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Sufficient information on the mechanisms of radiocesium translation from substrate to mushroom and long-term radiocesium accumulation is still not available, though high concentrations of radiocesium were reported in the fruiting bodies of various species of mushrooms especially after the Chernobyl accident. We studied the concentration and existing state of Cs in the cultured mycelium of the edible mushroom ( Pleurotus ostreatus (Fr.) Kummer Y-1) using NMR. The133Cs NMR resulting spectra exhibited two resonance signals arising from the mycelium whereas one resonance signal from the external medium and CsCl standard solution. The chemical form of the signal in the downfield found in the only mycelium might be concerned with Cs accumulation in the mycelium. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are the standard agents for treating patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer (ER + HER2 - ABC). However, markers predicting the outcomes of CDK4/6i treatment have yet to be identified. This study was a single-center retrospective cohort study. We retrospectively evaluated 101 patients with ER + HER2 - ABC receiving CDK4/6i in combination with endocrine therapy at Fukuyama City Hospital between November 2017 and July 2021. We investigated the clinical outcomes and the safety of CDK4/6i treatment, and the absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) as predictive markers for CDK4/6i. We defined the cut-off values as 1000/μL for ALC and 3 for NLR, and divided into "low" and "high" groups, respectively. We evaluated 43 and 58 patients who received abemaciclib and palbociclib, respectively. Patients with high ALC and low NLR had significantly longer overall survival than those with low ALC and high NLR (high vs. low; ALC: HR 0.29; 95% CI 0.12-0.70; NLR: HR 2.94; 95% CI 1.21-7.13). There was no significant difference in efficacy between abemaciclib and palbociclib and both had good safety profiles. We demonstrated that ALC and NLR might predict the outcomes of CDK4/6i treatment in patients with ER + HER2 - ABC., (© 2024. The Author(s).)

Background: Telomere biology diseases (TBD) result from defective telomere maintenance, leading to bone marrow failure. The only curative treatment for aplastic anemia related to TBD is a hematopoietic cell transplant (HCT). Although reduced-intensity conditioning (RIC) regimens decrease transplant-related mortality, non-hematological phenotypes represent a major challenge and are associated with poor long-term follow-up outcomes., Objective: To describe the outcome of TBD patients transplanted for marrow failure., Study Design: This is a retrospective, single-center study describing the outcomes of 32 consecutive transplants on 29 patients between 1993 and 2019., Results: The median age at transplantation was 14 years (range, 3-30 years). Most patients received a RIC regimen (n = 28) and bone marrow (BM) from an unrelated donor (n = 16). Four patients received a haploidentical transplant. Chimerism was available for 27 patients with a median time to neutrophil recovery of 20 days (13-36 days). Primary graft failure occurred in one patient, whereas second graft failure occurred in two. Acute GVHD grade II-IV and moderate to severe chronic GVHD occurred in 22% of patients at risk. Fourteen patients were alive after HCT at the last follow-up (median, 6 years; 1.4-19 years). The 5-year overall survival was better after matched sibling donor (MSD) transplantation compared to other hematopoietic stem cell sources (88.9% vs. 47.7%; p = .05; CI = 95%). Overall, 15 patients died after HCT, most of them (n = 11) after the first year of transplant, due to non-hematological disease progression or complication of chronic GVHD., Conclusions: Hematopoietic cell transplantation is a potentially curative treatment option for TBD, nonetheless the poor outcome reflects the progression of non-hematologic disease manifestations, which should be considered when transplantation is indicated., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/aim: It has been difficult to establish prognostic markers for overall survival (OS) in patients with advanced breast cancer (ABC). Although systemic immune markers were reported as prognostic markers in several cancers, their utility in ABC remains unclear., Patients and Methods: We retrospectively analyzed 331 ABC patients, who received treatment at Fukuyama City Hospital between April 2009 and December 2020., Results: Patients with high absolute lymphocyte count (ALC), low neutrophil-to-lymphocyte ratio (NLR), and high lymphocyte-to-monocyte ratio (LMR) had significantly longer OS (p=0.025, p=0.010, and p<0.001, respectively). High ALC and high LMR were independently associated with longer OS (p=0.020 and p=0.015, respectively). High ALC was also independently associated with longer time to treatment failure (p=0.014)., Conclusion: These systemic immune markers at diagnosis can predict not only a better OS but also a better TTF after first-line treatment., Competing Interests: Shogo Nakamoto has received lecture fees from Chugai Pharmaceuticals, Eisai CO. Ltd and Taiho Pharmaceuticals. Masahiko Ikeda has received lecture fees from AstraZeneca, Chugai Pharmaceuticals, Daiichi-Sankyo, Eisai, Eli-Lilly, Kyowa Kirin, Pfizer, Nippon Kayaku, Novartis, Mundipharma, Celltrion Healthcare Japan, and Sawai Pharmaceuticals outside the submitted work. The other Authors declare that they have no conflicts of interest in relation to this study., (Copyright 2021, International Institute of Anticancer Research.)

