CD44 expression is a feature of prostatic small cell carcinoma and distinguishes it from its mimickers

Small cell neuroendocrine carcinoma of the prostate is a rare variant of prostatic cancer that shares morphologic similarity with prostatic adenocarcinoma of Gleason 5 pattern. It has also been considered morphologically and immunohistochemically indistinguishable from small cell neuroendocrine carcinomas of other origins. CD44 is a cell-surface molecule proposed to identify cancer stem/progenitor cells in prostate cancer. We performed immunohistochemical study for CD44 expression in 11 cases of prostatic small cell neuroendocrine carcinoma and compared its patterns of expression with 73 cases of prostatic adenocarcinoma and 47 cases of small cell neuroendocrine carcinomas of other organs. Strong and diffuse membrane staining for CD44 was observed in 100% of the prostatic small cell neuroendocrine carcinomas. In conventional adenocarcinomas of the prostate, positive staining was only seen in rare, scattered tumor cells; and CD44 staining was negative in most of the small cell neuroendocrine carcinomas of nonprostate origin. The difference in CD44 expression between small cell neuroendocrine carcinomas of the prostate and those of other organs are statistically significant (P < .001). Our study demonstrates the utility of immunohistochemical staining for CD44 in distinguishing prostatic small cell neuroendocrine carcinoma from its mimickers including prostatic adenocarcinoma of Gleason 5 pattern and small cell neuroendocrine carcinomas of other organs. CD44 is the first marker that shows a high degree of tissue/organ specificity for small cell neuroendocrine carcinomas. Because CD44 is a putative marker of prostate cancer stem cells, the strong and diffuse expression of CD44 and the lack of expression of prostate luminal differentiation markers androgen receptor and prostatic specific antigen in prostatic small cell neuroendocrine carcinomas suggest that the tumor cells may retain cancer stem cell features.     

Clinical,hematologic, and immunologic effects of interleukin-10 in humans

We conducted a double-blind, placebo-controlled study to investigate the safety, pharmacokinetics, and immunological properties of interleukin-10 (IL-10) administration in healthy humans. Volunteers received a single intravenous bolus injection of recombinant human IL-10 (1, 10, or 25g/kg) or placebo. Cytokine production in whole blood and peripheral blood mononuclear cells (PBMC) was assessed before and 3, 6, 24, and 48 hr after the injection. Peak serum concentrations of IL-10 (15±1.1, 208±20.1, and 505±22.3 ng/ml) occurred after 2–5 min for 1, 10, and 25g/kg IL-10, respectively. The terminal-phase half-life was 3.18 hr. A transient leukocytosis (24–63% above baseline) was observed 6 hr after injection, which coincided with a dose-dependent decrease (12–24%) in neutrophil superoxide generation. There was a marked inhibition (60–95%) of endotoxin-induced IL-6 production from whole blood in each group receiving IL-10. Production of IL-8 in endotoxin-stimulated blood was reduced in the 10g/kg group. In PBMC stimulated with phytohemagglutinin and phorbol ester, there was a decrease (72–87%) in interferon- (IFN) production 6 hr after IL-10 with a return to pre-IL-10 levels after 24 hr. This reduction was only partially associated with a decrease in the number of CD2-bearing cells. We conclude that IL-10 administration into humans is without significant side effects, and a single injection reducesex vivo production of IL-6, IL-8, and IFN.     

Chromosome 2q terminal deletion: report of 6 new patients and review of phenotype-breakpoint correlations in 66 individuals

