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Biomedical subjects

S Tsuchiya

Publications and source records attributed to S Tsuchiya.

At least 109 records · Page 6Linked to original sources
PubMed1998

Prolonged release of drug from O/w emulsion and residence in rat nasal cavity.

The present study evaluated the usefulness of an o/w emulsion for slowing the release of chlorpheniramine maleate (CM) and prolonging drug residence in the nasal cavity. O/w emulsion formulations of medium chain triglycerides (MCT) were prepared, and their physicochemical properties and drug release kinetics were evaluated using the in vitro dialysis tube method. Drug disappearance from the rat nasal cavity was determined in in situ nasal experiments. CM partitioned in oil droplets by pH, as predicted by pH partition theory. With higher MCT concentration and pH, slower release of CM was observed. CM disappearance (kapp) from the rat nasal cavity was influenced by the amount of drug partitioned in the oil droplets with both the perfusion and deposit methods, and the kapp of CM decreased with increase in MCT concentration and pH. Moreover, with the deposit method, CM remaining in the nasal cavity exhibited a biphasic profile of disappearance, which complied with a saturated process. Because a very small portion of MCT might be adsorbed and formed a pseudooily layer on the mucous membranes, prolongation of CM residence on the mucous membrane was attained. These findings suggest that emulsion containing 30% MCT at pH 8 may be useful for inclusion in controlled-release formulations of CM for intranasal drug delivery in the treatment of allergy.

Administration, Intranasal↗
PubMed1998

Genetic polymorphisms and mutations of the lipoprotein lipase gene in Japanese schoolchildren with hypoalphalipoproteinemia.

Lipoprotein lipase (LPL) is an important enzyme for the hydrolysis of TG on lipoproteins, and its activity is positively correlated with the plasma levels of high density lipoprotein cholesterol (HDL-C). To investigate the association between the LPL gene and low HDL-C levels, we studied two polymorphisms (Hind III and Pvu II) and three mutations (Asn291Ser, Gly188Glu and LPL(Arita)) of the LPL gene in 114 children with low HDL-C levels (<40 mg/dl) and 194 control children using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques (PCR-RFLP). The frequency of the Pvu II +/+ genotype was significantly higher in the children with low-HDL/high-TG (TG>100 mg/dl, 90th percentile level among Japanese schoolchildren) than in the other children (vs the low-HDL/normal-TG children, chi2 = 7.49, p < 0.01; vs control children, chi2 = 7.23, p < 0.01). Pvu II+ allele of the LPL gene was associated with elevated TG levels in low HDL-C groups. In addition, we found one heterozygote of LPL(Arita) (deletion of G at base 916 in exon 5, the most common mutation of LPL deficiency in Japanese), among the low-HDL/high-TG subjects. The other two variants were not detected in either the low-HDL children or control children. LPL Asn291Ser and Gly188Glu have been presumed to be rare in the Japanese population. In conclusion, our results suggest that hypoalphalipoproteinemia with elevated TG level may be associated with genetic variations of the LPL gene.

Adolescent↗
PubMed1998

[Lifestyle, mental health, and awareness of health among Japanese bus drivers].

To examine lifestyle, mental health and awareness of health, a self-administered questionnaire survey was performed among 751 employees of a bus company in a rural city of Japan. From 597 (79.5%) respondents, we analyzed 130 male bus drivers and age-matched 130 male clerks. The questionnaire included eleven questions about lifestyle and mental health, three questions about awareness of health, and questions on personal concern about specific parts of the body or diseases, and health information they needed. Answers for lifestyle and mental health were classified into the categories of "good" or "not good" practices recommended by Breslow and Morimoto. The results were as follows; 1) Over 80 percent of subjects of both groups had good awareness of health, but bus drivers had significantly worse lifestyle with regard to nutritional intake (p < 0.05), daily walking (p < 0.001), sports (p < 0.05), and sleeping hours (p < 0.001). 2) Bus drivers had significantly greater prevalence of concern about their cardiovascular system, esophagus and gastrointestinal system, and joints and bones than clerks (p < 0.05). 3) Bus drivers had a significantly greater need for information about nutritional intake (p < 0.001), and methods for prevention of diseases (p < 0.01). From these results, the discrepancy between awareness of health and lifestyle seen in this study, especially in food intake, walking time, sports participation, and sleep, may have resulted from the bus driver's characteristics of job, for example, long and irregular working hours. Therefore, effective guidance on health and lifestyle changes to restore balance and improve their lifestyle.

