Localized idiopathic retroperitoneal fibrosis mimicking primary obstructive megaureter in a child.
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Child, Preschool↗
Biomedical subjects
C Wong
Publications and source records attributed to C Wong.
Parents' perceptions of chronic illness trajectories.
The notion of a small, generic set of chronic illness trajectories that can be independent of specific medical diagnoses, though controversial, has some theoretical, clinical, and qualitative research support. The purpose of this study was to quantitatively describe trajectories among parents of children with a chronic condition. It was hypothesized that factor analysis would confirm 3 trajectories similar to those in the qualitative literature and that parents' perceptions of their child's trajectory would differ significantly from medically based perceptions. A total of 140 parents provided data on their perceptions of the past, present, and future course of the condition of their repeatedly hospitalized child. Fourteen time-related items from the Coping Health Inventory for Parents Questionnaire on Resources and Stress and the Parenting Stress Index were analyzed. Pre- and post-hospitalization factor analyses extracted the same 8 items to construct 3 trajectories: Life Threatening; Declining; and Stable, Optimistic. The views of approximately one third of the parents differed from medically based classifications. Type of nursing care had no bearing on the perceptions of the parents.
Adaptation, Psychological↗
Coronary artery disease varies seasonably in subtropics.
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Adult↗
Tuberculosis in immigrants and visitors.
Immigrants and visitors are a significant factor in the epidemiology of tuberculosis (TB) in New Zealand, accounting for an increasing proportion of notifications in recent years. At present screening of immigrants from countries with a high incidence of TB is inadequate. There are deficiencies in procedures, inadequate screening coverage, ineffectual coordination between the Ministry of Health and New Zealand Immigration Service, incomplete follow-up on those at risk of TB, confusion over financial responsibility, inadequate data to describe the problems and monitor interventions, and a lack of commitment to assistance with TB control in neighbouring countries from which some of our TB arises. We make recommendations in all of these areas. Timely screening of high-risk immigrants should be seen as health protection for ethnic minorities.
Emigration and Immigration↗
Phospholipid membranes form specific nonbilayer molecular arrangements that are antigenic.
Hexagonal phase (H(II))-preferring lipids such as phosphatidate, cardiolipin, and phosphatidylserine form nonbilayer molecular arrangements in lipid bilayers. While their presence in biological membranes has not been established, in vitro studies suggest that alterations in membrane properties modify their function. In this study, antiphospholipid monoclonal antibodies were developed against nonbilayer structures. One of the monoclonal antibodies identifies nonplanar surfaces in liposomes and in membranes of cultured cells. These results are the first evidence that natural membranes maintain a fragile balance between bilayer and nonbilayer lipid arrangements. Therefore, these antibodies can be used to evaluate the role of H(II)-preferring lipids in the modulation of membrane activities. Our studies demonstrated that nonplanar surfaces are highly immunogenic. Although these structures are normally transient, their formation can be stabilized by temperature variations, drugs, antibiotics, apolar peptides, and divalent cations. Our studies demonstrated that abnormal exposure of nonbilayer arrangements may induce autoimmune responses as found in the antiphospholipid syndrome.
Animals↗
A role for T helper 2 cells in mediating skin fibrosis in tight-skin mice.
Mice heterozygous for the tight-skin (Tsk) mutation develop skin fibrosis. Previous studies have implicated a role for the immune system and, specifically, CD4(+) T cells, in the etiology of skin fibrosis in Tsk/+ mice. We have recently shown that the administration of neutralizing anti-IL-4 antibodies to Tsk/+ mice prevented the development of skin fibrosis in these mice. Since IL-4 is a major cytokine produced by T helper 2 (Th2) cells, we investigated the role of Th2 cells in mediating skin fibrosis in Tsk/+ mice. Previous studies have shown that the development of Th2 cells in non-Tsk mice is abrogated in mice with null mutation for either the IL-4 or the Stat6 gene. In this study we showed that the polarization of CD4(+) T cells from Tsk/+ mice toward the Th2 lineage is also dependent on a functioning IL-4 or Stat6 gene. More importantly, the development of skin fibrosis in Tsk/+ mice was abrogated by the IL4(-/-) or the Stat6(-/-) mutation. We also determined whether alteration of the TCR repertoire in Tsk/+ mice, achieved by the introduction of TCR transgenes, was able to prevent the development of skin fibrosis in Tsk/+ mice. We found that the exclusive usage of the Vbeta8.2 gene segment by T cells was sufficient to prevent skin fibrosis in Tsk/+ mice. This result suggests that the exclusive use of this Vbeta gene segment by T cells may have prevented the development of fibrosis-causing Th2 cells.
