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Biomedical subjects

A Sasaki

Publications and source records attributed to A Sasaki.

At least 19 recordsLinked to original sources
PubMed1992

Synthesis and structure-activity relationships of acetylcholinesterase inhibitors: 1-benzyl-4-(2-phthalimidoethyl)piperidine and related derivatives.

Following the discovery of a new series of 1-benzyl-4-[2-(N-benzoyl-N-methylamino)ethyl]piperidine (2) derivatives with a potent anti-acetylcholinesterase (anti-AChE) activity, we extended the structure-activity relationships (SAR) to rigid analogues (4) and 1-benzyl-4-[2-(N-benzoyl-N-phenylamino)ethyl]piperidine derivatives (3). Introduction of a phenyl group on the nitrogen atom of the amide moieties resulted in enhanced activity. The rigid analogue containing isoindolone (9) was found to exhibit potent anti-AChE activity comparable to that of 2. Furthermore, replacement of the isoindolone with other heterobicyclic ring systems was examined. Among the compounds prepared in these series, 1-benzyl-4-[2-[4-(benzoylamino)phthalimido]ethyl]piperidine hydrochloride (19) (IC50 = 1.2 nM) is one of the most potent inhibitors of AChE. Compound 19 showed a definite selectivity to AChE over the BuChE (about 34700-fold) and, at dosages of 10-50 mg/kg, exerted a dose-dependent inhibitory effect on AChE in rat brain.

Acetylcholinesterase↗
PubMed1992

Lipoprotein lipase release from BFC-1 beta adipocytes. Effects of triglyceride-rich lipoproteins and lipolysis products.

Lipoprotein lipase (LPL), synthesized by adipocytes and myocytes, must be transported to the luminal endothelial cell surface where it then interacts with circulating lipoproteins. The first step in this extracellular LPL transport pathway is LPL release from the surface of LPL-synthesizing cells. Because hydrolysis of triglyceride (TG)-rich lipoproteins releases LPL from the apical surface of endothelial cells, we hypothesized that the same substances dissociate LPL from adipocytes. 125I-LPL was bound to the surface of brown adipocytes (BFC-1 beta). LPL binding to the adipocyte surface was greater than to endothelial cell surfaces. Using low concentrations of heparin, more LPL was released from endothelial cells than BFC-1 beta, suggesting that the affinity of LPL binding to the adipocytes was greater than LPL affinity for endothelial cells. Greater than 3-fold more LPL was released from the cell surface when very low density lipoproteins (VLDL) were added to culture medium containing 3% bovine serum albumin. LPL remaining on the cell surface decreased with VLDL addition. Endogenously produced LPL activity was also released from the cells by VLDL. Low and high density lipoproteins did not release 125I-LPL or LPL activity from the adipocytes. To assess whether lipolysis was necessary for LPL release, BFC-1 beta were incubated with TG-rich lipoproteins from a patient with apoCII deficiency. The apoCII-deficient lipoproteins did not release LPL unless an exogenous source of apoCII was added. Apolipoproteins E and Cs and high molar ratios of oleic acid:bovine serum albumin did not release surface-associated LPL. Lysolecithin (25 and 100 microM), but not lecithin, monoglycerides, or diglycerides, released adipocyte surface LPL. Because lysolecithin also released LPL during a 4 degrees C incubation, cellular metabolic functions are not required for LPL dissociation from the cells. Lysolecithin also inhibited LPL binding to endothelial cells; however, this effect was abrogated by addition of bovine serum albumin. We hypothesize that lipolysis products from TG-rich lipoproteins release adipocyte surface LPL, which can then be transported to the luminal endothelial cell surface.

Adipose Tissue, Brown↗
PubMed1992

Proliferating cell nuclear antigen (PCNA) immunostaining as an alternative to bromodeoxyuridine (BrdU) immunostaining for brain tumours in paraffin embedded sections.

Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and BrdU using anti-PCNA and anti-BrdU monoclonal antibodies, respectively, was performed in 16 human brain tumours, including 3 glioblastomas multiforme, 2 anaplastic astrocytomas, 1 cerebellar astrocytoma, 2 recurrent meningiomas, 4 non-recurrent meningiomas, 3 neurinomas and 1 medulloblastoma. Patients with brain tumours received an injection of bromodeoxyuridine (BrdU) intravenously during surgery, and tumour specimens were fixed in 70% ethanol and embedded in paraffin. The percentage of positive cells for PCNA was compared with a BrdU labelling index using adjacent paraffin-embedded sections. The percentage of PCNA-positive cells was correlated with the BrdU labelling index and the histological malignancy of the brain tumours. The correlation coefficient was 0.84. This suggests that the immunohistochemical staining for PCNA in paraffin sections is a good alternative to the BrdU labelling index.

Antigens, Neoplasm↗
PubMed1992

Epidemiology of childhood diabetes in Osaka District, Japan, using the documents from the medical benefits system specific for childhood diabetes.

For an epidemiological study of childhood diabetes, application forms for medical benefits filed in Osaka Prefecture were collected and analyzed. A total of 465 patients with childhood diabetes under 18 yr of age were identified during the period between 1978 and 1988; 371 (175 boys and 196 girls) of them were classified as insulin-dependent diabetes mellitus (IDDM), and the others were either non-insulin-dependent diabetes mellitus (NIDDM) or an unidentified type of diabetes. The mean annual incidence of IDDM was 1.68 for boys and 2.00 for girls per 100,000 population, the rate being slightly higher for girls. The rates increased among older children, with a peak in the 10-14-yr age group. The prevalence estimated on the basis of the cumulative incidence in 1988 was 1.29 for boys and 1.60 for girls per 10,000 population, indicating a marked increasing trend with age. A significant seasonal variation was observed in the months of onset for IDDM, with higher rates during the winter. The mean birth weights of the male and female patients with IDDM were slightly lower than the national means. Use of official documents obtained from the medical benefits system was found to be an effective method for identification of cases of IDDM in the community, although further information is required for more accurate confirmation of such cases.

Adolescent↗
PubMed1992

The identity of cells expressing MHC class II antigens in normal and pathological human brain.

Major histocompatibility complex class II antigen (Ag) expression in human brain was investigated in autopsied human brain tissues, using anti-human class II monoclonal antibodies. In normal brains, class II Ag was usually absent or was low in positivity. When it was found immunohistochemically, it appeared more frequently in the meninges (meningeal macrophages) and the neurohypophysis (pituicytes) than in the cerebral cortex (microglia and perivascular cells). The identity of the latter cell types was confirmed by immunoelectron microscopy. Class II-positive microglial cells were usually present in the cerebral white matter, but in senile brains showing numerous senile plaques, their numbers were increased in the grey matter. In diseased brains, numerous reactive microglia and macrophages containing class II Ag were observed in the affected lesions of neural tissue destruction, neuronal degeneration, and inflammation. Astrocytes, which were identified with an antibody to glial fibrillary acidic protein, did not contain class II Ag, although a small number of reactive astrocytes showed an equivocal class II staining. Staining for class II Ag on cerebral endothelial cells was mostly negative; however, class II Ag was microscopically identified in a case of secondary CNS T-cell lymphoma.

Adolescent↗
PubMed1992

Periodic leg movements in sleep with restless legs syndrome: effect of clonazepam treatment.

Fifteen patients with restless legs syndrome underwent whole-night polysomnographic recordings before and during clonazepam treatment. The treatment with 0.5 to 1.5 mg clonazepam improved subjective complaints of all the 15 patients. All the patients presented periodic leg movements on the polysomnograms before the treatment. The clonazepam treatment significantly decreased the total numbers of leg movements and the numbers of leg movements per hour without affecting the mean intermovement interval.

Aged↗
PubMed1992

Nocturnal myoclonus observed in a patient with neuroleptic-induced akathisia.

