Arterial fraction of cerebral blood volume in humans measured by positron emission tomography

In quantitative functional neuroimaging with positron emission tomography (PET) and magnetic resonance imaging (MRI), cerebral blood volume (CBV) and its three components, arterial, capillary, and venous blood volumes are important factors. The arterial fraction for systemic circulation of the whole body has been reported to be 20-30%, but there is no report of this fraction in the brain. In the present study, we estimated the arterial fraction of CBV with PET in the living human brain. C(15)O and dynamic H2(15)O PET studies were performed in each of seven healthy subjects to determine the CBV and arterial blood volume (Va), respectively. A two-compartment model (influx: K1, efflux: k2) that takes Va into account was applied to describe the regional time-activity curve of dynamic H2(15)O PET. K1, k2 and Va were calculated by a non-linear least squares fitting procedure. The Va and CBV values were 0.011 +/- 0.004 ml/ml and 0.031 +/- 0.003 ml/ml (mean +/- SD), respectively, for cerebral cortices. The arterial fraction of CBV was 37%. Considering the limited first-pass extraction fraction of H2(15)O, the true arterial fraction of CBV is estimated to be about 30%. The estimated arterial fraction of CBV was quite similar to that of the systemic circulation, whereas it was greater than that (16%) widely used for the measurement of cerebral metabolic rate of oxygen (CMRO2) using PET. The venous plus capillary fraction of CBV was 63-70% which is a important factor for the measurement of CMRO2 with MRI.     

The thymus and negative selection

Summary: Maintenance of tolerance to self antigens is presumed to reflect a combination of central and peripheral tolerance. For T cells, central tolerance occurs during early T cell development in the thymus and causes cells with strong reactivity to self antigens to be destroyed in situ (negative selection). Here, we summarize evidence that negative selection can occur in the thymic medulla and affects a population of semimature HSA⁺ T cells. The influence of costimulatory molecules, Fas and cytokines on negative selection is discussed.     

Association between a large plasmid and 15- to 17-kilodalton antigens in virulent Rhodococcus equi.

Rhodococcus equi strains showing 15- to 17-kDa antigens in immunoblots were found to be virulent in mice. To study the genes specific to these antigens in virulent R. equi, we compared plasmid profiles, immunoblot profiles, and murine pathogenicity profiles of 10 strains of R. equi. All the strains showing 15- to 17-kDa antigens contained a large plasmid of approximately 85 kbp and were virulent in mice; however, the remaining strains lacked both the antigens and the large plasmid and were avirulent in mice. Mutants of virulent strains ATCC 33701 and L1, which were cured of the large plasmid by repeated passage at 38 degrees C, lacked the 15- to 17-kDa antigens and showed a dramatic decrease in lethality in mice. These results suggested that the presence of an 85-kbp plasmid may be essential for virulence and expression of 15- to 17-kDa antigens of R. equi and offered support for earlier observations that freshly isolated strains of R. equi killed mice, whereas laboratory-adapted strains did not.     

Hepatocyte growth inhibitory factor derived from HTLV-I(+) T cell lines: effect on the epidermal growth factor-dependent proliferation of rat hepatocytes

A human T cell leukemia virus-I infected T cell line, ATL-2, produces an interleukin-2 receptor inducing factor, adult T cell leukemia (ATL)-derived factor (ADF). In the conditioned medium (CM) of ATL-2, we found an inhibitory activity on the epidermal growth factor (EGF)-dependent proliferation of primary cultured rat hepatocytes, measured by cell number and [3H]thymidine incorporation. ATL-2 CM dose-dependently inhibited hepatocyte proliferation. This activity was fractionated by gel filtration at a molecular size of 15,000 to 40,000 and was tentatively called hepatocyte growth inhibitory factor (HGI). Further fractionation with the ion-exchange column indicated that HGI was separable from ADF. Nevertheless, there was a positive correlation between HGI and ADF production, because the HGI activity was also detected in the CM of another ADF producer cell line (HUT102), while no significant HGI activity was detected in the CM of low ADF producer cell lines, ED and MOLT4.     

Genetic Polymorphisms of 17β-Hydroxysteroid Dehydrogenase 3 and the Risk of Hypospadias

IntroductionHypospadias is a common congenital anomaly caused by incomplete fusion of urethral folds. Development of the urethra and external genital system in the male fetus is an androgen-dependent process. In this regard, enzymes 17β-hydroxysteroid dehydrogenase type 3 (17βHSD3, encoded by HSD17B3) and steroid 5α-reductase type 2 (encoded by SRD5A2) play crucial roles.AimTo investigate the possible associations between common polymorphisms in HSD17B3 as well as well-known V89L polymorphism in SRD5A2 and risk of hypospadias.MethodsA case-control study was performed between 1999 and 2005. There were 89 Japanese boys with hypospadias and 291 newborn controls. We genotyped HSD17B3?1999T>C, +10A>G, +20A>G, +139G>A (V31I), +913G>A (G289S), and SRD5A2+336G>C (V89L) polymorphisms by allelic discrimination assay. We measured mRNA expression of the wildtype G289 allele and the mutant S289 allele of the HSD17B3 gene in the transfected human fetal kidney HEK293 cells.Main Outcome MeasuresAssessment of hypospadias including its severity and HSD17B3 and SRD5A2 genes using DNA blood samples: allele and genotype distribution of single nucleotide polymorphisms in these two genes in cases and controls.ResultsIn our study, the risk of hypospadias was significantly higher in subjects carrying homozygous HSD17B3+913A (289S) alleles (odds ratio [OR]: 3.06; 95% confidence interval [CI]: 1.38–6.76). The risk of severe hypospadias was much higher in these subjects (OR: 3.93; 95% CI: 1.34–11.49). The mRNA expression levels of HSD17B3 G289 were higher than those of HSD17B3 S289 mutant (P < 0.001). In addition, the risk of severe hypospadias increased in boys carrying the SRD5A2+336C (89L) allele (OR: 3.19; 95% CI: 1.09–9.36).ConclusionsThese results suggest that the HSD17B3 G289S polymorphism may be a potential risk modifier for hypospadias. Our findings provide evidence that a certain genotype related to androgen production may potentiate risk of hypospadias. Sata F, Kurahashi N, Ban S, Moriya K, Tanaka KD, Ishizuka M, Nakao H, Yahata Y, Imai H, Kakizaki H, Nonomura K, and Kishi R. Genetic polymorphisms of 17β-hydroxysteroid dehydrogenase 3 and the risk of hypospadias.     

