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Biomedical subjects

T Sakai

Publications and source records attributed to T Sakai.

At least 415 records · Page 23Linked to original sources

[Regulation of the microtubule-dependent process formation. A review based on a comparison between the neuron and the renal glomerular podocyte].

Microtubular cytoskeletons play a crucial role in the morphogenesis of process-bearing cells, such as the neuron and the renal glomerular podocyte. Microtubules are bundled and stabilized by various microtubule-associated proteins, providing a mechanical basis to maintain the deviated morphology of cell processes. To support the process morphology, microtubules are also associated with other cytoskeletal elements such as actin and intermediate filaments. The microtubular polarity is uniformly plus-end-distal in neuronal axons, whereas in dendrites as well as in podocytes, the polarity is revealed to be non-uniform (i.e., both plus-end-distal and minus-end-distal microtubules are present in cell processes). Recently, this non-uniformity is reported to be established by a microtubule-dependent motor protein. Motor proteins are capable to drive the intracellular transport of cytoskeletal elements in addition to that of membrane vesicles. It is still an open question whether cytoskeletal elements are transported along cell processes as subunits or as polymers.

Animals↗

[Multiple chemical sensitivities: case definition, etiology and relations to allergy, poisoning, psychogenic illness etc].

Multiple Chemical Sensitivities (MCS) have been defined as an acquired disorder characterized by recurrent symptoms, referable to multiple organ systems, occurring in response to demonstrable exposure to many chemically unrelated compounds at doses far below those established in the general population to cause harmful effects; no single widely accepted test of physiologic function can be shown to correlate with symptoms (Cullen MR, 1987). The etiology of MCS is hypothesized as a toxicant-induced loss of tolerance to multiple chemicals with subsequent manifestation of multiple-organ symptoms triggered by low-level exposure to such chemicals. The involvement of multiple organs might be attributed to a neurogenic switching mechanism. The final diagnosis of MCS is to rely on provocation of symptoms in a exposure chamber by a double-blind method. Relations of MCS to allergy, poisoning, psychogenic illness, chemical sensitivity, idiopathic environmental intolerances etc. are discussed in terms of case definition and etiology of these disorders.

Diagnosis, Differential↗

[Selenium].

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Adolescent↗

[Bismuth].

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Bismuth↗

Stereoselective serum protein binding of ketoprofen in liver diseases.

The stereoselective binding of ketoprofen (KP) to human serum was studied in patients with liver diseases and was compared with that of normal volunteers. The serum protein binding of racemic KP was found to be decreased in hepatic patients whereas, interestingly, the stereoselectivity of KP was increased. The ratio of unbound concentrations of the KP enantiomers (FR/FS) showed positive linear correlation with albumin concentrations. Inhibition of KP binding to human serum albumin (HSA) induced by lithocholate, lithocholate sulfate and bilirubin was studied. The data presented in this paper strongly suggest that the variation of stereoselective binding of KP in patients suffering from liver diseases was mainly caused by the decrease of HSA levels and secondly by the stereoselective inhibition induced by the increased concentrations of bile acid and its metabolite.

Adult↗

HLA-DQB1 locus and the development of atrophic gastritis with Helicobacter pylori infection.

Helicobacter pylori is known to be involved in digestive diseases such as peptic ulcer, atrophic gastritis, and gastric cancer. It is supposed that the incidence of these digestive diseases associated with H. pylori is influenced by the strain diversity of H. pylori, factors involving the host or environment, and the duration of infection. In this study, we directed our attention to HLA, a host factor, and investigated the relation between HLA-DQB1 genotype of H. pylori-infected patients and the development of atrophic gastritis. HLA-DQB1 genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism method on 122 H. pylori-infected patients with atrophic gastritis and 28 uninfected Japanese controls. Infected patients with developed atrophic gastritis were classified as the open type and those with undeveloped atrophic gastritis as the closed type. To estimate the grade of atrophic gastritis reliably, histological and serological evaluations were also undertaken. The allele frequency of DQB1*0401 was significantly higher in the open-type group compared to either the closed-type or the uninfected group. These results suggest that immunogenic factors play an important role in the development of atrophic gastritis in H. pylori-infected patients, and that DQB1*0401 is a useful marker for determining susceptibility to this disease.

Adolescent↗

Sufficient effect of 1-week omeprazole and amoxicillin dual treatment for Helicobacter pylori eradication in cytochrome P450 2C19 poor metabolizers.

