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Biomedical subjects

K Murakami

Publications and source records attributed to K Murakami.

At least 505 records · Page 28Linked to original sources
PubMed1995

Enhanced insulin response relates to acetylcholine-induced vasoconstriction in vasospastic angina.

OBJECTIVES: This study investigated whether insulin response to an oral glucose load correlates to acetylcholine-induced coronary vasoconstriction in subjects with vasospastic angina. BACKGROUND: It has been suggested that coronary vasospasm is caused by augmented vascular responsiveness possibly exerted by atherosclerosis. Recently, insulin resistance syndrome has been proposed as a major promotor of atherosclerotic disease, potentially enhancing vascular smooth muscular tone. METHODS: Among subjects with angiographically smooth coronary arteries, we selected 14 subjects with vasospastic angina and 14 age- and gender-matched subjects with atypical chest pain. We compared coronary vasomotor response to acetylcholine infusion, glucose and insulin responses to an oral glucose load (75 g), serum lipid concentrations, obesity, heart rate, blood pressure and smoking habits in both groups. RESULTS: Fasting serum insulin concentrations and insulin response were higher in subjects with vasospastic angina than in those with atypical chest pain; however, glucose tolerance, obesity, heart rate, blood pressure and smoking habits did not differ between groups. In subjects with vasospastic angina, nearly all coronary segments, except distal segments of the left circumflex coronary artery, were constricted at peak acetylcholine infusion (20 to 100 micrograms), whereas all segments were dilated in subjects with atypical chest pain. Regression analysis for both groups demonstrated a correlation between coronary vasoconstriction and fasting serum insulin concentrations (r = 0.52, p < 0.01), insulin response (r = 0.71, p < 0.001), serum triglyceride concentrations (r = 0.51, p < 0.05) and atherogenic index (r = 0.44, p < 0.05). CONCLUSIONS: Results show that acetylcholine-induced coronary vasoconstriction in subjects with vasospastic angina correlates with hyperinsulinemia and enhanced insulin response, suggesting insulin resistance syndrome as a feature of vasospastic angina.

Acetylcholine↗
PubMed1995

Effect of galactosamine-induced hepatitis on the aerobic and anaerobic metabolism of the rat exposed to high-altitude hypoxia.

Galactosamine-induced hepatitis caused a marked increase in plasma lactate and pyruvate, but completely abolished the increase in ketone bodies in the rat exposed to an 8000 m simulated altitude. Plasma free fatty acid as the precursor of ketone bodies was higher in the galactosamine-treated rats during and after an exposure to 8000 m altitude. Treatment of the rat with galactosamine markedly reduced activities of citrate synthase, fumarase, glutamate dehydrogenase and fructose 1,6-bisphosphatase, but increased hexokinase and glucose 6-phosphate dehydrogenase in the liver. The effect of galactosamine-induced hepatitis on the energy metabolism can be explained by a reduction of mitochondrial oxidative enzymes and gluconeogenesis, and involves a shift of the aerobic metabolism to anaerobic glycolysis at high altitude.

Aerobiosis↗
PubMed1995

Evaluation of radioiodinated iodoclorgyline as a SPECT radiopharmaceutical for MAO-A in the brain.

An in vivo estimation of the newly synthesized MAO-A specific inhibitor, [125I]-labeled N-[3(2,4-dichloro-6-iodophenoxy)propyl]-N-methyl-2- propynylamine ([125I]-iodoclorgyline), was performed. Retention of the radioactivity of this radioligand was observed in the brain from 1 h post-injection. Pretreatments with clorgyline and l-deprenyl showed selective binding of [125I]-iodoclorgyline to MAO-A in the brain at 24 h post-injection. Moreover, a good correlation (r = 0.907) between the uptake of [125I]-iodoclorgyline and MAO-A enzyme activity in the cortex was observed in the pretreatment study with several doses of clorgyline. Although improvement to increase the brain/blood ratio is desirable because of slow blood clearance of the radioactivity, radioiodinated iodoclorgyline may serve as a useful SPECT radiopharmaceutical for quantitative analysis of MAO-A in the brain.

