Search PubMed⌕ Search

Biomedical subjects

M Takeuchi

Publications and source records attributed to M Takeuchi.

At least 307 records · Page 17Linked to original sources

High-turnover osteopenia in preterm infants: determination of urinary pyridinium cross-links of collagen.

Osteopenia is a frequent condition in preterm infants, but its pathogenesis is uncertain. In the present study, we measured longitudinal changes in the excretion of pyridinium cross-links of collagen (specific markers of bone resorption) and evaluated the relationship between collagen cross-links and other indexes of bone and renal function in preterm infants. In these infants, urinary collagen cross-links were markedly increased on day 7 and day 30 of life and at estimated full-term gestation. The values were several times higher than those of older children and almost comparable to those of healthy full-term infants. Cross-link excretion did not correlate with beta2-microglobulin (B2M) or N-acetyl-beta-D-glucosaminidase (NAG) activity (markers of renal function), indicating that cross-link excretion is not influenced directly by infantile renal function. High serum osteocalcin and low bone mineral density (BMD) in the lumbar spine were also observed at estimated full-term gestation. There was no significant correlation between collagen cross-link excretion and either serum osteocalcin or spine BMD. We conclude that a state of high bone turnover underlies the development of osteopenia in preterm infants.

Aging↗

Specific fluorescence assay for advanced glycation end products in blood and urine of diabetic patients.

Late rearrangement products that accumulate by glycation of proteins, known as advanced glycation end products (AGEs), have been implicated in the pathogenesis of complications related to diabetes. Circulating AGEs, especially in the form of a small peptide (AGE-peptide) of less than 10 kd, increase in the blood of diabetic patients with end-stage renal disease (ESRD). The aim of the study was to evaluate AGE-peptide levels by measuring AGE-specific fluorescence (excitation at 370 nm and emission at 440 nm) and to examine the relationship between AGE-peptide and diabetic nephropathy. AGE-specific fluorescence in serum and urine were examined in diabetic subjects with various levels of renal complications of varying severity: normoalbuminuria (N), microalbuminuria (Mi), macroalbuminuria (Ma), chronic renal failure (C), and hemodialysis (HD). We also assessed correlations among the AGE-peptide level and age, duration of diabetes, hemoglobin A1c (HbA1c), serum creatinine, and creatinine clearance. Serum and urine AGE-peptide levels in C and HD were significantly higher than in N, Mi, and Ma. Serum AGE-peptide levels were significantly correlated with serum creatinine (r=.866, P < .0001) and creatinine clearance (r=-.720, P < .0001) but not with duration of diabetes or age. There was a significant correlation between AGE-peptide levels measured by enzyme-linked immunosorbent assay (ELISA) and levels determined from the specific fluorescence intensity (r=.688, P < .0001). These findings suggest that renal function may play a greater role in the accumulation of AGEs than persistent hyperglycemia in diabetic patients. Measurement of AGE-specific fluorescence (ie, AGE-peptide) may serve as a simple and useful test to assess circulating AGE levels and monitor AGE excretion.

Creatinine↗

HVJ-liposome mediated gene transfer into hepatocytes in vivo.

BACKGROUND/AIMS: The efficient transduction of appropriate target cells will be critical for gene therapy. We evaluated the suitability of hemagglutinating virus of Japan (HVJ)-liposome-mediated gene transfer for gene therapy of liver diseases. METHODS: The Escherichia coli beta-galactosidase (beta-gal) gene was introduced into rat liver by HVJ-liposome to examine gene transfer efficacy and persistence of expression with or without partial hepatectomy prior to transfection. RESULTS: About 30% of hepatocytes were transduced after portal vein injection. Gene expression was transient, with only 2% of hepatocytes expressing beta-gal after 4 weeks. However, partial hepatectomy performed 24 h prior to injection resulted in persistently high levels of beta-gal for 4 weeks after injection. A 247-bp beta-gal polymerase chain reaction fragment transcript was detected in livers of transfected rats, but not in livers of control rats. The rat livers following gene transfer were histologically normal, and serum glutamic-pyruvic transaminase was not found to be elevated in rats. CONCLUSIONS: Our results demonstrate that HVJ-liposome-mediated gene transfer produced high gene transduction and persistent gene expression in the liver.

