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Biomedical subjects

K Shimada

Publications and source records attributed to K Shimada.

At least 739 records · Page 41Linked to original sources
PubMed1995

Radioimmunoassay method for the determination of 22-oxacalcitriol, a novel analog of 1 alpha,25-dihydroxyvitamin D3 having valuable clinical potency, in rat and human plasma.

22-Oxacalcitriol is a synthetic analog of 1 alpha,25-dihydroxyvitamin D3, which is expected to be a novel agent for the treatment of patients with secondary hyperparathyroidism, psoriasis, and/or breast cancer. A sensitive and practical RIA for 22-oxacalcitriol in rat and human plasma has been developed. A rabbit antiserum raised against 22-oxacalcitriol 3-hemiglutarate conjugated with bovine serum albumin was used in combination with a tritium-labeled 22-oxacalcitriol having high specific radioactivity. A plasma sample was extracted with ethyl ether and the extract was successively purified with Bond Elut C18 and a normal-phase HPLC prior to the RIA to remove interfering substances. Accuracy of the RIA was assessed by various studies including serial dilution and recovery tests. Intra- and inter-assay coefficients of variation were lower than 10%, and the quantification limit was low enough for practical use (33 pg/ml plasma). The present RIA will be useful for the pharmacokinetic studies of 22-oxacalcitriol in both preclinical and clinical stages.

Animals↗
PubMed1995

Synthesis and structure-activity relationships of gelatinase inhibitors derived from matlystatins.

To investigate a series of new inhibitors of gelatinases based on matlystatin B (1b), extensive structure-activity relationship studies were performed. The new derivatives were evaluated in vitro for the ability to inhibit gelatinases. The inhibitory activities against thermolysin were also assayed to test the compounds' selectivity. Among the compounds modified at the P'3 moiety, the N-methylamide derivative 5 g was virtually twice as effective on gelatinase B as the parent compound 1b (5g, IC50 = 0.27 microM vs. 1b, IC50 = 0.57 microM). Other derivatives, including 1) esters 7a and 7b having the ester portions P'2 and P'3, 2) the cyclic amino acids, L-proline or L-pipecolinic acid (13a and 13b) bearing P'2, and 3) compounds 29a and 29b representing an attachment of the pentyl side chain at C3' (P'1 side chain) instead of C2', all showed decreased potencies. The key discovery was the observation that the introduction of a nonyl group at the P'1 position yielded a compound (31f, IC50 = 0.0012 microM) with high inhibitory activity against gelatinases and high selectivity over thermolysin. This result suggested that the S'1 subsites of the gelatinases have a locally deep hydrophobic structure, since on the basis of the optimum inhibitory activity in the alkyl series, the nonyl group seems to fit best into this hydrophobic pocket. Thus 31f exhibited a 475-fold more potent inhibitory activity than 1b towards gelatinase B.

Acetylcysteine↗
PubMed1995

Changes of hepatic microsomal oxidative drug metabolizing enzymes in chronic renal failure (CRF) rats by partial nephrectomy.

Male SD rats, 7-weeks-old, were used to investigate the changes in the hepatic drug metabolizing system of chronic renal failure (CRF) model rats. Partial nephrectomy (5/6) was performed in a two-stage surgical procedure. After nephrectomy, the rats were housed under regular conditions at least 21 days. After confirming the CRF states, trimethadione (TMO, 100 mg/kg, i.p.) was administered for evaluation of the hepatic drug metabolizing capacity; the ratio of dimethadione (DMO: the only metabolite of TMO) to TMO (DMO/TMO) in the serum and the dialysate from the blood microdialysis method were ascertained. The hepatic drug metabolizing enzyme contents and activities were also determined. In the CRF rats, the DMO/TMO ratios decreased significantly; total cytochrome P450 (CYP) contents, aminopyrine N-demethylase activity and delta-aminolevulinic acid synthetase activity also decreased significantly in the CRF rats. The extent of the alterations of these enzyme contents and activities correlated well with the severity of the CRF states evaluated by the serum blood urea nitrogen and creatinine concentrations. With Western blot analysis, the levels of CYP2C6, CYP2C11 and CYP3A2 decreased considerably in the CRF rats. These results suggest that CRF states induce not only a reduction of renal function but also an alteration of hepatic metabolism.