An all-night polysomnogram was twice recorded in a patient with neuroleptic-induced akathisia (NIA). The polysomnogram revealed nocturnal myoclonus. After disappearance of akathisia by the administration of clonazepam, we recorded the second polysomnogram. At the second examination, sleep efficacy increased and the total number of nocturnal myoclonus decreased remarkably. The mean inter-movement interval of nocturnal myoclonus prolonged. These findings suggest a close relationship between the mechanisms of neuroleptic-induced akathisia and nocturnal myoclonus.

Adult↗
PubMed1992

Synthetic studies of carbapenem and penem antibiotics. II. Synthesis of 3-acetyl-2-azetidinones by (2 + 2) cycloaddition of diketene and Schiff bases.

It was found that (2 + 2) cycloaddition reaction of diketene with Schiff bases was effectively promoted by imidazole as a catalyst to afford 3-acetyl-2-azetidinone derivatives 4. As an application of this new method, a practical asymmetric synthesis of 4 and its conversion into (3S,4S)-4-carboxy-1-(di-p-anisylmethyl)-3-[(R)-1-hydroxyethyl]-2- azetidinone, which is a key intermediate for the synthesis of carbapenem and penem antibiotics, were accomplished.

Anti-Bacterial Agents↗
PubMed1992

Synthetic studies of carbapenem and penem antibiotics. III. A synthesis of a key intermediate for 1 beta-methylcarbapenem.

We synthesized useful intermediates 5 and 6 for 1 beta- and 1 alpha-methylcarbapenems from 4-carboxy-3-[(R)-1-hydroxyethyl]-2-azetidinone 4 as a starting material by using stereoselective hydrogenation and hydroboration, respectively. A practical synthetic route from 4 to the (3S,4S)-4-[(R)-1-carboxyethyl]-3-[(R)-1-hydroxyethyl]-2-azetidinone derivative 1, a useful intermediate for the synthesis of 1 beta-methylcarbapenem antibiotics, was established.

Anti-Bacterial Agents↗
PubMed1992

Analysis of tumor necrosis factor and lymphotoxin secreted by incubation of lymphokine-activated killer cells with tumor cells.

This study investigated the secretion of a tumor necrosis factor (TNF) and lymphotoxin (LT) from lymphokine-activated killer (LAK) cells during co-culture with glioblastoma cell lines, autologous glioma cells, and other non-gliomatous tumor cell lines (K562 and Daudi). Cytokine secretion from peripheral blood mononuclear cells (PBMC) was also examined. The TNF activity of culture supernatants was measured by L cell cytotoxic assay, and a neutralization test using anti-TNF and/or anti-LT antibodies determined whether the cytotoxic activity was due to TNF or LT. The results show that LAK cells secrete both TNF and LT during monoculture and release increased amounts of TNF and LT with non-gliomatous tumor cell stimulation, but PBMC secrete only TNF with tumor cell stimulation. Glioblastoma or anaplastic astrocytoma cells, however, did not stimulate cytokine secretion from either LAK cells or PBMC. This indicates a discrepancy between the capability of LAK cells to lyse malignant glioma cells and cytokine secretion from LAK cells, and suggests that malignant glioma cells may produce some factors which inhibit cytokine secretion from LAK cells.

Astrocytoma↗
PubMed1992

Antiproliferative cytokines secreted by lymphokine-activated killer cells stimulated with tumor cells.

Antiproliferative cytokine secretion by lymphokine-activated killer (LAK) cells during coculture with glioblastoma cell lines, autologous glioma cells, and nongliomatous tumor cell lines (Daudi and K562 cells) was assessed, as was the antiproliferative activity of the culture supernatants against the T98G (glioblastoma) cell line. A neutralization test using agents against interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), and lymphotoxin (LT) showed that antiproliferative activity was due to IFN-gamma, but not to TNF or LT. Nongliomatous tumor cells stimulated LAK cells to secrete cytokines, but gliomatous tumor cells did not. It was found that there is a discrepancy between the LAK cell capability to lyse malignant glioma cells and the ability to secrete cytokines. This may be due to the factors secreted by glioblastoma cells.

