The variation of plasma concentrations of a novel, adipocyte derived protein, adiponectin, in patients with acute myocardial infarction.
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Adipocytes↗
Biomedical subjects
K Fujimoto
Publications and source records attributed to K Fujimoto.
Evaluation of airway wall thickness and air trapping by HRCT in asymptomatic asthma.
The aim of this study was to examine the relationship between the structural changes in large and small airways in asymptomatic asthmatics quantified by high-resolution computed tomography (HRCT) and airflow obstruction. The bronchial wall thickness at the trunk of the apical bronchus (B1) of the right upper lobe was used for assessment of the large airways. Air trapping, evaluated by the ratio of the average CT-determined values for the bilateral upper and lower lung segments at full expiration to that at full inspiration (E/I ratio), was used for assessment of the small airways. Measurements were obtained with a helical HRCT in 24 asymptomatic asthmatics followed by optimal treatment with inhaled and/or oral corticosteroids for >6 months. Prior (20-30 min) to the HRCT examination, all patients were given an inhaled bronchodilator. The ratio of airway wall thickness to outer diameter (T/D) and the percentage wall area (WA%) at the B1 bronchus and the E/I ratio were significantly greater for the 14 asthmatics with deficient reversible airflow obstruction (forced expiratory volume in one second (FEV1) <80% prediced or FEV1/forced vital capacity <70% after bronchodilator inhalation) than for the 10 asthmatics with normal spirometry and seven normal subjects. T/D, WA%, and E/I ratio showed significant negative correlations with FEV1 % pred after bronchodilator inhalation. The E/I ratio also showed significant positive correlations with T/D, WA%, and residual volume/total lung capacity. These findings suggest that, in spite of optimal treatment, structural changes in both large and small airways may simultaneously occur in asthmatics with deficient reversible airflow obstruction.
Adult↗
International Council for Standardization in Haematology (ICSH) recommendations for "surrogate reference" method for the packed cell volume.
The spun packed cell volume (PCV, hematocrit) is a key measurement on which are based hematology instrument calibration, reference range determination, and assignment of values to calibrators/controls. In 2001, the International Council for Standardization in Haematology (ICSH) recommended a Reference PCV method, which is fully traceable to the ICSH reference hemoglobin method. Because of its complexity, however, this method is impractical for occasional use in routine laboratories and is therefore intended primarily for use by manufacturers of capillary microhematocrit tubes, liquid calibrators, and multichannel analyzers. In response to the need for a simpler method--accessible to all routine laboratories--the ICSH offers this "Surrogate Reference" PCV procedure. It is traceable to the original ICSH Reference PCV method and is based on spun PCVs obtained using borosilicate capillary tubes with an already-known relationship to this reference procedure. This ICSH "Surrogate Reference" PCV method is substantially simpler, thus putting it within the reach of most routine hematology laboratories.
Blood Specimen Collection↗
[New surgical approach "intrapulmonary septation technic" for Fontan candidates with unilateral pulmonary arterial hypoplasia and/or pulmonary venous obstruction].
Unilateral pulmonary arterial hypoplasia and/or pulmonary venous obstruction are serious hazards for Fontan candidates. For these patients, we have started new surgical approach "intrapulmonary septation technic". This consists of 3 components; (A) partial right heart bypass to well-grown side, (B) mandatory pulmonary blood flow to low-capacity side, (aorto-pulmonary shunt or others) and (C) a patch between partial right heart bypass and mandatory pulmonary blood flow. Thirteen patients underwent the approach. The source of partial right heart bypass was brought from superior vena cava (11 patients), inferior vena cava (1 patient) and fenestrated Fontan (1 patient). The mandatory pulmonary blood flow was supplied by aorto-pulmonary shunt (11 patients), pulmonary arterial banding (1 patient) and native pulmonary valve stenosis (1 patient). We added pulmonary artery enlargement (9 patients), release of pulmonary venous obstruction (8 patients) and/or atrio-ventricular valve plasty (5 patients), simultaneously. No hospital death. Early post-operative course was uneventful in all cases except 1, as pulmonary blood flow to low-capacity side had increased gradually after this intervention. Eight patients had reached Fontan operation. In this approach, nearly whole pulmonary artery can grow without any affect of volume overload through well-grown side from collateral arteries of low-capacity side. All procedures of "intrapulmonary septation technic" and reconstruction of pulmonary artery in Fontan operation can be easily performed in larger pulmonary artery of well-grown side, eliminating need for extensive dissection.
