Biomedical subjects

R A Anderson

Publications and source records attributed to R A Anderson.

At least 19 recordsLinked to original sources

PubMed2006

Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway.

BACKGROUND: Prostaglandin E(2) (PGE(2)) has been shown to modulate angiogenesis and tumour progression via the E-series prostanoid-2 (EP2) receptor. Endometrial adenocarcinomas may be exposed to endogenous PGE(2) and exogenous PGE(2), present at high concentration in seminal plasma. METHODS: This study investigated fibroblast growth factor 2 (FGF2) mRNA expression and cell signalling in response to seminal plasma or PGE(2), using an endometrial adenocarcinoma (Ishikawa) cell line stably expressing the EP2 receptor (EP2 sense cells) and endometrial adenocarcinoma explants. RESULTS: Seminal plasma and PGE(2) induced a significant up-regulation of FGF2 expression in EP2 sense but not parental untransfected Ishikawa (wild-type) cells (P < 0.05). These effects were inhibited by co-treatment with EP2 receptor antagonist or inhibitors of protein kinase A, c-Src, epidermal growth factor receptor (EGFR) kinase or extracellular signal-regulated kinase (ERK) signalling. The treatment of EP2 sense cells with seminal plasma induced cAMP accumulation and phosphorylation of c-Src, EGFR kinase and ERK via the EP2 receptor. Finally, seminal plasma and PGE(2) significantly increased FGF2 mRNA expression in endometrial adenocarcinoma tissue explants via the EP2 receptor (P < 0.05). CONCLUSIONS: Seminal plasma and PGE(2) can similarly activate FGF2 expression and EP2 receptor signalling in endometrial adenocarcinoma cells. These data highlight the potential for seminal plasma exposure to facilitate tumorigenesis-angiogenesis in endometrial adenocarcinomas in vivo.

Adenocarcinoma↗

PubMed2006

The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer.

BACKGROUND: Reproductive function following cancer treatment is of increasing importance with improving survival rates. We therefore assessed the markers of the ovarian reserve in premenopausal women, to investigate and compare the effects of chemotherapy and long-term gonadotrophin withdrawal on ovarian function. METHODS: Fifty premenopausal (age range 28-52 years) women with early breast cancer were recruited. Serum hormone and ovarian ultrasound measurements were taken before treatment and at intervals up to 1 year during chemotherapy or gonadotrophin suppressive therapy. RESULTS: Pretreatment samples indicated a fall in anti-Müllerian hormone (AMH) concentration with age before changes in other hormone concentrations. AMH concentration showed a rapid and marked fall during chemotherapy, with undetectable concentrations in many women (P<0.0001). Inhibin B concentration showed a lesser fall (P<0.0001), whereas estradiol (E2) concentrations were maintained. Both antral follicle count (AFC) and ovarian volume fell (P<0.0001 and P<0.05 respectively). Regimens containing taxanes in addition to cyclophosphamide showed increased gonadotoxicity. Gonadotrophin suppression resulted in expected falls in E2 (P<0.05) and inhibin B (P<0.001) levels, but also resulted in a delayed fall in AMH level after 6 months (P<0.0001). CONCLUSIONS: These data confirm the value of AMH concentration as an early indicator of ovarian ageing including assessment of chemotherapy-induced ovarian follicle loss. FSH and AMH concentration measurements may be useful for the comparison of ovarian toxicity of different chemotherapy regimens.

Adult↗

PubMed2006

Prolonged deterioration of endothelial dysfunction in response to postprandial lipaemia is attenuated by vitamin C in Type 2 diabetes.

