Chirality-transfer control using a heterotopic zinc(II) porphyrin dimer.
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Biomedical subjects
Publications and source records attributed to Y Ishimaru.
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Single cell cDNA libraries were constructed from taste bud cells of rat circumvallate papillae. Using three steps of screening, including differential hybridization, sequence analyses and in situ hybridization, a clone encoding a rat homolog of yeast adenylyl cyclase-associated protein (CAP) was identified to be highly expressed in a subset of taste bud cells.
We previously developed an alternative method for estimating the brain perfusion index (BPI) using technetium-99m compounds and spectral analysis (SA) for quantification of cerebral blood flow (CBF). In this study, we investigated the reproducibility of the BPI values obtained by SA (BPIS) using a double injection of technetium-99m ethyl cysteinate dimer without any intervention, and compared it with that of the BPI values obtained by graphical analysis (BPIG). The BPIS values in the first (x) and second sessions (y) correlated closely (y=0.921x+0.036; r=0.962; n=64; s.e.e.=0.058 min-1). Although the BPIG values in the first (x) and second sessions (y) also correlated (y=0.942x+0.040; r=0.916; n=64; s.e.e.=0.061 min-1), the correlation coefficient for BPIS was significantly higher than that for BPIG. The reproducibility was dependent on the injection dose ratio of the second session to the first (R). The difference in BPI between the first and second sessions tended to be smaller when 1.5<R<2.5 than when 0<R<1.5 or 2.5<R. These results suggest that the reproducibility of BPIS is satisfactory and that it can be applied to two sequential measurements of CBF using a double injection of 99mTc compounds. When applying our method to such measurements, it is recommended that R is taken as approximately 2.0.
PURPOSE: Long-term survival and cure cannot be achieved in patients with unresectable, advanced abdominal cancer, because no chemotherapeutic treatment has definite antitumor activity for malignant solid tumor and its dissemination. In this study, arterial and intraperitoneal administration of oily anticancer agents, which have properties that permit targeted chemotherapy for VX2 carcinoma implanted in the liver, was attempted to achieve long-term survival. MATERIALS AND METHODS: Rabbits bearing VX2 tumors in the liver measuring 1-2 cm in diameter received an arterial injection of 0.2 ml of nitrogen mustard N-Oxide (HN2-O) dissolved in Lipiodol (7.5 mg/ml), a newly developed oily anticancer agent, for the tumor and an intraperitoneal injection of a cocktail of oily anticancer agents for the prevention of intraperitoneal dissemination. RESULTS: Twelve out of thirteen rabbits survived and VX2 cancer was not observed in these 12 rabbits. The controls received a sham operation, an intraperitoneal injection of the cocktail of oily anticancer agents alone, or an arterial injection of HN2-O/Lipiodol alone. In these control groups, 27 out of 29 rabbits died of cancer. To examine the dose form for arterial injection, 14 rabbits received an arterial injection of the simple mixture of HN2-O dissolved in physiological saline and Lipiodol, with an additional intraperitoneal injection of the cocktail. Eight of these 14 rabbits died of enlargement of the hepatic tumor and peritoneal dissemination. CONCLUSION: Long-term survival and cure was achieved in almost all rabbits bearing VX2 tumor in the liver by simultaneous arterial and intraperitoneal injection of oily anticancer agents.
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Mammalian lefty and zebrafish antivin, highly related to lefty, are shown to be expressed asymmetrically and involved in the specification of the left body side of early embryos. We isolated a chick homologue of the antivin/lefty1 cDNA and studied its expression pattern during early chick development. We found that antivin/lefty1 is expressed asymmetrically on the left side of the prospective floorplate, notochord and lateral plate mesoderm of the chick embryo.
