A novel diagnostic method for evaluation of vascular lesions in the digestive tract using infrared fluorescence endoscopy.

BACKGROUND AND STUDY AIMS: We have developed an infrared fluorescence endoscope to evaluate gastrointestinal vascular lesions. Infrared endoscopy (IRE) after intravenous administration of indocyanine green (ICG) is used at present to examine vascular lesions such as esophageal varices. However, no previous study has compared the sensitivity of infrared fluorescence endoscopy (IRFE) with that of IRE. In this study, we compared the usefulness of IRFE and IRE. PATIENTS AND METHODS: For IRFE we used an infrared endoscope equipped with excitation and barrier filters and an intensified charge-coupled device camera. In preliminary experiments, the observable tissue depth was assessed by wrapping increasing numbers of layers of commercially available pork around a syringe containing a uniform concentration of ICG or by changing the concentration of ICG in a syringe covered by a piece of pork of uniform thickness. In the clinical part of the study, ICG was administered intravenously at different concentrations to patients with esophageal varices and the resulting infrared fluorescent images were evaluated. RESULTS: The preliminary experiments revealed that the depth of tissue that could be visualized was significantly greater in IRFE than it was in IRE (11.2 mm in IRFE vs. approximately 3.2 mm in IRE). Clear infrared fluorescence was obtained by IRFE at lower concentrations of ICG than the concentrations required to obtain clear images using IRE. In the clinical part of the study, clear infrared fluorescence was observed in a region where esophageal varices had been detected by conventional endoscopy when ICG was administered in doses of 0.005 mg/kg to 0.01 mg/kg, which was lower than the doses used in IRE. CONCLUSIONS: Compared with conventional IRE, IRFE facilitated the observation of deeper layers, and esophageal varices were observed by IRFE following the intravenous administration of a markedly reduced dose of ICG. IRFE, in combining the characteristics of reflected infrared light and fluorescence, may be a useful novel procedure in the diagnosis of vascular lesions in the gastrointestinal tract.

Clonal evolution from trisomy into tetrasomy of chromosome 8 associated with the development of acute myeloid leukemia from myelodysplastic syndrome.

Tetrasomy 8, though rare, is usually associated with trisomy 8, a far more common chromosomal abnormality in acute myeloid leukemia (AML). Yet the clonal relationship between trisomy 8 and tetrasomy 8 in the cases with these chromosomal abnormalities has been unclear. Here, we report a case of a 17-year-old male, diagnosed as having a myelodysplastic syndrome (MDS). Chromosome analysis showed the presence of trisomy 8. Five years later, he developed overt AML exhibiting tetrasomy 8 only. After chemotherapy, the blast cells in the bone marrow decreased to 3.4%, and the karyotype showed trisomy 8 alone. Fluorescence in situ hybridization using a probe specific for chromosome 8 showed that the percentages of cells exhibiting 2/ 3 /4 signals were 7.8/89.2/2.0 at the MDS stage, 20.5/36.1/41.0 when overt AML developed and 24.0/72.1/2.4 after chemotherapy. These results suggested that tetrasomy 8 is derived from the AML clone, possibly evolved from the MDS clone with trisomy 8. To our knowledge, this is the first detailed case report of clonal evolution from trisomy 8 into tetrasomy 8 associated with the development of AML from MDS.

[Molecular regulation of heme biosynthesis].

It is generally accepted that the major organs producing heme are erythroid cells and the liver. delta-Aminolevulinate synthase (ALAS) plays the key role to regulate heme biosynthesis in the liver as well as in erythroid cells. In the liver, nonspecific (or housekeeping) isozyme of ALAS (ALAS-N) is expressed to be regulated by its end product, heme, in the negative feedback manner. Not only erythroid isozyme of ALAS (ALAS-E) but also ALAS-N is expressed in erythroid tissues, and are regulated by distinctive manners. For example, heme regulates ALAS-N and ALAS-E in the negative and in the positive feedback manner, respectively. In this article, we describe the molecular mechanisms to regulate heme biosynthesis not only in the liver but also in erythroid cells.