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N Sato

Publications and source records attributed to N Sato.

At least 199 records · Page 11Linked to original sources
PubMed2001

[Drug induced pulmonary hypertension].

Primary pulmonary hypertension (PPH) is a rare, often fatal disease that tends to occur with particular frequency in woman. The factors leading to its development remain enigmatic. A variety of toxins and drugs have been implicated in the pathogenesis of pulmonary hypertension (PH). In the 1960s, the medical community was first alerted to the problem of an epidemic of PH in association with a particular anorexic agent, aminorex. Recent reports have indicated that anorexic drugs may have causative roles in PH. The International Primary Pulmonary Hypertension Study (IPPHS) showed a strong association between PPH and the use of appetite suppressants. But the mechanism by which these anorectic drugs cause PH is unknown.

Aminorex↗
PubMed2001

[Gastrostomy tube].

Explore the source record for details and available documents.

Enteral Nutrition↗
PubMed2001

[Recurrence and pulmonary metastasis of extradural paraganglioma in thoracic vertebral canal: report of a case].

A 70-year-old female was operated on for extradural spinal cord tumor in 1982. Microscopic examination revealed the tumor as paraganglioma. Tumor recurred at paravertebral twice in 1985 and 1989, and they were also resected. In 1995, her chest X-ray film showed round tumor in the right upper field. Exploratory open lung biopsy was performed in 1996, and right upper lobectomy was performed according to for malignant lung tumor because intra-operative microscopic findings showed carcinoid or lung metastasis of paraganglioma. Chest wall tumor at paravertebral was resected at the same time. Postoperative microscopic examination revealed the tumors were same as operated paraganglioma. The 2nd thoracotomy was done in 1999, and two chest wall tumors and a pulmonary nodule in right S8 segment were resected. They were recurrence and pulmonary metastasis of paraganglioma. Now 18 years after initial operation, she is out of hospital in tumor free.

Aged↗
PubMed2001

[Intermittent administration of 5-FU and isovorin to patients with advanced and recurrent colon cancer].

We attempted a new regimen of intermittent administration of 5-FU and low-dose Isovorin (F.I) to four patients with advanced and recurrent colon cancer. A partial response (PR) was achieved in two of four patients who had evaluable lesions for this treatment. We observed few side effects among these patients. Only one patient among four showed grade 1 neuropathy after two administrations of this chemotherapy. However, after a two-week pause in administration, the neuropathy disappeared and we could continue the therapy. This patient with multiple liver metastases achieved a partial response. Other patients had no side effects such as bone marrow suppression or digestive symptoms. This intermittent F.I treatment might be an effective and promising therapy with few side effects even for patients with poorer conditions.

Aged↗
PubMed2001

Long-term alcohol exposure changes sensitivity of rat Kupffer cells to lipopolysaccharide.

BACKGROUND: Chronic ethanol treatment enhances Kupffer cell sensitivity to lipopolysaccharide (LPS). In this model, CD14 in Kupffer cells was increased significantly 4 weeks after ethanol. Moreover, it was shown that prostaglandin E2 produced by activated Kupffer cells participated in the mechanism of ethanol-induced fatty liver. This study was designed to elucidate the temporal effect of chronic ethanol exposure on Kupffer cell sensitization to LPS. METHODS: Rats were given ethanol every 24 hr intragastrically for up to 12 weeks, and Kupffer cells were isolated 24 hr after the final ethanol administration and cultured in RPMI 1640 with 10% fetal bovine serum. After addition of LPS to Kupffer cells, intracellular calcium ([Ca2+]i) was measured. RESULTS: CD14 in Kupffer cells was increased approximately 2-fold, and then it decreased and returned to control levels. The LPS-induced increases in [Ca2+]i and tumor necrosis factor-alpha by Kupffer cells were also increased approximately 3-fold over control values, but they also returned to control levels. Triglyceride content increased with the duration of chronic ethanol treatment. At 8 weeks, prostaglandin E2 produced by Kupffer cells increased approximately 3-fold over control values and triglycerides by approximately 4-fold before gradually decreasing to basal levels. After 12 weeks of ethanol exposure, LPS-induced increases in [Ca2+]i and tumor necrosis factor-alpha production were only approximately 50% as high as peak levels at 4 weeks. Liver triglyceride content at 12 weeks was reduced significantly compared with values at 8 weeks. CONCLUSIONS: Kupffer cells at the early stage of chronic ethanol exposure exhibited sensitization to LPS, but this sensitivity was blunted later. This correlated with triglyceride accumulation in the liver. These data indicate that long-term alcohol exposure changes the sensitivity of rat Kupffer cells to LPS but that the magnitude of the effect is time dependent.

