1‐(2‐Hydroxyethyl)‐2‐imidazolidinone,a heparanase and matrix metalloproteinase inhibitor,improves epidermal basement membrane structure and epidermal barrier function

Daily exposure to sunlight is known to affect the structure and function of the epidermal basement membrane (BM), as well as epidermal differentiation and epidermal barrier function. The aim of this study is to clarify whether the inhibition of BM‐degrading enzymes such as heparanase and matrix metalloproteinase 9 (MMP‐9) can improve the epidermal barrier function of facial skin, which is exposed to the sun on a daily basis. 1‐(2‐hydroxyethyl)‐2‐imidazolidinone (HEI) was synthesized as an inhibitor of both heparanase and MMP‐9. HEI inhibited not only the BM damage at the DEJ but also epidermal proliferation, differentiation, water contents and transepidermal water loss abnormalities resulting from ultraviolet B (UVB). This was determined in this study by the use of UVB‐induced human cultured skins as compared with the control without HEI. Moreover, topical application of HEI improved epidermal barrier function by increasing water content and decreasing transepidermal water loss in daily sun‐exposed facial skin as compared with non‐treated skins. These results suggest that the inhibition of both heparanase and MMP‐9 is an effective way to care for regularly sun‐exposed facial skin by protecting the BM from damage.     

Expression of measles virus nucleocapsid protein in osteoclasts induces Paget's disease-like bone lesions in mice.

We targeted the MVNP gene to the OCL lineage in transgenic mice. These mice developed abnormal OCLs and bone lesions similar to those found in Paget's patients. These results show that persistent expression of MVNP in OCLs can induce pagetic-like bone lesions in vivo. INTRODUCTION: Paget's disease (PD) of bone is the second most common bone disease. Both genetic and viral factors have been implicated in its pathogenesis, but their exact roles in vivo are unclear. We previously reported that transfection of normal human osteoclast (OCL) precursors with the measles virus nucleocapsid (MVNP) or measles virus (MV) infection of bone marrow cells from transgenic mice expressing a MV receptor results in formation of pagetic-like OCLs. MATERIALS AND METHODS: Based on these in vitro studies, we determined if the MVNP gene from either an Edmonston-related strain of MV or a MVNP gene sequence derived from a patient with PD (P-MVNP), when targeted to cells in the OCL lineage of transgenic mice with the TRACP promoter (TRACP/MVNP mice), induced changes in bone similar to those found in PD. RESULTS: Bone marrow culture studies and histomorphometric analysis of bones from these mice showed that their OCLs displayed many of the features of pagetic OCLs and that they developed bone lesions that were similar to those in patients with PD. Furthermore, IL-6 seemed to be required for the development of the pagetic phenotype in OCLs from TRACP/MVNP mice. CONCLUSIONS: These results show that persistent expression of the MVNP gene in cells of the OCL lineage can induce pagetic-like bone lesions in vivo.     

Evaluation of renal first pass blood flow with a functional image technique in hypertensive patients

The renal circulation of patients with essential hypertension and renovascular hypertension was evaluated using ^99mTc-DTPA. The first renal peak count (the first C_max; FC_max), time phase distribution (the first T_max; FT_max), and blood velocity (the FC_max/FT_max) were calculated by digital imaging. This yields a visual image of the renal circulation. We consider that the increase in the renal first pass blood flow in patients with essential hypertension is best observed pixel by pixel. The FC_max and FC_max/FT_max images before and after treatment by percutaneous transluminal renal angioplasty in patients with renovascular hypertension clearly show its therapeutic effect. The FI technique, therefore, has the advantage that it can be performed at the same time as the conventional routine examinations of renal function. This makes it very useful clinically.     

Cleft lip-nose repair technique: Sequential repair

The results of repairing cleft lip by aesthetic plastic surgery are now excellent. However, the cleft lipnose deformity is still very difficult to repair with the present techniques. A technique that can repair the cleft lip-nose deformity with good results is presented. The technique is divided into three parts: Part I consists of nasal repair of the primary cleft lip. Part II is nasal reconstruction as a secondary operation with or without lip repair. For example, nasal reconstruction may be secondary to repair of deformities of the sill, rim, limen nasi, septum, or nasal bones. Part III is an aesthetic nasal operation such as rhinoplasty, mentoplasty, or zygomaplasty.     

