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Biomedical subjects

A C Gardiner

Publications and source records attributed to A C Gardiner.

At least 19 recordsLinked to original sources
PubMed2003

P2X7 polymorphism and chronic lymphocytic leukaemia: lack of correlation with incidence, survival and abnormalities of chromosome 12.

The P2X7 receptor, a plasma membrane ATP-gated ion channel that plays a role in lymphocyte apoptosis, has been suggested as an important contributory factor to the pathogenesis of chronic lymphocytic leukaemia (CLL). The P2X7 gene resides on chromosome 12 and is polymorphic in the population at large (1513A/C) with the A and C alleles encoding fully active and nonfunctional proteins, respectively. We have evaluated the significance of this polymorphism by genotyping 144 patients with CLL and 348 healthy controls using a tetraprimer ARMS assay. We found no significant difference in allele frequency between patients and controls. Although patients with the C allele (A/C heterozygotes or C/C homozygotes) had a marginally shorter survival than those who were homozygous for the A allele, this difference was not significant for either the patient group considered as a whole or for IgVH-mutated/unmutated subsets. Finally, no association was found between trisomy 12 and P2X7 genotype. We conclude that the influence, if any, of P2X7 genotype on susceptibility to CLL or clinical outcome is small.

Adolescent↗
PubMed2001

Lymphoid neoplasms.

The majority of B cell lymphomas, but only a minority of T cell lymphomas, are characterized by recurring chromosome translocations. Many involve the immunoglobulin or T cell receptor loci with various partner chromosomes and lead to abnormal proto-oncogene expression. Other recurring translocations result in the production of a novel fusion protein. The detection of translocations is of particular value in diagnosis and in the detection of minimal residual disease. Aneuploidy and deletion of specific chromosome regions are common secondary chromosomal events which are rarely specific to a particular type of lymphoma but provide valuable prognostic information. Analysis by G banding, 24-colour FISH and CGH provides global genomic information; however, more specifically directed investigations utilizing locus-specific FISH probes, PCR techniques or monoclonal antibodies may be more appropriate to answer particular questions regarding diagnosis and prognosis. The known molecular consequences of abnormalities and the appropriate methods of detection are discussed for each subtype of lymphoma.

Chromosome Aberrations↗
PubMed1998

Detailed molecular delineation of 13q14.3 loss in B-cell chronic lymphocytic leukemia.

A region of chromosome 13q14.3, telomeric to the Retinoblastoma gene RB-1 is frequently deleted in patients with B-cell chronic lymphocytic leukemia (B-CLL). A cosmid and P1-derived artificial chromosome (PAC) contig spanning over 600 kb has been constructed, which encompasses this locus. The contig clones have been used to order a number of markers along the minimally deleted region and to localize a series of CpG islands corresponding to possible candidate genes. A novel polymorphic dinucleotide repeat, 6E3.2, present in one of the ordered cosmid clones has been isolated for use in deletion mapping studies of patient DNA. Leukemic samples from 229 CLL patients have been screened for loss of heterozygosity using microsatellite markers and analyzed for hemizygous and homozygous deletions by Southern blot techniques using genomic probes selected from cosmids across the region. Hemizygous deletions were found in 31% of cases with an additional 10% showing homozygous loss. The use of these probes has defined the commonly deleted area to less than 130 kb, centromeric to the locus D13S272.

Chromosomes, Artificial, Yeast↗
PubMed1997

Cytogenetic, fluorescence in situ hybridisation, and clinical evaluation of translocations with concomitant deletion at 13q14 in chronic lymphocytic leukaemia.

Deletions and translocations of 13q14 are the most frequent structural chromosome abnormalities found in chronic lymphocytic leukaemia (CLL). We have identified 13q14 translocations in the blood of 30 of 450 (6.6%) CLL patients by conventional cytogenetics, using tetradecanoyl phorbol 12-myristate 13-acetate (TPA) as a mitogen. The translocations are characterised by multiple partner chromosomes and a high incidence, 6 of 30 cases, of complex rearrangements. Seven cases were also studied by fluorescence in situ hybridisation (FISH) using four previously ordered YACs, to define the breakpoints further. Deletions with varying proximal and distal breakpoints were found in six cases. Two of the cases had deletions of the cytogenetically normal chromosome 13 at q14, and in one case the 13q14 translocation was a secondary genetic event. No difference in the clinical features between the patients with 13q14 translocation and 54 patients with 13q14 deletions or four patients with both a translocation and a deletion was observed. These data suggest that the genetic consequence of 13q14 translocations in CLL is the loss of a tumour suppressor gene.

