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Presents information on a study that proposed the extended step-by-step method to map amorphous semiconductors. Brief review of representative analyzing methods of space-charge-limited current; Experimental test.

The authors report a case of idiopathic portal hypertension (IPH), which showed interesting RI accumulation on Single Photon Emission CT (SPECT) images, with Tc-99m galactosyl human serum albumin (GSA) scintigraphy. Accumulation of Tc-99m GSA was decreased in the periphery of the liver where strong enhancement was revealed only in the arterial phase on dynamic CT. These findings imply that portal flow is decreased in the periphery of the liver where arterial flow is dominant. It was thought that secondary reduced activity of GSA due to a decrease in portal flow results in reduced radioactivity in the periphery of the liver in IPH. This interesting accumulation of Tc-99m GSA may be one of the sign of IPH. [ABSTRACT FROM AUTHOR]

Background: Deep learning has great potential in digital kidney pathology. However, its effectiveness depends heavily on the availability of extensively labeled datasets, which are often limited due to the specialized knowledge and time required for their creation. This limitation hinders the widespread application of deep learning for the analysis of kidney biopsy images., Methods: We applied self-distillation with no labels (DINO), a self-supervised learning method, to a dataset of 10,423 glomerular images obtained from 384 PAS-stained kidney biopsy slides. Glomerular features extracted from the DINO-pretrained backbone were visualized using principal component analysis (PCA). We then performed classification tasks by adding either k-nearest neighbor (kNN) classifiers or linear head layers to the DINO-pretrained or ImageNet-pretrained backbones. These models were trained on our labeled classification dataset. Performance was evaluated using metrics such as the area under the receiver operating characteristic curve (ROC-AUC). The classification tasks encompassed four disease categories (minimal change disease, mesangial proliferative glomerulonephritis, membranous nephropathy, and diabetic nephropathy) as well as clinical parameters such as hypertension, proteinuria, and hematuria., Results: PCA visualization revealed distinct principal components corresponding to different glomerular structures, demonstrating the capability of the DINO-pretrained backbone to capture morphological features. In disease classification, the DINO-pretrained transferred model (ROC-AUC = 0.93) outperformed the ImageNet-pretrained fine-tuned model (ROC-AUC = 0.89). When the labeled data were limited, the ImageNet-pretrained fine-tuned model's ROC-AUC dropped to 0.76 (95% confidence interval [CI], 0.72-0.80), whereas the DINO-pretrained transferred model maintained superior performance (ROC-AUC 0.88, 95% CI 0.86-0.90). The DINO-pretrained transferred model also exhibited higher AUCs for the classification of several clinical parameters. External validation using two independent datasets confirmed DINO pre-training's superiority, particularly when labeled data were limited., Conclusions: The application of DINO to unlabeled PAS-stained glomerular images facilitated the extraction of histological features that can be effectively utilized for disease classification., (Copyright © 2024 by the American Society of Nephrology.)

