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.     

Flow cytometric analysis of the DNA content of thymomas

In this study, the prognostic value of determining the nuclear DNA content of thymomas by flow cytometry was evaluated. Of a total 31 resected thymomas, 10 (32%) showed DNA aneuploidy, the presence of which was significantly correlated with an advanced clinical stage of disease. The patients with an aneuploid tumor had a poorer prognosis than those with a diploid tumor, demonstrating a survival rate of 50% at 7 postoperative years, which was considerably less favorable than that of the patients with a diploid tumor, being 100% in the same period (p<0.05). Moreover, patients with a high DNA index (DI), i.e., a DI1.5, tended to have a poorer prognosis than those with a low DI. These findings indicated that the DNA content can be an important prognostic index in patients with thymomas.     

Association of Loss of Heterozygosity at the p53 Locus with Chemoresistance in Osteosarcomas

Although the osteosarcoma is considered to be among the most chemosensitive malignancies and preoperative chemotherapy is commonly applied, an appreciable proportion of cases are in fact quite insensitive. Predictive markers for chemosensitivity are therefore desirable in order to develop effective treatment strategies. Thirty-two cases of conventional osteosarcomas treated at the Cancer Institute Hospital, Tokyo, were analyzed. The sensitivity to preoperative chemotherapy was investigated with reference to loss of heterozygosity (LOH) at the 17p13 ( p 53) and 13q14 ( Rb ) loci and expression of the cell-cycle associated proteins, p53, Rb, p21/Waf-1, mdm-2 and Ki-67, as detected immunohistochemically. LOH was detected by analyzing polymerase chain reaction products at marker microsatellite loci. The efficacy of chemotherapy was evaluated both radiologically and histologically. LOH at p 53 or Rb loci was seen in 54% (13/24) and 58% (14/24) of cases, respectively. Only 15% of osteosarcomas with LOH at the p 53 locus were sensitive to preoperative chemotherapy, as compared to 64% of tumors without such loss ( P <0.05). A similar but much less distinct tendency was observed with LOH at the Rb locus. No relationship was evident between chemosensitivity and immunohistochemical staining patterns for p53, Rb, p21/Waf-1, mdm-2 or Ki-67. The results suggest that p 53 gene deletion, but not the other parameters investigated, may be useful for predicting chemoresistance of osteosarcomas.     

SLOW GROWING FLAT‐TYPE PRIMARY MALIGNANT MELANOMA OF THE ESOPHAGUS TREATED WITH CAP‐ASSISTED EMR

We report a rare case of flat‐type primary malignant melanoma of the esophagus treated with endoscopic mucosal resection (EMR). A 64‐year‐old woman was referred for examination of a small pigmented lesion located in the mid esophagus. On endoscopy, the lesion exhibited almost no change in size over the year. Cap‐assisted EMR was performed en bloc. The histopathological findings showed atypical melanocyte proliferation in the basal layer, spindle cells, and epithelioid cell proliferation with nuclear enlargement and a few mitotic figures. Histopathological examination confirmed the diagnosis of primary malignant melanoma. Immunostaining for S‐100 protein and HMB‐45 antibody were positive, and the Ki‐67 index was low. The patient was discharged without additional surgical resection and/or chemotherapy. The patient had no symptoms and no signs of recurrence 20 months after EMR. There has been no report on a slow growing esophageal melanoma. It is difficult to estimate the malignant behavior of this case.