Somatostatin modulates G-CSF-induced but not interleukin-3-induced proliferative responses in myeloid 32D cells via activation of somatostatin receptor subtype 2

Somatostatin, originally identified as a peptide involved in neurotransmission, functions as an inhibitor of multiple cellular responses, including hormonal secretion and proliferation. Somatostatin acts through activation of G-protein-coupled receptors of which five subtypes have been identified. We have recently established that human CD34/c-kit expressing hematopoietic progenitors and acute myeloid leukemia (AML) cells exclusively express SSTR2. A major mechanism implicated in the antiproliferative action of somatostatin involves activation of the SH2 domain-containing protein tyrosine phosphatase SHP-1. While 0.1-1 x 10(-9) M of somatostatin, or its synthetic stable analog octreotide, can inhibit G-CSF-induced proliferation of AML cells, little or no effects are seen on GM-CSF- or IL-3-induced responses.
MATERIALS AND METHODS: To study the mechanisms underlying the antiproliferative responses of myeloblasts to somatostatin, clones of the IL-3-dependent murine cell line 32D that stably express SSTR2 and G-CSF receptors were generated. RESULTS: Similar to AML cells, octreotide inhibited G-CSF-induced but not IL-3-induced proliferative responses of 32D[G-CSF-R/SSTR2] cells. Somatostatin induced SHP-1 activity and inhibited G-CSF-induced, but not IL-3-induced, activation of the signal transducer and activator of transcription proteins STAT3 and STAT5.
CONCLUSION: Based on these data and previous results, we propose a model in which recruitment and activation of the tyrosine phosphatase SHP-1 by SSTR2 is involved in the selective negative action of somatostatin on G-CSF-R signaling.

The incidence of all stroke and stroke subtype in the United Kingdom, 1985 to 2008 : a systematic review

Background : There is considerable geographic variation in stroke mortality around the United Kingdom (UK). Whether this is due to geographical differences in incidence or case-fatality is unclear. We conducted a systematic review of high-quality studies documenting the incidence of any stroke and stroke subtypes, between 1985 and 2008 in the UK. We aimed to study geographic and temporal trends in relation to equivalent mortality trends.

Methods : MEDLINE and EMBASE were searched, reference lists inspected and authors of included papers were contacted. All rates were standardised to the European Standard Population for those over 45, and between 45 and 74 years. Stroke mortality rates for the included areas were then calculated to produce rate ratios of stroke mortality to incidence for each location.

Results : Five papers were included in this review. Geographic variation was narrow but incidence appeared to largely mirror mortality rates for all stroke. For men over 45, incidence (and confidence intervals) per 100,000 ranged from 124 (109-141) in South London, to 185 (164-208) in Scotland. For men, premature (45-74 years) stroke incidence per 100,000 ranged from 79 (67-94) in the North West, to 112 (95-132) in Scotland. Stroke subtype data was more geographically restricted, but did suggest there is no sizeable variation in incidence by subtype around the country. Only one paper, based in South London, had data on temporal trends. This showed that there has been a decline in stroke incidence since the mid 1990 s. This could not be compared to any other locations in this review.

Conclusions : Geographic variations in stroke incidence appear to mirror variations in mortality rates. This suggests policies to reduce inequalities in stroke mortality should be directed at risk factor profiles rather than treatment after a first incident event. More high quality stroke incidence data from around the UK are needed before this can be confirmed.

Unique neuropsychological profiles in adhd subtype presentations

Learning and memory for verbal and visual information was compared in children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) of Combined Type and Predominantly Inattentive Type. Compared to a typically developing group, the ADHD groups were found to have unique difficulties. These findings add to the current research knowledge.

When social anxiety co-occurs with substance use: does an impulsive social anxiety subtype explain this unexpected relationship?

Although most conceptualizations of social anxiety emphasise that socially anxious individuals are overtly shy, and utilise avoidant behavioural strategies (e.g., risk-aversion, passivity, and submissiveness), there is tentative support for the existence of an approach-motivated subtype, characterised by risk taking and a greater propensity for substance misuse. It is likely that this subtype may help explain the reported co-occurrence of substance misuse and social anxiety. The current study sought to test via latent class analysis whether an approach-motivated social anxiety subtype could be identified within a community sample. A self-report questionnaire was completed by 351 participants (age: 18-74 years). Two distinct social anxiety subgroups were identified: one characterised by prototypical SAD symptomatology (i.e., behavioural inhibition and risk-avoidance), the second by elevated levels of rash impulsiveness, reward sensitivity, risk-taking and co-occurring substance use problems. The current findings provides support for the existence of a distinct approach-motivated social anxiety subtype and indicates that impulsivity may be critical to understanding the comorbid substance use symptomatology of these individuals.

Persistence and subtype stability of ADHD among substance use disorder treatment seekers

OBJECTIVE: To examine ADHD symptom persistence and subtype stability among substance use disorder (SUD) treatment seekers. METHOD: In all, 1,276 adult SUD treatment seekers were assessed for childhood and adult ADHD using Conners' Adult ADHD Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; CAADID). A total of 290 (22.7%) participants met CAADID criteria for childhood ADHD and comprise the current study sample. RESULTS: Childhood ADHD persisted into adulthood in 72.8% (n = 211) of cases. ADHD persistence was significantly associated with a family history of ADHD, and the presence of conduct disorder and antisocial personality disorder. The combined subtype was the most stable into adulthood (78.6%) and this stability was significantly associated with conduct disorder and past treatment of ADHD. CONCLUSION: ADHD is highly prevalent and persistent among SUD treatment seekers and is associated with the more severe phenotype that is also less likely to remit. Routine screening and follow-up assessment for ADHD is indicated to enhance treatment management and outcomes.

The relationship between divorce and the psychological well‐being of children with ADHD: differences in age, gender, and subtype

It is generally accepted that Attention‐Deficit/Hyperactivity Disorder (ADHD) results from a dysfunction of the central nervous system, which has led to a commonly held belief that environmental factors play little role in the behavioural problems of children identified as having ADHD. Therefore, the two studies reported in this article investigated the relationship between parental divorce and the psychological well‐being of children with ADHD. Subjects, aged 6 to 18 years, were diagnosed with either the inattentive or combined subtype of the disorder. Firstly, differences in children's behaviour between divorced and non‐divorced families were examined, and subtype, age, and gender differences were evaluated in terms of symptom severity and comorbid conditions. Secondly, parents' perceptions of the impact of their children's behaviour on marital status and family/parental functioning were examined. Parental divorce was associated with greater symptom severity, more externalizing/ internalizing behaviours, and poorer social functioning, but less with academic underachievement. Further, parental divorce was related to adjustment differences in ADHD subtypes, age, and gender. However, the correlation between behaviour problems of children with ADHD and marital/family dysfunction was weak. It may be concluded that parental divorce was associated with the psychological well‐being in children with ADHD, and there is some suggestion that ADHD should be viewed as a bio‐psychosocial disorder.