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Biomedical subjects

K Shimada

Publications and source records attributed to K Shimada.

At least 451 records · Page 25Linked to original sources

Differential inhibition of wild-type endothelin-converting enzyme-1 and its mutants.

The purpose of this study was to determine the effect of mutation of rat endothelin-converting enzyme-1 (ECE-1) on the potencies of various inhibitors. The two amino acids mutated were Cys(412), which was shown to link the two monomeric enzymes to form a dimer, and Glu(752), postulated to be involved in substrate and inhibitor binding. No significant effects were noted when Glu(752) was replaced by an acidic (E752D) or uncharged (E752Q) residue. Replacing Glu(752) by a basic residue (E752R) slightly weakened the potencies of the inhibitors. In contrast, a significant decrease in the potencies was observed with the monomeric enzyme C412S. Phosphoramidon inhibited the wild-type ECE-1 with an IC50 of 1.5 microM, but it was about sixfold weaker for the C412S mutant. CGS 31447, an aminophosphonic acid, inhibited the wild-type and C412S enzymes with IC50 values of 5.8 and 76 nM, respectively. A similar degree of change in the potencies was also seen with CGS 25015, a thiol-containing compound, which inhibited the respective enzymes with IC50 values of 17 and 190 microM. These results suggest that the charge in Glu(752) may not be important for inhibitor binding and that the dimeric ECE-1 is more susceptible to inhibition than the monomeric enzyme.

Animals↗

Renal endothelin-converting enzyme in rats with congestive heart failure.

The expression and immunoreactivity of endothelin-converting enzyme (ECE) were examined in the renal tissue of rats with experimental congestive heart failure (CHF). Reverse transcriptase polymerase chain reaction (RT-PCR) revealed that ECE mRNA was more abundant (about twofold) in the renal medulla than in the cortex. Induction of heart failure caused a significant enhancement in the expression of this key enzyme in the renal cortex of rats with compensated CHF (delta + 28%) and in animals with decompensated heart failure (delta + 58%). An identical trend was also observed in the renal medulla, although these increases were moderate compared to those in the cortex. Similar findings were observed with Western blot techniques applying two monoclonal antibodies to rat ECE (AEC32-236 and AEC27-121). Taken together, these data suggest that upregulation of ECE is an important component in the activated renal ET system in CHF.

Animals↗

Phylogeny and photosynthetic features of Thiobacillus acidophilus and related acidophilic bacteria: its transfer to the genus Acidiphilium as Acidiphilium acidophilum comb. nov.

Phylogenetic analyses based on 16S rDNA sequences and genomic DNA-DNA relatedness showed that the sulphur-oxidizing facultative chemolithotroph Thiobacillus acidophilus was closely related to members of the genus Acidiphilium, which is a group of strictly aerobic, heterotrophic acidophiles now categorized into aerobic photosynthetic bacteria. Lipophilic pigment analyses revealed that zinc-chelated bacteriochlorophyll a and carotenoids occurred in appreciable amounts in T. acidophilus and all established species of the genus Acidiphilium. PCR experiments showed that T. acidophilus as well as Acidiphilium species contained puf genes, encoding the photosynthetic reaction centre proteins and the core light-harvesting complex of the purple bacteria. There were high similarities between T. acidophilus and Acidiphilium species in the primary structure of their reaction centre proteins deduced from the nucleotide sequence data. The phylogenetic tree of the reaction centre proteins was in agreement with the 16S rDNA sequence-based phylogenetic tree in the relationship between T. acidophilus and Acidiphilium species and between the Acidiphilium cluster and other purple photosynthetic bacteria. Based on these results, together with previous phylogenetic and phenotypic information, it is proposed to reclassify T. acidophilus (Guay and Silver) Harrison 1983 as Acidiphilium acidophilum comb. nov. The type strain is ATCC 27807T (= DSM 700T).

Bacteriochlorophylls↗

Follow-up of children after fetal treatment for obstructive uropathy.