Animals↗
PubMed1995

Short-term treatment outcome study for the management of temporomandibular joint closed lock. A comparison of arthrocentesis to nonsurgical therapy and arthroscopic lysis and lavage.

OBJECTIVE: The aim of this study is to compare the clinical short-term results and efficacy of arthrocentesis with those of nonsurgical treatments and arthroscopic surgery for the management of temporomandibular joint closed lock. STUDY DESIGN: The three groups consisted of 63 consecutive patients treated nonsurgically, 20 patients treated with arthrocentesis, and 25 patients treated with arthroscopic surgery. All patients rated their pain level on a visual analogue scale and completed a pain, jaw dysfunction, and activity-limiting questionnaire before and 6 months after the procedure. Each patient's jaw opening was also scaled. The success rate of each procedure was calculated according to our success criteria. The clinical efficacy of each procedure was evaluated in successfully treated subgroups in which the between-group and within-group differences of the obtained data were statistically tested. RESULTS: The success rate was 55.6% in the nonsurgically treated group, 70% in the arthrocentesis group, and 91% in the arthroscopy group. With respect to efficacy, all posttreatment scores showed significant improvements in within-group differences, but no between-group differences were found between the arthrocentesis group and the other two groups. CONCLUSION: Arthrocentesis was considered as an intervening treatment modality between nonsurgical treatment and arthroscopic surgery on the basis of its short-term outcome. Although the treatment efficacy was comparable with arthroscopic surgery, this procedure was thought to be indicated for the patients with acute temporomandibular joint closed lock who were refractory to medication and mandibular manipulation rather than the alternative of arthroscopic surgery.

Activities of Daily Living↗
PubMed1995

Expression of Fas antigen and Bcl-2 in human glomerulonephritis.

To understand the regulatory mechanism of apoptosis in human glomerulonephritis, we examined the expression of Fas antigen (CD95) and Bcl-2 in five normal human kidney specimens and 80 tissues from patients with several types of glomerular diseases. These proteins were detected in glomeruli by immunofluorescence. The number of intraglomerular cells positive for Fas antigen was high in Henoch-Schönlein purpura nephritis and lupus nephritis, and that of Bcl-2-positive intraglomerular cells was high in lupus nephritis, focal glomerular sclerosis, and IgA nephritis. Dual-labeling and staining on serial sections indicated that mesangial cells and occasionally infiltrating leukocytes expressed Fas antigen and Bcl-2. In situ hybridization detected Bcl-2 mRNA in glomerular cells. Electron microscopy revealed apoptotic cells and apoptotic bodies in proliferated mesangial areas and within the glomerular capillaries. Fragmented DNA was detected in glomeruli by in situ nick end labeling, the data of which paralleled the number of Fas antigen-positive intraglomerular cells. In mesangial proliferative types of glomerulonephritis, the population of Bcl-2-positive intraglomerular cells, but not that of Fas antigen-positive cells, was significantly correlated with the number of proliferating cell nuclear antigen-positive glomerular cells, the grade of mesangial cell increase, and the magnitude of proteinuria. This study showed that Fas antigen and Bcl-2 are up-regulated in the glomeruli of several types of human renal diseases. Bcl-2 overexpression might play a role in the prolonged proliferation of mesangial cells and glomerular hypercellularity in glomerulonephritis.

Apoptosis↗
PubMed1995

Effect of troglitazone, a new oral antidiabetic agent, on fructose-induced insulin resistance.