Osteosarcoma (OS) in humans is characterized by alterations in the TP53 gene. In mice, loss of p53 triggers OS development, for which c-Myc (Myc) oncogenicity is indispensable. However, little is known about which genes are targeted by Myc to promote tumorigenesis. Here, we examined the role of γ-glutamylcyclotransferase (Ggct) which is a component enzyme of the γ-glutamyl cycle essential for glutathione homeostasis, in human and mouse OS development. We found that GGCT is a poor prognostic factor for human OS, and that deletion of Ggct suppresses p53-deficient osteosarcomagenesis in mice. Myc upregulates Ggct directly by binding to the Ggct promoter, and deletion of a Myc binding site therein by genome editing attenuated the tumorigenic potential of p53-deficient OS cells. Taken together, these results show a rationale that GGCT is widely upregulated in cancer cells and solidify its suitability as a target for anticancer drugs., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Increased dietary phosphate consumption intensifies renal phosphate burden. Several mechanisms for phosphate-induced renal tubulointerstitial fibrosis have been reported. Considering the dual nature of phosphate as both a potential renal toxin and an essential nutrient for the body, kidneys may possess inherent protective mechanisms against phosphate overload, rather than succumbing solely to injury. However, there is limited understanding of such mechanisms. To identify these mechanisms, we conducted single-cell RNA sequencing (scRNA-seq) analysis of the kidneys of control and dietary phosphate-loaded (Phos) mice at a time point when the Phos group had not yet developed tubulointerstitial fibrosis. scRNA-seq analysis identified the highest number of differentially expressed genes in the clusters belonging to proximal tubular epithelial cells (PTECs). Based on these differentially expressed genes, in silico analyses suggested that the Phos group activated peroxisome proliferator-activated receptor-α (PPAR-α) and fatty acid β-oxidation (FAO) in the PTECs. This activation was further substantiated through various experiments, including the use of an FAO activity visualization probe. Compared with wild-type mice, Ppara knockout mice exhibited exacerbated tubulointerstitial fibrosis in response to phosphate overload. Experiments conducted with cultured PTECs demonstrated that activation of the PPAR-α/FAO pathway leads to improved cellular viability under high-phosphate conditions. The Phos group mice showed a decreased serum concentration of free fatty acids, which are endogenous PPAR-α agonists. Instead, experiments using cultured PTECs revealed that phosphate directly activates the PPAR-α/FAO pathway. These findings indicate that noncanonical metabolic reprogramming via endogenous activation of the PPAR-α/FAO pathway in PTECs is essential to counteract phosphate toxicity. NEW & NOTEWORTHY This study revealed the activation of peroxisome proliferator-activated receptor-α and fatty acid β-oxidation in proximal tubular epithelial cells as an endogenous mechanism to protect the kidney from phosphate toxicity. These findings highlight noncanonical metabolic reprogramming as a potential target for suppressing phosphate toxicity in the kidneys.

This study aimed to examine the changes that took place between 2015-2019 and 2020 and reveal how the COVID-19 pandemic affected financial contributions from donors. We used the Creditor Reporting System database of the Organization for Economic Cooperation and Development to investigate donor disbursement. Focusing on the Group of Seven (G7) countries and the Bill and Melinda Gates Foundation (BMGF), we analyzed their development assistance for health (DAH) in 2020 and the change in their disbursement between 2015 and 2020. As a result, total disbursements for all sectors increased by 14% for the G7 and the BMGF. In 2020, there was an increase in DAH for the BMGF and the G7 except for the United States. The total disbursement amount for the "COVID-19" category by G7 countries and the BMGF was approximately USD 3 billion in 2020, which was 3 times larger than for Malaria, 8.5 times larger for Tuberculosis, and 60% smaller for STDs including HIV/AIDS for the same year. In 2020 as well, the United States, the United Kingdom, Japan, Italy, and Canada saw their disbursements decline for more than half of 26 sectors. In conclusion, the impact of COVID-19 was observed in the changes in DAH disbursement for three major infectious diseases and other sectors. To consistently address the health needs of low- and middle-income countries, it is important to perform a follow-up analysis of their COVID-19 disbursements and the influence of other DAH areas., Competing Interests: The authors have no conflicts of interest to disclose., (2023, National Center for Global Health and Medicine.)

Mitochondrial fatty acid β-oxidation (FAO) plays a key role in energy homeostasis. Several FAO evaluation methods are currently available, but they are not necessarily suitable for capturing the dynamics of FAO in vivo at a cellular-level spatial resolution and seconds-level time resolution. FAOBlue is a coumarin-based probe that undergoes β-oxidation to produce a fluorescent substrate, 7-hydroxycoumarin-3-( N -(2-hydroxyethyl))-carboxamide (7-HC). After confirming that 7-HC could be specifically detected using multiphoton microscopy at excitation/emission wavelength = 820/415-485 nm, wild-type C57BL/6 mice were randomly divided into control, pemafibrate, fasting (24 or 72 h), and etomoxir groups. These mice received a single intravenous injection of FAOBlue. FAO activities in the liver of these mice were visualized using multiphoton microscopy at 4.2 s/frame. These approaches could visualize the difference in FAO activities between periportal and pericentral hepatocytes in the control, pemafibrate, and fasting groups. FAO velocity, which was expressed by the maximum slope of the fluorescence intensity curve, was accelerated in the pemafibrate and 72-h fasting groups both in the periportal and the pericentral hepatocytes in comparison with the control group. Our approach revealed differences in the FAO activation mode by the two stimuli, i.e., pemafibrate and fasting, with pemafibrate accelerating the time of first detection of FAO-derived fluorescence. No increase in the fluorescence was observed in etomoxir-pretreated mice, confirming that FAOBlue specifically detected FAO in vivo. Thus, FAOBlue is useful for visualizing in vivo liver FAO dynamics at the single-cell-level spatial resolution and seconds-level time resolution. NEW & NOTEWORTHY Fatty acid β-oxidation (FAO) plays a key role in energy homeostasis. Here, the authors established a strategy for visualizing FAO activity in vivo at the cellular-level spatial resolution and seconds-level time resolution in mice. Quantitative analysis revealed spatiotemporal heterogeneity in hepatic FAO dynamics. Our method is widely applicable because it is simple and uses a multiphoton microscope to observe the FAOBlue-injected mice.

