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Introduction The hematology analyzer, Celltac G (Nihon Kohden), designed to improve platelet count (Plt) accuracy, is equipped with new sheath flow control technology. Clinical evaluation of the Celltac G was assessed by comparability with XN-9000 (Sysmex Corporation) and CELL-DYN Sapphire (Abbott Diagnostics). The accuracy of all three analyzers, which use different measuring principles, was compared with the immunoplatelet reference method (FCM-Ref). Methods Repeatability and within-laboratory imprecision were assessed using 10 clinical fresh whole blood samples and three control materials with differing levels. Carryover was evaluated using 6 clinical fresh whole blood samples. For method comparison between the three analyzers, 388 samples were used. Plt accuracy among the three analyzers was evaluated using 54 blood samples, including 42 samples with a platelet count less than 50x109 /L. The International Council for Standardization in Haematology method for Plt was used as the FCM-Ref. Results The Celltac G showed sufficient performance with regard to imprecision, carryover, and comparability. The Analytical Measurement Interval (AMI) and linearity for all parameters of Plt were validated within 4.6 to 809.1 (×109 /L). All hematology analyzers showed some disagreement in Plt when compared with the immunoplatelet reference method. Conclusion The Celltac G hematology analyzer is suitable for clinical use. Platelet count evaluation of the three analyzers suggests the need to determine a reportable measurement interval (RMI) in the clinical laboratory for adequate reporting of a Plt from multiple different values.

Background The automated hematology analyzer Celltac G (Nihon Kohden) was designed to improve leukocyte differential performance. Comparison with analyzers using different leukocyte detection principles and differential leukocyte count on wedge film (Wedge‐Diff) shows its clinical utility, and comparison with immunophenotypic leukocyte differential reference method (FCM‐Ref) shows its accuracy performance. Methods For method comparison, 598 clinical samples and 46 healthy volunteer samples were selected. The two comparative hematology analyzers (CAAs) used were XN‐9000 (Sysmex) and CELL‐DYN Sapphire (Abbott). The FCM‐Ref provided by the Japanese Society for Laboratory Hematology was selected, and a flow cytometer Navios (Beckman‐Coulter) was used. In manual differential, two kinds of automated slide makers were used: SP‐10 (Sysmex) for wedge technique and SPINNER‐2000 (Lion‐Power) for spinner technique. The spinner technique avoids the issue of Wedge‐Diff smudge cells by removing the risk of breaking cells and non‐uniformity of blood cell distribution on films (Spinner‐Diff). Results The Celltac G showed sufficient comparability (r = 0.67–1.00) with the CAAs for each leukocyte differential counting value at 0.00–40.87(109/L), and sufficient comparability (r = 0.73–0.97) with FCM‐Ref for each leukocyte differential percentage at 0.4–78.5. The identification ratio of the FCM‐Ref in CD45‐positive cells was 99.7% (99.4% to 99.8%). Differences were found between FCM‐Ref/Celltac G/XN‐9000/Spinner‐Diff and Wedge‐Diff for monocytes and neutrophils. The appearance ratio of smudge cells on wedge and spinner film was 12.5% and 0.5%. Conclusion The Celltac G hematology analyzer's leukocyte differential showed adequate accuracy compared with the CAAs, FCM‐Ref, and two manual methods and was considered suitable for clinical use., Leukocyte differential in two hematology analyzers and a manual leukocyte differential method on spinner film showed consistency compared with the reference flow cytometry method provided by an immunophenotypic leukocyte differential reference method, whereas in a manual leukocyte differential method on wedge film for percentages of monocytes and neutrophils showed inconsistency. Abbreviatons: TAA, Test automated analyzer; CAA: Comparative automated analyzer; BA, basophil; EO, eosinophil; LY, lymphocyte; MO, monocyte; NE, neutrophil; 5diff, number of identified normal five‐part leukocyte WBC cell differential events; CD45+, number of CD45‐positive cell events.

