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Background: The increasing incidence and prevalence of breast cancer alongside diagnostic and treatment technology advances have produced a debate about the financial burden cancer places on the healthcare system and concerns about access., Methods: This study was conducted at 51 hospitals belonging to the Breast Cancer Study Group of the Japan Clinical Oncology Group using a web-based survey. The survey period conducted from July 2021 to June 2022. The study population included patients with metastatic breast cancer who received the related treatment as their first-line therapy. The proportion of patients who selected that regimen as their first-line treatment was tabulated. The total cost increase for each current standard therapy in comparison to conventional treatments was calculated., Results: A total of 702 patients (pts) were surveyed. Of those enrolled, 342 (48.7%) received high-cost treatment [estimated monthly drug costs exceeding ~500 000 Japanese Yen (JPY)]. Of these, 16 pts (4.7%) were receiving very high-cost treatment, amounting to more than 1 000 000 JPY per month. Fifty three (15.5%) of the patients who received high-cost treatment were 75 years of age or older. Of these, 1 pt (0.3%) were receiving very high-cost treatment. Analyses of incremental costs by current drugs showed that abemaciclib was costly with total additional cost of 6 365 670 JPY per patient. The total additional cost of the regimen per patient that included palbociclib was the second highest at 4011248 JPY, followed by atezolizumab at 3209033 JPY., Conclusions: The findings indicate that evaluating the financial implications of high-cost treatments requires considering not only drug prices but also analysis of total cost increase., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In patients with APC-associated polyposis, the prevalence of upper gastrointestinal tumors and the relationship between these and Helicobacter pylori infection have not been clarified in detail. The present study aimed to clarify the features of upper gastrointestinal lesions in patients with APC-associated polyposis., Methods: Consecutive patients with APC-associated polyposis who underwent esophagogastroduodenoscopy between 2004 and 2018 were recruited., Results: In total, 36 patients were enrolled. The types of gastrointestinal tumor observed were fundic gland polyposis in 28 patients (77.8%), gastric adenoma in 15 patients (41.7%), duodenal adenoma in 27 patients (75.0%) and periampullary adenoma in 20 patients (55.6%). The phenotype of these upper gastrointestinal tumors was not necessarily the same in patients belonging to the same family. Germline variants in the APC gene were distributed across various sites, regardless of the presence or absence of upper gastrointestinal lesions, and none of the tumors correlated with the genotype or phenotype of upper gastrointestinal tumors. Fundic gland polyposis was observed in 28 of 31 patients without a H. pylori infection and in none of the patients with a H. pylori infection (P = 0.00015). After eradication therapy for H. pylori, fundic gland polyposis developed in one, previously infected patient., Conclusion: The upper gastrointestinal tumor phenotype was not associated with the genotype in patients with APC-associated polyposis. Ascertaining the H. pylori infection status is helpful for endoscopic surveillance of upper gastrointestinal tumors in patients with APC-associated polyposis., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Corals of the family Acroporidae are key structural components of reefs that support the most diverse marine ecosystems. Due to increasing anthropogenic stresses, coral reefs are in decline. Along the coast of Okinawa, Japan, three different color morphs of Acropora tenuis have been recognized for decades. These include brown (N morph), yellow green (G), and purple (P) forms. The tips of axial polyps of each morph exhibit specific fluorescence spectra. This attribute is inherited asexually, and color morphs do not change seasonally. In Okinawa Prefecture, during the summer of 2017, N and P morphs experienced bleaching, in which many N morphs died. Dinoflagellates (Symbiodiniaceae) are essential partners of scleractinian corals, and photosynthetic activity of symbionts was reduced in N and P morphs. In contrast, G morphs successfully withstood the stress. Examination of the clade and type of Symbiodiniaceae indicated that the three color-morphs host similar sets of Clade-C symbionts, suggesting that beaching of N and P morphs is unlikely attributable to differences in the clade of Symbiodiniaceae the color morphs hosted. Fluorescent proteins play pivotal roles in physiological regulation of corals. Since the A. tenuis genome has been decoded, we identified five genes for green fluorescent proteins (GFPs), two for cyan fluorescent proteins (CFPs), three for red fluorescent proteins (RFPs), and seven genes for chromoprotein (ChrP). A summer survey of gene expression profiles under outdoor aquarium conditions demonstrated that (a) expression of CFP and REP was quite low during the summer in all three morphs, (b) P morphs expressed higher levels of ChrP than N and G morphs, (c) both N and G morphs expressed GFP more highly than P morphs, and (d) GFP expression in N morphs was reduced during summer whereas G morphs maintained high levels of GFP expression throughout the summer. Although further studies are required to understand the biological significance of these color morphs of A. tenuis, our results suggest that thermal stress resistance is modified by genetic mechanisms that coincidentally lead to diversification of color morphs of this coral., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)