Fibroblast growth factor 23, parathyroid hormone, and 1,25-dihydroxyvitamin D are critical in phosphate homeostasis. Despite these factors' importance, regulators of phosphaturia in the acute postprandial phase remain largely unknown. This study investigated the mechanism of acute phosphate regulation in the postprandial phase in rats. Duodenal administration of radiolabeled phosphate ( 32 P) showed that 32 P levels in the inferior vena cava (IVC) blood were lower than those in the portal vein (PV) blood. Serum phosphate concentration transiently increased 5 min after phosphate solution administration through IVC, while it was maintained after the administration through PV. Phosphate administration through both IVC and PV resulted in increased fractional excretion of phosphate (FEPi) at 10 min without elevation of the known circulating factors, but urinary phosphate excretion during the period was 8% of the dose. Experiments using 32 P or partial hepatectomy showed that the liver was one of the phosphate reservoirs. The elevation of FEPi and suppression of sodium-phosphate cotransporter 2a in the kidney at 10 min was attenuated in rats with SCH23390, hepatic denervation, or renal denervation, thus indicating that the liver communicated with the kidney via the nervous system to promote phosphaturia. These results revealed previously unknown mechanisms for serum phosphate maintenance., (© 2023. The Author(s).)

Background: Phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type-1 domain-containing 7A (THSD7A) are the two major pathogenic antigens for membranous nephropathy (MN). It has been reported that THSD7A-associated MN has a higher prevalence of comorbid malignancy than PLA2R1-associated MN. Here we present a case of MN whose etiology might change from idiopathic to malignancy-associated MN during the patient's clinical course., Case Presentation: A 68-year-old man with nephrotic syndrome was diagnosed with MN by renal biopsy. Immunohistochemistry showed that the kidney specimen was negative for THSD7A. The first course of corticosteroid therapy achieved partial remission; however, nephrotic syndrome recurred 1 year later. Two years later, his abdominal echography revealed a urinary bladder tumor, but he did not wish to undergo additional diagnostic examinations. Because his proteinuria increased consecutively, corticosteroid therapy was resumed, but it failed to achieve remission. Another kidney biopsy was performed and revealed MN with positive staining for THSD7A. PLA2R1 staining levels were negative for both first and second biopsies. Because his bladder tumor had gradually enlarged, he agreed to undergo bladder tumor resection. Pathological examination indicated that the tumor was THDS7A-positive bladder cancer. Subsequently, his proteinuria decreased and remained in remission., Conclusions: This case suggests that the etiology of MN might be altered during the therapeutic course. Intensive screening for malignancy may be preferable in patients with unexpected recurrence of proteinuria and/or change in therapy response.