We report a new patient with terminal deletion of chromosome 2 with breakpoint at 2q36 and five additional new patients with 2q terminal deletion with breakpoint at 2q37. Hemidiaphragmatic hernia is a novel finding in one patient with a breakpoint at 2q37.1. In comparing these patients to 60 previously reported individuals with 2q terminal deletions, certain physical abnormalities are loosely associated with positions of breakpoint. For example, facial features (e.g., prominent forehead, depressed nasal bridge, and dysmorphic ears and nose), short stature, and short hands and feet were frequent in patients with breakpoints at or proximal to 2q37.3. Reports of horseshoe kidney and Wilms tumor were limited to patients with a breakpoint at 2q37.1, and structural brain anomalies and tracheal anomalies were reported only in patients with breakpoints at or proximal to 2q37.1. Cleft palate was reported only in patients with the most proximal breakpoints (2q36 or 2q35). Neurological effects including developmental delay, mental retardation, autistic-like behavior, and hypotonia were typical in this patient population but did not stratify in severity according to breakpoint. Terminal deletion of the long arm of chromosome 2 should be considered in the infant with marked hypotonia, poor feeding, gastroesophageal reflux, and growth delay, and the older child with developmental delay, autistic behavior, and the characteristic facial and integumentary features described herein. Assignment of clinical features to specific breakpoints and refinement of predictive value may be useful in counseling.     

HealthTrust: a social network approach for retrieving online health videos

Background

Social media are becoming mainstream in the health domain. Despite the large volume of accurate and trustworthy health information available on social media platforms, finding good-quality health information can be difficult. Misleading health information can often be popular (eg, antivaccination videos) and therefore highly rated by general search engines. We believe that community wisdom about the quality of health information can be harnessed to help create tools for retrieving good-quality social media content.

Objectives

To explore approaches for extracting metrics about authoritativeness in online health communities and how these metrics positively correlate with the quality of the content.

Methods

We designed a metric, called HealthTrust, that estimates the trustworthiness of social media content (eg, blog posts or videos) in a health community. The HealthTrust metric calculates reputation in an online health community based on link analysis. We used the metric to retrieve YouTube videos and channels about diabetes. In two different experiments, health consumers provided 427 ratings of 17 videos and professionals gave 162 ratings of 23 videos. In addition, two professionals reviewed 30 diabetes channels.

Results

HealthTrust may be used for retrieving online videos on diabetes, since it performed better than YouTube Search in most cases. Overall, of 20 potential channels, HealthTrust’s filtering allowed only 3 bad channels (15%) versus 8 (40%) on the YouTube list. Misleading and graphic videos (eg, featuring amputations) were more commonly found by YouTube Search than by searches based on HealthTrust. However, some videos from trusted sources had low HealthTrust scores, mostly from general health content providers, and therefore not highly connected in the diabetes community. When comparing video ratings from our reviewers, we found that HealthTrust achieved a positive and statistically significant correlation with professionals (Pearson r ₁₀ = .65, P = .02) and a trend toward significance with health consumers (r ₇ = .65, P = .06) with videos on hemoglobinA_{1 c}, but it did not perform as well with diabetic foot videos.

Conclusions

The trust-based metric HealthTrust showed promising results when used to retrieve diabetes content from YouTube. Our research indicates that social network analysis may be used to identify trustworthy social media in health communities.     

Fracture risk in monoclonal gammopathy of undetermined significance.