Troglitazone, a newly developed oral antidiabetic agent, improves hyperglycemia, and has been reported to improve insulin resistance and to decrease hepatic glucose production in diabetic animals. However, the exact mechanism of Troglitazone on the improvement of insulin resistance is not known. Chronic administration of fructose to normal rats leads to hyperglycemia, and hyperinsulinemia; it induces insulin resistance. To reveal the mechanism of Troglitazone, we studied the effect of Troglitazone on serum glucose and insulin in the fructose-induced, insulin-resistant rats. Male Sprague-Dawley (SD) rats were fed either on standard chow or one containing fructose. Troglitazone was administrated as a food admixture (150 mg/kg/day) for 8 weeks. The rats were fed on (1) standard chow, (2) standard chow and Troglitazone, (3) fructose-enriched chow, or (4) fructose-enriched chow and Troglitazone. Blood samples were obtained every two weeks, and the levels of serum glucose and insulin were measured. Fructose-enriched chow increased serum glucose and insulin levels and insulin-to-glucose ratios. Troglitazone improved the fructose-induced increases in serum glucose, insulin levels, and insulin/glucose ratios. In conclusion, Troglitazone improved the fructose-induced insulin resistance.

Aging↗
PubMed1995

Activation of the nuclear oncogenes N-myc and c-jun in carcinoid [correction of cartinoid] tumors of transgenic mice carrying the human adenovirus type 12 E1 region gene.

The adenovirus (Ad) E1 region genes, E1A and E1B, are well known cooperatively to transform primary rodent cells and activate a number of cellular promoters, including nuclear oncogenes such as N-myc and c-jun, in transfected cell lines. However, there is still less information available on the in vivo mechanism(s) by which the E1 region gene, when chromosomally integrated in the living animals, exerts its effect on nuclear oncogene activation coupled with transformation. To investigate such in vivo activity of E1A we have used a series of microinjection experiments into fertilized eggs to generate three transgenic mice carrying the Ad12-type E1A/E1B genes under the control of the human renin gene. This transgene caused an early onset of bowel cartinoid tumors that express neural cell adhesion molecules, but do not metastasize to any region. Northern blot analysis revealed that the transgenes were considerably expressed in the tumors, but not in other tissues at detectable levels. Interestingly, the levels of N-myc and c-jun mRNAs in the cartinoid tumors were elevated 19- and 8-fold, respectively, as compared with those found in the control intestine. In contrast, the major histocompatibility complex (MHC) class I mRNA level was not altered between the tumor and control intestines, suggesting that this unchanged expression may reflect the loss of tumor metastasis. These findings provide the first in vivo evidence that the expression of the Ad12 E1 region gene induces cartinoid tumors associated with the activation of the nuclear oncogenes N-myc and c-jun.

Adenovirus E1 Proteins↗
PubMed1995

Intracellular targeting of lysosomal cathepsin D in COS cells.

Cathepsin D carries a mannose 6-phosphate sorting signal which is recognized by a specific mannose 6-phosphate receptor, presumably at the site of the trans Golgi network, which segregates cathepsin D from the secretory proteins, and results in targeting of the enzyme to the acidic prelysosomal compartments and lysosomes in mammalian cells. Recent evidence implies that another sorting signal resides within the polypeptide backbone of the precursor cathepsin D. To evaluate the role of the propeptide region of cathepsin D in mannose 6-phosphate receptor-independent targeting to lysosomes, we prepared a deletion mutant of rat cathepsin D lacking the propeptide portion and analyzed its intracellular targeting mechanism after transfection of the mutant cDNA as well as the wild-type cDNA into COS cells. The glycosylated mutant protein was retained intracellularly, and extracellular release of mutant protein was not observed after a 48 h chase. A cell fractionation experiment demonstrated that in the cells expressing the wild-type cathepsin D, the processed form of 44 kDa cathepsin D was recovered in the dense lysosomal fraction. In contrast, in the cells expressing the mutant protein, virtually all of the cell-associated cathepsin D was present in the light fraction which was enriched in the marker enzyme NADPH cytochrome c reductase, and this molecular form of cathepsin D was not observed in the dense lysosomal fraction. An immunofluorescence study revealed that the deletion mutant protein was accumulated within the endoplasmic reticulum, unlike the wild-type protein. These results suggest that the mutant cathepsin D is not correctly recognized by the intracellular sorting system in the endoplasmic reticulum, implying that the propeptide region of cathepsin D is essential for the export of cathepsin D from the endoplasmic reticulum.

