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Hakuo Takahashi

Publications and source records attributed to Hakuo Takahashi.

At least 19 recordsLinked to original sources
PubMed2006

Novel digitalis-like factor, marinobufotoxin, isolated from cultured Y-1 cells, and its hypertensive effect in rats.

Marinobufagenin and telecinobufagin have been identified as digitalis-like factors in mammals. In toads, marinobufagenin-related compounds, such as marinobufotoxin (MBT), have been isolated in some tissues but not in mammals, and its biological action has not been elucidated. Herein, we aimed to explore the possible production and/or secretion of MBT and the biological action in rats. First, the MBT in culture supernatant of the adrenocortical-originated cell line Y-1 was analyzed by high-performance liquid chromatography and sensitive ELISA for marinobufagenin-like immunoreactivity. Moreover, the structural information was obtained by mass spectrometry. To determine the biological action, MBT (9.6 and 0.96 microg/kg per day) was intraperitoneally infused via an osmotic minipump for 1 week. Blood pressure and renal excretion of marinobufagenin-like immunoreactivity were measured. Marinobufagenin-like immunoreactivity was found in Y-1 cell culture media, and the concentration increased until 24 hours. The structural analysis suggested that marinobufagenin-like immunoreactivities were marinobufagenin and MBT, and tandem mass spectrum analysis revealed them with the specific daughter ions. The highest sensitive ELISA-positive peak of marinobufagenin-like immunoreactivity in the media was MBT. Continuous administration of MBT in rats for 1 week significantly increased systolic blood pressure and renal excretion of marinobufagenin-like immunoreactivity compared with control rats (135+/-3.0 versus 126+/-2.0 mm Hg and 1.41+/-0.286 versus 0.34+/-0.064 ng/day, respectively). These data suggest that MBT, arginine-suberoyl ester of marinobufagenin, can be a novel digitalis-like factor with hypertensive action and is secreted from the adrenocortical cells.

Adrenal Cortex↗
PubMed2006

Association of the circulating adiponectin concentration with coronary in-stent restenosis in haemodialysis patients.

BACKGROUND: Success of coronary stenting is limited by in-stent restenosis. We aimed to determine whether circulating levels of the cytokines, which have anti-inflammatory properties such as adiponectin or interleukin-10, could be associated with the occurrence of coronary in-stent restenosis in patients with end-stage renal disease (ESRD). METHODS: We enrolled 71 consecutive ESRD patients undergoing haemodialysis (mean age: 64.9+/-8.9 years; 19 women, 52 men; mean haemodialysis duration: 78.2+/-87.5 months), who received stenting for a single coronary lesion. Plasma concentrations of adiponectin and IL-10 were measured within one week before coronary stenting. RESULTS: Of the 71 patients who had received stenting, in-stent restenosis occurred in 37 patients (52.1%) within 6 months after stenting. In univariate logistic analysis, the homeostasis model assessment index of insulin resistance, blood haemoglobin, serum concentrations of high density lipoprotein-cholesterol or triglycerides and plasma concentrations of insulin or adiponectin were significantly associated with coronary in-stent restenosis. In a multiple logistic regression analysis among these variables, however, only the plasma adiponectin concentration was associated with the coronary in-stent restenosis: the odds ratio of the increase in 1 microg/ml of plasma adiponectin concentration for having restenosis was 0.651 (P = 0.001, 95% confidence interval: 0.506-0.839). Patients with restenosis had lower plasma adiponectin concentrations than those without [6.2+/-2.2 microg/ml (2.1-10.4 microg/ml; n = 37) vs 27.2+/-10.8 microg/ml (17.9-79.8 microg/ml; n = 34); P = 0.0001]. CONCLUSIONS: Circulating adiponectin concentrations may be associated with the occurrence of coronary in-stent restenosis in ESRD patients undergoing maintenance haemodialysis.

Adiponectin↗
PubMed2006

Epidemiological study of Candida infections in blood: susceptibilities of Candida spp. to antifungal agents, and clinical features associated with the candidemia.