Ezetimibe and pemafibrate are lipid-lowering drugs and promote reverse cholesterol transport. However, it is unknown whether cholesterol is mainly excreted by hepatobiliary excretion or by non-biliary transintestinal cholesterol efflux (TICE). We evaluated the effects of ezetimibe and pemafibrate on hepatic and intestinal cholesterol transporter regulation in Sham-operated rats, and examined the effects of these drugs on TICE in bile duct-ligated rats. Seven-week-old male Sprague-Dawley rats were treated as follows for two weeks: 1) Sham, Sham operation; 2) BDL, bile duct ligation; 3) E-Sham, Sham + ezetimibe; 4) E-BDL, BDL + ezetimibe; 5) P-Sham, Sham + pemafibrate; and 6) P-BDL, BDL + pemafibrate. Blood, liver, jejunum, and feces were collected 72 h post-surgery. Hepatic cholesterol levels were decreased in P-Sham and E-Sham, and were lower in E-BDL and P-BDL than in BDL. Fecal cholesterol levels increased in E-Sham and P-Sham compared with Sham, and were higher in E-BDL and P-BDL than in BDL. In liver, Abcg5 mRNA showed induction in E-Sham, Abcg5 and Abca1 mRNA were induced in P-Sham, Abcg5 mRNA was reduced in E-BDL, and Abca1 mRNA was increased in P-BDL. In jejunum, Abcg5 mRNA was induced in E-Sham. Abcg8 mRNA was induced in E-Sham and P-Sham. NPC1L1 mRNA showed reduced expression in P-Sham and P-BDL. SR-B1 mRNA was reduced in P-Sham, and the expression decreased in P-BDL. LDL receptor mRNA was induced in BDL and P-BDL. Ezetimibe and pemafibrate may promote TICE by increasing Abcg5/g8, while pemafibrate may inhibit intestinal cholesterol absorption by decreasing SR-B1 and NPC1L1.

Streptococcus pneumoniae is one of the most common bacteria causing community-acquired pneumonia and meningitis. The use of 7-valent pneumococcal conjugate vaccine (PCV7) has reduced the incidence of pneumococcal disease while changing pneumococcal population through herd immunity and non-vaccine pneumococci replacement. This study investigated molecular epidemiologic characteristics of pneumococcal strains in the Kinki region of Japan from 2008 to 2013. A total of 159 invasive pneumococcal isolates were characterized by serotyping, antibiotic susceptibility testing, PCR analysis of penicillin-binding protein genes, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). In adult populations, pediatric PCV7 introduction decreased isolates expressing PCV7 serotypes via herd immunity and increased isolates expressing non-PCV7 serotypes. The rate of penicillin resistance and isolates with alterations in all three pbp genes was higher in PCV7 type isolates than in non-PCV7 type isolates. In MLST analysis, all of serotype 19F isolates were of the same sequence type, ST236, which is the antimicrobial-resistant clone Taiwan19F-14, and the majority of serotypes 23F and 19A isolates were of ST1437 and ST3111 respectively, which are the predominant clones of antimicrobial-resistant pneumococci in Japan. In PFGE profiles, serotype 6B-ST2224, serotype 19F-ST236, serotype 19A-ST3111, and serotype 23F-ST1437 formed six separate clusters composed of genetically identical strains, and genetically identical serotype 22F-ST433 formed two different clusters between the pre- and post-PCV7 period. The results of molecular analysis suggest the spread and persistence of these identical antimicrobial resistant clones in the Kinki region and genetic changes of epidemic clone serotype 22F-ST433 before and after pediatric PCV7 introduction.