Astrocytoma↗
PubMed1992

[Promotive effects of intravesical instillation of dimethylsulfoxide on bladder carcinogenesis in mice].

The effect of intravesical instillation of dimethylsulfoxide (DMSO) on bladder carcinogenesis was examined in mice. Experiment 1: Fifty-five female C3H/He mice were administered 0.05% N-butyl-N-(4-hydroxy-butyl) nitrosamine (BBN) in their drinking water for 8 weeks. In week 9 they were divided into two groups consisting of 25 mice each. Then, under nembutal anesthesia the first group was given weekly intravesical inatillations of 0.1 ml DMSO (minimum 99.0%) for 10 weeks. The second group received no treatment except anesthesia. All mice were killed 30 weeks after the begining of the experiment and their urinary bladder resected for histological examination. The incidence of bladder carcinoma was 93.7% (15.16) and 27.7% (6/22) in groups 1 and 2, respectively. These incidences differed significantly between the two groups. Experiment 2: One hundred and twenty female C3H/He mice were divided into two groups. The first group was given 0.05% BBN in their drinking water for 5 weeks and then tap water. The second group was not given BBN. In week 6, the first group was divided again into three groups (1, 2 and 3) consisting of 28, 26, and 27 mice, respectively. The second group was divided into groups 4 and 5 consisting of 21 and 18 mice, respectively. Under nembutar anaesthesia groups 1 and 4 received weekly intravesical instillation of 0.05 ml DMSO (minimum 99.0%) from weeks 6 to 13, Group 2 received weekly intravesical instillation of 0.05 ml distilled water from weeks 6 to 13. Groups 3 and 5 received no treatment except anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗
PubMed1992

[Antitumor effect of combined use of purified human natural tumor necrosis factor (N-TNF) and cis-diamminedichoroplatinum (II) (cisplatin) on the implanted bladder carcinoma (MBT-2) in mice].

The antitumor effect of tumor necrosis factor (TNF) in combination with Cis-diammine-dichloroplatinum (II) (Cisplatin) upon implanted bladder carcinoma (MBT-2) in mice was analysed together with the toxicity. Mice were implanted into the bladder wall with about 10(4) cells MBT-2 viable cells. TNF was the purified human natural tumor necrosis factor. The antitumor effects were evaluated by the volume of the tumor thus implanted and the drug-toxicity by the body weight of mice and microscopic as well as macroscopic findings of the main organs. As a result, 1) The toxicity of TNF to mice was not enhanced in a dose-dependent fashion when combined with Cisplatin. 2) The antitumor effect by combination of TNF and Cisplatin was significantly increased compared to control group. 3) The effects of TNF was enhanced in a dose-dependent fashion when combined with Cisplatin. 4) The antitumor effects was confirmed by pathological findings. These results suggest that the combined use of n-TNF and Cisplatin is promising as a clinically effective treatment against bladder cancer in human.

Animals↗
PubMed1992

[Adjunctive methods during surgery for thoracoabdominal aneurysms--effect of selective visceral arteries perfusion incorporated with partial femoro-femoral bypass].

In this study, we report the effect of selective perfusion to the visceral arteries during aortic cross-clamping at surgery for thoracoabdominal aortic aneurysms with an adjunct of femoro-femoral (F-F) extracorporeal bypass. The total series comprising 28 patients were divided into 3 groups according to the perfusion mode to the celiac and the renal arteries, i.e., group I; the arteries were continuously perfused by the extracorporeal bypass, group II; aortic cross-clamp excluded the branches from the bypass flow but selective perfusion was employed, and group III; the liver or the kidneys were subjected to ischemia. As a result, group III developed hepatic failure at the incidence of 50% which was characterized by hepatocellular damage followed by cholestatic dysfunction. As for postoperative renal function, this group revealed persistently high level of serum creatinine, and 60% of this series resulted in renal failure. On the contrary, group II showed a comparable effect to group I on the preservation of hepato-renal function, and there were no differences in the incidence of hepatic or renal failure between the two groups. Multiple organ failure was a predominant cause of hospital death, and it developed only in the cases with aortic cross-clamp time more than 90 minutes. However, avoiding ischemia achieved in group I or II significantly reduced the incidence of MOF and its related deaths. It is concluded that selective perfusion system incorporated with an aid of F-F partial bypass was a useful measure to protect vulnerable organs from ischemia and to reduce postoperative mortality and morbidities.