To assess fractures in monoclonal gammopathy of undetermined significance (MGUS), the precursor of multiple myeloma, we followed 488 Olmsted County, MN, residents with MGUS in a retrospective cohort study. There was a 2.7-fold increase in the risk of axial fractures but no increase in limb fractures. The pathophysiologic basis for the increased axial fractures should be determined. INTRODUCTION: Multiple myeloma is often preceded by monoclonal gammopathy of undetermined significance (MGUS). Fractures are common in myeloma as a result of lytic bone lesions, generalized bone loss, and elevated bone turnover from excessive cytokine production. Whether fractures are also increased in MGUS is unknown. MATERIALS AND METHODS: In a population-based retrospective cohort study, 488 Olmsted County, MN, residents with MGUS first diagnosed in 1960-1994 (52% men; mean age, 71.4 +/- 12.8 years) were followed for 3901 person-years; follow-up was censored at progression to myeloma. The relative risk of fractures was assessed by standardized incidence ratios (SIRs), and risk factors were evaluated in proportional hazards models. RESULTS AND CONCLUSIONS: Altogether, 200 patients experienced 385 fractures. Compared with expected rates in the community, statistically significant increases were seen for fractures at most axial sites, for example, vertebrae (SIR, 6.3; 95% CI, 5.2-7.5). There was a slight increase in hip (SIR, 1.6; 95% CI, 1.2-2.2) but not distal forearm fractures (SIR, 0.8; 95% CI, 0.4-1.5). The relative risk (SIR) of any axial fracture was 2.7 (95% CI, 2.3-3.1) compared with only 1.1 (95% CI, 0.9-1.4) for all limb fractures combined. In a multivariate analysis, the independent predictors of any subsequent fracture were age (hazard ratio [HR] per 10-year increase, 1.4; 95% CI, 1.2-1.6) and corticosteroid use (HR, 1.8; 95% CI, 1.2-2.6); greater weight at diagnosis (HR per 10 kg, 0.8; 95% CI, 0.8-0.9), and IgG monoclonal protein (HR, 0.7; 95% CI, 0.5-0.97) were protective. Baseline monoclonal protein level, a determinant of myeloma progression, did not predict fracture risk. Thus, the risk of axial, but not peripheral, fractures is increased among MGUS patients even before progression to myeloma. The pathophysiologic basis for this should be determined because elevated bone turnover, for example, might be treatable.     

Fitness, fatness, and cardiovascular risk factors in type 2 diabetes: look ahead study

PURPOSE: Most studies comparing the effects of fitness and fatness on cardiovascular (CVD) risk have been done with young, healthy participants with low rates of obesity and high levels of fitness. The present study examined the association of cardiorespiratory fitness and obesity with CVD risk factors in an ethnically diverse sample of overweight/obese individuals with type 2 diabetes. METHOD: Baseline data from Look AHEAD, a study of 5145 overweight or obese individuals with type 2 diabetes, were used to examine the association of BMI categories (overweight, class I, II, or III obesity) and cardiorespiratory fitness (assessed with a maximal graded exercise test and categorized by age- and gender-specific quintiles) on cardiovascular risk factors and on the odds of having hypertension, hyperlipidemia, or HbA1c > or = 7%. RESULTS: BMI categories and fitness quintiles were highly associated with each other (P < 0.0001), with the heaviest participants being the least fit. Only 2-3% of participants had class III obesity and were in the two fittest quintiles or, conversely, were overweight and in the two least-fit quintiles. When fitness and BMI were included in the same model (adjusting for age, smoking, diabetes duration, and race), HbA1c, ankle/brachial index (ABI), and Framingham risk score were most strongly associated with fitness. Systolic blood pressure was most strongly associated with BMI category. Similar results occurred when waist circumference and fitness were considered together. CONCLUSION: In this large, ethnically diverse sample of overweight/obese individuals with type 2 diabetes, fitness and fatness were highly related to each other but seemed to have different impact on specific CVD risk factors.     

In vitro translation of hypoxanthine/guanine phosphoribosyltransferase mRNA: characterization of a mouse neuroblastoma cell line that has elevated levels of hypoxanthine/guanine phosphoribosyltransferase protein.

Antibody specific for the native form of Chinese hamster hypoxanthine/guanine phosphoribosyltransferase (HPRT; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) was used to detect the synthesis of HPRT protein in a rabbit reticulocyte lysate translation system primed with mRNA from Chinese hamster tissues and cultured cells. Electrophoretic analysis of the immunopurified products from the translation of mRNA from wild-type and a series of mutant Chinese hamster cells indicated that HPRT synthesis in vitro qualitatively and quantitatively corresponded to synthesis in vivo. The translation system was used to identify two mRNA sources producing high levels of HPRT protein: Chinese hamster brain and a mouse neuroblastoma HPRT revertant cell line, NBR4. Translation of NBR4 mRNA generated 25-50 times more HPRT protein than mRNA from wild-type cells. The basis for HPRT overproduction is considered in view of an X chromosome alteration found in NBR4 cells.