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Biomedical subjects

K Asakawa

Publications and source records attributed to K Asakawa.

At least 19 recordsLinked to original sources

Heme oxygenase-1 gene expression by a glutathione depletor, phorone, mediated through AP-1 activation in rats.

This study shows that induction of heme oxygenase-1 (HO-1) gene expression by a glutathione (GSH) depletor, phorone, is inhibited by cycloheximide pretreatment and involves changes in c-jun, not c-fos, mRNA. Buthionine sulfoximine (BSO) enhanced markedly both c-jun and HO-1 gene expression evoked by phorone. Phorone dramatically increased AP-1 binding activity, which was blocked by unlabeled AP-1 oligonucleotide and abolished by anit-Jun antibodies, but not anti-Fos antibodies. In addition, pretreatment with dexamethasone, an inhibitor of AP-1 DNA binding, inhibited phorone-mediated HO-1 mRNA induction. These findings suggest that HO-1 induction by phorone is likely to involve in the activation of AP-1 (Jun/Jun) binding, which could be associating with GSH depletion.

Animals

[Artificial defect on myocardial SPECT image due to extra-cardiac MIBI accumulation].

If 99mTc-methoxy isobutylisonitrile (MIBI) myocardial scintigraphy was performed on the rest-stress protocol, MIBI accumulated in extra-cardiac area, gallbladder or liver, on rest image significantly. The purpose of this study was to evaluate whether extra-cardiac MIBI accumulation influences the quality of myocardial images. Rest-stress MIBI myocardial scintigraphy was performed in 90 patients. Fifteen patients showed defects on rest image in spite of normal findings on stress image. Before and after removing the area of extra-cardiac MIBI accumulation on projection images, SPECT was reconstructed in the 15 patients. Perfusion defect on rest image improved in 66% of patients (10/15) and 37% of total segments (33/89) by removing the area of extra-cardiac MIBI accumulation. Furthermore, it was 21% (4/19), 38% (11/29), 43% (16/37) and 50% (2/4) in anterior, septum, posterior and lateral segments respectively. Significant MIBI extra-cardiac accumulation, especially in the gallbladder, is one of the causes of artificial defects on rest image. Thus, reconstruction of SPECT after removing area of MIBI extra-cardiac accumulation will be an appropriate method to improve the quality of MIBI images.

Female

[Efficacy of simultaneous function and perfusion imaging on 99mTc-tetrofosmin myocardial scintigraphy].

The aim of this study was to determine whether the diagnosis for coronary artery disease (CAD) with 99mTc-tetrofosmin (Tf) myocardial scintigraphy was improved by the combination of function image and perfusion image as compared with perfusion alone. Tf myocardial scintigraphy was performed with one-day protocol (stress/rest) in 51 patients (CAD: 32, Non-CAD: 19) without previous myocardial infarction. Function image was obtained by first pass method, and perfusion image by SPECT. Number of diseased vessels was 14 in right coronary artery (RCA), 18 in left anterior descending (LAD), and 12 in left circumflex (LCX). Ischemia was diagnosed by 2 different parameters 1) perfusion image alone, 2) combination of perfusion image and regional ejection fraction (rEF). On perfusion image, accuracy was 53%, 94% and 86% in RCA, LAD, and LCX respectively. On perfusion + rEF, accuracy was 76%, 90% and 84% in RCA, LAD, and LCX respectively. Specificity in RCA was 45% on perfusion, 84% on perfusion + rEF. Sensitivity in RCA was 77% on perfusion, 54% on perfusion + rEF. LAD and LCX did not change by the addition of function image. By addition of function image, accuracy and specificity of diagnosis in area of RCA improved significantly (p < 0.01). Thus the addition of function image in Tf myocardial scintigraphy would be useful to improve the diagnosis, especially in region of RCA.

Aged

[Bathing in bed accelerates the recovery of skin temperature after ethanol-loading].