Background/aim: We investigated the efficacy and safety of sorafenib in Japanese patients and the prognostic value of systemic immunity markers for predicting clinical outcomes after sorafenib therapy in patients with radioiodine refractory differentiated thyroid cancer (RR-DTC)., Patients and Methods: We retrospectively evaluated 26 patients with RR-DTC who underwent sorafenib therapy between July 2014 and December 2020. The systemic immunity markers were calculated from blood cell counts., Results: The median overall survival (OS) was 2,002 days, and the clinical benefit rate was 80.8%. The high lymphocyte-to-monocyte ratio (LMR) group had significantly longer OS than the low LMR group (hazard ratio=0.21; 95% confidence interval=005-0.88; log-rank p=0.019). Adverse events observed in this study were acceptable, and no new safety signals associated with sorafenib were found., Conclusion: Sorafenib therapy is efficacious and safe for Japanese patients with RR-DTC, and baseline LMR may be useful as a sorafenib therapy prognostic marker., Competing Interests: Shogo Nakamoto has received lecture fees from Chugai Pharmaceuticals, Eisai, and Taiho Pharmaceuticals. Masahiko Ikeda has received lecture fees from Beyer, AstraZeneca, Chugai Pharmaceuticals, Daiichi-Sankyo, Eisai, Eli-Lilly, Kyowa Kirin, Pfizer, Nippon Kayaku, Novartis, Mundipharma, Celltrion Healthcare Japan, and Sawai Pharmaceuticals outside the submitted work. The other Authors have no conflicts of interest to declare., (Copyright 2021, International Institute of Anticancer Research.)

In this study, we developed an analytical method for simultaneous determination of 14 quinolones and 4 tetracyclines in livestock and fishery products using LC-MS/MS. The analytes were extracted from food samples with citrate buffer (containing EDTA)-methanol-acetonitrile (3 : 1 : 1, v/v/v) in the presence of n-hexane, and the extract was purified with an Oasis PRiME HLB cartridge column. It was suggested that this analytical method can also extract analytes from solid samples containing fat by using n-hexane. In addition, using methanol-acetonitrile (3 : 7, v/v) containing 0.1 vol% formic acid as an eluent from the cartridge column, the purification effect could be improved, while minimizing the impairment of the recovery rate. As a result of the validation using six types of food samples, trueness (accuracy) was 70.6%-113.8%, the RSD of repeatability was 9.0% or less, and the RSD of within-laboratory reproducibility was 15.5% or less. Using this approach, the standard values mentioned in the Japanese guideline were successfully met.