Child↗
Changes in the prevalence of rotavirus G and P types in diarrheic calves from the Kagoshima prefecture in Japan.
G8 bovine group A rotavirus was the most predominant serotype in calf diarrheal fecal specimens examined between 1995 and 1996 in Japan [Vet. Microbiol. 66 (1999) 301]. To date, no evidence that G8 was the most predominant in the typeable specimens has been observed outside Japan. To investigate whether G8 continues to be as common as G6 and G10, the incidence of the main serotypes was determined in the same area (Kagoshima prefecture) between 1997 and 1998 by reverse transcription-polymerase chain reaction. From a total of 104 rotavirus-positive specimens, we successfully identified G type in 79 (76.0%) and P type in 71 (68.3%). The combination of G and P types varied periodically; in 1995, G10P[11] was most common. The most predominant types changed drastically in 1996, and G8 and mixed P types were the most predominant. A dramatic shift of the most predominant type occurred again in 1997 when G6P[5] was most common. This frequency of G6P[5] also continued in 1998. These results suggest that the serotypes prevailing in certain areas change periodically.
Animals↗
Effects of an eosinophil chemotaxis inhibitor, TAK-661, on antigen-induced asthmatic responses in allergic sheep.
Eosinophils have been shown to play a role in allergen-induced airway responses. The aim in this study was to examine the effects of TAK-661, a newly developed product as a specific inhibitory agent of eosinophil chemotaxis, on antigen-induced asthmatic responses in allergic sheep model. Seven Ascaris-sensitive, "dual-respondent" allergic sheep were provocated by an Ascaris suum antigen or phosphate-buffered saline 2 hrs after intra-stomach administration of TAK-661 or a placebo. Pulmonary resistances were measured throughout the experiment, and airway responsiveness to methacholine, bronchoalveolar lavage (BAL), and histological examination were performed 8 hrs after the antigen challenge. Antigen provocation induced dual-phase bronchoconstriction, eosinophilia in BAL and eosinophil infiltration into the airway wall, and an increase in airway responsiveness in placebo-treated sheep. The administration of TAK-661 significantly reduced the bronchoconstriction during the late phase, along with the inhibition of eosinophilia in BAL and the eosinophil infiltration into the airway wall. TAK-661 had a tendency to reduce early-phase bronchoconstriction and airway hyperresponsiveness, but there were no significant differences. These findings suggest that the eosinophil accumulation into the airway induced by antigen provocation may contribute to the development of late-phase bronchoconstriction, however, the development of airway hyperresponsiveness during late asthmatic response may not always be due to only eosinophilic inflammation in the airway.
Animals↗
Antiproliferative activity induced by the somatostatin analogue, TT-232, in human pancreatic cancer cells.