Alanine Transaminase↗

Insertion/deletion polymorphism in intron 16 of the ACE gene and left ventricular hypertrophy in patients with end-stage renal disease.

We studied the relationship between polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene and left ventricular (LV) hypertrophy in uremic patients treated with hemodialysis therapy. The LV parameters were not different for age-, hematocrit-, and blood pressure-matched patients in DD, ID, and II genotype groups. The most important factor for LV hypertrophy was systolic blood pressure, which correlated with the posterior wall thickness (r=0.35; P=0.001) and LV mass index (LVMI; r=0.23; P=0.032). Among nonhypertensive patients, the frequency of interventricular septum (IVS) hypertrophy (>12 mm) and hypertrophy in LVMI (>145 g/m2) was significantly greater in patients with the DD genotype than in I allele-positive (+) patients. The odds rate for IVS hypertrophy was 5.04 (95% confidence interval, 1.15 to 24.8). These data suggest that the DD genotype of the ACE gene polymorphism is a contributory factor for the development of LV hypertrophy in patients with end-stage renal disease (ESRD).

Age Factors↗

The effect of early burn wound excision on regional gastric blood flow in rats.

This study examined the effects of early burn wound excision on gastric blood flow and on morphologic changes in mucosal vessels. Wistar rats were given a 30% total body surface area burn and divided into four groups, consisting of control animals (group 1), animals with burn injury without and with fluid resuscitation (groups 2 and 3, respectively), and animals with both fluid resuscitation and early wound excision (group 4). Gastric mucosal blood flow (GMBF) was measured by the hydrogen gas clearance method up to 24 h post-burn. Morphologic changes in mucosal vessels were examined by scanning electron microscopy (SEM) at 3 and 24 h post-burn. The GMBF sharply decreased in the acute period after the burn. In group 4, however, it recovered to the initial value by 6 h post-burn and there was no significant change throughout the experiment. Morphologically, although the mucosal capillaries revealed some changes such as irregularity in diameter in groups 2-4 at 3 h, most of mucosal capillaries retained their original appearance in group 4 at 24 h post-burn. These result suggest that early excision does not aggravate the state of gastric ischemia.

Animals↗

Value of mild hypothermia in patients who have severe circulatory insufficiency even after intra-aortic balloon pump.

STUDY OBJECTIVE: To evaluate the effectiveness of mild hypothermia in postcardiac surgical patients with severe heart failure in spite of conventional medical therapy and the use of intra-aortic balloon pumping (IABP). DESIGN: Prospective, clinical study. SETTING: Teaching hospital. PATIENTS: 10 postcardiac surgical patients with severe heart failure despite the use of IABP with massive doses of catecholamine. INTERVENTIONS: Patients underwent mild hypothermia produced by surface cooling (to approximately 34.5 degrees C). Hemodynamic criteria for the induction of hypothermia included a cardiac index (CI) of less than 2.2 L/min/m2 with a pulmonary capillary wedge pressure (PCWP) of up to 18 mmHg despite the use of IABP with massive doses of catecholamine. MEASUREMENTS AND MAIN RESULTS: After control measurements had been taken at normal core body temperature (37 degrees C), patients were cooled to approximately 34.5 degrees C (using a cooling blanket and gastric lavage with cold water) to decrease tissue oxygen (O2) demand. Patients showed significant improvements in CI (1.9 +/- 0.3 to 2.2 +/- 0.3 L/min/m2), mixed venous O2 saturation, (SvO2; 55 +/- 7 to 64 +/- 6%), and urine output (2.1 +/- 1.1 to 3.4 +/- 2.2 ml/kg/hr). Patients were rewarmed while SvO2 was being monitored. The duration of the hypothermia was 38 +/- 41 hours. Oxygen delivery increased in 8 of the 10 patients, the mean value (+/- SD) for the group rising from 309 +/- 65 ml/min/m2 to 358 +/- 57 ml/min/m2 as temperature was reduced from 36.7 +/- 0.4 degrees C to 34.7 +/- 0.3 degrees C. All patients were successfully weaned from IABP at 140 +/- 107 hours after admission to the intensive care unit. CONCLUSIONS: Mild hypothermia is a simple and useful procedure for improving the circulation of postcardiac surgical patients with severe heart failure despite the use of IABP.

