Asian dust-deposition flux to the subarctic Pacific estimated using single quartz particles.

Iron availability limits marine ecosystem activities in large areas of the ocean. However, the sources and seasonal supply of iron, critically important for controlling surface ocean biogeochemistry and carbon cycling, are poorly understood. The western subarctic Pacific is a high-nutrient and low-chlorophyll region, and despite high concentrations of macronutrients, iron limits phytoplankton production in summer. Here, we determine the seasonal deposition flux of Asian dust using scanning electron microscope-cathodoluminescence analysis of single quartz particles derived from the western subarctic Pacific during 2003-2022 to trace provenance. We found a high (up to 6.9 mg m-2 day-1) deposition flux of Asian dust in May, June, and early July, with an annual average of 1.0 ± 0.2 mg m-2 day-1. The supply of dissolved-iron flux calculated from Asian dust was 0.9 ± 0.3 µg m-2 day-1 during the high productivity season (April-July), which is approximately half that from the deeper part of the ocean, calculated from vertical profiles of dissolved iron. Our study provides a reliable approach for estimating iron supply from dust to the surface ocean that may be critical for sustaining biological productivity under future ocean stratification, which suppresses nutrient supply from the subsurface ocean.

Prenatally diagnosed large mediastinal lymphangioma: A case report.

Thoroughly planned labor with immediate postnatal resuscitation and percutaneous decompression is mandatory for a large mediastinal lymphangioma that compromises the cardiopulmonary function, and close observation with the administration of Eppikajutsuto (TJ-28), a Japanese herbal medicine, may be a reasonable treatment, especially when resection of the lesion seems technically challenging.

Temporal changes in radiocesium contamination derived from the Fukushima Dai-ichi Nuclear Power Plant accident in oceanic zooplankton in the western North Pacific.

We investigated temporal changes of the contamination of oceanic zooplankton with radiocesium (134Cs and 137Cs) derived from the Fukushima Dai-ichi Nuclear Power Plant accident one month to three years after the accident at subarctic and subtropical stations (1900 and 900-1000 km from the plant, respectively) in the western North Pacific. The maximum activity concentrations of 137Cs in zooplankton were two orders of magnitude higher than the pre-accident level. In the first four months after the accident, the activity concentrations of radiocesium in subtropical zooplankton decreased rapidly, but no similar change was observed at the subarctic station. The radiocesium derived from atmospheric deposition rapidly decreased as a result of seawater mixing. Thus, most of the subtropical zooplankton (with short lifespans) that had taken up radiocesium just after the accident were probably replaced by newly hatched zooplankton within four months of the accident, whereas subarctic zooplankton (with long lifespans) that were highly contaminated with radiocesium were still alive four months after the accident. By the end of the study, 137Cs activity concentrations in subtropical zooplankton were still high, whereas the activity concentrations in subarctic zooplankton had decreased to nearly the pre-accident level. The former concentrations were probably influenced by a secondary supply of radiocesium via advection of subtropical mode water that was highly contaminated with Fukushima-derived radiocesium. Unexpectedly, at the subarctic station, the radiocesium activity concentrations in surface zooplankton were lower than those in subsurface zooplankton, whereas the opposite relationship was observed in surface and subsurface seawater. Because carnivores predominated in the subsurface zooplankton community, we hypothesize that the higher radiocesium activity concentrations in subsurface zooplankton were influenced by bioaccumulation. We conclude that radiocesium activity concentrations in zooplankton are influenced not only by the supply of radiocesium to the environment but also by the characteristics of the zooplankton community.

Tracking the Fate of Particle Associated Fukushima Daiichi Cesium in the Ocean off Japan.

A three year time-series of particle fluxes is presented from sediment traps deployed at 500 and 1000 m at a site 115 km southeast of Fukushima Daiichi Nuclear Power Plant (FDNPP). Results show a high fraction of lithogenic material and mass flux peaks that do not align between the trap depths, suggesting a lateral source of sediments. Fukushima cesium-137 and cesium-134 were enhanced in flux peaks that, given variations in trap (137)Cs/(210)Pbex ratios, are characteristic of material derived from shelf and slope sediments found from <120 to >500 m. These lateral flux peaks are possibly triggered by passing typhoons. The Cs fluxes are an order of magnitude higher than were previously reported for the trap located 100 km due east of FDNPP. We attribute this large difference to the position of our trap under the southeasterly currents that carry contaminated waters and resuspended sediments away from FDNPP and into the Pacific. These higher Cs sedimentary fluxes offshore are still small relative to the inventory of Cs currently buried nearshore. Consequently, we do not expect them to effect any rapid decrease in Cs levels for the coastal sediments near FDNPP that have been linked to enhanced Cs in demersal fish.

Positive C4d staining of the portal vein endothelium in the liver of patients with biliary atresia: a role of humoral immunity in ongoing liver fibrosis.