Allogeneic hematopoietic stem cell transplantation (HCT) can cure primary immunodeficiency diseases (PID). When a HLA-matched donor is not available, a haploidentical family donor may be considered. The use of T cell-replete haploidentical HCT with post-transplantation cyclophosphamide (haplo-PTCy) in children with PID has been reported in few case series. A donor is usually readily available, and haplo-PTCy can be used in urgent cases. We studied the outcomes of 73 patients with PID who underwent haplo-PTCy, including 55 patients who did so as a first transplantation and 18 who did so as a salvage transplantation after graft failure of previous HCT. The median patient age was 1.6 years. Most of the children were male (n = 54) and had active infection at the time of transplantation (n = 50); 10 children had severe organ damage. The diagnosis was severe combined immunodeficiency (SCID) in 34 patients and non-SCID in 39 (Wiskott-Aldrich syndrome; n = 14; chronic granulomatous disease, n = 10; other PID, n = 15). The median duration of follow-up of survivors was 2 years. The cumulative incidence of neutrophil recovery was 88% in the SCID group and 84% in non-SCID group and was 81% for first transplantations and 83% after a salvage graft. At 100 days, the cumulative incidence of acute GVHD grade II-IV and III-IV was 33% and 14%, respectively. The majority of patients reached 200/μL CD4 + and 1000/μL CD3 + cell counts between 3 and 6 months. The estimated 2-year overall survival was 66%; it was 64% for SCID patients and 65% for non-SCID patients and 63% for first HCT and 77% for salvage transplantations. Twenty-five patients died, most of them due to infection early after transplantation (before 100 days). In conclusion, haplo-PTCy is a feasible procedure, can cure two-thirds of children with PID, and can be used as rescue treatment for previous graft failure. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to analyze the outcomes of children with Diamond-Blackfan anemia (DBA) treated in Brazil with hematopoietic cell transplantation (HCT)., Methods: We performed a retrospective analysis of 44 pediatrics patients transplanted between 1990 and 2018. The median age of patients was 5 years, and 57% were male. Twenty-five received their first HCT from an HLA-matched sibling donor (MSD), 12 from a HLA matched unrelated bone marrow donor (MUD 10/10, n = 12) and 7 other HLA mismatched donors (MMD)., Results: After a median follow-up of 4 years, estimate 5-year overall survival (OS) for the entire cohort was 70%, 80% for MSD group, 73% for MUD, and 29% for MMD. Thirty-eight out of the 44 evaluable patients engrafted successfully. Primary and secondary graft failure was observed in five and three patients, respectively. Rates of grade II-IV and III-IV acute graft-versus-host disease (aGVHD) were 25% and 18%, respectively. Nine patients developed chronic GVHD (cGVHD)., Conclusion: Overall survival rates observed after HLA matched donors transplant for DBA were comparable to those reported from higher-income countries and international registries., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In this study, we report on major MRD or URD BMT outcomes in pediatric patients with SAA in Brazil. This was a retrospective study, which included 106 patients ≤18 years old who received a first BMT for SAA. All patients received bone marrow as graft source from an MRD (n = 69) or a URD (n = 37). Conditioning regimen was non-myeloablative in 73.6% of cases, and GVHD prophylaxis comprised a calcineurin inhibitor plus methotrexate in 89.6% of patients. After a median follow-up of 4.5 years after BMT, 81 patients are alive, with a 4-year OS of 77% and no statistically significant difference between the MRD and URD groups (82% vs. 69%, respectively; P = .08). Grade III-IV aGVHD at 6 months and cGVHD at 2 years were observed in 8% and 14% of cases, respectively, and were not statistically different between the groups. Twenty-five (23%) patients died at a median of 2.9 months after BMT. Our study showed that 4-year OS after BMT was not statistically different between MRD and URD recipients. This study shows that the outcomes of pediatric patients transplanted for SAA with a URD in Brazil are approaching those of MRD transplants. In contrast, OS after MRD BMT was lower than we would expect based on previous reports. The wide range of preparatory regimens used by the study centers highlights the need for standardized protocols for these children. Our findings provide a benchmark for future studies focused on improving BMT outcomes in this setting in Brazil., (© 2019 Wiley Periodicals, Inc.)