BACKGROUND: Endothelial dysfunction (ED) has been described in Type 2 diabetes (T2DM). We have described previously a diminution of flow-mediated arterial dilatation and, by implication, further ED in T2DM in response to postprandial lipaemia (PPL) at 4 h. This is possibly mediated by oxidative stress/alteration of the nitric oxide (NO) pathway. T2DM subjects tend to exhibit both exaggerated and prolonged PPL. We therefore studied the relationship of PPL to the duration of ED in T2DM subjects and oxidative stress with or without the antioxidant, vitamin C. METHODS: Twenty subjects with T2DM with moderate glycaemic control (mean HbA1c 8.4%) were studied. After an overnight fast, all subjects consumed a standard fat meal. Endothelial function (EF), lipid profiles, and venous free radicals were measured in the fasting, peak lipaemic phase (4 h) and postprandially to 8 h. The study was repeated in a double-blinded manner with placebo, vitamin C (1 g) therapy for 2 days prior to re-testing and with the fat meal. Oxidative stress was assessed by lipid-derived free radicals in plasma, ex vivo by electron paramagnetic resonance spectroscopy (EPR) and by markers of lipid peroxidation (TBARS). Endothelial function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery. RESULTS: There was a significant decrease in endothelial function in response to PPL from baseline (B) 1.3 +/- 1.3% to 4 h 0.22 +/- 1.1% (P < 0.05) and 8 h 0.7 +/- 0.9% (P < 0.05) (mean +/- sem). The endothelial dysfunction seen was attenuated at each time point with vitamin C. Baseline EF with vitamin C changed from (fasting) 3.8 +/- 0.9-2.8 +/- 0.8 (at 4 h) and 2.9 +/- 1.3 (at 8 h) in response to PPL. Vitamin C attenuated postprandial (PP) oxidative stress significantly only at the 4-h time point [301.1 +/- 118 (B) to 224.7 +/- 72 P < 0.05] and not at 8 h 301.1 +/- 118 (B) to 260 +/- 183 (P = NS). There were no changes with placebo treatment in any variable. PPL was associated with a PP rise in TG levels (in mmol/l) from (B) 1.8 +/- 1 to 2.7 +/- 1 at 4 h and 1.95 +/- 1.2 at 8 h (P = 0.0002 and 0.33, respectively). CONCLUSION: PPL is associated with prolonged endothelial dysfunction for at least 8 h after a fatty meal. Vitamin C treatment improves endothelial dysfunction at all time points and attenuates PPL-induced oxidative stress. This highlights the importance of low-fat meals in T2DM and suggests a role for vitamin C therapy to improve endothelial function during meal ingestion.

Administration, Oral↗

PubMed2005

A multicentre study investigating subcutaneous etonogestrel implants with injectable testosterone decanoate as a potential long-acting male contraceptive.

BACKGROUND: The combination of etonogestrel implants with injectable testosterone decanoate was investigated as a potential male contraceptive. METHODS: One hundred and thirty subjects were randomly assigned to three treatment groups, all receiving two etonogestrel rods (204 mg etonogestrel) and 400 mg testosterone decanoate either every 4 weeks (group I, n = 42), or every 6 weeks (group II, n = 51) or 600 mg testosterone decanoate every 6 weeks (group III, n = 37) for a treatment period of 48 weeks. RESULTS: One hundred and ten men completed 48 weeks of treatment. Sperm concentrations of <1 x 10(6)/ml were achieved in 90% (group I), 82% (group II) and 89% (group III) of subjects by week 24. Suppression was slower in group II, which also demonstrated more frequent escape from gonadotrophin suppression than groups I and III. Peak testosterone concentrations remained in the normal range throughout in all groups. Mean trough testosterone concentrations were initially subphysiological but increased into the normal range during treatment. Mean haemoglobin levels increased in group I, and a non-significant increase in weight and decline in high-density lipoprotein cholesterol was observed in all groups. Fourteen subjects discontinued treatment due to adverse events. CONCLUSIONS: Subcutaneous etonogestrel implants in combination with injectable testosterone decanoate resulted in profound suppression of spermatogenesis that could be maintained for up to 1 year. Efficacy of suppression was less in group II, probably due to inadequate testosterone dosage. This combination has potential as a long-acting male hormonal contraceptive.

Administration, Cutaneous↗

PubMed2005

Separate functions of gelsolin mediate sequential steps of collagen phagocytosis.

Collagen phagocytosis is a critical mediator of extracellular matrix remodeling. Whereas the binding step of collagen phagocytosis is facilitated by Ca2+-dependent, gelsolin-mediated severing of actin filaments, the regulation of the collagen internalization step is not defined. We determined here whether phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] regulation of gelsolin is required for collagen internalization. In gelsolin null fibroblasts transfected with gelsolin severing mutants, actin severing and collagen binding were strongly impaired but internalization and actin monomer addition at collagen bead sites were much less affected. PI(4,5)P2 accumulated around collagen during internalization and was associated with gelsolin. Cell-permeable peptides mimicking the PI(4,5)P2 binding site of gelsolin blocked actin monomer addition, the association of gelsolin with actin at phagosomes, and collagen internalization but did not affect collagen binding. Collagen beads induced recruitment of type 1 gamma phosphatidylinositol phosphate kinase (PIPK1gamma661) to internalization sites. Dominant negative constructs and RNA interference demonstrated a requirement for catalytically active PIPK1gamma661 for collagen internalization. We conclude that separate functions of gelsolin mediate sequential stages of collagen phagocytosis: Ca2+-dependent actin severing facilitates collagen binding, whereas PI(4,5)P2-dependent regulation of gelsolin promotes the actin assembly required for internalization of collagen fibrils.

