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Biomedical subjects

K Nakajima

Publications and source records attributed to K Nakajima.

At least 19 recordsLinked to original sources

A novel method for measuring human hepatic lipase activity in postheparin plasma.

The objective of this study was to establish a hepatic lipase (HL) assay method that can be applied to automatic clinical analyzers. Seventy-four hyperlipidemic subjects (men/women 45/29) were recruited. Lipase activity was assayed measuring the increase in absorbance at 546 nm due to quinonediimine dye production. Reaction mixture R-1 contained 50 mM Tris-HCl (pH 9.5), 0.5 mM glycerol-1,2-dioleate, 0.4% (unless otherwise noted) polyoxyethylene-nonylphenylether, 3 mM ATP, 3 mM MgCl(2), 1.5 mM CaCl(2), monoacylglycerol-specific lipase, glycerol kinase, glycerol-3-phosphate oxidase, 0.075% N,N-bis-(4-sulfobutyl)-3-methylaniline-2 Na, peroxidase, ascorbic acid oxidase. Reaction mixture R-2 contained 50 mM Tris-HCl (pH9.5), 0.15% 4-aminoantypirine. Automated assay for activity was performed with a Model 7080 Hitachi analyzer. In the lipase assay, 160 microl of R-1 was incubated at 37 degrees C with 3 microl of samples for 5 min, and 80 microl of R-2 was added. Within-run coefficient of variations was 0.9-1.0%. Calibration curve of lipase activity was linear (r = 0.999) between 0 and 320 U/l. Analytical recoveries of purified HL added to plasma were 96.6-99.8%. HL activity in postheparin plasma measured in this method had a closer correlation with HL mass by a sandwich ELISA (r = 0.888, P < 0.0001) than those in the conventional method using [(14)C-]triolein (r = 0.730, P < 0.0001). This assay method for HL activity can be applied to an automatic clinical analyzer.

Adult↗

Value of 123I-MIBG radioactivity in the differential diagnosis of DLB from AD.

OBJECTIVE: To evaluate the diagnostic reliability of cardiac iodine-123 metaiodobenzylguanidine ((123)I-MIBG) radioactivity in discriminating dementia with Lewy bodies (DLB) from Alzheimer disease (AD) regardless of parkinsonism. BACKGROUND: The diagnosis of DLB may be confounded by the absence of parkinsonism. This highlights the need to improve the accuracy of antemortem diagnosis of DLB without parkinsonism. METHODS: Cardiac sympathetic denervation was examined using myocardial (123)I-MIBG scintigraphy in 37 patients with DLB, 42 patients with AD, and 10 normal elderly controls. The DLB patients consisted of seven patients without parkinsonism (DLB/P-) and 30 patients with parkinsonism (DLB/P+) at the time of the study. RESULTS: The heart-to-mediastinum uptake ratio (H/M ratio) of myocardial MIBG uptake was decreased in both the DLB groups vs the AD group (p < 0.0001) and control group (p < 0.0001). The washout rate (WR) was higher in the DLB group than in the control group (p < 0.0001) and AD group (p < 0.0001). No differences were found between the AD and control groups or between the DLB/P+ and DLB/P- groups in either the early or delayed H/M ratio or WR. In discriminating between DLB and AD, regardless of parkinsonism, the delayed H/M ratio had a sensitivity of 100%, a specificity of 100%, and a positive predictive value of 100% at a cutoff value of 1.68. CONCLUSIONS: Our results indicate that dementia with Lewy bodies results in cardiac sympathetic denervation and that iodine-123 metaiodobenzylguanidine myocardial scintigraphy is a sensitive tool for discriminating dementia with Lewy bodies from Alzheimer disease even in patients without parkinsonism.

3-Iodobenzylguanidine↗

Laparoscopically assisted total gastrectomy with jejunal pouch interposition.