The purpose of this study was to evaluate the susceptibility to antifungal agents of Candida spp. isolated from blood samples from patients in our hospital, located in Osaka, Japan. We also examined the clinical background of these patients. We analyzed fungi isolated from clinical blood samples obtained in our hospital over a period of 10 years (1993 to 2002). Antifungal susceptibility testing was carried out for six agents, using the National Committee of Clinical Laboratory Standards (NCCLS) M-27-A2 method. The clinical backgrounds were reviewed using the medical records of 125 patients who were diagnosed as having candidemia. The major fungi isolated were Candida parapsilosis (39.2%) and C. albicans (30.1%), and both were sensitive to fluconazole. One strain of C. glabrata and six strains of C. krusei were resistant to fluconazole, and they constituted 4.4% of all Candida spp. isolated. With the exception of C. parapsilosis, most fungi were susceptible to micafungin, although there is no universally agreed breakpoint for this drug. Analysis of the patients' clinical backgrounds revealed that the major underlying disease was cancer (46.4% excluding hematological malignancies). C. krusei was detected almost exclusively in patients with hematological malignancies. Indwelling venous catheters had been responsible for infection in 93.6% of the infected patients. The clinical outcomes of the 125 patients were favorable in 52% and poor in 48%, and subsequent removal of the indwelling catheters was effective in about half of the patients in whom this was done, with good prognosis. To prevent mycosis and its complications, indwelling catheters should be avoided as much as possible. Attention must be paid to the possibility that resistant isolates of Candida spp. can be selected as a result of the use of antifungal agents.

Adolescent↗
PubMed2006

Clinical monitoring of innate cellular immunity of monocytes/macrophages by tumor necrosis factor alpha productivity in whole blood stimulated by lipopolysaccharide in patients with pancreatic cancer.

OBJECTIVE: The aim of this study was to evaluate the tumor necrosis factor alpha (TNF-alpha) releasing capacity in whole blood stimulated by lipopolysaccharide (LPS) in patients with pancreatic cancer during the perioperative period, and before and after chemotherapy. METHODS: The current study involved a total of 39 patients with pancreatic cancer (PC), who were further divided into a PC-Op group (n = 16, underwent pancreatectomy) and a PC-chemo group (n = 23, received chemotherapy). The control groups consisted of patients with hepatocellular carcinoma (n = 27, HCC group) and with benign diseases (n = 15, control group). Serial changes in TNF-alpha in whole blood stimulated by LPS were compared in various clinical settings. RESULTS: Preoperative TNF-alpha levels in the PC-Op group were significantly lower than those in the HCC and control groups (P = 0.034). The TNF-alpha variable surgical index (s-index) was defined as the ratio of the preoperative TNF-alpha level to postoperative level in the PC-Op and HCC groups. Although the TNF-alpha s-index in the PC-Op group was significantly decreased on postoperative day 1 and recovered on postoperative day 3 (P < 0.002), there were no significant changes in the TNF-alpha s-index in the HCC group. The TNF-alpha variable chemotherapeutic index (c-index) was defined as the ratio of the TNF-alpha level before to that after chemotherapy in the PC-chemo group. The TNF-alpha c-index in all 7 patients was reduced to less than 0.3 until leukopenia appeared. Patients who had an increase in TNF-alpha production (TNF-alpha c-index >1.0) on day 3 or 7 after chemotherapy had significantly better cumulative survival than those with no increase (P < 0.033). CONCLUSIONS: TNF-alpha production stimulated by LPS in the whole blood of patients with pancreatic cancer was low. Surgical stress and depressed immunocompetence might induce such profound decreases. A method of assessing the capability of leukocytes, particularly macrophages, to produce TNF-alpha could be useful for prognostis and for monitoring immunocompetence in patients with pancreatic cancer who have undergone chemotherapy.

Adult↗
PubMed2005

Increased soluble FcgammaRIIIa(Mphi) in plasma from patients with coronary artery diseases.