Actins↗

PubMed2005

Germ cell proliferation and apoptosis in the developing human ovary.

CONTEXT: The regulation of germ cell proliferation and loss during human ovarian development is poorly understood. This is of particular interest at the time leading up to the formation of primordial follicles, at 18 wk gestation onward. OBJECTIVE: The objective of the study was to identify and quantify germ cell proliferation and apoptosis and expression of caspases in the human fetal ovary. DESIGN: This study was a laboratory investigation. SETTING: The study was conducted at a research institute. METHODS: Cell proliferation and apoptosis were detected using immunohistochemical localization of phosphorylated histone H3 and cleaved caspase-3, respectively. Caspases were also detected by immunoblotting. RESULTS: The overall proportion of germ cells in mitosis remained constant between 14 and 19 wk but showed increasing clustering. Caspase-2, -3, -7, -8, and -9 were detected by immunoblotting. There was a significant increase in germ cell apoptosis. A specimen of 20 wk gestation showed similar phosphorylated histone H3 but markedly lower cleaved caspase-3 expression than earlier gestations. Cleaved caspase-3 was not expressed in oocytes that had formed primordial follicles. CONCLUSIONS: These results indicate that as primordial follicle formation is initiated and progresses, there is an increase in both mitotic activity and apoptosis of those germ cells that have not reached the apparently protective environment of the primordial follicle.

Apoptosis↗

PubMed2005

Drugs in oral fluid Part I. Validation of an analytical procedure for licit and illicit drugs in oral fluid.

A qualitative and quantitative analytical method was developed and validated for the determination of 49 licit and illicit drugs in oral fluid. Small oral fluid samples, volume 1mL, were collected from volunteers using a modified Omni-Sal device and the analytes were extracted from an oral fluid/buffer mixture using a single Bond Elut Certify solid phase extraction cartridge. Liquid chromatography-tandem mass spectrometry (LC-MS-MS) and gas chromatography-repetitive full scan mass spectrometry (GC-MS) were used in parallel to analyze the extracts for the targeted drugs. Extracts were analyzed by GC-MS in their underivatized form and as their pentafluoropropionyl derivatives. Deuterated internal standards were used for quantification of drugs of abuse by LC-MS-MS to minimize matrix effects. Methadone-d(9) and tumoxetine were used as the internal standards for quantification of non-derivatized and derivatized analytes respectively by GC-MS. Linearity was demonstrated over the range 5-200 ng/mL and limits of detection were less than 4 ng/mL for each drug analyzed. The method demonstrated acceptable recoveries for most of the analytes and good intra- and inter-day precision. Acquisition of data by repetitive full scan GC-MS allows the addition of further analytes to the target menu.

Chromatography, Liquid↗

PubMed2005

Alterations of antioxidant trace elements (Zn, Se, Cu) and related metallo-enzymes in plasma and tissues following burn injury in rats.

To improve the nutritional support for burn patients, we evaluated the alterations of selenium, zinc and copper (Se, Zn and Cu) and their possible contributions to an unbalanced antioxidant response to burn injury. These trace elements and the related antioxidant enzymes, glutathione peroxidase (GPx) and superoxide dismutase (SOD), were studied both in plasma (or serum) and tissues of 20% total body surface area (TBSA) burned rats for 10 days. While plasma Se and serum Zn levels significantly decreased 6 h after burn injury, serum Cu levels increased after 1 day and remained elevated the following 9 days. Selenium levels increased in kidney but decreased progressively in liver. The hepatic Zn and Cu concentrations followed a biphasic increase following burn injury. During the first day, GPx activity decreased in plasma and remained unchanged in the organs, except for a moderate diminution in the liver. Liver Cu/Zn SOD activity increased from 6 h to 4 days. In summary, following burn injury, copper and zinc were redistributed to the liver and selenium to the kidney with non-detectable changes in the muscle and brain. Changes in antioxidant enzyme activities following burn injury were significant mainly in the plasma. Early combined antioxidant supplementation to maintain and restore antioxidant status in burn patients requires further study.