Aged↗

A novel second isoenzyme of the human UDP-N-acetylglucosamine:alpha1,3-D-mannoside beta1,4-N-acetylglucosaminyltransferase family: cDNA cloning, expression, and chromosomal assignment.

We isolated a novel cDNA encoding a second isoenzyme of UDP-N-acetylglucosamine:alpha1,3-D-mannoside beta1,4-N-acetylglucosaminyltransferase (GnT-IV; EC 2.4.1.145). The nucleotide and deduced amino acid sequences of the cDNA were homologous to those of the previously cloned human GnT-IV cDNA (63% and 62% identity, respectively). The new cDNA is also confirmed to express GnT-IV activity, suggesting that two isoenzymes of human GnT-IV exist. Although genomic Southern analysis suggested that both genes exist in many mammalian species and the chicken, northern analysis revealed that both genes are expressed in different ways in human tissues. This is the first report concerning the gene family of an N-acetylglucosaminyltransferase in mammals.

Amino Acid Sequence↗

Crescentic glomerulonephritis developing 3 months after autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

A 64-year-old woman underwent an ileocecal resection for ileus. The specimen revealed a diffuse large B cell lymphoma. The diagnosis was stage IIA non-Hodgkin's lymphoma. She received chemotherapy with the CHOP-etoposide regimen, resulting in partial remission. High-dose etoposide was used for PBSC mobilization before auto-PBSCT. Conditioning was ranimustine, carboplatin, etoposide and cyclophosphamide. Her renal function deteriorated gradually, starting 3 months post-PBSCT. Eight months post-transplant, serum creatine concentration was 7.1 mg/dl, and BUN was 59.2 mg/dl. Her hemoglobin concentration decreased to 5.3 g/dl, with no evidence of hemolysis. Renal biopsy revealed fibrous crescent formations in glomeruli, and mononuclear cell infiltration in interstitial spaces. Renal injury in this patient differs from BMT nephropathy, which is similar to hemolytic uremic syndrome, and represents another type of late renal injury after PBSCT.

Female↗

8-hydroxydeoxyguanosine in urine as an index of oxidative damage to DNA in the evaluation of atopic dermatitis.

8-hydroxydeoxyguanosine (8-OHdG) is one of the products which are excreted in urine as a result of oxidative damage to DNA. We investigated the feasibility of using 8-OHdG in urine as an index for oxidative damage to DNA in atopic dermatitis (AD). Seventeen patients with long-standing AD and 17 healthy volunteers were enrolled in this study. The severity of AD was evaluated by SCORAD index. Eosinophils, total IgE and lactate dehydrogenase-5 in peripheral blood were measured as clinical parameters for AD. A newly developed enzyme-linked immunosorbent assay method was used to measure urine 8-OHdG. The AD patients showed significantly higher levels (P < 0.0001) of 8-OHdG in their urine than corresponding controls. Urine 8-OHdG levels showed as strong a positive correlation as other haematological parameters did using the SCORAD index. Thus, we conclude that the urine 8-OHdG levels can also serve as a biochemical index of tissue damage and can act as a useful tool in the clinical evaluation of AD.

8-Hydroxy-2'-Deoxyguanosine↗

Platelet-like particle formation in the human megakaryoblastic leukaemia cell lines, MEG-01 and MEG-01s.