Chromosome Deletion↗
PubMed1997

Day 3 serum inhibin-B is predictive of assisted reproductive technologies outcome.

OBJECTIVE: To determine if women with day 3 serum inhibin-B concentrations < 45 pg/mL (conversion factor to SI unit, 1.00) demonstrate a poorer response to ovulation induction and assisted reproductive technologies outcome relative to women with inhibin-B values > or = 45 pg/mL. DESIGN: Analysis of inhibin-B, FSH, and E2 concentrations in day 3 serum samples. SETTING: Academic clinical practice. PATIENT(S): One hundred fifty-six women who underwent 178 assisted reproductive technology (ART) cycles with luteal phase GnRH agonist suppression plus hMG and urofollitropin stimulation. MAIN OUTCOME MEASURE(S): Serum E2 on day of hCG, number of oocytes retrieved per patient, fertilization rate, cleavage rate, clinical pregnancy rate (PR) per initiated cycle, cancellation rate per initiated cycle, and spontaneous abortion rate. RESULT(S): Women with day 3 serum inhibin-B < 45 pg/mL demonstrated 70% of the E2 response, had 66.6% of the number of oocytes retrieved per patient, with 28% of the clinical PR per initiated cycle, and three times the cancellation rate per initiated cycle than women with day 3 inhibin-B > or = 45 pg/mL. After controlling for age, day 3 serum FSH, day 3 serum E2, patient cycle number, and method of ART, day 3 serum inhibin-B > or = 45 pg/mL was noted to be prognostic of the number of oocytes retrieved and clinical PR. The adjusted odds ratio of clinical pregnancy for those with day 3 serum inhibin-B > or = 45 pg/mL versus those with inhibin-B < 45 pg/mL was 6.8 (95% confidence interval 1.8 to 25.6). CONCLUSION(S): Women with low day 3 serum inhibin-B concentrations demonstrate a poorer response to ovulation induction and are less likely to conceive a clinical pregnancy through ART relative to women with high day 3 inhibin-B.

Adult↗
PubMed1996

Apoptosis as a function of ovarian reserve in women undergoing in vitro fertilization.

OBJECTIVE: To test the hypothesis that preovulatory follicles from women with diminished ovarian reserve contain fewer numbers of luteinized granulosa cells and have a greater percentage of cells undergoing apoptosis as compared with women with uncompromised ovarian reserve undergoing superovulation for IVF-ET. DESIGN: Comparative study. SETTING: Academic clinical practice. PATIENTS: Luteinized granulosa cell counts were determined from follicular aspirates harvested from 19 women with day 3 serum FSH < or = 6 mIU/mL (conversion factor to SI unit, 1.00) and from 15 women with FSH levels > or = 10 mIU/mL. The second part examined the percent of proliferating and apoptotic cells harvested from nine women with day 3 serum FSH < or = 6 mIU/ mL and from eight women with FSH levels > or = 10 mIU/mL. MAIN OUTCOME MEASURES: Cell counts by hemacytometer and percent of proliferating and of apoptotic granulosa cells by flow cytometry. RESULTS: The mean number of viable cells isolated per follicle were 2.7 x 10(5) (95% confidence interval [CI] 2.3 to 3.1 x 10(5) from the low FSH group and 1.8 x 10(5) (95% CI 1.4 to 2.3 x 10(5) from the high FSH group. Although the percentage of proliferating cells was the same, the mean percentage of apoptotic cells was 0.5% (95% CI 0.2% to 1.4%) from the low group and 2.0% (95% CI 1.1% to 3.7%) from the high group. CONCLUSIONS: Women undergoing IVF with day 3 serum FSH > or = 10 mIU/mL have preovulatory follicles with fewer luteinized granulosa cells and an increase in the percentage of cells undergoing apoptosis as compared with women with day 3 serum FSH < or = 6 mIU/mL.

Adult↗
PubMed1996

Differential secretion of dimeric inhibin in cultured luteinized granulosa cells as a function of ovarian reserve.