Animals↗
The area postrema of newborn swine is activated by hypercapnia: relevance to sudden infant death syndrome?
This study was performed to investigate a role of the neonatal area postrema (AP) in the chemoreceptor response to hypercapnia which is defective in sudden infant death syndrome (SIDS). AP responses to CO2 inhalation were monitored in 1 to 5 week old piglets by mapping neurons that were induced to express the c-fos gene product, Fos--a marker of functional activation. Interpretive confounds were minimized by controlling for hypoxia, the effects of surgical procedures and ambient environmental stressors on neuronal activity (c-fos expression). The AP demonstrated a powerful and reproducible response in neonatal swine breathing 10% CO2 for 1 h. Intensely immunolabeled nuclei were detected throughout the longitudinal extent of the circumventricular organ, and were especially heavily concentrated at rostral levels proximal to obex. Quantitative analysis verified statistically significant increases in numbers of cells that were induced to express Fos-like immunoreactivity (FLI) in the AP of CO2- stimulated piglets as compared to control groups. No detectable age-related differences were observed in AP response patterns. Conclusions. The AP responds to hypercapnic stress in the newborn piglet. A mature circumventricular organ response in the neonate may be crucial in defending against common environmental stressors, such as nicotine exposure--an emetic agent acting via the AP and a major risk factor in SIDS. Hence, a defect of the AP or its network may underlie a loss of state-dependent controls over cardiopulmonary reflex function in SIDS.
Animals↗
Limitation of Tat-associated transcriptional processivity in HIV-infected PBMC.
The ability of HIV to match levels of viral mRNA to the activation state of the host cell may play a role in its ability to persist as well as to replicate. This linkage depends on the function of the viral transcriptional regulatory protein, Tat, which increases the efficiency of RNA elongation (transcriptional processivity) in response to cellular activation. To quantify levels of Tat function in vivo, a quantitative competitive RT-PCR assay was developed that reflects levels of TAR leader fragments (nonprocessive transcripts) and viral mRNA (processive transcripts), indicating low or high levels of Tat function, respectively. The abundance of these RNA species was measured in peripheral blood mononuclear cells (PBMC) of 22 HIV-1-positive individuals (CD4(+) T cell counts 63-934/mm3) and in established cell line models of HIV constitutive replication (H9IIIB) and reversible latency (U1 and ACH-2). In PBMC, the level of total viral transcripts ranged over four orders of magnitude; however, nonprocessive transcription predominated: 70% of PBMC samples had a ratio of processive to total transcripts of <0.3 and none of the samples had 100% processivity. The cell line studies revealed that, even in activated H9IIIB cells, nonprocessive transcription dominates and that latently infected cells can have different transcriptional responses to activation. This is the first study that enumerates degrees of transcriptional processivity in the circulating mononuclear cell compartment and the results suggest that limitation of Tat function may be a common phenotype throughout the course of the disease.
Cell Line↗
Smads bind directly to the Jun family of AP-1 transcription factors.
Smad3 and Smad4 are sequence-specific DNA-binding factors that bind to their consensus DNA-binding sites in response to transforming growth factor beta (TGFbeta) and activate transcription. Recent evidence implicates Smad3 and Smad4 in the transcriptional activation of consensus AP-1 DNA-binding sites that do not interact with Smads directly. Here, we report that Smad3 and Smad4 can physically interact with AP-1 family members. In vitro binding studies demonstrate that both Smad3 and Smad4 bind all three Jun family members: JunB, cJun, and JunD. The Smad interacting region of JunB maps to a C-terminal 20-amino acid sequence that is partially conserved in cJun and JunD. We show that Smad3 and Smad4 also associate with an endogenous form of cJun that is rapidly phosphorylated in response to TGFbeta. Providing evidence for the importance of this interaction between Smad and Jun proteins, we demonstrate that Smad3 is required for the activation of concatamerized AP-1 sites in a reporter construct that has previously been characterized as unable to bind Smad proteins directly. Together, these data suggest that TGFbeta-mediated transcriptional activation through AP-1 sites may involve a regulated interaction between Smads and AP-1 transcription factors.
