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The authors have examined the characteristics of Typhoon Haiyan (Yolanda), which made landfall on the coast of the Philippines on November 2013, generating a substantial storm surge. In order to better understand the storm surge phenomenon, its nature and severity were analysed by means of a numerical simulation and a field survey. Unlike most other tropical cyclones that weaken before they hit land, Haiyan struck Leyte Island at near peak strength, with maximum sustained wind speeds of 160 knots, the strongest in the recorded history of the Western North Pacific. Haiyan approached very quickly with a forward speed of 41 km/h towards Leyte, which was also the fastest among typhoons with similar intensities. As a result of these extreme gusts and the exceptionally low central pressure of the typhoon (895 hPa), Haiyan caused the largest storm surge in the recorded history of the Philippines. Numerical simulations show that the maximum storm surges occurred in Leyte Island and Samar Island. A storm surge field survey conducted by the authors corroborated this, with maximum inundation height of 7 m recorded in Tacloban, located at the northern end of Leyte Gulf. The simulation results also corroborate the fact that water levels at some locations first lowered and then rapidly began to increase after an hour. [ABSTRACT FROM AUTHOR]

Objective We applied immunocytochemistry to fine needle aspiration ( FNA) breast lesion slides in an attempt to enhance their objectivity and specificity. Methods We analysed 56 FNA specimens from patients with histologically confirmed breast lesions, using 34βE12 and p63 antibodies. Immunostained slides were examined in terms of both solitary positive cells (within clusters and non-clusters) and positive clusters within a slide. Results Positive scores (≥2) for p63+ cells and percentages of p63+ clusters differed significantly ( P < 0.001) between malignant (3 of 34; 9%) and benign (11 of 22; 50%) cases and varied between benign and malignant groups: intraductal papilloma ( IDP) (2 of 8), other benign lesions (9 of 14), ductal carcinoma in situ ( DCIS) (1 of 11) and invasive carcinoma ( IC) (2 of 23). Similarly, 34βE12 scores were higher in benign cases ( IDP, 8 of 8; other benign, 9 of 14) than in malignant cases ( DCIS, 1 of 11; IC, 3 of 23). As well as a significant difference between benign and malignant cases (17 of 22, 77% versus 4 of 34, 12%; P < 0.001), the percentage of 34βE12+ clusters was significantly higher in IDP compared with DCIS ( P = 0.001). Conclusions The immunostaining of FNA breast specimens for p63 and 34βE12 may help in difficult diagnoses. [ABSTRACT FROM AUTHOR]

The techniques and protocols used to successfully capture, transport and breed Arctic cod Boreogadus saida, as well as to rear their larvae through to adulthood are summarized. Breeding B. saida will increase the opportunity to study this fish species, which is a critical part of the Arctic food web. [ABSTRACT FROM AUTHOR]

The first twin was diagnosed SCD by postnatal computed tomography (CT). Spondylocostal dysostosis (SCD) is a rare congenital disorder characterised by vertebral segmentation and formation defect. Despite not having a prenatal diagnosis of SCD, we remade images of 3D ultrasound from the data during pregnancy, and then we got findings like as CT. [Extracted from the article]

After birth, the large neonate was diagnosed as BWS by protruding tongue and little abdominal wall defects. Furthermore, swollen gallbladder, left hydrnephrosis, left-sided inferior vena cava, goiter and ventricular septal defect was suspected with sonography and MRI. Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome, characterised by macroglossia, abdominal wall defect and overgrowth as three main signs, and has a relative risk of fetal tumour. [Extracted from the article]