Amino Acid Sequence↗
PubMed1995

Effects of semotiadil fumarate (SD-3211) and its enantiomer, SD-3212, on the changes in cytosolic Ca2+ and tension caused by KCl and norepinephrine in isolated rat aortas.

Semotiadil fumarate (SD-3211), a Ca2+ channel blocker of benzothiazine derivative and its (S)-(-)-enantiomer (SD-3212), inhibited K(+)- and norepinephrine (NE)-induced contractions in isolated rat aortas. Inhibition of NE contraction induced by both drugs was greater than that induced by diltiazem or bepridil, whereas inhibition of K(+)-contraction was similar to that induced by diltiazem or bepridil. Semotiadil and SD-3212 (10 microM) inhibited the increase in cytosolic Ca2+ ([Ca2+]i) induced by 65.4 mM K+ in fura-2-loaded preparations as well as diltiazem and bepridil (10 microM). On the other hand, semotiadil and SD-3212 (10 microM) inhibited only the early phase of increase in [Ca2+]i induced by 1 microM NE. After 5 min, no significant effect on [Ca2+]i was observed with these compounds despite the significant decrease in the contraction. In contrast to these compounds, diltiazem and bepridil 10 microM affected neither the increase in [Ca2+]i nor the contraction induced by NE. Semotiadil and SD-3212 inhibited the transient contraction induced by 1 microM NE in the absence of external Ca2+. Both compounds partially but significantly inhibited the NE-induced contraction in nifedipine-treated muscles. These results suggest that semotiadil and SD-3212 inhibit contractions of vascular smooth muscle (VSM) not only through blockade of voltage-dependent Ca2+ channels but also through other mechanisms, such as inhibition of Ca2+ release from Ca2+ stores or decrease in sensitivity of the contractile elements to Ca2+.

Animals↗
PubMed1995

Impaired mechanical response to calcium of diabetic rat hearts: reversal by nifedipine treatment.

Streptozotocin-induced diabetic and age-matched control rats were treated with 0.03% nifedipine-containing chow for 6 weeks, and mechanical response to Ca2+ was studied using isolated working hearts. At 14 weeks of age, 7 weeks after a streptozotocin injection, diabetic rats had a lower body weight and heart weight than controls, and an increase in heart weight-to-body weight ratio. Nifedipine treatment did not alter these parameters of controls, but decreased the heart weight and heart weight-to-body weight ratio of diabetic rats without affecting the body weight. In diabetic rats, systolic blood pressure was decreased compared to controls (124 +/- 5 vs. 137 +/- 6 mm Hg, p < 0.01), and reduced more by nifedipine treatment (111 +/- 4 mm Hg, p < 0.01). In control rats, LV developed pressure, LV +/- dP/dt, and cardiac work were unchanged regardless of the increment in preload at 1.25, 1.88, and 2.50 mM Ca2+. However, the responses of diabetic rats were decreased with an increment in preload at 2.5 mM Ca2+. Nifedipine treatment produced a partial recovery of all four parameters at 2.5 mM Ca2+ in diabetic rats. The myocardial Ca2+ content and sarcolemmal lipid peroxidation were similar in hearts from control and diabetic rats at all Ca2+ concentrations and nifedipine treatment did not affect these values. Results suggest that chronic nifedipine treatment improve the contractility of diabetic rat hearts under high Ca2+ conditions.

Analysis of Variance↗
PubMed1995

Malignant hemangioendothelioma.

BACKGROUND: The administration of interleukin-2 (IL-2) has recently been reported to be favorable for treating malignant hemangioendothelioma (MHE). METHODS: Two patients with MHE responded well to intralesional injections of recombinant IL-2 (rIL-2) without major side effects. The purpose of this study was to characterize cells infiltrating the regressing tumor following rIL-2 treatment. Immunohistochemical studies were performed on biopsy specimens taken from rIL-2-injected lesional skin. RESULTS: It was shown that CD8+ lymphocytes and CD56+ natural killer (NK) cells infiltrated at the rIL-2-injection sites, suggesting that these cells contributed to the tumor regression. In addition, MHE cells bore intercellular adhesion molecule-1 (ICAM-1) whose expression was augmented by rIL-2 injections. CONCLUSIONS: These findings suggested, that rIL-2 not only induces lymphokine-activated killer (LAK) cells and NK cells, but also facilitates these cytotoxic cells to adhere to MHE cells by enhancing ICAM-1 expression of tumor cells.