The platelet-sized particle formation in the human megakaryoblastic leukaemia cell line MEG-01 and its subline MEG-01s was examined. MEG-01 and MEG-01s cells spontaneously released platelet-sized particles into the culture medium, in which the cells occasionally extended cytoplasmic processes similar to those of megakaryocyte proplatelets. Scanning electron microscopic images showed cytoplasmic processes elongated from blebs on the MEG-01 and MEG-01s cell surface and were constricted between segments of platelet size. Immunofluorescence staining with anti-tubulin antibody showed that the cytoplasmic processes contained microtubules that were organized into a ring, which is a characteristic of circulating platelets. Some platelet-sized particles, probably released by ruptures at the sites of the process constriction, were metabolically active in an MTT assay (about 50%). Some particles also expressed the platelet-specific glycoproteins GPIIb, IIIa and GMP-140. Rarely, in response to thrombin, particles underwent a shape change from spherical to a shape with irregular membrane protrusions and fine filopodia, and aggregating with one another. The particles also had increased GMP-140 (P-selectin) expression with the addition of thrombin. These results show the usefulness of the MEG-01 and MEG-01s cell lines for the study of thrombopoiesis.

Blood Platelets↗

Mite antigen-induced IL-4 and IL-13 production by basophils derived from atopic asthma patients.

BACKGROUND: There is increasing evidence for the role of basophils in the pathogenesis of atopic diseases such as bronchial asthma, atopic dermatitis and atopic rhinitis. Recently, it has been reported that basophils derived from healthy donors produce the immunoregulatory cytokines interleukin (IL)-4 and IL-13 after cross-linking of cell surface IgE. In addition to well-known inflammatory mediators, such as histamine and leukotriene C4. these cytokines produced by basophils are also considered to be associated with atopic diseases. OBJECTIVE: Our first objective was to determine whether or not mite-sensitive atopic asthmatic basophils produce IL-4 and IL-13 in response to mite antigens. Our second objective was to investigate the relationship between antigen-specific or nonspecific IgE in the serum and the production of these cytokines in order to determine the association of basophil-derived cytokines with the pathogenesis of atopic asthma. Our final objective was to study how production of these cytokines could be regulated by some anti-asthma drugs. METHODS: Basophils were purified from peripheral venous blood of 67 atopic asthma patients with elevated RAST for the house dust mite. Cells were stimulated with mite antigens for 6 hours and then IL-4 and IL-13 levels in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Mite-sensitive asthmatic basophils produced IL-4 and IL-13 when stimulated with mite antigens. Mite-induced IL-4 production peaked at 6 hours after the stimulation. whereas IL-13 production continued up to 24 hours. The higher the concentration of mite-specific IgE but not total IgE released in the serum, the more IL-4 and IL-13 were produced by basophils in response to mite antigens. The production of these cytokines was significantly suppressed by the anti-asthma drugs theophylline (IL-4, p<0.001, n=6; IL-13, p<0.001, n=10) and dexamethasone (IL-4, p<0.001, n=15; IL-13, p<0.001, n=10). CONCLUSION: Mite-antigen-induced IL-4 and IL-13 production by basophils derived from mite-sensitive asthma patients was associated with the concentration of mite-specific IgE and may play an important role in the pathogenesis of atopic asthma. The inhibitory effect of dexamethasone and theophylline on allergic inflammation may be due to the inhibition of IL-4 and IL-13 production not only by T cells but also by basophils.

Administration, Topical↗

Cardiac surgery and inhaled nitric oxide: indication and follow-up (2-4 years).

