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N Sasaki

Publications and source records attributed to N Sasaki.

At least 145 records · Page 8Linked to original sources

In vitro retinoid-induced growth inhibition and morphologic differentiation of canine osteosarcoma cells.

OBJECTIVE: To determine differentiation and growth inhibition effects of retinoids on canine osteosarcoma cells. SAMPLE POPULATION: 3 osteosarcoma cell lines established from osteosarcomas in dogs. PROCEDURE: Osteosarcoma cells were incubated with various concentrations of all-trans-retinoic acid and 9-cis-retinoic acid or control medium, counted daily for 10 days, and evaluated for morphologic changes. Synthesis of DNA was measured by use of a cell proliferation ELISA. To analyze effect of retinoids on colony formation on plastic dishes, cells were cultured for 14 days, fixed, and stained; number of colonies was counted. RESULTS: In a dose-dependent manner, both retinoids induced morphologic differentiation and growth inhibition in the 3 osteosarcoma cell lines and inhibited each cell's ability to form anchorage-dependent colonies. CONCLUSION AND CLINICAL RELEVANCE: Retinoids induced differentiation of osteosarcoma cells of dogs, resulting in altered expression of their malignant phenotype. Induction of differentiation by retinoids may have potential as an adjunctive treatment for osteosarcoma in dogs.

Alitretinoin↗

Abnormal magnesium status in patients with cardiovascular diseases.

To investigate magnesium status in patients with cardiovascular diseases and in those presenting high factors for these diseases, we measured the concentrations of serum total Mg, serum ionized Mg and intra-erythrocyte Mg. Mg is an important cofactor for many enzymes, especially those involved in phosphate transfer reactions. Mg deficiency has been shown to be associated with fatal cardiovascular diseases, as well as with risk factors for these diseases. Only measurement of the serum concentration of total Mg is routinely available, but ionized Mg is the physiologically active component. Furthermore, most of the body's Mg is present in the intracellular space. Subjects included patients with ischaemic heart disease (n=80), cardiac arrhythmia (n=60), diabetes mellitus (n=36), essential hypertension (n=194) and hypercholesterolaemia (n=60). The same measurements were made in healthy controls (30 men and 26 women; mean age 58+/-11 years). The serum ionized Mg concentration was measured with a selective ion electrode. The intra-erythrocyte Mg concentration was measured by atomic absorption. No gender difference was found for any Mg parameter, nor was age related to any Mg parameter. The serum albumin concentration was positively correlated only with the serum total Mg concentration. Although the serum total Mg concentration was similar in all groups, patients with diabetes mellitus and arrhythmia had lower serum levels of ionized Mg. Patients with essential hypertension exhibited higher intra-erythrocyte Mg concentrations than the healthy controls. Thus the measurement of serum total Mg concentration may obscure the presence of extracellular Mg deficiency in patients with arrhythmia and diabetes mellitus. Furthermore, the intracellular accumulation of Mg does not support the hypothesis of Mg deficiency in patients with essential hypertension.

Biomarkers↗

[Pulmonary infection caused by Mycobacterium gordonae in immunocompetent patient].

We report a case of 67-year-old female immunocompetent patient admitted to our hospital because of hemoptysis. Computed tomography (CT) of the lung showed bronchiectasis in the right S5 and small nodules in the right S6 and left S5. The cultures of sputum and bronchial washing specimen repeatedly revealed acid-fast bacilli identified as Mycobacterium gordonae (M. gordonae) by DNA-DNA hybridization (DDH) method. Thus, she was diagnosed to be infected with M. gordonae. She was treated with isoniazid, rifampicin, ethambutol and streptomycin. After treatment, the cultures of sputum and bronchial washing specimen converted to negative, and the chest CT showed improvement of small nodules. M. gordonae is a nontuberculous mycobacterium of very low pathogenic potency. Recently there have been a few reports of infection by M. gordonae not only in immunocompromised patients but also in immunocompetent patients. These cases were considered to be sensitive to initial standard antimycobacterial therapy, therefore, it is important to examine for M. gordonae in cases suspected of nontuberculous mycobacterial infection.