Objective: To investigate optimal beam quality for chest flat panel detector (FPD) system by semi-quantitatively assessment using a realistic lung phantom., Materials and Methods: Chest FPD radiographs were obtained on a realistic lung phantom with simulated lung opacities using various X-ray tube voltage levels (90-140 kV) with/without copper filter. Entrance skin dose was set to maintain identical for all images (0.1 mGy). Three chest radiologists unaware of the exposure settings independently evaluated the image quality of each simulated opacity and normal structure using a 5-point scale (+ 2: clearly superior to the standard; + 1: slightly superior to the standard; 0: equal to the standard; - 1: slightly inferior to the standard; - 2: clearly inferior to the standard). The traditional FPD image obtained at a tube voltage of 120 kV was used as the standard. The scores of image quality were statistically compared using the Wilcoxon rank test with Bonferroni correction., Results: FPD images using 90-kV shot with copper filter were superior to the traditional 120-kV shot without filter with respect to the visibility of vertebra, pulmonary vessels, and nodules overlapping diaphragm and heart (p < 0.05). There was no significant difference with respect to the visibility of all other simulated lung opacities (lung nodules except for overlying diaphragm/heart and honeycomb opacity) between each tube voltage level with/without copper filter and the traditional 120-kV shot without filter., Conclusion: Image quality of FPD images using 90 kV with copper filtration is superior to that using standard tube voltage when dose is identical., Key Points: • FPD image quality using 90 kV with filter is superior to that using traditional beam. • Ninety-kilovolt shot with copper filter may be suitable for chest FPD image. • Clinical study dealing with chest FPD beam optimization would be warranted.

Purpose: To compare T2* values of the triangular fibrocartilage (TFC) obtained by ultrashort time-to-echo (UTE) techniques at the neutral position, ulnar flexion of the wrist, and pronation of the forearm., Materials and Methods: MR imaging was performed in ten healthy volunteers with a 3-T MR system by using an eight-channel knee coil. Coronal wrist T2* maps from three-dimensional cone UTE pulse sequences were obtained at the neutral, ulnar flexion, and pronation positions (TR: 19 ms, TE: 0.032 ms/4 ms/8 ms/12 ms, FOV: 18 cm, matrix: 430 × 430, section thickness: 1.5 mm, scan time: 8 min 31 s). UTE-T2* maps were calculated on a pixel-by-pixel basis for all structures of the wrist visualized in the coronal planes. The entire region of interest (ROI) for TFC was manually delineated, and the average T2* value was calculated for each ROI by three radiologists. The Kruskal-Wallis test, Wilcoxon signed-rank test, or intraclass correlation coefficients (ICC) were used for statistics., Results: The difference in the average T2* value among the three groups according to the forearm/wrist position was significant (p < 0.001). The T2* value of the TFC at pronation (mean ± 2 SD: 7.92 ± 1.37 ms) was significantly lower than those at the neutral (10.08 ± 1.90 ms) and ulnar flexion positions (9.15 ± 1.03 ms) (p < 0.017). The ICC showed a substantial interobserver agreement in the T2* value measurements of the TFC (ICC = 0.986)., Conclusion: T2* relaxation time measurement of the TFC using UTE may be useful for assessing the loading effect by the forearm/wrist position., Key Points: • The T2* value of the TFC may reflect the biomechanics of the wrist joint. • Acute loading at pronation results in a decrease in the T2* value of the TFC. • Quantitative wrist UTE MRI was successfully performed in vivo.

The results of hematopoietic stem cell transplant (HSCT) for primary immunodeficiency diseases (PID) have been improving over time. Unfortunately, developing countries do not experience the same results. This first report of Brazilian experience of HSCT for PID describes the development and results in the field. We included data from transplants in 221 patients, performed at 11 centers which participated in the Brazilian collaborative group, from July 1990 to December 2015. The majority of transplants were concentrated in one center (n = 123). The median age at HSCT was 22 months, and the most common diseases were severe combined immunodeficiency (SCID) (n = 67) and Wiskott-Aldrich syndrome (WAS) (n = 67). Only 15 patients received unconditioned transplants. Cumulative incidence of GVHD grades II to IV was 23%, and GVHD grades III to IV was 10%. The 5-year overall survival was 71.6%. WAS patients had better survival compared to other diseases. Most deaths (n = 53) occurred in the first year after transplantation mainly due to infection (55%) and GVHD (13%). Although transplant for PID patients in Brazil has evolved since its beginning, we still face some challenges like delayed diagnosis and referral, severe infections before transplant, a limited number of transplant centers with expertise, and resources for more advanced techniques. Measures like newborn screening for SCID may hasten the diagnosis and ameliorate patients' conditions at the moment of transplant.