Animals↗
PubMed1995

Nucleotide sequence of the Clostridium stercorarium xynB gene encoding an extremely thermostable xylanase, and characterization of the translated product.

The nucleotides of the xynB gene of Clostridium stercorarium F-9 were sequenced. The structural gene consists of an open reading frame of 1161 bp encoding a xylanase (XynB) in family F of 387 amino acids with a molecular weight of 44,377. The molecular weight of the enzyme purified from a recombinant Escherichia coli was around 41,000, smaller than the predicted value, on SDS-polyacrylamide gel electrophoresis due to the lack of 32 amino acids at the N-terminus. Intact XynB with a molecular weight of around 43,000 was immunologically detected in the total cell proteins of a recombinant E. coli and C. stercorarium F-9. The purified XynB was active toward xylan, carboxymethylcellulose, p-nitrophenyl-beta-D-xylopyranoside and p-nitrophenyl-beta-D-cellobioside. The pH optimum was 7.0 and it was quite stable over the pH range of 5 to 12 at 4 degrees C. This enzyme was optimally active at 80 degrees C and retained about 50% of the original activity even after incubation at 100 degrees C for 10 min.

Amino Acid Sequence↗
PubMed1995

Differential effects of an alpha 1-blocker (doxazosin) on diurnal blood pressure variation in dipper and non-dipper type hypertension.

A study was conducted to determine whether sympathetic nerve activity, one of the main regulators of blood pressure, is involved in high blood pressure in the night-time and morning. Twenty-seven untreated hypertensive subjects, in whom hypertension was diagnosed by ambulatory blood pressure (ABP) measurement, who showed a 24 h systolic ABP value over 140 mmHg and/or 24 h diastolic ABP over 90 mmHg were recruited. They also showed a night-time systolic ABP value of over 130 mmHg and/or a night-time diastolic ABP of over 80 mmHg. They were divided into two groups: "dippers (D)" whose night-time ambulatory blood pressure fell by more than 10% of the day-time blood pressure, and "non-dippers (ND)" in whom this phenomenon was absent. We examined the effect of a long-acting alpha 1-blocker (doxazosin) on diurnal blood pressure variation in these subjects with essential hypertension. Baseline casual blood pressure and 24 h systolic ABP were not significantly different between the two groups. However, both night-time and morning ABP in ND were higher than those in D. Administration of doxazosin (mean 73 +/- 13 (SE) d) significantly decreased casual blood pressure, and 24 h, day-time, night-time and morning systolic ABP in the whole cohort. When subjects were divided into D and ND, the day-time and morning systolic ABP decreased significantly after doxazosin treatment in both groups, whereas the night-time systolic ABP decreased significantly only in ND but not in D. These results suggest that sympathetic nerve activity involved in elevating blood pressure during the night may differ between D and ND.

Adrenergic alpha-Antagonists↗
PubMed1995

Effect of prolonged beta-adrenergic blockade induced by atenolol on left ventricular remodeling after acute myocardial infarction in the rat.