Very few studies have been published on the long-term histopathologic follow-up of spherical embolic agents after their injection. To our knowledge, there are no reports in the literature regarding pathological analysis of the transvascular migration of HepaSphere particles. We here report a case of a patient with hepatocellular carcinoma (HCC) who underwent liver transplantation 12 months after drug eluting microsphere transcatheter arterial chemoembolization (DEM-TACE), and long-term histopathologic follow-up of the microspheres was performed. Furthermore, to our knowledge, this is the first report in which transvascular migration of a HepaSphere particle was confirmed histologically. A 60-year-old male with chronic hepatitis B was treated with entecavir and seroconversion was obtained. The patient had decompensated cirrhosis, and desired to undergo living donor liver transplantation (LDLT). However, 2 HCC tumors of 3  cm or less were detected in his liver. The transplantation surgeon proposed DEM-TACE as a bridge therapy. The HCCs were located in the right lobe and lateral segment of the liver. A 1.9  F preshaped microcatheter (ProgreatΣ, Terumo, Japan) was selectively inserted into the A3 and anterior segmental branch, 10  mg of epirubicin was injected into each artery, and the arteries were embolized with 7  mg and 13  mg of HepaSphere loaded with epirubicin, respectively. Two months later, contrast-enhanced CT displayed a complete response. At that time, lung metastasis was suspected, but after partial lung resection, the patient was diagnosed as having inflammatory granuloma. One year after DEM-TACE treatment, LDLT was performed. No cancerous cells were detected in the area where the tumor was present, but 22 HepaSphere particles were detected. All particles were present in the interstitium. Furthermore, the transvascular migration of a HepaSphere particle was histologically confirmed. The largest and smallest HepaSphere diameters were 241.6  ±  52.5  µm and 186.5  ±  41.4  µm, respectively, and deformity was 22.6% ± 13.0 %. All the HepaSpheres detected in the examined pathological specimen were noted to be extravascular.

Portal vein thrombosis (PVT) after hepatobiliary surgery is rare but can cause lethal and severe complications. If early diagnosis and recanalization can be achieved, the PVT is expected to be eliminated. A 70-year-old male was diagnosed as having hepatocellular carcinoma occupying the right lobe of the liver. As oligometastatic lung tumors were simultaneously detected on contrast-enhanced CT (CECT), hepatectomy was not indicated. However, the primary tumor was very large, and as large tumor size can be associated with an unfavorable prognosis, and owing to the strong desire of the patient, he underwent right lobe hepatectomy. Jaundice appeared on post-operative Day (POD) 2 and CECT displayed slight intraheptatic bile duct dilation. However, a PVT did not exist at this time. Percutaneous transhepatic biliary drainage was performed and Doppler echo displayed intrahepatic and extrahepatic PVT on post-operative Day 5. Emergent thrombectomy was performed using a Vasplyser Plus TM thrombus aspiration catheter (Johnson & Johnson K.K. Medical Company, Tokyo, Japan) via the ileocolic vein under laparotomy. The mesenteric catheter was placed at the distal point of the residual PVT. Thrombolysis and anticoagulant therapy were performed using heparin and urokinase. In the CECT performed 16 days after the additional operation, the PVT had disappeared and the portal vein was completely recanalized. The mesenteric catheter was removed on the same day and oral anticoagulant therapy was continued. At the time of writing, 14 months have passed with no recurrence of PVT. Early diagnosis of PVT enables treatment with emergent thrombectomy, thrombolysis, and anticoagulant therapy. These treatments result in the improvement of portal vein flow and the complete disappearance of PVT.

Background: The aim of this study was to clarify clinicopathological features, frequencies of molecular biomarkers, and prognoses in Japanese colorectal cancer patients and compare them with right-sided colon cancer (RCC) and left-sided colorectal cancer (LCRC)., Methods: We consecutively selected 575 colorectal cancer patients who underwent surgical resection from 2008 to 2011. RCC was located from the cecum to the transverse colon, and LCRC was located from the splenic flexure to the rectum. Frequencies of KRAS gene mutation, BRAF gene mutation, microsatellite instability (MSI), l18qLOH and CpG island methylator phenotype (CIMP) were statistically analyzed between groups., Results: Tumors were located in the RCC in 26.3% of patients and in the LCRC in 73.7%. Elderly patients, females and advanced diseases were significantly more frequent in the RCC group than in the LCRC group. However, venous invasion was significantly more frequent in LCRC than in RCC. Between groups, BRAF mutant type, KRAS mutant type, MSI and CIMP+ were significantly more frequent in RCC, whereas 18qLOH was significantly more frequent in LCRC. In overall survival, RCC demonstrated poor prognosis compared with LCRC; however, age, gender, stage, lymphatic invasion, KRAS status and BRAF status rather than tumor location were independent prognostic factors. In addition, the independent prognostic factors in RCC were different from those in LCRC in each stage. However, the consistency between OS and DFS was not observed in this study, excluding lymphatic invasion in LCRC., Conclusion: Comparing RCC with LCRC, RCC is different from LCRC in clinicopathological features, molecular biomarkers and prognostic factors in Japanese colorectal cancer patients. Since the proportions of molecular biomarkers of CRC in this study are different from Western CRCs, further studies are required to clarify the clinicopathological differences between Japanese CRCs and Western CRCs.

The fibrinolysis system is thought to play an important role in liver regeneration. We previously found that plasminogen (Plg) is localized to the cell surface of regenerating liver tissue as well as proliferating hepatocytes in vitro. Here, we investigated the significance of Plg binding to the cell surface during liver regeneration. Pre-administration of tranexamic acid (TXA), which is a competitive inhibitor of Plg binding, to hepatectomized rats mildly delayed restoration of liver weight in vivo. Although binding of Plg to the cell membrane decreased following TXA administration, TXA showed little effect on hepatocyte proliferation in rats. We also discovered that Plg treatment did not stimulate proliferation of primary rat hepatocytes in vitro. These results suggest that Plg/plasmin potentiates liver regeneration via a pathway distinct from those through which hepatocyte proliferation is stimulated.