Day 3 serum FSH is an indirect assessment of ovarian reserve and has been shown to be prognostic of outcome in ovulation induction and assisted reproductive technology programs. The precise physiologic basis for day 3 serum FSH screening is unknown. We tested the hypothesis that dimeric inhibin is differentially secreted from luteinized granulosa cells collected from women in preparation for in vitro fertilization with low vs. high day 3 serum FSH levels. This prospective study consisted of luteinized granulosa cells harvested from 7 women with low day 3 serum FSH levels (< or = 6 IU/L) and from 8 women with high FSH levels (> or = 10 IU/L) in preparation for in vitro fertilization-embryo transfer. Following retrieval, cells were isolated and then pooled within each individual patient and plated at 50,000 cells per well. Media was removed at 24 and 48 h and analyzed for dimeric and total inhibin concentrations by immunoassay as well as estradiol and progesterone concentrations by RIA. Dimeric inhibin was secreted at 2-fold higher concentrations in the low FSH group 43.2 pg/ml (30.8-60.6) (geometric mean and 95% confidence interval) compared with the high FSH group, 21.0 pg/ml (15.0-29.6), P < 0.004. Total inhibin was secreted at 1.8-fold higher concentrations in the low FSH group, 1148.2 pg/ml (931.1-1415.8) compared with the high FSH group, 639.7 pg/ml (428.5-955.0), P < 0.013. No significant differences in either estradiol or progesterone concentrations were noted. These data suggest that day 3 serum FSH is an indirect bioassay of dimeric inhibin production at the granulosa cell level. Thus, these data provide a potential physiological basis for day 3 serum FSH screening in ovulation induction and ART programs.

Cells, Cultured↗
PubMed1996

Autologous granulosa cell coculture demonstrates zygote suppression of granulosa cell steroidogenesis.

OBJECTIVE: To determine if embryos can modulate steroid hormone production by luteinized granulosa cells. DESIGN: Granulosa cells obtained from follicular aspirates were cultured alone or in the presence of a two-pronuclear zygote. The production of E2 and P by these cultures was evaluated by RIA. SETTING: In Vitro Fertilization Unit in an academic research environment. PATIENTS: Sixteen women undergoing IVF. INTERVENTIONS: Standard IVF-ET treatment cycle using leuprolide acetate for pituitary desensitization before hMG or urofollitropin for ovarian stimulation. MAIN OUTCOME MEASURES: Estradiol and P concentration in culture media of luteinized granulosa cells alone or granulosa cells cocultured with a two-pronuclear embryo. RESULTS: Both E2 and P production by luteinized granulosa cells was reduced when cultured in the presence of an embryo. CONCLUSIONS: Human embryos secrete a factor that regulates granulosa cell steroidogenesis.

Adult↗
PubMed1987

Clinical, biochemical and pathological study of perinatal lambs in a commercial flock.

The birth and fate of 818 lambs born to 571 ewes on a low-ground farm in the Scottish Borders with a history of substantial perinatal mortality were monitored with a range of physiological, biochemical and pathological measurements. In lambs which survived, the rectal temperature, birthweight and plasma concentrations of fructose, insulin, thyroxine and the third component of complement at birth, and the weight at four months of age, decreased with litter size. One hundred and thirty-seven lambs were stillborn or died within four days and seven others died later. The mothers of 77 per cent of these lambs had low condition scores, but the lamb deaths did not correlate significantly with the condition scores. From data relating to birthweight, temperature, packed cell volume and plasma composition it was deduced that placental insufficiency was involved in 24 per cent of these deaths; acute hypoxaemia at birth accounted for 35 per cent, inadequate thermogenesis for 12 per cent and starvation for 13 per cent. The remaining 16 per cent of dead lambs could not be assigned to any of these categories. Using only clinicopathological criteria, 37 per cent of the lamb deaths were attributed to antenatal influences which included immaturity, developmental anomalies, and degenerative or inflammatory changes. Thirty-three per cent of the deaths were due to post natal factors which included, in declining order of frequency, starvation, enteritis, misadventure, pneumonia, navel infections and septicaemia. No conclusions could be drawn from the pathological examinations alone in the remaining 30 per cent, although almost half of these had low rectal temperatures after birth, death being attributed to hypothermia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Border disease without nervous signs or fleece changes.