Adolescent↗
PubMed1998

Evaluation of drug disappearance from nasal cavity by the deposit method.

In order to evaluate antiallergic intranasal formulations, the rates of drug disappearance from rat nasal cavity were estimated by the deposit and perfusion methods. The deposit method, which estimates changes in the amount of residual drug in the nasal cavity following washout of the deposited drug over time after application, yielded a good correlation between apparent disappearance rate constant and the combination of lipophilicity and molecular weight. Since the deposit method can be used only with delivery of small amounts of drug to the nasal cavity, the physiological characteristics of the nasal membrane readily affect drug disposition in tests performed with it, and adsorptive drugs such as parabens exhibited rapid disappearance. Doses used clinically for intranasal administration are usually small, and in the case of antiallergic formulations, it is important to maintain the drug concentration in the nasal mucous membrane. The deposit method should be useful for evaluating intranasal antiallergic drug formulations.

Administration, Intranasal↗
PubMed1998

[Telomerase activity in benign proliferative breast disease and breast cancer].

The application of telomerase activity is expected to serve as a reliable indicator of biological malignancy in breast tumors. We performed a study to quantify telomerase activity, the results of which revealed that this activity tends to be unexpectedly low in scirrhous carcinoma having low histological differentiation. It is therefore felt that additional studies at the tissue level using in situ hybridization will be required in the future. Although we think that atypical cystic duct is a true pre-cancerous lesion in the sense of having a high possibility of progressing into breast cancer, it will be interesting to determine whether or not the tissue is composed of cells having telomerase activity.

Breast Diseases↗
PubMed1998

Clinical significance of the increased multidrug resistance-associated protein (MRP) gene expression in patients with primary breast cancer.

The efficacy of cancer treatment is limited by either intrinsic or acquired resistance to various chemotherapeutic agents. To evaluate the clinically important factors related to prognosis in primary breast cancer retrospectively, we investigated the expression of the following genes involving acquirement of drug resistance: multidrug resistance 1 (MDRl), multidrug resistance-associated protein (MRP), and topoisomerase (Topo) I, II alpha, and II beta. Using an RT-PCR method, we semiquantified the gene expression level in untreated stage II breast cancer tissue (n = 27) and noncancerous breast tissue (n = 10). Among the 27 cancer patients, who were all treated by adjuvant chemoendocrine therapy after surgery, 10 patients showed relapse within the following 10 years whereas 17 patients did not. The gene expression levels of MDRl, MRP, and Topo I, II alpha, and II beta were normalized to the level of the beta 2-microglobulin RT-PCR product. MRP mRNA expression was detected in 70% of the breast cancer tissues and its expression levels were significantly increased in the cancer group compared with the noncancerous breast tissues. Furthermore, the MRP level was much higher in the relapsed patient group. On the other hand, there were no significant differences in the MDRl mRNA levels between the noncancerous and cancer groups. Although Topo II alpha mRNA was not detected in noncancerous breast tissues, it was detected in 52% of the breast cancer tissues. In cancer patients, no significant difference in Topo II alpha mRNA levels was observed between the relapsed and nonrelapsed groups. These findings suggest that MRP might be used as one of the markers for poor prognosis in patients with breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

[Analysis of air pollution and prevalence rate of allergic diseases among elementary school children in Kawaguchi and Hatogaya city].

Kawaguchi and Hatogaya City are located on the northern edge of Tokyo. We analysed between air pollution and prevalence rate of allergic diseases among elementary school children in this area. A prevalence rate of allergic diseases in 1996 May and June was as follows; bronchial asthma 13.5%, atopic dermatitis 24.5%, allergic rhinitis and/or conjunctivitis 22.8%, urticaria 12.4%, food allergy 7.8% and drug allergy 2.2%, respectively. Air pollution of this area was analysed to check the levels of nitrogen dioxide (NO2), sulfur dioxide (SO2) and suspended particulate matters (SPM). NO2 pollution was relatively high in urban area, and SPM pollution was especially high around the highways. SO2 pollution was lower than the environmental standard. No relationship was found between the prevalence rate of bronchial asthma, atopic dermatitis, allergic rhinitis and/or conjunctivitis and air pollution, but it was found that these diseases are slightly related to population density (p < 0.1, p < 0.01, p < 0.1, respectively).