Objective: To investigate risk factors for radiation-induced pneumonitis (RP) after hypofractionated stereotactic body radiotherapy (SBRT) in patients with lung tumours., Methods: From May 2004 to January 2016, 66 patients with 71 primary or metastatic lung tumours were treated with SBRT; these 71 cases were retrospectively analyzed for RP. To explore the risk factors for RP, the following factors were investigated: age, sex, performance status, operability, number of treatments, respiratory gating, pulmonary emphysema, tumour location and subclinical interstitial lung disease (ILD). Irradiated underlying lung volumes of more than 5 Gy, 10 Gy, 20 Gy and 30 Gy (Lung V 5 , V 10 , V 20 and V 30 ), mean lung dose and volumes of gross tumour volume (in cubic centimetre) and planning target volume were calculated for possible risk factors of RP., Results: The median follow-up period was 32 months. RP of Grade 2 or more, according to the Common Terminology Criteria for Adverse Events v. 4.0, was detected in 6 (8.4%) of the 71 cases. Grade 5 RP was identified in two cases. Of the risk factors of RP, subclinical ILD was the only factor significantly associated with the occurrence of RP of Grade 2 or more (p < 0.001). Both cases with Grade 5 RP had ILD with a honeycombing image., Conclusion: Subclinical ILD was the only significant factor for Grade 2-5 RP. In addition, the cases with honeycombing had a high potential for fatality related to severe RP. Patients with subclinical ILD should be carefully monitored for the occurrence of severe RP after SBRT. Advances in knowledge: Hypofractionated SBRT for primary or metastatic lung tumours provides a high local control rate and safe treatment.

The proband was a 32-year-old man with sparse type of familial adenomatous polyposis with fundic gland and duodenal polyps and congenital hypertrophy of the retinal pigment epithelium without osteoma, dental abnormalities and desmoid tumors. Direct DNA sequencing did not detect germline mutations in any APC exon. However, using the multiplex ligation-dependent probe amplification method, we detected germline deletions of all APC exons. Using dual-color fluorescence in situ hybridization, we identified germline deletion of locus 5q22.1-22.2 that includes APC. Analysis of colorectal tumors identified somatic APC mutations in the cluster region in all polyps, but no loss of heterozygosity was detected in any polyp., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: Vitamin K2 (VitK2) is reported to induce not only bone mineralization of human osteoblasts and apoptosis of osteoclasts, but also apoptosis of rheumatoid arthritis (RA) synovial cells, while its clinical effect on disease activity of RA remains unknown., Methods: 158 female RA patients (mean age 62.5 years) who had not been treated with warfarin, biologics, or teriparatide were enrolled in this study. VitK2 (45 mg/day) was administered in 70 patients with a serum undercarboxylated osteocalcin level of >4.5 ng/ml or with decreased bone mineral density in spite of the treatment with other anti-osteoporosis medications, regardless of RA disease activity. A longitudinal study was conducted in 52 patients who were additionally treated with VitK2 without changing their other medications for three months., Results: In the cross-sectional study, as compared to the VitK2-naïve group (n = 88), the VitK2-treated group (n = 70) showed lower serum CRP (1.7 ± 0.2 vs. 0.5 ± 0.1 mg/dl; P < 0.001), MMP-3 (220.4 ± 21.9 vs. 118.0 ± 14.4 ng/ml; P < 0.001), and DAS28-CRP (2.9 ± 0.1 vs. 2.4 ± 0.1; P < 0.05). In the longitudinal study, patients who were additionally treated with VitK2 showed significant decreases in serum CRP (1.1 ± 0.2 to 0.6 ± 0.2 mg/dl; P < 0.001), MMP-3 (160.1 ± 25.6 to 125.0 ± 17.8 ng/ml; P < 0.05), and DAS28-CRP (3.1 ± 0.2 to 2.4 ± 0.1; P < 0.001)., Conclusions: VitK2 may have the potential to improve disease activity besides osteoporosis in RA.

Replacement of an artificial graft in a redo lateral thoracotomy is extremely difficult with a high risk of lung injury. Endovascular intervention may be an ideal option in such conditions, as in the following case. A 75-year old man with a history of coronary artery bypass graft surgery developed a proximal anastomotic pseudoaneurysm 1 year after undergoing artificial proximal descending aorta replacement surgery. Thoracic endovascular aneurysm repair was performed successfully using the periscope graft technique to preserve the flow into the left subclavian artery from the distal side of the aortic stent graft. Since the patient had coronary artery bypass grafting, debranching of the left subclavian artery was considered too risky. Using the periscope graft technique, the pseudoaneurysm was successfully repaired preserving the left subclavian artery patency, thus obviating a side-to-side subclavian artery crossover bypass.

Urgent single-staged replacement of the aortic dissection involving the entire thoracic aorta was performed by using the modified pull-through technique via median sternotomy. Distal anastomosis was achieved via posterior pericardium to avoid the lateral thoracotomy and then the graft was pulled through the false lumen of the descending aorta into the aortic arch. Each lumen between proximal and distal anastomosis was closed for hemostasis. The aortic arch was replaced with a four-branched graft. Postoperative course was uneventful. This procedure might be an alternative in selected patients to the left thoracotomy.

Rice (Oryza sativa) endosperm accumulates a massive amount of storage starch and storage proteins during seed development. However, little is known about the regulatory system involved in the production of storage substances. The rice flo2 mutation resulted in reduced grain size and starch quality. Map-based cloning identified FLOURY ENDOSPERM2 (FLO2), a member of a novel gene family conserved in plants, as the gene responsible for the rice flo2 mutation. FLO2 harbors a tetratricopeptide repeat motif, considered to mediate a protein-protein interactions. FLO2 was abundantly expressed in developing seeds coincident with production of storage starch and protein, as well as in leaves, while abundant expression of its homologs was observed only in leaves. The flo2 mutation decreased expression of genes involved in production of storage starch and storage proteins in the endosperm. Differences between cultivars in their responsiveness of FLO2 expression during high-temperature stress indicated that FLO2 may be involved in heat tolerance during seed development. Overexpression of FLO2 enlarged the size of grains significantly. These results suggest that FLO2 plays a pivotal regulatory role in rice grain size and starch quality by affecting storage substance accumulation in the endosperm.

