COMPUTER‐AIDED ULTRASONOGRAPHY (HISTOSCANNING): A NOVEL TECHNOLOGY FOR LOCATING AND CHARACTERIZING PROSTATE CANCER

OBJECTIVE

To test the hypothesis that exposure of a renal epithelial cell line, NRK52E, to calcium oxalate monohydrate crystals (COM) would up‐regulate NADPH oxidase subunit p47^phox, enhance superoxide production and increase monocyte chemoattractant protein‐1 (MCP‐1) and osteopontin mRNA levels.

MATERIALS AND METHODS

Confluent cultures of NRK52E cells were exposed to COM (66.7 µg/cm²) with or with no pretreatment with diphenileneiodium chloride (DPI, 10 × 10^?6m ) an inhibitor for NADPH oxidase, under serum‐free conditions. The conditioned medium was collected and total cellular RNA isolated from the cells, and subjected to enzyme‐linked immunosorbent assay and real‐time polymerase chain reaction (PCR). Production of reactive oxygen species (ROS) was estimated by dihydroethidium (DHE) staining using a fluorescence microscope. Immunohistochemistry and real‐time PCR were used to analyse p47^phox in NRK52E cells.

RESULTS

In COM treated NRK52E cells there was enhanced expression of p47^phox and production of superoxide. COM‐induced production of MCP‐1 and osteopontin was significantly reduced after treatment with DPI.

CONCLUSIONS

While the generation of a lot of ROS might play a major role in tissue injury or death, the regulated generation of low concentration of ROS, possibly by NADPH oxidase, may represent a second messenger system for generation of COM‐induced MCP‐1 and osteopontin production in the renal tubules.     

Acromegaly caused by growth hormone-releasing hormone-producing tumors: long-term observational studies in three patients

We report on three newly diagnosed patients with extracranial ectopic GHRH-associated acromegaly with long-term follow-up after surgery of the primary tumor. One patient with a pancreatic tumor and two parathyroid adenomas was the index case of a large kindred of MEN-I syndrome. The other two patients had a large bronchial carcinoid. The first patient is still in remission now almost 22 years after surgery. In the two other patients GHRH did not normalize completely after surgery and they are now treated with slow-release octreotide. IGF-I normalized in all patients. During medical treatment basal GH secretion remained (slightly) elevated and secretory regularity was decreased in 24 h blood sampling studies. We did not observe development of tachyphylaxis towards the drug or radiological evidence of (growing) metastases. We propose life-long suppressive therapy with somatostatin analogs in cases with persisting elevated serum GHRH concentrations after removal of the primary tumor. Independent parameters of residual disease are elevated basal (nonpulsatile) GH secretion and decreased GH secretory regularity.     

Ascorbic acid inhibits PMP22 expression by reducing cAMP levels

Charcot-Marie-Tooth [CMT] syndrome is the most common hereditary peripheral neuropathy. CMT1A, which accounts for 50% of all CMT cases, usually results from triploidy of the PMP22 gene. Preclinical trials using an animal model show that disabled mice force-fed with high doses of ascorbic acid partially recover muscular strength after a few months of treatment, and suggest that high doses of ascorbic acid repress PMP22 expression. In this study, we demonstrated that ascorbic acid represses PMP22 gene expression by acting on intracellular cAMP levels and adenylate cyclase activity. This action is dose dependent and specific to ascorbic acid, since repression is not observed after treatment with other antioxidants. The new properties of ascorbic acid are discussed, along with the implications of these findings for CMT disease treatment.     