Somatostatin analogues have been developed as antiproliferative agents, but their administration as general antitumour agents is limited, mainly because of the wide distribution of somatostatin receptors throughout the human body. TT-232, a new somatostatin structural analogue, was reported to have tumour-selective antiproliferative activity without an antisecretory action. We examined whether TT-232 had antiproliferative activity in human pancreatic cancer cell lines, and compared its antiproliferative activity with that of RC-160 and other TT-232 derivatives. TT-232 inhibited the growth of all of the cell lines used in this study and induced apoptotic cell death. RC-160 showed no such growth inhibition. TT-232 also inhibited tumour formation in a xenograft model. A competitive binding assay was performed using the cell membrane fraction and 111In-DTPA-TT-232 in order to show the existence of a specific binding site on the cells. A specific binding site was detected in MIAPaCa-2 cells. It has been shown that the activation of protein tyrosine phosphatase (PTPase) is one of the main intracellular pathways responsible for somatostatinergic inhibition of cell growth. We found a significant PTPase stimulation after TT-232 administration using an immunoblot analysis assessing the level of protein tyrosine phosphorylation, and also a direct measurement of the PTPase activity. We also demonstrated that PTPase stimulation by TT-232 was involved in its antiproliferative activity as this activity was reversed by the addition of sodium orthovanadate, a PTPase inhibitor. Our results indicate that TT-232 could be a potentially useful therapeutic agent if these data are translated into clinical practice.
Antineoplastic Agents↗
Effect of treatment with nifedipine, an L-type calcium channel blocker, on muscular atrophy induced by hindlimb immobilization.
The purpose of this study was to investigate whether the prevention of calcium influx through L-type calcium channels contributed to the attenuation of muscular atrophy induced by hindlimb immobilization (HI) in a shortened position. Mice were divided into four groups (8 mice/group): control; nifedipine; HI; and HI with nifedipine. Mice received nifedipine at a dose of 5 mg/kg one day before and during the 8 days of HI. Quantitative alterations in the amount of myosin heavy chain (MyHC) and actin proteins in the soleus muscle were analyzed using SDS-PAGE. The weight of the soleus muscle decreased significantly by 40.8% (P<0.05) and 27.0% (P<0.05) after the hindlimb immobilization in the HI and HI with nifedipine groups, respectively, when compared to that of the control or nifedipine groups. Treatment with nifedipine alone appeared to have no effect on muscle mass or the amount of myofibrillar proteins. The level of MyHC proteins decreased significantly by 25.1% (P<0.001) and 17.4% (P<0.001) in the HI and HI with nifedipine groups, respectively. The level of MyHC protein in the HI with nifedipine group was significantly greater than that of the HI group (P<0.05), although there were no significant differences in the amount of actin protein. These findings suggest that nifedipine treatment may have a beneficial effect on muscular atrophy.
Actins↗
Delayed delivery of AAV-GDNF prevents nigral neurodegeneration and promotes functional recovery in a rat model of Parkinson's disease.
Glial cell line-derived neurotrophic factor (GDNF) is a strong candidate agent in the neuroprotective treatment of Parkinson's disease (PD). We investigated whether adeno-associated viral (AAV) vector-mediated delivery of a GDNF gene in a delayed manner could prevent progressive degeneration of dopaminergic (DA) neurons, while preserving a functional nigrostriatal pathway. Four weeks after a unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA), rats received injection of AAV vectors expressing GDNF tagged with FLAG peptide (AAV-GDNFflag) or beta-galactosidase (AAV-LacZ) into the lesioned striatum. Immunostaining for FLAG demonstrated retrograde transport of GDNFflag to the substantia nigra (SN). The density of tyrosine hydroxylase (TH)-positive DA fibers in the striatum and the number of TH-positive or cholera toxin subunit B (CTB, neuronal tracer)-labeled neurons in the SN were significantly greater in the AAV-GDNFflag group than in the AAV-LacZ group. Dopamine levels and those of its metabolites in the striatum were remarkably higher in the AAV-GDNFflag group compared with the control group. Consistent with anatomical and biochemical changes, significant behavioral recovery was observed from 4-20 weeks following AAV-GDNFflag injection. These data indicate that a delayed delivery of GDNF gene using AAV vector is efficacious even 4 weeks after the onset of progressive degeneration in a rat model of PD.
Animals↗
Caffeine test in predicting flutamide-induced hepatic injury in patients with prostate cancer.