Aged↗

[A case of pulmonary tuberculosis complicated with multiple bone and joint tuberculosis].

A 29-year-old male complaining of fever and general fatigue was admitted to our hospital. On admission chest X-ray showed infiltrative shadows with cavities in the bilateral lung apical areas, and sputum examination for acid fast bacilli was smear positive, Gaffky 1. He was treated as pulmonary tuberculosis (TB), and chest X-ray findings and sputum examination improved after a few months of treatment with antituberculous chemotherapy (INH, RFP, EB, PZA). However, tuberculous cold abscess appeared in retropharyngeal area, subcutaneous tissue of thoracic cage and retroperitoneal space, and shortly later, bone and joint TB were recognized in shoulder and wrist joints and vertebrae. The findings of vertebral foci were not recognized by a simple X-ray picture of vertebrae. at that time, but MRI of vertebrae showed low intensity areas with ring enhancement in the cervical, thoracic and lumbar vertebrae. Despite treatment with antituberculous agents, new bone and joint TB had developed in many tissues and had accompanied with cold abscess in adjacent tissue, whereas pulmonary TB had improved after the initial transient worsening. The appearance of bone and joint TB was most probably caused by the initial transient worsening of hidden bone and joint TB as a part of the initial systemic transient worsening of tuberculosis. After treatment for 4 months, pulmonary TB as well as bone and joints TB had improved. Tuberculous cold abscess in retropharyngeal may be secondary to cervical vertebral TB but is now rarely seen. In this case, involvement in many tissues such as retropharyngeal area, subcutaneous tissue of thoracic cage and retroperitoneal space were seen, and these findings are now uncommon and usually represents involvement secondary to contiguous infection.

Adult↗

[MALT lymphoma producing IgG-kappa type M-protein].

A 72-year-old woman, who has been administered prednisolone and azathioprine with diagnoses of idiopathic thrombocytopenic purpura (ITP) and autoimmune hepatitis (AIH), underwent a complete medical examination because of monoclonal gammopathy (IgG-kappa). Tumors were found in the ileum and descending colon. Pathological examination of biopsy specimens suggested a diagnosis of marginal zone B-cell lymphoma of the MALT type with a high-grade component. Flow cytometric analysis by two-color staining revealed that the neoplastic B cells expressed CD38, CD19, IgG and kappa, but not CD5 or CD10. There were no abnormal plasma cells in bone marrow smears. The patient achieved complete remission after receiving three cycles of THP-COP chemotherapy, which resulted in a decrease of the IgG level to within the normal range. These findings indicated that monoclonal IgG-kappa might be produced by lymphoma cells. However, the relationship of the immunosuppressive agents to the pathogenesis of the MALT lymphoma remains to be clarified.

Aged↗

[Results of surgery in Mycobacterium avium complex pulmonary disease].

Recently, several studies have revealed the usefulness of surgical therapy for nontuberculous mycobacterial (NTM) disease. We have encountered and taken many opportunities for surgical therapy in Mycobacterium avium complex (MAC) disease. From April 1995 through March 1999, 14 patients with MAC disease underwent 16 pulmonary resections. NTM was diagnosed at our hospital in all subjects according to the criteria of the American Thoracic Society. There were 8 women and 6 men, with a mean age of 54 years. The most common indications for surgery were localized lesion (7 cases), severe symptoms (5 cases) and progressive disease (2 cases). Twelve patients were receiving multidrug chemotherapy, 10 of whom were also receiving clarithromycin. The mean period of preoperative chemotherapy was 17 months. Ten patients had a variety of symptoms, with some combination of cough, sputum, hemosputum, dyspnea, fever and anorexia. About 30% of the symptoms were improved after preoperative chemotherapy. The symptoms disappeared in all except one patient, who underwent pneumonectomy. After surgery, all patients attained a sputum-negative status. Nine patients underwent 11 partial resections, comprising 3 thoracotomies and 8 video-assisted thoracic surgeries (VATS). There was no operative mortality. Re-operation was performed in a patient with bronchopleural fistula after initial surgery. Currently, 2 months after the last operation, we have encountered no other severe complication and no relapse. Surgery may play an important role in treatment of MAC disease. We recommend partial resection with VATS for localized MAC disease.