Bathing in bed (BB) is an essential nursing technique applied to patients with restricted physical abilities. The aim of this technique is to keep the functions of the skin as an external barrier and to prevent the patients from infection and decubitus. However, the effect of BB on the blood circulation of the skin has not yet been identified, and the data observed are controversial. We have evaluated the effects of BB on the blood circulation of the skin by use of thermography. BB was applied on the right side of the back (RB) in 6 healthy female subjects who exposed both sides of their back (RB and LB) at room temperature. Ethanol was applied on the 5 x 5 cm area of RB and LB after BB, and recovery of the skin temperature was observed. After BB, the average temperature of RB was significantly lower than that of LB. This shows that BB decreases temperature of the skin exposed in the air probably due to the supply of water by washcloth. Recovery of the skin temperature after the ethanol-loading was accelerated on RB. This indicates that BB facilitates the response of the blood vessels in the skin.

Adult

Symptomatic Chiari malformation and associated pathophysiology in pediatric and adult patients without myelodysplasia.

The clinical characteristics of eight pediatric and five adult patients with Chiari malformation were evaluated. Six pediatric and five adult patients had associated syringomyelia. All patients initially underwent a suboccipital craniectomy with upper cervical (C-1 and/or C-2) laminectomy and duraplasty, and/or shunting procedures. The clinical characteristics of the pediatric and adult groups were compared. The mean interval between onset of symptoms and operation was shorter in the pediatric group (3 yrs 6 mos) than in the adult group (7 yrs 1 mo). Pediatric patients without syringomyelia had the shortest mean interval of 1 year 8 months. Preoperatively, the clinical features were more severe in the adult patients than in the pediatric patients. Postoperatively, seven of eight pediatric patients improved and one stabilized, while two of five adult patients improved, one stabilized, and in two the disease continued to progress despite multiple corrective procedures. Cine magnetic resonance imaging revealed correction of the abnormal cerebrospinal fluid (CSF) flow at the craniovertebral junction and decreased to-and-fro movement in the syrinx after posterior fossa decompression, which were closely correlated with the improvement of clinical features in pediatric patients. However, adult patients required further procedures because of the multifactorial nature of the disease. Evaluation of abnormal CSF pathways at the craniovertebral junction is important for investigating the pathogenesis of Chiari malformation and associated syringomyelia.

Adolescent

Responses of insulin-like growth factor binding protein-1 (IGFBP-1) and the IGFBP-3 complex to administration of insulin-like growth factor-I.

The importance of insulin-like growth factor binding proteins (IGFBPs) in modulating the bioactivity of administered IGFs is poorly understood. This study examines responses of IGFBP-1 and the IGFBP-3 complex to recombinant human IGF-I. Eight fasted subjects received a single dose of 0.1-0.125 mg/kg IGF-I sc. This caused a 10-fold rise in IGFBP-1 over 6 h, falling rapidly after food intake. Peak (6-h) IGFBP-1 values were highly correlated with peak post-prandial (8-h) glucose values (r = 0.941). IGFBP-3 showed little response, decreasing slightly over the 48-h period following IGF-I. Adaptive changes in IGFBPs were studied in fed adults injected daily for 7 days with IGF-I, 0.1 mg/kg sc. Following the first injection, IGFBP-1 had a markedly blunted response compared to that in fasted subjects. However, after the seventh IGF-I injection, a 3.5-fold greater IGFBP-1 response to the same IGF-I dose was seen. Concomitantly with the increased IGFBP-1 responsiveness, mean immunoreactive IGFBP-3 and acid-labile subunit levels decreased significantly (p < 0.005), whereas IGFBP-2 detected by immunoblotting increased. Thus IGF-I administration causes changes in IGFBPs which may be important in regulating IGF-I bioavailability.

Adult

[A case report of BWG syndrome in an elderly patient performed with mitral valve replacement 11 years after single CABG].

