Meningeal Carcinomatosis Presenting with Bilateral Loss of Vision.

Meningeal carcinomatosis (MC) has an extremely poor prognosis and can present with various neurological symptoms. A 68-year-old man presented to our hospital with a 1 month history of headache and nausea followed by sudden decrease in vision in both eyes. Whilst being examined in the ophthalmology department he lost consciousness and had a generalised tonic clonic seizure. Accordingly, he was transferred to the Emergency Department. Head magnetic resonance imaging showed hydrocephalus. Abdominal contrast-enhanced computed tomography scanning reported changes suggestive of gastric carcinoma. Cerebrospinal fluid cytological examination showed numerous atypical cells, leading to the diagnosis of MC. An upper gastrointestinal endoscopy revealed an advanced gastric tumour. Systemic chemotherapy was initiated, however, he died within 16 days of admission. At autopsy, poorly differentiated adenocarcinoma was identified in the subarachnoid space, however it had not invaded the brain parenchyma or optic chiasm. This is the first report of loss of vision being the first presenting symptom of new-onset gastric carcinoma with MC. Although rare, MC should be suspected in cases where patients present with sudden loss of vision and symptoms of meningeal irritation, where there are no ophthalmological findings to explain the vision loss.

Comparison of Long-Term Corneal Astigmatic Changes After Cataract Surgery in Eyes With Superior or Horizontal Clear Corneal Incisions.

PURPOSE: To compare long-term corneal astigmatic changes after stabilization of surgically induced astigmatism (SIA) subsequent to phacoemulsification between eyes that underwent superior clear corneal incision (CCI) or horizontal CCI. DESIGN: Retrospective, comparative case series. METHODS: We examined the anterior corneal astigmatism of eyes that underwent a 2.4-mm superior CCI (superior CCI group, n = 43) or horizontal CCI (horizontal CCI group, n = 43) preoperatively, on the postoperative day that SIA stabilized (baseline), and at ≥7 years post-baseline using an autokeratometer. Corneal astigmatic changes from baseline to ≥7 years post-baseline (mean duration 8.74 years in the superior CCI group and 9.05 years in the horizontal CCI group) were decomposed to vertical/horizontal (Rx) and oblique astigmatic change components (Ry) and were compared between the 2 groups. RESULTS: The mean corneal astigmatism components changed significantly toward against-the-rule (ATR) astigmatism in the superior CCI group and with-the-rule astigmatism in the horizontal CCI group within 6 months postoperatively. After stabilization of the SIA, both groups showed a significant increase in the mean Rx and no significant change in the mean Ry over approximately 9 years, indicating a long-term ATR shift. The mean changes in the Rx and Ry did not differ significantly between the superior and horizontal CCI groups. Double-angle plots revealed a similar degree of ATR shift between the 2 groups over the 9 years. CONCLUSIONS: After stabilization of the SIA, a similar degree of ATR change occurred subsequent to superior and horizontal CCIs over approximately 9 years, suggesting that CCI direction does not affect long-term astigmatic changes.

Posterior vitreous detachment after cataract surgery in eyes with high myopia: an optical coherence tomography study.

PURPOSE: To compare the progression of posterior vitreous detachment (PVD) after cataract surgery in eyes with high myopia with that in eyes without high myopia. STUDY DESIGN: Prospective observational study. METHODS: Eighty eyes of 80 patients with high myopia and 160 eyes of 160 patients without high myopia scheduled for phacoemulsification were recruited. PVD status was examined using swept-source optical coherence tomography at 2 days postoperatively (baseline) and at 3, 6, and 12 months postbaseline and classified into 5 stages: 0 (no PVD), 1 (paramacular PVD), 2 (perifoveal PVD), 3 (peripapillary PVD), and 4 (complete PVD). The PVD stage and incidence of progression to complete PVD of the 2 groups were compared. RESULTS: The mean PVD stage did not differ significantly between the groups at baseline or at 3 months postbaseline but was significantly more progressed in the high myopia group than in the nonhigh myopia group at 6 months and 12 months postbaseline (P ≤ 0.0201). The Kaplan-Meier survival rate for complete PVD was significantly lower in the high myopia group (P = 0.0129). After adjusting for age, sex, and baseline PVD stage, the hazard ratio for complete PVD was 1.68-fold higher in the high myopia group than in the nonhigh myopia group (P = 0.0326, 95% CI 1.04-2.70). CONCLUSION: After cataract surgery, PVD progressed significantly faster in eyes with high myopia than in eyes without high myopia, and the relative risk for complete PVD was 1.68-fold higher in eyes with high myopia, suggesting that highly myopic eyes are at considerably high risk for retinal disease postoperatively.

