Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 847 records · Page 47Linked to original sources

PubMed1995

Growth effects of electrically stimulated contraction on adult feline cardiocytes in primary culture.

The purpose of this study was to determine effects of long-term electrical stimulation of cardiocyte contraction on protein synthesis rates and total protein content. Adult feline cardiocytes were plated on laminin-coated culture trays and maintained in a serum-free medium consisting of M199 supplemented with ascorbate, bovine serum albumin, creatine, carnitine, taurine, and 10(-7) M recombinant insulin. Cardiocytes were electrically stimulated to contract with use of continuous electrical pulses of alternating polarity at a frequency of 1 Hz and pulse duration of 5 ms. Nonstimulated cardiocytes are normally quiescent and were used as the control group. In control quiescent cardiocytes, protein synthesis rate decreased by 14% between days 1 and 4 in culture and then remained stable through day 7. In electrically stimulated cardiocytes, protein synthesis rates increased by 19% between days 1 and 7. Protein synthesis rates were 18% higher on day 4 and 43% higher on day 7 in electrically stimulated than in quiescent cardiocytes. Protein content per cell was determined by measuring total fluorescence per cell by use of confocal microscopy of fluorescein isothiocyanate-stained cells. Electrical stimulation significantly increased cellular protein content by 52% after 7 days compared with controls. Quiescent and electrically stimulated cardiocytes remained rod shaped, retained their myofibrillar architecture, and were responsive to electrical stimulation over the 7-day period. These data demonstrated that electrically stimulated contraction of adult cardiocytes resulted in cell growth, as assessed by an increase in protein content per cell over 7 days in culture. This increase was due, at least in part, to an acceleration of steady-state protein synthesis rates.

Animals↗

PubMed1995

Inhibition of collagen cross-linking: effects on fibrillar collagen and ventricular diastolic function.

The fibrillar collagen network is postulated to be a primary determinant of left ventricular diastolic stiffness. This hypothesis was tested by examining the structural and physiological effects of a reduction in fibrillar collagen content and cross-linking in the intact left ventricle. Collagen cross-linking was inhibited by treating five normal adult pigs with beta-aminopropionitrile (BAPN; 10 g/day po) for 6 wk; five normal untreated pigs served as controls. Left ventricular volume, mass, and function were determined by simultaneous echocardiography and catheterization. Chamber stiffness, defined by pressure vs. volume data, and myocardial stiffness, defined by stress vs. dimension data, were determined from variably loaded beats during dextran infusion. Collagen distribution (% area) and integrity (% confluence) were determined by light microscopy. Collagen content was measured by hydroxyproline assay, and collagen cross-linking was measured by salt extraction. BAPN decreased collagen distribution (% area decreased from 12 +/- 1% in control to 7 +/- 1% in BAPN, P < 0.05), collagen integrity (% confluence decreased from 8 +/- 1% in control to 4 +/- 1% in BAPN, P < 0.05), collagen content (from 36 +/- 2 mg/g dry wt in control to 27 +/- 2 mg/g dry wt in BAPN, P < 0.05), and collagen cross-linking (extractable collagen increased from 21 +/- 2% in control to 28 +/- 2% in BAPN, P < 0.05). BAPN decreased chamber stiffness (0.13 +/- 0.02 in control to 0.06 +/- 0.01 in BAPN, P < 0.05) and myocardial stiffness (10.4 +/- 0.5 in control to 6.6 +/- 0.5 in BAPN, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopropionitrile↗

PubMed1995

Gene expression of retinoic acid receptors, retinoid-X receptors, and cellular retinol-binding protein I in bone and its regulation by vitamin A.