Beta-adrenergic receptor blockade reduces the mortality rate after acute myocardial infarction (AMI) in humans. However, the effects of beta blockade on left ventricular remodeling remain unknown. Therefore, in the present study we investigated the effect of prolonged beta-adrenergic receptor blockade with atenolol on left ventricular remodeling following AMI in rats. Myocardial infarction (MI) was produced in Wistar-Kyoto rats by ligating the coronary artery. Four groups of rats were studied: sham-operated (n = 10); atenolol (1 g/l in drinking water) treated sham-operated (n = 8); untreated MI (n = 11); atenolol treated MI (n = 10). Hemodynamic measurements were made about 3 weeks after the operation. Infarct size was similar in treated and untreated MI rats (31.2 +/- 2.5% cf. 33.5 +/- 2.0%). MI rats were characterized by increases in left ventricular end-diastolic pressure (LVEDP), right atrial pressure (RAP), right ventricular systolic pressure (RVSP), and left ventricular end-diastolic volume index (LVEDVI), as compared with sham-operated rats. In sham-operated rats, prolonged beta-adrenergic receptor blockade produced only a reduced HR. Atenolol-treated MI rats had a significantly higher LVEDP, RAP and LVEDVI than did rats with untreated MI. Prolonged beta-adrenergic receptor blockade with atenolol appeared to promote left ventricular remodeling after AMI. Thus, the treatment of AMI with beta-adrenergic receptor blockade in the clinical setting should be evaluated with respect to ventricular remodeling during prolonged therapy.

Animals↗
PubMed1995

Aneurysmal dilatation of the pulmonary trunk with mild pulmonic stenosis.

We present the unusual case of a 72-year-old woman whose chest X-ray showed an abnormal left hilar shadow. A pulmonary angiogram revealed an aneurysm in the pulmonary artery with a diameter of 55 mm that extended from the main pulmonary trunk to its bifurcation. Mild pulmonic stenosis with a systolic pressure gradient of 18 mmHg across the pulmonic valve was recognized. Mild dilatation of the ascending aorta was also present. The pressure gradient across the pulmonic valve was lower than is typical for an aneurysmal dilatation, suggesting that this patient represented a case of idiopathic pulmonary artery dilatation. We suspected the presence of a congenital structural alteration common to the pulmonary artery and the ascending aorta.

Aged↗
PubMed1995

Three-dimensional structure of the perimysium in sternocleidomastoid muscle.

The morphology of the sternocleidomastoid muscle (SCM) of human fetuses, ranged from 12 to 32 weeks gestation, was investigated by a light microscopy and a scanning electron microscopy. The collagenous fibers of the perimysium of the SCM formed complex structures from 24 weeks gestation by contrast to fibers of the endomysium of the SCM. The cross-sectional area (CSA) of the bundle of muscle fibers and the CSA of the individual muscle fibers of the SCM increased during development from 12 to 32 weeks gestation, in a process linked to the development of the perimysium. Therefore the perimysium affects and controls to the muscle fiber of the developed SCM and acts to resisting stretch forces in the movements. The changes in the arrangement and development of the collagenous fibers in the perimysium may be correlated to with these of the muscle fibers.

Clavicle↗
PubMed1995

Morphology of the nerve terminals of laryngeal muscles in the Japanese monkey (Macaca fuscata).

Laryngeal muscles, namely, the cricothyroid (CT), lateral crico-arytenoid (LCA), thyrio-arytenoid (TA), posterior crio-arytenoid (PCA), interarytenoid (IA) muscles, of Japanese monkeys (body weight, 4.4-8.3 kg; 3-10 years old, male) were examined histologically and by light and scanning electron microscopy. The diameter of muscle fibres with nerve terminals in the CT of the Japanese monkey was larger than that of other laryngeal muscles. However, the areas of nerve terminals varied among laryngeal muscles. The mean diameters of nerve terminals of the CT and PCA were large and basically resembled those of other laryngeal muscles. They contribute mainly to maintenance of phonation which the adductor muscles contribute mainly to postural adjustments of the cartilage. The differences in features of nerve terminals of each muscle suggest the CT and PCA may contribute mainly to the frequency or pitch of voice and intensity of the voice during vocalization and to respiration.

Animals↗
PubMed1995

Classification of the ophthalmic artery that arises from the middle meningeal artery in Japanese adults.