We studied the effect of inhaled nitric oxide (NO) on 80 patients who had undergone cardiac surgery in our center. The indications for receiving NO inhalation and the number of patients were as follows: Pp/Ps > 0.5 for pulmonary hypertension (PH) (n = 32; 21 children and 11 adults), severe PH crisis (n = 9), high pulmonary vascular tone (Glenn pressure more than 18 mm Hg after bidirectional Glenn operation) or arterial oxygen saturation (SaO2) less than 70% despite an FiO2 of 1.0 after Blalock-Taussig shunt (n = 6), mean pulmonary artery pressure (PAP) > 15 mm Hg and transpulmonary gradient (TPG) (mean PAP - left atrial pressure [LAP]) > 8 mm Hg after Fontan-type operation (n = 18), elevated pulmonary vascular tone (mean PAP > 30 mm Hg and left ventricular assist system [LVAS] flow rate < 2.5 L/min/m2) in patients with LVAS (n = 3), and impaired oxygenation (PaO2/FiO2 < 100 under positive end-expiratory pressure [PEEP] > 5 cm H2O) (n = 12). Low dose inhaled NO (10 ppm) had the following effects. In adult PH patients, it significantly reduced the mean PAP (from 37.3 to 27.0 mm Hg; average values are given) and increased the mean systemic arterial pressure (SAP) (64.7 to 75.3 mm Hg). In infant PH patients, it increased the mean SAP (51.8 to 56.1 mm Hg). In patients with a PH crisis, it significantly reduced the central venous pressure (CVP) (13.3 to 8.8 mm Hg) while increasing both the mean SAP (49.4 to 57.9 mm Hg) and PaO2/FiO2 (135 to 206). In patients after a Fontan-type operation, it significantly reduced the mean PAP (16.8 to 13.8 mm Hg) and TPG (9.5 to 5.8 mm Hg). In patients under LVAS, it reduced the CVP (11.7 to 8.0 mm Hg) and mean PAP (32.0 to 24.7 mm Hg). In impaired oxygenation patients, PaO2/FiO2 was increased (75 to 106). Sixty-five patients were all followed for 2.0-4.3 years (average, 3.1 years). All 65 patients remained free from oxygen requirement, and possible chronic adverse effects including the occurrence of malignant tumors or chronic inflammation in the respiratory tract were not observed.

Administration, Inhalation↗

Endoscopically assisted tissue expander insertion using balloon dissection.

A method of tissue expander insertion using balloon dissection and endoscopy is presented. In tissue expander operations, accuracy and atraumatic techniques are important for preventing complications, and the endoscopic balloon provides safer and faster dissection of the fascial plane than can be achieved with endoscopic scissors, allowing the creation of subcutaneous pockets for tissue expander placement. The balloon can separate loose areolar tissue between deep and superficial fascia, forming a fascial cleft. The procedure has been used in 10 cases with satisfactory results.

Adolescent↗

Thumb reconstruction, after Marjolin's ulcer resection by microvascular transfer of a burn-contracted little finger: a case report of spare part surgery.

Thumb reconstruction after amputation due to a squamous cell carcinoma in a burn scar sustained in infancy was accomplished by microvascular transfer of the ipsilateral scar-contracted little finger. This transfer achieved a successful functional and aesthetic thumb reconstruction and at the same time removed a 'cumbersome' little finger which had often snagged on things. This case emphasises the merits of unused part transfer in hand reconstructive surgery, made possible by microvascular techniques.

Aged↗

Structural determination of metabolites of S-1153, a new, potent, non-nucleoside, anti-HIV agent in rat liver microsomes.

1. S-1153, a non-nucleoside agent that is under development in the USA as a new anti-HIV agent, has potent antiviral activity based on the inhibition of reverse transcriptase. 2. S-1153 was incubated with rat liver microsomes and NADPH, and seven metabolites were formed. The main metabolites were identified as the S-oxide, N-oxide and sulphone of S-1153. 3. Two other minor metabolites were assumed to be S-1153 hydroxylated on the isopropyl moiety. 4. Our findings confirmed the existence of at least three oxidative metabolic pathways of S-1153.

Animals↗

Pharmacokinetics of a novel benzodiazepine partial inverse agonist in the F344 rat, SD rat and B6C3F1 mouse.

1. The pharmacokinetics of a novel benzodiazepine partial inverse agonist (S-8510) were studied in the Fischer 344 (F344) rat and B6C3F1 mouse to obtain information for the planning of carcinogenicity studies. Sprague-Dawley (SD) rats were also included for comparison. 2. Clear non-linear elimination of S-8510 was observed after single oral administration of S-8510 in all animals tested (F344 rat, 1-50 mg/kg; SD rat and B6C3F1 mouse, 1-150 mg/kg). 3. Exposure of S-8510 after single oral administration was in the order F344 rat > B6C3F1 mouse > SD rat. 4. Multiple oral administration to F344 rat and B6C3F1 mouse decreased the exposure to S-8510. 5. These results indicate that it is very important to evaluate pharmacological and toxicological studies based on exposure and to be careful in selecting the species and strains of animal used in toxicology studies.

Administration, Oral↗