A 46-year-old female who had undergone single CABG for BWG syndrome 11 years ago was referred to our hospital for paroxysmal atrial fibrillation. The roentgenogram showed slightly cardiomegaly and the enlargement of LA. Ischemic changes of ECG appeared at I, aVL, V5, V6, as inverted T wave, and low voltage R wave at V1-V4, but non Q wave. The thallium-201 emission computed tomogram at exercise revealed poor perfusion at apical region without redistribution pattern. Catheterization showed mitral regurgitation (grade III), big right coronary artery (RCA) arising from aorta, rich collateral to poor left coronary artery (LCA), and bypass graft was obstructed. The proximal end of LCA was closed, and didn't arise from both pulmonary artery and ascending aorta. In this cases, MVR only without re-CABG to LCA was selected and performed. Postoperative course was uneventful. The result of this case suggested that MVR was an effective surgical procedure for MR of BWG syndrome in the adult case and it was better to add CABG to LCA as much as possible if the ischemic region was large.

Coronary Artery Bypass

[Late malfunction of the Björk-Shiley valve prosthesis due to Delrin disc defacement].

A 55-year-old woman eighteen years after mitral valvular replacement with Delrin disc Björk-Shiley valve prosthesis underwent a reoperation of prosthetic valve replacement for the prosthetic malfunction due to disc defacement. The patient suffered from faintness and vertigo at rest. An echocardiographic examination showed a moderate mitral insufficiency with a normal disc movement. Precise examination on the removed prosthesis revealed accelerated defacement of disc margin which made the ring-disc clearance up to 0.35 mm and strut-shaped groove formation on the inlet surface of the disc occluder. These findings suggested a pronouncedly earlier disc wear than predicted by Björk and co-workers. We concluded, therefore, that a patient undergone a valve replacement with Delrin disc Björk-Shiley valve should be examined periodically by echocardiography even though being without any symptoms.

Female

[Scintigraphic comparison of graft patency between the left internal thoracic artery and saphenous vein graft after coronary bypass surgery].

Graft patency after coronary bypass surgery (CABG) was evaluated with stress 201-thallium scintigraphy (stress 201Tl) in 26 cases, including 13 cases using the left internal thoracic artery (LITA group) in situ and 13 cases with saphenous vein graft (SVG group). All of them had effort or unstable angina caused by LAD lesion without apparent infarction. Stress 201Tl using a symptom-limited, graded bicycle exercise test was performed before CABG and 1 month, 6 months to 1 year, 1 year to 1.5 years after surgery. Five tomographic images including the apical side of the area fed by the bypass anastomosed to LAD in short axial sections were picked out and piled up. Fan-shaped ROI was made on this area and % Tl uptake was calculated using the following formula. 201Tl counts in ROI--Background counts/Maximum counts--Background counts x 100 (%) The normal % Tl uptake calculated in the control group (n = 11) in this ROI was 68.2 +/- 4.8%. Preoperative % Tl uptake showed 49.3 +/- 0.2% in the LITA group and 54.3 +/- 13.2% in the SVG group. % Tl uptake of the SVG group 1 month after CABG was slightly higher than that of the LITA group, (62.0 +/- 7.0% vs. 56.3 +/- 7.6%). However 6 months to 1 year after, % Tl uptake of the LITA group increased to 60.8 +/- 6.4%, inspite of a tendency on the decrease of that in the SVG group, (59.0 +/- 8.5%), and further more, 1 year to 1.5 years after CABG, increased to 62.3 +/- 5.1% near the normal % Tl uptake of the control group and the SVG group decreased to 58.8 +/- 6.8%. This result suggested that arterial in situ bypass graft might have an auto-regulation and "growing property" corresponding to flow demand, and this helps the excellent long-term patency of arterial bypass grafts.

Adult

Effects of insulin-like growth factor I or human growth hormone in fasted rats.