We investigated the activation of transient receptor potential cation channel (TRP) subfamily V, member 1 (TRPV1) and TRP subfamily A, member 1 (TRPA1) by 1'-acetoxychavicol acetate (ACA), the main pungent component in galangal. ACA did not activate TRPV1-expressing human embryonic kidney (HEK) cells, but strongly activated TRPA1-expressing HEK cells. ACA was more potent than allyl isothiocyanate, the typical TRPA1 agonist.

Cell type-specific fluorescent gene expression markers are a prerequisite for various strategies in functional genomics and developmental biology. To increase the resolution of vascular tissue analysis and to identify more genes expressed in the vasculature, we searched for expression in vascular tissues within a new collection of transactivated enhancer trap lines. Among 33 lines with vascular expression, we identified five lines with expression profiles marking procambial or procambium-associated cell states. In stem cross-sections we identified one line with phloem- and four with xylem-specific expression, as well as nine lines with expression in both phloem and xylem and two with cambial expression. For all lines, we also report the expression patterns in different organs and developmental stages. Special features of expression patterns include a line with auxin-dependent expression domains. We determined the flanking sequences of 21 enhancer trap insertions, 16 of which are found in, or in close proximity to, annotated genes and thus may reflect the expression patterns of natural promoters. Finally, we analyzed the loss-of-function phenotypes of 14 putatively affected genes. Remarkably, mutations in a gene encoding a putative F-box protein were associated with an auxin-hypersensitive hypocotyl elongation response. Our compendium provides a diverse selection of markers for different vascular cell states, which can be used for targeted gene expression, cell type-specific transcript profiling and gene function assignment in the plant vascular system.

The myocardial protective effects of active and passive coronary perfusion were compared during off-pump coronary artery bypass grafting (OPCAB) in coronary stenosis model. An internal shunt tube was placed in the proximal left anterior descending arteries of adult dogs to produce a 75% coronary stenosis model. In 10 animals passive coronary perfusion was performed using an internal shunt tube placed in a pseudo-anastomotic site, and active coronary perfusion was performed through an external shunt tube. Ischemia was examined at normal and low blood pressure, based on hemodynamics, regional myocardial blood flow, and oxygen and lactate extraction in the perfused area. With passive perfusion, regional myocardial blood flow decreased and oxygen extraction and regional lactate production increased at normal blood pressure, indicating myocardial ischemia. Regional myocardial blood flow further decreased at low blood pressure. In contrast, regional myocardial blood flow with active perfusion did not change at normal or low blood pressure, and oxygen and lactate extraction were unchanged, indicating prevention of myocardial ischemia. Myocardial ischemia can occur with passive perfusion even at normal blood pressure. Active coronary perfusion that provides sufficient regional perfusion prevents myocardial ischemia during coronary artery anastomosis in OPCAB.

The rice CM2088 mutant is the wilty phenotype and wilts markedly under well-watered sunny conditions. The leaf water potential and epidermal (mainly stomatal) conductance of CM2088 plants decreased significantly under conditions that induced intense transpiration, as compared with those of wild-type plants, revealing that the wilty phenotype was not the result of abnormal stomatal behavior but was due to an increase in resistance to water transport. The resistance to water transport was dramatically elevated in the node and the sheath and blade of a leaf of the mutant, but not in the root or stem. The diameter of xylem vessels in the large vascular bundles of the leaf sheath and the internode tended to be small, and the numbers of vessel elements with narrowed or scalariform perforation plates in the leaf blade and sheath were greater in the mutant than in the wild type. Most xylem vessels were occluded, with air bubbles in the leaf sheath of the mutant during the midday hours under intense transpiration conditions, while no bubbles were observed in plants that were barely transpiring, revealing that the significant increase in resistance to water transport was a result of the cavitation. The additive effects of cavitation in xylem vessels and the decreased diameter and deformed plates of vessel elements might be responsible for the wilty phenotype of CM2088.

Objective: Antegrade perfusion for type A acute aortic dissection prevents malperfusion and retrograde cerebral embolism during cardiopulmonary bypass. Prompt establishment of antegrade perfusion via ascending aorta may improve the surgical results of type A dissections, especially in the situations of hemodynamic instability. Thus, we evaluated the efficacy of use of the dissected ascending aorta as an alternative arterial inflow., Methods: Between 2002 and 2006, 32 patients underwent prosthetic graft replacement of the ascending aorta or hemiarch for acute type A aortic dissection. The ascending aorta was routinely cannulated, in addition to the femoral artery, with a heparin-coating flexible cannula for arterial inflow, using Seldinger technique, and by epiaortic ultrasonographic guidance (n=6). Antegrade systemic perfusion via ascending aorta was performed., Results: Ascending aorta cannulation was safely performed in all cases. There was no malperfusion or thromboembolism due to ascending aorta cannulation. Cardiopulmonary bypass was established within 30 min after skin incision. There was one in-hospital death due to duodenal bleeding (1/32=3.1%), two cases of cerebral infarction (2/32=6.3%), and one case of pulmonary embolism. Twenty-nine patients (29/32=90.6%) were discharged in New York Heart Association class I and have been followed up uneventfully for a mean of 17 months., Conclusions: Antegrade perfusion via the ascending aorta was successfully performed with low mortality and morbidity. With ultrasound-guided Seldinger technique, ascending aorta cannulation has a potential to be a simple and safe option that enables rapid establishment of antegrade systemic perfusion in patients with acute type A aortic dissection.