We investigated the gene expression of retinoic acid (RA) receptors (RARs) and retinoid-binding proteins, and the effect of vitamin A on gene expression in the rat tibia to understand the actions of vitamin A on bone tissue. The transcripts of all three subtypes of all-trans RAR (alpha, beta, and gamma) and two of three subtypes of retinoid-X receptor (alpha and beta) were detected by Northern blotting. Among cellular retinol-binding protein I (CRBP-I) and CRBP-II and cellular retinoic acid-binding protein I and II, only the CRBP-I gene was expressed. These results indicated that in bone, the actions of vitamin A are exerted through these nuclear receptors by regulating target gene expression, and through CRBP-I by modulating the intracellular transport of vitamin A. Moreover, using rats of various retinoid status, we investigated whether the expression of target genes for vitamin A (RAR beta and CRBP-I) is regulated by retinoic acid (RA) in the adult rat tibia. The messenger RNA levels of these genes in vitamin A-deficient rats decreased to half of those in normal rats and were quickly restored (4 h) by either all-trans-RA or 9-cis-RA. Excess RA given to normal rats doubled the messenger RNA levels of these two genes. These results verified that, like other target tissues, bone is a target for vitamin A in terms of gene expression. In addition, we examined the effect of RAs on the expression of the target genes for vitamin D, because it is possible that 9-cis-RA is involved in the transcriptional control of vitamin D receptor by forming a heterodimer complex with retinoid-X receptor. The vitamin D-regulated osteopontin gene was induced 4 h after the administration of RA regardless of retinoid or vitamin D status. RA also induced osteopontin gene expression in concert with vitamin D in normal rats. Specific inhibitors of transcription showed that gene expression may be regulated by RA at the transcriptional level. Thus, the results presented here clarified at the molecular level that bone is a target organ for vitamin A in terms of gene expression.

Animals↗

PubMed1995

Chondroitin sulfate immobilized onto culture substrates modulates DNA synthesis, tyrosine aminotransferase induction, and intercellular communication in primary rat hepatocytes.

Newly prepared phosphatidylethanolamine (PE) conjugates of glycosaminoglycans (GAGs) enabled us to immobilize GAGs to solid phase through hydrophobic interaction. Using these compounds, called GAG-PEs, we studied the effects of GAGs immobilized to culture plates coated with various extracellular matrix (ECM) proteins in terms of cell-substrate adhesion, DNA synthesis, tyrosine aminotransferase (TAT) induction, and intercellular communication in primary rat hepatocytes. Treatment with chondroitin sulfate (CS)-PE at 10 micrograms/ml made laminin, fibronectin, vitronectin, and collagens type I-V less adhesive as substrates for cell attachment and inhibited cell spreading on these substrates. The effect on cell attachment was lost after long incubations over 2 h. Dermatan sulfate (DS)-PE was also inhibitory, but less effective. The conjugates of heparan sulfate (HS), heparin, and hyaluronan were much less effective. DNA synthesis initiated by EGF in the culture on laminin substrates was inhibited most strongly by CS-PE, as well as by DS-PE and hyaluronan-PE, but not by either HS-PE or heparin-PE. With type I collagen substrates, GAG-PEs had similar effects but to lesser extent. TAT induction in the culture on laminin substrates but not on type I collagen substrates was significantly enhanced by CS-PE. In terms of DNA synthesis and TAT induction, the culture on laminin substrates treated with CS-PE was comparable to that at higher cell density on the non-treated laminin substrates. Intercellular communication assessed by dye coupling was maintained longer on the substrates treated with CS-PE. Taken together, our results demonstrate that CS immobilized especially onto laminin substrates inhibits the growth of hepatocytes and enhances their differentiated functions by modulating cell-ECM protein interactions.

Animals↗

PubMed1995

Synthesis and structure-activity relationships of 4-amino-5-chloro-2-ethoxybenzamides with six- and seven-membered heteroalicycles as potential gastroprokinetic agents.

