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Biomedical subjects

Hitoshi Imaizumi

Publications and source records attributed to Hitoshi Imaizumi.

15 recordsLinked to original sources

New high mobility group box 1 assay system.

BACKGROUND: High-sensitivity sandwich ELISA methods have been developed using chemiluminescent substrates. HMGB1 (high mobility group box 1) protein has been shown to play a critical role in several inflammatory diseases and it may be involved in the development of atherosclerosis. METHODS: Anti-human HMGB1 monoclonal antibodies and anti-peptide polyclonal antibodies against the peptide sequence (KPDAAKKGVVKAEK) with high antigenicity and different from the sequence of HMGB2 were developed, and the antibodies were used to construct sandwich ELISA methods with a chromogenic substrate (TMBZ) and a chemiluminescent substrate (PS-atto). Highly purified human HMGB1 was used as a standard material and high-sensitivity CRP was measured to compare with HMGB1. RESULTS: The analytical characteristics of the ELISA method we developed were validated inter-assay and intra-assay CVs were <10%, and the detection limit was 0.3 microg/l by the chemiluminescent method and 1 microg/l with the chromogenic substrates. HMGB1 was detected in the serum of patients with acute coronary syndrome (ACS). When a cut-off of 0.6 microg/l HMGB1 upon admission to the intensive care unit (ICU) was used, the risk of developing an acute cardiac event within 1 month after discharge of ACS patients with an abnormal HMGB1 was significantly higher than for the patients with normal values (P<0.0001). The usefulness of HMGB1 as an acute prognostic marker was suggested. CONCLUSIONS: The assay is easy to perform and suitable for use in the hospital laboratory and for screening large populations. HMGB1 is detectable in the serum of ACS patients and that the serum concentration of HMGB1 may be a prognostic indicator in ACS patients.

Amino Acid Sequence↗

Anandamide absorption by direct hemoperfusion with polymixin B-immobilized fiber improves the prognosis and organ failure assessment score in patients with sepsis.

PURPOSE: Direct hemoperfusion (DHP) with polymixin B-immobilized fiber (PMX) has been reported to be effective for patients with septic shock. The aim of this study was to clarify the mechanism of PMX-DHP effect on septic shock. METHODS: The following parameters were measured in septic shock patients who were treated with PMX-DHP: survival rate, sepsis-related organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE-II) score, and plasma concentrations of cannabinoids [anandamide (ANA) and 2-arachidonyl glyceride (2-AG)], cytokines [interleukin (IL)-6, IL-8, IL-10], transforming growth factor beta (TGF-beta), and calcitonin gene-related peptide (CGRP)]. The primary end point was mortality from all causes at day 28 after intensive care unit (ICU) admission or discharge. RESULTS: The survival rate of all patients at 28 days after ICU admission was 37.5% (9/24). The survival group showed significantly lower SOFA and APACHE-II scores than the nonsurvival group after PMX-DHP treatment (P = 0.008 and 0.028, respectively). The improved SOFA score group showed a better survival rate than the nonimproved SOFA score group (71.4% versus 23.5%, P = 0.028). Plasma ANA level significantly decreased after PMX-DHP treatment both in the improved SOFA score group and in the survival group. The level of 2-AG, however, showed no significant change in either group. CONCLUSION: ANA, an intrinsic cannabinoid that induces hypotension in septic shock, is inferred to be the main mechanism of the PMX-DHP effect. Removal of ANA by PMX-DHP could be key to successful septic shock treatment.

APACHE↗

Neuronal cell injury in patients after cardiopulmonary resuscitation: evaluation by diffusion-weighted imaging and magnetic resonance spectroscopy.

Neuronal cell injury after global cerebral ischemic insult is not well understood in humans. We performed serial examination of diffusion-weighted imaging and magnetic resonance spectroscopy in three patients after cardiopulmonary resuscitation. The presence of the signal for lactate in magnetic resonance spectroscopy in the acute stage after cardiopulmonary resuscitation was closely correlated to irreversible damage. In addition, high intensity in diffusion-weighted magnetic resonance image in the acute stage also predicted a poor outcome. Lesions that were positive for these factors in the acute stage led to serious brain damage in the subacute and chronic stages. The results indicated that after cardiopulmonary resuscitation, diffusion-weighted magnetic resonance imaging and magnetic resonance spectroscopy is an extremely useful modality to estimate the prognosis of patients, which is not always easy using conventional methods.