Omeprazole is widely used for the treatment of Helicobacter pylori infection. It is metabolized by cytochrome P450 2C19 enzyme (CYP2C19) in the liver. Because this enzyme exhibits a genetic polymorphism, patients with low metabolic activity (poor metabolizers) may be exposed to higher concentrations of this drug than are patients who are extensive metabolizers. Eighty-six patients with cultured H. pylori-positive gastritis or peptic ulcers who completed the treatment and assessment of anti-H. pylori therapy were analyzed for CYP2C19 genotyping using a polymerase chain reaction-restriction fragment length polymorphism method [the wild-type or two mutant genes (ml in exon 5 and m2 in exon 4), or both]. Patients were classified into three groups according to the H. pylori eradication regimen: group I (n = 21; omeprazole 40mg/ day and amoxicillin 2000mg/day for 1 week); group II (n = 21; group I regimen plus sucralfate 4000mg/day, for 1 week); group III (n = 44; group I regimen plus clarithromycin 800mg/day, for 1 week). The combination of two mutant alleles (ml/ml, ml/m2, m2/m2-poor metabolizers) was observed in 13 of 86 patients (15%), and all poor metabolizer patients achieved H. pylori eradication regardless of their treatment regimens. In addition, the eradication rates of the poor metabolizers were significantly higher than those of other genotypes who carry homozygous or heterozygous normal allele (extensive metabolizers) in group I or groups I and II combined. CYP2C19 genotyping can provide a new strategy to choose an optimal regimen, and this genotyping is especially useful for Japanese, as the frequency of poor metabolizers is five times greater than that found among Caucasians.

Amoxicillin↗

[The present situation of home infusion therapy (HIT) and the problems of coordinated service].

Fujisawa Pharmaceutical Co., Ltd. established its home care business division in April, 1995. On the assumption that the patients have the final say in decision making, we aim at smooth operation of home care, adjusted to each patient's needs, which will lead to improvements in quality of life (QOL). Approximately 700 patients took advantage of our pharmacy service between April, 1995 and March, 1999; of them, almost 80 percent had a malignant tumor in the terminal stage and were receiving home parenteral nutrition (HPN). Patient ages ranged from the 50s to the 80s. The number of patients with a malignant disease who take advantage of medical treatment by family doctors or a visiting nurse station is less than that of patients with a benign disease. Following are the problems of coordination for HIT patients: 1) difficulty in understanding the patient's or their family's actual thoughts about home care, 2) insufficient information from the medical staff to the patient or their family for decision making, 3) insufficient coordination in the medical organization, and 4) failure of information exchange between the medical organization's staff and the home-care staff. In order to operate a home care service which can improve QOL, information exchange and cooperation among the members of the home care team is essential.

Aged↗

Effects of sodium hyaluronate on experimental osteoarthritis in rabbit knee joints.

The aim of this study was to examine the effects of intraarticular administration of hyaluronan (HA) on cartilage degradation. Using a partial menisectomy model of osteoarthritis (OA) in the rabbit knee, the authors investigated the catabolic and anabolic changes induced by intraarticular injection of HA. To analyze anabolic changes, the authors assessed cell proliferation by measuring [3H] thymidine uptake, and proteoglycan biosynthesis by noting [35S] sulfate incorporation. For catabolic changes, messenger ribonucleic acid (mRNA) expression of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in cartilage and synovium were detected with reverse transcriptase polymerase chain reaction (RT-PCR). Of significance for blocking the development of early OA in chondrocytes was the finding that total proteoglycan synthesis in the HA treatment group was significantly higher than in the controls. At the mRNA level in cartilage and synovium, HA inhibited MMP-3 and TIMP-1 production in the same way in the HA treatment group, while not affecting MMP-1 production. Thus it can be concluded that HA affects cartilage catabolism and anabolism to prevent the progress of OA.

Animals↗

Dye-enhanced selective laser ablation for surgical mucosectomy.

The diode laser operates at a wavelength of 805 nm; indocyanine green (ICG) has a maximum energy absorption of a wavelength of approximately 800 nm. The effect of the diode laser as a laser knife can be significantly enhanced with an injection of ICG. In the present study, this dye-enhanced photothermal effect was investigated in the field of surgical endoscopy. A 9-cm2 region of the canine gastric mucosa was removed by the laser after injection of 5 ml of ICG solution at a concentration of 0.5 mg/mL into the submucosal space. The diode laser was used at a power output of 10 watts. The canine stomach was removed 10 days after the operation to investigate the site histologically. Clinical application using transanal endoscopic microsurgery (TEM) was employed using a dye-enhanced laser in five patients with a rectal adenoma. The pathological changes in the canine gastric wall resected 10 days after the operation showed that the low-power laser enhanced by ICG produced less fibrosis in the submucosal space than electrocautery. Mucosal resection using a dye-enhanced laser was easily performed in these five patients. It was concluded that this easy removal of the mucosa by a dye-enhanced laser was due to its ability to produce hemostasis of the vessels and its excellent tissue-cutting effect.

Adenoma↗

Effects of vector-averaged gravity on NF-kappa B activation in human osteoblast-like cells.

We have recently demonstrated that a transcription factor, nuclear factor kappa B (NF-kappa B), plays a key role in the production of cytokine and cell adhesion molecules in osteoblastic cells. In the present study, we investigated the effects of vector-averaged gravity (clinostat rotation) on tumor necrosis factor (TNF)-alpha-induced activation of NF-kappa B in human osteoblastic HOS-TE85 cells. After a 72-hr clinostat culture, the cells were treated with TNF-alpha for 30 min. Electrophoretic mobility shift assay using the nuclear extracts revealed that the DNA-binding activity of NF-kappa B was substantially reduced in clinostat-cultured cells compared with the stationary control. Concomitantly, the transactivation of NF-kappa B was examined by a transfection study. The cells were transfected with a plasmid expressing a luciferase reporter gene driven by multimerized NF-kappa B sites. They were cultured in the clinostat for 48-hr, followed by a 4-hr treatment with TNF-alpha. Clinostat culture resulted in a significant decrease in the luciferase activities, being consistent with the decreased binding of NF-kappa B. These results indicate that exposure of HOS-TE85 cells to vector-averaged gravity impairs NF-kappa B activation by TNF-alpha.

