Survey on antiemetic therapy in ambulatory cancer chemotherapy and medical economics for standardization

A cancer chemotherapy unit was established to support therapy for outpatients with cancer in Hirosaki University Hospital. It is essential to standardize antiemetic therapy, since a wide variety of the therapy provided to the unit from the diagnosis and treatment departments were conventional and empirical. We surveyed the use conditions and compatibility of the therapy based on reliable guidelines, and then considered the medical economics for standardization. In moderate-grade emetogenic chemotherapy, 5-HT(3) receptor antagonists tended to be used frequently instead of the recommended steroids. From this survey, the standardization of the cost of 5-HT(3) receptor antagonists and the relatively inexpensive steroids used in cancer chemotherapy might reduce either the nausea or vomiting suffered by patients with cancer and their economic burden as well.     

Evaluation of the anti-allergic activity of Citrus unshiu using rat basophilic leukemia RBL-2H3 cells as well as basophils of patients with seasonal allergic rhinitis to pollen

The anti-allergic activity of the 50% methanol extract of Citrus unshiu powder (MEC) was examined. Fifty percent methanol extract of MEC powder showed potent inhibitory activity against histamine release from basophils of patients suffering from seasonal allergic rhinitis to ceder pollen. To examine this anti-allergic mechanism in detail, we next used rat basophlilic leukemia RBL-2H3 cells. MEC significantly inhibited IgE-induced histamine and beta-hexosaminidase release from RBL-2H3 cells. Since MEC contains a variety of flavonoids, we selected nobiletin, hesperetin, and hesperidin (hesperetin glycoside) as representative compounds, and further evaluated these inhibitory activities. Among the flavonoids tested, hesperetin was the most potent, while hesperidin had far less, if any, inhibitory activity. The mechanism by which flavonoids inhibited the degranulation process was then examined. As a result, hesperetin and nobiletin suppressed the phosphorylation of Akt-1, direct downstream effector of phosphatidylinositol 3-kinase (PI3-K). Thus, it was assumed that these flavonoids suppressed IgE-mediated stimulation of basophils through PI3-K pathway and that proper intake of Citrus unshiu would be favorable for managing seasonal allergic rhinitis to ceder pollen.     

Skeletal muscle energetics with PNMR: personal views and historic perspectives

This article reviews historical and current NMR approaches to describing in vivo bioenergetics of skeletal muscles in normal and diseased populations. It draws upon the first author's more than 70 years of personal experience in enzyme kinetics and the last author's physiological approaches. The development of in vivo PNMR jointly with researchers around the world is described. It is explained how non-invasive PNMR has advanced human exercise biochemistry, physiology and pathology. Further, after a brief explanation of bioenergetics with PNMR on creatine kinase, anerobic glycolysis and mitochondrial oxidative phosphorylation, some basic and controversial subjects are focused upon, and the authors' view of the subjects are offered, with questions and answers. Some of the research has been introduced in exercise physiology. Future directions of NMR on bioenergetics, as a part of system biological approaches, are indicated.     

The superior group of vessels in the falciform ligament: anatomical and radiological correlation

AIM: The purpose of this study was to clarify the anatomical detail of the superior group of vessels in the falciform ligament in terms of the relationship with the internal thoracic vessels, inferior phrenic vessels, and the intrahepatic portal vein. MATERIALS AND METHODS: (1) Anatomical study: we dissected eight adult human cadavers (seven normal and one cirrhotic liver) to determine the relationship between the superior group of vessels in the falciform ligament, the internal thoracic vessels, and the inferior phrenic vessels. (2) Clinical study: we determined the origin and destination of the superior group of veins demonstrated in 8 of 4,006 patients with chronic liver disease who underwent the contrast enhanced CT scans. RESULTS: (1) Anatomical study: the superior group of vessels anastomosed the right (n = 4), left (n = 2), and both (n = 2) internal thoracic vessels. They also anastomosed the left (n = 4), right (n = 1), and both (n = 2) inferior phrenic vessels. (2) Clinical study: the origin of the veins was identified as the left medial branch (n = 4), left lateral branch (n = 1), both the lateral and medial branches (n = 1), and the vein from the umbilical portion (n = 2) of the left portal vein. The drainage vein was identified as the left (n = 3), right (n = 2), and the both (n = 1) internal thoracic veins. CONCLUSION: We demonstrated the anastomoses between the superior group of vessels of the falciform ligament, the internal thoracic vessels, the inferior phrenic vessels, and the intrahepatic portal vein. These pre-existing anastomoses would develop as porto-systemic shunt in patients with portal hypertension.     