Animals↗

PubMed2005

GI complications in pediatric patients post-BMT.

This retrospective study comprehensively examined hepatic and gastrointestinal complications post-bone marrow transplant (BMT) in a heterogeneous group of 132 pediatric patients that underwent 142 transplants. Hyperbilirubinemia occurred in 28% of this population with clinically evident jaundice in 16%. Acute graft-versus-host disease (GVHD) occurred in 46% of the population, with liver involvement in 39% and intestinal involvement in 60% of those with acute GVHD. Veno-occlusive disease (VOD) occurred in 18% of the population. A greater increase in hepatic transaminases was noted in GVHD and VOD than nonspecific liver injury. Serum bilirubin may help to differentiate between VOD and hepatic GVHD. Biliary sludging occurred in 20% of patients and was associated with increased morbidity. Common post transplant gastrointestinal complications included mucositis in 90%, vomiting in 85% and abdominal pain in 71%. TPN support post transplant was required in 91%. Diarrhea occurred in 67% with the most common identified etiologies reported as GVHD (27%), viral (6%), Clostridium difficile (8%) infections and unknown (28%). Typhilitis developed in 3.5%. Melena or hematochezia occurred in 11 patients (8%). However, gastrointestinal bleeding was disproportionately represented in intensive care unit admissions (5/27) and 100 day mortality (5/21). Gastrointestinal and hepatic complications represent a major cause of morbidity and mortality in pediatric BMT recipients.

Bile↗

PubMed2005

Brain-derived neurotrophic factor promotes bovine oocyte cytoplasmic competence for embryo development.

The ability of an oocyte to support early embryonic development requires both nuclear and cytoplasmic maturation. We have investigated the effects of brain-derived neurotrophic factor (BDNF) on maturation of the bovine oocyte and embryo development after parthenogenetic activation. By RT-PCR and immunohistochemistry, cumulus and oocytes were shown to express mRNA and protein for BDNF and the p75 common neurotrophin receptor. However, mRNA for the BDNF-specific full length and truncated isoforms of the TrkB receptor are only detected in cumulus, suggesting that oocytes and cumulus differ in their capacity to respond to neurotrophin signalling. In in vitro maturation experiments, the proportion of cumulus oocyte complexes maturing to metaphase II was not altered by BDNF in groups lacking fetal calf serum (FCS), but was significantly lower than the positive control containing 10% FCS (P < 0.01). However, after maturation, the proportion of parthenogenetically activated oocytes forming blastocysts was highest for 10 ng/ml BDNF (24%, n = 95) followed by 100 ng/ml BDNF (18%, n = 91) and 10% FCS (15%, n = 103), which in turn were greater than no serum (10%, n = 83; P < 0.01). Maturation in the presence of a BDNF blocking antibody resulted in a blastocyst yield that was comparable to the absence of serum, and lower than in the presence of BDNF (P < 0.01). Similar effects on progression to metaphase II and blastocyst formation were observed using oocytes matured without cumulus. Together, these results provide the first evidence for a role for neurotrophins in promoting oocyte cytoplasmic competence to support embryonic development, despite being insufficient in the absence of serum to enhance nuclear maturation.

Animals↗

PubMed2004

Does the addition of recombinant LH in WHO group II anovulatory women over-responding to FSH treatment reduce the number of developing follicles? A dose-finding study.

BACKGROUND: In anovulatory women undergoing ovulation induction, addition of recombinant human LH (rLH) to FSH treatment may promote the dominance of a leading follicle when administered in the late follicular phase. The objective of this study was to find the optimal dose of rLH that can maintain the growth of a dominant follicle, whilst causing atresia of secondary follicles. METHODS: Women with infertility due to anovulation and over-responding to FSH treatment were randomized to receive, in addition to 37.5 IU recombinant human FSH (rFSH), either placebo or different doses of rLH (6.8, 13.6, 30 or 60 microg) daily for a maximum of 7 days. The primary efficacy endpoint was the proportion of patients who had exactly one follicle > or = 16 mm on hCG day. RESULTS: Among 153 enrolled patients, the five treatment groups were similar in terms of baseline characteristics. The proportion of patients with exactly one follicle > or = 16 mm ranged from 13.3% in the placebo group to 32.1% in the 30 microg rLH group (P = 0.048). The pregnancy rate ranged from 10.3% in the 60 microg group to 28.6% in the 30 microg rLH group. Adverse events were similar between groups. CONCLUSIONS: In patients over-responding to FSH during ovulation induction, doses of up to 30 microg rLH/day appear to increase the proportion of patients developing a single dominant follicle (> or = 16 mm). Our data support the 'LH ceiling' concept whereby addition of rLH is able to control development of the follicular cohort.