Growth hormone secretion and immunological function of a male patient with a homozygous STAT5b mutation

OBJECTIVE: STAT5b is a component of the GH signaling pathway. Recently, we described a 31-year-old male patient (height, -5.9 SDS) with a novel homozygous inactivating mutation in the STAT5b gene. The purpose of this study is to describe the phenotype in detail, including GH secretion and immunological function. In addition, we report four family members of this patient, all heterozygous carriers of the mutation. DESIGN AND METHODS: Twenty-four hour GH and prolactin secretion characteristics were assessed by blood sampling at 10-min intervals. An IGF-I generation test was performed. Monocyte function was tested by stimulation of whole blood with lipopolysaccharide (LPS) in the presence or absence of Interferon-gamma (IFN-gamma). In addition, T cell function was determined by measuring proliferative responses of peripheral blood mononuclear cells (PBMC) after stimulation by various polyclonal activators and Interleukin-2 (IL-2). Clinical and biochemical characteristics were determined in the carriers of the mutation. RESULTS: GH secretory parameters were comparable with that of healthy male controls (mean fat percentage 25), but likely increased in relation to the patient's 40% body fat. The regularity of GH secretion was diminished. Prolactin secretion was increased by sixfold. The IGF-I generation test showed a small increase in IGF-I and IGF-binding protein-3 on lower GH doses and an increase in IGF-I to -2.4 SDS on the highest dose of GH. In vitro, IL-12p40, IL 10, and tumour necrosis factor-alpha (TNF-alpha) production rates by PBMC increased to values within the normal range upon stimulation of LPS. Heterozygous carriers of the mutation did not show abnormalities, although the height of the males was below the normal range. CONCLUSIONS: This report shows that GH and prolactin secretion were increased in this patient homozygous for a new STAT5b mutation. Although STAT5b plays a role in signaling within immune cells, clinical immunodeficiency is not an obligatory phenomenon of STAT5b deficiency per se. Heterozygous carriers of a STAT5b mutation show no signs of GH insensitivity.     

No hyperactive–impulsive subtype in teacher-rated attention-deficit/hyperactivity problems

The aim of this study was to investigate which homogeneous groups, according to teacher reports of attention-deficit/hyperactivity (ADH) Problems on the Teacher's Report Form (TRF), can be identified in a referred sample (n = 4,422; age = 6-18 years; mean age = 9.9 years; 66% boys, 34% girls). Latent class analysis (LCA) was conducted on ADH Problems. In addition, co-morbidity levels in the different ADH Problems groups were compared. LCA yielded three different groups of children and adolescents with both Inattention and hyperactivity-impulsivity, and one group with high scores on Inattention but low scores on hyperactivity-impulsivity. A group of patients with predominantly hyperactivity and impulsivity was not found. Individuals in groups with higher levels of ADH Problems had significantly higher levels of oppositional defiant (OD) and conduct problems, and, although to a lesser extent, significantly higher levels of affective and anxiety problems than individuals in groups with lower levels of ADH Problems. It may not be useful to discern the hyperactive-impulsive type of ADHD.     

Attachment styles and sleep measures in a community-based sample of older adults

BackgroundMeasures of attachment style are often used to appraise social and emotional health. In developmental literature, the concept of attachment is used to explain relationships between children and their adult caregivers. While both attachment styles and sleep patterns are conceived as developmentally organized systems, very few studies have explored the link between the two. The present study examined whether attachment styles and sleep measures are associated among older adults.MethodsRelationships between attachment styles (i.e., secure, fearful, preoccupied, and dismissive) and subjective sleep measures were assessed utilizing data from 70 older participants (mean age: 68 ± 6 years; Blacks: 59% and Whites: 41%) in a community-based study assessing subjective health characteristics. After obtaining informed consent, each participant provided demographic and socioeconomic data, as well as relevant medical and subjective data.ResultsIndependent of participants’ demographic and subjective factors, significant correlations were found between the preoccupied attachment dimension and sleep measures. Specifically, individuals scoring high on the preoccupied attachment dimension were more likely to report daytime napping (r_p = 0.31, p < 0.01) and to use sleep-inducing medications (r_p = 0.37, p < 0.05). No significant correlations were found among sleep measures and the secure, dismissive, and fearful dimensions.ConclusionsImportant relations have been observed between specific attachment styles and subjective sleep factors in our data. Although only one-dimension (preoccupied) demonstrated statistical significance, a trend was observed, suggesting possible associations between the secure attachment style dimension and subjective sleep measures. Future studies are needed to broaden our understanding of the relationship between attachment styles and sleep patterns.     