BACKGROUND: Jejunal pouch interposition (JPI) is known as a useful gastric replacement procedure after total gastrectomy. The JPI procedure, however, has not been applicable to laparoscopically assisted total gastrectomy (LATG) because of its technical complexity and difficulty. This study aimed to describe our modified LATG/JPI technique, and to evaluate its feasibility, safety, and early postoperative functional outcome. METHODS: Between September 2002 and August 2003, LATG/JPI was attempted for five patients (3 men and 2 women) with early gastric cancers in the upper portion of the stomach. The mean age of the patients was 57 years, and their BMI was 21 kg/m2. Using a 5-port technique, the gastric arteries were laparoscopically clipped and divided with adequate lymphatic dissection. After completion of gastric resection, the anvil of a circular stapling device was placed in the esophageal stump. An 8-cm minilaparotomy then was performed, and the 12-cm pouch was created extracorporeally in the "reverse U" fashion. The stapled pouch-esophagostomy was performed under laparoscopic monitoring. The remainder of the procedure was accomplished under direct vision. RESULTS: All cases were managed laparoscopically without any complications. The mean operating time was 407 min, and the blood loss was 279 ml. All the patients showed rapid and uneventful recovery. Postoperative studies, including dual scintigraphy, showed that all jejunal pouches were satisfactorily functioning. CONCLUSIONS: This study showed LATG/JPI to be feasible and safe. With technical modifications, LATG/JPI can become a potentially effective option for improving patients' quality of life after total gastrectomy.

Feasibility Studies↗

Search for the invisible decay of neutrons with KamLAND.

The Kamioka Liquid scintillator Anti-Neutrino Detector is used in a search for single neutron or two-neutron intranuclear disappearance that would produce holes in the -shell energy level of (12)C nuclei. Such holes could be created as a result of nucleon decay into invisible modes (inv), e.g., n--> 3v or nn--> 2v. The deexcitation of the corresponding daughter nucleus results in a sequence of space and time-correlated events observable in the liquid scintillator detector. We report on new limits for one- and two-neutron disappearance: tau(n--> inv) > 5.8 x 10(29) years and tau (nn--> inv) > 1.4 x 10(30) years at 90% C.L. These results represent an improvement of factors of approximately 3 and >10(4) and over previous experiments.

Journal Article↗

Requirement of STAT3 activation for maximal collagenase-1 (MMP-1) induction by epidermal growth factor and malignant characteristics in T24 bladder cancer cells.

Signal transducers and activators of transcription (STATs) are latent transcription factors that mediate cytokine- and growth factor-induced transcription. Constitutive activation of STAT3 has been shown in human cancers and transformed cell lines. We report that STAT3, but not STAT1 and STAT5, becomes phosphorylated in response to epidermal growth factor (EGF) and achieves maximal induction of collagenase-1 (MMP-1) transcription by interacting with c-JUN. Phosphorylation of STAT3 protein is biphasic: the first peak within 30 min and the second peak between 4 and 8 h. Association of STAT3 with c-JUN is detected and its constituting STAT3 is increasingly phosphorylated. The STAT and AP-1 elements are necessary for effective induction of MMP-1 promoter by EGF. Mutation of AP-1 element closely located at the STAT site abolishes the binding not only of c-JUN but also of STAT3 to MMP-1 promoter, resulting in the loss of the responsiveness to EGF. By blocking STAT3 activity with the dominant-negative form, we show the requirement of STAT3 for EGF induction of MMP-1 and MMP-10 (stromelysin-2). Furthermore, expression of the dominant-negative STAT3 is sufficient to inhibit the constitutive and EGF-inducible cell migration and invasion and the tumor formation in nude mice. These results demonstrate that STAT3 phosphorylation and its possible interaction with c-JUN are required for the strong responsiveness of MMP-1 to EGF, and STAT3 activation is crucial for exhibition of malignant characteristics in T24 bladder cancer cells.

Animals↗

Carbon dioxide insufflation attenuates parietal blood flow obstruction in distended colon: potential advantages of carbon dioxide insufflated colonoscopy.

