Modeling circadian and sleep-homeostatic effects on short-term interval timing

Short-term interval timing i.e., perception and action relating to durations in the seconds range, has been suggested to display time-of-day as well as wake dependent fluctuations due to circadian and sleep-homeostatic changes to the rate at which an underlying pacemaker emits pulses; pertinent human data being relatively sparse and lacking in consistency however, the phenomenon remains elusive and its mechanism poorly understood. To better characterize the putative circadian and sleep-homeostatic effects on interval timing and to assess the ability of a pacemaker-based mechanism to account for the data, we measured timing performance in eighteen young healthy male subjects across two epochs of sustained wakefulness of 38.67 h each, conducted prior to (under entrained conditions) and following (under free-running conditions) a 28 h sleep-wake schedule, using the methods of duration estimation and duration production on target intervals of 10 and 40 s. Our findings of opposing oscillatory time courses across both epochs of sustained wakefulness that combine with increasing and, respectively, decreasing, saturating exponential change for the tasks of estimation and production are consistent with the hypothesis that a pacemaker emitting pulses at a rate controlled by the circadian oscillator and increasing with time awake determines human short-term interval timing; the duration-specificity of this pattern is interpreted as reflecting challenges to maintaining stable attention to the task that progressively increase with stimulus magnitude and thereby moderate the effects of pacemaker-rate changes on overt behavior

Case Report Ovarian Seromucinous Borderline Tumor and Clear Cell Carcinoma: An Unusual Combination

Ovarian seromucinous borderline tumors (SMBTs) are rare. They architecturally resemble serous borderline tumors but are much more frequently associated with endometriosis. The coexistence of other tumors with seromucinous tumors is also extremely rare. Here, we report an unusual combination of bilateral ovarian SMBT and clear cell carcinoma associated with polypoid endometriosis of the colon, in a 62-year-old woman. There was no transitional lesion between the two tumors. Immunohistochemistry showed different staining patterns in tumor components. Seromucinous tumor cells were positive for estrogen receptor (ER) and progesterone receptor (PgR) but negative for Napsin A, p504S, and HNF1B. Clear cell tumor cells were positive for Napsin A and p504S and focally positive for HNF1B but negative for ER and PgR. Loss of ARID1A expression was not observed in SMBTs, clear cell tumors, or endometriosis. These findings suggest that these tumors arose from separate endometriosis foci and collided within the same ovary. To the best of our knowledge, this is the first case of this unusual combination of ovarian seromucinous tumor and clear cell carcinoma to be reported in the English literature

京都府舞鶴湾の鉛を中心とした重金属汚染実態調査4ー2009年度調査結果と総括ー

Lead concentrations were determined in sediment, blue mussel (Mytilus galloprovincialis), seafood, selttling particles, atmospheric deposition, collected from Maizuru Bay, a semi-enclosed marine inlet of the Japan Sea in 2009, in order to elucidate lead contamination levels and distribution. Higher lead concentrations in sediment (824-4, 592ug/g dry) were detected in samples at 200m far from the pollution source. The highest lead concentration in settling particles (1,347ug/g dry) was detected in samples at 60m far from the pollution source. Lead concentrations in blue mussels transplanted from mon-polluted area to polluted area were increased definitely in 2 weeks,lead was not detected in the edible parts of 18 fishes and 2 shellfishes collected in Maizuru Bay. Extremely high lead pollution was kept in about 100m area from the pollution source. Reserch results from 2007-2009 on the lead pollution in Maizuru Bay were summarized

A distinct subtype of Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorder: adult patients with chronic active Epstein-Barr virus infection-like features

The characteristics of adult patients with chronic active Epstein-Barr virus infection are poorly recognized, hindering early diagnosis and an improved prognosis. We studied 54 patients with adult-onset chronic active Epstein-Barr virus infection diagnosed between 2005 and 2015. Adult onset was defined as an estimated age of onset of 15 years or older. To characterize the clinical features of these adults, we compared them to those of 75 pediatric cases (estimated age of onse

Ovarian Seromucinous Borderline Tumor and Clear Cell Carcinoma: An Unusual Combination

Ovarian seromucinous borderline tumors (SMBTs) are rare. They architecturally resemble serous borderline tumors but are much more frequently associated with endometriosis. The coexistence of other tumors with seromucinous tumors is also extremely rare. Here, we report an unusual combination of bilateral ovarian SMBT and clear cell carcinoma associated with polypoid endometriosis of the colon, in a 62-year-old woman. There was no transitional lesion between the two tumors. Immunohistochemistry showed different staining patterns in tumor components. Seromucinous tumor cells were positive for estrogen receptor (ER) and progesterone receptor (PgR) but negative for Napsin A, p504S, and HNF1B. Clear cell tumor cells were positive for Napsin A and p504S and focally positive for HNF1B but negative for ER and PgR. Loss of ARID1A expression was not observed in SMBTs, clear cell tumors, or endometriosis. These findings suggest that these tumors arose from separate endometriosis foci and collided within the same ovary. To the best of our knowledge, this is the first case of this unusual combination of ovarian seromucinous tumor and clear cell carcinoma to be reported in the English literature

Critical role of von Willebrand factor and platelet interaction in venous thromboembolism