The plant circadian clock controls various physiological phenomena that are important for adaptation to natural day-night cycles. Many components of the circadian clock have been identified in Arabidopsis thaliana, the model plant for molecular genetic studies. Recent studies revealed evolutionary conservation of clock components in green plants. Homologues of clock-related genes have been isolated from Lemna gibba and Lemna aequinoctialis, and it has been demonstrated that these homologues function in the clock system in a manner similar to their functioning in Arabidopsis. While clock components are widely conserved, circadian phenomena display diversity even within the Lemna genus. In order to survey the full extent of diversity in circadian rhythms among duckweed plants, we characterised the circadian rhythms of duckweed by employing a semi-transient bioluminescent reporter system. Using a particle bombardment method, circadian bioluminescent reporters were introduced into nine strains representing five duckweed species: Spirodela polyrhiza, Landoltia punctata, Lemna gibba, L. aequinoctialis and Wolffia columbiana. We then monitored luciferase (luc+) reporter activities driven by At CCA1, Zm UBQ1 or Ca MV35S promoters under entrainment and free-running conditions. Under entrainment, At CCA1::luc+ showed similar diurnal rhythms in all strains. This suggests that the mechanism of biological timing under day-night cycles is conserved throughout the evolution of duckweeds. Under free-running conditions, we observed circadian rhythms of At CCA1::luc+, Zm UBQ1::luc+ and Ca MV35S::luc+. These circadian rhythms showed diversity in period length and sustainability, suggesting that circadian clock mechanisms are somewhat diversified among duckweeds. [ABSTRACT FROM AUTHOR]

Background and Purpose: The RhoA/Rho associated kinases (ROCK) pathway has been implicated in the pathophysiology of diabetic nephropathy (DN). Early stages of diabetes are associated with renal haemodynamic changes, contributing to later development of DN. However, the role of RhoA/ROCK, known regulators of vascular tone, in this process has not been studied.Experimental Approach: Blood pressure (BP), glomerular filtration (GFR), effective renal plasma flow and filtration fraction (FF) in response to the ROCK inhibitors Y27632 (0.1 and 0.5 mg·kg(-1) ) and fasudil (0.3 and 1.5 mg·kg(-1) ) were examined in streptozotocin-diabetic rats and non-diabetic controls.Key Results: Diabetic rats demonstrated baseline increases in GFR and FF. In contrast to similar decreases in BP in diabetic and control rats, renal vasodilator effects and a decrease in FF, following ROCK inhibition were observed only in diabetic rats. The vasodilator effects of Y27632 and a further decrease in FF, were also detected in diabetic rats pretreated with the angiotensin antagonist losartan. The effects of ROCK inhibitors in diabetic rats were modulated by prior protein kinase C (PKC)β inhibition with ruboxistaurin, which abolished their effects on FF. Consistent with the renal vasodilator effects, the ROCK inhibitors reduced phosphorylation of myosin light chain in diabetic kidneys.Conclusions and Implications: The results indicate greater dependence of renal haemodynamics on RhoA/ROCK and beneficial haemodynamic effects of ROCK inhibitors in diabetes, which were additive to the effects of losartan. In this process, the RhoA/ROCK pathway operated downstream of or interacted with, PKCβ in some segments of the renal vascular tree. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses four cases of breast schistosomiasis japonica in Japan.

The effects of cellulose and the interindividual variations on the transit time in the small intestine remain unclear, but no previous study has to date taken these factors into sufficient consideration. We assessed the oro-ileal transit time and the recovery percentage of cellulose in the terminal ileum looking at interindividual variations. Seven healthy males received 100 mL of a dietary fiber-free basal diet with 5 g cellulose and 5 g of polyethylene glycol 4000. The ileal contents were aspirated every 30 min via an experimental tube placed in the terminal ileum to assess the oro-ileal transit time and the recovery percentage of cellulose. The mean percentage (with standard deviation) of the amounts of cellulose collected in the terminal ileum was 98.4%± 16.5% (ranging from 67.4% to 114.5%) with a coefficient variation of 16.8%. The average times (in hours) taken for 20%, 40%, 60%, and 80% of cellulose to reach the terminal ileum were 5.5 ± 1.1, 6.7 ± 0.7, 8.5 ± 1.3, and 8.8 ± 1.2, respectively, with large interindividual variations. In conclusion, the averaged recovery percentage of cellulose in the terminal ileum was approximately 100%, in accordance with the present generally accepted definition of dietary fiber. However, there were large interindividual variations in the oro-ileal transit time and the percentage of cellulose recovered. [ABSTRACT FROM AUTHOR]

