Stromal mesenchyme cell genes of the human prostate and bladder

Background

Stromal mesenchyme cells play an important role in epithelial differentiation and likely in cancer as well. Induction of epithelial differentiation is organ-specific, and the genes responsible could be identified through a comparative genomic analysis of the stromal cells from two different organs. These genes might be aberrantly expressed in cancer since cancer could be viewed as due to a defect in stromal signaling. We propose to identify the prostate stromal genes by analysis of differentially expressed genes between prostate and bladder stromal cells, and to examine their expression in prostate cancer.

Methods

Immunohistochemistry using antibodies to cluster designation (CD) cell surface antigens was first used to characterize the stromas of the prostate and bladder. Stromal cells were prepared from either prostate or bladder tissue for cell culture. RNA was isolated from the cultured cells and analyzed by DNA microarrays. Expression of candidate genes in normal prostate and prostate cancer was examined by RT-PCR.

Results

The bladder stroma was phenotypically different from that of the prostate. Most notable was the presence of a layer of CD13⁺ cells adjacent to the urothelium. This structural feature was also seen in the mouse bladder. The prostate stroma was uniformly CD13^-. A number of differentially expressed genes between prostate and bladder stromal cells were identified. One prostate gene, proenkephalin (PENK), was of interest because it encodes a hormone. Secreted proteins such as hormones and bioactive peptides are known to mediate cell-cell signaling. Prostate stromal expression of PENK was verified by an antibody raised against a PENK peptide, by RT-PCR analysis of laser-capture microdissected stromal cells, and by database analysis. Gene expression analysis showed that PENK expression was down-regulated in prostate cancer.

Conclusion

Our findings show that the histologically similar stromas of the prostate and bladder are phenotypically different, and express organ-specific genes. The importance of these genes in epithelial development is suggested by their abnormal expression in cancer. Among the candidates is the hormone PENK and the down-regulation of PENK expression in cancer suggests a possible association with cancer development.     

Comparison of the Canadian CT Head Rule and the New Orleans Criteria in patients with minor head injury

Context  Current use of cranial computed tomography (CT) for minor head injury is increasing rapidly, highly variable, and inefficient. The Canadian CT Head Rule (CCHR) and New Orleans Criteria (NOC) are previously developed clinical decision rules to guide CT use for patients with minor head injury and with Glasgow Coma Scale (GCS) scores of 13 to 15 for the CCHR and a score of 15 for the NOC. However, uncertainty about the clinical performance of these rules exists. Objective  To compare the clinical performance of these 2 decision rules for detecting the need for neurosurgical intervention and clinically important brain injury. Design, Setting, and Patients  In a prospective cohort study (June 2000-December 2002) that included 9 emergency departments in large Canadian community and university hospitals, the CCHR was evaluated in a convenience sample of 2707 adults who presented to the emergency department with blunt head trauma resulting in witnessed loss of consciousness, disorientation, or definite amnesia and a GCS score of 13 to 15. The CCHR and NOC were compared in a subgroup of 1822 adults with minor head injury and GCS score of 15. Main Outcome Measures  Neurosurgical intervention and clinically important brain injury evaluated by CT and a structured follow-up telephone interview. Results  Among 1822 patients with GCS score of 15, 8 (0.4%) required neurosurgical intervention and 97 (5.3%) had clinically important brain injury. The NOC and the CCHR both had 100% sensitivity but the CCHR was more specific (76.3% vs 12.1%, P<.001) for predicting need for neurosurgical intervention. For clinically important brain injury, the CCHR and the NOC had similar sensitivity (100% vs 100%; 95% confidence interval [CI], 96%-100%) but the CCHR was more specific (50.6% vs 12.7%, P<.001), and would result in lower CT rates (52.1% vs 88.0%, P<.001). The values for physician interpretation of the rules, CCHR vs NOC, were 0.85 vs 0.47. Physicians misinterpreted the rules as not requiring imaging for 4.0% of patients according to CCHR and 5.5% according to NOC (P = .04). Among all 2707 patients with a GCS score of 13 to 15, the CCHR had sensitivities of 100% (95% CI, 91%-100%) for 41 patients requiring neurosurgical intervention and 100% (95% CI, 98%-100%) for 231 patients with clinically important brain injury. Conclusion  For patients with minor head injury and GCS score of 15, the CCHR and the NOC have equivalent high sensitivities for need for neurosurgical intervention and clinically important brain injury, but the CCHR has higher specificity for important clinical outcomes than does the NOC, and its use may result in reduced imaging rates.      

