Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs.

The main pathogenesis of intervertebral disc (IVD) herniation involves disruption of the annulus fibrosus (AF) caused by ageing or excessive mechanical stress and the resulting prolapse of the nucleus pulposus. Owing to the avascular nature of the IVD and lack of understanding the mechanisms that maintain the IVD, current therapies do not lead to tissue regeneration. Here we show that homeobox protein Mohawk (Mkx) is a key transcription factor that regulates AF development, maintenance and regeneration. Mkx is mainly expressed in the outer AF (OAF) of humans and mice. In Mkx(-/-) mice, the OAF displays a deficiency of multiple tendon/ligament-related genes, a smaller OAF collagen fibril diameter and a more rapid progression of IVD degeneration compared with the wild type. Mesenchymal stem cells overexpressing Mkx promote functional AF regeneration in a mouse AF defect model, with abundant collagen fibril formation. Our results indicate a therapeutic strategy for AF regeneration

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Revascularization of Malignant Coronary Instent Restenosis Resulting From Takayasu's Arteritis Using Sirolimus-Eluting Stents

A 37 year-old female who had suffered from arteritis for 20 years underwent a Bentall operation. Since severe stenosis was observed in her left main coronary artery (LMCA) the following year, a minimally invasive direct coronary artery bypass (MIDCAB) operation was performed. Unfortunately, she again complained of angina about 6 months after the second surgery and coronary angiography (CAG) revealed that her left internal thoracic artery graft was totally occluded. Although a 4.0 × 15 mm S670 stent was placed in her LMCA, the LMCA restenosed every 3 months and she underwent reintervention 8 times. We placed 2 sirolimus-eluting stents for treating the LMCA using the culottes stenting technique. CAG 6 months after the index procedure showed no stenosis at her LMCA. Sirolimus-eluting stents were effective for treating stenosis resulting from arteritis as well as that caused by atherosclerosis

Chronic beta-adrenergic receptor stimulation enhances the expression of G-Protein coupled receptor kinases, GRK2 and GRK5, in both the heart and peripheral lymphocytes

Background: Enhanced expression of G protein-coupled receptor kinase (GRK) has been reported in failing hearts and in the present study the stability of enhanced GRK mRNA expression, and the correlation between the expression level of GRK mRNA in peripheral lymphocytes and in the heart were both evaluated. Methods and Results: Isoproterenol was injected into rats for 2 weeks, and then GRK5 mRNA was assessed by quantitative reverse transcriptase-palymerase chain reaction. An enhanced expression of cardiac GRK5 mRNA was observed even after 4 weeks of recovery. The isoproterenol-induced increased expression of GRK2 and GRK5 mRNA was equally observed in the heart and lymphocytes, and there was a close correlation between the heart and lymphocytes in the level of expression of each GRK mRNA. Conclusions: The GRK mRNA level is maintained at a high level for a long period without continuous β-adrenergic receptor stimulation. The level in circulating lymphocytes could be used as a surrogate marker to estimate the level of cardiac GRK expression and, presumably, the β-adrenergic receptor function of cardiomyocytes. (Circ J 2005; 69: 987-990

Angiotensin converting enzyme inhibitors attenuated the expression of G-protein coupled receptor kinases in heart failure patients

Background: There are few biological markers, which strictly show the severity of congestive heart failure (CHF). Methods and Results: Lymphocyte G-protein coupled receptor kinase (GRK) mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction in 15 CHF patients: 5 patients classified as New York Heart Association class-II treated with angiotensin converting enzyme inhibitor (ACEI) (IIA), 5 patients in class-II without ACEI (IIC), and 5 patients in class-III treated with ACEI (IIIA). GRK mRNA level in IIIA was significantly higher than those in IIA (p<0.05). GRK mRNA level in IIA were significantly lower than those in IIC (p<0.05). Conclusions: The expression level of lymphocyte GRK might show the severity of CHF, and ACEI treatment could reduce the level of GRK in CHF patients. (Circ J 2006; 70: 362 - 363