Maternal high-fat diet (HFD) consumption during pregnancy and lactation affects metabolic outcomes and lipid metabolism of offspring in later life in a gender-specific manner. However, it is not known whether maternal HFD alters bile acid metabolism in adult mice offspring. The purpose of this study was to elucidate the relationship between maternal HFDinduced metabolic diseases and bile acid metabolism in male and female adult mice offspring. Female mice were fed either standard chow (C) or HFD (H) for 10 weeks pre-pregnancy until lactation. After weaning, offspring were fed a chow diet until 11 weeks of age, then challenged with either C or H diet for 4 weeks, and divided into eight groups in accordance with mother's and offspring's diets: male(M) CC, MHC, MCH, MHH, female(F) CC, FHC, FCH, and FHH. MHH showed greater weight gain compared to FHH. Liver weight was higher in MHH than in FHH. Serum total cholesterol levels were higher in MHH than in MHC, and tended to be higher in MHH than in FHH. Serum glucose levels were higher in MHH than in MHC. Hepatic triglyceride levels were higher in MHH than in MHC. Hepatic mRNA expression of bile acid uptake transporters Oatp1a1 and Oatp1b2 was increased in MHH, compared to MCH. Hepatic mRNA expression of HMGCoAR, Cyp7a1, Sult2a1, and Oatp1a4 was increased in FHH, compared to FCH. In conclusion, maternal HFD consumption may promote bile acid synthesis, sulfation and excretion in female offspring fed a HFD, which may confer resistance to HFDinduced metabolic phenotypes.

Objective The menstrual cycle-related changes in clinical laboratory values were analysed by use of data obtained in the Asian multicentre study aimed at derivation of common reference intervals for 85 major clinical laboratory tests. Methods Among 1876 healthy female volunteers, 893 had regular menstruation. They were classified into five groups according to dates between sample collection and the start of the last menstrual cycle: early follicular phase (1–6 days), late follicular phase (7–12 days), ovulatory phase (13–16 days), early luteal phase (17–22 days), and late luteal phase (23–31 days). Multiple linear regression analysis was performed to evaluate the menstrual cycle-related changes in test results. The magnitude was expressed as a standard deviation ratio of between-phase standard deviation to between-individual standard deviation based on nested ANOVA. Results Aside from obvious changes for four sex hormones (oestradiol, progesterone, follicle-stimulating hormone, and luteinizing hormone), we observed statistically significant menstrual cycle-related changes in the following tests (standard deviation ratio >0.15): Na, Cl, creatine kinase, C-reactive protein, serum amyloid A, carbohydrate antigen 125, and parathyroid hormone were higher during the early follicular phase, while insulin, total cholesterol, and white blood cell were higher during the luteal phase. Significant associations of those test items with the four sex hormones were revealed. Conclusions The menstrual cycle-related changes in laboratory test results were revealed in some commonly tested items other than sex hormones. The findings are of interest in understanding female physiology in relation to hormonal changes, but the magnitude of changes is rather small and not very relevant in interpreting test results.

The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced among children in Japan in 2010. There are no long-term multicenter surveillance studies of antimicrobial resistance in S. pneumoniae before and after the introduction of PCV7. Therefore, we examined chronological trends in antimicrobial resistance among 4534 strains of S. pneumoniae isolated from both children and adults in the Kinki region of Japan during 2001–2015. High-level penicillin and third-generation cephalosporin resistance in S. pneumoniae increased among both children and adults during the period before the introduction of PCV7 (2001–2010). Besides penicillin and cephalosporin, pneumococcal carbapenem and macrolide resistance increased among children. The rate of resistance to these antibiotics was higher among children than among adults. The introduction of PCV7 decreased the rate of non-susceptibility to β-lactam antibiotics and the rate of multidrug resistant S. pneumoniae among children, but not among adults.

Background We encountered a rare case of Waldenstrom macroglobulinemia with temporary appearance of 7S IgM half molecule and with monoclonal proteins binding to agarose gel. Methods The patient's serum and urine were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. The N-terminal amino acid sequences of the IgM with abnormal mass (68 kDa) were determined and compared with those of known immunoglobulin. Results The 68 kDa IgM consisted of a defective μ chain (36 kDa) and an intact κ chain. N-terminal amino acid sequence analysis demonstrated that the defective μ chain had the variable region of IgM. The agarose gel-binding ability of the IgM-κ M-protein was lost after reduction or alkaline treatment of serum. Conclusions The 7S half molecule IgM in the present case may miss a large part of the constant region of the µ chain.