To study the effect of insulin-like growth factor I (IGF-I) treatment on growth and metabolism in fasted rats and compare it with the effect of human growth hormone (hGH), we infused 120 micrograms/ml IGF-I continuously or injected 200 micrograms hGH twice a day in fasted rats. After a 3 1/2-day administration of IGF-I in fasted rats, the body weights, kidney, spleen and adrenal gland weights were greater than those for untreated fasted rats (control). The body weights and the organ weights in hGH treated rats did not differ from those in control rats. Serum IGF-I levels in control, hGH treated and IGF-I treated rats were 64.0 +/- 6.1, 107.5 +/- 6.9 and 129.8 +/- 6.3 ng/ml, respectively, which were significantly different from each other. Blood urea nitrogen (BUN) levels were 13.9 +/- 1.1 ng/ml in IGF-I treated rats, which were significantly lower than those of control rats. Human GH treatment did not change BUN but affected nonesterified fatty acid (NEFA) and triglyceride. In IGF-I treated rats three-day urinary excretion of nitrogen and creatine were 163.5 +/- 14.6 mg and 9.53 +/- 1.53 mg, which were significantly less than those in control rats. These data indicate that IGF-I infusion inhibits body weight loss and catabolism in fasted rats and might be a useful therapy in catabolic conditions.

Adrenal Glands

Single sc administration of insulin-like growth factor I (IGF-I) in normal men.

Total and free form of IGF-I in plasma increased in a dose dependent manner after sc IGF-I administration. Peak values of total IGF-I were obtained at 3-4 h after the administration, and then the values decreased gradually. However, peak values of free form of IGF-I were obtained at 2 h, and then rapidly decreased thereafter. The blood glucose, serum insulin and C-peptide levels decreased until 4 h after IGF-I administration in a dose dependent manner. Plasma IGF-II values significantly decreased at 4-12 h after IGF-I administration. Urinary urea nitrogen and sodium excretion decreased after IGF-I administration. Urinary GH excretion also decreased after 0.06 mg/kg IGF-I administration. These data demonstrate that IGF-I may play a role in glucose, protein and electrolyte metabolism, and plasma IGF-II levels and GH secretion might be regulated by IGF-I in man.

Adult

Measurement of free form of insulin-like growth factor I in human plasma.

A method to measure free form of insulin-like growth factor I (IGF-I) in human plasma using octadecylsilyl silica (Sep-Pak C18) cartridge has been developed. IGF-I was adsorbed by Sep-Pak C18 cartridge and eluted with 75% ethanol--0.01 M HCl. Labeled and non-labeled IGF-I were recovered in yields 92.5 +/- 2.1% (Mean +/- SEM) and 94.4 +/- 6.3% after adsorption to and elution from the Sep-Pak, respectively. When EDTA plasma was applied to the Sep-Pak, less than 5% of total IGF-I was recovered in the eluate. However, when acid-ethanol extracted plasma was applied to the Sep-Pak, IGF-I was recovered in yields greater than 75% of total IGF-I. When the Sep-Pak eluate was gel filtered, 88.4 +/- 4.0% of immunoreactive IGF-I eluted in the same fraction as synthetic IGF-I did, but the fraction passed through the Sep-Pak was observed as a high molecular weight form (bound form) of IGF-I. These data indicate that this Sep-Pak method does not extract all of the IGF-I in plasma, but extracts mainly the free form IGF-I. Using this method, IGF-I values of free form (fIGF-I) in EDTA plasma were measured. The fIGF-I values in normal adults, patients with acromegaly, and patients with growth hormone (GH)-deficiency were 2.4 +/- 0.1, 13.8 +/- 1.6, and 1.1 +/- 0.1 ng/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly

Repeated sc administration of recombinant human insulin-like growth factor I (IGF-I) to human subjects for 7 days.