Aged↗
PubMed1995

Development of polyuria in Tsukuba hypertensive mice carrying human renin and angiotensinogen genes.

1. Tsukuba hypertensive mice (THM) carry both human renin and angiotensinogen genes, and develop hypertension. The animal has high levels of renin activity and angiotensin II concentration in the plasma. 2. Urinary excretion in THM was greater than in the control animal, non-transgenic C57BL/6j. THM showed a greater amount of daily water intake. The osmolality of 24 h urine was lower than that of the control animal. 3. When water was deprived for 12 h and then loaded with 0.25 mL/10 g bodyweight, the osmolality of urine at the first 0-3 h period was the same in THM and control, but significantly lower in THM at the following 3-6 h period, indicating that the urine concentrating activity is insufficient in THM compared with the control animal. 4. Urinary excretion of vasopressin was significantly higher in THM. Plasma aldosterone concentration and urinary excretion of aldosterone were also higher in THM. Plasma potassium level was significantly low. 5. The mechanism underlying the pathophysiology of polyuria is not totally explained; however, hypokalaemia, which was probably the result of hyperaldosteronism, may be at least partially involved, since hypokalaemia is considered to be a factor hampering the action of vasopressin for concentration of urine at the site of the collecting duct of the kidney.

Aldosterone↗
PubMed1995

A role of lysine-43 in the inactivation of rat prorenin.

1. Lysine-43 (Lys43) in the prosegment region was located within 3 x 10(-1) of catalytic sites, Asp81 and Asp266, in a stereo structure model of rat prorenin. 2. A mutant prorenin, Lys43Leu, was produced to elucidate a role of Lys43 in the inactivation of prorenin. Lys43Leu as well as the wild type were inactive at a neutral pH, and activated at an acidic pH. Its acid-activation speed was three times higher than that of the wild type. The mutant prorenin was more labile than the wild type at 55 degrees C and a neutral pH. 3. These results indicate that Lys43 forms ionic bonds with Asp81 and Asp266 to inactivate and stabilize prorenin.

Animals↗
PubMed1995

[Current occurrence and infection control of MRSA enteritis for surgical patients in Japan (first report)].

We investigated the current occurrence and the infection control of MRSA enteritis in the surgical facilities in Japan from July 1990 to June 1992. In this two years, MRSA enteritis was encountered in 831 cases in 144 of 279 facilities (51.6%) which had replied to our survey. Frequency of onset of MRSA enteritis in the surgical specialty was 95% in abdominal surgery and general surgery. Nosocomial infection controls for MRSA infection were done in 92.1% of 261 facilities who replied to our questionnaire. Preventive control in the preoperative and postoperative periods were performed in 23.8%. Various controls for MRSA enteritis were recognized and enforced in 56.7% with restriction of postoperative antibiotics, 65.5% with environmental controls, 70.5% with preventive control for the medical staff and 42.9% with the control for the expansion of nosocomial MRSA infections.

Cross Infection↗
PubMed1995

[Prevalence of pertussis in Fukuoka: incidence and MICs of antibiotics for Bordetella pertussis isolate].