Aged↗

Septic thrombophlebitis of the portal and superior mesenteric veins as a complication of appendicitis: report of a case.

Pylephlebitis is extremely rare and associated with high mortality, even in this modern era. It usually occurs secondary to infection in the region drained by the portal systems or in the structure contiguous to the portal vein. We report a case of septic thrombophlebitis of the portal and superior mesenteric veins (SMV) with multiple liver abscesses caused by acute appendicitis with an abscess of the mesoappendix. We performed appendectomy and successfully removed the thrombi using a Fogarty catheter. Postoperative histopathological examination confirmed a diagnosis of appendicitis and septic thrombophlebitis of the portal vein and SMV. The patient recovered completely with appropriate medical and surgical treatment.

Adolescent↗

Transient phrenic nerve palsy after cardiac operation in infants.

OBJECTIVE: The aims of this study were to prove the presence of transient phrenic nerve palsy in children after cardiac surgery by successive recordings of diaphragmatic action potentials (DAPs), and to decide the indication of diaphragmatic plication in infants with postoperative phrenic nerve palsy. METHODS: The DAPs were recorded from 11 infants (age 0-54 months) under artificial ventilation after cardiac surgery. The successive DAP recordings were performed within 3-4 days (0W), 1 week (1W) and 2 weeks (2W) after operation to make a final decision for diaphragmatic plication to wean artificial ventilation. RESULTS: The patients were divided into 3 groups according to the DAP changes in successive recordings, namely, patients with normal DAPs at 0W, patients with transient depression of DAPs at 0W followed by recovery to normal DAPs by 1W and/or 2W, and patients with persistent depression of DAPs of the affected side necessitating plication of hemidiaphragm. CONCLUSIONS: In infants with phrenic nerve palsy after cardiothoracic surgery, persistently abnormal DAPs in repeated electrophysiologic examinations for at least 2 weeks after surgery are a useful guidance to support clinical and radiological evidence for an indication of diaphragmatic plication.

Action Potentials↗

[A case of pulmonary thromboembolism after cardiac surgery].

It has been reported that pulmonary thromboembolism (PTE) is a major complication in the post-operative period. However, there have been few reports on PTE after cardiopulmonary bypass (CPB). We report a case of PTE that occurred after cardiac surgery using CPB. A 76-year-old female patient underwent aorto-coronary graft bypass and mitral valve plasty because of ischemic heart disease and mitral valve regurgitation, respectively. The results of blood gas analysis after cardiopulmonary bypass showed no abnormalities. Immediately after ICU admission, the oxygenation index (PaO2/FIO2) of the patient was below 100, and the low level persisted despite decrease in interstitial fluid volume of the lung. Evaluations of hemodynamics using ultrasound echography and a Swan-Ganz catheter showed no findings associated with right heart failure. The results of lung perfusion scintigraphy performed on the 6th postoperative day (POD), revealed the decline in radioactivities in the upper and middle lobe areas of the right lung. Urokinase was therefore administered intravenously from the 6th to 9th POD. The oxygenation index increased dramatically after urokinase administration. Although the use of thrombolytic therapy in an early postoperative period is controversial, our patient was successfully treated with urokinase without a life-threatening bleeding tendency.

Aged↗

[Two cases of negative pressure pulmonary edema after induction of anesthesia and extubation].

Two cases of negative pressure pulmonary edema are described. In one case, tracheal intubation was not successful and airway obstruction occurred after induction of anesthesia. Spontaneous breathing was restored by reversal of neuromuscular blocking action, but airway obstruction persisted. Urgent tracheostomy was therefore performed. A chest x-ray and clinical features indicated pulmonary edema immediately after tracheostomy. Treatment with mechanical ventilation and positive end-expiratory pressure improved pulmonary edema. In the other case, airway obstruction occurred after extubation. Removal of secretion in the oral cavity and assisted ventilation improved airway obstruction, but pulmonary edema was found by chest x-ray. Forced diuresis using furosemide and oxygen inhalation resulted in the improvement of pulmonary edema. Fortunatetly, in both cases, significant complications associated with pulmonary edema did not occur. Care should be taken of the risk of pulmonary edema when the airway was obstructed after induction of anesthesia or extubation under spontaneous breathing.