We evaluated the diagnostic utility of peripheral blood neutrophil distribution patterns obtained using the CELL-DYN SAPPHIRE hematology analyzer in patients with myelodysplastic syndrome (MDS). Peripheral blood was obtained from 467 individuals including 32 patients with MDS, and the respective neutrophil distribution patterns were observed using two light scatters [7-degree complexity (7D) and 90-degree lobularity (90D)]. These scattering intensities are shown as median (median neutrophil distribution: MND) and coefficient of variation (neutrophil distribution width: NDW). Generally, MDS patients showed lower 7D MND, higher 7D NDW, lower 90D MND and higher 90D NDW than other comparable groups. Whereas 90D parameters were more diagnostically efficient than 7D ones in patients with MDS. The sensitivity and specificity of 90D MND for MDS patients became 78.1 and 78.9%, respectively (cut-off value = 14,514). 90D NDW was most diagnostically effective with 87.5% sensitivity and 91.0% specificity (cut-off value = 21.2%). Both 90D parameters showed no evident correlation with the degree of either leukocytopenia or peripheral blood dysgranulopoiesis. In conclusion, neutrophil distribution parameters, especially 90D NDW, appear to provide convenient and objective markers for the screening of patients with MDS in routine laboratory hematology.

Background: Despite advances in endoscopic treatment methods for upper GI hemorrhage, hemostasis is often difficult to achieve. This study evaluated the usefulness of endoscopic band ligation for upper GI hemorrhage exclusive of hemorrhage from chronic gastroduodenal ulcer and varices. Methods: This prospective study included 27 patients who underwent endoscopic band ligation and 31 patients in whom bipolar electrocoagulation was performed for upper GI hemorrhage. In both groups, the causes of hemorrhage included Dieulafoy's ulcer, Mallory-Weiss tear, gastric ulcer after polypectomy, and gastric angiodysplasia. Patients with esophageal varices and those with chronic gastroduodenal ulcer were excluded. Results: Hemostasis was achieved in all 27 patients in the endoscopic band ligation group and in 26 of 31 patients (83.9%) in the bipolar electrocoagulation group. The median procedure time required for achieving hemostasis was 17.0 minutes (interquartile range: 11.5-23.5) in the endoscopic band ligation group versus 27.0 minutes (interquartile range: 20.5-40.0) in the electrocoagulation group. No major complications occurred in either group. Conclusion: Endoscopic band ligation is efficient, simple, and safe. Therefore, this technique should be considered as a treatment option for nonvariceal, nonchronic gastroduodenal ulcer upper GI hemorrhage. (Gastrointest Endosc 2002;55:214-8.)

Human chorionic gonadotropin (hCG) is generally quantified in serum, but spot urine samples are also used to assess hCG levels in Japan. The purpose of the present study was to elucidate whether urinary hCG can be used clinically as a substitute for serum hCG. A total of 189 samples of serum and spot urine were collected from patients, including cases of normal pregnancy (NP) -13, abortion (AB) -21, extrauterine pregnancy (EP) 25, and hydatidiform mole (MOL) -7, during medical treatment and comparisons were made concerning serum and urinary hCG levels. The histogram of relative urinary/serum hCG(U-hCG.act/S-hCG) of the samples showed a wide distribution of values, but tended to converge to a narrow distribution by creatinine correction (U-hCG.cor/S-hCG). U-hCG.cor/S-hCG of the AB, EP, and MOL groups decreased 1 day to 14 days or was no earlier than 15 days postoperatively compared to preoperatively. The alteration of serum Intact/Total tended to be similar to that of U-hCG.cor/S-hCG in clinical course. The presented case indicated that U-hCG.act/S-hCG did not correspond to serum hCG levels. Because urinary hCG levels are inconsistent depending on whether spot urine is concentrated or diluted, the levels of hCG in spot urine do not always correlate with serum levels of hCG. Therefore, the data of urinary hCG should be interpreted after creatinine correction. Overall, it is recommended to determine serum hCG levels rather than creatinine corrected urinary hCG levels, considering that the relative urinary/serum hCG was not constant postoperatively.