Air Pollutants↗
PubMed1997

Scavenger receptors may regulate nitric oxide production from macrophages stimulated by LPS.

The effects of scavenger receptor (SR) ligands on nitric oxide (NO) production were investigated using mouse peritoneal macrophages stimulated by LPS. Pretreatment of macrophages with oxidized LDL, heparin, maleylated BSA, or liposomes composed of phosphatidylserine (PS-liposomes) inhibited NO production, but native LDL, acetyl LDL dextran sulfate, did not. Immunoblotting analysis suggests that the inhibitory effects could be a result of the inhibition of inducible NO synthase (iNOS) induction, but not enzyme activity. Further, tyrosine phosphorylation of a 41 kDa protein was also inhibited by OxLDL, heparin, maleylated BSA, and PS-liposomes. Chloroquine did not affect the extent of inhibition of NO production induced by these ligands, suggesting that the binding of these ligands to SR generates a signal(s) which is involved in the inhibition of NO production from macrophages stimulated by LPS. SR, which has an affinity to these ligands, may strictly regulate NO production from macrophages, and this inhibitory effect may be due to the inhibition of LPS-induced tyrosine phosphorylation of 41 kDa protein.

Animals↗
PubMed1997

Negatively charged liposomes inhibit tyrosine phosphorylation of 41-kDa protein in murine macrophages stimulated with LPS.

Examination was made of the mechanism of the inhibitory effects of liposomes on NO production using thioglycollate-induced mouse peritoneal macrophages stimulated by LPS. NO production was inhibited dose dependently by negatively charged liposomes containing phosphatidylserine (PS-liposomes) but not neutral liposomes composed with phosphatidylcholine. To clarify this mechanism, the effect of liposomes on protein tyrosine phosphorylation was investigated by Western blot analysis, and tyrosine phosphorylation of protein with 41 kDa was inhibited by PS-liposomes dose dependently. NO production and tyrosine phosphorylation of p41 were also inhibited by herbimycin A, a tyrosine kinase inhibitor. TNF-alpha production was also inhibited by PS-liposomes. The inhibition of tyrosine phosphorylation of protein with 41 kDa by PS-liposomes may thus lead to the suppression on NO and TNF-alpha productions from macrophages stimulated by LPS.

Animals↗
PubMed1997

The Japan Society of Coloproctology: a brief history.

The Japan Society of Proctology was inaugurated in 1940 by a number of proctologists in the hope of confirming the independence of their special field of medicine. Originally, it was a small society, consisting mainly of proctologists in practice. Afterward, the scope of the specialty was enlarged, so the name of the society changed to the Japan Society of Coloproctology in 1967. The number of members increased steadily after the 1970s because of the remarkable increase of colorectal lesions in Japan and the rapid progress of coloproctology in the world. The number of societal members reached 5,000 in 1994. Annual meetings of the Society have been held regularly ever since, and the 50th meeting was commemorated in Tokyo in 1995. Also, regular journals of the Society have been issued since its establishment. In addition, the Society has supported many international and domestic societies and has collaborated with them.

Colorectal Surgery↗
PubMed1997

Precordial leads QRST time integrals for evaluation of right ventricular overload in children with congenital heart diseases.

It was previously shown that body surface QRST isointegral maps of the anterior chest were abnormal in patients with right ventricular overload and that the abnormalities varied with hemodynamic status. The QRST isointegral maps were first characterized by using a departure index map for normal controls. The study group consisted of 14 patients with pulmonary stenosis (PS), 20 with tetralogy of Fallot, (TOF) and 43 with atrial septal defect (ASD). The QRST isointegral maps of these three groups were compared with the data on 23 to 65 age-matched normal children. In mean departure index maps, the patients with right ventricular pressure overload (PS or TOF) showed an increase in departure index on the anterior midchest, while those of right ventricular volume overload (ASD) showed two maxima on the anterior and left lateral chest, with a trough-like negative area between them. Since the abnormal findings were seen on the anterior chest, we evaluated the diagnostic usefulness of QRST time integral values for precordial leads of the routine electrocardiogram (ECG) in a second part of this study. The precordial QRST time integral values from 9 patients with PS and 11 with TOF (0-2 years of age, mean 1.1 years) and 22 ASD patients (6-15 years, mean 10.1 years) were compared with those of the age-matched control children. The QRST time integral values of the precordial leads in right ventricular pressure overload were significantly increased in the right precordial leads (V1, V2). In right ventricular volume overload, the QRST time integral values of the V1, V2, V4, and V6 leads demonstrated a significant deviation from those of the control group. Therefore, a discrimination formula was constructed by using the values of these leads, and the criteria derived from this formula revealed good (98%) diagnostic accuracy. In detection of right ventricular overload, the QRST time integral values of the precordial lead ECG, if confirmed in a larger data set, may be useful as a simple screening method.