In a study of Japanese adults, we found that the orbital branch (OB) passing through the superior orbital fissure frequently anastomosed with the lacrimal artery or the ophthalmic artery (12/20). However, the OB passing through the meningo-orbital foramen (mof) only associationaly anastomosed with branches of the ophthalmic artery (4/79). Furthermore, the OB in the orbit, excluding the lacrimal gland as previously reported. We examined 116 cases in which the OB passed through the mof in 129 adult Japanese cadavers (45.0% in 258 sides). The OB passing through the mof was always distributed to the periorbital region and the area that it supplied was limited to the periorbita in about half of those cases. In another half of the cases (58/116), the area supplied included the lacrimal gland.

Adult↗
PubMed1995

Morphometric analysis of neurons in ganglia: geniculate, submandibular, cervical spinal and superior cervical.

The geniculate ganglia (GG), the submandibular ganglion (SG), the cervical spinal ganglion (CSG) and the superior cervical ganglion (SCG) are clinically important. But details of these ganglia have not been included in textbook descriptions. We conducted research to bring precise figures to light. We prepared serial sections of these ganglia in five Japanese adults after precise dissections to count the numbers, measure the perimeters and the areas, and calculate the circularity ratios (CRs) of the ganglion cells. The numbers of neurons were in the following order: SCG > CSG > SG > GG, and the average neuronal areas in the following order: CSG > GG > SG > SCG. Average neuronal CRs were around 0.90 in all ganglia. In other words, the morphometric evaluation showed that neurons in such ganglia are practically circular in shape. Our morphometry thus reveals that the neurons in these ganglia are sensory neurons in the broad definition of the word from a quantitative point of view.

Adult↗
PubMed1995

Determination of the thickness of the fixed aqueous layer around polyethyleneglycol-coated liposomes.

The zeta potentials of adriamycin-encapsulating liposomes containing 1-(monomethoxy polyethyleneglycol)-2,3-dimyristoylglycerol (PEG-DMG) were measured in an isotonic solution of 10mM lactate buffer (pH 4.0) with sodium chloride and sucrose. The negativity of the zeta potentials of adriamycin-encapsulating liposomes containing PEG-DMG decreased with increases in NaCl concentration more steeply than that of adriamycin-encapsulating liposomes without PEG coating. From this observation, the electrical potential distributions near the membrane surfaces were shown to be different between adriamycin-encapsulating liposomes with and without PEG coating. Based on these zeta potential data, the thickness of the fixed aqueous layer around PEG-DMG-containing adriamycin liposomes was determined from the slope of 1n zeta potential versus Debye-Hückel parameter plot. As a result, a correlation was indicated to exist between the circulation time of liposomes and the thickness of the aqueous layer around the liposomes.

Chemistry, Pharmaceutical↗
PubMed1995

A space-occupying lesion in the liver due to Capillaria infection.

A space-occupying lesion 3.5 by 2.0 cm in size caused by Capillaria infection was revealed ultrasonographically in segment 6 (S6) of the liver of a 32-year-old woman from Okinawa, Japan, who was hospitalized with a complaint of pain in the right upper quadrant. Laboratory examination showed leukocytosis of 10,400/mm3 with 22% eosinophils and slight impairment of liver function. The tumor was removed surgically and found to be a necrotic granuloma with eosinophilic infiltration formed around a degenerated nematode. The causative agent was presumed to be Capillaria hepatica based on the morphology of the bacillary bands and stichosome observed in the sectioned worm and in the fragments of worm recovered by dissecting the tumor tissue that was embedded in paraffin.

Adult↗
PubMed1995

[Urinary tract abnormalities associated with anorectal malformations].