Aim: We sought to confirm the presence of halophilic and alkaliphilic lactic acid bacteria (HALAB) of marine origin in cheeses and thus contribute to the understanding of the roles of LAB flora in cheese ripening., Methods and Results: We used 7% NaCl glucose-yeast extract-peptone-fish extract broth and agar media (pH 9.5) for pour-plating and enrichment culture for 16 cheese samples produced in six European countries. HALAB were present in 9 of the 16 samples at < 20 --> 10(7) CFU g(-1). In three mould-ripened soft cheeses, HALAB counts ranged from 10(6) to 10(7) CFU g(-1) and were one order (two samples) and six orders (one sample) of magnitude greater than that of nonhaloalkaliphilic, common LAB, as enumerated on lactobacilli MRS agar. The 16S rRNA gene sequences (500 bp) of 51 of the 55 isolates examined were identical or similar to that of Marinilactibacillus psychrotolerans or Alkalibacterium olivapovliticus and related species, all of which are HALAB., Conclusions: HALAB of possible marine origin were present in various soft, semi-hard and semi-soft cheeses and were highly predominant in some mould-ripened cheeses., Significance and Impact of the Study: HALAB of possible marine origin are members of the microflora of various cheeses and, when dominant, may play a role in the ripening of cheeses. Microbial analysis of LAB flora in cheeses should take into consideration the presence of HALAB.

Aims: Effects of amino acid on morphological development and nucleus formation of arachidonic acid-producing filamentous micro-organism, Mortierella alpina were investigated using flow-through chamber., Methods and Results: Mortierella alpina CBS 754.68 was cultivated in flow through chamber using nutrient-rich, minimal and specific amino acid-containing minimal media. To investigate the effect of amino acid on morphological parameters either 0.28 g l(-1) alanine, 0.53 g l(-1) sodium glutamate one hydrate or 0.42 g l(-1) valine was added to the minimal medium. In a flow-through chamber, the growth of hyphal elements and nucleus formation of arachidonic acid-producing fungus M. alpina were studied on-line, using image analysis techniques. When the Ala- and Val-containing media were used, the hyphal growth units (HGUs) were 90.2 and 86.7 microm per tip, respectively, which were 2.4-fold higher than that in the nutrient-rich medium, indicating that Ala and Val stimulate the elongation of hyphae. The specific nucleus formation rates were Glu->Val-containing media>minimal and nutrient-rich media>Ala-containing medium. The nucleus doubling times in Glu- and Val-containing media were 1.9 and 2 h, respectively, which were not significant different., Conclusions: Ala and Val stimulate the elongation of M. alpina hyphae, and nucleus formation rates were Glu->Val->Ala-containing media., Significance and Impact of the Study: Formation of fungal morphology and nucleus were shown using the flow-through chamber coupled with image analysis, which making possible to discuss the relationship between mycelial morphology and nucleus formation of M. alpina.

Here, we describe a case of severe pancreatitis in overlap syndrome of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) in an adult female patient. Treatment with plasmapheresis and high-dose prednisone successfully saved her life and led to remission of the pancreatitis. This is the first case report of severe acute pancreatitis in the setting of overlap syndrome of SLE and SSc. The advantages and disadvantages of the use of corticosteroids are discussed.

Objectives: No detailed studies exist of coronary artery bypass graft flow during atrial fibrillation. We examined the effects on bypass graft flow of atrial fibrillation following coronary artery bypass grafting., Methods: Immediately after surgical revisualization, atrial fibrillation was induced in 18 patients by high frequency atrial pacing. Hemodynamic variables were measured in sinus rhythm and atrial fibrillation. The graft flow in pedicled left internal thoracic artery grafts and in saphenous vein grafts was also measured using transit-time flowmetry., Results: Left internal thoracic artery graft flow had a greater diastolic component than saphenous vein graft flow, as shown by the percent diastolic time-flow integral (86 +/- 10% in the left thoracic artery and 62 +/- 12% in the saphenous vein, P < 0.0001). The induced atrial fibrillation caused significant deterioration in hemodynamics: heart rate and central venous pressure increased, and mean arterial pressure and cardiac index decreased (all P < 0.0025). In left internal thoracic artery grafts (n = 18) and also in saphenous vein grafts (n = 20), graft flow decreased significantly with atrial fibrillation (44.3 +/- 26.2 to 26.2 +/- 20.7 ml/min in the left internal thoracic artery, P = 0.0003; 39.7 +/- 15.6 to 33.3 +/- 14.3 ml/min in the saphenous vein, P = 0.001). The reduction in graft flow due to atrial fibrillation was much larger in left internal thoracic artery grafts than in saphenous vein grafts (P = 0.0008)., Conclusions: Direct measurement of coronary artery bypass graft flow shows that atrial fibrillation after surgery significantly reduces graft flow. The effect is much larger in left internal thoracic artery grafts with their strong diastolic component than in saphenous vein grafts., (Copyright 2002 Elsevier Science B.V.)

Rhodococcus erythropolis KA2-5-1 can desulfurize dibenzothiophene (DBT) into 2-hydroxybiphenyl. A cryptic plasmid, pRC4, which was derived from R. rhodochrous IFO3338, was combined with an Escherichia coli vector to construct an E. coli-Rhodococcus shuttle vector. The complete nucleotide sequence of 2582-bp pRC4 was analyzed. Based on the characteristics of its putative replication genes, pRC4 was assigned to the family of pAL5000-related replicons. The desulfurization gene cluster, dszABC, and the related reductase gene, dszD, cloned from KA2-5-1, were reintroduced into KA2-5-1 and efficiently expressed. The DBT desulfurization ability of the transformant carrying two dszABC clusters and one dszD on the vector was about 4-fold higher than that of the parent strain, and the transformant also showed improved desulfurization activity for light gas oil (LGO). Sulfur components in LGO before and after the reaction were analyzed with gas chromatography-atomic emission detection.