A new series of 4-amino-5-chloro-2-ethoxybenzamides 3b--f and 5--8 bearing six- and seven-membered heteroalicycles was prepared and evaluated for gastroprokinetic activity. Compounds 3b--e, derived by replacement of the morpholine oxygen of 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-5- chloro-2-ethoxybenzamide (3a) with other atoms (sulfur, nitrogen and carbon), generally exhibited a potent gastric emptying activity. N-(4-Benzyl-3-morpholinyl)methylbenzamide (5a) and its analogues 5b--e had weaker activity. However, N-(4-benzyl-3-morpholinyl)ethylbenzamide 8 was as potent as 3a. Benzamides 6a--e, having seven-membered heteroalicycles, showed fairly potent activity. Molecular superimpositions of 5a, 6a and 8 upon 3a using computer graphics suggested that the direction of the N-benzyl group greatly influences the gastric emptying activity, whereas the location of the alicyclic nitrogen is less critical.

Animals↗

PubMed1995

Development of potent serotonin-3 (5-HT3) receptor antagonists. I. Structure-activity relationships of 2-alkoxy-4-amino-5-chlorobenzamide derivatives.

A new series of 2-alkoxy-4-amino-5-chlorobenzamide derivatives bearing five- to seven-membered heteroalicyclic rings in the amine moiety was synthesized and evaluated for serotonin-3 (5-HT3) receptor antagonistic activity by assaying the ability to antagonize the von Bezold-Jarisch reflex in rats. The five- to seven-membered heteroalicycles comprise pyrrolidine, morpholine, 1,4-thiazine, piperidine, piperazine, 1,4-oxazepine, 1,4-thiazepine, azepine, and 1,4-diazepine rings. Among them, some benzamide derivatives having a 1,4-diazepine ring showed a potent 5-HT3 receptor antagonistic activity. In particular, 4-amino-5-chloro-N-(1,4-dimethylhexahydro-1H-1,4-diazepin-6- yl)-2- ethoxybenzamide (96) and the 1-benzyl-4-methylhexahydro-1H-1,4-diazepine analogue 103 showed potent 5-HT3 receptor antagonistic activity without 5-HT4 receptor binding affinity.

Animals↗

PubMed1995

Development of potent serotonin-3 (5-HT3) receptor antagonists. II. Structrue-activity relationships of N-(1-benzyl-4-methylhexahydro-1H-1,4- diazepin-6-yl)carboxamides.

Our studies on 4-amino-5-chloro-2-ethoxybenzamides led to the discovery that the N-(1,4-dimethylhexahydro-1H-1,4-diazepin-6-yl)benzamide 9 and the 1-benzyl-4-methylhexahydro-1H-1,4-diazepine analogue 10 are potent serotonin-3 (5-HT3) receptor antagonists. Structure-activity relationship (SAR) studies on the influence of the aromatic nucleus of 9 and 10 upon inhibition of the von Bezold-Jarisch reflex in rats are described. Heteroaromatic rings such as pyrrole, thiophene, furan, pyridine, pyridazine, 1,2-benzisoxazole, indole, quinoline, and isoquinoline rings showed weak 5-HT3 receptor antagonistic activity. Within this series, use of the 1H-indazole ring as an aromatic moiety led to a substantial increase of the activity; the 1H-indazolylcarboxamides 54, 57, 97, and 102 showed potent 5-HT3 receptor antagonistic activity. The optimal compound identified via extensive SAR studies was N-(1-benzyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)-1H-indaz ole-3- carboxamide (54), whose effect was superior to that of the corresponding benzamide 10 and essentially equipotent to those of ondanbsetron (1) and granisetron (4).

Animals↗

PubMed1995

Synthesis and biological activities of metabolites of mosapride, a new gastroprokinetic agent.

In order to confirm the proposed structures of two metabolites 3 and 4 of the gastroprokinetic agent mosapride [4-amino-5-chloro-2-ethoxy-N-([4-(4-fluorobenzyl)-2-morpholinyl] methyl)benzamide, 2], the compounds were synthesized and their biological activity was examined. The structures of the metabolites were confirmed by means of comparison with the synthetic compounds. The serotonin 5-HT4 receptor agonistic activities of the metabolites were found to be less than that of mosapride.