Anorectal malformation (ARM) is often associated with urological problems such as congenital urogenital anomalies, recto-urinary fistula, neurogenic bladder due to vertebral anomalies and operative complications. We analyzed 57 cases of ARM and discussed about the management of associated urogenital anomalies during neonatal and infantile period. The incidence of urogenital anomalies was 85.7% in high type, 65.5% in intermediate type and 38.1% in low type. Among these urinary tract anomalies, VUR was most common and was documented in 38.6% of ARM patients. Renal dysplasia, PUJ stenosis, megaureter and urethral stenosis was also common in these patients. Renal dysfunction was documented in 5 cases (2 in high type, 2 in intermediate and 1 in low type), mainly due to VUR and renal aplasia. These results show the need for evaluation of urinary tract during the neonatal and early infantile period even in low type ARM. The management of urinary tract anomalies associated with ARM is firmly related with the management of ARM itself, and we must be closely in co-operation with pediatric surgeons.

Abnormalities, Multiple↗
PubMed1995

Genetic determinants of plasma factor VII activity in the Japanese.

We investigated the frequency of the factor VII Gln353 (FVII Gln353) allele in Japan, where coronary artery disease is much less common and factor VII coagulant activity (FVIIc) is lower than in Western countries. Japanese males (n = 144) aged 40-59 years living in 2 different districts were studied, and the FVIIc and activated factor VII (FVIIa) levels were measured with human (FVIIa Hum) and bovine soluble tissue factor (FVIIa Bov). The frequency of the FVII Gln353 allele in the 2 districts was 0.026 and 0.052 (combined: 0.034), which was about one third of that in a European population. Thus, the lower FVIIc level in Japanese is not due to the effect of FVII Gln353 allele. Ten individuals with the Gln353 allele showed a 39% decrease of FVIIa Hum levels and a 29% decrease of the FVIIa Bov level compared with 134 individuals homozygous for the FVII Arg353 allele. These decreases of FVIIa were greater than the decrease of FVIIc (17%), suggesting that FVII Gln353 may be difficult to activate in vivo. The marked decrease of FVIIa levels in individuals with the FVII Gln353 allele suggests that they are genetically protected against cardiovascular disease irrespective of ethnic background, by virtue of their decreased FVIIa level.

Adult↗
PubMed1995

Nitric oxide synthesis in cardiac myocytes and fibroblasts by inflammatory cytokines.

OBJECTIVE: The aim was to investigate nitric oxide (NO) synthase activity in cultured neonatal rat cardiac myocytes and fibroblasts upon treatment with inflammatory cytokines interleukin 1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha), IL-2, IL-6, IL-8, transforming growth factor beta (TGF-beta) and gram negative bacterial lipopolysaccharide (LPS). METHODS: NO and guanosine 3',5'-cyclic monophosphate (cGMP) synthesis was measured in cultured neonatal rat cardiac myocytes and fibroblasts, using Griess reagent and an enzyme immunoassay kit, respectively. The expression of inducible NO synthase (iNOS) mRNA and protein was assayed by northern and western blotting, respectively. RESULTS: Incubation of cardiac myocytes for 24 h with IL-1 beta (10 ng.ml-1) or LPS (1 microgram.ml-1) caused significant increases in NO and cGMP production. TNF-alpha, IL-2, IL-6, IL-8, and TGF-beta showed no significant effect on their production. IL-1 beta induced NO and cGMP production in a time and dose dependent manner. IL-1 beta also increased iNOS mRNA and protein accumulation in cardiac myocytes. Simultaneous incubation of IL-1 beta with NG-monomethyl-L-arginine, genistein, calphostin C, cycloheximide, or actinomycin D completely inhibited the IL-1 beta induced NO production by cardiac myocytes. TGF-beta, dexamethasone, or cyclosporin A also dose dependently inhibited the IL-1 beta induced NO production. Exposure to IL-1 beta for 12-24 h decreased the beating rate of cardiac myocytes, but addition of dexamethasone completely overcame this inhibition. In contrast to cardiac myocytes, incubation of cardiac fibroblasts for 24 h with IL-1 beta or LPS showed no significant effect on NO or cGMP production. CONCLUSIONS: These observations suggest that IL-1 beta/LPS responsive iNOS, which is an important regulator of contractile function of the heart, is present in cardiac myocytes but not in cardiac fibroblasts.

Amino Acid Oxidoreductases↗