Progression of posterior vitreous detachment after cataract surgery.

PURPOSE: To compare the progression of posterior vitreous detachment (PVD) between eyes that underwent cataract surgery and eyes that did not undergo surgery in non-highly myopic patients. METHODS: One-hundred twenty-five eyes of 125 patients scheduled for phacoemulsification and 125 eyes of 125 age-matched patients who did not undergo surgery were enrolled. PVD status was evaluated using swept-source optical coherence tomography at 2 days (baseline), and 1, 3, 6, and 12 months postoperatively, and classified into five stages: 0 (no), 1 (paramacular), 2 (perifoveal), 3 (peripapillary), and 4 (complete). The PVD stage and incidence of progression to complete PVD were compared between groups. RESULTS: The mean PVD stage significantly progressed over the 12 months in the surgery group (P = 0.0004), but did not change significantly in the non-surgery group. The PVD stage did not differ significantly between groups at 2 days, or 1, 3, and 6 months postoperatively, but was significantly more progressed in the surgery group than in the non-surgery group at 12 months (P = 0.0390). After adjusting for age, sex, axial length, and baseline PVD stage, the relative risk for progression to complete PVD was 7.1-fold higher in the surgery group than in the non-surgery group (P < 0.0001, 95% confidence interval 2.9-17.3). CONCLUSION: PVD progressed significantly faster in eyes after cataract surgery compared with eyes that did not undergo surgery, and the relative risk of progression to complete PVD was approximately seven-fold higher within 1 year, indicating that the risk for PVD-related diseases is high after cataract surgery.

Long-term changes in the refractive effect of a toric intraocular lens on astigmatism correction.

PURPOSE: To examine the long-term changes in the astigmatism-correcting effect of a toric intraocular lens (IOL) after stabilization of surgically induced astigmatic changes due to cataract surgery. METHODS: Unilateral eyes of 120 patients that received a toric IOL for against-the-rule (ATR) or with-the-rule (WTR) astigmatism were enrolled. Manifest refractive and anterior corneal astigmatism, and ocular residual astigmatism which is mainly derived from internal optics were examined preoperatively, at approximately 2 months postoperatively (baseline) and at 5 ~ 10 years postbaseline. The astigmatism was decomposed to vertical/horizontal (Rx) and oblique components (Ry), which was compared between baseline and 5 ~ 10 years postbaseline. RESULTS: In the eyes having ATR astigmatism, the mean Rx and Ry of the manifest refractive and corneal astigmatism significantly changed toward ATR astigmatism between the baseline and 5 ~ 10 years postbaseline (p ≤ 0.0304), but those of ocular residual astigmatism did not change significantly between the 2 time points. In the eyes having WTR astigmatism, the Rx and Ry of refractive, corneal, and ocular residual astigmatism did not change significantly between the 2 time points. Double-angle plots revealed an ATR shift in refractive and corneal astigmatism and no marked change in the ocular residual astigmatism in the eyes with ATR astigmatism, and there is no change in this astigmatism in the eyes with WTR astigmatism. CONCLUSION: The long-term changes with age in the effect of a toric IOL significantly deteriorated due to an ATR shift of corneal astigmatism in the eyes having ATR astigmatism, while it was maintained in eyes having WTR astigmatism, suggesting that ATR astigmatism should be overcorrected.

Observation of Chronic Graft-Versus-Host Disease Mouse Model Cornea with In Vivo Confocal Microscopy.

Graft-versus-host disease (GVHD) is a major complication after hematopoietic stem cell transplantation (HSCT), and ocular GVHD can cause severe dry eye disease that can lead to visual impairment. Epithelial damage, vascular invasion, corneal fibrosis, and corneal perforation may occur in severe cases. It is generally accepted that inflammatory cells such as dendritic cells and T cells contribute to this pathological condition. However, it is still unknown what pathological condition occurs on the ocular surface after HSCT, and when. We therefore observed the dynamics of inflammatory cells in the cornea of chronic GVHD (cGVHD) model mice from 1 to 4 weeks after bone marrow transplantation (BMT) by in vivo confocal microscopy (IVCM) and considered the relationship with the pathophysiology of ocular GVHD (tear volume, corneal epithelial damage). In the allogeneic group, neovascularization occurred in all eyes at 1 week after BMT, although almost all vessels disappeared at 2 weeks after BMT. In addition, we revealed that infiltration of globular cells, and tortuosity and branching of nerves in the cornea occurred in both cGVHD mice and human cGVHD patients. Thus, we consider that cGVHD mouse model study by IVCM reproduces the state of ocular GVHD and may contribute to elucidating the pathological mechanism for ocular GVHD.