The caffeine test measures the activity of cytochrome p450 (CYP1A2) which is a major enzyme involved in the activation of flutamide. The usefulness of this test in predicting flutamide-induced hepatic injury in patients with prostate cancer was examined. The subjects were: (1). five patients whose aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level rose to 100 IU/l or higher following the start of flutamide (moderately injured group); (2). four patients whose AST and ALT levels were higher than normal but less than 100 IU/l (mildly injured group); and (3). two patients whose hepatic function remained normal (normal group). The subjects were each given canned coffee to drink. Urinary caffeine (137X), paraxanthine (17X) and 1, 7-dimethyluric acid (17U) levels were measured 4-5 h later. The metabolite ratio, (17U+17X)/137X, was calculated to serve as an indicator of CYP1A2 activity. The metabolite ratio for the moderately injured group (3.98+/-1.56) and the mildly injured group (5.55+/-1.42) were lower than that for the normal group (9.56). The results suggest that a decrease in CYP1A2 activity is involved in the onset of flutamide-induced hepatic injury, and that the caffeine test seems to provide a useful means of its prediction.
Aged↗
Exogenous cysteine and cystine promote cell proliferation in CaCo-2 cells.
Previous studies have shown that intracellular glutathione, a ubiquitous intracellular thiol, is related to cell proliferation and that cysteine or its disulphide form, cystine, also induces cell proliferation. Cysteine is a thiol containing amino acid and a rate-limiting precursor of glutathione. Therefore, it is still unresolved as to whether the proliferative effect of cysteine or cystine is entirely mediated by a change in the intracellular glutathione status. The objective of this study was to delineate the relationship among cysteine/cystine (thereafter referred to as cyst(e)ine), intracellular glutathione and cell proliferation in the human colon cancer CaCo-2 cell line. CaCo-2 cells were cultured in cyst(e)ine-free Dulbecco's Modified Eagle Medium without serum, and treated with 200 microm cysteine and/or 200-400 microm cystine for 24 h. In the presence of DL-buthionine-[S, R]-sulfoximine (BSO), a glutathione synthesis inhibitor, exogenously administered cyst(e)ine did not change the intracellular glutathione content, but increased the intracellular cysteine as well as cystine level. Addition of exogenous cyst(e)ine following 5 mm BSO treatment significantly increased cell proliferation as measured by 3H-thymidine incorporation and protein content. Cell cycle analyses revealed that cyst(e)ine promoted cell progression from the G1 phase to the S phase. Correspondingly, cyst(e)ine treatment induced expression of cyclin D1 and phosphorylation of retinoblastoma protein (Rb). In conclusion, these data indicate that both cysteine and cystine have proliferative effects in CaCo-2 cells independent of an increase in intracellular glutathione. Induction of cyclin D1, phosphorylation of Rb, and subsequent facilitation of G1-to-S phase transition were involved in the proliferative effect of exogenous cyst(e)ine.
Antimetabolites↗
Usefulness of automatic detection of fragmented red cells using a hematology analyzer for diagnosis of thrombotic microangiopathy.
We previously reported an automatic method for quantitative analysis of schistocytes or fragmented red cells using an automatic hematology analyzer, XE-2100. In the study reported here, we evaluated the accuracy of this detection method in patients with thrombotic microangiopathy (TMA). A follow-up study was performed on 14 patients with two types of TMA, thrombotic thrombocytopenic purpura or hemolytic uremic syndrome. Schistocyte percent was evaluated both with an automatic counter and by means of microscopic observation. Total activity and isoenzyme pattern of lactate dehydrogenase (LD) were also determined. In these patients, schistocyte percent determined by automatic counting correlated highly with that determined by manual counting under microscopic observation (r = 0.852, P < 0.0001). Schistocyte percent was shown to correlate significantly with isoenzyme fractions 1 and 2 of LD (r = 0.732, P < 0.02), reflecting hemolysis. Nine of 11 patients tested had high concentrations of LD isoenzyme five without distinct liver damage, and schistocyte percent did not relate to fraction 5 of LD. Automatic detection of schistocyte percent using a hematology analyzer was useful for an accurate diagnosis and follow-up of thrombotic microangiopathy. The origin of LD fraction 5 remains to be determined.