Background and Objective: In periodontitis, matrix metalloproteinases (MMPs) are upregulated in response to locally released inflammatory cytokines, resulting in pathologic processes. Roxithromycin is a 14-membered ring macrolide antibiotic with broad-spectrum antibacterial effects against oral pathogens and immunomodulatory effects. Recently, we reported that roxithromycin inhibits tumor necrosis factor (TNF)-α-induced vascular endothelial growth factor expression in human periodontal ligament (HPDL) cell cultures. In the present study, we examined the effect of roxithromycin on TNF-α-induced MMP-1 production by HPDL cells. Material and Methods: Cultured cells were incubated with 1% fetal bovine serum for 24 h, followed by treatment with 10 ng/ml TNF-α, 10 µm roxithromycin, and mitogen-activated protein kinase inhibitor at various concentrations. Culture supernatants and sediments were collected at different time-points and used for enzyme-linked immunosorbent assays, and northern and western blot analyses. Results: In HPDL cell cultures, roxithromycin strongly inhibited TNF-α-induced MMP-1 mRNA expression and production. The inhibition of MMP-1 gene expression by roxithromycin was dependent on de novo protein synthesis and was regulated at the transcriptional level. Roxithromycin significantly inhibited TNF-α-induced c-Jun N-terminal kinase activation (JNP) and marginally inhibited extracellular signal-regulated kinase (ERK) 1/2 activation, but not p38 mitogen-activated protein kinase activation. Furthermore, roxithromycin reduced the induction of Ets-1, one of the critical factors in MMP-1 transcription. Conclusion: Roxithromycin inhibits TNF-α-mediated MMP-1 induction through the downregulation of ERK1/2 and JNK activation and the subsequent reduction of Ets-1, suggesting that roxithromycin may have therapeutic use in periodontitis and other chronic inflammatory conditions involving MMP-1 induction. [ABSTRACT FROM AUTHOR]

The article discusses stromal tumors of the kidney. Mixed epithelial and stromal tumor of the kidney (MESTIK), a rare benign neoplasm of unknown aetiology, is a recently established entity unifying several neoplasms such as adult mesoblastic nephroma, cystic hamartoma of the pelvis, adult type cystic nephroma, multilocular renal cysts, and solid and cystic biphasic tumour of the kidney. In cases reported as MESTK, recurrence or fatal outcome has, to date, never been reported. In a case study of a 43 year old Japanese woman, nine months after extirpation of the recurrent tumour, she developed another local recurrence, associated with severe hemorrhage which could not be sufficiently controlled even by three trials of transarterial embolization.

Background: Tertiary lymphoid structures (TLSs) are observed in cancer-invasive sites of various organs, and show evidence of tumor-specific B and/or T cells, suggesting an active humoral antitumor response. The aim of this study was to evaluate the relationship between TLSs and prognosis in patients with tongue squamous cell carcinoma (TSCC) after preoperative S-1 chemotherapy., Methods: Among 196 TSCC cases, 111 patients who received preoperative S-1 chemotherapy were compared to 85 patients who did not receive chemotherapy. We investigated the incidence of TLSs in both preoperative biopsy and resected specimens., Results: TLSs were present in 24 (12%) biopsy specimens and 31 (16%) resected specimens. TLSs were associated with clinicopathologically advanced cases and positivity for lymphatic invasion. None of the cases with pStage 0 (i.e., noninvasive cancer) showed TLSs. In preoperative S-1 chemotherapy cases, TLSs were significantly more common in those treated with S-1 for more than 21 days and in those with treatment effects 0, Ia, and Ib. TLSs may not be a favorable prognostic factor by themselves but maybe a prognostic factor when combined with preoperative S-1 treatment., Conclusion: The presence of TLSs was suggested to be a factor indicating a favorable prognosis when considering the indication for preoperative S-1 chemotherapy. The synergistic effect of S-1 by activating antitumor immunity may be associated with a better prognosis in TSCC patients with TLSs., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The prognosis of multiple myeloma (MM) has dramatically improved with the development of new drugs, and it has become important to determine the appropriate combinations of these novel agents. This study was a systematic review and network meta-analysis (NMA) of randomized trials in patients with relapsed and/or refractory (RR) MM. The PubMed, Cochrane, and Embase databases were searched for randomized trials from 1 January 2002 to 28 February 2022 of patients treated for MM. The primary end-point was progression-free survival (PFS), evaluated as a hazard ratio (HR) with a 95% confidence interval (95% CI) compared to dexamethasone (DEX). The p-score was used to rank treatments. Of a total of 1136 abstracts screened, 37 studies were selected, including 34 treatment options for RRMM. Daratumumab, lenalidomide and DEX was found to be the best treatment for RRMM, with the best HR compared to DEX (HR, 0.13; 95% CI, 0.08-0.20; p-score 0.9796). There was no evidence of significant heterogeneity (I 2 , 41.3%; p = 0.146). The current NMA confirmed the excellent efficacy of three-drug regimens including anti-CD38 antibodies to treat RRMM and provides background data to evaluate the efficacy of chimeric antigen receptor T-cell treatments and bispecific T-cell engager therapies., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Genomic profiling in lung cancer is essential for precision medicine. Cytological specimens provide an alternative to formalin-fixed paraffin-embedded (FFPE) samples for comprehensive genomic analysis. However, this approach remains challenging when a limited number of tumor cells are available. We applied whole genome amplification (WGA) to cytology specimens to overcome this limitation., Methods: Using a lung cancer panel targeting 58 genes, we performed next-generation sequencing of whole genome-amplified DNA extracted from cytological specimens containing 10-20 tumor cells (cyto-WGA) and DNA from corresponding FFPE tumor tissue. We compared sequencing data from cyto-WGA and FFPE samples to examine the detection accuracy of copy number variations and oncogenic and drug-matched variants., Results: The DNA quality and quantity from cyto-WGA were higher than those from FFPE samples (p < .0005 and p < .05, respectively). Sequencing metrics of cyto-WGA and FFPE tissues showed no difference in the number of mapped reads and mean coverage depth, but there were significant differences in the on-target rate (p < .05) and uniformity (p < .0005). Copy number variations in cyto-WGA samples (n = 211) were higher than in FFPE samples (n = 9) (p < .0001). Fourty nine oncogenic variants were detected in cyto-WGA and 39 in FFPE. Of these variants, 34 (63%) were present in both samples. In addition, all 16 drug-matched variants were detected in FFPE and cyto-WGA samples with 100% concordance., Conclusion: Cyto-WGA can be a feasible and alternative method to detect oncogenic and drug-matched variants., (© 2022 American Cancer Society.)