Profilin (PFN) is an ubiquitous, low-M(r), actin-binding protein involved in the organization of the cytoskeleton of eukaryotes including higher plants. PFNs are encoded by a multigene family in Arabidopsis. We have analyzed in vivo functions of Arabidopsis PFN by generating transgenic plants carrying a 35S-PFN-1 or 35S-antisense PFN-1 transgene. Etiolated seedlings underexpressing PFN (PFN-U) displayed an overall dwarf phenotype with short hypocotyls whose lengths were 20% to 25% that of wild type (WT) at low temperatures. Light-grown PFN-U plants were smaller in stature and flowered early. Compared with equivalent cells in WT, most cells in PFN-U hypocotyls and roots were shorter, but more isodiametric, and microscopic observations of etiolated PFN-U hypocotyls revealed a rough epidermal surface. In contrast, light-grown seedlings overexpressing PFN had longer roots and root hair although etiolated seedlings overexpressing PFN were either the same size or slightly longer than WT seedlings. Transgenic seedlings harboring a PFN-1-GUS transgene directed expression in root and root hair and in a ring of cells at the elongating zone of the root tip. As the seedlings matured PFN-1-GUS was mainly expressed in the vascular bundles of cotyledons and leaves. Our results show that Arabidopsis PFNs play a role in cell elongation, cell shape maintenance, polarized growth of root hair, and unexpectedly, in determination of flowering time.
OBJECT: Of all intracranial dural arteriovenous fistulas (DAVFs), those with cortical venous drainage associated with cortical venous ectasia or varices are predisposed to an aggressive course and produce progressive neurological symptoms or hemorrhages. The authors undertook a histological examination of venous aneurysms and arterialized veins in the proximity of these aneurysms that had been surgically removed in patients with DAVFs. METHODS: Surgical specimens were obtained in eight patients. The excised venous aneurysms and the arterialized veins in their proximity were stained using hematoxylin and eosin, van Gieson's elastic, and Masson's trichrome stain. Immunostaining was also performed for alpha smooth-muscle actin, desmin, and factor VIII antigen. Five of the patients had presented with venous hypertension, and three had intracranial hemorrhages. The arterialized vein obtained in the proximity of the venous aneurysm exhibited local irregular intimal thickening; the internal elastic lamina (IEL) was grossly preserved. All venous aneurysms in patients with venous hypertension manifested medial thickening and local intimal thickening with loss of IEL; the thickness of the wall was relatively uniform. In contrast, the wall thickness of venous aneurysms in patients with hemorrhage was extremely irregular and there was no clear delineation between the media and the intima. In media with complete disappearance of IEL, there was scant muscle tissue. CONCLUSIONS: Degenerative changes in venous aneurysms in patients with hemorrhage were much greater than in patients with venous hypertension, possibly because hemorrhages result from a more complicated interplay of anatomical, hemodynamic, and degenerative factors.
Cyclic nucleotide-gated (CNG) channels are essential proteins that contribute to the intracellular signal transduction of the senses of sight and smell. Recently, we found a novel CNG channel (CNGgust) in rat taste buds, and demonstrated its possible involvement in taste signal transduction. In the present study, we used RT-PCR and immunostaining to prove that this gustatory CNG channel is expressed in the outer segments of rat cone photoreceptor cells. The study strongly suggests that the senses of taste and sight share, at least in part, a common signal transduction pathway.