Alpha-D-mannosyl-maltotriose (Man-G3) were synthesized from methyl alpha-mannoside and maltotriose by the transfer action of alpha-mannosidase. (Man-G3)-betaCD and (Man-G3)2-betaCD were produced in about 20% and 4% yield, respectively when Aerobacter aerogenes pullulanase (160 units per 1 g of Man-G3) was incubated with the mixture of 1.6 M Man-G3 and 0.16 M betaCD at 50 degrees C for 4 days. The reaction products, (Man-G3)-betaCD were separated to three peaks by HPLC analysis on a YMC-PACK A-323-3 column and (Man-G3)2-betaCD were separated to several peaks by HPLC analysis on a Daisopak ODS column. The major product of (Man-G3)-betaCDs was identified as 6-O-alpha-(6(3)-O-alpha-D-mannosylmaltotriosyl)-betaCD by FAB-MS and NMR spectroscopies. The structures of (Man-G3)2-betaCDs were analyzed by TOF-MS and NMR spectroscopies, and confirmed by comparison of elution profiles of their hydrolyzates by alpha-mannosidase and glucoamylase on a graphitized carbon column with those of the authentic di-glucosyl-betaCDs. The structures of three main components of (Man-G3)2-betaCDs were identified as 6(1),6(2)-, 6(1),6(3)- and 6(1),64-di-O-(63-O-alpha-D-mannosyl-maltotriosyl)-betaCD.

Thirty-five bacterial strains capable of converting dibenzothiophene into 2-hydroxybiphenyl were isolated. Among them Rhodococcus erythropolis KA2-5-1 was chosen for further characterization because of its ability to retain high desulfurization activity stably. PCR cloning and DNA sequencing of a KA2-5-1 genomic DNA fragment showed that it was practically identical with dszABC genes from Rhodococcus sp. IGTS8, a representative carbon-sulfur-bond-targeted dibenzothiophene-degrading bacterium. KA2-5-1 desulfurized a variety of alkyl dibenzothiophenes through the specific cleavage of their C-S bonds. In addition, unexpectedly, KA2-5-1 also attacked alkyl benzothiophenes in a C-S-bond-targeted fashion. The purified monooxygenase, encoded by dszC of KA2-5-1, converted benzothiophene and dibenzothiophene into benzothiophene sulfone and dibenzothiophene sulfone, respectively, with the aid of an NADH-dependent oxidoreductase. This result raises the possibility that the same enzymatic step may be involved in desulfurization of alkylated forms of both dibenzothiophene and benzothiophene in KA2-5-1 cells.

From the mixture of 4(2)-O-beta-D-galactosyl-maltose (Gal-G2) and beta-cyclodextrin (betaCD), novel heterobranched betaCDs, (Gal-G2)-betaCD and (Gal-G2)2-betaCDs, were synthesized by the reverse action of debranching enzyme. The optimum conditions for the production of (Gal-G2)2-betaCDs were examined. A mixture of (Gal-G2)2-betaCDs was produced in about 4% yield when Aerobacter aerogenes pullulanase (64 units per 1 g of Gal-G2) was incubated with 1.6 M Gal-G2 and 0.16 M betaCD at 50 degrees C for 4 days. The reaction products, (Gal-G2)2-betaCDs, were separated into three peaks by HPLC analysis on a Hypercarb S column. Their structures were analyzed by fast atom bombardment mass spectroscopy and NMR spectroscopies, and confirmed by comparison of their hydrolyzates by beta-galactosidase with the authentic (G2)2 -betaCDs. The structures of (Gal-G2)-betaCD and three components of (Gal-G2)2-betaCDs were identified as 6-O-(GalG2)-betaCD, 6(1),6(2)-, 6(1),6(3)- and 6(1),6(4)-di-O-(Gal-G2)2-betaCD, respectively.

Background: To evaluate whether tumor markers can be used to assess response to systemic chemotherapy, we analyzed preliminarily the relationship between the response to chemotherapy based on serial imaging and on change in serum tumor marker level of CEA, CA19-9 and CA125., Methods: We analyzed 26 patients with advanced gastric cancer in whom at least one of the tumor markers CEA, CA19-9 and CA125 was elevated before systemic chemotherapy with regard to the relationship between the change in serum tumor marker level and response assessment by imaging studies throughout the treatment course. A responder was defined as showing a > or = 50% drop in tumor marker level for more than 4 weeks., Results: The sensitivity and negative predictive value of falling tumor marker level after chemotherapy for a partial response in imaging was 100%. When patients were categorized as responders or non-responders, a significant correlation was observed between the assessment of response by tumor markers and by imaging studies. The survival time of responders assessed by tumor markers was significantly longer than that of non-responders., Conclusions: The measurement of tumor markers might be useful in monitoring response and in predicting the prognosis of patients with advanced gastric cancer treated with systemic chemotherapy. Tumor markers may be used as a means of monitoring treatment in patients when in an imaging study it is difficult to assess response to chemotherapy in clinical practice. Further studies are required to confirm these findings.

Novel heterobranched cyclodextrins (CDs), N-acetylglucosaminyl-cyclodextrins (GlcNAc-CD), were synthesized from a mixture of GlcNAc and alpha, beta, or gamma CD by the reverse reaction of N-acetylhexosaminidase from jack bean. Optimum pH and temperature for the production of GlcNAc-alpha CD by N-acetylhexosaminidase were pH 4.9 and 50-70 degrees C, respectively. The maximum yield of GlcNAc-alpha CD was 17.5% (mol/mol) at the concentration of 1 M GlcNAc and 0.25 M alpha CD. The reverse reaction product, GlcNAc-alpha CD, was separated into two peaks by HPLC analysis on the ODS column. Their structures were identified as 6-O-beta-D-N-acetylglucosaminyl-alpha CD and 2-O-beta-D-N-acetylglucosaminyl-alpha CD by FAB-MS and NMR spectroscopies. N-Acetylhexosaminidase from jack bean also synthesized N-acetylgalactosaminyl-alpha CD from N-acetylgalactosamine and alpha CD.