Background: Molecular testing is critical for identifying actionable variants in lung cancer for precision medicine. When tumor tissue samples are unavailable, archived cytological specimens (ACSs) can be used. The authors examined whether oncogenic variants could be accurately detected in ACSs versus paired formalin-fixed, paraffin-embedded (FFPE) tumor tissues with in vitro diagnostic tests., Methods: The authors collected 18 ACSs and 15 FFPE tissues from 15 patients with lung cancer and investigated genomic profiles with the Oncomine Dx Target Test Multi-CDx system, which is an integrated next-generation sequencing platform that comprehensively examines 4 companion diagnostic target genes (epidermal growth factor receptor [EGFR]; B-Raf proto-oncogene, serine/threonine kinase [BRAF]; anaplastic lymphoma kinase [ALK]; and ROS proto-oncogene 1, receptor tyrosine kinase [ROS1]). They compared the quantity and quality of extracted nucleic acids, the sequencing quality control (QC), and the detected variants between ACSs and FFPE tissues., Results: The total amount of DNA and RNA obtained from 1 slide was higher in FFPE tissues than ACSs. The RNA integrity number was higher in ACSs. There were no differences in sequencing QC between ACSs and FFPE tissues. A total of 21 variants, including EGFR mutations and ALK and ROS1 fusion genes, were detected in both ACSs and FFPE tissues with 100% concordance., Conclusions: ACSs can be a feasible alternative with which to identify actionable mutations and fusion genes via the Oncomine Dx Target Test Multi-CDx system., (© 2021 American Cancer Society.)