The Overlap Syndrome: A Case Report of Chronic Graft-Versus-Host Disease After the Development of a Pseudomembrane.

BACKGROUND: Ocular graft-versus-host disease (GVHD) is one of the most severe complications of hematopoietic stem cell transplantation. It manifests as an impairment of the ocular surface, such as severe dry eye disease, and deteriorates the recipient's visual function and quality of life. We encountered an "overlap syndrome" of ocular GVHD, which is characterized by the presence of both acute and chronic GVHD symptoms. In this report, we present the treatment progress of the overlap syndrome in a case with ocular GVHD. CASE PRESENTATION: A 57-year-old man with acute myeloblastic leukemia underwent hematopoietic stem cell transplantation. Six weeks after the treatment, the recipient complained of eye pain and discharge. He was diagnosed with the overlap syndrome due to low tear volume, severe corneal epithelitis, hyperemia, and a pseudomembrane on the conjunctiva. Immune cells infiltration, fibrinoid degeneration, fibroblastic and spindle-shaped cells, and fibrosis were observed in the pathology of the pseudomembrane. The recipient was treated with topical immunosuppression and pseudomembrane removal. One week after the initial treatment, ocular GVHD improved. Twelve weeks after the treatment, the topical steroid was discontinued due to the elevation of intraocular pressure. CONCLUSIONS: The assessment of conjunctival pseudomembrane in ocular GVHD is important to determine the stage of the case and to assess systemic GVHD. Furthermore, prompt removal of the pseudomembrane after diagnosis is an appropriate management to reduce the symptoms of ocular GVHD. The combination of topical steroids and immunosuppressive agents is suggested to be an effective treatment in management of overlap syndrome.

Short-Term Changes in Prediction Error after Cataract Surgery in Eyes Receiving 1 of 3 Types of Single-Piece Acrylic Intraocular Lenses.

PURPOSE: To compare short-term changes in refractive prediction error (PE) after phacoemulsification among eyes receiving different types of single-piece acrylic intraocular lenses (IOLs). DESIGN: Randomized clinical trial. METHODS: A total of 195 eyes of 195 patients scheduled for implantation of a single-piece acrylic IOL were randomly assigned to receive 1 of 3 IOLs: 1) an Alcon model SN60WF, 2) a Hoya model XY-1, or 3) an AMO model ZCB00V. Manifest spherical equivalent (MRSE) value, PE, and changes in PE were examined at 1 day and at 1 and 2 months postoperatively and were compared among groups. RESULTS: The mean MRSE and PE significantly changed toward myopia between 1 day and 2 months postoperatively in all groups (P < .0001). The MRSE and PE did not differ significantly among groups at 1 day and 1 month postoperatively and were significantly smaller in the SN60WF group than in the XY-1 and ZCB00V groups at 2 months (P ≤ .0006). The PE change between 1 day and 2 months postoperatively was significantly smaller in the SN60WF group than in the other groups (P = .0062). IOL type and changes in anterior chamber depth and corneal curvature independently correlated with PE changes. CONCLUSIONS: The MRSE and PE showed a significant myopic change for 2 months postoperatively in eyes implanted with 1 of 3 types of single-piece acrylic IOLs and were significantly smaller in the SN60WF than in the XY-1 and ZCB00V groups. Changes in PE during the 2 postoperative months were smaller in the SN60WF IOLs than in the other IOLs, suggesting that postoperative refractive stability differs among single-piece acrylic IOLs.

Multiple glassy dynamics in dipole functionalized triphenylene-based discotic liquid crystals revealed by broadband dielectric spectroscopy and advanced calorimetry - assessment of the molecular origin.