Atherosclerosis is the underlying disease process in patients affected with coronary artery diseases (CAD). Macrophages play a major role in the development of vascular lesions in atherogenesis. The cells express Fcgamma receptor type IIIa (FcgammaRIIIa: CD16) identical to that in natural killer cells (NK cells), but with a cell type-specific glycosylation. In contrast, neutrophils express FcgammaRIIIb. These FcgammaRIIIs are released from the cell surface on activation, and these soluble forms (sFcgammaRIII) are present in the plasma. We measured sFcgammaRIIIa(Mphi) in the plasma with a newly developed anti-FcgammaRIII mAb, MKGR14, which recognizes FcgammaRIIIa(Mphi) specifically. The level of sFcgammaRIIIa(Mphi), as well as the level of sFcgammaRIIIa (sFcgammaRIIIa(Mphi) plus sFcgammaRIIIa(NK)) or the level of total sFcgammaRIII (sFcgammaRIIIa plus sFcgammaRIIIb), were significantly increased in patients with CAD, but not in patients with vasospastic angina (VSA) or intact coronary arteries, compared with age-matched healthy donors. The sFcgammaRIIIa(Mphi) level was related to the number of significantly affected coronary arteries, and positively correlated with LDL-cholesterol to HDL-cholesterol ratios, but negatively with HDL-cholesterol. No correlation among the levels of three sFcgammaRIIIs was observed in CAD patients, as well as in healthy donors. The macrophages are activated during the process of atherosclerosis, and sFcgammaRIIIa(Mphi) may serve as a novel marker for atherosclerosis.

Aged↗
PubMed2005

Close association of Chlamydia pneumoniae IgA seropositivity by ELISA with the presence of coronary artery stenosis in haemodialysis patients.

BACKGROUND: Traditional risk factors of cardiovascular disease do not fully explain the accelerated atherosclerosis present in patients with end-stage renal disease (ESRD). The goal of this study was to identify the association of clinical and laboratory factors including seropositivity for Chlamydia pneumoniae determined by a specific enzyme-linked immunosorbent assay (ELISA) with the presence of coronary artery disease identified by coronary angiography in ESRD patients. METHODS: We prospectively enrolled 161 consecutive ESRD patients undergoing haemodialysis for >6 months (106 men, 55 women; mean age 63.1+/-10.2 years; mean dialysis duration 91.3+/-90.1 months). All patients underwent coronary angiography within 1 week after blood sampling. The associations of coronary artery disease with clinical parameters including C. pneumoniae IgA and IgG seropositivity were analysed using multiple logistic regression models. RESULTS: Coronary stenosis >50% was found in 102 of 161 haemodialysis patients (63.4%). Of the 102 patients, 75.5% were asymptomatic. Seropositivity for C. pneumoniae IgA was found in patients with coronary stenosis (77 out of 102, 75.5%) more frequently (P<0.001) than in patients without coronary stenosis (10 out of 59, 16.9%). Seropositivity for C. pneumoniae IgA but not IgG was strongly associated with the presence of coronary stenosis in multiple logistic regression analysis (odds ratio, 18.440; 95% confidence interval, 7.500-45.337), independently of the Framingham coronary risk factors, factors peculiar to ESRD or serum C-reactive protein levels. CONCLUSIONS: C. pneumoniae IgA seropositivity determined by ELISA is an independent laboratory factor indicating the presence of coronary artery stenosis in ESRD patients undergoing maintenance haemodialysis.

Aged↗
PubMed2005

Mobilization of bone marrow cells by G-CSF rescues mice from cisplatin-induced renal failure, and M-CSF enhances the effects of G-CSF.

Cisplatin, which is a broadly used anticancer drug, is widely known to induce acute renal failure as a result of renal tubular injury. This article examines whether G-CSF and/or M-CSF rescues mice from renal failure induced by cisplatin. BALB/c mice received intraperitoneal injections with or without G-CSF and/or M-CSF for 5 d (from day -5 to day -1). The day after the last injection of G-CSF and/or M-CSF (day 0), the mice received an intraperitoneal injection of cisplatin. When pretreated with G-CSF or G-CSF + M-CSF, the mice showed longer survival and lower serum creatinine and blood urea nitrogen levels than mice that had been received injections of M-CSF or saline. Histologically, pretreatment with G-CSF or G-CSF + M-CSF attenuated the damage to renal tubules induced by cisplatin. BALB/c mice that had received a transplant of bone marrow cells of enhanced green fluorescent protein (EGFP)-transgenic mice ([EGFP-->BALB/c] mice) were treated with or without G-CSF and/or M-CSF, followed by injection of cisplatin as well as above. [EGFP-->BALB/c] mice that were treated with G-CSF or G-CSF + M-CSF showed a significantly higher number of EGFP(+) tubular epithelial cells in the kidney than mice that were treated with only M-CSF or saline. These results suggest that bone marrow cells mobilized by G-CSF accelerate the improvement in renal functions and prevent the renal tubular injury induced by cisplatin and that M-CSF enhances the effects of G-CSF.