Introduction: Foot process effacement and mitochondrial fission associate with kidney disease pathogenesis. Electron microscopy is the gold-standard method for their visualization, but the observable area of electron microscopy is smaller than light microscopy. It is important to develop alternative ways to quantitatively evaluate these microstructural changes because the lesion site of renal diseases can be focal., Methods: We analyzed elastica-Masson trichrome (EMT) and periodic acid-Schiff (PAS) stained kidney sections using structured illumination microscopy (SIM)., Results: EMT staining revealed three-dimensional (3D) structures of foot process, whereas ponceau xylidine acid fuchsin azophloxine solution induced fluorescence. Conversion of foot process images into their constituent frequencies by Fourier transform showed that the concentric square of (1/4) 2 -(1/16) 2 in the power spectra (PS) included information for normal periodic structures of foot processes. Foot process integrity, assessed by PS, negatively correlated with proteinuria. EMT-stained sections revealed fragmented mitochondria in mice with mitochondrial injuries and patients with tubulointerstitial nephritis; Fourier transform quantified associated mitochondrial injury. Quantified mitochondrial damage in patients with immunoglobulin A (IgA) nephropathy predicted a decline in estimated glomerular filtration rate (eGFR) after kidney biopsy but did not correlate with eGFR at biopsy. PAS-stained sections, excited by a 640 nm laser, combined with the coefficient of variation values, quantified subtle changes in the basement membranes of patients with membranous nephropathy stage I., Conclusions: Kidney microstructures are quantified from sections prepared in clinical practice using SIM., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Purpose: Left ventricular hypertrophy (LVH) is a cardiovascular complication highly prevalent in patients with chronic kidney disease (CKD). Previous studies analyzing 1α-hydroxylase or vitamin D receptor (Vdr) knockout mice revealed active vitamin D as a promising agent inhibiting LVH progression. Paricalcitol, an active vitamin D analog, failed to suppress the progression of LV mass index (LVMI) in pre-dialysis patients with CKD. As target genes of activated VDR differ depending on its agonists, we examined the effects of maxacalcitol (22-oxacalcitriol: OCT), a less calcemic active vitamin D analog, on LVH in hemodialysis patients and animal LVH models with renal insufficiency., Methods: In retrospective cohort study, patients treated with OCT who underwent hemodialysis were enrolled. Using cardiac echocardiography, LV mass was evaluated by the area-length method. In animal study, angiotensin II (Ang II)-infused Wister rats with heminephrectomy or Ang II-stimulated neonatal rat ventricular myocytes (NRVM) were treated with OCT., Results: OCT significantly inhibited the progression of LVMI in hemodialysis patients. In Ang II-infused heminephrectomized rats, OCT suppressed the progression of LVH in a blood pressure-independent manner. OCT also suppressed the activity of calcineurin in the left ventricle of model rats. Specifically, OCT reduced the protein levels of calcineurin A, but not the mRNA levels of Ppp3ca (calcineurin Aα). Luciferase assays showed that OCT increased the promoter activity of Fbxo32 (atrogin1), an E3 ubiquitin ligase targeting calcineurin A. Finally, OCT promoted ubiquitination and degradation of calcineurin A., Conclusion: Our works indicated that OCT retards progression of LVH through calcineurin-NFAT pathway, which reveal a novel aspect of OCT in attenuating pathological LVH.

Kidney development requires the coordinated growth and differentiation of multiple cells. Despite recent single cell profiles in nephrogenesis research, tools for data analysis are rapidly developing, and offer an opportunity to gain additional insight into kidney development. In this study, single-cell RNA sequencing data obtained from embryonic mouse kidney were re-analyzed. Manifold learning based on partition-based graph-abstraction coordinated cells, reflecting their expected lineage relationships. Consequently, the coordination in combination with ForceAtlas2 enabled the inference of parietal epithelial cells of Bowman's capsule and the inference of cells involved in the developmental process from the S-shaped body to each nephron segment. RNA velocity suggested developmental sequences of proximal tubules and podocytes. In combination with a Markov chain algorithm, RNA velocity suggested the self-renewal processes of nephron progenitors. NicheNet analyses suggested that not only cells belonging to ureteric bud and stroma, but also endothelial cells, macrophages, and pericytes may contribute to the differentiation of cells from nephron progenitors. Organ culture of embryonic mouse kidney demonstrated that nerve growth factor, one of the nephrogenesis-related factors inferred by NicheNet, contributed to mitochondrial biogenesis in developing distal tubules. These approaches suggested previously unrecognized aspects of the underlying mechanisms for kidney development.