PURPOSE: This study aimed to clarify the role of complement activation in fibrogenesis in BA. METHODS: In total, 27 paraffin-embedded liver biopsy samples were immunohistochemically analyzed using C4d polyclonal antibody, vascular cell adhesion molecule-1 (VCAM-1), and CD45. The liver samples were obtained from 25 patients during Kasai operation, and two additional specimens were obtained from 2 patients by needle biopsy later at the time of liver function deterioration. The degree of liver fibrosis was histologically graded 1-3. RESULTS: Among the 25 samples, 9 showed C4d-positive immunostaining localized on the endothelia of a few portal veins in the portal tract. The degree of fibrosis was correlated with C4d staining (p = 0.025). The age at Kasai operation correlated with the degree of fibrosis and the C4d positivity. Two needle biopsy samples were positive for C4d. Among 13 samples submitted for VCAM-1 staining, 2 negative samples were C4d negative and all positive C4d samples were VCAM-1 positive with CD45 mononuclear cell infiltration. CONCLUSION: These findings suggest that ongoing cirrhosis could be a result of progressive "vasculopathy" of the portal vein caused by humoral and cell-mediated immune interaction.

Long-term survival with cloacal dysgenesis sequence.

Cloacal dysgenesis sequence (CDS) is a rare and lethal malformation. We report such a case of long-term survival, currently to 12 years of age. In the fetal period, she received a timely placement of vesico-amniotic shunt for a megabladder due to a severe urethral obstruction. Postnatally, cystostomy and colostomy were created because of no perineal opening of urethra, vagina, and anus. Anorectoplasty, construction of efferent conduit, and colostomy closure were performed at 4 years of age. Ileovaginoplasty and ileovesicostomy which was a Mitrofanoff-type of conduit, and labioplasty were performed at the age of 11 years. To the best of our knowledge, only five survivors with CDS over 1 year of age have been reported.

Minimally invasive repair of hypospadiac urethral duplication.

Urethral duplication is a rare congenital anomaly with various clinical presentations, and multiple techniques have been described for its repair. We report a 1-year-old boy with hypospadiac urethral duplication who presented with double urinary stream. Voiding cystourethrography, retrograde urethrography, and cystourethroscopy showed the normal-caliber ventral urethra was dominant and the distal dorsal (non-dominant) urethra had a good caliber. Urethral reconstruction was performed with an incision of the adjoining walls of the both urethra in a side-to-side urethrourethrostomy fashion.

Novel piperidinylpyrimidine derivatives as inhibitors of HIV-1 LTR activation.

Piperidinylpyrimidine derivatives, previously prepared as inhibitors of TNF-alpha production, were evaluated for their inhibitory activity against HIV-1 LTR activation. Some of these derivatives inhibited activation of HIV-1 LTR-directed CAT gene expression induced by PMA in Jurkat cells. In this report, we describe SAR in this series of compounds and show that the 3,4-methylenedioxybenzoyl (piperonyloyl) group on the nitrogen of piperidine and lipophilic substitution at the C(6)-position of pyrimidine are important for this inhibitory activity. Some of the synthesized compounds also inhibited HIV-1 LTR transactivation induced by viral protein Tat. These results suggest that piperidinylpyrimidines are useful as potent AIDS therapeutics that directly inhibit HIV-1 LTR activation and indirectly suppress TNF-alpha production.

Surface water mixing estimated from 228Ra and 226Ra in the northwestern North Pacific.

We investigated the horizontal distributions of (228)Ra and (226)Ra in surface waters of the northwestern North Pacific Ocean and Okhotsk Sea. Ratios of (228)Ra/(226)Ra were relatively large in the Tsugaru Current (0.6-0.8) and Okhotsk Sea (0.4-0.5), and small in the Western Subarctic Gyre (<0.2) and the Oyashio (0.25-0.3). (228)Ra/(226)Ra ratios in western Subarctic Water (SAW) rose slightly upon mixing with Okhotsk Water (OKW), before becoming the Oyashio Water (OYW). Also, ratios in the OYW increased during mixing with Tsugaru Current Water (TCW). Estimating from (228)Ra/(226)Ra ratios and (226)Ra activities with a simple two-end members-mixing model, we assumed that approximately 23% of the OYW originated from the OKW and the coastal region off northern Honshu (Japan) was strongly influenced by the TCW. From a diagram of (228)Ra activities against salinity, we could roughly divide surface seawater in the study area into the five water masses, which were SAW, OYW, OKW, TCW, and Subtropical Water (STW).

Perforation of the colon in neonates.