BACKGROUND: Improvement in the ability to evaluate fetuses with obstructive uropathy, combined with technologic advances, has allowed successful fetal treatment of these conditions in Japan. We analyzed the prenatal and postnatal clinical courses of patients who underwent shunt placement in utero. METHODS: We treated 6 patients who underwent fetal intervention and were transferred to us for urologic management. Gestational age at detection of abnormalities ranged from 11 weeks to 31 weeks, and fetal intervention was done between 16 weeks and 32 weeks. Excluding 1 infant who was delivered 6 days after the intervention, the mean period between shunt placement and delivery was 17 weeks. RESULTS: Urologic pathology included prune belly syndrome with urethral hypoplasia in 3 patients, cloacal anomaly in 1, posterior urethral valves in 1, and pelviureteric junction stenosis of a solitary kidney in 1. Four patients required ventilation support in the neonatal period, and 2 of them suffered frequent infections during follow-up. Five patients who underwent vesico-amniotic shunt placement continue to require clean intermittent catheterizations via vesicostomy because of hypoactive detrusors and hypoplastic urethras. After urologic treatment, serum creatinine in 5 patients reached a minimum of less than 0.4 mg/dL at some time during the first year of life. Another patient with a minimum creatinine level of 1.0 mg/dL has moderate renal insufficiency. CONCLUSION: From our series, it appears that early (before 20 weeks of gestation) shunt placement in severe lower urinary tract obstruction may benefit renal and pulmonary function. However, its efficacy in regard to bladder function remains questionable: shunt placement does not permit regular storage and evacuation, which may be essential for functional bladder development.

Female↗

Endogenous calcitonin gene-related peptide modulates tachycardiac but not bradycardiac baroreflex in rats.

Effects of intracisternally administered human calcitonin gene-related peptide (8-37) [hCGRP-(8-37)], an antagonist, and hCGRP, an agonist of the CGRP receptor in the rat central nervous system, on baroreflex sensitivity (BRS) were studied in conscious male rats. Each rat sequentially received intracisternally injected 0.9% saline and then hCGRP-(8-37) at doses of 1, 2.5, and 5 nmol in a volume of 10 microliters at an interval of 15 min. Five minutes after each injection, sodium nitroprusside (SNP, 10 micrograms/kg) or phenylephrine hydrochloride (PE, 2 micrograms/kg) was intravenously administered to induce reflex tachycardia or bradycardia, respectively. Intracisternally administered hCGRP-(8-37) increased BRS of the reflex tachycardia induced by SNP in a dose-related manner but did not change the BRS after PE. Intracisternally injected hCGRP significantly decreased the BRS after SNP. The lowering effect of hCGRP on BRS after SNP was inhibited by hCGRP-(8-37) injected before hCGRP. These results suggest that endogenous CGRP in the lower brain stem is selectively involved in the tachycardiac but not the bradycardiac baroreflex and modulates the baroreflex in an inhibitory rather than facilitatory fashion.

Animals↗

Atrial natriuretic peptide enhances IL-1 beta-stimulated nitric oxide production in cultured rat vascular smooth muscle cells.

OBJECTIVE: To elucidate the effect of atrial natriuretic peptide (ANP) on cytokine-induced nitric oxide (NO) production, we examined whether ANP affects IL-1 beta-stimulated NO production and inducible NO synthase (iNOS) mRNA expression in cultured rat vascular smooth muscle cells (VSMC). METHODS: VSMC were incubated with test agents for 24 h. The nitrite concentration of the culture medium, a stable-end product of NO, was measured by the column reduction method. NOS mRNA expression was analyzed by Northern blotting. The intracellular cAMP content was measured by enzyme immunoassay. cAMP-dependent kinase (PKA) activity was determined by a PKA assay system. RESULTS: IL-1 beta stimulated nitrite production in VSMC. ANP (10 nM to 1 mM) enhanced the nitrite production and iNOS mRNA expression in the presence of IL-1 beta. Both 8-bromo-guanosine 3',5'-cyclic monophosphate (8-br-cGMP) and dibutylyl adenosine 3',5'-cyclic monophate enhanced IL-1 beta-induced nitrite production. The effects of these two nucleotide donors on the nitrite production were not additive, suggesting a common pathway. KT 5720, an inhibitor of PKA, abolished the enhancement of nitrite production by ANP and 8-br-cGMP, while KT 5823, an inhibitor of cGMP-dependent protein kinase, did not inhibit the enhancement. In the in vitro assay 8-br-cGMP increased PKA activity. CONCLUSIONS: ANP and cGMP enhanced IL-1 beta-induced NO production in VSMC. PKA rather than PKG may be involved in the enhancement.

Animals↗

Relationship between extreme dippers and orthostatic hypertension in elderly hypertensive patients.