Clinical Differences Between Angiographically Negative, Diffuse Subarachnoid Hemorrhage and Perimesencephalic Subarachnoid Hemorrhage

Objective  To identify prognostic factors for vasospasm, hydrocephalus, and clinical outcomes in patients with angiographically negative, non-traumatic, diffuse subarachnoid hemorrhage (d-SAH). Methods  Retrospective review of patients who experienced angiographically negative SAH at our institution over the past 6 years was undertaken. The patients were stratified based on grade at presentation, severity, and pattern of SAH on initial non-enhanced, computed tomography (CT) of the head into perimesencephalic and diffuse subtypes. The patients were further differentiated based on the development of vasospasm, hydrocephalus and required treatments, and clinical outcomes. Patients were excluded if a causative lesion was discovered subsequently. Results  Ninety-four patients with angiographically negative SAH were identified. A total of 31 patients were considered to have the perimesencephalic (p-SAH) subtype, while 63 patients fit criteria for the diffuse (d-SAH) subtype. Compared to the p-SAH subtype, those patients with d-SAH subtype had significantly higher risk for complications related to SAH with an increased incidence of hydrocephalus (50.8% vs. 9.6%), requirement for external ventricular drainage (41% vs. 9.6%), and for the hydrocephalus requiring eventual permanent cerebrospinal fluid diversion (20.6% vs. 0%). Patients with d-SAH were also at an increased risk for symptomatic vasospasm (28.6% vs. 9.6%). Ultimately, only 76% of d-SAH patients achieved complete recovery and independent living, compared to 96.7% of p-SAH patients. Conclusion  The angiographically negative d-SAH pattern is associated with worse presentations and outcome. These patients are at increased risk for vasospasm and hydrocephalus requiring aggressive treatment and should therefore be cared for with a higher level of surveillance.     

Baseline cortisol measures and developmental pathways of anxiety in early adolescence

Objective: This study investigated whether baseline cortisol measures predicted future anxiety, and compared cortisol values of groups with different developmental pathways of anxiety. Method: Cortisol levels were assessed in 1768 individuals (10–12 years). Anxiety levels were assessed at the same age and 2 years later. Results: Cortisol measures did not predict future anxiety levels. Individuals with persistent anxiety problems did not show higher morning cortisol levels than those with persistently low, decreasing, or increasing anxiety levels. Instead, individuals with persistently high anxiety levels showed significantly lower evening cortisol levels than all other individuals. Further, participants with increasing anxiety levels showed higher morning cortisol levels (area under the curve; AUC) than individuals with persistently low anxiety levels. Conclusion: The extent to which the HPA‐axis – by itself – plays a role in the aetiology of anxiety is questionable. Interactions of the HPA‐axis with other biological or environmental factors may be more important.     

Ferredoxin:NADPH oxidoreductase is recruited to thylakoids by binding to a polyproline type II helix in a pH-dependent manner

Ferredoxin:NADPH oxidoreductase (FNR) is a key enzyme of photosynthetic electron transport required for generation of reduction equivalents. Recently, two proteins were found to be involved in membrane-anchoring of FNR by specific interaction via a conserved Ser/Pro-rich motif: Tic62 and Trol. Our crystallographic study reveals that the FNR-binding motif, which forms a polyproline type II helix, induces self-assembly of two FNR monomers into a back-to-back dimer. Because binding occurs opposite to the FNR active sites, its activity is not affected by the interaction. Surface plasmon resonance analyses disclose a high affinity of FNR to the binding motif, which is strongly increased under acidic conditions. The pH of the chloroplast stroma changes dependent on the light conditions from neutral to slightly acidic in complete darkness or to alkaline at saturating light conditions. Recruiting of FNR to the thylakoids could therefore represent a regulatory mechanism to adapt FNR availability/activity to photosynthetic electron flow.