The Human MitoChip: a high-throughput sequencing microarray for mitochondrial mutation detection

Somatic mitochondrial mutations are common in human cancers, and can be used as a tool for early detection of cancer. We have developed a mitochondrial Custom Reseq microarray as an array-based sequencing platform for rapid and high-throughput analysis of mitochondrial DNA. The MitoChip contains oligonucleotide probes synthesized using standard photolithography and solid-phase synthesis, and is able to sequence >29 kb of double-stranded DNA in a single assay. Both strands of the entire human mitochondrial coding sequence (15,451 bp) are arrayed on the MitoChip; both strands of an additional 12,935 bp (84% of coding DNA) are arrayed in duplicate. We used 300 ng of genomic DNA to amplify the mitochondrial coding sequence in three overlapping long PCR fragments. We then sequenced >2 million base pairs of mitochondrial DNA, and successfully assigned base calls at 96.0% of nucleotide positions. Replicate experiments demonstrated >99.99% reproducibility. In matched fluid samples (urine and pancreatic juice, respectively) obtained from five patients with bladder cancer and four with pancreatic cancer, the MitoChip detected at least one cancer-associated mitochondrial mutation in six (66%) of nine samples. The MitoChip is a high-throughput sequencing tool for the reliable identification of mitochondrial DNA mutations from primary tumors in clinical samples.     

The prevalence of TT virus (TTV) infection and its relationship to hepatitis in children

TT virus (TTV) is a newly discovered virus from a patient with post-transfusion hepatitis. We investigated the frequency and pathogenesis of TTV infection in children. A semi-nested PCR assay was used to amplify TTV-DNA in serum samples from 254 ambulatory children without liver disease, 20 with hepatitis of unknown etiology, and 18 transfusion recipients or hemophiliacs. In positive samples, TTV-DNA was quantified by real-time quantitative PCR using a fluorescent probe. We detected TTV-DNA in 20% of children with hepatitis of unknown etiology, which was not statistically different from the 23% prevalence in ambulatory children. In transfusion recipients or hemophiliacs, the frequency was higher (50%) than that in ambulatory children (P = 0.01). Among ambulatory children, TTV-DNA was frequently detected in children with acute gastroenteritis (36%). TTV-DNA was detected in 10% of the infants under 6 months old, and 20% of the children from 7 to 12  months old. The prevalence was constant after the age of 1 year; however, the copy number of TTV-DNA was significantly higher in children under 1 year of age (mean: 10^5.4 versus 10^3.8 copies/ml, P= 0.008). Finally, TTV-DNA was quantified serially in three children with chronic hepatitis who were positive for TTV-DNA. The presence or amount of TTV-DNA was unrelated to the serum alanine aminotransferase level. These results indicate that TTV infection is common in children. The larger quantity of TTV-DNA in infants and the high prevalence of TTV in children of all ages suggest that TTV may be transmitted in early childhood. Its relationship to hepatitis is doubtful in children. Received: 8 April 1999     

Blood compatibility of surfaces modified by plasma polymerization

Tubular blood-contacting polymeric materials were modified by plasma polymerization and evaluated in the baboon with respect to their capacity to induce both acute and chronic arterial thrombosis. Polymer surface composition was determined by electron spectroscopy for chemical analysis. Steady-state arterial thromboembolism was initiated by introducing tubular segments into chronic arteriovenous shunts. Rates of platelet destruction induced by the test materials were calculated from 111In-platelet survival measurements. Nine plasma polymers based on tetrafluoroethylene, hexafluoroethane, hexafluoroethane/H2, and methane, when deposited on silicone rubber, consumed platelets at rates ranging from 1.1-5.6 x 10(8) platelets/cm2-day. Since these values were near the lower detection limit for this test system, the plasma polymers were considered relatively nonthrombogenic. Acute thrombus formation was initiated by inserting expanded Teflon (Gore-Tex PTFE) vascular grafts into the shunt system. 111In-platelet deposition was measured by scintillation camera imaging over a 1-h exposure period. Standard PTFE grafts (10 cm x 4 mm i.d.) accumulated approximately 1 x 10(10) platelets over this interval. While modification of PTFE grafts with a plasma polymer based on hexafluoroethane/H2 did not alter graft surface morphology, platelet deposition was reduced by 87% as compared to the controls (p less than 0.001). We conclude that both the surface chemistry and texture of prosthetic materials influence thrombogenesis. The method of plasma polymerization may be useful for assessing the importance of these variables independently and, perhaps, for minimizing certain adverse blood-material interactions.