Animals↗
PubMed2001

Tumor targeting and imaging of intraperitoneal tumors by use of antisense oligo-DNA complexed with dendrimers and/or avidin in mice.

To establish an effective nonviral gene delivery and a corresponding imaging method for i.p.-disseminated tumors, various oligonucleotide-carrier complexes were synthesized, and their in vitro and in vivo properties were examined. The 20-mer multiamino-linked oligonucleotide (oligo), synthesized as antisense against the c-erbB-2 sequence, and the 3'-biotinylated form of the same oligonucleotide (oligo-Bt) were (111)In labeled through a diethylenetriaminepentaacetic acid chelate. (111)In-oligo was mixed with generation 4 polyamidoamine dendrimer (G4) or with biotinylated G4 (G4-Bt), which are positively charged to form electrostatic complexes. (111)In-oligo/G4-Bt and (111)In-oligo-Bt were conjugated to avidin ((111)In-oligo/G4-Av and (111)In-oligo-Av, respectively). (111)In-oligo/G4, (111)In-oligo/G4-Av, (111)In-oligo-Av, and carrier-free (111)In-oligo (2.96 kBq/22.4-45.9 ng of oligo) were examined for internalization in vitro in human ovarian cancer cells (SHIN3). Biodistribution of (111)In-oligo-carrier complexes or (111)In-oligo was examined in normal (n = 4-7) or i.p. SHIN3 tumor-bearing (n = 6-10) mice 2-24 h after i.p. injection (74 kBq/125-300 ng). Scintigraphy of i.p. tumor-bearing and normal mice was performed at various times postinjection of (111)In-oligo-carrier complex or (111)In-oligo (1.85 MBq/2.2 ng). (111)In-oligo-carrier complexes bound to the tumor cells were internalized at a rate of 34-56% at 24 h. In vivo, G4, G4-Av, and Av significantly enhanced tumor delivery of (111)In-oligo [9.1, 14.5, and 24.4% of injected dose per g of tissue (ID/g) at 24 h; P < 0.05, < 0.01, and < 0.0001, respectively] compared with delivery without carrier (0.8% ID/g). Scintigrams of (111)In-oligo delivered to the i.p.-disseminated tumors by the carriers were successfully obtained. In conclusion, G4, G4-Av, and Av can effectively deliver (111)In-oligo to i.p.-disseminated tumors. (111)In-oligo-carrier complexes also have potential as tracers for imaging and monitoring of gene delivery.

Animals↗
PubMed2001

[Genomic medicine].

The International Human Genome Sequencing Consortium announced they have got a draft sequence of the human genome that covers about 94% of the human genome in February, 2001. This statement implies that we will soon have the complete human genome sequence and that we will be able to use genomic information in every field including medicine, drug production as well as prophylaxis of many diseases. Two major advances in technology have made it possible to apply genomic information for medicine: microarray technology and high-throughput sequencing technology. Microarray provides us a new method to classify various diseases on the basis of gene expression and high-throughput sequencing enables us to draw high-resolution SNPs map.

Chromosome Mapping↗
PubMed2001

Analysis of gene expression of lymphocytes in microgravity.

It has been reported that lymphocyte function decreases under microgravity. Though molecular mechanism of the immunosuppression in microgravity still remains enigmatic, it is suggested that gene expression of lymphocytes may be altered in microgravity. In this study we developed automatic flash-freezing equipment which can be utilized for exposing lymphocytes to microgravity by drop shaft experiments in Japan Microgravity Center (JAMIC). Gene expression profiles were analyzed by using DNA array in ground control lymphocytes and microgravity-exposed lymphocytes.