Animals↗

PubMed1995

Effect of vasoactive intestinal polypeptide (VIP) on the net movement of electrolytes and water and glucose absorption in the jejunal loop of sheep.

The effect of vasoactive intestinal polypeptide (VIP) on glucose absorption and the net movement of electrolytes and water in the jejunum of sheep was investigated using a Thiry-Vella loop. Intraluminal perfusion of glucose solution (10 mM) containing NaCl (149 mM) and PEG (1 mg/ml) was done at 1 ml/min and the outflow solution was collected every ten minutes. After a 30 min control period. VIP was infused into the jugular vein for 30 min at rates of 10, 30, 100, 300 and 1,000 pmol/kg/hr. In the control period, water, sodium, chloride and glucose were absorbed, while bicarbonate and potassium were secreted. VIP decreased water absorption at 10 and 30 pmol/kg/hr and converted to secretion at over 100 pmol/kg/hr in a dose-dependent manner. Sodium flux changed to secretion only at 1,000 pmol/kg/hr, but chloride flux remained absorptive even at the highest dose. Bicarbonate secretion was stimulated dose-dependently by VIP. Potassium secretion was also increased at all doses, though this response was not dose-dependent. The net glucose absorption was not altered by VIP at any dose. Our findings indicate that VIP stimulates the jejunal secretion of water, sodium, potassium and bicarbonate and that VIP does not inhibit glucose absorption when the secretion of luminal fluid is accelerated by VIP in the jejunal loop of sheep.

Animals↗

PubMed1995

Renal responses to atrial natriuretic peptide (ANP) in rats with non-oliguric acute renal failure induced by cisplatin.

This study was designed to compare the renal effects of atrial (A-type) natriuretic peptide (ANP) on control (saline-injected) rats and rats with non-oliguric acute renal failure induced by cisplatin. The results obtained here are summarized as follows: (1) In the metabolic cage study, cisplatin-treated rats showed increases in blood urea nitrogen and serum creatinine while creatinine clearance decreased to the lowest levels on day 4. A transient increase in urinary protein was observed at day 4. (2) ANP infusion significantly increased urine flow rate (UFR), creatinine clearance (CCr), fractional excretion rates of sodium (FENa) and chloride (FECl), and urinary phosphorus and magnesium (Mg) excretions in a dose-dependent manner without affecting renal plasma flow and fractional excretion rates of potassium and urea in cisplatin-treated rats. (3) Renal effects of ANP on UFR, CCr, FENa, FECl and excretion of Mg were more pronounced in cisplatin-treated rats compared to control rats although markedly blunted responses to ANP have been reported in nephrotic patients and nephrotic animals induced by adriamycin and aminonucleoside. (4) Histological examination showed extensive necrosis of the S3 segment of the proximal tubule located in the outer stripe of the outer medulla with minimal glomerular abnormalities in the kidney of cisplatin-treated rats. In conclusion, the main mechanism of the increased renal responses to ANP is considered to be due to an increased delivery of sodium, fluid and ANP itself to the inner medullary collecting duct which is the major renal site of action of ANP under the condition of acute proximal tubular necrosis by cisplatin.

Acute Kidney Injury↗

PubMed1995

Dexamethasone-induced changes in glucose transporter 4 in rat heart muscle, skeletal muscle and adipocytes.

To clarify the effect of glucocorticoid on glucose transporters (GLUT) in adipocytes and muscle, we examined the changes of GLUT4 in rat heart muscle, skeletal muscle and adipocytes during long-term administration of dexamethasone and the translocation of GLUT4. The levels of GLUT4 in the plasma membrane and the low-density microsome fraction were measured by Western blotting using anti-GLUT4 peptide antibody. The levels of GLUT4 in the heart and skeletal muscles of rat were unchanged by treatment of dexamethasone. In the adipocytes the level of GLUT4 in plasma membrane was changed, but it was decreased in the low-density microsome fraction. Although adipocytes are less involved in blood sugar regulation than skeletal muscle, this finding suggests that glucose metabolism in Cushing's syndrome is affected partly by a decrease of GLUT4 in the adipocytes.