Intracellular localization and translocation of 1 alpha, 25-dihydroxyvitamin D3 receptor in osteoblasts.

The intracellular localization and translocation of the 1 alpha,25-dihydroxyvitamin D3 receptor (1 alpha,25(OH)2D3 receptor) in osteoblasts of mouse parietal bone and MC3T3-E1 cells were examined immunocytochemically using a rat monoclonal antibody to 1 alpha,25(OH)2D3 receptor. In osteoblasts of parietal bones in vivo, immunoreactivity for 1 alpha,25(OH)2D3 receptor was detected not only in the nuclei but also in lysosomal structures, and also sparsely in the cytoplasmic matrix. The transport of 1 alpha,25(OH)2D3 receptor was investigated immunocytochemically after incubation with 1 alpha,25(OH)2D3. In osteoblasts of parietal bones, after 1 min incubation with 10(-8) M 1 alpha,25(OH)2D3, the perinuclear cytoplasm showed intense immunoreactivity for 1 alpha,25(OH)2D3 receptor. After 10 min incubation, immunoreactivity was intense in the nuclei, especially in the heterochromatin. In MC3T3-E1 cells, after 1 min incubation with 1 alpha,25(OH)2D3, immunoreactivity for 1 alpha,25(OH)2D3 receptor was found in the form of a fibrillar structure extending radially to the periphery of the cells. The immunostaining pattern of anti-1 alpha,25(OH)2D3 receptor was similar to the distribution of microtubules stained with anti-beta-tubulin antibody. After 10 min incubation, the nuclei showed intense immunoreactivity for 1 alpha,25(OH)2D3 receptor. Incubation with colchicine dissociated the fibrillar structures and inhibited the intranuclear localization of the 1 alpha,25(OH)2D3 receptor. These findings suggest that the 1 alpha,25(OH)2D3 receptor is located in the nuclei, in lysosomal structures and also sparsely in the cytoplasmic matrix of osteoblasts in vivo, and that the receptor is transported to the perinuclear cytoplasm via microtubules to be then translocated into the nucleus, especially into the heterochromatin.     

Flow-cytometric analysis of immune cell populations in human decidua from various types of first-trimester pregnancy.

We undertook an investigation in which flow cytometry was used to characterize immune cell populations in the decidua of first-trimester normal pregnancies, spontaneous abortions, and ectopic pregnancies in comparison to the nonpregnant endometrium to demonstrate how the proportions of immunocompetent cell populations at the fetomaternal interface are influenced by the presence and state of a fetoplacental allograft. No significant differences were found in the decidua of the different types of first-trimester pregnancy in the proportions of the CD45+, CD14+, CD3+, CD4+, CD8+, CD19+, CD3-/CD16+ and/or CD56+, CD3+/CD16+ and/or CD56+, CD4+/Leu-8+, CD4+/Leu-8-, CD8+/CD11b+, CD8+/CD11b-, and CD3+/HLA-DR- decidual leukocyte subsets. However, the percentage of decidual CD3+/HLA-DR+ cells, which are characteristic of activated T cells, was significantly higher in spontaneous abortions than in normal pregnancies (p less than 0.05). This suggests that the accumulation of decidual leukocytes may be regulated mainly by hormones and/or cytokines rather than by the presence and state of an intrauterine conceptus and that on/off-switching of activation of decidual T cells may be associated with successful maintenance of the implanted embryo.     

Photo-crosslinking of polymers containing pendant epoxy groups

The photo-crosslinking of polymers containing pendant epoxy groups was carried out at room temp. in the presence of a photosensitive sulfonium salt which is an initiator of cationic polymerization. The crosslinking reactivity of the epoxide-containing polymers was found to depend on the mobilities of both the backbone of the polymers and the pendant epoxy groups, and on the epoxide structure. The introduction of spacer chains between the polymer backbone and the epoxy groups increases the mobilities of the backbone and the epoxides, resulting in an increases crosslinking reactivity. The introduction of a methyl group at the epoxy ring of the polymers with glass transition temp. (T_g) lower than room temp. enhances the crosslinking reactivity, whereas it diminishes the reactivity for the polymers with T_g higher than room temp. This result can be explained by assuming that the presence of the methyl group results not only in an increase of the epoxide reactivity due to both the inductive effect of the methyl group and the increased ring strain, but also the decreased mobility of the epoxy groups. Thus, the reactivity of the rubbery polymers is principally controlled by the intrinsic reactivity of the epoxides, and the reactivity of the rigid polymers is mainly controlled by the mobility of the reactive sites.