Adolescent↗
PubMed1997

Expression of GATA transcription factors in myelogenous and lymphoblastic leukemia cells.

In the hematopoietic lineage, the transcription factors GATA-1 and GATA-2 show restricted and largely overlapping expression profiles, but GATA-2 is uniquely expressed in early hematopoietic progenitors. GATA-3 is found exclusively in T cells of hematopoietic lineage. To clarify whether these expression profiles are preserved or changed during the development of malignancies, we analyzed the expression of GATA factors in the blasts from leukemic children. A total of 18 myelogenous leukemia and 24 lymphoblastic leukemia (ALL) cases were investigated. In the majority of the former cases, GATA-2 mRNA expression and the expression of CD34 and c-kit antigens on leukemic cells were demonstrated. In contrast, GATA-2 mRNA and c-kit antigen could not be detected in CD34-positive cells from ALL patients. GATA-3 mRNA was expressed in all T-ALL cases, but not in any precursor B-ALL. These findings suggest that down-regulation of GATA-2 and expression of GATA-3 are important events for the commitment of cells to lymphoid and T cell lineage, respectively. The expression profiles of GATA factors in leukemic cells are generally consistent with those in their normal counterparts, and thus provide a useful tool to determine the lineage commitment of unclassified leukemia.

Adult↗
PubMed1997

Effects of oligodeoxynucleotides on the physicochemical characteristics and cellular uptake of liposomes.

We studied the effects of a phosphodiester oligodeoxynucleotide (ODN), which is antisense to the site in the neighborhood of the AUG initiation codon of the mouse tumor necrosis factor alpha gene (TNF-alpha), on the physicochemical characteristics and the cellular association of three types of liposomes with different surface charges. The physicochemical characteristics of the liposomes changed after adding ODN. When the ODN/lipid molar ratio was approximately 0.15 in cationic (TMAG) liposomes [consisting of N-(alpha-trimethylammonioacetyl)didodecyl-D-glutamate chloride (TMAG), dilauroylphosphatidylcholine (DLPC), and dioleolylphosphatidylethanolamine (DOPE) in a 1:2:2 ratio], but not in neutral and negatively charged liposomes, then the liposomes aggregated and fused. At higher molar ratios, these changes in TMA liposomes were not evident. In addition, ODN inverted the zeta-potential of TMAG liposomes from positive to negative at an ODN/lipid molar ratio of approximately 0.15. Therefore, the aggregation and fusion induced by ODN could be explained by a lower surface charge repulsion between TMAG liposomes. On the other hand, the association of ODN with RAW264.7 cells, a mouse macrophage-like cell line, was very slight. The cellular association of ODN was significantly enhanced compared with neutral and negatively charged liposomes by encapsulation in TMAG liposomes. The ODN added to liposome suspensions did not affect the rate and extent of TMAG liposome cellular association, even at an ODN/lipid molar ratio of approximately 0.15. These results indicate that the lipid composition and ODN/lipid molar ratio are critical for the physicochemical characteristics of cationic liposomes. However, the changes had less influence on the cellular uptake properties of cationic liposomes.

Animals↗
PubMed1997

Contribution of trypsin-sensitive proteins to binding of cationic liposomes to the mouse macrophage-like cell line RAW264.7.

We studied the binding of cationic liposomes, including didodecyl N-(alpha-(trimethylammonio)acetyl)-D-glutamate chloride (TMAG), to a mouse macrophage-like cell line RAW264.7 to clarify which molecules contribute to the binding of TMAG liposomes to the cell surface. Several types of TMAG liposomes encapsulating [3H]inulin, intra-aqueous markers of liposomes, were prepared and their binding characteristics were compared with those of neutral and negatively charged liposomes. The binding of TMAG liposomes to cells was superior to those of neutral and negatively charged liposomes and increased with increasing TMAG content. Scatchard plots for the binding of TMAG liposomes to the cells were approximately linear, indicating a single class of binding sites. Pretreatment of the cell surface with heparinase, heparitiase, chondroitinase ABC, or neuraminidase did not reduce the binding of TMAG liposomes. These results suggested that neuraminic acid and glycosaminoglycan on the cell surface have little contribution to TMAG liposome binding. Pretreatment of the cells with trypsin reduced the binding of TMAG liposomes in a concentration-dependent manner but did not detach the cells from the culture plates. In addition, alpha-chymotrypsin pretreatment had no effect even up to 5 micrograms/mL. Post-treatment with trypsin enhanced the release of TMAG liposomes from the cell surface in a concentration-dependent manner. These results demonstrated that TMAG liposomes bind to trypsin-sensitive proteins on the cell surface.