Adult↗

[Comparison of surgical versus endovascular stent-graft repair of thoracic and thoracoabdominal aortic aneurysms in terms of postoperative organ failure].

BACKGROUND: We conducted this study to clarify whether the incidence of organ failure after endovascular stent-graft repair of thoracic aneurysm (TAA) and thoracoabdominal aneurysm (TAAA) is much higher than that after surgical repair. METHODS: The diseases for surgical repair (surgical group) were TAA in 29 patients and TAAA in 19 patients. Fourteen patients underwent stent-graft repair for TAA and TAAA (stent group). Incidences of preoperative complications in the two groups were compared. Postoperative organ failures, changes in SOFA score and numbers of SIRS criteria were assessed over a period of 7 postoperative days. RESULTS: Although the incidence of preoperative complications in the stent group was significantly higher than that in the surgical group, postoperative organ failure in the surgical group was more frequent than that in the stent group. SOFA score in the stent group during the first 3 postoperative days was significantly smaller than that in the surgical group. However, the number of SIRS criteria in the stent group was significantly higher than that in the surgical group on the first postoperative day. CONCLUSIONS: Endovascular stent-graft repair for arotic aneurysm may be less invasive, leading to a reduction in the incidence of postoperative organ failure in high-risk patients.

Aged↗

Direct binding of Toll-like receptor 2 to zymosan, and zymosan-induced NF-kappa B activation and TNF-alpha secretion are down-regulated by lung collectin surfactant protein A.

The lung collectin surfactant protein A (SP-A) has been implicated in the regulation of pulmonary host defense and inflammation. Zymosan induces proinflammatory cytokines in immune cells. Toll-like receptor (TLR)2 has been shown to be involved in zymosan-induced signaling. We first investigated the interaction of TLR2 with zymosan. Zymosan cosedimented the soluble form of rTLR2 possessing the putative extracellular domain (sTLR2). sTLR2 directly bound to zymosan with an apparent binding constant of 48 nM. We next examined whether SP-A modulated zymosan-induced cellular responses. SP-A significantly attenuated zymosan-induced TNF-alpha secretion in RAW264.7 cells and alveolar macrophages in a concentration-dependent manner. Although zymosan failed to cosediment SP-A, SP-A significantly reduced zymosan-elicited NF-kappaB activation in TLR2-transfected human embryonic kidney 293 cells. Because we have shown that SP-A binds to sTLR2, we also examined whether SP-A affected the binding of sTLR2 to zymosan. SP-A significantly attenuated the direct binding of sTLR2 to zymosan in a concentration-dependent fashion. From these results, we conclude that 1) TLR2 directly binds zymosan, 2) SP-A can alter zymosan-TLR2 interaction, and 3) SP-A down-regulates TLR2-mediated signaling and TNF-alpha secretion stimulated by zymosan. This study supports an important role of SP-A in controlling pulmonary inflammation caused by microbial pathogens.

Animals↗

Membrane cholesterol but not putative receptors mediates anandamide-induced hepatocyte apoptosis.

The endogenous cannabinoid anandamide, a lipid mediator, induces various physiologic events such as vascular relaxation, inhibition of gap-junctions formation, tumor proliferation, neurologic analgesia, and apoptosis. Although increased concentration of anandamide in plasma has been implicated in pathophysiologic states including endotoxin-induced hypotension, the effects of anandamide on hepatocytes still remain unclear. In this study, we present evidence that plasma anandamide concentration is highly increased in severe hepatitis and cirrhosis patients. In addition, concentrations of anandamide within the pathophysiologic range potently induced apoptosis of hepatoma cell line (Hep G2) and primary hepatocytes, suggesting a possible link between increased anandamide level and hepatocyte damage. Anandamide-induced cell death was preceded by G0/G1 cell-cycle arrest, activation of proapoptotic signaling (i.e., p38 MAPK and JNK), and inhibition of antiapoptotic signaling (i.e., PKB/Akt) pathways. Moreover, anandamide increased susceptibility to oxidative stress-induced hepatocyte damage. In this context, methyl-beta-cyclodextrin (MCD), a membrane cholesterol depletor, or mevastatin, an HMG-CoA reductase inhibitor, or N-acetyl cysteine, an antioxidant, potently inhibited the anandamide-induced proapoptotic events and cell death, whereas putative cannabinoid receptor antagonists did not exhibit an inhibitory effect on anandamide-induced cell death. Furthermore, binding assay using polymyxin beads revealed that anandamide could interact with cholesterol. In conclusion, our data suggest that cholesterol present in the cell membrane determines the fate of hepatocytes exposed to anandamide, possibly functioning as an anandamide receptor.