Freezing↗
PubMed2000

Absence of endoproteolysis but no effects on amyloid beta production by alternative splicing forms of presenilin-1, which lack exon 8 and replace D257A.

It is well known that presenilin-1 (PS1) is involved in cleavage of amyloid precursor protein (APP) at the gamma-secretase site, and that the amino acids residues of D257 and D385 in PS1 are critical for this cleavage of APP and the endoproteolysis of itself. An alternatively spliced form of PS1 skipping exon 8 (PS1d8), which has D257A at the splice junction of exon 7/9, is expressed in human brain and in some cell lines. In this study, we examined production of Amyloid beta (A beta) and the endoproteolysis of the holoproteins in PS1d8-expressing neuroblastoma cells. Western blotting showed an absence of endoproteolysis in PS1d8. However, PS1d8 did not affect the production of A beta, which is different from the artificial point mutant PS1D257A. These results suggest that endoproteolysis of PS1 and gamma-secretase activity could be independent.

Alternative Splicing↗
PubMed2000

Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary.

Loss of heterozygosity (LOH) at locus 10q23.3 and mutation of the PTEN tumor suppressor gene occur frequently in both endometrial carcinoma and ovarian endometrioid carcinoma. To investigate the potential role of the PTEN gene in the carcinogenesis of ovarian endometrioid carcinoma and its related subtype, clear cell carcinoma, we examined 20 ovarian endometrioid carcinomas, 24 clear cell carcinomas, and 34 solitary endometrial cysts of the ovary for LOH at 10q23.3 and point mutations within the entire coding region of the PTEN gene. LOH was found in 8 of 19 ovarian endometrioid carcinomas (42.1%), 6 of 22 clear cell carcinomas (27.3%), and 13 of 23 solitary endometrial cysts (56.5%). In 5 endometrioid carcinomas synchronous with endometriosis, 3 cases displayed LOH events common to both the carcinoma and the endometriosis, 1 displayed an LOH event in only the carcinoma, and 1 displayed no LOH events in either lesion. In 7 clear cell carcinomas synchronous with endometriosis, 3 displayed LOH events common to both the carcinoma and the endometriosis, 1 displayed an LOH event in only the carcinoma, and 3 displayed no LOH events in either lesion. In no cases were there LOH events in the endometriosis only. Somatic mutations in the PTEN gene were identified in 4 of 20 ovarian endometrioid carcinomas (20.0%), 2 of 24 clear cell carcinomas (8.3%), and 7 of 34 solitary endometrial cysts (20.6%). These results indicate that inactivation of the PTEN tumor suppressor gene is an early event in the development of ovarian endometrioid carcinoma and clear cell carcinoma of the ovary.

Adenocarcinoma, Clear Cell↗
PubMed2000

Activated cAMP-response element-binding protein regulates neuronal expression of presenilin-1.

Upon binding to the cAMP-response element of a gene's promoter, the transcription factor known as cAMP-response element-binding protein (CREB) facilitates transcription of many different neuronal genes including those involved with synaptic function. Based on our previous reports of gene structure (GenBank accession number AF029701 ), we now demonstrate that activated CREB binds to the proximal promoter of the human presenilin-1 (PS-1) gene to activate PS-1 transcription in rat and in human neuronal cells. Specific stimulation of the N-methyl-d-aspartate subtype of neuronal glutamate receptors activates CREB and results in increased PS-1 expression. Similarly, treatment with brain-derived neurotrophic factor activates CREB and increases PS-1 expression in a dose-dependent fashion. By using adenovirus vectors expressing dominant negative forms of CREB, we were able to show that induction of PS-1 expression requires the activation of CREB. Conversely, constitutive expression of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) results in activation of CREB and increased PS-1 expression that can be blocked by the addition of selective MEK inhibitors. Our findings suggest a hypothesis where stimulation of N-methyl-d-aspartate receptors signals CREB activation to enhance PS-1 gene product expression that contributes to normal neuronal functions.

Adenoviridae↗
PubMed2000

Nine polymorphisms of angiotensinogen gene in the susceptibility to essential hypertension.