Among elderly hypertensive subjects, extreme dippers with marked nocturnal fall in blood pressure (BP) as well as nondippers with absent nocturnal fall in BP are more prone to cerebrovascular disease when compared with those with appropriate nocturnal BP fall. However, the relationship between these abnormal diurnal BP variation patterns and postural BP variation has not been investigated. We investigated the diurnal BP variation by ambulatory BP monitoring and postural BP variation during 70 degrees head-up tilt in 110 asymptomatic hypertensive elderly subjects, who consisted of 29 subjects with white-coat hypertension and 81 with sustained hypertension with various patterns of nocturnal fall in BP (14 extreme dippers, with asleep systolic BP decrease by > or =20% of awake systolic BP; 56 dippers, with decrease by > or =0% to <20%; 11 nondippers, with decrease by <0%). During tilt, the mean (SD) systolic BP increased 10 (19) mm Hg in the extreme dippers (P<.02), and it decreased by 7.5 (13) mm Hg in the nondippers (P<.05), whereas it did not change in the dippers and white-coat hypertensive subjects. The heart rate increased in all four groups to similar degrees during tilt. Orthostatic hypertension defined as systolic BP rise of 10 mm Hg or more during tilt was found in 10 (72%) of the 14 extreme dippers, 6 (11%) of the 56 dippers, and 1 (9%) of the 11 nondippers, while orthostatic hypotension defined as systolic BP decrease of 20 mm Hg or more was found in 3 (27%), 5 (9%), and 1 (7%) of the nondippers, dippers, and extreme dippers, respectively (chi2=29.3, P<.0001). In conclusion, the abnormal diurnal BP variation is closely related to the abnormal postural BP variation in elderly hypertensive patients, with extreme dippers showing orthostatic hypertension and nondippers showing orthostatic hypotension. The upright position during the daytime, which increases the BP in the extreme dippers and decreases it in the nondippers, may in part produce abnormal diurnal BP variation.

Aged↗

Apolipoprotein E epsilon 4 allele and whole brain atrophy in late-onset Alzheimer's disease.

OBJECTIVE: Diffuse brain atrophy is one of the gross pathological features of Alzheimer's disease and is a result of degenerative changes. The epsilon 4 allele of apolipoprotein E (APOE) is a risk factor or susceptibility gene in late-onset sporadic Alzheimer's disease and may influence the pathological changes associated with the disease. The aim of this study was to examine the relationship between the APOE epsilon 4 allele and whole brain atrophy. METHOD: Whole brain volume was quantified by using high-resolution magnetic resonance imaging and the computerized brain segmentation technique in 178 patients with late-onset sporadic Alzheimer's disease who carried no APOE epsilon 4 alleles (N = 62), one epsilon 4 allele (N = 93), or two (N = 23) and had comparable clinical severity of dementia. RESULTS: An apparent positive correlation was found between normalized whole brain volume (relative to total intracranial volume) and number of APOE epsilon 4 alleles; i.e., patients carrying two APOE epsilon 4 alleles had the least brain atrophy. This association between the APOE epsilon 4 allele and brain volume was similar in women and men and was independent of age, level of education, duration of illness since symptom onset, and severity of dementia. CONCLUSIONS: The results indicate that cognitive dysfunction progresses before severe brain atrophy develops in patients carrying the APOE epsilon 4 allele and suggest that an APOE epsilon 4-allele-related mechanism that affects neuronal function before a decrement in brain matter is involved in the development of dementia.

Aged↗

Determination of free fatty acids in human bile by high-performance liquid chromatography.

We developed a high-performance liquid chromatography (HPLC) method for free fatty acids (FFAs) analysis in bile. In this method, FFAs were extracted from bile in a single step using an Isolute ODS cartridge, derivatized with 9-anthryldiazomethane (ADAM). ADAM was chosen because of its high reactivity with carboxylic acid at room temperature. Then, HPLC was used for separating and quantifying FFAs. This method proved to be simple and time-saving. The mean recovery of FFA added to human gallbladder bile was 97.6%, and the detection limit was 100-250 pg. Using this method, we determined FFA concentrations in the gallbladder bile of 11 gallstone patients. The mean concentration of total FFA was 0.61 (SD = 0.41) mmol/L, and there was wide variation in the individual FFAs.

Adult↗

Hormonal and cardiorenal responses to acute saline loading in mild congestive heart failure--the effect of angiotensin converting enzyme inhibition.