Recombinant human insulin-like growth factor I (rhIGF-I) was administered subcutaneously to 6 normal subjects and 2 patients with GH deficiency at a dose of 0.1 mg/kg for 7 consecutive days after breakfast. In normal subjects, plasma IGF-I levels increased from 217 +/- 22 ng/ml (Mean +/- SEM) to maximal levels of 581 +/- 6 ng/ml 4 h after the first administration of IGF-I. The blood glucose levels were statistically depressed 4 h after injection at 69 +/- 2 mg/dl. Similar plasma IGF-I and blood glucose profiles were observed after the seventh administration of IGF-I. The free form of IGF-I in plasma was 2.3 +/- 0.3 ng/ml in normal subjects and increased to maximal levels of 43.5 +/- 5.1 ng/ml 2 h after the first IGF-I administration. A similar pattern for the free form of IGF-I was observed after the seventh administration; however, the values obtained at 0, 1 and 2 h were greater after the seventh administration. In patients with G-deficiency, the plasma IGF-I and blood glucose profiles were similar to those observed in normal subjects, although the total IGF-I levels were low in these patients at all sampling points during the study. Slight decreases in serum insulin, uric acid, and creatinine were observed after the seventh administration of IGF-I. There were no changes in the excretion of urea nitrogen, creatine, creatinine, sodium, potassium, chlorine, calcium or C-peptide in the urine during the 7 days of IGF-I administration.

Adult

Effects of short-term growth hormone therapy in short children without growth hormone deficiency.

Evaluation of 24-hour endogenous growth hormone (GH) secretion was carried out in 62 children, aged 7-16 years, who did not have classic GH deficiency (GHD). The mean 24-hour GH concentration, determined at 20-minute intervals over 24 hours, was variable, ranging from 1.28 to 11.39 micrograms/l with a mean of 4.95 +/- 2.55 micrograms/l (+/- SD). There was a positive correlation between mean 24-hour GH concentration and plasma insulin-like growth factor I (IGF-I) values (r = 0.54; p less than 0.01). Recombinant human GH, 0.1 IU/kg/day was administered to 30 of the 62 children for 6 months followed by 6 months' observation without treatment. Thereafter, GH was administered at the same dose for a further 6 months to 16 children. The mean height velocities before, during, and after the first treatment period were 4.3 +/- 0.9, 7.3 +/- 1.9 and 4.9 +/- 2.0 cm/year (mean +/- SD), respectively. The height velocity during treatment was greater than pre- and post-treatment values (p less than 0.001). The height velocity increased again during the second treatment period to a mean of 8.5 +/- 2.0 cm/year (p less than 0.001). Nine other children were treated continuously in a similar manner for 1 year and their height velocity increased significantly from 4.1 +/- 1.4 to 6.0 +/- 1.9 cm/year (p less than 0.001). According to our criteria, 29 of the 39 children (74.4%) who were treated for 6-12 months showed a GH-dependent height increase during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Effects of sc administration of recombinant human insulin-like growth factor I (IGF-I) on normal human subjects.

Recombinant human insulin-like growth factor I (IGF-I) was administered subcutaneously to each of 5 normal human subjects at doses of 0 mg/kg (control), 0.06 mg/kg, or 0.12 mg/kg successively at one week intervals. After 0.06 mg/kg or 0.12 mg/kg IGF-I injections, plasma IGF-I levels increased from 185 +/- 17 ng/ml (mean +/- SEM) to maximal levels of 396 +/- 21 ng/ml at 3 hours and from 169 +/- 14 ng/ml to 480 +/- 27 ng/ml at 4 hours, respectively. These two peak values were statistically different (p less than 0.05). After 0.06 mg/kg and 0.12 mg/kg IGF-I administration, blood glucose levels decreased from 85 +/- 2 mg/dl to minimal levels of 73 +/- 3 mg/dl at 3 hours and from 83 +/- 1 mg/dl to 50 +/- 4 mg/dl at 2 hours, respectively. These two minimal values were statistically different (p less than 0.001). Serum insulin and C-peptide levels were decreased in a dose dependent manner after IGF-I administration. There were no changes between blood urea nitrogen levels before and 4 hours after IGF-I administration. The urinary GH concentration decreased after 0.06 mg/kg IGF-I administration, but increased and maintained normal values after 0.12 mg/kg IGF-I administration.