A natural infection with border disease virus occurred in a flock on low ground in Argyll in the spring of 1984. The outbreak was unusual in that the typical clinical signs of border disease, ie, tremor and, or, fleece changes were not present; manifestations of disease were restricted to abortion and the birth of small weak lambs. The disease was shown to have been introduced to the flock by four healthy ewes persistently infected with border disease virus among a group of 39 purchased in October 1983. Further investigations in late August 1984 detected viraemia in six of seven ill-thriven lambs and four of 24 apparently healthy lambs. Attempted 'natural vaccination' of susceptible sheep by mixing them at grass for three months with groups of ewes and lambs known to contain virus excretors was largely unsuccessful as only four of 22 'sentinel' sheep seroconverted. In October 1984 the persistently infected purchased animals and all that year's lamb crop were removed from the farm. No disease occurred in 1985 when the lambing percentage was 129 per cent compared with 100 per cent in 1984. Two of the four persistently infected purchased ewes were mated at Moredun Research Institute in December 1984 and both produced healthy but persistently infected lambs.

Abortion, Veterinary↗
PubMed1986

Persistent bovine virus diarrhoea virus infection in a bull.

Investigation of a sight defect in a pedigree bull, born as a result of artificial insemination and ovum transplantation, led to the finding that the animal was persistently infected with bovine virus diarrhoea virus. Virus was cultured from blood and from nasal and ocular swabs and was present in semen in high titre. At necropsy, virus was cultured from a wide range of tissues. The pathological findings are described and discussed as are the potential hazards of such infections.

Animals↗
PubMed1983

The pathology of a spontaneous and experimental mucosal disease-like syndrome in sheep recovered from clinical border disease.

The pathological changes which accompanied a severe clinical syndrome characterized by intractable diarrhoea and/or respiratory distress in sheep recovered from clinical Border disease consisted of inflammatory lymphoproliferative lesions in several organs, notably the CNS and intestinal tract. The syndrome has been reproduced experimentally by "super-infection" with homologous Border disease virus. The differential diagnosis is discussed and attention drawn to the similarity between the enteric lesions and those of bovine mucosal disease.

Animals↗
PubMed1983

Virology and immunology of a spontaneous and experimental mucosal disease-like syndrome in sheep recovered from clinical border disease.

A disease similar to mucosal disease (MD) of cattle has occurred spontaneously in sheep clinically recovered from Border disease (BD). Evidence is presented to suggest that, in such animals, a specific and dynamic equilibrium exists between an attenuated form of the virus and the immunotolerant host. Upset of this equilibrium either by injection of BD virus of the same strain or by some unknown spontaneous event appears to lead to the reassertion of viral pathogenicity with fatal consequences.

Animals↗
PubMed1982

Recombinant chromosome 18 in two offspring of a chromosome 18 inversion heterozygote.

A case of partial trisomy of chromosome 18 due to a recombinant pericentric inversion is described. Prenatal diagnosis in a subsequent pregnancy identified a foetus with the recombinant chromosome 18, and the pregnancy was terminated. A comparison is made between the risks reported in the relevant literature where recombinant offspring have resulted from chromosome 18 inversion heterozygotes and those observed in this case.

Abnormalities, Multiple↗
PubMed1980

Mesangiocapillary glomerulonephritis in lambs: the ultrastructure and immunopathology of diffuse glomerulonephritis in newly born Finnish Landrace lambs.

Renal biopsies were obtained by laparotomy from eight newborn C3 deficient Finnish Landrace lambs, and examined by light, electron and immunofluorescence microscopy. The capillaries of all glomeruli contained numerous neutrophils and peripheral capillary walls were thickened and refractile at high magnifications. Almost continuous subendothelial electron-dense deposits were seen in peripheral capillary walls. Large amounts of C'3, and small amounts of IgM and IgA were also seen in these sits. No IgG was seen in these glomeruli. Four lambs died within 96 hr of birth. The remaining four lambs all had severe clinical mesangiocapillary glomerulonephritis (MCGN) by 21 to 42 days after birth. Amounts of C'3, IgM and IgA in glomeruli had increased by comparison with amounts at birth, and IgG was present in the deposits. It was concluded that the processes ultimately expressed as MCGN in these lambs were initiated before birth.

Animals↗