We describe haploidentical bone marrow transplantation with post-transplant cyclophosphamide (PT-CY) for 30 patients with Fanconi anemia (FA). Twenty-six patients were transplanted upfront, and the preparatory regimens included fludarabine 150 mg/m 2  + total body irradiation 200 to 300 cGy ± CY 10 mg/kg without (n = 12) or with rabbit antithymocyte globulin (r-ATG) 4 to 5 mg/kg (n = 14). Four patients were rescued after primary or secondary graft failure after related or unrelated donor transplantation with the above regimen with (n = 2) or without r-ATG (n = 2). PT-CY at 25 mg/kg/day (total dose, 50 mg/kg) followed by cyclosporine and mycophenolate mofetil was given to all patients. All patients engrafted in the subgroup of patients who did not receive r-ATG (n = 14), but their transplant course was complicated by high rates of acute and chronic graft-versus-host disease (GVHD), and only 8 patients are alive. In the subgroup that received r-ATG (n = 16), 14 patients had sustained engraftment, severe GVHD rates were lower, and 13 patients are alive. Hemorrhagic cystitis occurred in 50% of patients, whereas cytomegalovirus reactivation occurred in 75%. One-year overall survival for the entire cohort was 73% (95% CI, 64% to 81%), and all surviving patients achieved full donor chimerism. In conclusion, haploidentical donor transplantation with PT-CY is a suitable option for FA patients without a matched related or unrelated donor., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Feline morbillivirus (FmoPV) is an emerging virus in domestic cats and considered to be associated with tubulointerstitial nephritis. Although FmoPV was first described in China in 2012, there has been no report of the isolation of this virus in other countries. In this report, we describe the isolation and characterization of FmoPV from domestic cats in Japan. By using reverse transcription (RT)-PCR, we found that three of 13 urine samples from cats brought to veterinary hospitals were positive for FmoPV. FmoPV strains SS1 to SS3 were isolated from the RT-PCR-positive urine samples. Crandell-Rees feline kidney (CRFK) cells exposed to FmoPV showed cytopathic effects with syncytia formation, and FmoPV N protein was detected by indirect immunofluorescence assays. In addition, pleomorphic virus particles with apparent glycoprotein envelope spikes were observed by electron microscopy. By sequence analysis of FmoPV H and L genes, we found that FmoPVs showed genetic diversity; however, signatures of positive selection were not identified., (© 2014 The Authors.)

A filamentous soil bacterium, strain K202, was isolated from soil where an edible mushroom (Boletopsis leucomelas) was growing and identified as belonging to the genus Streptomyces on the basis of its morphological characteristics and the presence of LL-2, 6-diaminopimelic acid. We studied the existence states of Cs and its migration from extracellular to intracellular fluid in the mycelia of Streptomyces sp. K202. The results indicated that Cs accumulated in the cells through at least 2 steps: in the first step, Cs(+) was immediately and non-specifically adsorbed on the negatively charged cell surface, and in the second step, this adsorbed Cs(+) was taken up into the cytoplasm, and a part of the Cs entering the cytoplasm was taken up by an energy-dependent transport system(s). Further, we confirmed that a part of the Cs(+) was taken up into the mycelia competitively with K(+), because K(+) uptake into the intact mycelia of the strain was significantly inhibited by the presence of Cs(+) in the culture media. This suggested that part of the Cs is transported by the potassium transport system. Moreover, (133)Cs-NMR spectra and SEM-EDX spectra of the mycelia that accumulated Cs showed the presence of at least 2 intracellular Cs states: Cs(+) trapped by intercellular materials such as polyphosphate and Cs(+) present in a cytoplasmic pool., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The characteristics of Cs accumulation and localization in edible mushrooms were examined using the mycelia of Pleurotus ostreatus-Y1. Scanning electron microscope images revealed the existence of white spots, and energy dispersive X-ray microanalyzer analysis indicated the presence of larger amounts of Cs and P in these spots in mycelia cultured on medium containing 25 mM CsCl. The (137)Cs activities in the mycelia were approximately 4-6 times higher than those in water used for (137)Cs elution. Higher Cs concentrations in the sediment fraction including vacuolar pellets were obtained compared to the upper fractions. It was observed that yellowish spots caused by the fluorescence of 4',6-diamidino-2-phenylindole (DAPI)-stained polyphosphate were localized in the mycelia. The higher fluorescence intensity of the yellowish-grained spots was measured in comparison with other regions in the mycelium. These results suggested that Cs in the mycelia was trapped by polyphosphate in vacuoles or other organelles.