5'-Nucleotidase↗

PubMed1995

The double omohyoid muscle in humans: report of one case and review of the literature.

An anomalous muscle was found in the right anterior cervical region of a 68-year-old Japanese man. The muscle was investigated anatomically, with special reference to its supply. Few such reports are available. The anomalous muscle arose from the upper margin of the scapula as an aponeurotic sheet, ran medialocranialward and separated into the superficial and profound fasciculi at the lateral edge of the sternohyoid muscle. The former fasciculus was inserted into the lower border of the hyoid bone without fusing with adjacent muscles, or as an independent fasciculus. Meanwhile, the latter fasciculus incompletely fused with the lateral portion of the sternohyoid muscle. This muscle was supplied from its posterior surface and the upper edge by two slender nerves from the ansa cervicalis (roots of origin: C1, C2 and C3). Based on the nerve supply and a review of the literature, the muscle is discussed in terms of its true nature and its mechanism of formation. As a result of the investigation, this muscle is assumed to be a vestigial structure in humans reduced from the M. episterno-cleido-hyoideus sublimis (Fürbringer), which is observed in lower types of vertebrates (reptilies, etc.).

Aged↗

PubMed1995

Reduced muscle uptake of oxygen during exercise in patients with systemic lupus erythematosus.

OBJECTIVE: To assess the factors limiting aerobic exercise capacity in patients with systemic lupus erythematosus (SLE). METHODS: The anaerobic threshold (AT) and O2 pulse, i.e., VO2/heart rate (HR), were measured in 21 patients with SLE without cardiopulmonary complications by the analysis of expired gas during incremental work load in exercise testing. The relationships between work rate (WR) and VO2, HR and VO2/weight (Wt), and lupus activity index (LAI) and AT were analyzed. RESULTS: The AT of the patients with SLE was significantly lower than for a control group. Little increase in O2 pulse and very low delta VO2/delta WR and delta VO2/Wt@delta HR were found during work load in some patients with SLE, especially those with a low AT and high LAI. Patients with SLE with a high LAI tended to show a low AT. CONCLUSION: The low aerobic exercise capacity of patients with SLE appeared to be mainly due to a small increase in O2 pulse. This may have resulted from impaired oxygen diffusion in the inflamed peripheral muscles in patients with active SLE. Low AT may explain in part why patients with SLE become easily fatigued.

Adult↗

PubMed1995

Hyposensitivity of peripheral alpha-adrenoceptors in respirator-dependent amyotrophic lateral sclerosis assessed by intravenous norepinephrine infusion.

Intravenous norepinephrine infusion test was performed in eight patients with amyotrophic lateral sclerosis (ALS) supported by respirators and nine control subjects, to examine alpha-adrenoceptor function of peripheral resistant blood vessels. Baseline plasma norepinephrine concentrations in ALS patients were significantly higher than those in control subjects, indicating basal sympathetic hyperactivity (normal 218.2 +/- 59.7 pg/ml; ALS 450.0 +/- 288.4 pg/ml). The stimulus-response curves in the patients were similar to those in control subjects, and there were no significant differences between mean gains of the stimulus-response curves in both groups (normal 18.7 +/- 5.5; ALS 15.2 +/- 11.2). However, three ALS patients, two of whom had circulatory fluctuation and sympathetic hyperactivity, revealed lower gain levels than the mean minus 2 SD in control subjects (4.7, 1.1 and 3.7). This indicates hyposensitivity or down-regulation of the alpha-adrenoceptor function of peripheral blood vessels in these ALS patients. For early detection of sympathetic hyperactivity and prediction of circulatory collapse, it would be useful to measure the plasma norepinephrine concentration and the gain of the norepinephrine infusion curve in respirator-dependent ALS patients.