Bilirubin is taken up from blood into hepatocytes by sinosuidal membrane transporters and then excreted into bile through the bile canalicular membrane mainly as bilirubin glucuronides. (1) Mechanism of bilirubin uptake into hepatocytes: many organic anions are incorporated into hepatocytes by organic anion transporting polypeptides (rat, oatp 1, oatp2, oatp3; human, OATP), liver-specific transporter (rlst/HLST), and/or by organic anion transporters (OAT2, OAT3). Oatp1 and HLST transport bilirubin monoglucuronide. However, a transporter of unconjugated bilirubin in the sinusoidal membrane has not as yet been identified. Unconjugated bilirubin may also go across the hepatocyte sinusoidal membrane by a diffusion process. (2) Intrahepatic transport and conjugation of bilirubin: ligandin carries bilirubin to the endoplasmic reticulum (ER) of hepatocytes. In the ER, bilirubin is conjugated by bilirubin uridine diphosphate (UDP)-glycosyltransferase (bilirubin UGT; UGT1A1) to form mono- and diglucuronides of bilirubin. (3) Transport mechanism of bilirubin glucuronides across the hepatocyte canalicular membrane: at the canalicular membrane, bilirubin glucuronides are excreted into bile by multidrug resistance-associated protein 2 (MRP2), a member of the ATP-binding cassette transporter family. (4) Regurgitation of bilirubin glucuronides into blood: MRP3, which is located in the lateral membrane, transports bilirubin glucuronides into blood under conditions of impaired biliary bilirubin excretion.

Background Bilirubin has antioxidant properties and is known to have a role in the prevention of cardiovascular disease. Bilirubin is known to be negatively associated with serum parameters related to atherosclerosis. Triglyceride-rich lipoprotein is known to play an important role in the progression of atherosclerosis. The aim of the present study was to elucidate the relationship between serum bilirubin and serum remnant lipoprotein cholesterol (RLP-c). Methods We examined 270 Japanese males (mean age 64.8 years) without liver dysfunction and anemia from the Outpatient Clinic of Kinki University Hospital. Serum bilirubin, cholesterol, LDL cholesterol, HDL cholesterol, triglyceride and RLP-c levels were measured. Results Serum RLP-c level was significantly lower in patients in the high bilirubin group than those in the low bilirubin group. Conclusions The findings of this study show that serum bilirubin within physiological levels may affect the serum RLP-c and suggest bilirubin may have a role in preventing atherosclerosis.

In systemic IgG4-related disease, an elevation of the serum IgG4 level(IgG4: 135 mg/dl or higher) and IgG4-positive plasma cell infiltration occurs. Since the total IgG and sum of subclasses, IgG1 through IgG4, were markedly different in a patient suspected of having Mikuliez's disease, we investigated the relationship between total IgG and sum of IgG subclasses. The subjects were healthy individuals, and low IgG4, high IgG4, hyper-gamma globulinemia and hypo-y globulinemia groups. Total IgG was measured using 'N-assay TIA IgG-SH' (Nittobo) and Hitachi 7700, and IgG subclasses were measured using BS-NIA reagent (Binding Site) and BN II (Siemens). Designation of total IgG and the sum of IgG subclasses was established in the healthy control subjects. However the total IgG level and sum of IgG1-4 levels were different when the balance among the IgG subclasses was lost. In case such as :1) the IgG4 level was high and 2) IgG1-type M protein was present. These results indicate that the reevaluation of measured data is necessary when the IgG4 concentration is high and the difference between total IgG concentration and the sum of IgG subclasses is large.