Interaction of LDL receptor-related protein 4 (LRP4) with postsynaptic scaffold proteins via its C-terminal PDZ domain-binding motif, and its regulation by Ca/calmodulin-dependent protein kinase II

We cloned here a full-length cDNA of Dem26[Tian et al. (1999)Mol. Brain Res., 72, 147-157], a member of the low-density lipoprotein (LDL) receptor gene family from the rat brain. We originally named the corresponding protein synaptic LDL receptor-related protein (synLRP) [Tian et al. (2002) Soc. Neurosci. Abstr., 28, 405] and have renamed it LRP4 to accord it systematic nomenclature (GenBank(TM) accession no. AB073317). LRP4 protein interacted with postsynaptic scaffold proteins such as postsynaptic density (PSD)-95 via its C-terminal tail sequence, and associated with N-methyl-D-aspartate (NMDA)-type glutamate receptor subunit. The mRNA of LRP4 was localized to dendrites, as well as somas, of neuronal cells, and the full-length protein of 250 kDa was highly concentrated in the brain and localized to various subcellular compartments in the brain, including synaptic fractions. Immunocytochemical study using cultured cortical neurons suggested surface localization in the neuronal cells both in somas and dendrites. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) phosphorylated the C-terminal cytoplasmic region of LRP4 at Ser1887 and Ser1900, and the phosphorylation at the latter site suppressed the interaction of the protein with PSD-95 and synapse-associated protein 97 (SAP97). These findings suggest a postsynaptic role for LRP4, a putative endocytic multiligand receptor, and a mechanism in which CaMKII regulates PDZ-dependent protein-protein interactions and receptor dynamics.     

Human MT/V5 activity on viewing eye gaze changes in others: A magnetoencephalographic study

The present study used magnetoencephalography (MEG) to investigate human MT/V5 activity when observing changes in eye gaze. Subjects viewed a face in which the eyes changed to look either directly at (BACK) or away from (AWAY) the subject in a series of apparent motion conditions. BACK involved 2 directions, from left to center (LC) and from right to center (RC). Likewise, AWAY involved 2 directions, from center to left (CL) and from center to right (CR). A clear MEG component, 1M, was elicited with all eye gaze changes. Mean peak latency was 157 ms and was unaffected by stimulus condition. The equivalent current dipole (ECD) was localized to human MT/V5. Two main effects were noted: (1) ECD moment was significantly larger for BACK than for AWAY; and (2) 1M ECD locations were more posterior for AWAY than for BACK. Gaze direction, with LEFT involving CL and RC and RIGHT involving CR and LC, showed no significant effects. These data indicate that MT/V5 responds to gaze direction rather than eye position, and that eye movements directed at the viewer elicit the strongest effects. Processing of gaze change is NOT sensitive to eye direction per se but rather is modulated by eye gaze relative to the viewer.     

Cerebral ischemia and angiogenesis

Angiogenesis occurs in a wide range of conditions. As ischemic tissue usually depends on collateral blood flow from newly produced vessels, acceleration of angiogenesis should be of therapeutic value to ischemic disorders. Indeed, therapeutic angiogenesis reduced tissue injury in myocardial or limb ischemia. In ischemic stroke, on the other hand, angiogenic factors often increase vascular permeability and thus may deteriorate tissue damage. In order to apply safely the therapeutic angiogenesis for ischemic stroke treatment, elucidating precise mechanism of brain angiogenesis is mandatory. In the present article, we review previous reports which investigated molecular mechanisms of angiogenesis. Endothelial cell mitogens, enzymes that degrade surrounding extracellular matrix, and molecules implicated in endothelial cells migration are induced rapidly in the ischemic brain. Their possible neuroprotective or injury exacerbating effects are discussed. Because therapeutic potential of angiogenic factors application had gained much attention, we here extensively reviewed relevant previous reports. In the future however, there is a need to consider angiogenesis in relation with regenerative medicine, as angiogenic factors sometimes possess neuron producing property.     

Functional analysis of a novel missense NBC1 mutation and of other mutations causing proximal renal tubular acidosis

Mutations in the cotransporter NBC1 cause severe proximal tubular acidosis (pRTA) associated with ocular abnormalities. Recent studies have suggested that at least some NBC1 mutants show abnormal trafficking in the polarized cells. This study identified a new homozygous NBC1 mutation (G486R) in a patient with severe pRTA. Functional analysis in Xenopus oocytes failed to detect the G486R activity due to poor surface expression. In ECV304 cells, however, G486R showed the efficient membrane expression, and its transport activity corresponded to approximately 50% of wild-type (WT) activity. In Madin–Darby canine kidney (MDCK) cells, G486R was predominantly expressed in the basolateral membrane domain as observed for WT. Among the previously identified NBC1 mutants that showed poor surface expression in oocytes, T485S showed the predominant basolateral expression in MDCK cells. On the other hand, L522P was exclusively retained in the cytoplasm in ECV304 and MDCK cells, and functional analysis in ECV304 cells failed to detect its transport activity. These results indicate that G486R, like T485S, is a partial loss of function mutation without major trafficking abnormalities, while L522P causes the clinical phenotypes mainly through its inability to reach the plasma membranes. Multiple experimental approaches would be required to elucidate potential disease mechanism by NBC1 mutations.     

Sequence analysis of the capsid gene of Aichi viruses detected from Japan, Bangladesh, Thailand, and Vietnam

Sequence analysis of the capsid gene of Aichi viruses was performed on 12 strains detected in Japan, Bangladesh, Thailand, and Vietnam during 2002-2005. The phylogenetic tree constructed from 17 nucleotide sequences of the capsid gene of the strains studied and reference strains demonstrated that Aichi virus strains clustered into two branches. A classification of Aichi viruses based on the capsid gene was proposed, in which lineage I consists of the Aichi virus strains detected from Japan, Thailand, Vietnam, and Germany, and lineage II includes Bangladeshi strains and a Brazilian strain.