Mannosylated derivatives of cyclodextrins (CDs), mannosyl-α, β, and γCD were synthesized from a mixture of mannose and α, β, and γCD by the reverse action of α-mannosidase from jack bean, respectively. Their structures were analyzed by FAB-MS and 13 C-NMR spectroscopies, and they were identified as 6-O-α-d-mannosyl-α, β, and γCD. The optimum conditions for the production of 6-O-α-d-mannosyl-αCD by α-mannosidase were examined. Optimum pH and temperature were pH 4.5 and 60°C, respectively. Yield of mannosyl-αCD increased with increasing mannose concentration and reached more than 35% (mol/mol) at the concentration of 2 m mannose and 0.4 m αCD.

Transgalactosylated derivatives of cyclodextrins (CDs) and glucosyl and maltosyl CDs (G1- and G2-CDs) were synthesized by alpha-galactosidases from coffee bean and Mortierella vinacea (M. vinacea). The structures of the transfer products were analyzed by FAB-mass, 13C-NMR and methylation. Coffee bean alpha-galactosidase transferred a galactosyl residue not only to side chains of G1-CDs and G2-CDs, but also directly to CD rings. M. vinacea alpha-galactosidase transferred a galactosyl residue only to side chains of G2-CDs.

The structures of hetero-oligosaccharides obtained by the action of transglycosylation of Arthrobacter sp. K-1 beta-fructofuranosidase, using sucrose as the fructosyl donor, and several mono- and di-sacchrides as the acceptors were investigated. The main transfer products to most reducing mono- and di-sacchrides were non-reducing oligosaccharides with a fructosyl residue linked to a hemiacetal hydroxyl group. In the presence of L-sorbose, the enzyme produced 2-O-beta-D-fructofuranosyl-alpha-L-sorbopyranoside as the major product. With D-galactose or L-arabinose, the enzyme produced not only non-reducing oligosaccharides, but also reducing oligosaccharides, which were identified as 3-O-beta-D-fructofuranosyl-D-galactopyranose and 4-O-beta-D-fructofuranosyl-L-arabinopyranose, respectively. When a non-reducing sugar such as methyl alpha-glucoside was used as an acceptor, the product formed had a fructosyl residue linked at the C6 hydroxyl group.

Jack bean alpha-mannosidase had a wide acceptor specificity and could transfer mannosyl residues to various acceptors such as D-fructose, L-arabinose, maltose, lactose, and sucrose. The structures of the transferred products of branched cyclodextrins (CDs) (glucosyl-beta CD, maltosyl-alpha CD, and maltosyl-beta CD) were found to be alpha-D-mannosyl-(1-->6)-alpha-D-glucosyl-(1-->6)-beta CD, alpha-D-mannosyl- (1-->6)-alpha-D-glucosyl-(1-->4)-alpha-D-glucosyl-(1-->6)-alpha CD and alpha-D-mannosyl-(1-->6)-alpha-D-glucosyl-(1-->4)-alpha-D-glucosyl-(1--> 6)- beta CD, respectively. Almond alpha-mannosidase also produced the same transmannosylated products of branched CDs.

Bacillus stearothermophilus CGTase had a wider acceptor specificity than Bacillus macerans CGTase did and produced large amounts of transfer products of various acceptors such as D-galactose, D-mannose, D-fructose, D- and L-arabinose, D- and L-fucose, L-rhamnose, D-glucosamine, and lactose, which were inefficient acceptors for B. macerans CGTase. The main component of the smallest transfer products of lactose was assumed to be alpha-D-glucosyl O-beta-D-galactosyl-(1----4)-beta-D-glucoside.

The galactosyl transfer reaction to branched cyclodextrins (CDs) was investigated using lactose as a donor substrate and branched CDs as acceptors by various beta-galactosidases. Bacillus circulans beta-galactosidase synthesized galactosyl transfer products to branched CDs, of which the galactose residues were linked at side chains of branched CDs, not directly at CD rings. Aspergillus oryzae and Penicillium multicolor beta-galactosidases also produced derivatives galactosylated at side chains of branched CDs. The structures of main transgalactosylation products of branched CDs by these beta-galactosidases seem to be different from those by B. circulans beta-galactosidase, judging from the retention times on high performance liquid chromatography.

Phospholipase A activities in plasma membranes (PMs), isolated from rat ascites hepatoma cells (AH 130, AH 130FN, AH 7974, and AH 7974F), were determined and compared with those in PMs isolated from normal rat livers (neonatal, resting adult, and regenerating adult livers). All the PMs had a hydrolyzing action on 1-acyl-2[14C]oleyl-sn-glycero-3-phosphoethanolamine but not on similarly labeled phosphatidylcholine. After hydrolysis, the radioactivity was recovered in both the lyso derivative and the free fatty acid produced. Thus, the presence of phospholipases A1 and A2 in the PMs, with an optimal pH around pH 9, was demonstrated. In all the hepatoma PMs, te phospholipase A2 activity was greatly reduced or almost lacking, whereas in the PMs from normal resting and growing livers strong phospholipase A2 activity was detected equally but with a specific activity higher than that of phospholipase A1. Triton X-100 treatment had an activating effect on phospholipase A1 but an inhibitory effect on phospholipase A2 of the resting liver PMs, while the same treatment was inhibitory for both the phospholipase A1 and A2, activities of the hepatoma PMs.