Adult↗

PubMed2004

Depot testosterone with etonogestrel implants result in induction of azoospermia in all men for long-term contraception.

BACKGROUND: Combined testosterone and progestogen preparations are a promising approach to male hormonal contraception. We investigated the effect of s.c. etonogestrel with depot testosterone on spermatogenesis in normal men over a period of 48 weeks. METHODS: Fifteen healthy men received three s.c. 68 mg etonogestrel implants. Testosterone pellets (400 mg) were administered at 12 weekly intervals. RESULTS: Nine men completed 48 weeks of treatment. Four subjects chose to discontinue after 6 months, one man withdrew from the study early for personal reasons and one was withdrawn due to illness. Sperm concentrations of <1 x 10(6)/ml were achieved in all men by 16 weeks of treatment. All men became azoospermic, although the time to achieve this varied from 8 to 28 weeks. Azoospermia was maintained in eight of the nine men treated for 48 weeks, one subject showing partial recovery from 40 weeks. Testosterone levels remained in the physiological range throughout. Treatment did not result in weight gain, change in body composition or decline in high-density lipoprotein cholesterol concentrations. CONCLUSIONS: The combination of three etonogestrel implants with depot testosterone results in rapid and consistent suppression of spermatogenesis. This can be maintained for up to 1 year and may therefore be a suitable approach for a long-acting male hormonal contraceptive.

Adolescent↗

PubMed2004

Spontaneous conception in a young woman who had ovarian cortical tissue cryopreserved before chemotherapy and radiotherapy for a Ewing's sarcoma of the pelvis: case report.

We report the case of a 14 year old girl who presented with a non-metastatic Ewing's sarcoma involving her superior pubic ramus. She received 14 courses of alkylating agent-based chemotherapy and direct radiation to her hemi-pelvis (55 Gy) and is alive and disease-free 8 years later. Multiple biopsies of ovarian cortical tissue were cryopreserved, with her written consent, before treatment began. Ovarian failure was confirmed on completion of treatment with cessation of menses and persistently elevated serum gonadotrophin and low estradiol levels on repeated measurement over 2 years. HRT was initiated. Irregular vaginal bleeding occurred due to radiation vaginitis. Reimplantation of ovarian cortical tissue was considered at 19 years as fertility was desired, but the decision deferred. A spontaneous conception occurred 1 year later and a healthy boy (birthweight 2.9 kg, 3rd-10th centile) was delivered at term by elective Caesarean section. This is the first case of a spontaneous conception occurring in a young woman with documented ovarian failure in whom ovarian cortical tissue had been cryopreserved. Clinicians should be aware of the possibility of spontaneous conception despite confirmed ovarian failure in young women successfully treated for cancer.

Adolescent↗

PubMed2004

Expression of activin subunits and receptors in the developing human ovary: activin A promotes germ cell survival and proliferation before primordial follicle formation.

The formation of the essential functional unit of the ovary, the primordial follicle, occurs during fetal life in humans. Factors regulating oogonial proliferation and interaction with somatic cells before primordial follicle formation are largely unknown. We have investigated the expression, localisation and functional effects of activin and its receptors in the human fetal ovary at 14-21 weeks gestation. Expression of mRNA for the activin betaA and betaB subunits and the activin receptors ActRIIA and ActRIIB was demonstrated by RT-PCR. Expression of betaA mRNA increased 2-fold across the gestational range examined. Activin subunits and receptors were localised by immunohistochemistry. The betaA subunit was expressed by oogonia, and the betaB subunit and activin receptors were expressed by both oogonia and somatic cells. BetaA expression was increased in larger oogonia at later gestations, but was low in oocytes within newly formed primordial follicles. Treatment of ovary fragments with activin A in vitro increased both the number of oogonia present and oogonial proliferation, as detected by bromodeoxyuridine (BrdU) incorporation. These data indicate that activin may be involved in the autocrine and paracrine regulation of germ cell proliferation in the human ovary during the crucial period of development leading up to primordial follicle formation.

Activin Receptors, Type II↗

PubMed2004

Determinants of platelet responsiveness to nitric oxide in patients with chronic heart failure.