Adult↗

Deletion of the myopathy loop of Dictyostelium myosin II and its impact on motor functions.

One of the putative actin-binding sites of Dictyostelium myosin II is the beta-strand-turn-beta-strand structure (Ile(398)-Leu-Ala-Gly-Arg-Asp(403)-Leu-Val(405)), the "myopathy loop, " which is located at the distal end of the upper 50-kDa subdomain and next to the conserved arginine (Arg(397)), whose mutation in human cardiac myosin results in familial hypertrophic cardiomyopathy. The myopathy loop contains the TEDS residue (Asp(403)), which is a target of the heavy-chain kinase in myosin I. Moreover, the loop contains a cluster of hydrophobic residues (Ile(398), Leu(399), Leu(404), and Val(405)), whose side chains are fully exposed to the solvent. In our study, the myopathy loop was deleted from Dictyostelium myosin II to investigate its functional roles. The mutation abolished hydrophobic interactions of actin and myosin in the strong binding state during the ATPase cycle. Association of the mutant myosin and actin was maintained only through ionic interactions under these conditions. Without strong hydrophobic interactions, the mutant myosin still exhibited motor functions, although at low levels. It is likely that the observed defects resulted mainly from a loss of the cluster of hydrophobic residues, since replacement of Asp(403) or Arg(402) with alanine generated a mutant with less severe or no defects compared with those of the deletion mutant.

Actins↗

Gastric and duodenal polyps in Smad4 (Dpc4) knockout mice.

The SMAD4 (DPC4) gene was initially isolated as a candidate tumor suppressor from the convergent site of homozygous deletions on 18q in a panel of pancreatic carcinoma cell lines. It encodes a common cytoplasmic signaling molecule shared by the transforming growth factor-beta, activin, and bone morphogenic pathways. We recently inactivated its mouse homologue Smad4 and demonstrated its role in the malignant progression of benign adenomas to invasive adenocarcinomas by analyzing mice with Apc and Smad4 compound mutations. Although simple Smad4 homozygotes were embryonically lethal, the heterozygotes were fertile and appeared normal up to the age of 1 year. Upon further investigation, however, they have developed inflammatory polyps in the glandular stomach and duodenum. By PCR genotyping and immunohistochemical staining, the wild-type Smad4 allele has been lost in the polyp epithelial cells, ie., loss of heterozygosity. On the other hand, we have not found any mutations in such genes as K-Ras, H-Ras, N-Ras, p53, or PTEN. Histologically, the polyps are similar to human juvenile polyps showing moderate stromal cell proliferation and infiltrations by eosinophils and plasma cells. In addition, foci of adenocarcinoma with signet ring cells are also found. These results are consistent with a recent report that germ-line SMAD4 mutations are found in a subset of familial juvenile polyposis.

Animals↗

Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects: role of endothelium-derived nitric oxide.