Adult↗
Long-term disposition of a novel lipophilic platinum complex SM-11355 in dog after intrahepatic arterial administration: highly sensitive detection of platinum and radioactivity.
1. The disposition of SM-11355, an anticancer platinum complex for hepatocellular carcinoma, was investigated in dog by measuring platinum (Pt) and radioactivity levels following intrahepatic arterial administration of (14)C-SM-11355 suspended in Lipiodol, an oily lymphographic agent. Plasma and excretion profiles were monitored in six animals, with tissue distribution studied after 1 day, 4 and 13 weeks (n = 2/time point). 2. SM-11355 was released very slowly into the systemic circulation from Lipiodol, resulting in very low levels of Pt compounds in plasma, urine, faeces and organs. Plasma levels of Pt and radioactivity declined with apparent half-lives of 5-7 weeks. Excretion continued even at 3 months after the administration with proportions excreted for Pt and radioactivity up to 30-60% in urine and 8-10% in faeces. 3. The Pt and radioactivity in the liver accounted for 80-100% of the dose at 1 day and for 20-50% at 13 weeks after the administration, predominately as intact SM-11355. The concentrations were highest in the left lobe of the liver, the administration site, but levels in the remainder of the liver were also markedly higher than those in plasma and other tissues. 4. The results strongly support the concept that SM-11355 targets the liver with highly selectivity and sustained release of Pt compounds.
Animals↗
RGD-CAP (betaig-h3) exerts a negative regulatory function on mineralization in the human periodontal ligament.
In our previous studies, RGD-CAP/betaig-h3 was isolated from a fiber-rich fraction of cartilage and was found to have a negative function on mineralization of hypertrophic chondrocytes. However, the expression and biological function of RGD-CAP in the periodontal ligament (PDL) are not known. We hypothesized that RGD-CAP could be expressed in the PDL and regulate its mineralization. To test this, we investigated the expression of RGD-CAP in human PDL and the effects of RGD-CAP on mineralization of cultured PDL cells. RGD-CAP was detected in the human PDL as multimeric proteins greater than 200 kDa. The RGD-CAP mRNA level decreased in cultured PDL cells exposed to 10(-8) M dexamethasone or 10(-8) M 1alpha,25-dihydroxyvitamin D(3) when these steroids increased alkaline phosphatase (ALP) activity. Furthermore, exogenous RGD-CAP suppressed the ALP activity and bone nodule formation of cultured PDL cells. These findings suggest that RGD-CAP in the PDL modulates the mineralization which affects adjacent alveolar bone metabolism.
Alkaline Phosphatase↗
[Surgical treatment of traumatic rupture of the bicuspid aortic valve; report of a case].
A 27-year-old man was injured during a motocross game. He was suffered from dyspnea, orthopnea, and hemoptysis. The to-and-fro murmur was noticed 3 days after the accident and then the patient was admitted to our hospital. Echocardiography revealed severe aortic regurgitation. Computerized tomography also showed severe pulmonary contusions. Seventeen days after the accident the aortic valve replacement was performed. The aortic valve was anterior-posterior type bicuspid valve (fusion of right coronary cusp and light coronary cusp) and the tear was detected in the anterior cusp. The postoperative course was uneventful. Rupture of the aortic valve due to a blunt chest trauma is rare and reported in 20 cases previously in Japan. This case is the second report of traumatic rupture of the bicuspid aortic valve.
Adult↗
Second national external quality assessment scheme in hematology: the Philippine experience.