Aged↗

PubMed1995

[Blood coagulation and fibrinolysis in relation to endotoxemia in liver cirrhosis and hepatocellular carcinoma].

The blood coagulation and fibrinolysis of 33 patients with compensated liver cirrhosis and 31 patients with hepatocellular carcinoma were examined using several markers, namely thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC), antithrombin-III (AT-III) and prothrombin time, and the relationship between these markers, endotoxemia, and TNF-alpha was examined. These patients had no complications due to hepatic failure, such as infections, encephalopathy, ascites, G-I bleeding and clinical DIC. PIC was not elevated, but TAT tended to be elevated in LC and significantly elevated in HCC. AT-III was decreased in LC and HCC, and the blood endotoxin was partly positive in LC and HCC, but was not correlated with AT-III or PT. The TAT level in the blood-endotoxin-positive patients measured by endospecy methods was higher than that in the negative patients, and was significantly correlated with the blood endotoxin level in the LC and HCC patients (r = 0.57, r = 0.88, p < 0.01). No relationship was observed between TNF-alpha and blood endotoxin. In conclusion, (1) blood coagulability was activated already in compensated LC and HCC, but was not connected with fibrinolysis, (2) the activation of coagulability was closely related with endotoxemia, and (3) TNF-alpha was not correlated with blood endotoxin or TAT.

Blood Coagulation↗

PubMed1995

[Morphological analysis of the gallbladder elevated lesions--Macroscopic, stereoscopic, and histological study].

I analyzed morphological pathology of elevated lesions of gallbladder (ELGB) 136 cases, 177 lesions. According to the characteristic morphological feature, I can reach to differential diagnosis of ELGB. Most of I s and II a type carcinoma is papillary adenocarcinoma, which have irregular papillary surface. A few of II a type carcinoma is tubular adenocarcinoma, which is macroscopically granular and nodular, but, have stereoscopically small, uneven pits. Adenoma, most of which is tubular adenoma, is pedunculated, and have macroscopically multinodular, stereoscopically smooth surface. Whereas, hyperplastic polyp can be classified to "papillary type" and "nodular type", according to surface structure. "Papillary type" is pedunculated or sessile, but, "nodular type" is only sessile. This morphological feature is different from adenoma's. Pedunculated carcinoma (I p type) is frequently localized in mucosa. Whereas, if we can exclude adenomyomatosis, sessile lesion, more than 13mm is frequently advanced carcinoma, which invade to subserosa or more deeply. But, sessile carcinoma, smaller than 11mm, is frequently early carcinoma, which is localized in mucosa or muscle layer.

Adenocarcinoma, Papillary↗

PubMed1995

[Spinal anesthesia for patients with progressive muscular dystrophy].

Spinal anesthesia was applied on 8 occasions to 7 patients with progressive muscular dystrophy (PMD) undergoing orthopedic lower limb surgery. No postoperative complication occurred in all patients. During the operations, however, two patients were subjected to high spinal anesthesia, which caused ventilatory suppression in one patient and bronchial asthma attack in another. Both respiratory complications were easily managed by ventilatory assistance with endotracheal intubation or by administration of bronchodilator, respectively. High spinal anesthesia should be avoided in applying spinal anesthesia to patients with PMD.

Adolescent↗

PubMed1995

[A case of rubella encephalitis: rubella virus genome was detected in the cerebrospinal fluid by polymerase chain reaction].

We studied a 2-year-old boy who had been diagnosed as having rubella encephalitis by detection of rubella virus genome in his cerebrospinal fluid with the reverse transcription-polymerase chain reaction (PCR). PCR was considered to be very useful not only to make an early diagnosis of rubella encephalitis but also to be applied generally to that of various viral encephalitis.

Cerebrospinal Fluid↗