Adult↗
PubMed1992

[The evaluation of pre and intraoperative factors influencing the false lumen after graft replacement surgery to the extended dissecting aneurysm].

We evaluated the residual false lumen of type I and IIIb dissecting aneurysm by CT, MRI and angiography postoperatively. The 19 patients with type I dissecting aneurysm were included eleven men and eight women, the average age was 55.8 +/- 10.2 years old. The 20 patients with type IIIb dissecting aneurysm were included sixteen men and four women, the average age was 56.2 +/- 8.5 years old. The rate of distal patent false lumen was 52.6% of type I and 35% of type IIIb dissecting aneurysm after graft replacement surgery. In type I dissecting aneurysm, the rate of distal patent false lumen was 40% of acute stage vs 66.7% of chronic stage, 66.7% of ascending and partial arch replacement vs 46.2% of ascending and total arch replacement, and 90% of graft inclusion technique vs 11.1% of graft exclusion technique. The distal patent false lumen was the lowest (12.5%) with type I dissecting aneurysm of ascending and total arch replacement using graft exclusion technique. In type IIIb dissecting aneurysm, the rate of patent false lumen was 66.7% of acute stage vs 29.4% of chronic stage, 30% of graft exclusion technique vs 40% of graft inclusion technique. The size of false lumen preoperatively were larger (11.1 +/- 4.5 cm2) in patients with distal patent false lumen than that (6.7 +/- 3.2 cm2) of in patients with distal occlusive false lumen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Effects of blood-diltiazem-nitroglycerin-cardioplegia in coronary artery bypass grafting].

Forty-seven patients who underwent coronary artery bypass grafting using blood cardioplegia (BCP) were studied clinically. They were divided into 3 groups based on concentration of diltiazem (DTZ) and nitroglycerin (NTG). Group I (n = 12); DTZ 5 mg plus NTG 5 mg in BCP 1,000 ml, Group II (n = 10); NTG 25 mg in BCP 1,000 ml, Group III (n = 25); DTZ 5 mg plus NTG 25 mg in BCP 1,000 ml. From the standpoint of serum enzyme analysis, there was no significant difference between 3 groups, however, the incidence of perioperative myocardial infarction (PMI) and perioperative coronary spasm (PCS) were significantly higher in Group I than that in other groups. The present data suggests that intramyocardial concentration of NTG in Group II and III were 5 times higher than Group I. Increased dose of NTG in BCP would be benefit for myocardial protection in CABG.

Adult↗
PubMed1992

[Concomitant graft replacement of the total aortic root and the transverse aortic arch for type A aortic dissection associated with annuloaortic ectasia].

Between April 1988 and February 1992, eight patients with type A aortic dissection associated with annuloaortic ectasia (AAE) underwent the concomitant graft replacement of the total aortic root and the transverse aortic arch at our institution. The acuity of the aortic dissection was acute stage in 3 patients and chronic stage in 5 including 3 cases of re-do operation. All operations were performed with an aid of extracorporeal circulation, blood cardioplegia, selective cerebral perfusion and open distal anastomosis. The operative techniques employed in this series consisted of total aortic root replacement using a composite graft (Bentall, Cabrol or Piehler's technique), and total arch replacement using en bloc arch reconstruction or three vessels graft replacement. One patients underwent re-do operation for coronary anastomotic false aneurysm following Bentall operation and aneurysmal dilatation of the false lumen at the aortic arch, and died of LOS because of the prolonged myocardial ischemia. Other seven patients survived the operation, and lead the normal life at the present time. The present data suggests that type A aortic dissection associated with AAE involving aortic arch could be treated by concomitant graft replacement of the total aortic root and the transverse aortic arch.

Adult↗