A 58-year-old Japanese man was admitted to our hospital with appendicitis and marked unconjugated hyperbilirubinemia (11.6 mg/dl). The jaundice worsened following appendectomy, and the direct-reacting bilirubin increased, probably due to the ceftizoxime administered postoperatively. Bilirubin diglucuronide was the main component of the serum direct-reacting bilirubin (51%) in serum measured by liquid chromatography. Because the discontinuation of ceftizoxime did not markedly improve the jaundice, epomediol, 200 mg tid, was administered orally. There was a marked decrease of serum bilirubin with an increase in the delta bilirubin/(conjugated bilirubin + delta bilirubin) ratio. After improvement of jaundice to below the pre-surgical level (4.4 mg/dl), we analyzed the duodenal bile for bilirubin fractions; those showed a marked reduction in bilirubin diglucuronide and a marked increase in bilirubin monoglucuronide, which was consistent with type II Crigler-Najjar syndrome. A marked increase of bilirubin diglucuronide in serum of this patient during cholestasis suggests that bilirubin conjugation proceeds in this syndrome when excretion of conjugated bilirubin decreases.

The members of 23 laboratories, ten clinical laboratory centers and thirteen hospital laboratories in the Kinki District participated in share their clinical laboratory data. In this joint work, we cross-checked twenty-seven serum values, and all data from the 23 laboratories well accorded; however, several values, such as urea nitrogen, calcium, and albumin needed to be standardized to share the laboratory data.

The innate immunity to viral infections induces a potent antiviral response mediated by interferons (IFN). Although IFN-gamma is detected during the acute stages of illness in the upper respiratory tract secretions and in the serum of influenza A virus-infected individuals, control of influenza A virus is not dependent upon IFN-gamma as evidenced by studies using anti-IFN-gamma Ab and IFN-gamma(-/-) mice. Thus, we hypothesized that IFN-gamma is not critical in host survival because influenza A virus has mechanisms to evade the antiviral activity of IFN-gamma. To test this, A549 cells, an epithelial cell line derived from lung adenocarcinoma, were infected with influenza virus strain A/Aichi/2/68 (H3N2) (Aichi) and/or stimulated with IFN-gamma to detect IFN-gamma-stimulated MHC class II expression. Influenza A virus infection inhibited IFN-gamma-induced up-regulation of HLA-DRalpha mRNA and the IFN-gamma induction of class II transactivator (CIITA), an obligate mediator of MHC class II expression. Nuclear translocation of Stat1alpha upon IFN-gamma stimulation was significantly inhibited in influenza A virus-infected cells and this was associated with a decrease in Tyr701 and Ser727 phosphorylation of Stat1alpha. Thus, influenza A virus subverts antiviral host defense mediated by IFN-gamma through effects on the intracellular signaling pathways.

Regulation of bilirubin glucuronide transporters during hyperbilirubinemia in hepatic and extrahepatic tissues is not completely clear. In the present study, we evaluated the regulation of the bilirubin glucuronide transporters, multidrug resistance-associated proteins (MRP)2 and 3, in rats with obstructive jaundice. Bile duct ligation (BDL) or sham operation was performed in Wistar rats. Liver and kidneys were removed 1, 3, and 5 days after BDL ( n = 4, in each group). Serum and urine were collected to measure bilirubin levels just before animal killing. MRP2 And MRP3 mRNA expressions were determined by real-time RT-PCR. Protein expression of MRP2 and MRP3 was determined by Western blotting. Renal MRP2 function was evaluated by para-aminohippurate (PAH) clearance. The effect of conjugated bilirubin, unconjugated bilirubin, human bile, and sulfate-conjugated bile acid on MRP2 gene expression was also evaluated in renal and hepatocyte cell lines. Serum bilirubin and urinary bilirubin excretion increased significantly after BDL. In the liver, the mRNA expression of MRP2 decreased 59, 86, and 82%, and its protein expression decreased 25, 74, and 93% compared with sham-operated animals after 24, 72, and 120 h of BDL, respectively. In contrast, the liver expression of MRP3 mRNA increased 138, 2,137, and 3,295%, and its protein expression increased 560, 634, and 612% compared with sham-operated animals after 24, 72, and 120 h of BDL, respectively. On the other hand, in the kidneys, the mRNA expression of MRP2 increased 162, 73, and 21%, and its protein expression increased 387, 558, and 472% compared with sham-operated animals after 24, 72, and 120 h of BDL, respectively. PAH clearance was significantly increased after BDL. The mRNA expression of MRP2 increased in renal proximal tubular epithelial cells after treatment with conjugated bilirubin, sulfate-conjugated bile acid or human bile. Upregulation of MRP2 in the kidneys and MRP3 in the liver may be a compensatory mechanism to improve bilirubin clearance during obstructive jaundice.