Plasma membranes were isolated from lymphoid cells of benign thymomas obtained from inbred BUF/Mna rats (21 mo old) and from normal thymocytes obtained from young rats (7 wk old) of the same strain. The isolated plasma membranes were electron microscopically pure, and the specific activities of Na+, K+-ATPase, and 5'-nucleotidase were enhanced. The lipid compositions of the plasma membranes from these two sources were analyzed and compared. The cholesterol and plasmalogen contents of membranes from both sources were similar, but the phospholipid content of the benign thymoma lymphoid cell membranes was slightly lower than that of the normal thymocytes, resulting in a somewhat higher molar ratio of cholesterol to phospholipid. The plasma membranes of the thymoma lymphoid cells also exhibited a slightly higher microviscosity as measured with fluorescence polarization. No significant differences were observed in the phospholipid compositions of the two membrane preparations.

Hyperplastic nodules and hepatomas were induced in livers of rats fed a diet containing 0.05% N-2-fluorenylacetamide (2-FAA). The lipid contents, and phospholipid and fatty acid compositions were analyzed in plasma membranes (PM's) isolated from these tissues and normal rat liver, and the following trends were observed. The molar ratio of cholesterol to phospholipid-phosphorus (phospholipid-P) increased in the order: hepatoma less than normal liver less than hyperplastic nodules. The molar percentage of plasmalogen to phospholipid-P decreased in the order: hepatoma = hyperplastic nodules greater than normal liver. The percentages of choline phosphoglycerides (sum of phosphatidylcholine and lysophosphatidylcholine) and ethanolamine phosphoglycerides (sum of phosphatidylethanolamine and lysophosphatidylethanolamine) both decreased in the order: hepatoma greater than hyperplastic nodules greater than normal liver. On the other hand, the percentages of sphingomyelin and phosphatidylserine both increased in the order: hepatoma less than hyperplastic nodules less than normal liver. As regards fatty acid composition, the percentages of both 18:1 and 18:2 decreased in the order: hepatoma greater than hyperplastic nodules greater than normal liver. Those of 18:0 and 20:4 increased in the order: hepatoma less than hyperplastic nodules less than normal liver. These results suggested that the lipid bilayer in PM of hyperplastic nodules has characteristics roughly intermediate between those of hepatoma and liver PM's, although the molar ratio of cholesterol to phospholipid-P in hyperplastic nodules PM was not intermediate.

Plasma membranes (PM) were isolated from island-forming types of rat ascites hepatoma (AH 130, AH 602, and AH 7974) and from their free-cell sublines (AH 130FN and AH 7974F), and were characterized in terms of electron-microscopic morphology, marker enzyme activities, and lipid contents. The results were compared with those of the PM isolated in a similar way from newborn, regenerating, and adult livers. The marker enzyme activities, such as Na+, K+-insensitive Mg2+-ATPase [EC 3.6.1.3] (Mg2+-ATPase) and 5'-nucleotidase [EC 3.1.3.5], as well as the phospholipid composition of the PM isolated from hepatomas by Wallach's nitrogen gas cavitation method were similar to those obtained with the PM isolated by a modification of Emmelot's method, although the former method gave a much lower yield in terms of protein than the latter. Based on the modified Emmelot method, sufficiently pure PM preparations could be obtained from the hepatomas in the form of large membrane sheets without any contamination by other identifiable components, as determined with an electron microscope, and with high specific activities of the marker enzymes, such as Na+, K+-sensitive ATPase [EC 3.6.1.3] (Na+, K+ -ATPase), Mg2+ -ATPase, and 5'-nucleotidase. As for the characteristics of the hepatoma PM, lower specific activity of 5'-nucleotidase and higher fatty aldehyde molar percentages in total phospholipids were noted in all the PM from the hepatomas in comparison with normal liver PM of various origins. The PM from the hepatomas showed an increased amount of cholesterol (mumole per mg protein), whereas actively growing newborn and regenerating livers gave rather lower amounts in comparison with that of normal adult liver.

Two pituitaries from 7-week-old female rats were grafted under the capsule of the left kidney of 50-day-old male rat to induce hyperprolactinemia. All of the pituitary-grafted and sham-operated rats were hypophysectomized at 56 days of age. The hypophysectomized rats in groups of 4 were given daily sc injections of saline or 9 micrograms NIADDK-ovine-(o)LH-23 for 4 and 5 days starting from days 58 and 70, respectively (short and long term hypophysectomized groups). The metabolism of [3H]progesterone or [14C]androstenedione by testicular homogenates, concentrations of testosterone and 5 alpha-androgens (androsterone plus 5 alpha-androstane-3 alpha, 17 beta-diol) in the serum and testes, and testicular LH receptors were estimated. Hypophysectomy caused significant decreases in testicular enzyme activities per gram of tissue, androgen production, and testicular LH receptors. In the testes of hypophysectomized rats, LH treatment significantly stimulated 5 alpha-reductase and 17-hydroxylase activities. Although pituitary grafts alone showed little or no effect on these testicular enzyme activities, hyperprolactinemia induced by the grafts markedly enhanced the LH-stimulated 5 alpha-reductase activity in both groups, especially in the long term hypophysectomized group. Therefore, androsterone and 5 alpha-androstane-3 alpha,17 beta-diol were shown to be the major C19-steroid products (immature type of testicular androgen production) in the LH- and PRL-stimulated testes of long term hypophysectomized adult rats. On the other hand, hyperprolactinemia was associated with a significant inhibition and a slight increase of the LH-stimulated 17-hydroxylase activities in the short and long term hypophysectomized groups, respectively. This difference can be attributed to both a PRL-induced increase in testicular LH receptors and a PRL-induced inhibition of 17-hydroxylase via a postreceptor mechanism(s). The present findings demonstrate for the first time that PRL directly stimulates LH-induced 5 alpha-reductase activity in the testes. It appears that PRL may play a role in the increased production of 5 alpha-C19-steroids and the parallel decrease of testosterone production in immature rat testes.