The Group of 20 Summit (G20) in Osaka, which Japan chaired for the first time in June 2019 has created a tailwind for achieving universal health coverage (UHC) globally. In response to the rapid digitalization, the G20 leaders commenced negotiations for the Osaka Track framework to formulate international rules on data flow across borders and systematize the concept of 'Data Free Flow with Trust (DFFT).' The strategic harnessing of the power of data to strengthen the healthcare system can allow for rapid and affordable progress toward achieving UHC. However, world leaders have yet to discuss what data governance approaches the Osaka Track will follow, or even on what values it will seek to create and maximize. In this paper, we propose a people-centered, trust-oriented approach as the key principle of data governance toward achieving UHC, using Japan's experience as an example. We believe that this approach is compatible with other prevailing approaches (e.g. the General Data Protection Regulation (GDPR) in the European Union), and can serve as a bridge to their conceptual differences. We hope that our proposed principles will be fully discussed in post-G20 Osaka Summit meetings.

Dietary phosphate intake is closely correlated with protein intake. However, the effects of the latter on phosphate-induced organ injuries remain uncertain. Herein, we investigated the effects of low (10.8%), moderate (23.0%), and high (35.2%) dietary casein and egg albumin administration on phosphate-induced organ injuries in rats. The moderate and high casein levels suppressed renal tubulointerstitial fibrosis and maintained mitochondrial integrity in the kidney. The serum creatinine levels were suppressed only in the high casein group. Phosphate-induced muscle weakness was also ameliorated by high dietary casein. The urinary and fecal phosphate levels in the early experiment stage showed that dietary casein did not affect phosphate absorption from the intestine. High dietary egg albumin showed similar kidney protective effects, while the egg albumin effects on muscle weakness were only marginally significant. As the plasma branched-chain amino acid levels were elevated in casein- and egg albumin-fed rats, we analyzed their effects. Dietary supplementation of 10% branched-chain amino acids suppressed phosphate-induced kidney injury and muscle weakness. Although dietary protein restriction is recommended in cases of chronic kidney disease, our findings indicate that the dietary casein, egg albumin, and branched-chain amino acid effects might be reconsidered in the era of a phosphate-enriched diet.

Phosphate/calcium homeostasis is crucial for health maintenance. Lithocholic acid, a bile acid produced by intestinal bacteria, is an agonist of vitamin D receptor. However, its effects on phosphate/calcium homeostasis remain unclear. Here, we demonstrated that lithocholic acid increases intestinal phosphate/calcium absorption in an enterocyte vitamin D receptor-dependent manner. Lithocholic acid was found to increase serum phosphate/calcium levels and thus to exacerbate vascular calcification in animals with chronic kidney disease. Lithocholic acid did not affect levels of intestinal sodium-dependent phosphate transport protein 2b, Pi transporter-1, -2, or transient receptor potential vanilloid subfamily member 6. Everted gut sac analyses demonstrated that lithocholic acid increased phosphate/calcium absorption in a transcellular pathway-independent manner. Lithocholic acid suppressed intestinal mucosal claudin 3 and occludin in wild-type mice, but not in vitamin D receptor knockout mice. Everted gut sacs of claudin 3 knockout mice showed an increased permeability for phosphate, but not calcium. In patients with chronic kidney disease, serum 1,25(OH) 2 vitamin D levels are decreased, probably as an intrinsic adjustment to reduce phosphate/calcium burden. In contrast, serum and fecal lithocholic acid levels and fecal levels of bile acid 7α-dehydratase, a rate-limiting enzyme involved in lithocholic acid production, were not downregulated. The effects of lithocholic acid were eliminated by bile acid adsorptive resin in mice. Thus, lithocholic acid and claudin 3 may represent novel therapeutic targets for reducing phosphate burden., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and do not have any conflicts of interest to declare.