Absorbable cyanoacrylate as a vascular hemostatic sealant: a preliminary trial

No absorbable cyanoacrylate tissue adhesive for safe internal surgical use is available. This prospective multicenter preliminary study was designed to evaluate the safety and effectiveness of an investigational absorbable cyanoacrylate (IAC) as an adjunct to hemostasis in arteriovenous shunt (AVS) procedures for dialysis access. Consenting adults (10) underwent placement of expanded polytetrafluoroethylene (ePTFE) upper extremity vascular grafts for AVS access using continuous 5-0 or 6-0 polypropylene after heparinization (> or =3000 units i.v.). Arterial anastomoses were evaluated after sealing with IAC followed by 120 seconds of polymerization time. After vascular clamp removal, the mean time to hemostasis was 9.1 +/- 28.8 seconds. Additionally, 90 per cent (9/10) and 100 per cent (10/10) achieved hemostasis by 1 and 5 minutes, respectively. No patients required further adjunctive hemostatic measures. Adverse event safety data analysis through 12 weeks revealed occlusion of graft or vessel in four patients and graft thrombosis in one patient, all thought unrelated to sealant use. Other unrelated adverse events (bleeding, death, deep venous thrombosis, edema, erythema, hematoma, infection, and rash) occurred in single patients. Thus, IAC could be a useful sealant for vascular procedures with a potentially satisfactory safety profile. Larger, randomized, multicenter, prospective trials to further evaluate the use of this material are indicated and appropriate.     

An unusual case of pleural, epididymal and sternoclavicular tuberculosis

A patient with pleural, epididymal and sternoclavicular tuberculosis is described in whom the history suggests that primary infection occurred near the time when he was involved in a fight. Epididymal and sternoclavicular lesions represent infection of loci minoris resistentiae secondary to traumatic injuries sustained in the fight and provide evidence for the concept of tuberculous bacillaemia accompanying primary infection.     

NMR imaging in the recognition of giant intracranial aneurysms

Most giant aneurysms present clinically as intracranial mass lesions. Many contain an organized lamellated thrombus with only a small eccentric lumen remaining that can be opacified at angiography. Four patients with such aneurysms were studied using flow-dependent nuclear magnetic resonance scanning sequences. The aneurysms show a smooth rounded margin, and the thrombus within is clearly distinguishable from the blood flowing through the patent lumen, which gives a low signal. By using different scan sequences it is possible to prove that the area of low signal is indeed fluid in rapid motion, thus confirming the diagnosis.     

Influence of serotonin transporter gene polymorphisms on cognitive decline and cognitive abilities in a nondemented elderly population

Dysfunction of the serotonergic pathway disrupts normal cognitive functioning and is believed to be the underlying basis for a variety of psychiatric disorders. Two functional polymorphisms within the serotonin transporter (SLC6A4) gene (promoter 44 bp insertion/deletion (HTTLPR) and an intron two 16 or 17 bp variable number tandem repeat (VNTR2)) have been extensively studied in psychiatric conditions but not in the cognitive functioning of normal individuals. We have investigated these two polymorphisms for association with both the level of cognitive abilities and their decline with age using a cohort consisting of over 750 elderly nondemented individuals with a follow-up of up to 15 years. We found that volunteers homozygous for the VNTR2 12 allele had a faster rate of decline for all cognitive tests. This reached significance for both tests of fluid intelligence (novel problem solving) (AH1 P=0.002, AH2 P=0.014), the test of semantic memory (P=0.010) and general cognitive ability (P=0.006). No association was observed between the HTTLPR polymorphism and the rate of cognitive decline when analysed either independently or in combination with the VNTR2 polymorphism based on their influence on expression in vitro. No associations were observed between the two polymorphisms and the baseline level of cognitive abilities. This is only the second gene that has been reported to regulate the rate of cognitive decline in nondemented individuals and may be a target for the treatment of cognitive impairment in the elderly.     

Looking back: developments in our understanding of the genetic epidemiology of rheumatoid arthritis over the last 50 years

The contribution of the arc Epidemiology Unit over its 50-yr history to the study of the genetic epidemiology of rheumatoid arthritis (RA) has been reviewed. Early family and population based studies carried out by John Lawrence were important in establishing the role of both genetic and environmental factors in determining susceptibility to RA. More recently, under the leadership of Alan Silman, population-based cohorts, twin- and family-based studies have formed the basis for an extensive programme of research aimed at identifying specific genetic factors that might influence susceptibility and outcome. A review of linkage and association studies is presented.     

Failure of aneurysm sac shrinkage after endovascular repair; the effect of mural calcification

AIM: To evaluate the effect of abdominal aortic aneurysm wall calcification on subsequent sac shrinkage after endovascular repair. MATERIALS AND METHODS: Seventy-three patients underwent endovascular aneurysm repair. The degree of sac wall calcification on pre-procedural computed tomography (CT) examination was graded from 1 to 4 according to the degree of circumferential involvement. On follow-up CT imaging, the maximum transverse diameter (MTD) of the sac was recorded, as well as the presence or absence of endoleak. In those patients with a non-shrinking aneurysm, but no CT evidence of endoleak, contrast-enhanced ultrasound (USS) was performed. Any patient with an endoleak, however diagnosed, was excluded from the study. Kruskal-Wallis and Spearman's rank correlation coefficient testing was applied to compare the degree of calcification and change in MTD. RESULTS: Sixty-three pre-procedural CT images were available for calcification grading. Six of this group had endoleaks resulting in 57 sets of data being available for the study. A reduction in MTD occurred in 68.25% of these patients by 1 year post-procedure. Our figures show aortic calcification is inversely associated with MTD reduction at 6 months (p = 0.01), 1 year (p = 0.05) and 2 years (p = 0.05). CONCLUSION: This study indicates that the degree of aortic wall calcification is significant in predicting MTD reduction post-endovascular repair. The possible mechanisms and implications of this are discussed.