A selected series of dipole functionalized triphenylene-based discotic liquid crystals (DLCs) was synthesized and investigated in a systematic way to reveal the phase behavior and molecular dynamics. The later point is of particular importance to understand the charge transport in such systems which is the key property for their applications such as organic field-effect transistors, solar cells or as nanowires in molecular electronics, and also to tune the properties of DLCs. The mesomorphic properties were studied by polarizing optical microscopy, X-ray diffraction, and differential scanning calorimetry, which were compared to the corresponding unfunctionalized DLC. The molecular dynamics were investigated by a combination of state-of-the-art broadband dielectric spectroscopy (BDS) and advanced calorimetry such as fast scanning calorimetry (FSC) and specific heat spectroscopy (SHS). Besides localized fluctuations, surprisingly multiple glassy dynamics were detected for all materials for the first time. Glassy dynamics were proven for both processes unambiguously due to the extraordinary broad frequency range covered. The α1-process is attributed to fluctuations of the alky chains in the intercolumnar space because a polyethylene-like glassy dynamics is observed. This corresponds to a glass transition in a confined three-dimensional space. The α2-process found at temperatures lower than α1-process, is assigned to small scale rotational and/or translational in plane fluctuations of the triphenylene core inside distorted columns. This can be considered as a glass transition in a one-dimensional fluid. Therefore, obtained results are of general importance to understand the glass transition, which is an unsolved problem of condensed matter science.

Desflurane inhibits endothelium-dependent vasodilation more than sevoflurane with inhibition of endothelial nitric oxide synthase by different mechanisms.

The effects of desflurane on endothelium-dependent vasodilation remain uncertain, whereas sevoflurane is known to inhibit it. Endothelium-dependent vasodilation is mainly mediated by endothelial nitric oxide synthase. The effects of desflurane on endothelium-dependent vasodilation were compared with those of sevoflurane, and inhibition mechanisms, including phosphorylation of endothelial nitric oxide synthase and the calcium pathway, were evaluated for the two anesthetics. We hypothesized that desflurane would inhibit endothelium-dependent vasodilation in a concentration-dependent manner more than sevoflurane, with inhibition of a calcium pathway. Isolated rat aortic rings were randomly assigned to treatment with desflurane or sevoflurane for measurements of the vasodilation ratio. To determine NO production with desflurane and sevoflurane, an in vitro assay was performed with cultured bovine aortic endothelial cells. These cells were also used for measurement of intracellular calcium or Western blotting. For endothelium-dependent vasodilation, the ratio of vasodilation was more significantly inhibited by 11.4% desflurane than by 4.8% sevoflurane. Inhibition did not between 5.7% desflurane and 2.4% sevoflurane. No inhibitory effect of desflurane or sevoflurane was observed in endothelium-denuded aorta. Desflurane inhibited nitric oxide production caused by stimulation of bradykinin significantly more than sevoflurane. Desflurane had a greater suppressive effect on the bradykinin-induced increase in intracellular calcium concentration than did sevoflurane. Sevoflurane, but not desflurane, inhibited phosphorylation of the serine 1177 residue by bradykinin stimulation. Desflurane inhibited endothelium-dependent vasodilation more than sevoflurane through inhibition of a calcium pathway. Sevoflurane inhibited endothelium-dependent vasodilation by inhibition of phosphorylation of the serine 1177 residue of endothelial nitric oxide synthase.

Nitrite administration improves sepsis-induced myocardial and mitochondrial dysfunction by modulating stress signal responses.

PURPOSE: A specific therapeutic strategy in sepsis-induced myocardial dysfunction remains to be determined. Nitrite may have cardioprotective effects against sepsis-induced myocardial dysfunction. This study investigated the cardioprotective effects of nitrite on myocardial function, mitochondrial bioenergetics, and its underlying molecular mechanisms in severe septic rats. METHODS: Sepsis was induced in male Wistar rats by cecal ligation and puncture (CLP). After CLP, we administered normal saline (NS group) or nitrite (nitrite group) subcutaneously. We administered nitrite at different doses (0.1-10 mg/kg) to ascertain the most effective dose and examined cardiac function in an isolated heart experiment 8 h after CLP. We investigated mitochondrial bioenergetics and molecular mechanisms underlying the administration of nitrite in vitro. RESULTS: In isolated heart experiments, the left ventricular developed pressure (96 ± 5 mmHg) at a moderate nitrite dose (1.0 mg/kg) was significantly higher than that in the NS group (75 ± 4 mmHg, P < 0.05). Mitochondrial oxidative phosphorylation in the nitrite group was significantly higher than that in the NS group (P < 0.01). Immunoblotting revealed that nitrite significantly increased the phosphorylation of Akt (P < 0.05) and reduced the nuclear translocation of NF-κB (P < 0.05) compared with the NS group. Nitrite was also shown to improve the rate of survival in severe septic rats (P < 0.001). CONCLUSIONS: Our results showed that a moderate nitrite dose improved septic myocardial dysfunction at organ, cellular, and molecular levels via modulation of stress signal responses, which resulted in an improvement in survival.