Congestive heart failure (CHF) is associated with oxidative stress. Platelet responsiveness to nitric oxide (NO) donors, are impaired in patients with angina pectoris, possibly by increasing oxidative stress. We investigated the occurrence of platelet resistance to NO in patients, with ischaemic or non-ischaemic cardiomyopathy compared with normal subjects. Anti-aggregatory effects of sodium nitroprusside (SNP), oxidative stress and whole blood superoxide anion content were determined, with correlates of responsiveness to SNP. Inhibition of platelet aggregation by SNP was 65.4+/-3.55% in controls and 59.3+/-4.1% in CHF (P=ns) despite increased oxidative stress and post-aggregation O2- in CHF patients. However, subsets of CHF patients have NO-resistant platelets: this is associated with increasing age and/or increased oxidative stress (both p<0.05).

Adult↗

PubMed2004

Neurotrophin signaling in oocyte survival and developmental competence: a paradigm for cellular toti-potency.

While not fulfilling the criterion of a "stem cell" in being capable of self-renewal, mature and fertilized oocytes are the original "toti-potent" cells, whose capacity for expansion and differentiation can only be approximated by stem cells of embryonic or adult origin in vitro. As such, the mechanisms by which oocytes acquire and manifest competence to support embryo development is of fundamental interest to efforts to control and re-specify somatic cell fate and toti-potency. This is underscored by the unparalleled capacity of oocyte cytoplasm to successfully re-specify the genetic program of animal development following cell nuclear replacement (i.e., cloning). Thus, the knowledge gained by understanding the acquisition of oocyte developmental competence could ultimately facilitate the creation of adult stem cells in vitro from terminally differentiated cells, ex ovo. In this paper, we review the concept of oocyte developmental competence, and focus on our own research and that of others implicating a role for neurotrophins in this process, and that of oocyte cell survival. Lastly we propose a role for neurotrophin signalling in embryo stem cell survival.

Cell Nucleus↗

PubMed2003

Phosphatidylinositol phosphate kinases put PI4,5P(2) in its place.

Phosphatidylinositol 4,5 bisphosphate (PI4,5P(2)) is a critical second messenger that regulates a myriad of diverse cellular activities including modulation of the actin cytoskeleton, vesicle trafficking, focal adhesion formation, and nuclear events. In order to effectively regulate these disparate cellular events, synthesis of PI4,5P(2) by phosphatidylinositol phosphate kinases (PIP kinases) must be both spatially and temporally regulated. Two subfamilies of PIP kinases, types I and II, allow the generation of PI4,5P(2) from independent pools of substrate, PI(4)P and PI(5)P respectively. In turn, type I and II PIP kinases show different subcellular localization and thus are involved in distinct signaling pathways. Additionally, several type I isoforms, and their splice variants, have now been shown to be differentially localized throughout the cell and to be involved in the synthesis of PI4,5P(2) at distinct sites. These findings implicate PIP kinases as the major regulators of PI4,5P(2)-mediated events, making them key signaling enzymes in a variety of processes. Understanding the mechanisms regulating spatial and temporal synthesis of PI4,5P(2) by PIP kinases is vital for understanding these processes as a whole. This review examines both structural and regulatory features that modulate activity, localization, and substrate usage of PIPKs.

Actins↗

PubMed2003

Incidence, survival and risk factors for the development of veno-occlusive disease in pediatric hematopoietic stem cell transplant recipients.

The incidence, risk factors and mortality of veno-occlusive disease (VOD) were identified for 142 pediatric hematopoietic stem cell (HSC) transplant recipients with hematological malignancies (83), solid tumors (41) and nonmalignant diseases (18). This historical cohort of 142 HSC transplant patients, from January 1993 through June 2000, was assessed by chart review. Risk factors for the development of VOD and mortality were assessed by multiple logistic regression and Kaplan-Meier survival curves respectively. The incidence of VOD was 18.3% (26/142 transplants). Multivariate analysis reconfirmed the known pretransplant risk factors of induction therapy with busulfan and transplantation with matched unrelated donor cells as significant risk factors for the development of VOD. In addition, two new risk factors, positive CMV serology in the recipient and TPN provided in the 30 days prior to transplant, were identified. Mortality in transplant patients at 100 days was greater in the VOD-positive group (10/26 (38.5%)) compared to the VOD-negative group (11/116 (9.5%) (P=0.001)). The risk of death was 4.97 times higher with 95% CIs (2.11, 11.71) for the VOD-positive group. Decreasing the risk factors for VOD may decrease mortality in this patient population.

Busulfan↗