The Philippine Council for Quality Assurance In Clinical Laboratories has conducted two National External Quality Assessment Schemes (NEQAS) in Hematology. The first survey was conducted in December 1999 and the second in August 2000, with 95 and 187 laboratories, using mostly automated analyzers, participating respectively. Control materials were distributed during a two-week period by human network, and analyzed over a six to eight week period. For the first survey, only 36 laboratories (38.0%) submitted results. Data was divided into 4 peer groups based on the manufacturer. Since most of the samples were hemolysed upon analysis, only WBC and HGB parameters were evaluated. No outliers were detected in each peer group after analysis by the 'Peer Group Mean and SDI' method. Using the clinical laboratory improvement act of 1988 proficiency testing criteria (CLIA'88), only 5 results (13.9%) were unsatisfactory for WBC, and all results were satisfactory for HGB. For the second survey, 87 laboratories (47%) responded. Data was divided into 5 peer groups. There were few incidents of sample deterioration. Although majority of the coefficient of variations were acceptable, about 23 (12.6%) participants showed abnormality in at least one parameter after analysis by the 'Peer Group Mean and SDI'. Using CLIA'88, 5 WBC (6.5%), 6 RBC (7.6%), 8 HGB (9.7%), 15 HCT (19.0%), and 7 PLT (8.0%) results were unsatisfactory. In summary, the first NEQAS study served as a pilot study. Valuable lessons were learned for the improvement of the second NEQAS. The second NEQAS study was marked by a much larger sample size and better results.
Hematologic Tests↗
Interleukin-1beta stimulates galectin-9 expression in human astrocytes.
Galectin-9 is an eosinophil chemoattractant produced by activated T lymphocytes. We have addressed expression of galectin-9 in normal human astrocytes in culture. Expression of galectin-9 mRNA and protein were examined by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescent staining. Interleukin-1beta (IL-1beta) was found to enhance the galectin-9 expression in time- and concentration-dependent manners. Galectin-9 protein was detected in the membrane fraction, 105 000 x g precipitate, and immunofluorescent staining revealed diffuse cellular and perinuclear distributions. Dexamethasone pretreatment almost completely suppressed the production. We conclude that astrocytes produce galectin-9 in response to the stimulation with IL-1beta, and this may contribute to inflammatory reactions in the CNS.
Anti-Inflammatory Agents↗
Determination of amino acid sequence responsible for suppression of bone resorption by serum calcium-decreasing factor (caldecrin).
We previously reported on the serum calcium-decreasing activity of recombinant protein factor referred to as caldecrin [Tomomura et al. (1995) J. Biol. Chem. 270, 30315-30321]. To address the mechanism of this serum calcium-decreasing activity, we investigated the effect of rat caldecrin on osteoclastic bone-resorbing activity. Wild-type caldecrin suppressed resorption pit formation by osteoclast on a dentine slice in a dose-dependent manner. The suppressive effect on the bone resorption was not affected by treatment of caldecrin with phenylmethyl sulfonyl fluoride or by use of protease-deficient mutant caldecrins. Recombinant procaldecrin (-13-239), and its fragments (-13-125), (1-111), (1-46), (47-111), and (126-239) were expressed as His-tagged thioredoxin fusion proteins and investigated for their ability to suppress bone resorption. The proform (-13-239) and fragment (-13-125) did not affect the suppressive activity, whereas fragments (1-111) and (126-239) did suppress the bone resorption. The bone-resorbing activity was also suppressed by fragment (47-111), not by fragment (1-46). Overlapping fragments (47-62), (47-79), (47-98), (56-111), (71-111), and (85-111) were compared for their suppressive activity. The fragments (47-62) and (85-111) did not affect the activity, but the other fragments suppressed the bone resorption. A synthetic peptide having the (71-79) sequence suppressed the bone resorption. These results suggest that amino acid sequence corresponding to rat caldecrin (aa 71-79) is responsible for the suppression of bone resorption by caldecrin.
Amino Acid Sequence↗