Rikkunshito prevents paclitaxel-induced peripheral neuropathy through the suppression of the nuclear factor kappa B (NFκB) phosphorylation in spinal cord of mice.

Peripheral neuropathy is the major side effect caused by paclitaxel, a microtubule-binding antineoplastic drug. Paclitaxel-induced peripheral neuropathy causes a long-term negative impact on the patient's quality of life. However, the mechanism underlying paclitaxel-induced peripheral neuropathy is still unknown, and there is no established treatment. Ghrelin is known to attenuate thermal hyperalgesia and mechanical allodynia in chronic constriction injury of the sciatic nerve, and inhibit the activation of nuclear factor kappa B (NFκB) in the spinal dorsal horn. Rikkunshito (RKT), a kampo medicine, increases the secretion of ghrelin in rodents and humans. Thus, RKT may attenuate paclitaxel-induced peripheral neuropathy by inhibiting phosphorylated NFκB (pNFκB) in the spinal cord. We found that paclitaxel dose-dependently induced mechanical hyperalgesia in mice. Paclitaxel increased the protein levels of spinal pNFκB, but not those of spinal NFκB. NFκB inhibitor attenuated paclitaxel-induced mechanical hyperalgesia suggesting that the activation of NFκB mediates paclitaxel-induced hyperalgesia. RKT dose-dependently attenuated paclitaxel-induced mechanical hyperalgesia. Ghrelin receptor antagonist reversed the RKT-induced attenuation of paclitaxel-induced mechanical hyperalgesia. RKT inhibited the paclitaxel-induced increase in the protein levels of spinal pNFκB. Taken together, the present study indicates that RKT exerts an antihyperalgesic effect in paclitaxel-induced neuropathic pain by suppressing the activation of spinal NFκB.

Chemical structure and biological activity of a quorum sensing pheromone from Bacillus subtilis subsp. natto.

Bacillus subtilis subsp. natto secrets a peptide pheromone, named ComXnatto pheromone, as an inducer for biofilm formation containing poly-γ-glutamic acid. Recently, the ComXnatto pheromone was identified to be a hexapeptide with an amino acid sequence of Lys-Trp-Pro-Pro-Ile-Glu, and the tryptophan residue was post-translationally modified with a farnesyl group. In order to determine the precise modification of the tryptophan residue, ComXnatto pheromone was synthesized using solid-phase peptide synthesis. Biological activity of the ComXnatto pheromone was then investigated. It was demonstrated that poly-γ-glutamic acid production were accelerated by ComXnatto pheromone at more than 1 nM in natto.

Identification of a quorum sensing pheromone posttranslationally farnesylated at the internal tryptophan residue from Bacillus subtilis subsp. natto.

Bacillus subtilis subsp. natto produces poly-γ-glutamic acid under the control of quorum sensing. We identified ComXnatto pheromone as the quorum-sensing pheromone with an amino acid sequence of Lys-Trp-Pro-Pro-Ile-Glu and the tryptophan residue posttranslationally modified by a farnesyl group. ComXnatto pheromone is unique in the sense that the 5th tryptophan residue from the C-terminal is farnesylated.

Mechanochemical approach for selective deactivation of external surface acidity of ZSM-5 zeolite catalyst.

The acid sites associated with the external surface of zeolite particles are responsible for undesirable consecutive reactions, such as isomerization, alkylation, and oligomerization, resulting in a lower selectivity to a target product; therefore, the selective modification (deactivation) of the external surface of zeolite particles has been an important issue in zeolite science. Here, a new method for surface deactivation of zeolite catalyst was tested via a mechanochemical approach using powder composer. Postsynthetic mechanochemical treatment of ZSM-5 zeolite causes a selective deactivation of catalytically active sites existing only on the external surface, as a potentially useful catalyst for highly selective production of p-xylene.

A region corresponding to second aspartate-rich motif in tryptophan isoprenylating enzyme, ComQ, serves as a substrate-binding site.

Posttranslational isoprenylation of a tryptophan residue identified from Bacillus quorum sensing pheromone, ComX pheromone, is unique and essential for the bioactivity. A modifying enzyme, ComQ, forms ComX pheromone from the ComX precursor and isoprenyl pyrophosphate and exhibits moderate similarity to isoprenyl pyrophosphate synthases. We investigated non-conserved region in ComQ, corresponding to isopentenyl pyrophosphate binding region of the synthases, using in vitro cell-free isoprenylation. These results suggested that the only conserved aspartic acid residue in the region of ComQ is critical for enzyme activity and responsible for ComX binding. Our findings should contribute to basic understanding of the mechanism of tryptophan isoprenylation.