BACKGROUND: Bowel distention after colonoscopy has been considered as a cause of blood flow disturbance. Carbon dioxide (CO2), with its higher absorbability and vasodilating effect, may reduce parietal blood flow disturbance of distended colon when used for intraluminal insufflation instead of air. The purpose of this study was to assess parietal blood flow of the colon distended with intraluminal air/CO2 insufflation. METHODS: A 5-cm segment of rat colon was insufflated with either air (air group) or CO2 (CO2 group). Two insufflation methods were employed: temporary insufflation up to an intraluminal pressure of 60 mmHg and continuous insufflation at a pressure of 5, 15, and 30 mmHg. Bowel distention and parietal blood flow measured by laser Doppler imaging were evaluated. RESULTS: For temporary insufflation, bowel distention was prolonged in the air group, whereas it rapidly resolved in the CO2 group. Parietal blood flow decreased in both groups; however, it recovered within 5 min in the CO2 group. For continuous insufflation, under 5 mmHg insufflation, blood flow decreased in the air group, whereas it increased in the CO2 group. Blood flow decreased in both groups under 15 mmHg insufflation; however, it decreased less in the CO2 group. There was a reverse relationship between insufflation pressure and blood flow difference. Inhibition of nitric oxide synthase, ATP-sensitive K+ channel, or heme oxygenase was ineffective against a CO2-induced increase in blood flow. CONCLUSION: CO2 insufflation preserved parietal blood flow not only by rapid resolution of bowel distention but also by its potential vasodilative effect.

Air↗

Lack of alpha2-antiplasmin improves cutaneous wound healing via over-released vascular endothelial growth factor-induced angiogenesis in wound lesions.

BACKGROUND: The fibrinolytic system is supposed to play an important role in the degradation of extracellular matrices for physiological and pathological tissue remodeling; however, the detailed mechanism regarding how this system affects cutaneous wound healing remains to be clarified. METHODS AND RESULTS: We performed experimental cutaneous wounding in mice with a deficiency of alpha(2)-antiplasmin (alpha(2)AP), which is a potent and specific plasmin inhibitor. We found that an accelerated wound closure was observed in alpha(2)AP-deficient (alpha(2)AP-/-) mice in comparison with wild type (WT) mice. Moreover, we observed that a greater increase of angiogenesis occurred in the process of wound healing in alpha(2)AP-/- mice than in the WT mice. Intriguingly, mRNA expression of vascular endothelial growth factor (VEGF), which is the best characterized positive regulator of angiogenesis, in wound lesions was found to show a greater increase in the early phase of the healing process in alpha(2)AP-/- mice than in WT mice. In addition, the amount of released-VEGF from the explanted fibroblasts of alpha(2)AP-/- mice increased dramatically more than in the WT mice. Finally, the intra-jugular administration of anti-VEGF antibody clearly suppressed the increased angiogenesis and accelerated wound closure in the wound lesion of alpha(2)AP-/- mice. CONCLUSION: The lack of alpha(2)AP markedly causes an over-release of VEGF from the fibroblasts in cutaneous wound lesions, thereby inducing angiogenesis around the area, and thus resulting in an accelerated-wound closure. CONCLUSIONS: This is the first report to describe the crucial role that alpha(2)AP plays following angiogenesis in the process of wound healing. Our results provide new insight into the role of alpha(2)AP on cutaneous wound healing.

Animals↗

Restraint stress enhances alveolar bone loss in an experimental rat model.