We investigated cardiorenal responses to acute saline loading in patients with mild congestive heart failure (CHF) with and without angiotensin-converting enzyme (ACE) inhibition. Saline loading (infusion of 250 ml of normal saline) was performed on 10 patients with mild CHF and 10 control subjects. Although saline loading reduced plasma renin activity and plasma angiotensin II to a similar extent in both groups, it increased cardiac output, renal blood flow, and the ratio of renal blood flow to cardiac output in the mild CHF group but not in the control group. After saline loading, urinary sodium excretion was higher in the control than in the mild CHF group. In the mild CHF group, saline loading was performed again after an ACE inhibitor (delapril) had been administered for 5 days. Although delapril increased cardiac output and renal blood flow under basal conditions, saline loading did not affect these variables. Delapril improved urinary sodium excretion after saline loading. Thus, the renin-angiotensin-aldosterone axis may contribute to cardiorenal hemodynamics and renal sodium handling in patients with mild CHF. This effect may attenuate the natriuretic response to acute saline loading, and administration of an ACE inhibitor improves this attenuation.

Adult↗

A psychobehavioral factor, alexithymia, is related to coronary spasm.

The aim of this study was to assess whether the psychobehavioral pattern alexithymia is related to coronary artery spasm. Alexithymia, deficient psychological awareness, was examined using the Minnesota Multiphasic Personality Inventory Alexithymia Scale in 100 patients with angina pectoris in whom coronary spasm, defined as > or = 99% coronary narrowing, was documented upon ergonovine provocation, and in 109 patients with chest pain syndrome who were shown to have almost normal coronaries without inducible coronary spasm on coronary angiogram (control group). Alexithymia was approximately twice as prevalent in the coronary spasm group (31%) as in the control group (14%) (p<0.01). Among various conventional risk factors including hyperlipidemia, obesity, diabetes mellitus, hypertension, hyperuricemia, or family history of ischemic heart disease, only male sex and smoking were more prevalent in the coronary spasm group than in the control group (p<0.001). The odds ratios of coronary spasm adjusted for all the other risk parameters including sex and age were 4.14 [95% confidence interval (CI) 1.81-9.47] for alexithymia and 2.38 (95, CI 1.18-4.82) for smoking. A psychobehavioral pattern, alexithymia, relates to coronary spasm. This relationship is independent of the conventional coronary risk factors.

Adult↗

Liberation of phospholipids from Z-disks of chicken skeletal muscle myofibrils by 0.1 mM calcium ions: weakening mechanism for Z-disks during post-mortem aging of meat.

Weakening of the Z-disks of skeletal muscle myofibrils contributes to the tenderization of meat during post-mortem aging. To elucidate the weakening mechanism, we compared Z-disks weakened by post-mortem aging of chicken breast muscle with those of myofibrils treated with a solution containing 0.1 mM CaCl2 and 1 microM calpastatin domain I. In both cases, the Z-disks were weakened with a corresponding liberation of their constituent phospholipids (PLs). The liberation of PLs specific to 0.1 mM calcium ions was minimal at pH 6.5 and maximal at 35 degrees C together with the Z-disk weakening. Binding of calcium ions to PLs in the Z-disks was determined by 45Ca-autoradiography. Acidic PLs were strongly radioactive and neutral PLs were appreciably radioactive. It is very probable that acidic PLs would bind electrostatically to alpha-actinin under physiological conditions, and that this interaction would be broken by the binding of calcium ions at 0.1 mM to PLs, resulting in the partial liberation of PLs from Z-disks. We conclude, therefore, that the liberation of PLs by the binding of 0.1 mM calcium ions was the main cause for Z-disk weakening during the post-mortem aging of chicken.

Animals↗

A case of Cushing's syndrome due to ACTH-independent bilateral macronodular hyperplasia associated with excessive secretion of mineralocorticoids.

A 74-year-old man developed Cushing's syndrome and hypokalemia due to ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH) with excessive secretion of mineralocorticoid hormones. Plasma concentrations of weak mineralocorticoids were high. The increase in plasma cortisol did not have a diurnal rhythm, and was not suppressed by a high dose of dexamethasone. Plasma ACTH was undetectable, but plasma cortisol was increased by ACTH administration. The concentrations of mineralocorticoids, especially deoxycorticosterone and corticosterone were increased, and augmented the response to ACTH administration. Plasma renin activity and aldosterone concentrations were rather suppressed. Both adrenal glands, with a total weight of 110 g, were enlarged and contained several macronodules. These nodules were composed of hyperplasia of small cortical cells and usual clear cells. This is a rare case of ACTH-independent bilateral macronodular adrenocortical hyperplasia because there were excessive secretion of mineralocorticoid and hypokalemia.

