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Biomedical subjects

C Wood

Publications and source records attributed to C Wood.

At least 19 recordsLinked to original sources
PubMed1997

Immunogenicity of DNA damaged by reactive oxygen species--implications for anti-DNA antibodies in lupus.

Reactive oxygen species (ROS) are implicated in the inflammatory, autoimmune, connective tissue disease, systemic lupus erythematosus (SLE), particularly in respect of processes leading to the formation of pathological anti-DNA antibodies. Exposure to ROS increases the antigenicity of DNA for SLE antibodies, but data on the immunogenicity of ROS-DNA are not conclusive. In this study, we have examined the immunogenicity in rabbits, of DNA modified by three hydroxyl radical generating systems. Additionally, we investigated the antigenicity of UVA, UVB, and UVC irradiated DNA for lupus anti-DNA antibodies. Modification of DNA by both ROS and far UV dramatically increased its immunogenicity; the Fe2+ and H2O2 system resulted in antibodies that recognized both native and modified DNA. In our ELISA system, none of the UV antigens showed any antigenicity above native DNA for SLE sera. The data suggested that different profiles of antigenicity and immunogenicity arise dependent on the method of ROS production, but also that ROS-DNA may be a factor in antigen-driven immune complex formation in SLE.

Adult↗
PubMed1996

Structural organization of the human PON1 gene.

Serum paraoxonase/arylesterase (PON) is an "A" esterase found in the HDL2 fraction of mammalian sera closely associated with apolipoproteins A1 and J. This enzyme hydrolyzes the active metabolites (oxons) of several organophosphate (OP) insecticides as well as the P-F bond of the nerve agents soman and sarin. PON also destroys biologically active, multioxygenated phospholipids. Two factors result in large individual variations in PON serum levels, a substrate-dependent activity polymorphism and large individual differences in PON protein levels that are stable over time. Animal model studies indicate that PON activity levels are likely to play a major role in determining sensitivity to OPs. The arg192 PON isoform appears to be a risk factor in coronary artery disease. We report here the characterization of a 28-kb contig encompassing 300 bp of 5' sequence, the entire coding region, and 2 kb of 3'-flanking sequence of the PON gene. The structural portion of the paraoxonase protein is encoded by nine exons that form the primary transcript through the use of typical splice donor and acceptor sites. DNA sequences of the regions surrounding all the coding exons have been determined. A polymorphic CA repeat is located in intron 4.

Aryldialkylphosphatase↗
PubMed1996

The differentiating agent phenylacetate increases prostate-specific antigen production by prostate cancer cells.

The prostatic-specific antigen (PSA) is the tumor marker most widely relied upon for the monitoring of patients with prostate cancer. Recently, declines in the serum concentrations of PSA have been advocated as a surrogate marker of tumor response in clinical trials of investigational antitumor agents. We examined the hypothesis that this postulate may not apply to the evaluation of drugs such as phenylacetate, a differentiating agent endowed with mechanisms of action different from those of classic cytotoxic chemotherapy. Using human prostatic carcinoma LNCaP cells as a model, we show that phenylacetate induces PSA production despite inhibition of tumor cell proliferation. Incubation of LNCaP cultures with cytostatic doses of phenylacetate (3-10 mM) resulted in a three- to fourfold increase in PSA secretion per cell. This appears to result from upregulation of PSA gene expression, as indicated by elevated PSA mRNA steady-state levels in treated cells. The increase in PSA production per cell was confirmed in rats bearing subcutaneous LNCaP tumor implants that were treated systemically with phenylacetate. Further comparative studies indicate that upregulation of PSA is common to various differentiation inducers, including all-trans-retinoic acid, 1,25-dihydroxyvitamin D3, and butyrate but is not induced by other antitumor agents of clinical interest such as suramin. We conclude that declines in PSA may be treatment specific and that the exclusive use of this criterion as a marker of disease response may mislead the proper evaluation of differentiating agents in prostate cancer patients.

Animals↗
PubMed1996

AtJ1, a mitochondrial homologue of the Escherichia coli DnaJ protein.