BACKGROUND AND OBJECTIVE: The purpose of the present study was to examine the effects of restraint stress on periodontal breakdown resulting from Porphyromonas gingivalis-challenged periodontitis in rats. MATERIAL AND METHODS: To examine the influence of restraint stress on periodontal breakdown, rats were orally challenged with the periodontal pathogen P. gingivalis. Twenty male, specific pathogen-free (SPF) 3-wk-old, Sprague-Dawley rats were divided into four groups: group A (controls), group B (exposed to restraint stress for 12 h/d for 22 d), group C (orally challenged with P. gingivalis), and group D (exposed to restraint stress for 12 h/d for 22 d and orally challenged with P. gingivalis). After 22 d, all animals were killed. The distance from the alveolar bone crest to the cemento-enamel junction was determined, concentrations of adrenocorticotropic hormone were measured as stress markers, and atrophy of the thymus and spleen were assessed. In addition, the furcation area of the maxillary molars was examined histologically, while gingival cytokine gene expression was assessed by mRNA using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In the restrained group, all stress markers were elevated, and the thymus and spleen were atrophied. Combined restraint stress and oral challenge with P. gingivalis resulted in significantly higher bone loss, and osteoclasts were observed. RT-PCR analysis revealed low cytokine gene expression in the restrained groups. CONCLUSION: These results suggest that the presence of restraint stress significantly enhances the progression of P. gingivalis-challenged periodontitis in rats.

Alveolar Bone Loss↗

[Successful removal of aberrant needles in the pericardium and lung].

A 28-year-old woman who had been diagnosed as schizophrenia was admitted to our hospital, complaining of chest pain. Her chest X-ray demonstrated 9 foreign bodies in the pericardium, lung and others. Her chest computed tomography (CT) confirmed needle-like shadows in the pericardium and lung. They were diagnosed as aberrant needles, and surgically removed. The intrapulmonary aberrant needle was removed with video-assisted thoracoscopic surgery. Aberrant needle in pericardium or lung should be removed surgically, because it is very dangerous. Intraoperative chest X-ray is always necessary before closing the wound to avoid leaving the residual fragments.

Adult↗

A versatile dual-channel carbon dioxide (CO2) insufflator for various CO2)applications. The prototype.

BACKGROUND: Carbon dioxide (CO2), with its rapid absorptive nature, has been proven superior to atmospheric air as an insufflating agent in various clinical settings. However, CO2 insufflation has not gained wide clinical acceptance, mainly because there has been no suitable feeding system. The authors therefore have developed a versatile "dual-channel" CO2 insufflator that facilitates wider use of CO2. The objectives of this study were to introduce the authors' prototype insufflator, to evaluate its safety and performance, and to validate CO2 application using the prototype. METHODS: The prototype insufflator provides one CO2 inlet connected to a regular CO2 gas cylinder and two CO2 outlets positioned on the front and back of the device, respectively. The CO2 gas fed from the cylinder is pressure-regulated and divided into two independent conduits inside the device. The front outlet feeds CO2 gas for pneumoperitoneum at an electronically controlled pressure and flow rate. The back channel supplies CO2 gas at a fixed flow rate, allowing manual control of insufflation for various purposes. The device was evaluated with canine models. RESULTS: The prototype was safe and performed well. The CO2 application (colonoscopy in this series) using the back channel was feasible while intact CO2 pneumoperitoneum was simultaneously maintained via the front channel. There were no device malfunctions. The serial abdominal x-rays indicated that intraluminal CO2 insufflation such as that used for CO2 colonoscopy caused less residual intestinal gas than conventional air insufflation. CONCLUSIONS: The dual-channel CO2 insufflator enabled two different modes of CO2 insufflation at the same time from a single CO2 cylinder. The authors are now improving the prototype to allow safer and wider usage of CO2 in the operating room.

Animals↗

Experimental investigation of geologically produced antineutrinos with KamLAND.

The detection of electron antineutrinos produced by natural radioactivity in the Earth could yield important geophysical information. The Kamioka liquid scintillator antineutrino detector (KamLAND) has the sensitivity to detect electron antineutrinos produced by the decay of 238U and 232Th within the Earth. Earth composition models suggest that the radiogenic power from these isotope decays is 16 TW, approximately half of the total measured heat dissipation rate from the Earth. Here we present results from a search for geoneutrinos with KamLAND. Assuming a Th/U mass concentration ratio of 3.9, the 90 per cent confidence interval for the total number of geoneutrinos detected is 4.5 to 54.2. This result is consistent with the central value of 19 predicted by geophysical models. Although our present data have limited statistical power, they nevertheless provide by direct means an upper limit (60 TW) for the radiogenic power of U and Th in the Earth, a quantity that is currently poorly constrained.