Background: As demonstrated by the United Nations High-Level Meeting on tuberculosis (TB) held in September 2018, the political momentum for TB has been increasing. The aim of this study was to analyze the current challenges and opportunities for global TB control and, with specific focus on policies surrounding TB control, to reveal what kinds of efforts are needed to accelerate global TB control., Methods: We organized two expert meetings with the purposes of assessing the current situation and analyzing challenges regarding TB control. By applying Shiffman and Smith's framework which contains four categories; Actor, Ideas, Political context, and Issue characteristics, we analyzed the challenges and opportunities for global TB control based on the findings from the two expert meetings., Results: In the Actor Category, we found that although there has already been active engagement by non-governmental organizations (NGOs), civil society organizations (CSOs) and private sectors, there still remained an area with room for improvement. In particular, the complexities behind varying drug regulatory and procurement systems per country hindered the active participation of the private sector in this area. As for the Ideas category, due to an increasing threat of antimicrobial resistance and growing number of global migrations, TB is now widely recognized as a health security issue rather than a purely health issue. This makes TB an easier target for political attention. As for the Political category, having the UN High-Level Meeting itself is not enough; such meetings must be followed up by actual commitments from heads of states. Lastly the issue characteristic indicates that the amount of funding for R&D for new drugs, vaccines and diagnostics for TB is not at an adequate level, and investment in childhood TB and missing cases are particularly in need., Conclusions: This study provides important insight into the current status of global efforts toward end TB epidemic. The outcomes from the UN high-level meeting on TB need to be closely monitored will be crucial for the progress towards this goal.

The diboration of the C≡N bond in organic nitriles, and the N=N bond in azobenzene and pyridazine, by the highly Lewis-acidic tetra(o-tolyl)diborane(4) are reported. In the reactions with nitriles, azobenzene, and pyridazine, the addition of diborane(4) to the C≡N and N=N bonds was observed. Conversely, the N=N bond in phthalazine was cleaved by an addition/rearomatization sequence., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The reaction of highly Lewis acidic tetra(o-tolyl)diborane(4) with CO afforded a mixture of boraindane and boroxine by the cleavage of the C≡O triple bond. 13 C labeling experiments confirmed that the carbon atom in the boraindane stems from CO. Simultaneously, formation of boroxine 3 could be considered as borylene transfer to capture the oxygen atom from CO. The reaction of diborane(4) with t Bu-NC afforded an azaallene, while the reaction with Xyl-NC furnished cyclic compounds by direct C-H borylations., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The reaction of pinB-BMes 2 (pin = pinacolato, Mes = 2,4,6-Me 3 C 6 H 2 ) with Xyl-NC (Xyl = 2,6-Me 2 C 6 H 3 ) and pyridine results in the formation of a pyridine-coordinated boraalkene that exhibits an intense color caused by an intramolecular charge-transfer interaction. In the presence of an excess of pyridine, the ortho C-H bond of pyridine was selectively functionalized to afford a quinoid compound or an isocyanide-coupled product. Based on the concentration effect, the reaction stoichiometry, and previously reported DFT calculations, a reaction mechanism that involves several rearrangement reactions was proposed. Using the present method, substituted pyridines and N-heterocycles afforded the corresponding functionalized derivatives. A subsequent hydrolysis of one of the resulting products furnished an aminomethylated pyridine derivative in two steps from parent pyridine.

The purpose of this study was to evaluate the effect of an iterative reconstruction method (IR) on shape reproducibility in three-dimensional (3D) computed tomography images. We used an IR (sinogram-affirmed iterative reconstruction: SAFIRE) implemented in a 64-channel multi slice computed tomography system (Siemens, SOMATOM Definition AS). We scanned a simulated vessel phantom with 180-HU vessel contrast at various radiation doses and reconstructed axial images of filtered back projection (FBP) and SAFIRE. Then we reconstructed multi-planar reconstruction (MPR) and volume rendering (VR) images from the axial images. Roundness was evaluated from MPR images and vessel surface roughness was evaluated from pixel value profiles of a vessel in VR images and visual evaluation by radiological technologists. In comparison on equivalent dose, the roundness and roughness were improved with increase of SAFIRE strength level. However, in comparison on equivalent noise (standard deviation: SD) of axial images, SAFIRE strength levels of 2 to 5 were significantly inferior to FBP (p<0.05). SAFIRE strength of 1 with a dose reduction of 19% maintained the shape reproducibility in all evaluations. Therefore, it would be not appropriate to use the SD of axial image as index for the dose reduction rate determination of 3D-CT images.

A 68-year-old man had been followed up since March, 1997 because of a cystic tumor of the pancreas head. The patient developed obstructive jaundice and was admitted to our hospital in June, 2007. The tumor size on CT scan had increased from 3.6 cm to 5.9 cm during the 10-year period. After endoscopic biliary drainage, pancreatoduodenectomy was performed. Pathological diagnosis of the resected specimen was serous cystadenoma. Serous cystadenoma of the pancreas is known as a benign tumor with indolent progression and is likely to be symptomatic if the tumor size exceeds 4 cm. However, biliary obstruction is a rare complication of serous cystadenoma. We report this rare case here with references to the literature.