It has been generally considered that platelets are less important in venous thrombus formation. However, clinical studies have shown an association between venous thromboembolism (VTE) and von Willebrand factor (VWF). We therefore investigated the contribution of VWF and platelet interaction to the onset of VTE using tissues from autopsies and from an animal model. An immunohistochemical study revealed that glycoprotein (GP) IIb/IIIa, fibrin, glycophorin A (erythrocyte-specific protein) and VWF were consistently localized in ilio-femoral venous thrombi and in pulmonary thromboemboli from 8 autopsied cases who died of VTE, and VWF was closely associated with GPIIb/IIIa and fibrin. Venous thrombi and pulmonary emboli contained significant amounts of GPIIb/IIIa and VWF, in addition to glycophorin A and fibrin, and the factors did not significantly differ between them. A rabbit model of VTE was developed by inserting a polyethylene tube into the iliac vein. The constituents of the induced thrombi were quite similar to those of human VTE. An antibody against VWF (AJW200), which inhibits interactions between the VWF A1 domain and platelet GPIb, significantly reduced venous thrombus formation and pulmonary thromboembolism in the model. These results suggest that VWF A1-platelet GPIb interaction plays a significant role in venous thrombus formation

Gefitinib successfully administered in a lung cancer patient with leptomeningeal carcinomatosis after erlotinib-induced pneumatosis intestinalis

Abstract Background Pneumatosis intestinalis (PI) is a rare complication of chemotherapy, characterized by multiple gas accumulations within the bowel wall. Case presentation A 71-year-old woman with epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma was admitted to our hospital because of reduced consciousness. She was diagnosed as having leptomeningeal carcinomatosis (LM) using lumbar puncture. Because she could not swallow a tablet, erlotinib was administered via a feeding tube. Her state of consciousness gradually improved, but she experienced diarrhea several times a day. After 3 weeks of erlotinib therapy, PI occurred. Erlotinib was discontinued and PI was resolved after treatment with conservative therapies. Erlotinib was re-administrated and PI occurred again. After improvement of erlotinib-induced PI, gefitinib was administered by a feeding tube and the patient did not experience PI or diarrhea. The patient survived 8 months from the diagnosis of LM. Conclusion PI is one of the side effects of erlotinib, and consecutive therapies are useful for the treatment of PI. In this patient, gefitinib was successfully administered after erlotinib-induced PI

Pneumatosis intestinalis induced by osimertinib in a patient with lung adenocarcinoma harbouring epidermal growth factor receptor gene mutation with simultaneously detected exon 19 deletion and T790 M point mutation: a case report

Abstract Background Pneumatosis intestinalis is a rare adverse event that occurs in patients with lung cancer, especially those undergoing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Osimertinib is the most recently approved EGFR-TKI, and its usage is increasing in clinical practice for lung cancer patients who have mutations in the EGFR gene. Case presentation A 74-year-old woman with clinical stage IV (T2aN2M1b) lung adenocarcinoma was determined to have EGFR gene mutations, namely a deletion in exon 19 and a point mutation (T790 M) in exon 20. Osimertinib was started as seventh-line therapy. Follow-up computed tomography on the 97th day after osimertinib administration incidentally demonstrated intra-mural air in the transverse colon, as well as intrahepatic portal vein gas. Pneumatosis intestinalis and portal vein gas improved by fasting and temporary interruption of osimertinib. Osimertinib was then restarted and continued without recurrence of pneumatosis intestinalis. Overall, following progression-free survival of 12.2 months, with an overall duration of administration of 19.4 months (581 days), osimertinib was continued during beyond-progressive disease status, until a few days before the patient died of lung cancer. Conclusions Pneumatosis intestinalis should be noted as an important adverse event that can occur with administration of osimertinib; thus far, such an event has never been reported. This was a valuable case in which osimertinib was successfully restarted after complete recovery from pneumatosis intestinalis, such that further extended administration of osimertinib was achieved

Increased Metabolite Levels of Glycolysis and Pentose Phosphate Pathway in Rabbit Atherosclerotic Arteries and Hypoxic Macrophage

<div><p>Aims</p><p>Inflammation and possibly hypoxia largely affect glucose utilization in atherosclerotic arteries, which could alter many metabolic systems. However, metabolic changes in atherosclerotic plaques remain unknown. The present study aims to identify changes in metabolic systems relative to glucose uptake and hypoxia in rabbit atherosclerotic arteries and cultured macrophages.</p><p>Methods</p><p>Macrophage-rich or smooth muscle cell (SMC)-rich neointima was created by balloon injury in the iliac-femoral arteries of rabbits fed with a 0.5% cholesterol diet or a conventional diet. THP-1 macrophages stimulated with lipopolysaccharides (LPS) and interferon-γ (INFγ) were cultured under normoxic and hypoxic conditions. We evaluated comprehensive arterial and macrophage metabolism by performing metabolomic analyses using capillary electrophoresis-time of flight mass spectrometry. We evaluated glucose uptake and its relationship to vascular hypoxia using ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) and pimonidazole, a marker of hypoxia.</p><p>Results</p><p>The levels of many metabolites increased in the iliac-femoral arteries with macrophage-rich neointima, compared with those that were not injured and those with SMC-rich neointima (glycolysis, 4 of 9; pentose phosphate pathway, 4 of 6; tricarboxylic acid cycle, 4 of 6; nucleotides, 10 of 20). The uptake of ¹⁸F-FDG in arterial walls measured by autoradiography positively correlated with macrophage- and pimonidazole-immunopositive areas (r = 0.76, and r = 0.59 respectively; n = 69 for both; p<0.0001). Pimonidazole immunoreactivity was closely localized with the nuclear translocation of hypoxia inducible factor-1α and hexokinase II expression in macrophage-rich neointima. The levels of glycolytic (8 of 8) and pentose phosphate pathway (4 of 6) metabolites increased in LPS and INFγ stimulated macrophages under hypoxic but not normoxic condition. Plasminogen activator inhibitor-1 protein levels in the supernatant were closely associated with metabolic pathways in the macrophages.</p><p>Conclusion</p><p>Infiltrative macrophages in atherosclerotic arteries might affect metabolic systems, and hypoxia but not classical activation might augment glycolytic and pentose phosphate pathways in macrophages.</p></div