Anti-transcription intermediary factor 1γ (anti-TIF1γ) antibody (Ab) is significantly associated with internal malignancies in adult patients with dermatomyositis (DM). Although pathogenesis of cancer-associated DM is unknown, TIF1γ overexpression in tumors has been considered to be critical for the development of DM. The objective of this study was to investigate clinical characteristics of patients with anti-TIF1γ Ab-positive DM and elucidate risk factors that are potentially associated with internal malignancy. In addition, we compared the expression of TIF1γ in tumor tissues of patients with anti-TIF1γ Ab-positive DM, anti-TIF1γ Ab-negative DM and without DM in order to investigate the pathogenesis of cancer-associated DM. We analyzed 77 Japanese patients with DM, and found 19 patients to be positive for anti-TIF1γ Ab. Patients with anti-TIF1γ Ab-positive DM were older and presented heliotrope rash and flagellate erythema more frequently than patients without anti-TIF1γ Ab (P < 0.05). Interstitial lung disease (ILD) and rapidly progressive ILD, as well as palmar violaceous erythema, were less frequent in patients with anti-TIF1γ Ab than in patients without. Furthermore, internal malignancy and dysphagia were significantly more frequent in the anti-TIF1γ Ab-positive group (P < 0.01). Male sex and dysphagia were significantly associated with internal malignancy in patients with anti-TIF1γ Ab-positive DM (P < 0.01 and <0.05, respectively). Using immunohistochemistry, we examined the TIF1γ expression in tumors of 11 patients with cancer-associated DM (anti-TIF1γ Ab-positive, nine; anti-TIF1γ Ab-negative, two) and 25 patients without DM. TIF1γ was highly expressed in all tumors, and there was no significant difference in TIF1γ expression between patients with and without DM. Furthermore, TIF1γ expressions in tumors were similar irrespective of the presence of anti-TIF1γ Ab. These results suggest that anti-TIF1γ antibody may not be simply induced by overexpression of TIF1γ in tumors in patients with DM, but that other mechanisms may exist., (© 2020 Japanese Dermatological Association.)

Background: S-1 is an oral anticancer agent containing tegafur, a prodrug of 5-fluorouracil (5-FU). Preoperative S-1 chemotherapy is performed to prevent tumor proliferation before surgery in oral squamous cell carcinoma (OSCC). The aim of this study was to evaluate the effects of preoperative S-1 chemotherapy on tumor budding., Methods: We examined 248 cases of OSCC and evaluated the budding scores in biopsy and resected specimens by keratin immunohistochemistry., Results: In S-1-untreated patients, the budding scores in resected specimens tended to show a mild increase. S-1 treatment had the effect of lowering the budding score, although some cases with dramatically increased budding scores in resected specimens were found in the early phase of administration. Relapse-free survival showed a significant difference (P < .01) according to the presence or absence of S-1 treatment among patients with high budding scores., Conclusions: The present findings indicate that S-1 administration may be more effective in patients with high budding scores than in those with lower budding scores., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family, which is defined as transcriptional factors that are activated by the binding of ligands to their ligand-binding domains (LBDs). Although the three PPAR subtypes display different tissue distribution patterns and distinct pharmacological profiles, they all are essentially related to fatty-acid and glucose metabolism. Since the PPARs share similar three-dimensional structures within the LBDs, synthetic ligands which simultaneously activate two or all of the PPARs could be potent candidates in terms of drugs for the treatment of abnormal metabolic homeostasis. The structures of several PPAR LBDs were determined in complex with synthetic ligands, derivatives of 3-(4-alkoxyphenyl)propanoic acid, which exhibit unique agonistic activities. The PPARalpha and PPARgamma LBDs were complexed with the same pan agonist, TIPP-703, which activates all three PPARs and their crystal structures were determined. The two LBD-ligand complex structures revealed how the pan agonist is adapted to the similar, but significantly different, ligand-binding pockets of the PPARs. The structures of the PPARdelta LBD in complex with an alpha/delta-selective ligand, TIPP-401, and with a related delta-specific ligand, TIPP-204, were also determined. The comparison between the two PPARdelta complexes revealed how each ligand exhibits either a ;dual selective' or ;single specific' binding mode.

Background and Objective: Matrix metalloproteinase (MMP)-13 has wide substrate specificity compared with other MMPs and appears to be involved in periodontitis. Previously, we reported that roxithromycin (RXM) inhibits vascular endothelial growth factor expression induced by tumour necrosis factor-alpha in human periodontal ligament cells, but little is known about the effect of RXM on MMP-13 expression in human gingival epithelial cells. We therefore examined the effect of RXM on MMP-13 mRNA expression and production in cultured human gingival epithelial cells., Material and Methods: Human epithelial cell lines (Ca9-22, TU4, SCCTF and HSC-3) were plated in tissue culture dishes. Then, the culture supernatants and sediments were collected and the production of MMP-13 was analysed using enzyme-linked immunosorbent assay; the expression of MMP-13 mRNA and runt-related gene 2 mRNA was assessed using reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR. We also studied the effect of Runx2 short interfering RNA (siRNA) on the induction of MMP-13., Results: Roxithromycin downregulated the induction of MMP-13 in Ca9-22 cells. Roxithromycin suppressed the expression of MMP-13 mRNA not only in Ca9-22 cells, but also in other human epithelial cell lines. Roxithromycin strongly inhibited the expression of Runx2 mRNA. Furthermore, Runx2 siRNA inhibited the induction of MMP-13 in Ca9-22 cells., Conclusion: These results indicate that RXM suppresses MMP-13 via the downregulation of Runx2 in human gingival epithelial cell cultures.

