Maternal blood during pregnancy, cord blood, and placental villous tissues at the time of delivery were obtained from subjects to measure the HTLV-1 proviral load (PVL) using real-time PCR. As shown in Figure 1A, HTLV-1 provirus was detected in the maternal blood of 248 of 254 subjects (97.6%), in the placental villous tissues of 140 of 254 subjects (55.1%), and in the cord blood samples of 6 of 254 subjects (2.4%). Overall, 248 women had PVL in the maternal blood, of whom 140 also had PVL in the placenta. Of these 140 women, 6 had PVL in the cord blood. Significant differences in the PVL were observed between the maternal blood, cord blood, and placental villous tissues (Figure 1A). The 248 pregnant carriers with PVL in the maternal blood were divided into those with PVL (n = 140) and without PVL (n = 108) in the placental tissue, and their clinical backgrounds were compared. Women with PVL in the placental tissue had a significantly higher peripheral blood PVL, higher antibody titers, and more multiparas compared with women with no PVL in the placental tissue (Table 1 and Figure 1B). These 2 groups did not differ in terms of birth weight and pregnancy complications (Table 1). There was no significant difference in the clinical backgrounds of pregnant women with HTLV-1 in the placenta when divided into those who tested positive versus negative for HTLV-1 in the cord blood (Supplemental Table 1). This was at least in part due to the small number of pregnant women testing positive for HTLV-1 in the cord blood. In addition, there were insufficient numbers of follow-up surveys of cases of MTCT by intrauterine transmission to allow statistical analysis. These issues are subjects for future investigation. A weak positive correlation between the PVLs in the maternal blood and in the placental villous tissues was observed (Figure 1C), whereas PVL in HTLV-1-positive cord blood samples did not correlate with PVL in the maternal blood or placental villous tissues of the same subject (Figure 1, D and E). To test the possibility that HTLV-1 provirus detected in cord blood was derived from maternal blood contamination of cord blood, microsatellite analysis was performed using short tandem repeat (STR) markers (25). Differences in the patterns of representative STR markers were observed between maternal blood-derived DNA and fetal placental villous tissue-and cord blood-derived DNA (Figure 1F). Similar results were obtained for all 6 samples that tested positive for HTLV-1 provirus in the cord blood. Furthermore, STR analysis and HTLV-1 PVL assay were used to examine how much maternal blood in the cord blood was required to detect a positive signal. A mixing rate of 20% (maternal/fetal cell ratio = 20:80) was the detection limit in the STR analysis, and a mixing rate of 5% (maternal/fetal cell ratio = 5:95) was the detection limit in the HTLV-1 PVL assay (Supplemental Figure 1). A previous study reported that the median rates of maternal blood contamination in the cord blood were 0.27% and 0.

To clarify functional neural pathways originating from the thalamic nucleus ventralis posterolateralis (VPL) in humans, the responses of regional CBF (rCBF) and regional CMRO2 (rCMRO2) to VPL stimulation were investigated by positron emission tomography in five patients who had undergone chronic implantation of electrodes into the VPL for therapeutic purposes. Measurement of rCBF and rCMRO2 under continuous inhalation of C15O2 and 15O2 by steady-state methods revealed significant increases of rCBF and rCMRO2 in the frontal, postcentral, and thalamic regions. The increases in rCBF and rCMRO2 of the postcentral regions were clearly predominant in the stimulated hemisphere insofar as the stimulation produced moderate paresthesia in restricted areas of the body. These results indicate that the VPL relays peripheral somatosensory information, which has previously been demonstrated to be transmitted to the frontal as well as postcentral regions.

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The measurement of human T-cell leukemia virus type 1 (HTLV-1) proviral DNA levels by using polymerase chain reaction has been beneficial for confirming HTLV-1 infection during pregnancy. However, the influence of pregnancy on HTLV-1 infection and proviral DNA levels among pregnant women with HTLV-1 has not been clarified. We prospectively gathered blood samples from 36 pregnant women in whom HTLV-1 carriage was previously diagnosed and sequentially measured their proviral DNA levels. The HTLV-1 proviral DNA levels remained at a plateau during pregnancy but were elevated after delivery. Moreover, flow cytometry and serological analyses revealed that the regulatory T-cell population and soluble interleukin 2 receptor levels were similarly elevated after birth in comparison with those in control pregnant women. This study is the first to provide data on sequential changes in HTLV-1 proviral DNA levels during and after pregnancy. These findings will guide the establishment of a better program to prevent mother-to-child transmission of HTLV-1.

Pyruvate-1-11C was prepared enzymatically by the exchange reaction of 11CO2 with the carboxyl group of pyruvic acid using pyruvate-ferredoxin oxidoreductase from Clostridium butyricum. 11C-Labeled pyruvate was purified by sublimation in specially made glassware. The radiochemical yield of pure pyruvate-1-11C was 80% 35 min after the end of bombardment. The distribution of 11C in tumor-bearing rabbits after an i.v. injection of pyruvate-1-11C was observed using a gamma camera. In contrast to normal organs, the tumor was positively visualized. We also conducted a number of successful clinical studies. A case of brain tumor which exhibited a positive image on positron-emission tomography (PET) using pyruvate-1-11C is presented.

We report the differentiation potential of an immortalized non-tumorigenic human liver epithelial cell line, THLE-5b. Under basic culture conditions THLE-5b showed undifferentiated phenotypes. When grown as cell aggregates, THLE-5b exhibited a hepatocyte-like ultrastructure, ammonia metabolic activity and several other indicators that suggest hepatocytic maturation, including up-regulation or induction of liver-specific genes such as albumin and tryptophane 2,3-dioxygenase, and down-regulation of biliary cell markers such as gamma-glutamyl transpeptidase (GGT). Under these conditions, transcriptional factors such as HNF-1 and HNF-4alpha were also up-regulated or induced. In Matrigel culture, expression of GGT was up-regulated. THLE-5b expressed both albumin and alpha 1-antitrypsin, but lost expression of CK19 in severe combined immunodeficient mice. Thus, THLE-5b can be aligned with progenitor cells, which are committed to the hepatocytic or biliary epithelial cell lineage. These results imply that bipotent progenitor cell populations similar to THLE-5b cells may exist in adult human liver.

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