Even if the importance of angiotensinogen (AGT) gene has been known in gene targeting animals and humans genetic studies, its precise mechanism and the interaction among AGT gene variants, plasma AGT concentration and risk for hypertension remain uncertain. We examined whether AGT gene variants predispose to hypertension via an increase of plasma AGT concentration. Plasma AGT concentration was estimated from plasma angiotensin I which was cleaved by an excess amount of human renin and measured by RIA. Using 9 AGT gene variants which included new polymorphisms (G-152A and T+31C), we examined the association with hypertension and with plasma concentration by a case-control study. Haplotype analysis revealed that G-6A, T+31C and M235T polymorphisms were in absolute linkage disequilibrium and were associated with hypertension but not with plasma AGT level. On the other hand, -1074t;T235 haplotype was associated with an increase of AGT level but not with hypertension. In the haplotype analysis, only H3 haplotype frequency, which contained G-6, T+31 and M235 alleles, was significantly increased in normotensive subjects, suggesting that this haplotype is associated with a hypotensive effect. According to combined haplotype analysis of diallele and microsatellite markers, it remains a possibility that M235T, T+31C, G-6A, A-20C and G-1074T polymorphisms may play an important role in increased risk for essential hypertension. Our results suggest that the positive association between AGT polymorphism and hypertension is not simply explained by an increase of plasma AGT concentration.

Alleles↗
PubMed2000

Increased plasma P-selectin and decreased thrombomodulin in pulmonary arterial hypertension were improved by continuous prostacyclin therapy.

BACKGROUND: Thrombosis in situ related to endothelial cell injury may contribute to the development of pulmonary hypertension (PH). P-selectin, a leukocyte adhesion receptor present in endothelial cells and platelets, reflects endothelial injury and platelet activation, and thrombomodulin (TM), a receptor for thrombin and a major anticoagulant proteoglycan on the endothelial membrane, reflects the anticoagulant activity of the endothelium. METHODS AND RESULTS: To assess abnormal coagulation due to endothelial injury in patients with PH, plasma levels of soluble P-selectin and TM were measured in 32 patients with primary PH (PPH), 25 with secondary pulmonary arterial hypertension (sPAH), 31 with pulmonary venous hypertension (PVH), and 17 healthy subjects (Control). These measurements were repeated after continuous infusion of prostacyclin in 15 patients with PPH and 3 with sPAH. P-selectin levels in both the sPAH and PPH groups were significantly higher than those in the Control and PVH groups (P<0.05). Plasma TM level in the PPH group was significantly lower than those in the other groups (P<0.01). After prostacyclin therapy, the lower TM level was increased and the higher P-selectin level was decreased (P<0.05). CONCLUSIONS: Decreased TM and increased P-selectin in PPH and sPAH may reflect in situ thrombosis due to endothelial injury. Prostacyclin may act not only as a vasodilator but also as an agent that improves endothelial injury and altered hemostasis in pulmonary arterial injury.

Adult↗
PubMed2000

Tolerance and sensitization to endotoxin in Kupffer cells caused by acute ethanol involve interleukin-1 receptor-associated kinase.

Ethanol changes sensitivity of Kupffer cells to endotoxin. Here, the hypothesis that interleukin-1 receptor-associated kinase (IRAK), a downstream signaling molecule of toll-like receptors, regulates the response to LPS in Kupffer cells after ethanol treatment was evaluated. C57BL/6 mice were given ethanol intragastrically, and LPS was injected 1 or 21 h later. One hour after ethanol treatment, serum transaminases after LPS were 60% of control, while ethanol increased these parameters about 3-fold 21 h after ethanol. Pretreatment with antibiotics blocked these effects of ethanol. In Kupffer cells from mice treated with ethanol 1 h earlier, LPS-induced TNFalpha production, and IRAK expression and activity and NFkappaB were decreased 50-60% of control. In contrast, in Kupffer cells from mice treated with ethanol 21 h earlier, LPS-induced TNFalpha production, expression and activity of IRAK were increased 1.5-fold over controls, while NFkappaB was elevated 3-fold. These data indicate that ethanol-induced tolerance and sensitization of Kupffer cells to endotoxin in mice involve IRAK.

Animals↗