The nucleotide sequence of a cDNA clone from Arabidopsis thaliana ecotype Columbia was determined, and the corresponding amino sequence deduced. The open reading frame encodes a protein, AtJ1, of 368 residues with a molecular mass of 41 471 Da and an isoelectric point of 9.2. The predicted sequence contains regions homologous to the J- and cysteine-rich domains of Escherichia coli DnaJ, but the glycine/phenylalanine-rich region is not present. Based upon Southern analysis, Arabidopsis appears to have a single atJ1 structural gene. A single species of mRNA, of 1.5 kb, was detected when Arabidopsis poly(A)+ RNA was hybridized with the atJ1 cDNA. The function of atJ1 was tested by complementation of a dnaJ deletion mutant of E. coli, allowing growth in minimal medium at 44 degrees C. The AtJ1 protein was expressed in E. coli as a fusion with the maltose binding protein. This fusion protein was purified by amylose affinity chromatography, then cleaved by digestion with the activated factor X protease. The recombinant AtJ1 protein was purified to electrophoretic homogeneity. In vitro, recombinant AtJ1 stimulated the ATPase activity of both E. coli DnaK and maize endosperm cytoplasmic Stress70. The deduced amino acid sequence of AtJ1 contains a potential mitochondrial targeting sequence at the N-terminus. Radioactive recombinant AtJ1 was synthesized in E. coli and purified. When the labeled protein was incubated with intact pea cotyledon mitochondria, it was imported and proteolytically processed in a reaction that depended upon an energized mitochondrial membrane.

Adenosine Triphosphatases↗
PubMed1996

Production of embryos from in vitro-matured primary human oocytes.

OBJECTIVE: To determine the factors that influence the number and quality of embryos produced from primary oocytes collected from untreated regularly ovulating and irregular or anovulatory polycystic women. DESIGN: A direct comparison between two patient groups whose oocytes were matured in vitro and a comparison of the embryo development of in vitro-matured oocytes from untreated patients with in vivo-matured oocytes of superovulated IVF-ET patients obtained during the same period. SETTING: The Monash IVF Clinic, involving patients who expressed the desire to avoid super-ovulation with fertility drugs. MAIN OUTCOME MEASURES: The completion of nuclear maturation of oocytes after 36 or 48 hours culture, fertilization in vitro, and embryo development ratio. RESULTS: Oocytes from regular cycling patients matured and fertilized at significantly higher rates than irregular cycling and anovulatory women and their embryos had significantly higher mean embryo development ratio. The mean embryo development ratio of embryos of regular cycling patients was similar to superovulated IVF patients but irregular cycling and anovulatory patients had a significantly lower embryo development ratio. Culture of oocytes for 48 hours increased maturation of oocytes from 57% to 82% but did not affect fertilization or cleavage rates. Embryo development was not affected significantly by the grade of follicular cell cover of oocytes. CONCLUSIONS: The developmental capability of primary oocytes is higher in regular cycling women than in irregular cycling and anovulatory women with polycystic ovary disease.

Anovulation↗
PubMed1996

Functional integrity of granulosa cells from polycystic ovaries.

OBJECTIVE: The polycystic ovarian syndrome is frequently associated with human infertility and is a partially characterized syndrome of unknown aetiology. The aim of this study was to describe the functional integrity of granulosa cells from polycystic ovaries. PATIENTS: Follicular aspirates were collected from polycystic ovaries of ovulatory (n = 24) and anovulatory (n = 7) patients. Follicular aspirates were also collected from normal ovaries of untreated (n = 24) and superovulated (n = 10) subjects. All patients were enrolled for the recovery of their oocytes for in vitro maturation and fertilization. MEASUREMENTS: FSH receptors and apoptosis were measured in the granulosa cells of the different patients. FSH-stimulated oestradiol and LH-stimulated progesterone production by granulosa cells of the different patients were also measured. RESULTS: The binding of 125I-labelled human recombinant FSH to granulosa cells from anovulatory subjects with polycystic ovaries was significantly higher than that found in granulosa cells from normal (180%) and superovulated (163%) ovaries. However, the ligand binding to granulosa cells from ovulatory subjects with polycystic ovaries was not significantly higher than that found in normal granulosa cells. Also, granulosa cells obtained from anovulatory subjects with polycystic ovaries cultured with FSH produced more oestradiol than normal granulosa cells but oestradiol production was similar to that of granulosa cells from superovulated ovaries (mean +/- SEM, 224.94 +/- 22.02, 24.23 +/- 2.92, 211.87 +/- 50.39 nmol/l/24 h, respectively). Flow cytometric analysis showed that the proportions of viable and apoptotic granulosa cells (mean +/- SDM, 70 +/- 5 and 7 +/- 1%, respectively) were similar in normal subjects and in those with polycystic ovaries. CONCLUSION: We conclude that most of the granulosa cells of polycystic ovaries are healthy and non-apoptotic, expressing high levels of FSH receptors and highly responsive to this hormone in culture. These data provide direct evidence that most of the follicles of polycystic ovaries are not atretic.