Mushrooms and soils samples collected from a sub-alpine forest of Mt. Fuji in Japan were measured for 137Cs and stable Cs. The ranges of 137Cs specific activities and stable Cs concentrations in the mushrooms were 291-7950 Bq kg(-1) dry weight and 4.69-58.1 mg kg(-1) dry weight, respectively. Both 137Cs specific activities and stable Cs concentrations in the mushrooms were higher than those in common agricultural plants. The 137Cs specific activities and stable Cs concentrations in the soils were 3.18-149 Bq kg(-1) dry weight and 0.618-2.18 mg kg(-1) dry weight, respectively. The appearance frequencies of filamentous actinomycetes and planktonic bacteria from the soils decreased according to increasing Cs contents in the medium. No relationship was observed between the appearance frequencies of those and the stable Cs concentrations in the soils. The filamentous actinomycetes from any soil sample could not grow in the presence of 25 mM Cs, although the planktonic bacteria from the soil samples could grow with up to 50 mM Cs in YM agar. In addition, the planktonic bacteria from approximately 70% of the soil samples could grow even in the presence of 100 mM Cs. Filamentous actinomycetes were more sensitive to Cs than planktonic bacteria. In in vitro experiments, Cs uptake by these strains of filamentous actinomycetes and planktonic bacteria was high in the presence of 5 mM CsCl and the strains accumulated Cs, the same as in mushrooms. Our results indicate that filamentous actinomycetes in the soils have higher sensitivity to Cs than planktonic bacteria, and several strains of filamentous actinomycetes have a high Cs accumulation in the presence of 5 mM Cs.

It is known that 17beta-estradiol (E2-beta) increases the production of nitric oxide. We have demonstrated that E2-beta prevents renal injury and suppresses renal endothelin-1 overproduction in ischemic acute renal failure in rats. In the present study, we investigated whether N(G)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, can reverse the effect of E2-beta in ischemic acute renal failure. Ischemic acute renal failure was induced by clamping the left renal artery and vein for 45 minutes followed by reperfusion, 2 weeks after contralateral nephrectomy. Pre-ischemic treatment with E2-beta (100 microg/kg, intravenously) attenuated the ischemia/ reperfusion-induced renal dysfunction and suppressed the increment of renal endothelin-1 content 24 hours after reperfusion. The effects of E2-beta on renal dysfunction and increased endothelin-1 content in acute renal failure rats were reversed by pretreatment with N(G)-nitro-L-arginine methyl ester (0.3 mg/kg, intravenously). An in vivo microdialysis study revealed that the concentration of nitric oxide metabolites in the kidney was reduced during ischemia, and quickly recovered after reperfusion in E2-beta-treated acute renal failure rats, compared with cases in untreated acute renal failure rats. This recovery of renal nitric oxide metabolite concentration with E2-beta was abolished by the pretreatment with N(G)-nitro-Larginine methyl ester. These findings suggest that nitric oxide is closely related to suppressive effect of E2-beta on renal endothelin-1 overproduction in acute renal failure rats and this suppression is probably involved in the beneficial effect of E2-beta on ischemia/reperfusion-induced renal injury.