Amino Acid Sequence↗
Distribution of tracer levels of cocaine in the human brain as assessed with averaged [11C]cocaine images.
The Ability of cocaine to block the dopamine transporter (DAT) in the nucleus accumbens, as well as its non-striatal and non-DAT actions, appears to be crucial for its reinforcing/rewardig effects. However, we have been unable to use PET and [11C]cocaine to map small regions with greater sensitivity due in part to the low specific to non-specific binding ration of [11C]cocaine. In order to increase the signal to noise ratio of the individual [11]cocaine images, we averaged the distribution volume (DV) PET images of 17 normal controls. In addition we also obtained averaged images for the dynamic set (14 time frames) and for the K1 values. The dynamic images were used to generate the average time activity curves from which we obtained the time required to half maximum clearance (T50). Twenty-nine ROIs were identified in the Talarach-Tournoux atlas and were then projected to the corregistered average PET image. The brain regions clustered in 3 groups according to their DV values. The highest activity (Group DV.1, 4.6-3.7) included putamen > accumbens > caudate. Intermediate DVs (Group DV.2, 3.2-2.8) included thalamus (mediodorsal and ventrolateral nucleus) > precuneus and posterior cingulate gyrus > amygdala, hippocampus, and temporal pole. Group DV.3 with low DVs (2.6-2.1) included the orbital cortex, precentral gyrus, and cerebellum. The brain regions clustered in 3 groups according to their T50 values. Regions with the faster clearance rates (15-20 minutes) included the orbital cortex, posterior cingulate, dorsomedial thalamus, precuneus, and cerebellum. Intermediate clearance rates (20-25 minutes) included caudate, putamen and accumbens regions with the slowest clearance rates (25-30 minuters) included caudate, putamen, and accumbens. In addition to the previously documented high binding of cocaine in striatum and moderate binding in thalamus in the living human brain this study also documents binding of cocaine in limbic and paralimbic brain regions. Further work is required to characterize the binding properties of cocaine in these brain areas and to elucidate their role in the reinforcing and addictive properties of cocaine.
Adult↗
Heparin is essential for a single keratinocyte growth factor molecule to bind and form a complex with two molecules of the extracellular domain of its receptor.
Keratinocyte growth factor (KGF or FGF-7) is a member of the heparin binding fibroblast growth factor (FGF) family and is a paracrine mediator of proliferation and differentiation of a wide variety of epithelial cells. To examine the stoichiometry of complexes formed between KGF and its receptor, we have utilized a soluble variant of the extracellular region of the KGF receptor containing two tandem immunoglobulin-like loops, loops II and III (sKGFR). Ligand-receptor complexes were examined by size exclusion chromatography, light scattering, N-terminal protein sequencing, and sedimentation velocity. In the presence of low-molecular mass heparin ( approximately 3 kDa), we demonstrate the formation of complexes containing two molecules of sKGFR and one molecule of KGF. In the absence of heparin, we were unable to detect any KGF-sKGFR complexes using the above techniques, and additional studies in which sedimentation equilibrium was used show that the binding is very weak (Kd >/= 70 microM). Furthermore, using heparin fragments of defined size, we demonstrate that a heparin octamer or decamer can promote formation of a 2:1 complex, while a hexamer does not. Utilizing the highly purified proteins and defined conditions described in this study, we find that heparin is obligatory for formation of a KGF-sKGFR complex. Finally, 32D cells, which appear to lack low-affinity FGF binding sites, were transfected with a KGFR-erythropoeitin receptor chimera and were found to require heparin to achieve maximal KGF stimulation. Our data are consistent with the previously described concept that cell- or matrix-associated heparan sulfate proteoglycans (HSPGs) and FGF ligands participate in a concerted mechanism that facilitates FGFR dimerization and signal transduction in vivo.
Amino Acid Sequence↗
p21(CIP1) and p57(KIP2) control muscle differentiation at the myogenin step.
Cell-cycle arrest is thought to be required for differentiation of muscle cells. However, the molecules controlling cell-cycle exit and the differentiation step(s) dependent on cell-cycle arrest are poorly understood. Here we show that two Cdk inhibitors, p21(CIP1) and p57(KIP2), redundantly control differentiation of skeletal muscle and alveoli in the lungs. Mice lacking both p21 and p57 fail to form myotubes, display increased proliferation and apoptotic rates of myoblasts, and display endoreplication in residual myotubes. This point of arrest during muscle development is identical to that of mice lacking the myogenic transcription factor myogenin, indicating a role for cell-cycle exit in myogenin function. Expression of myogenin, p21, and p57 is parallel but independent, and in response to differentiation signals, these proteins are coordinately regulated to trigger both cell-cycle exit and a dependent muscle-specific program of gene expression to initiate myoblast terminal differentiation and muscle formation.