PURPOSE: Gastrointestinal perforation is a catastrophic condition in neonates, especially in premature neonates. Although perforation is commonly observed in the small intestine during the neonatal period, perforation of the colon is a rare condition. This study analyzed the clinical findings and results of perforation of the colon in neonates. METHODS: Between 1989 and 2004, 8 neonates were treated for spontaneous perforation of the colon at our institute. These patients were retrospectively reviewed. RESULTS: Gestational ages ranged from 36 to 41 weeks. Seven patients weighed above 2500 g, whereas one patient weighed 1800 g at birth. Perforations developed within 7 days after birth in 6 patients and before birth in two. Associated bowel diseases included rectosigmoid type of Hirschsprung's disease in two patients, immature ganglia in one, imperforate anus in one, colonic atresia in one, and necrotizing enterocolitis in one. An obvious cause was not identified in the remaining two. Six patients without definite anatomic obstructions, such as imperforate anus or colonic atresia, required evaluations for suspected Hirschsprung's disease. All 8 patients underwent colostomy and recovered from peritonitis. Seven survived, but one died of sudden infant death syndrome. CONCLUSIONS: In this study, perforation of the colon during the neonatal period mostly occurred in term or near-term neonates and carried a good prognosis. During management, it was important to identify Hirschsprung's and its allied disorders as a cause of perforation.

Prodrugs of 9-benzyl-8-hydroxy-2-(2-hydroxyethylthio)adenine: potent interferon inducing agents in monkeys.

In order to improve the oral bioavailability of 9-benzyl-8-hydroxy-2-(2-hydroxyethylthio)adenine (SM-295072), a potent interferon (IFN) inducing agent, we synthesized prodrugs of it by utilizing the hydroxy groups at the C(2)-side chain and/or the C(8)-position. The carbonate prodrug at the C(8)-position was more effective than that at the C(2)-side chain for oral absorption in rats. Among the compounds prepared, compound 6 demonstrated the most preferable prodrug properties, and the maximum plasma concentration of 6 was approximately 4-fold higher than that of SM-295072. Furthermore, compound 6 was dose-dependently absorbed in monkeys by oral administration, and exhibited a potent IFN-inducting activity that correlated well with its plasma drug concentration.

Synthesis and evaluation of 2-substituted 8-hydroxyadenines as potent interferon inducers with improved oral bioavailabilities.

In order to create novel compounds which possess potent interferon (IFN) inducing activities with excellent oral bioavailabilities, a series of 8-hydroxyadenines, which have various alkoxy or alkylthio moieties at the adenine C(2)-position, were synthesized and evaluated. The introduction of hydrophobic groups was not considered to be effective for potentiating the IFN-inducing activity, but several compounds having hydrophilic groups were effective. Among the compounds tested, compound 13f induced IFN from the dosage of 0.03 mg/kg, which was approximately 100-fold more potent than that of Imiquimod, and showed an excellent oral bioavailability (F=40%) which was 10-fold improved over 5, a lead compound (F=4%).

Synthesis and structure-activity relationships of 2-amino-8-hydroxyadenines as orally active interferon inducing agents.

Recently, we have reported the 8-hydroxyadenine derivatives (2-4) as a novel class of interferon (IFN) inducing agents. In the present study, a series of 8-hydroxyadenines, which possess various amino moieties at the adenine C(2)-position, were synthesized and evaluated for their ability to induce endogenous IFN in comparison to the known active agent, Imiquimod. Among the compounds prepared, compound 9o possessing a 2-methoxyethylamino group at C(2)-position of adenine was found to exhibit potent IFN inducing activity in vivo. Compound 9o induced IFN from the dosage of 0.1 mg/kg, which was 30-fold potent than that of Imiquimod, and showed a good oral bioavailability (F=81%).

Synthesis and structure-activity relationships of 2-substituted-8-hydroxyadenine derivatives as orally available interferon inducers without emetic side effects.

Recently we reported the adenine derivatives (2-4) as new interferon (IFN) inducers. In the present study, we conducted a detailed structure and activity relationship study of 4 and its related derivatives on IFN inducing activity. From this study, we found that compound 4 exhibited the most potent IFN inducing activity in vitro with a minimum effective concentration of 0.01 microM, and 4 also showed strong IFN-inducing activity at doses of more than 0.3mg/kg by oral administration in mice. This potency was 10-fold stronger than that of Imiquimod. Moreover, 4 did not cause emesis in ferrets even at doses as high as 10mg/kg, whereas, 80% of animals were emetic when orally administered with the same dose of Imiquimod. These results indicate that compound 4 is superior to Imiquimod with respect to efficacy and safety.

Discovery of 8-hydroxyadenines as a novel type of interferon inducer.

9-Benzyl-8-hydroxyadenine (6) was found to possess interferon-inducing activity in vitro as a lead compound. Although replacement of the 9-benzyl group of 6 did not improve the activity, the introduction of a substituent such as alkyl, alkylthio, alkylamino, and alkoxy groups into the 2-position of the adenine ring resulted in a remarkable increase in the activity. The 2-alkylthio (30-32), 2-butylamino (41), and 2-butoxy (47) analogues indicated the highest activities by oral administration to mice.