Aldehyde oxidase (EC 1.2.3.1) in monkey (Macaca fascicularis) liver was characterized. Liver cytosol exhibited extremely high benzaldehyde and phthalazine oxidase activities based on aldehyde oxidase, compared with those of rabbits, rats, mice and guinea pigs. Monkey liver aldehyde oxidase showed broad substrate specificity distinct from that of the enzyme from other mammals. Purified aldehyde oxidase from monkey liver cytosol showed two major bands and two minor bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). These bands were also observed in Western blotting analysis using anti-rat aldehyde oxidase. The molecular mass of the enzyme was estimated to be 130-151 kDa by SDS-PAGE, and to be about 285 kDa by HPLC gel filtration. The results suggest that isoforms of aldehyde oxidase exist in monkey livers.

Aldehyde oxidase was purified from hamster liver cytosol by ammonium sulfate fractionation, chromatography on DEAE-cellulose and Phenyl-Toyopearl, and HPLC-gel filtration on TSK-gel G3000SW(XL) column. The purified enzyme was homogeneous by the criterion of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Its molecular weight was determined to be 144800 by SDS-PAGE and 288000 by HPLC gel filtration. The isoelectric point was pH 5.1. The apparent Km and Vmax for benzaldehyde and 2-hydroxypyrimidine were 19.0 and 4.4 microM, and 165 and 211 nmol/min/mg protein, respectively. The benzaldehyde oxidase activity was markedly inhibited by menadione and chlorpromazine. The substrate specificity was different from those of the enzymes from other animals.

A new method of visualizing the three-dimensional architecture of the cytokeratin filaments of the intact rat hepatocyte in situ has been achieved. Frozen sections of liver cut 10 micron thick were serially extracted to remove all elements of the cells except the intermediate filaments. Parallel sections were stained with monoclonal antibodies to the two main cytokeratins found in bile duct and liver cells. Immunofluorescent antibody and immunogold electron microscopy techniques were used to identify the proteins morphologically. Several new observations resulted from these studies. The pericanalicular sheath of intermediate filaments was visualized using steropairs as an uninterrupted branching tubular structure composed of cytokeratins located in the cell cortex of adjacent hepatocytes. Intermediate filaments in the cell cortex formed a distinct sheet of matted filaments which enveloped the entire hepatocyte. The cortical intermediate filaments were in continuity with the pericanalicular sheath and the filaments located within the cytoplasm. The intermediate filaments are attached to the centrioles and appeared to tent the nuclear lamina-pore complex at points of contact. Monoclonal antibodies to rat liver intermediate filament cytokeratins (CK49 and CK55) each stained intermediate filaments located in the cell cortex, within the cytoplasm and at the nucleus. By immunogold staining, some of the intermediate filament filaments were shown to contain both cytokeratins. Filaments which did not stain were thought to be either actin at the cell periphery or nuclear lamins around the nucleus. It is concluded that the cytokeratins form a specialized framework for the cell cortex, canaliculus, centrioles and the nucleus of hepatocytes. The filaments run continuously throughout the cytoplasm without terminating.

Little is known about the pathologic characteristics of viral hepatitis A in humans. The authors compared the histologic features in liver biopsy specimens taken within 30 days of the onset of illness from 15 patients with hepatitis A and 14 patients with acute hepatitis B. In both hepatitis A and B, liver cell damage and necrosis were diffusely located, with accentuation in the centrilobular and midzonal areas in which ballooning degeneration and variation in cytoplasmic staining quality were observed frequently. One case of epidemic hepatitis A showed prominent periportal liver cell necrosis with inconspicuous centrilobular liver cell alterations. Kupffer cell mobilization was mild in hepatitis A, but more striking in hepatitis B. The portal inflammation was more pronounced and rich in plasma cells in hepatitis A than in hepatitis B. In summary, there were no major differences in the pathologic features of acute hepatitis A and B as sampled within 30 days of the onset of illness.