Animals↗
Clomipramine vs desipramine crossover trial in body dysmorphic disorder: selective efficacy of a serotonin reuptake inhibitor in imagined ugliness.
BACKGROUND: Body dysmorphic disorder (preoccupation with an imagined or slight defect in appearance) is a common and disabling disorder associated with high rates of delusional symptoms and suicide attempts. Although preliminary studies suggest that serotonin reuptake inhibitors may be effective for body dysmorphic disorder, to date no controlled treatment studies have been published. METHODS: Forty patients were enrolled and 29 were randomized into a 16-week, double-blind, crossover-design study of clomipramine, a potent serotonin reuptake inhibitor, and active control desipramine, a selective norepinephrine reuptake inhibitor. Outcome measures included specific ratings of body dysmorphic disorder severity, delusionality, and functional impairment. RESULTS: Clomipramine was superior to desipramine in the acute treatment of body dysmorphic disorder symptoms as measured by assessment of patients' obsessive preoccupation with perceived body defects, repetitive behaviors in response to this preoccupation, and global ratings of symptom severity. Treatment efficacy was independent of the presence or severity of comorbid diagnoses of obsessive-compulsive disorder, depression, or social phobia. Likewise, clomipramine was equally effective regardless of whether the patients had insight or held their dysmorphic misperception with delusional intensity. Clomipramine was also superior to desipramine in improving functional disability. CONCLUSIONS: Clomipramine is more effective than desipramine in the treatment of body dysmorphic disorder and is effective even among those patients who are delusional.
Adrenergic Uptake Inhibitors↗
Oliguria, an unusual presentation of primary signet ring-cell adenocarcinoma of the urinary bladder: a case report and review of the literature.
Adenocarcinomas represent approximately 2% of primary bladder epithelial malignancies. Of these, the signet ring-cell variant is the rarest form. We report such a case, with the unusual presentation of oliguria, including radiologic and histopathologic findings. The current literature is reviewed.
Aged↗
Effect of a media-led education campaign on breast and cervical cancer screening among Vietnamese-American women.
BACKGROUND: Previous research has shown that breast and cervical cancer screening rates are low among Vietnamese women. METHODS: Over a 24-month period, we implemented a media-led community education campaign to promote recognition, intention, receipt, and currency of routine checkups, clinical breast examinations, mammograms, and Pap tests among Vietnamese-American women in Alameda and Santa Clara Counties in northern California. Women in Los Angeles and Orange Counties in southern California served as controls. To evaluate its impact, pretest telephone interviews were conducted of 451 randomly selected women in the intervention area and 482 women in the control area and posttest interviews with 454 and 422 women, respectively. RESULTS: At posttest, after controlling for demographic differences in the surveyed populations, the odds ratios for the intervention effect were statistically significant for having heard of a general checkup, Paptest, and clinical breast examination (CBE); planning to have a checkup, Pap test, CBE, and mammogram; and having had a checkup and Pap test. The intervention had no effect on being up to date for any of the tests. CONCLUSIONS: A media-led education intervention succeeded in increasing recognition of and intention to undertake screening tests more than receipt of or currency with the tests.
Adult↗
Prenatal diagnosis of hydronephrosis: impact on renal function and its recovery after pyeloplasty.