Purpose: To report a patient with Takayasu disease with severe proliferative retinopathy progressing to bilateral blindness. A 57-year-old Japanese woman suffering from Takayasu disease for 16 years manifested severe proliferative retinopathy in both eyes, leading to blindness due to optic atrophy., Design: Interventional case report., Methods: A 57-year-old Japanese woman suffering from Takayasu disease for 16 years underwent a comprehensive opthalmologic examination. Panretinal photocoagulation and vitrectomy were performed on both eyes., Settings: Institutional practice., Results: At initial examination, the patient was found to have severe proliferative retinopathy with tractional retinal detachment in both eyes. The retinal detachments were repaired by the vitrectomy, however, the patient developed bilateral blindness due to optic atrophy., Conclusions: Patients with a long history of Takayasu disease can demonstrate severe proliferative retinopathy that may be resistant to photocoagulation and/or vitreous surgery. Ocular ischemia can lead to blindness from ischemic optic neuropathy.

In order to understand the fundamental and putative roles of PrP(c) in the central nervous system, neuronal cell lines were established. Cells were immortalized by recombinant retrovirus vector-mediated transduction of SV40 T-antigen gene. Among these, two cell lines were selected based on their RT-PCR expressions of neuron-specific neurofilament (NF-H, NF-M) and cell morphology. These cell lines showed the properties of neuronal progenitor cells in antigenicity, morphology and responses to differentiating agents. Expression of PrP(c) was detected by immunocytochemical analysis. These cell lines responded to differentiating agents such as dibutyl cyclic AMP (dcAMP) and phorbol 12-myristate 13-acetate (PMA) before developing into neuronal-like cells. Neurite extensions were observed 20 min after incubation with the differentiating agents. Treatment with nerve growth factor (NGF) and insulin induced cell differentiation and enhanced expression of PrP gene (Prnp) mRNA and protein. The latter phenomenon was not inhibited by wortmannin, which is a specific inhibitor of phosphatidylinositol 3-kinase. These results suggest that PrP(c) plays an important role in the differentiation-mediated classic signaling pathway of neuronal cell., (Copyright 2000 Academic Press.)

We investigated the time courses of the plasma ethanol, acetaldehyde, gastrin and cholecystokinin (CCK) levels after the ingestion of ethanol (1g/kg, 21.5%, whisky) in healthy male adult volunteers. The ethanol level reached a peak at 15 to 45 minutes after the ingestion and then decreased almost linearly. The acetaldehyde level of the group who became flushed after drinking (the F group) peaked earlier than that of the other group whose faces became only slightly flushed (the N group). The gastrin level increased significantly and remained elevated for about 3 hours. In three of the nine subjects, the CCK level increased 75 minutes after drinking. As a result, the absorption of the ingested ethanol is more rapid than 15 minutes, followed by a quick catabolism of the absorbed ethanol to acetaldehyde, but the catabolic action of acetaldehyde in the F group is later than that in the N group. The plasma gastrin level is certified to increase after the ingestion of ethanol and this is not mediated by acetaldehyde because the intra-venous infusion of acetaldehyde was not increased the plasma gastrin level in dogs. CCK which stimulate the pancreatic enzymes may be considered to have a possibility relating to the development of alcoholic acute pancreatitis but the ingestion of ethanol showed no increase of the plasma CCK level. But we cannot deny the possibility of the individual differences in the hormonal reaction in these experiments.

Alcohol and maternal hyperthermia have been implicated in human birth defects. Both ethanol and heat can induce neural tube defects (NTDs) and other developmental abnormalities in mice when large doses are given during pregnancy. To explore the teratogenic interaction of both agents, pregnant ICR mice were injected with a single dose of 25% ethanol and/or were heat-stressed in a water bath at 42 degrees C on the morning of Day 8 of gestation. Combined treatment with ethanol (0.01-0.02 ml/g) and heat (10 min), when they were given concurrently or 1 hr apart, resulted in a significant increase of resorptions and externally malformed fetuses. Skeletal malformations and visceral variations also increased significantly following a concurrent exposure to both agents. These results indicate that ethanol and heat can be synergistically teratogenic in mice when the doses of each agent are below the teratogenic threshold. It was also suggested that pretreatment with a small dose of ethanol may not enhance the teratogenicity of heat when the hyperthermic stress is strong enough and teratogenic by itself.