Background: Serum antibody to Helicobacter pylori is tested in mass screening for gastric cancer along with the level of serum pepsinogens (PG) I and II. Recently, stool antigen tests have been developed as a new non-invasive test. We examined H. pylori infection by both serology and stool antigen test in a mass survey and compared the results to estimate applicability of stool antigen test for mass survey., Methods: A total of 994 healthy adults who received mass survey in April 2005 were tested. There were 379 men and 615 women, and the mean age was 57.7 years old. Stool samples were used to measure a H. pylori-specific antigen by enzyme immunoassay. Serum samples were tested for the prevalence of IgG antibody to H. pylori, and the level of PGs I and II was also measured to determine the presence of atrophic gastritis., Results: Infection of H. pylori was defined as positive 61.4% and 56.4% by serology and stool antigen test, respectively. The concordance of both tests was not affected by gender and age of the subjects but difference was seen in subjects with atrophic gastritis. In particular, positivity of stool antigen test (81.8%) was significantly lower than that of serology (88.7%, p < .05) in 303 subjects with severe atrophic gastritis., Conclusions: Stool antigen test, which detects present but not previous infection of H. pylori, would be applicable to diagnose H. pylori infection in mass survey. Usefulness of stool antigen tests for the screening of gastric cancer should be examined.

Objective: Although it is known that the chemokines CXCL12 and CCL20 are expressed in the intestine, their contribution to lymphocyte homing has not been investigated in detail. The authors investigated whether the CXCL12-CXCR4 and CCL20-CCR6 systems are involved in T lymphocyte-endothelial interaction in microvessels of the small and large intestines., Methods: Labeled lamina proprial lymphocytes (LPLs) were administered to mice, and their adhesion to microvessels of normal and TNF-alpha -induced inflamed intestinal mucosa was observed under an intravital microscope. Antibodies against CXCL12, CCL-20, or CCL-25 were administered prior to lymphocyte administration, and in some experiments CXCR4 or CCR6 on LPLs was desensitized with an excess amount of chemokine., Results: LPLs adhered to microvessels of the ileum and colon, and TNF-alpha induced a significant accumulation at both sites. Blocking of the CXCL12-CXCR4 system significantly inhibited the LPL adhesion in the ileum and colon under both normal and TNF-alpha -treated conditions. However, blocking of the CCL20-CCR6 system significantly attenuated LPL adhesion only under a TNF-alpha -treated condition. There was an additive inhibitory effect on LPL adherence by CXCL12 and CCL20 blocking in TNF-alpha -induced inflamed intestines. There was also an additive function of the CCL25-CCR9 system in LPL accumulation in the small intestine., Conclusion: Several chemokine systems may play significant roles cooperatively in vivo in LPL adherence to microvessels of intestinal mucosa.

Pax6 is a member of the Pax family of transcription factors and is essential for eye development. Pax6 has two DNA-binding domains: the paired domain and the homeodomain. The Pax6 paired domain is involved in Pax6 gene autoregulation by binding to its enhancer. In this study, crystallization and preliminary X-ray diffraction analysis of the mammalian Pax6 paired domain in complex with the Pax6 gene enhancer was attempted. The Pax6 paired domain complexed with an optimized 25 bp DNA fragment was crystallized by the hanging-drop vapour-diffusion method. The crystal diffracted synchrotron radiation to 3.0/3.7 A resolution and belongs to the monoclinic space group P2(1), with unit-cell parameters a = 62.21, b = 70.69, c = 176.03 A, beta = 90.54 degrees. Diffraction data were collected to 3.7 A resolution.