Animals↗

Changes in circulating levels of calcitonin gene-related peptide and nitric oxide metabolites in septic patients during direct hemoperfusion with polymyxin B-immobilized fiber.

BACKGROUND/AIMS: This study evaluated the mechanism of hemodynamic improvement in polymyxin B-immobilized fiber (PMX) treatment. METHODS: Fifteen septic patients with endotoxemia and/or gram negative infection were treated with PMX. Plasma concentrations of calcitonin gene-related peptide (CGRP) and nitric oxide metabolites were measured. RESULTS: CGRP and nitric oxide metabolites before treatment were significantly higher than in healthy controls. CGRP had a significantly inverse correlation with diastolic blood pressure and a positive correlation with the Septic Severity Score and the number of failed organs. Systolic and diastolic blood pressure and systemic vascular resistance index increased significantly both immediately after and 24 h after PMX treatment. CGRP decreased significantly 24 h after the treatment. In contrast, there were no significant changes in nitric oxide metabolites. CONCLUSION: PMX treatment improved hemodynamic parameters in septic patients, and CGRP increased with increasing severity of sepsis. We conclude that a decrease in CGRP levels may be related to hemodynamic improvement resulting from PMX treatments.

Aged↗

[Anesthesia for a patient with xeroderma pigmentosum].

The anesthetic management of a patient with xeroderma pigmentosum is described. A 17-year-old woman underwent tracheostomy because of progressive recurrent nerve palsy. The operation was performed uneventfully under general anesthesia using propofol and fentanyl. Xeroderma pigmentosum (XP) is an autosomal recessive disease that is characterized by hypersensitivity to sunlight with a high incidence of skin cancer and exhibits variable neurological abnormalities. Classical types of XP have a defect in nucleotide excision repair (NER). It has been reported that volatile anesthetics such as halothane deranged NER in cells obtained from an XP patient. Thus, general anesthesia using volatile agents should be avoided, if possible, because inhalation anesthetics may worsen the symptoms of XP.

Adolescent↗

Hyperbaric oxygen stimulates cell proliferation and normalizes multidrug resistance protein-2 protein localization in primary rat hepatocytes.

Hyperbaric oxygen therapy (HBO) has been used for many clinical treatments, including primary liver non-function. However, the cellular mechanism by which HBO treatment ameliorates liver function is not understood. Therefore, the purpose of this study was to elucidate this cellular mechanism using primary cultured rat hepatocytes in in vitro studies. Hepatocytes were treated with HBO at 1 day after plating, and the morphological and functional characteristics of bile canaliculi formed in cultured hepatocytes were observed by time-lapse microscopy. Multidrug resistance protein-2 localization was observed by confocal laser microscopy. In cultured hepatocytes, the labeling index in the HBO group at 2 days after treatment was significantly higher than that in the control group. In addition, the proliferating cellular nuclear antigen level in the HBO group was significantly higher than that in the control group. The contraction of the bile canaliculi in the HBO group was slower than in the control group and the dilatation of bile canaliculi in the HBO group was much larger than in the control group. Multidrug resistance protein-2 in the HBO group was localized at the apical membrane. These results show that HBO stimulates hepatocytes to proliferate and HBO normalizes multidrug resistance protein-2 localization to the apical membrane, which could dilate bile canaliculi.

ATP Binding Cassette Transporter, Subfamily B↗