Adult↗
PubMed1996

Human herpesvirus type 8 DNA sequences in cell-free plasma and mononuclear cells of Kaposi's sarcoma patients.

Human herpesvirus (HHV) type 8 has been detected in both classical and AIDS-related Kaposi's sarcoma, body-cavity lymphomas, and other types of tumors. HHV-8 has also been detected in DNA from peripheral blood mononuclear cells (PBMC) of some Kaposi's sarcoma patients and more readily in B cell fractions derived from panned cell subpopulations. Two patients were followed using several methods; in situ hybridization, solution-based polymerase chain reaction (PCR), and in situ PCR. HHV-8 was intermittently detected in plasma, and detection correlated with detection in PBMC. In situ PCR demonstrated HHV-8 sequences in both peripheral blood B lymphocytes and, to a lesser extent, T lymphocytes. HHV-8 may undergo periods of viremia while at other times it is undetectable and infects circulating B cells and some T cells.

Adult↗
PubMed1996

Aspects of patient satisfaction with communication in surgical care: confirming qualitative feedback through quantitative methods.

This paper reviews the results of a two-phase study of patient satisfaction with surgical services. Phase one adopted a qualitative approach using interviews and observation of surgeons and patients. Phase two was based on a questionnaire survey using questions generated by the qualitative study. Selected data reported here focus on the principal areas of concern for surgical patients and the importance of a patient's medical condition in accounts of satisfaction with care. The results reveal the importance of interview data as a means to explain the meanings behind questionnaire responses. However, where personal accounts are not sustained statistically, it may be necessary to reconsider the assumption that such methodologies may simply be "triangulated" to elicit an identical patient perspective and agenda. This is important in view of the fact that health research is increasingly reliant on standardized measures of quality-of-life, symptom-scoring and patient satisfaction, all of which use questionnaires whose claim to validity is their equivalence to the results of prior interviewing.

Adolescent↗
PubMed1996

Twin sibling differences in parental reports of ADHD, speech, reading and behaviour problems.

Differences between twins and siblings in behaviour problems were investigated in a non-selected sample of 1938 families with children aged 4-12 years. Families were sent a questionnaire based on DSM-III-R criteria for Attention Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), Conduct Disorder (CD) and Separation Anxiety (SA), which was validated by formal clinical interview. The questionnaire also included measures of speech and reading problems. There were significant differences between twins and siblings for ADHD symptoms, but not for symptoms of ODD, CD or SA. Twins and siblings differed significantly for gestational age, birth weight, speech and reading problems. While there was little evidence for birth weight or gestational age contributing to the difference in ADHD symptoms, there was a strong association between ADHD symptoms and speech and reading problems.

Anxiety, Separation↗
PubMed1996

Removal of fibromyomas by laparoscopic surgery after preoperative GnRH analogue--an alternative to abdominal hysterectomy or myomectomy.

Nineteen patients with fibromyomas who had been recommended to have a hysterectomy or abdominal myomectomy were referred as they wished to avoid a hysterectomy (14) or laparotomy incision for a myomectomy (5). Following administration of the GnRH analogue goserelin, laparoscopic surgery was performed on all these patients. Hysterectomy was avoided in all but 1 of the 14 patients and laparotomy myomectomy was avoided in 4 of the 5 patients recommended to have these procedures. The combination of a GnRH analogue and laparoscopic-based surgery may be an acceptable alternative to both laparotomy myomectomy and hysterectomy in women with fibromyomas requiring surgery.

Adult↗
PubMed1996

Peritoneal surgery in the treatment of endometriosis--excision or thermal ablation?

Twenty patients with Stage 2 to 4 endometriosis were referred to an Endometriosis Clinic with an average of 3.4 previous medical and surgical treatments. All were treated by peritoneal excision. Follow-up was for 9-36 months and 14 had a further laparoscopy. Seventeen of 20 patients are free of symptoms. In 1 patient recurrence occurred in a separate site and in 2 there were lesions close to the original lesion in the pouch of Douglas and bladder wall. In addition, 1 of the 14 patients having further laparoscopy had mild adhesions. The satisfactory results of the study suggest that a controlled trial comparing peritoneal excision and thermal ablation is worthwhile. There are considerable theoretical advantages in using peritoneal excision rather than peritoneal thermal ablation.