DNA↗

Structural requirements for galactosylceramide recognition by CD1-restricted NK T cells.

The reactivity of a group of mouse Valpha14+ NK T cell hybridomas was tested with a panel of analogs of the glycolipid alpha-galactosylceramide (alpha-GalCer). Interestingly, the nearly complete truncation of the acyl chain from 24 to 2 carbons does not significantly affect the mouse NK T cell response to glycolipid presented by either mouse CD1 (mCD1) or its human homolog CD1d (hCD1d). Therefore, we propose that only one of the two hydrophobic pockets of the CD1 Ag-binding groove needs to be filled by Ag. In terms of the sphingosine base, the mCD1 binding groove has less-demanding structural requirements for presentation to NK T cells than hCDld. Tests of NK T cell reactivity to analogs presented by hCDld demonstrates that the invariant TCRs expressed by mouse and human NK T cells are surprisingly similar in their requirements for glycolipid recognition.

Animals↗

Acein-1, a novel angiotensin-I-converting enzyme inhibitory peptide isolated from tryptic hydrolysate of human plasma.

A novel angiotensin-I-converting enzyme (ACE) inhibitory peptide, designated acein-1, was isolated from the tryptic hydrolysate of human plasma. Gel filtration and cation exchange chromatography were performed to purify this peptide, followed by reversed-phase gradient and isocratic high-performance liquid chromatography. Acein-1 was found to be a heptapeptide, Tyr-Leu-Tyr-Glu-Ile-Ala-Arg, corresponding to f(138-144) of human serum albumin. The synthetic heptapeptide, hexapeptide (Tyr-Leu-Tyr-Glu-Ile-Ala, des-7R acein-1) and octapeptide (Tyr-Leu-Tyr-Glu-Ile-Ala-Arg-Arg, acein-1R) showed dose-dependent inhibitions of ACE, and their IC50 values were 16 micromol/l, 500 micromol/l and 86 micromol/l, respectively. Acein-1 might be a non-competitive inhibitor, while acein-1R may be an uncompetitive inhibitor, as shown by Lineweaver-Burk plots.

Amino Acid Sequence↗

The monoamine oxidase-A gene and major psychosis in Japanese subjects.

BACKGROUND: Monoamine oxidase (MAO) is a critical enzyme in deamination of biogenic amines and may be involved in the pathophysiology of major psychosis, including mood disorder and schizophrenia. Recently, evidence for genetic association between the MAO-A gene and bipolar mood disorder was obtained in Caucasians. METHODS: We investigated the polymorphisms of the MAO-A gene, which may be related to enzyme activity (T/941/G, A/1609/G), with amino-acid change (A/1609/G), in Japanese patients with bipolar disorder patients (n = 132), unipolar major depression (n = 43), or schizophrenia (n = 95), and controls (n = 169). RESULTS: No difference in the allele frequencies or genotype distribution of the T/941/G variation was observed between any disease group and the control group. As for the A/1609/G variation, no G allele was found in the Japanese subjects. CONCLUSIONS: No evidence for the genetic association between the MAO-A gene and major psychosis was obtained in the Japanese subjects.

Adult↗

p53-Independent activation of the gadd45 promoter by Delta12-prostaglandin J2.

A p53-inducible gene, the growth arrest and DNA damage-inducible gene 45 (gadd45), is associated with cell growth inhibition, DNA damage response and DNA repair. Here we report that Delta12-prostaglandin J2 (Delta12-PGJ2), an in vivo metabolite of arachidonic acid, which inhibits cell proliferation, induces gadd45 mRNA in HeLa cells. Because the p53 protein in HeLa cells is inactivated by papilloma virus E6, this type of gadd45 induction appears to be p53-independent. The induction was dose-dependent, and the maximum induction was observed at a concentration of 7.5 microgram/ml. In a time course study, gadd45 mRNA was induced 3 h after the addition of 7.5 microgram/ml Delta12-PGJ2. To investigate the transcriptional mechanism of gadd45 mRNA induction, we cloned a human genomic DNA fragment containing the gadd45 promoter region, and investigated the effect of Delta12-PGJ2 on the gadd45 promoter activity. In HeLa cells, 7.5 microgram/ml Delta12-PGJ2 markedly stimulated the gadd45 gene promoter about 20-fold or more. On the other hand, Delta12-PGJ2 did not stimulate the promoter activity of a reporter plasmid containing only p53 binding sites in HeLa cells, indicating that the gadd45 promoter activation by Delta12-PGJ2 was not mediated by p53. These results suggest that one of the mechanisms of cell growth arrest by Delta12-PGJ2 is mediated through a p53-independent induction of gadd45.

Cell Division↗