Journal Article↗

Polymorphism of the solute carrier family 12 (sodium/chloride transporters) member 3, SLC12A3, gene at exon 23 (+78G/A: Arg913Gln) is associated with elevation of urinary albumin excretion in Japanese patients with type 2 diabetes: a 10-year longitudinal study.

AIMS/HYPOTHESIS: We have shown previously that the SLC12A3 +78G/A polymorphism in exon 23 (Arg913Gln) was a new candidate for conferring susceptibility to diabetic nephropathy. The aim of this study was to confirm the effect of this polymorphism on the elevation of urinary albumin excretion in type 2 diabetic patients. METHODS: We retrospectively studied 264 Japanese patients with type 2 diabetes over a ten-year period. The subjects were classified into two groups: (1) persistent normoalbuminuria or microalbuminuria, or improvement from microalbuminuria to normoalbuminuria (group N); and (2) progression from normoalbuminuria to microalbuminuria or overt proteinuria, or progression from microalbuminuria to overt proteinuria (group P). They were assessed for association with the +78G/A polymorphism. RESULTS: The frequency of the +78A allele was significantly higher in group N than in group P (10% vs 1%, p=0.021). By logistic regression analysis and discriminant analysis, the substituted allele was shown to be an independent factor correlating negatively to the elevation of albumin excretion (p=0.043 and 0.022, respectively). CONCLUSIONS/INTERPRETATION: The SLC12A3 +78A(+) genotype may have a protective effect against the development and/or progression of diabetic nephropathy in Japanese type 2 diabetic patients.

Albuminuria↗

A simple technique for circular-stapled Billroth I reconstruction in laparoscopic gastrectomy.

A simple surgical technique that facilitates circular-stapled Billroth I gastroduodenostomy in laparoscopic distal gastrectomy is described. After standard laparoscopic mobilization of the distal stomach, a small duodenotomy is made just distal to the pyloric ring. The anvil of a circular-stapling device, secured with a Vicryl suture, is introduced via the duodenotomy. The Vicryl suture is advanced anteriorly so that a center rod penetrates the anterior duodenal wall. The duodenum is staple-transected at this point, and the center rod is wrapped with the stapled duodenal stump by approximation of both edges using a suturing device. The circular-stapled gastroduodenostomy then is completed in a standard fashion. The authors have used this technique for three patients, and their early outcomes are promising.

Gastrectomy↗

Measurement of neutrino oscillation with KamLAND: evidence of spectral distortion.

We present results of a study of neutrino oscillation based on a 766 ton/year exposure of KamLAND to reactor antineutrinos. We observe 258 nu (e) candidate events with energies above 3.4 MeV compared to 365.2+/-23.7 events expected in the absence of neutrino oscillation. Accounting for 17.8+/-7.3 expected background events, the statistical significance for reactor nu (e) disappearance is 99.998%. The observed energy spectrum disagrees with the expected spectral shape in the absence of neutrino oscillation at 99.6% significance and prefers the distortion expected from nu (e) oscillation effects. A two-neutrino oscillation analysis of the KamLAND data gives Deltam(2)=7.9(+0.6)(-0.5)x10(-5) eV(2). A global analysis of data from KamLAND and solar-neutrino experiments yields Deltam(2)=7.9(+0.6)(-0.5)x10(-5) eV(2) and tan((2)theta=0.40(+0.10)(-0.07), the most precise determination to date.

Journal Article↗

Electron acceleration by a nonlinear wakefield generated by ultrashort (23-fs) high-peak-power laser pulses in plasma.