Acute Kidney Injury↗
PubMed2005

Screening of antibiotics resistance to Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii by an advanced expert system.

The VITEK2 advanced expert system (AES) gives information about the antibiotics-resistance mechanisms based on the biological validation derived from the VITEK2 susceptibility result. In this study, we investigated whether or not this system correctly categorized the beta-lactamase resistance mechanism data derived from the VITEK2 susceptibility result using the testing card, AST-N025, with Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii. We used 131 strains, and their phenotypes were determined according to the biological and genetic screening. The AES analysis result matched the phenotype testing in 120 (91.6%) of the 131 strains. Incorrect findings were found in six strains, including three strains of Serratia marcescens. The resistance mechanism could not be determined in five strains, including three strains of Providencia rettgeri. The analysis of those phenotypes agreed in 34 (97.1%) among 35 strains with extended spectrum beta-lactamase (ESBL), and in 27 (96.4%) among 28 strains with high-level cephalosporinase. The agreement ratio in the phenotype was very high as we expected. The incorrect and nondeterminable samples were strains with relatively high cephalosporinase that has variation of outer membrane protein. The AES was able to detect the phenotype for carbapenemase. The AES is a clinically useful system that allows taking prompt measures to treat patients because it can provide information about the resistance mechanism in less than half a day after starting the analysis.

Acinetobacter baumannii↗
PubMed2005

Polymorphism of Fc gamma RIIa may affect the efficacy of gamma-globulin therapy in Kawasaki disease.

We evaluated whether there is a possible relationship between the effectiveness of gamma-globulin treatment for patients with Kawasaki disease (KD) and the polymorphism of Fcgamma RIIa, IIIb, and IIIa. Genomic DNA was extracted from whole blood collected from 56 patients with KD who received gamma-globulin treatment. The genotypes for Fcgamma RIIIb-NA(1, 2), Fcgamma RIIa-H/R131, and FcgammaRIIIa-F/V158 were determined to investigate the association between these polymorphisms and the development of coronary lesions (CALs). Twenty-three percent of patients with the HH allele for the Fcgamma RIIa polymorphism progressed to CALs, compared with 60% with the HR and RR alleles. HR and RR alleles may be a predictor of the progression of CALs in KD before the initiation of gamma-globulin therapy.

Antigens, CD↗
PubMed2005

A novel endogenous digitalis, telocinobufagin, exhibits elevated plasma levels in patients with terminal renal failure.

BACKGROUND AND OBJECTIVES: There are several potential endogenous digitalis-like factors (EDLF) in mammalian body fluids, and marinobufagenin (MBG) may be the most potent EDLF. Improved assays are needed to confirm the potency of these metabolites. In the present study, we have identified MBG and telocinobufagin (TCB) in human plasma by high-resolution mass spectrometry (MS) and nuclear magnetic resonance (NMR). METHODS AND RESULTS: The high-resolution MS analysis revealed the molecular masses of TCB and MBG to be the same as their respective theoretical values. Using a tandem mass spectrometer, the mass-charge ratio for TCB was determined to be 403.2 for the parent ion and 349.2 for the daughter ion. The mass-charge ratio for MBG was m/z 383.2 and m/z 401.2. The NMR study revealed that the signals for MBG and TCB were the same as those obtained by MS analysis. In human blood, MBG and TCB were also identified by liquid chromatography (LC) as well as MS. In the LC/MS assay, proscillaridin A was used as an internal standard. The plasma was pretreated with Sep-Pak C18, and then 50 microL was applied to the C8 high-performance liquid chromatography (HPLC) column. The mean plasma concentration of MBG in healthy volunteers (0.94 +/- 0.28 ng/mL) was significantly lower than that in patients undergoing regular hemodialysis (3.81 +/- 1.92 ng/mL). The concentration of TCB in the healthy volunteers (1.80 +/- 0.55 ng/mL) was also significantly lower than that in patients with terminal renal failure (6.86 +/- 4.30 ng/mL). CONCLUSION: These results indicate that the major EDLF is TCB because its plasma concentration is the highest among the reported endogenous digitalis candidates.

