Multi-potent mesenchymal stromal cells in blood.

Peripheral blood-derived multi-potent mesenchymal stromal cells circulate in low number. They share, though not all, but most of the surface markers with bone marrow-derived multi-potent mesenchymal stromal cells, possess diverse and complicated gene expression characteristics, and are capable of differentiating along and even beyond mesenchymal lineages. Although their origin and physio-pathological function are still unclear, their presence in the adult peripheral blood might relate to some interesting but controversial subjects in the filed of adult stem cell biology, such as systemic migration of bone marrow-derived multi-potent mesenchymal stromal cells and the existence of common hematopoietic-mesenchymal precursors. In this review, current studies/knowledge about peripheral blood-derived multi-potent mesenchymal stromal cells is summarized and the above-mentioned topics are discussed.

Polymorphims in the Interferon-y/Interleukin 26 Gene Region Contribute to Sex Bias in Susceptibility to Rheumatoid Arthritis

Objective:

To determine whether polymorphisms in the interferon-? (IFN?)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA).

Methods:

Four microsatellite markers, located in a 118-kb interval that contains both the IFN? and IL-26 genes on chromosome 12q15, were typed in 251 patients with RA and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction–based fragment analysis.

Results:

Marker D12S2510, which is located 3 kb 3' from the IL-26 gene, was significantly associated with RA in women (corrected P [Pcorr] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with RA (odds ratio 0.50, 95% confidence interval 0.32–0.78; P = 0.002, Pcorr = 0.03) but not in men with RA.

Conclusion:

Our results demonstrate that common polymorphisms in the IFN?/IL-26 gene region may contribute to sex bias in susceptibility to RA, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, multiple sclerosis.

Ectopic ACTH-syndrome due to a thymic carcinoid tumor

Investigating a recently developed Cushing Syndrome, we diagnosed in a 47-year-old woman an ectopic ACTH syndrome due to a metastatic carcinoid tumor, most likely a thymic carcinoid tumor. Combined therapy with sandostatin and nizoral and later on with sandostatin, metopirone and orimeten, was not able to suppress the hypercortisolism. A few weeks after surgical adrenalectomy, clinical deterioration ensued, culminating in the patient's death 7 months after diagnosis.

Inhibition of tumor necrosis factor-alpha improves physiological angiogenesis and reduces pathological neovascularization in ischemic retinopathy

The present study was undertaken to test whether inhibition of the proangiogenic inflammatory cytokine tumor necrosis factor (TNF)-alpha can modulate retinal hypoxia and preretinal neovascularization in a murine model of oxygen-induced retinopathy (OIR). OIR was produced in TNF-alpha-/- and wild-type (WT) control C57B6 neonatal mice by exposure to 75% oxygen between postnatal days 7 and 12 (P7 to P12). Half of each WT litter was treated with the cytokine inhibitor semapimod (formerly known as CNI-1493) (5 mg/kg) by daily intraperitoneal injection from the time of reintroduction to room air at P12 until P17. The extent of preretinal neovascularization and intraretinal revascularization was quantified by image analysis of retinal flat-mounts and retinal hypoxia correlated with vascularization by immunofluorescent localization of the hypoxia-sensitive drug pimonidazole (hypoxyprobe, HP). HP adducts were also characterized by Western analysis and quantified by competitive enzyme-linked immunosorbent assay. TNF-alpha-/- and WT mice showed a similar sensitivity to hyperoxia-induced retinal ischemia at P12. At P13 some delay in early reperfusion was evident in TNFalpha-/- and WT mice treated with semapimod. However, at P17 both these groups had significantly better vascular recovery with less ischemic/hypoxic retina and preretinal neovascularization compared to untreated retinopathy in WT mice. Immunohistochemistry showed deposition of HP in the avascular inner retina but not in areas underlying preretinal neovascularization, indicating that such aberrant vasculature can reduce retinal hypoxia. Inhibition of TNF-alpha significantly, improves vascular recovery within ischemic tissue and reduces pathological neovascularization in OIR. HP provides a useful tool for mapping and quantifying tissue hypoxia in experimental ischemic retinopathy.

Necrospermia and chronic spinal cord injury.

OBJECTIVE: To determine whether improvement in quality of semen over 4 consecutive days of electroejaculation in men with chronic spinal cord injury (SCI) was consistent with epididymal necrospermia. DESIGN: Prospective study of a random sample of men with SCI. SETTING: A southeastern Australian SCI management center in collaboration with the specialist andrology service of a university-based department of obstetrics and gynecology in a tertiary referral hospital. PATIENT(S): Nine men with chronic spinal cord injury. INTERVENTION(S): Semen samples were obtained by using electroejaculation, and testicular biopsy samples were obtained by using fine-needle tissue aspiration. MAIN OUTCOME MEASURE(S): Semen analysis was performed according to World Health Organization criteria. Testicular biopsy and electron microscopy were done by using standard techniques. RESULT(S): During up to 4 days of consecutive-day electroejaculation, sperm motility and viability in semen obtained from men with chronic SCI increased by an average of 23% on days 2 and 3. The severity of the degenerative changes and the numbers of spermatozoa affected on day 1 became less marked by day 4. The changes were not present in late spermatids obtained from testicular biopsies. CONCLUSION(S): The asthenospermia of chronic SCI is similar to epididymal necrospermia and can be improved by consecutive-day electroejaculation.