BACKGROUND: Several nonpharmacological interventions, including exercise, are recommended in primary prevention of hypertension and other cardiovascular diseases in which the pathogenetic role of endothelial dysfunction has been suggested. We studied the effects of long-term aerobic exercise on endothelial function in patients with essential hypertension. METHODS AND RESULTS: The forearm blood flow was measured by strain-gauge plethysmography. The responses of forearm vasculature to acetylcholine were smaller in the hypertensive patients than in the normotensive subjects. There was no significant difference in forearm vascular responses to isosorbide dinitrate in the normotensive and hypertensive subjects. We evaluated the effects of physical exercise for 12 weeks on forearm hemodynamics in untreated patients with mild essential hypertension who were divided randomly into an exercise group (n=10) and a control group (n=7). After 12 weeks, the forearm blood flow response to acetylcholine increased significantly, from 25.8+/-9.8 to 32.3+/-11.2 mL. min(-1). 100 mL tissue(-1) (P<0.05), in the exercise group but not in the control group. The increase in the forearm blood flow after isosorbide dinitrate was similar before and after 12 weeks of follow-up in both groups. The infusion of N(G)-monomethyl-L-arginine abolished the exercise-induced enhancement of forearm vasorelaxation evoked by acetylcholine in the exercising group. In normotensive subjects also, long-term aerobic exercise augmented acetylcholine-stimulated nitric oxide release. CONCLUSIONS: These findings suggest that long-term physical exercise improves endothelium-dependent vasorelaxation through an increase in the release of nitric oxide in normotensive as well as hypertensive subjects.

Acetylcholine↗

Enhancing effects of salicylate on tonic and phasic block of Na+ channels by class 1 antiarrhythmic agents in the ventricular myocytes and the guinea pig papillary muscle.

OBJECTIVE: To study the interaction between salicylate and class 1 antiarrhythmic agents. METHODS: The effects of salicylate on class 1 antiarrhythmic agent-induced tonic and phasic block of the Na+ current (INa) of ventricular myocytes and the upstroke velocity of the action potential (Vmax) of papillary muscles were examined by both the patch clamp technique and conventional microelectrode techniques. RESULTS: Salicylate enhanced quinidine-induced tonic and phasic block of INa at a holding potential of -100 mV but not at a holding potential of -140 mV; this enhancement was accompanied by a shift of the hinfinity curve in the presence of quinidine in a further hyperpolarized direction, although salicylate alone did not affect INa. Salicylate enhanced the tonic and phasic block of Vmax induced by quinidine, aprindine and disopyramide but had little effect on that induced by procainamide or mexiletine; the enhancing effects were related to the liposolubility of the drugs. CONCLUSIONS: Salicylate enhanced tonic and phasic block of Na+ channels induced by class 1 highly liposoluble antiarrhythmic agents. Based on the modulated receptor hypothesis, it is probable that this enhancement was mediated by an increase in the affinity of Na+ channel blockers with high lipid solubility to the inactivated state channels.

Action Potentials↗

Computer Simulations for the Growth Process of Peanut-Type Hematite Particles.

The growth process of a monodispersed peanut-type hematite particle consisting of much smaller elongated subcrystals has been reproduced by computer simulation. On the basis of the microscopic internal structure, the simulation was performed by replacing the sequential events of surface nucleation and the subsequent growth of each subcrystal in the actual process with an arranged deposition of rectangular segments of fixed dimensions under different conditions in their site-dependent deposition rate and in the flexibility of their tilt angles. The most successful simulation model was obtained on the assumptions of a relatively fast deposition of the segments on the outermost side-surface of the ellipsoidal particle and the flexible tilt angle of each segment depending on the position of a neighboring new segment placed afterward. The result of the simulation strongly supported the previous elucidation of the growth mechanism in terms of the outward bending of adjoining subcrystals by nucleation and growth of a new subcrystal in each space between them. Enhancement of the outward bending of subcrystals by a large amount of sulfate ions adsorbed to the growing subcrystals was also suggested. Copyright 1999 Academic Press.

Journal Article↗

Clinical need for both scintigraphy with technetium-99m GSA and per-rectal portal scintigraphy in some patients with chronic liver disease.