Palladium-catalyzed double alkylation of 3-aryl-2-fluoroallyl esters with malonate nucleophiles through the carbon-fluorine bond cleavage.

The alkylation of (Z)-3-aryl-2-fluoroallyl acetate with the malonate anion by the [Pd(C3H5)(cod)]BF4/2,2'-bpy catalyst proceeds through the carbon-fluorine bond cleavage, and 2 equiv of the malonate nucleophile was introduced to the allyl substrate.

Idiopathic pneumonia syndrome with thrombotic microangiopathy-related changes after allogeneic hematopoietic stem cell transplantation.

Idiopathic pneumonia syndrome (IPS), defined as widespread alveolar injury, is a severe complication of hematopoietic stem cell transplantation (HSCT) and a clinical syndrome with variable histopathologic correlates and multiple etiologies. Transplantation-associated thrombotic microangiopathy (TMA) is another severe complication of HSCT. TMA occurs when endothelial injury causes thrombosis and fibrin deposition in the organ microcirculation. We present a case of IPS with TMA-related changes in the lungs following HSCT. A 54-year-old woman underwent an allogeneic HSCT for refractory multiple myeloma. During transplantation, cyclosporine was administered for prophylaxis against graft-versus-host disease, but she developed respiratory failure after she was weaned off the drug. A computed tomography scan revealed ground-glass attenuation and reticular opacity in the bilateral whole-lung fields. Bronchoscopy indicated no evidence of infection, and IPS was diagnosed. High-dose steroids and etanercept were ineffective, and she died 1 month after the onset of IPS. Autopsy revealed diffuse alveolar damage, and stenosis or obstruction due to intimal thickening and thrombi resulting from endothelial injury in the arterioles of both lungs. We retrospectively diagnosed TMA based on the histological and clinical findings. To our knowledge, this is the first report suggesting the possible role of TMA in the clinical course of IPS.

[Usefulness of subarachnoid phenol-glycerin block therapy for enabling cancer patients with refractory anal pain to proceed to home-based care].

In recent years, the number of cancer patients and their families desiring palliative home-based care in Japan has increased. Subarachnoid phenol-glycerin block therapy is offered to relieve refractory anal pain in cancer patients, and to reduce the side effects of systemic administration of opioids, such as drowsiness. The effects of phenol-glycerin, which is a medicine used for neurodegenerative diseases, lasted for 1 week to 3 months. Eight patients with this manipulation showed a significant improvement in their pain level, calculated by the numerical rating scale(NRS). Five of these patients could proceed to homebased care. It is important to establish common guidelines for the management of phenol-glycerin. The participation of pharmacists in the palliative care team will contribute to further growth of home-based care.

Evaluation of a hybrid artificial liver module based on a spheroid culture system of embryonic stem cell-derived hepatic cells.

Hybrid artificial liver (HAL) is an extracorporeal circulation system comprised of a bioreactor containing immobilized functional liver cells. It is expected to not only serve as a temporary liver function support system, but also to accelerate liver regeneration in recovery from hepatic failure. One of the most difficult problems in developing a hybrid artificial liver is obtaining an adequate cell source. In this study, we attempt to differentiate embryonic stem (ES) cells by hepatic lineage using a polyurethane foam (PUF)/spheroid culture in which the cultured cells spontaneously form spherical multicellular aggregates (spheroids) in the pores of the PUF. We also demonstrate the feasibility of the PUF-HAL system by comparing ES cells to primary hepatocytes in in vitro and ex vivo experiments. Mouse ES cells formed multicellular spheroids in the pores of PUF. ES cells expressed liver-specific functions (ammonia removal and albumin secretion) after treatment with the differentiation-promoting agent, sodium butyrate (SB). We designed a PUF-HAL module comprised of a cylindrical PUF block with many medium-flow capillaries for hepatic differentiation of ES cells. The PUF-HAL module cells expressed ammonia removal and albumin secretion functions after 2 weeks of SB culture. Because of high proliferative activity of ES cells and high cell density, the maximum expression level of albumin secretion function per unit volume of module was comparable to that seen in primary mouse hepatocyte culture. In the animal experiments with rats, the PUF-HAL differentiating ES cells appeared to partially contribute to recovery from liver failure. This outcome indicates that the PUF module containing differentiating ES cells may be a useful biocomponent of a hybrid artificial liver support system.