We study experimentally the interaction of the shortest at present (23-fs) , relativistically intense (20-TW), tightly focused laser pulses with underdense plasma. MeV electrons constitute a two-temperature distribution due to different plasma wave-breaking processes at a plasma density of 10(20) cm(-3). These two groups of electrons are shown numerically to constitute bunches with very distinctive time durations.

Journal Article↗

Intraoperative carbon dioxide colonoscopy: a safe insufflation alternative for locating colonic lesions during laparoscopic surgery.

BACKGROUND: Intraoperative colonoscopy (IOC) is useful for locating colonic pathologies during laparoscopy, but bowel distention compromises the subsequent visualization and procedure. Carbon dioxide (CO2), with its rapid absorption, has been proved effective for alleviating bowel distention in ambulatory settings. Its intraoperative role, however, has never been studied. This study aimed to assess the feasibility, safety, and advantages of CO2-insufflated IOC during laparoscopy. METHODS: For this study, CO2-insufflated IOC was performed for 20 patients under CO2 pneumoperitoneum. Parameters, including end-tidal CO2 (ETCO2) and minute volume, were prospectively registered. Time until resolution of bowel distention was determined by laparoscopic evaluation. RESULTS: All lesions were located by CO2-insufflated IOC in 15 min. During IOC, ETCO2 increased, but remained within normal values, and was quickly compensated with minimal hyperventilation. Bowel distention totally disappeared in 21 min, allowing immediate initiation of laparoscopic procedures under adequate visualization. CONCLUSIONS: The findings show that CO2-insufflated IOC during laparoscopy is feasible, safe, and of practical value for minimizing bowel distention without impeding the subsequent visualization and procedure.

Adult↗

A heteroplasmic mitochondrial DNA 3310 mutation in the ND1 gene in a patient with type 2 diabetes, hypertrophic cardiomyopathy, and mental retardation.

A mentally retarded 57-year-old Japanese man with maternally-inherited type 2 diabetes was found to have hypertrophic cardiomyopathy (HCM) that was associated with pathological changes in the myocardial mitochondria. The mitochondrial DNA (mtDNA) of this patient was examined and a C3310 T mutation was found in the ND1 gene, which resulted in the substitution of serine for proline. The normal 3310 mtDNA band could not be detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in mtDNA from his myocardium, pancreas, cerebral tissue, skeletal muscle, and lymphocytes. However two clones sequenced from his pancreatic tissue did not show this C3310 T mutation while forty-eight did. Mitochondria isolated from the lymphocytes of his two sisters also had this mutation. mtDNA point mutations in the ND1 gene region reported thus far have been mostly homoplasmic. However, the C3310 T point mutation that was found in this patient was heteroplasmic, which is a high level of mutation and may represent the pathogenic gene that was responsible for causing mitochondrial disease.

Cardiomyopathy, Hypertrophic↗

Isolation, identification and excretion profile of the principal urinary metabolite of the recently banned designer drug 1-(3-trifluoromethylphenyl)piperazine (TFMPP) in rats.

The metabolism of 1-(3-trifluoromethylphenyl)piperazine (TFMPP), a recently banned designer drug, in rats was studied by analysing its urinary metabolites. p-Hydroxy-TFMPP (p-OH-TFMPP) was isolated and identified as the main metabolite by using nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry and high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI MS). The time-course excretion profiles of TFMPP and p-OH-TFMPP in rats were investigated following a single intraperitoneal dosing of 5 mg kg(-1) TFMPP by using an optimized analytical procedure that combined solid-phase extraction and LC-ESI MS techniques. The cumulative amount of p-OH-TFMPP excreted within the first 48 h reached approximately 64% of the dose, of which 70% was the glucuronide conjugated form. The cumulative amount of parent TFMPP excreted was less than 0.7% of the dose. The results suggest that p-OH-TFMPP would be the most relevant metabolite to be detected for TFMPP exposure in the forensic and clinical analysis of human urine.

Animals↗