Scintigraphy with 99mTc-diethylenetriaminepentaacetate with galactosyl human serum albumin (99mTc-GSA) and per-rectal portal scintigraphy are useful for evaluating hepatic functional reserve and portal circulation, respectively. We did the procedures simultaneously in some patients to examine the relationship between hepatic functional reserve and portal circulation in chronic liver disease. Scintigraphy with 99mTc-GSA was done in 10 healthy subjects, 45 patients with chronic hepatitis, and 165 patients with cirrhosis. Fifty-seven patients (13 with hepatitis and 44 with cirrhosis) also underwent per-rectal portal scintigraphy with 99mTc-pertechnetate within two weeks. A receptor index was calculated by dividing the radioactivity of the liver region of interest (ROI) by that of the liver-plus-heart ROI at 15 min after the injection of 99mTc-GSA. The index of blood clearance was calculated by dividing the radioactivity of the heart ROI at 15 min by that of the heart ROI at 3 min. A solution containing 99mTc-pertechnetate was instilled into the rectum, and serial scintigrams were taken while radioactivity curves for the liver and heart were recorded sequentially. A per-rectal portal shunt index was determined by calculating the ratio of counts for the liver to counts for the heart integrated for 24 seconds immediately after the appearance of the liver time-activity curve. The median receptor index was lower for more severe liver disorders, increasing in the order of chronic hepatitis, compensated cirrhosis and decompensated cirrhosis, and the median index of blood clearance was higher. The median receptor index was significantly lower when a complication (varices, ascites, or encephalopathy) was present, and the median index of blood clearance was higher. The shunt index was correlated significantly with the two other indices, but these values for some one-third of the patients disagreed in either indices. Scintigraphy with 99mTc-GSA and per-rectal portal scintigraphy with 99mTc-pertechnetate are both needed for accurate assessment of the severity of chronic liver disease before treatment-making decisions, because in some patients, results are not correlated.

Administration, Rectal↗

Two cases of focal nodular hyperplasia of the liver: value of scintigraphy with Tc-99m GSA and positron emission tomography with FDG.

Focal nodular hyperplasia (FNH) of the liver is relatively rare, and can be difficult to differentiate from other benign tumors arising in the liver. We describe a 23-year-old woman and a 25-year-old man with FNH. They were hospitalized for further evaluation of a space-occupying lesion in the liver. Scintigraphy with Tc-99m diethylenetriaminepentaacetic acid galactosyl human serum albumin (Tc-99m GSA) revealed increased radioactivity in the tumor in one patient and radioactivity similar to that in the normal part of liver in the other. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) showed uptake similar to that of the normal liver in both patients. FNH was diagnosed on the basis of angiographic findings and histological findings in liver biopsy specimens. Our results show that scintigraphy with Tc-99m GSA and FDG-PET may provide information helpful in the diagnosis of FNH.

Adult↗

Sarcomere length during contraction of isolated guinea-pig ventricular myocytes.

An improved method was developed for measuring sarcomere length (SML) during twitch contractions of single cardiac ventricular myocytes, using a charge-coupled photodiode array self-scanning at a rate of 1.5 ms/element. The average resting SML of 111 cells was 1.88+/-0.04 microm (mean +/-SD). When contractions were triggered by action potentials under perforated-patch conditions, the time course of SML shortening closely followed changes in cell length. A large variation was observed in contraction time course between myocytes, some cells having a phasic component with a duration at 50% shortening (full-width at half-maximum; FWHM) of approximately 40 ms, while others shortened more slowly (FWHM of phasic component @100 ms). FWHM was highly correlated with relaxation half-time, but with neither action potential duration nor resting SML. The kinetics of slowly contracting cells could not be converted to the rapid type by using conditioning trains or applying isoprenaline. The steady-state SML/pCa relation in ventricular myocytes was measured by applying solutions of various pCa immediately after localized punctures of the surface membrane using a focal laser beam. The Hill coefficient, nH, was @4-5 and K1/2@400-500 nM, but there was no evidence of two populations of cells with different Ca2+ sensitivities.

Action Potentials↗