We report two cases of early gastric cancer with distant metastases (stage IV). At our institute 1428 cases of primary gastric cancer were resected between 1980 and 1997; 536 were diagnosed as early gastric cancer based on the resected specimens (304 cases of mucosal cancer, Tis – TNM classification – and 232 of submucosal cancer, T1). 528 of these 536 cases were classified as histological stage I, six as stage II, none as stage III and two as stage IV. The incidence of stage IV early gastric cancer was 0.14% of all gastric cancers and 0.37% of the early gastric cancers. The two patients with stage IV early gastric cancer were women. Both tumors were defined as early cancer because they were confined to the submucosa. One was a type 0 IIc + III early cancer, histologically classifiable as a small, moderately differentiated adenocarcinoma (tub2 according to the Japanese Classification of Gastric Carcinoma1,2, G2; TNM classification: ICD-0 C16), size 10 × 8 mm; the other was a surface spreading type 0 lic, classifiable as a signet-ring cell carcinoma (sig, G3), size 50 × 35 mm. Stage IV factors were N3 in the first and ovarian metastasis (Krukenberg tumor) in the second case.

Crigler-Najjar syndrome (CN) type II is caused by a reduction in hepatic bilirubin uridine 5′-diphosphate (UDP)-glucuronosyltransferase activity. Recently, there has been progress in mutation analysis of patients with CN type II. Here, we analyzed both the coding and the promoter regions of the gene in seven Japanese patients with CN type II from five unrelated families. The mutations found in this study were classified into three types. The first type was composed of double homozygous missense mutations (Gly71Arg and Tyr486Asp) in exons 1 and 5. These mutations, which were detected in five patients from three unrelated families, were the commonest. The second type, which was detected in one patient, consisted of a single homozygous missense mutation (Arg209Trp) in exon 1. The third type, which was detected in one patient and was a new type of mutation combination, was composed of a homozygous insertion mutation of the TATAA element and a heterozygous missense mutation (Pro229Gln) in exon 1. Although the first and the second type of mutations are recessive, the third type appears to be dominant with incomplete penetrance, since the allele frequency of the insertion mutation of the TATAA element is very high (40%).

Crigler-Najjar syndrome type II (CN-II) is caused by a severely reduced hepatic activity of bilirubin UDP-glucuronosyltransferase (UGT). Recently, by the analysis of the genetic background of CN-II patients, it has been clarified that the patients carry homozygous missense mutations or nonsense plus missense mutations on the gene for UGT, and CN-II was inherited as an autosomal recessive trait. We encountered a new case which had a nonsense mutation caused by a single nucleotide substitution on one allele. This indicates that CN-II is also inherited as a dominant trait as well as a recessive trait. Expression study in vitro strongly suggests that the disease in this case is caused by a dominant negative mutation by forming a heterologous subunit structure.

A 45 year old Japanese man with alcoholic hepatitis developed thrombocytopenia together with an increase in the level of platelet-associated immunoglobulin G (PAIgG). Bone marrow aspiration revealed a normal nucleated cell count and a slight increase of megakaryocytes. After abstinence from alcohol, laboratory and symptomatic improvement occurred in association with a prompt increase in the platelet count and a corresponding decrease of PAIgG. These findings suggest that PAIgG may have been involved in the development of thrombocytopenia in this patient.