Seventeen solitary renal cysts were punctured with the ultrasound-guided procedure and 26-91% of the cyst volume was replaced with 95% ethanol used as a sclerosing agent of the cyst wall. Ethanol was injected through a 7 F pigtail ureteral catheter, allowed to remain in place for 20 minutes and removed through the catheter. Recovery rate of ethanol was 82.4%. The maximum blood level of ethanol was obtained 30 to 60 minutes after injection, while the maximum urinary excretion rate was observed after 60 to 120 minutes. The maximum blood levels of ethanol ranged from 0.015 to 0.339 mg/ml. There was a positive correlation between injected volume of ethanol and the maximum blood level (r = 0.66) or the total amount of urinary excretion during 12 hours (r = 0.72). Residual ethanol concentrations in the body were calculated from injected volume and recovery rate of ethanol. Only 2.3% of the residual ethanol in the body was excreted in the urine during the first 12 hours after injection. However, urine/blood ratio of ethanol 1 hour after injection was tremendously high with a wide variation between 1.6 and 230.5. Therefore, a large part of the ethanol absorbed from the cyst wall seems to be excreted directly from the kidney, not entering general circulation. From the estimation of the blood and urine levels of ethanol, it is concluded that 95% ethanol can be applied to the renal cyst wall as a sclerosing agent through the percutaneous ultrasound-guided procedure in the case of good recovery of ethanol.

Blood cyanide concentration was determined in rabbits intoxicated orally or by inhalation. Experiments were carried out under urethane anaesthesia. In the inhalation experiments, rabbits inhaled a combustion product containing HCN via the tracheal cannula and in the oral studies animals were administered NaCN solution into the stomach. In addition to the carotid artery and jugular vein blood samples, postmortem samples were obtained from both sides of the heart and the descending vena cava. The arterial cyanide concentration in the inhalation group showed a close relationship with ventilation. After an initial rise, blood levels decreased a little, in some cases with transient apnea. At the last stage it again increased with gasping, reaching its maximal value. After ultimate apnea, the blood cyanide concentration declined. The blood cyanide values were higher in the oral group than in the inhalation group. The difference between the two groups became larger in the inferior order, the left heart blood--the right heart blood--blood in the descending vena cava. The left heart/right heart ratio of the inhalation group was significantly higher than that of the oral group (1.28+/- 0.28 vs. 0.95+/- 0.09). The coefficient of variation (c.v.) of the inhalation group was larger than that of the other group. Within the inhalation group, the left heart blood showed the largest c.v. values and this was probably due to redistribution of the cyanide by bloodstream after attainment of the maximal concentration.

Acute toxicity at single and combined exposures of CO and HCN was studied on rats in terms of concentration-time product (ppm . min) necessary to kill animals (lethal CT). The animal was exposed individually to test gas in an animal chamber made of transparent plastics, and test gas was made in gas chamber connected to the animal chamber by a wide and short piece of plastic tube. HCN was produced by addition of NaCN solution to H2SO4 and in case of CO exposure, various amounts of pure CO were introduced. During exposure, gas samples were frequently taken. After exposure, blood sample was withdrawn from the right side of the heart. CO concentrations in the gas and blood were determined gas chromatographically. HCN in the gas sample was measured spectrophotometrically, after being absorbed into NaOH solution in a glass vessel devised by our laboratory. At single exposures, mean lethal CT for CO was 78,000 +/- 22,000 and for HCN was 4,700 +/- 940. In combined exposure, various combinations of CO and HCN were used. A fractional CT, defined as a ratio of CT to lethal CT, multiplied by 100, was calculated for each gas. A linear relationship between fractional CTs of HCN and CO was considered to show a simple additive action between the two gases. The sum of both fractional CTs averaged 100 +/- 26. On the other hand, linear relation was not observed between blood levels of the two toxicants at death.