Adult↗
PubMed1996

Underutilization of laparoscopic oophorectomy.

The objective of this study was to compare the use and effectiveness of laparoscopic and laparotomy oophorectomy in 3 hospitals in Melbourne. A retrospective analysis was made of medical records of 140 patients having laparoscopic or laparotomy oophorectomy in the Mercy Hospital for Women (41), Monash Medical Centre (37), and Cliveden Hill Private Hospital (62). Both public hospitals used the laparoscopic procedure, 12% and 22% respectively, less often than the private hospital, 94%. The average number of hospital days for procedures completed by laparoscopy was 1.3 and for laparotomy 6.9. Fourteen percent of laparoscopic procedures were converted to laparotomy. Adjusting for this the average hospital stay was 1.6 days of procedures started laparoscopically. Assuming 1,000 oophorectomies are performed each year in Australia of which 80% could be performed laparoscopically, there may be cost savings to health care providers of over $1.5 million. Laparoscopic oophorectomy is a safe, effective and cost-efficient method of removing the ovary and gynaecologists should be encouraged to learn and perform this procedure.

Adult↗
PubMed1996

Infection of primary human fetal astrocytes by human herpesvirus 6.

Human herpesvirus 6 (HHV-6) is a lymphotropic betaherpesvirus which productively infects human CD4+ T cells and monocytes. HHV-6 is the etiologic agent for exanthem subitum (roseola), and it is well-known that central nervous system complications occur frequently during the course of HHV-6-associated disease. In addition, HHV-6 has been associated with encephalitis or encephalopathy. However, very little is known about its tropism for neural cells. There are reports that HHV-6 may infect some glial cell lines, but whether it can infect any primary neural cells is not known. Our studies show that both HHV-6A (GS) and HHV-6B (Z-29) can infect highly purified primary fetal astrocytes in vitro. Infected cells showed cytopathic effects, forming giant syncytia. In dual immunofluorescence assays, the infected cells were detected by antibodies against the HHV-6 p41 nuclear antigen and glial fibrillary acidic protein, indicating that the infected cells are indeed astrocytes. PCR and Northern (RNA) blot analyses also confirmed that the astrocytes are infected by HHV-6. The progeny virus did not alter its host range and could reinfect T cells as well as primary astrocytes. These findings suggest that infection of primary human astrocytes may play a role in the neuropathogenesis of HHV-6.

Astrocytes↗
PubMed1996

Longitudinal studies of viral sequence, viral phenotype, and immunologic parameters of human immunodeficiency virus type 1 infection in perinatally infected twins with discordant disease courses.

Perinatal human immunodeficiency virus type 1 (HIV-1) infections cause a broad spectrum of clinical disease and are variable in both the age of the patient at onset of serious disease and the progression of the clinical course. Heterozygotic perinatally infected twins with a marked difference in their clinical courses were monitored during the first 2 years of life. Twin B, the second-born twin, developed AIDS by 6 months of age and died at 22 months of age, while twin A remained minimally symptomatic through the first 2 years. Sequential blood specimens were obtained from the twins in order to characterize the immunologic properties of the children and the phenotypes and genotypes of the HIV-1 isolates at various times. Twin A developed neutralizing antibodies and a high-level antibody-mediated cellular cytotoxicity (ADCC) response, while twin B had no neutralizing antibody and a much lower ADCC response. The virus isolates obtained from the two children at various time points proliferated equally well in peripheral blood mononuclear cells, were nonsyncytium inducing, and could not infect established T-cell lines. They differed in their ability to infect primary macrophages. In parallel to the biological studies, the HIV-1 tat and part of the env gene sequences of the longitudinal isolates at four time points were determined. Sequences of virus from both twins at different time points were highly conserved; the viruses evolved at a similar rate until the last analyzed time point, at which there was a dramatic increase in sequence diversity for the sicker child, especially in the tat gene. Our results show that the viruses isolated at different times do not have significant changes in growth properties. The absence or low levels of neutralizing antibodies may correlate with disease progression in the twins.

Acquired Immunodeficiency Syndrome↗