Bufanolides↗
PubMed2005

Chronic reductions in carotid blood flow cause salt-sensitive hypertension in rats.

OBJECTIVE: We determined whether chronic reductions in carotid blood flow elicit salt-sensitive hypertension through regulation of the brain renin-angiotensin system (RAS). DESIGN AND METHODS: Both internal carotid arteries of male Wistar rats were ligated over a 1-week period. Carotid-ligated or sham-operated rats were treated with a high-salt (8% NaCl diet and 1% NaCl drinking water) or low-salt (0.3% NaCl diet and distilled water) diet for 6 weeks. At the end of the experiment, expression of the RAS mRNAs in the brain was measured. Effects of a 6-day intracerebroventricular infusion of CV-11974, a selective non-peptide angiotensin II type 1 (AT1) receptor blocker, were investigated in carotid-ligated rats administered high-salt diet. RESULTS: High-salt administration increased systolic arterial pressure compared with low-salt administration in sham-operated rats [168 +/- 4 mmHg (n = 10) versus 149 +/- 3 mmHg (n = 10), P < 0.001] and in carotid-ligated rats [202 +/- 5 mmHg (n = 10) versus 153 +/- 2 mmHg (n = 10), P < 0.0001]. Systolic arterial pressure, urinary excretion of vasopressin and norepinephrine, and expression of renin, angiotensin I converting enzyme, and AT1 receptor mRNAs in the hypothalamus were greater in carotid-ligated rats than in sham-operated rats treated with high salt. In contrast, these parameters did not differ between carotid-ligated and sham-operated rats treated with low salt. Intracerebroventricular infusion of CV-11974 abolished the increase in these parameters in carotid-ligated rats treated with the high-salt diet. CONCLUSIONS: Chronic reductions in carotid blood flow may cause salt-sensitive hypertension in normotensive rats by activating the hypothalamic RAS.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

[Consulting work performed by the hospital laboratory. Laboratory information from the screening test of blood coagulation].

Clinical laboratory physicians and scientists/technologists in the clinical laboratory of a hospital can provide much more information about laboratory data to medical doctors, by the interpretation of laboratory data, and can provide strategies to understand laboratory results. For example, in a case of circulating anticoagulant without hemorrhage, interpretation of the slightly abnormal APTT is important for precise diagnosis, although it is very difficult to interpret the data in the early stages of the disease. Recently, we experienced a patient (female, age: 61) with strong anti-phospholipid antibody and lymphoma but without thrombosis, and found spuriously elevated FDP and CRP in the patient's immunoglobulin. The information from the laboratory was invaluable in indicating the need for splenorectomy. Another case with abnormalities in blood coagulation tests was discussed. From these experiences, we confirmed that our consultations are very important and can assist in the diagnosis of patients.

Adult↗
PubMed2005

[Assessment of immunotoxicity of irinotecan determined by the novel method, by which productivity of TNF-alpha from whole blood is stimulated by lipopolysaccharide].

Irinotecan hydrochloride shows much different responses in each patient, and it has severe adverse effects. Therefore, a sensitive marker for the side effect of irinotecan on immunotoxicity may be able to prevent the severe complications by the early detection. We have recently developed a method to assess the immunotoxicity by measuring the productivity of TNF-alpha from whole blood containing monocytes when stimulated by lipopolysaccharide. By using this method, the effects of continuous low-dose irinotecan therapy on immunotoxicity were assessed in 10 patients with advanced gastric or colon cancer. When compared this method with the others such as white blood cell count, lymphocyte blastoid transformation by phytohem agglutinin (PHA), and natural killer cell activity in terms of the sensitivity, immunotoxicity by this method was found earlier than the other methods. Because our original method is easy to perform and sensitive as compared to the conventional methods, it can be widely used as one of the laboratory tests useful for patients treated with immunosuppressive agents.

Adult↗