Animals↗
PubMed1997

Specific inhibition of nitric oxide production in macrophages by phosphorothioate antisense oligonucleotides.

The effects of antisense oligonucleotides (ODNs) on nitric oxide (NO) production induced by lipopolysaccharide (LPS) were investigated using thioglycollate-induced mouse peritoneal macrophages. Antisense phosphorothioate ODNs (S-oligo) corresponding to a sequence in the neighborhood of the AUG initiation codon of a mouse inducible nitric oxide synthase (iNOS) mRNA, which has a G-quartet motif in its antisense sequence, inhibited NO induction in a dose-dependent manner. Antisense phosphodiester ODNs (D-oligo), 5'- and 3'-terminal phosphorothioate-modified antisense ODNs and control scramble and missense S-oligos had no such effect. In addition, control nonsense and two mismatched S-oligos, which include G-quartet motif in their sequences, inhibited NO induction to approximately 50% of those in the control. Antisense S-oligo showed the inhibitory effect on NO production by exposure of macrophages to various concentrations of LPS. Western blot analysis using anti-mouse inducible nitric oxide synthase (iNOS) antibody revealed that antisense S-oligo specifically removed an immunoreactive band at 130 kDa. In addition, the results of reverse transcription-polymerase chain reaction (RT-PCR) revealed that the antisense effect originated from a specific reduction of the targeted iNOS mRNA by hybridization with the antisense S-oligo. Furthermore, no ODNs affected beta-actin mRNA and tumor necrosis factor alpha (TNF-alpha) expression in macrophages stimulated by LPS. These findings demonstrated that antisense S-oligo inhibited NO production derived from iNOS expression in macrophages by an antisense mechanism, including the aptameric effect partially mediated by the G-quartet motif.

Animals↗
PubMed1997

Conformation of an Shc-derived phosphotyrosine-containing peptide complexed with the Grb2 SH2 domain.

We have determined the structure of an Shc-derived phosphotyrosine-containing peptide complexed with Grb2 SH2 based on intra- and intermolecular NOE correlations observed by a series of isotope-filtered NMR experiments using a PFG z-filter. In contrast to an extended conformation of phosphotyrosine-containing peptides bound to Src, Syp and PLC gamma SH2s, the Shc-derived peptide formed a turn at the +1 and +2 positions next to the phosphotyrosine residue. Trp121, located at the EF1 site of Grb2 SH2, blocked the peptide binding in an extended conformation. The present study confirms that each phosphotyrosine-containing peptide binds to the cognate SH2 with a specific conformation, which gives the structural basis for the binding specificity between SH2s and target proteins.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Successful treatment of steroid-resistant severe acute GVHD with 24-h continuous infusion of FK506.

We report our findings in two cases of steroid-resistant severe acute GVHD after allogeneic BMT successfully treated with FK506 (tacrolimus). An 18-year-old female (patient 1) who underwent BMT from an HLA-identical sibling for ALL in first CR, developed generalized erythema and profuse watery diarrhea, which progressed to acute GVHD of grade III severity, resistant to steroid control. After continuous 24-h administration of FK506, the diarrhea improved within 10 days. Patient 2, a 9-year-old girl with AML who underwent unrelated BMT, had skin, gut and liver lesions of acute GVHD grade IV, which did not respond to high-dose steroid therapy. They were controlled, however, by continuous intravenous infusion of FK506. Both patients are still surviving after more than 1 year without any acute GVHD sequelae or signs of chronic illness. The adverse effects of FK506 were mild and tolerable in both cases. Comparison of our findings with those in the literature suggests that it is important to give FK506 at plasma concentrations as high as 25-35 ng/ml by continuous intravenous infusion for extended periods to control steroid-resistant severe acute GVHD.

Acute Disease↗