Adrenal Cortex↗

Induction of torsades de pointes by dobutamine infusion in a patient with idiopathic long QT syndrome.

We used a provocative test with dobutamine infusion to diagnose long QT syndrome (LQTS) in a girl with a history of syncope. When dobutamine was infused at a rate of 10 microg/kg/min, the QT interval corrected for heart rate (QTc) was prolonged from 460 ms to 620 ms with abnormal TU complexes and torsades de pointes developed. In 5 control subjects the QTc did not change significantly during low-dose dobutamine infusion. Low-dose dobutamine, in addition to isoproterenol, may be useful for evaluation of prolongation of the QT interval and abnormal TU complexes in patients in whom LQTS is suspected.

Adolescent↗

Earthquake-induced cardiovascular disease and related risk factors in focusing on the Great Hanshin-Awaji Earthquake.

The major earthquake increases cardiovascular disease during the period from night-time to morning, especially in the elderly patients living around the epicenter. Earthquake-induced stress increased BP and blood viscosity determinants, and enhanced fibrin turnover with endothelial cell stimulation in a group of hypertensive elderly subjects. Earthquake might trigger the cardiovascular events through the potentiation of these acute risk factors. Reduction of stress and related acute risk factors in this period may suppress cardiovascular deaths following a major earthquake. Further investigation of the mechanisms triggering cardiovascular events after the a major event such as a major earthquake is a necessary part of the strategy for the prevention of cardiovascular disease.

Aged↗

[Perinatal management of posterior urethral valves detected by prenatal ultrasonography].

PURPOSES: Posterior urethral valves (PUV) are the most common cause of mechanical infravesical obstruction in children. It is emphasized that this disorder has broad spectrum of severity, and patients presenting signs and symptoms in neonates or early infancy are at high risks for renal failure. The clinical pictures changed dramatically with the introduction of prenatal diagnosis by ultrasonography (USG). We report on perinatal management of PUV detected by prenatal USG, especially stressing on the significance of early delivery in risky fetuses. PATIENTS AND METHOD: From 1987 to 1996, we treated 6 patients with PUVs who had been detected by prenatal USG. Fetal hydronephrosis was noticed between 26 to 29 weeks of gestation. Oligohydramnios was apparent at the same weeks of the detection or 2 to 7 weeks later. Fetal conference including obstetrician, neonatologist, anesthesist and urologist was taken place to discuss the date and mode of delivery. Among the patients, 5 were induced early delivery around 30 weeks of gestation. After birth, serum Cr was monitored, and small feeding tube was placed in the urethra. Primary valve ablation was indicated in 4 patients whose Cr returned to near normal after the urethral drainage. One required upper tract diversion because of the continuous elevation of Cr levels. RESULTS: Of the patients, one died of respiratory failure from lung hypoplasia. Ventilation support was needed in 3 patients. The patient who required upper tract division went into ESRF when he was 6 months old. Except for this patient, renal function improved in 4 patients with nadir Cr levels between 0.4 mg/dl to 0.6 mg/dl. Transurethral valve ablation was done on 5 patient between 16th to 40th days after birth with the lowest body weight at operation of 1450 g. Cystometric studies in neonatal periods showed small capacity, and hypertonic bladder in all patients. Valve ablation and administration of anticholinergics improved bladder function. CONCLUSION: Prenatal ultrasonography clearly demonstrate the pathological features of the fetus with PUVs. Because oligohydramnios started in the early 3rd trimester indicates acute renal failure of the fetus, early delivery followed by emergency treatment may salvage the most severe type of this entity.

Female↗

[Lung transplantation: present international status and basic approach].

Lung transplantation has been established as an optional treatment for irreversible diffuse lung disease. To date, more than 8,000 patients have undergone lung transplantation, while heart-lung transplantation is confined to a very limited number of cases due to the severe shortage of donors. There are various problems in clinical lung transplantation, including limited preservation time, post-transplantation edema, acute and chronic rejection, and a shortage of donor organs. Several solutions to these problems have been found in recent experimental studies. For example, potential therapies for posttransplantation edema have been proposed, and the possibility of long-term preservation has been suggested. Research on xenotransplantation and cadaveric lung transplantation is ongoing, and this may result in options to solve the problem of the shortage of donor organs. In particular, we believe that cadaveric lung transplantation has the potential to become a clinically useful therapy in the near future.

Child↗