PURPOSE: We reviewed our experience with corrective surgery for congenital ureteropelvic junction obstruction to assess the impact of mode of presentation on renal function at diagnosis and on postoperative recovery of function. MATERIALS AND METHODS: We reviewed the records of consecutive children who underwent pyeloplasty or nephrectomy for ureteropelvic junction obstruction during a 5-year period at our hospitals. Patients were divided into those with and without a prenatal diagnosis of hydronephrosis. In each group we compared preoperative and postoperative differential renal function, as measured by nuclear renography. RESULTS: We identified 89 patients, of whom 51 (57%) and 38 (43%) presented with prenatal and postnatal hydronephrosis, respectively. Kidneys in which hydronephrosis was diagnosed prenatally had better average differential renal function than those in which the condition was detected postnatally (45 versus 37%). This difference was even more significant in kidneys with less than 40% initial function (31 versus 21%). Presentation with a palpable mass was associated with worst renal function (mean 23%). Postoperatively renal function did not recover significantly in either group. There was a minimal increase in postoperative differential renal function in the subgroup of patients in whom initial differential renal function was less than 40%, although there was no significant difference in the 2 groups (6.5 versus 4.8%). CONCLUSIONS: The early diagnosis of hydronephrosis provided by prenatal ultrasonography is associated with less obstructive nephropathy. Prolonged followup is necessary for studies of the natural history of hydronephrosis because relevant obstruction manifests clinically years later. Despite successful pyeloplasty function recovery is minimal in kidneys with poor function and hydronephrosis diagnosed prenatally. Our findings do not support previous observations that poor function markedly improves after obstruction is relieved.
Child, Preschool↗
Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain.
The reinforcing effects of cocaine and methylphenidate have been linked to their ability to block dopamine transporters (DAT). Though cocaine and methylphenidate have similar in vitro affinities for DAT the abuse of methylphenidate in humans is substantially lower than of cocaine. To test if differences in in vivo potency at the DAT between these two drugs could account for the differences in their abuse liability we compared the levels of DAT occupancies that we had previously reported separately for intravenous methylphenidate in controls and for intravenous cocaine in cocaine abusers. DAT occupancies were measured with Positron Emission Tomography using [11C]cocaine, as a DAT ligand, in 8 normal controls for the methylphenidate study and in 17 active cocaine abusers for the cocaine study. The ratio of the distribution volume of [11C]cocaine in striatum to that in cerebellum, which corresponds to Bmax/Kd +1, was used as measure of DAT availability. Parallel measures were obtained to assess the cardiovascular effects of these two drugs. Methylphenidate and cocaine produced comparable dose-dependent blockade of DAT with an estimated ED50 (dose required to block 50% of the DAT) for methylphenidate of 0.07 mg/kg and for cocaine of 0.13 mg/kg. Both drugs induced similar increases in heart rate and blood pressure but the duration of the effects were significantly longer for methylphenidate than for cocaine. The similar in vivo potencies at the DAT for methylphenidate than for cocaine are in agreement with their reported relative in vitro affinities (Ki 390 nM and 640 nM respectively), which is likely to reflect the similar degree of uptake (8-10% of the injected dose) and regional distribution of these two drugs in the human brain. Thus, differences in the in vivo potency of these two drugs at the DAT cannot be responsible for the differences in their rate of abuse in humans. Other variables i.e. longer duration of methylphenidate's side effects may counterbalance its reinforcing effects.
Adult↗
Perineal talc exposure and subsequent epithelial ovarian cancer: a case-control study.
OBJECTIVE: To evaluate the role of talcum powder use as a risk factor for the development of epithelial ovarian cancer. METHODS: In a case-control study, 499 patients with epithelial ovarian cancer were frequency matched for age at diagnosis (-5 years) with a control population of 755 patients. The odds ratio (OR) for the development of epithelial ovarian cancer was estimated using logistic regression analysis with adjustment for age at diagnosis, parity, oral contraceptive use, smoking history, family history of epithelial ovarian cancer, age at menarche, menopausal status, income, education, geographic location, history of tubal ligation, and previous hysterectomy. RESULTS: Two hundred twenty-one of 462 patients (47.8%) in the study population and 311 of 693 patients (44.9%) in the control population had ever used talcum powder (OR 0.92; 95% confidence interval [CI] 0.24, 3.62). A significant association between duration of talc use and development of epithelial ovarian cancer was not demonstrable for 1-9 years (OR 0.9; 95% CI 0.6, 1.5), for 10-19 years (OR 1.4; 95% CI 0.9, 2.2), or for more than 20 years (OR 0.9; 95% CI 0.6, 1.2). To eliminate the possible confounding variable of surgery for the management of ovarian cancer, we omitted 135 patients in the study population who underwent hysterectomy within 5 years of the diagnosis of ovarian cancer. Within this subgroup of patients, tubal ligation or hysterectomy among talc users still failed to demonstrate an increased risk for the development of ovarian cancer (OR 0.9; 95% CI 0.4, 2.2). CONCLUSION: A significant association between the use of talcum powder and the risk of developing epithelial ovarian cancer is not demonstrable, even with prolonged exposure.
Case-Control Studies↗