Cerebral blood flow (CBF) has been quantified non-invasively using the brain perfusion index (BPI) determined from radionuclide angiographic data generated by technetium-99m hexamethylpropylene amine oxime( )((99m)Tc-HMPAO) or technetium-99m ethyl cysteinate dimer( )((99m)Tc-ECD). The BPI is generally calculated using graphical analysis (GA). In the present study, BPI was measured using spectral analysis (SA), and its usefulness evaluated in comparison with GA. The BPI was calculated from the sum of spectral data obtained by SA. We applied this method to radionuclide angiographic data collected from the bilateral brain hemispheres of 20 patients with various brain diseases using (99m)Tc-HMPAO and from those of 20 patients using (99m)Tc-ECD. We also measured BPI using GA. The BPI values obtained by SA (BPI(S)) (x) and by GA (BPI(G)) (y) correlated closely (y=0.708x+0.038, r=0.945 for (99m)Tc-HMPAO and y=0.559x+0.093, r=0.931 for (99m)Tc-ECD). However, the BPI(G) values were underestimated by 22.9%+/-6.6% (mean+/-SD) for (99m)Tc-HMPAO and by 27.9%+/-7.5% for (99m)Tc-ECD as compared with the BPI(S) values. The extent of underestimation tended to increase with increasing BPI(S) values. These findings were considered to be a result of the BPI(G) values being affected by the first-pass extraction fraction of the tracer. We also compared the BPI(S) and BPI(G) values with those of CBF measured using N-isopropyl-p-[(123)I]iodoamphetamine (CBF(IMP)) in 16 patients (six for (99m)Tc-HMPAO and ten for (99m)Tc-ECD). Although both BPI(S) and BPI(G) values correlated significantly with the CBF(IMP) values, the correlation coefficient in BPI(S) was always better than that in BPI(G) (r=0.869 for (99m)Tc-HMPAO and r=0.929 for (99m)Tc-ECD in BPI(S), r=0.629 for (99m)Tc-HMPAO and r=0.856 for (99m)Tc-ECD in BPI(G)). These results suggest that SA can provide a more reliable BPI for quantifying CBF using (99m)Tc-HMPAO or (99m)Tc-ECD than the conventional method using GA. Our method will be useful especially when using a tracer with a low first-pass extraction fraction and/or when performing activation studies using pharmacological intervention.
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The present study was designed to investigate a possibility of substitution of the venous blood radioactivity counts sampled 26 min post injection for the octanol-extracted arterial blood radioactivity counts obtained at 5 min after the injection of N-isopropyl-p-[123I]iodoamphetamine (123I-IMP). Furthermore, we investigated whether the integral of input function can be estimated from the venous blood radioactivity counts sampled 26 min post injection and the whole-brain time-activity curves early after 123I-IMP injection. There was a good correlation between the arterial blood radioactivity counts sampled 5 min post injection (y) and those obtained at 26 min (r = 0.902; n = 91; y = 2.348x - 867.063). There was also a good correlation between the arterial (x) and venous blood radioactivity counts (y) sampled 26 min post injection (r = 0.954; n = 14; y = 0.761x + 924.336). The venous blood radioactivity counts sampled at 26 min (x) correlated well with the octanol-extracted arterial blood radioactivity counts sampled at 5 min (y) (r = 0.964; n = 32; y = 0.173x - 21.598). There was a good correlation between the integrals of input function obtained from the regression equation obtained above and the whole-brain time-activity curves acquired during 7 min post injection (y) and those obtained by 5-min continuous arterial blood sampling (x) (r = 0.965; n = 41; y = 0.957x + 2665.208). These results indicate that this noninvasive and simple method can estimate the integral of input function for quantification of cerebral blood flow using 123I-IMP.
Signaling molecules such as Activin, Sonic hedgehog, Nodal, Lefty, and Vg1 have been found to be involved in determination of left-right (L-R) asymmetry in the chick, mouse, or frog. However, a common signaling pathway has not yet been identified in vertebrates. We report that Pitx2, a bicoid-type homeobox gene expressed asymmetrically in the left lateral plate mesoderm, may be involved in determination of L-R asymmetry in both mouse and chick. Since Pitx2 appears to be downstream of lefty-1 in the mouse pathway, we examined whether mouse Lefty proteins could affect the expression of Pitx2 in the chick. Our results indicate that a common pathway from lefty-1 to Pitx2 likely exists for determination of L-R asymmetry in vertebrates.
We report an unusual pedunculated polyp in the stomach in a 41-year-old woman. She was hospitalized because of epigastric discomfort. Endoscopy revealed a polyp with a long stalk in the fundus of the stomach. The polypectomyzed polyp measured 23 x 18 x 9 mm and was characterized by submucosal proliferation of glands and cystic dilatation. The surface of the polyp was covered with gastric mucosa of fundic or pyloric gland type. The glandular structures consisted of various types of lining cells, including pyloric or mucous-neck cell type, surface mucous (foveolar) cell type, parietal-like cells, and somatostatin-positive cells. The submucosal glandular or cystic elements were connected with the overlying gastric mucosa through a defect of the muscularis mucosa, suggesting that this polyp may have been formed by the heterotopic inverted downgrowth of mucous glands into the submucosa. We discuss the histogenesis of this rare polyp and present a review of the literature.