Adult

Radioimmunoassay for insulin-like growth factor II (IGF-II).

Insulin-like growth factor II (IGF-II) levels in human plasma were measured in physiological and pathological conditions by radioimmunoassay (RIA) with biosynthetic IGF-II. This RIA was specific for IGF-II and cross-reactivity with IGF-I was 1%. The sensitivity was 15 pg/tube with 50% displacement at 50 pg/tube. The intra- and inter-assay coefficients of variation for IGF-II were 6.3 and 9.3%, respectively. The plasma IGF-II levels in normal adults, patients with hypopituitarism and patients with active acromegaly were 589.6 +/- 15.8, 800.9 +/- 45.6 and 330.3 +/- 24.3 ng/ml, respectively. After human growth hormone (hGH) treatment in hypopituitarism, IGF-II slightly increased, but not significantly. After adenomectomy in patients with acromegaly, IGF-II significantly decreased. These data indicate that IGF-II concentrations in plasma were partially GH dependent. This GH dependency was less than that of IGF-I. IGF-II was low in patients with anorexia nervosa and with liver cirrhosis and high in patients with renal failure. In two cases with extrapancreatic tumor-associated hypoglycemia, plasma IGF-II was increased to 1123.8 and 843.5 ng/ml, and returned to normal after tumor resection. These data showed that IGF-II was partly dependent on GH and nutritional conditions and that IGF-II was the most likely cause of some cases of hypoglycemia with extrapancreatic tumor. This specific and sensitive RIA of IGF-II would be useful in evaluating its physiological and pathological role in plasma and tissue.

Acromegaly

Growth hormone and insulin-like growth factor I stimulate Leydig cell steroidogenesis.

Leydig cells from 40 days old rats were incubated with or without human growth hormone (hGH) or insulin-like growth factor I (IGF-I) in the presence or absence of human chorionic gonadotropin (hCG), and testosterone and cyclic AMP (cAMP) levels in the medium were measured. Neither hGH nor IGF-I increased testosterone production in the absence of hCG in concentrations up to 1000 and 100 ng/ml, respectively. However, both peptides increased hCG-induced testosterone production in a dose-dependent manner. The maximal stimulatory concentrations of hGH and IGF-I were 100 and 50 ng/ml, respectively. Human GH did not further enhance the IGF-I-stimulated steroidogenesis. The hGH-augmented steroidogenesis was inhibited by anti-hGH IgG and anti-IGF-I IgG. hGH also enhanced hCG-stimulated cAMP production time dependently, suggesting that the stimulatory effect of hGH on steroidogenesis was due to an increased cAMP production. These data suggest that the effect of hGH might be mediated by locally produced IGF-I, which may act as a modulator on gonadal development in the presence of gonadotropin.

Animals

Human growth hormone stimulates liver regeneration in rats.

To study the effect of human growth hormone (hGH) on liver regeneration in rats, 200 micrograms hGH was administered to partial hepatectomized rats twice a day for three days. The bw of hGH-treated rats was higher than that in untreated rats. After three day administration, the liver weight was 3.18 +/- 0.13 g, significant higher than that of untreated rats (2.68 +/- 0.17 g). Human GH also stimulated the mitosis in the liver. Serum insulin-like growth factor I (IGF-I) and albumin levels were significantly increased and urea nitrogen levels were significantly decreased in hGH-treated rats compared with those in untreated rats. When 120 micrograms/day IGF-I was continuously administered to partial hepatectomized rats for three days, the bw and the liver weight were not higher than those of controls. These data indicate that hGH directly stimulates liver regeneration and recover liver dysfunction in rats.

Animals