Background: Previously, we created an aldehyde dehydrogenase 2 gene transgenic (Aldh2-/-) mouse as an aldehyde dehydrogenase (ALDH) 2 inactive human model and demonstrated low alcohol preference. In addition, after a free-choice drinking test, no difference in the acetaldehyde level was observed between the Aldh2-/- and wild type (Aldh2+/+) mice. The actual amounts of free-choice drinking were so low that it is uncertain whether these levels are pharmacologically and/or behaviorally relevant in either strain. To elucidate this uncertainty, we compared the ethanol and acetaldehyde concentration in the blood, brain, and liver between the Aldh2-/- and Aldh2+/+ mice after ethanol gavages at the same dose and time., Method: We measured differences in the ethanol and acetaldehyde levels between the Aldh2-/- and Aldh2+/+ mice by headspace gas chromatography-mass spectrometry (GC-MS) after ethanol gavages at the same dose and time., Results: Significantly higher blood acetaldehyde concentrations were found in the Aldh2-/- mice than in the Aldh2+/+ mice 1 hr after the administration of ethanol gavages at doses of 0.5, 1.0, 2.0, and 5.0 g/kg. The blood acetaldehyde concentrations in the two strains were 2.4 vs. 0.5, 17.8 vs. 1.9, 108.3 vs. 4.3, and 247.2 vs. 14.0 (microM), respectively. In contrast, no significant difference was observed in the blood ethanol concentrations between the Aldh2+/+ and Aldh2-/- mice. The aldehyde dehydrogenase 2 enzyme metabolized 94% of the acetaldehyde produced from the ethanol as calculated from the area under the curve (AUC) of acetaldehyde when ethanol was administered at a dose of 5.0 g/kg., Conclusions: These data indicate that mouse ALDH2 is a major enzyme for acetaldehyde metabolism, and the Aldh2-/- mice have significantly high acetaldehyde levels after ethanol gavages.

Two different fragments of the ligand-binding domain of LOX-1, the major receptor for oxidized low-density lipoprotein (LDL) on endothelial cells, have been crystallized in different forms. One crystal form contains the disulfide-linked dimer, which is the form of the molecule present on the cell surface; the other contains a monomeric form of the receptor that lacks the cysteine residue necessary to form disulfide-linked homodimers. The crystal of the monomeric ligand-binding domain belongs to space group P2(1)2(1)2(1), with unit-cell parameters a = 56.79, b = 67.57, c = 79.02 A. The crystal of the dimeric form belongs to space group C2, with unit-cell parameters a = 70.86, b = 49.56, c = 76.73 A, beta = 98.59 degrees. Data for the dimeric form of the LOX-1 ligand-binding domain have been collected to 2.4 A. For the monomeric form of the ligand-binding domain, native, heavy-atom derivative and SeMet-derivative crystals have been obtained; their diffraction data have been measured to 3.0, 2.4 and 1.8 A resolution, respectively.

Monoclonal antibodies against etiological agents of Weil's disease were produced by cell fusion technology. Twenty hybridomas were produced through the fusion of P3X63Ag8 .653 cells with spleen cells from BALB/c mice immunized against Leptospira interrogans serovar icterohaemorrhagiae RGA strain and serovar copenhageni Shiromizu and M20 strains. Reactivities of the antibodies produced by the hybridomas were determined by the microscopic agglutination test. Among the five hybridoma antibodies to the RGA strain, two reacted specifically to serovar icterohaemorrhagiae, two reacted to serovar icterohaemorrhagiae at a high titer and serovar copenhageni at a low titer, and one reacted to serovars icterohaemorrhagiae, copenhageni, pyrogens, and canicola. Of the ten hybridoma antibodies to the Shiromizu strain, one reacted specifically to serovar copenhageni, seven reacted to both serovars copenhageni and icterohaemorrhagiae at almost the same titer, and two exhibited intermediate properties. Of the five hybridoma antibodies to the M20 strain, three reacted to both serovars copenhageni and icterohaemorrhagiae at almost the same titer, one reacted to serovar copenhageni at a low titer and serovar icterohaemorrhagiae at a high titer, and one reacted to serovars copenhageni, icterohaemorrhagiae, and pyrogens. The results revealed that each serovar has its own antigen(s) and their common antigens. In addition, 20 strains of leptospires were recently isolated and tested with three monoclonal antibodies characterized by different reactivities. Twenty strains were clearly identified by their antibodies, i.e., 16 strains were identified as serovar icterohaemorrhagiae and three strains were identified as serovar copenhageni. The remaining strain, which was not agglutinated by three antibodies, was identified as serovar autumnalis by an agglutination test with immune rabbit sera.