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In this study, we examined the possibility of targeting drug delivery to tumours by dissolving the cytotoxic drug in a lipid fluid that is selectively deposited in tumours. Rabbits bearing VX2 tumour 10-20 mm in diameter in the large bowel received arterial injections of 0.2 ml of mitomycin C (MMC) dissolved in Lipiodol (MMC/Lipiodol), and the antitumour activity and adverse effects were examined. One week after treatment complete necrosis of the tumour was observed in 8 of 10 rabbits that received MMC/Lipiodol (3 mg/ml) without severe adverse effects on the surrounding caecum. In comparison 3/12 control animals that received MMC in saline and Lipiodol also showed complete necrosis. 6 of 7 rabbits killed eight weeks after the injection of MMC/Lipiodol were cured, with no viable tumour cells and with a normal appearance of the surrounding large bowel. In conclusion, MMC dissolved in Lipiodol may be adaptable for the treatment of colon cancer and may achieve antitumour activity without severe adverse effects.
We have developed a new method to replace the conventional method of quantitatively measuring cerebral blood flow (CBF), in which octanol-extracted radioactivity counts are measured in continuous arterial blood samples. With the new method, the whole-brain time-activity curves early after the intravenous injection of N-isopropyl-p-[123I]iodoamphetamine were first obtained by the least-squares curve-fitting method. The equation thus obtained was differentiated and the radioactivity counts were corrected by the 5-min octanol-extracted radioactivity counts of the arterial blood sample obtained at a single time point. In the present study, the value obtained by integrating the equation from 0 to 5 min, which was obtained by curve-fitting, was compared with the octanol-extracted radioactivity counts obtained by 5-min continuous arterial blood sampling in 160 patients with cerebrovascular disorders. The results showed good agreement between the values obtained by the two procedures (y = 1.049x - 1522.4; r = 0.987). Using the CBF obtained by the 5-min continuous arterial blood sampling as the standard, the errors using the present integral values of the input function were 7.1 +/- 4.9%. Measurements of the integral of the input function by the present one-point arterial blood sampling method has the potential for use in the routine measurement of CBF, because it is less invasive and more convenient than the conventional method, and it is unaffected by cardiopulmonary disease or smoking.
It has been reported that members of the fibroblast growth factor (FGF) family can induce additional limb formation in the flank of chick embryos. The phenotype of the ectopic limb depends on the somite level at which it forms: limbs in the anterior flank resemble wings, whereas those in the posterior flank resemble legs. Ectopic limbs located in the mid-flank appear chimeric, possessing characteristics of both wings and legs; feather buds are present in the anterior halves with scales and claws in the posterior halves. To study the mechanisms underlying the chimerism of these additional limbs, we cloned chick Tbx5 and Tbx4 to use as forelimb and hindlimb markers and examined their expression patterns in FGF-induced limb buds. We found that Tbx5 and Tbx4 were differentially expressed in the anterior and posterior halves of additional limb buds in the mid-flank, respectively, consistent with the chimeric patterns of the integument. A boundary of Tbx5/Tbx4 exists in all ectopic limbs, indicating that the additional limbs are essentially chimeric, although the degree of chimerism is dependent on the position. The boundary of Tbx5/Tbx4 expression is not fixed at a specific position within the interlimb region, but dependent upon where FGF was applied. Since the ectopic expression patterns of Tbx5/Tbx4 in the additional limbs are closely correlated with the patterns of their chimeric phenotypes, it is likely that Tbx5 and Tbx4 expression in the limb bud is involved in determination of the forelimb and hindlimb identities, respectively, in vertebrates.