in rabbit CCD cells.

We have used an established cell line of rabbit cortical collecting duct (RCCD) epithelial cells representing a mixed population of principal and intercalated cell types to determine which phospholipase A2 (PLA2) enzyme therein is responsible for bradykinin (BK)-stimulated arachidonic acid (AA) release and how its activation is regulated. BK-stimulated AA release was reduced 92% by arachidonyl trifluoromethyl ketone, an inhibitor of cytosolic PLA2 (cPLA2). Examination of PLA2 activity in vitro demonstrated that BK stimulation resulted in a greater than twofold increase in PLA2 activity and that this activity was dithiothreitol insensitive and was inhibited by an antibody directed against cPLA2. To determine a possible role for protein kinase C (PKC) in the BK-mediated activation of cPLA2, we used the PKC-specific inhibitor Ro31-8220 and examined its effects on AA release, cPLA2 activity, and phosphorylation. Ro31-8220 reduced BK-stimulated AA release and cPLA2 activity by 51 and 58%, respectively. cPLA2 activity stimulated by phorbol ester [phorbol 12-myristate 13-acetate (PMA)] displayed a similar degree of activation and was associated with an increase in serine phosphorylation identical to that caused by BK. The phosphorylation-induced activation of this enzyme was confirmed by the phosphatase-mediated reversal of both BK- and PMA-stimulated cPLA2 activity. In addition, we have also found that PMA stimulation did not cause a synergistic potentiation of BK-stimulated AA release as did calcium ionophore. This occurred despite membrane PKC activity increasing 93% in response to PMA vs. 42% in response to BK. These data, taken together, indicate that cPLA2 is the enzyme responsible for BK-mediated AA release, and, moreover, they indicate that PKC is involved in the onset responses of cPLA2 to BK.

Animals↗