For bacteriological examinations of whooping cough patients, nasopharyngeal specimens were directly inoculated on the cyclodextrin solid medium (CSM) supplemented with 5 micrograms of cephalexin (CEX) per ml. The inoculated plates were cultured in an incubator at 35 degrees C for 3 to 7 days. During the period from 1990 to 1993, B. pertussis (43 strains) and B. parapertussis (1 strain) were isolated from 145 whooping cough patients and 34 relatives. B. pertussis were isolated sufficiently in June to December during the year. It was suggested that during this period epidemics of whooping cough occurred. All isolates of B. pertussis had K antigen consisting of 1, 3, and 6. The determination of minimal inhibitory concentrations (MIC) of antibiotics to B. pertussis was carried out by the micro dilution technique modified from the standard methods. The Stainer-Scholte broth, supplemented with heptakis (2,6-O-dimethyl) beta-cyclodextrin, was used for dilution of the drug, and also for cultivation of bacteria. For determining susceptibility of bacteria to antibiotics, twenty seven isolates of B. pertussis and one of B. parapertussis were precultured on CSM at 35 degrees C for 2 days. The turbidity of broth cultures was adjusted to that of McFarland no. 0.5, and diluted to the concentration of 10(6) CFU/ml. One hundred microliters of these suspensions were added to 25 microliters of each antibiotic solution. After incubation for 3 days at 35 degrees C, the turbidity of the bacteria was read macroscopically for determining the MICs. On the other hand, we compared the agar dilution MICs of 23 antibiotics to the broth microdilution MICs for 27 B. pertussis isolates.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1995

Pharmacokinetics of dideoxypurine nucleoside analogs in plasma and cerebrospinal fluid of rhesus monkeys.

The pharmacokinetics of 2',3'-dideoxyadenosine (ddA), didanosine, 2',3'-dideoxyguanosine (ddG), and 6-halogenated prodrugs of ddG, 6-chloro-ddG and 6-iodo-ddG, in plasma and cerebrospinal fluid (CSF) were studied in a non-human primate model. ddA was rapidly and completely deaminated to didanosine, such that didanosine concentration profiles in plasma and CSF were identical following administration of ddA and didanosine. The mean clearance of didanosine was 0.50 liters/h/kg, the terminal half-life was 1.8 h, and the CSF-to-plasma ratio was 4.8%. The disposition of ddG was similar, with a clearance of 0.70 liters/h/kg and a half-life of 1.7 h. The adenosine deaminase-mediated conversion of the 6-halogenated-ddG prodrugs to ddG was rapid but incomplete (48% for 6-chloro-ddG and 29% for 6-iodo-ddG). The CSF-to-plasma ratios of ddG with equimolar doses of ddG, 6-chloro-ddG, and 6-iodo-ddG were 8.5, 24, and 17%, respectively, but the actual ddG exposures in CSF (area under the CSF concentration-time curve) were comparable for ddG (12.1 microM.h) and the 6-halogenated-ddG prodrugs (18.8 microM.h for 6-chloro-ddG, 9.3 microM.h for 6-iodo-ddG).6-Chloro-ddG was not detectable in plasma or CSF, and the CSF-to-plasma ratio of 6-iodo-ddG was 9.4%, so the higher CSF-to-plasma ratios of ddG with the administration of the 6-halogenated-ddG prodrugs does not appear to be the result of enhanced penetration of the prodrug and subsequent dehalogenation to ddG. The penetration of ddG into CSF exceeds that of didanosine and is enhanced by administration of the 6-halogenated prodrugs, although the mechanism of this enhanced penetration is unclear.

Animals↗
PubMed1995

C1Q complexes with beta-2-microglobulin and amyloid P-component in sera of patients with dialysis-associated amyloidosis.

We studied complexes composed of C1q and beta 2-microglobulin (C1q.beta 2M) or serum amyloid P-component (C1q.SAP) in the sera of 38 patients receiving hemodialysis (HD) and 20 healthy control subjects using an enzyme-linked immunoassay. We also compared complex levels in HD patients with and without symptoms of HD-associated amyloidosis (HA). Serum C1q-beta 2M levels were significantly higher in HD patients without HA than in healthy control subjects and significantly higher in HD patients with HA than in HD patients without HA. Serum C1q.SAP levels were significantly lower in patients with HA than in those without HA. These results suggest that C1q.beta 2M may contribute to HA.

Amyloidosis↗