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Biomedical subjects

S Kitagawa

Publications and source records attributed to S Kitagawa.

At least 91 records · Page 5Linked to original sources

[A desmoid tumor of the chest wall].

Desmoid tumors develop in the muscle or aponeurosis, but rarely in the chest wall. We report a patient with desmoid tumor in the chest wall. A 30-year-old female visited our hospital due to an abnormal shadow in the chest detected at a health examination. No definite diagnosis could be made by chest CT, MRI, or Ga scintigraphy, and finally a biopsy demonstrated desmoid tumor. The left anterior chest and posterolateral chest (lung apex) were opened, and tumors were resected together with the chest wall. No radiotherapy was performed. No recurrence has been observed for 1.5 years after operation. This tumor does not yield distant metastasis, but its recurrence rate is very high. Therefore, we intend to follow this patient for a long period.

Adult↗

Tyrosine phosphorylation of p38 but not extracellular signal-regulated kinase in normal human neutrophils stimulated by tumor necrosis factor: comparative study with granulocyte-macrophage colony-stimulating factor.

We investigated the cytokine-specific involvement of two members of the microtubule-associated protein kinase family, extracellular signal-regulated kinase (ERK)(1 and 2) and p38, in normal human neutrophils. Both tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) induced tyrosine phosphorylation of a 42-kDa protein in human neutrophils, though the time course of its phosphorylation and its band pattern in electrophoresis differed for each of the cytokines. In addition, GM-CSF, but not TNF, induced a mobility shift of 42-kDa ERK2 in human neutrophils. By using immunoprecipitation followed by immunoblotting, we clarified that GM-CSF, but not TNF, induced tyrosine phosphorylation of ERK2 and that TNF, but not GM-CSF, induced tyrosine phosphorylation of p38. Results of a combined stimulation study showed that tyrosine phosphorylation of ERK2 and that of p38 do not interfere or interact with each other at least in human neutrophils. These results indicate cytokine specific involvement and an independent activating system of ERK and p38 in normal human neutrophils stimulated by two cytokines which share many biological activities in these cells.

Adult↗

Polyploidization and functional maturation are two distinct processes during megakaryocytic differentiation: involvement of cyclin-dependent kinase inhibitor p21 in polyploidization.

The mechanism of megakaryocytic differentiation was investigated using human megakaryocytic leukemia cell line UT-7. Polyploidization of UT-7 cells was induced by the microtubule-depolymerizing agent, nocodazole, and 12-O-tetradecanoylphorbol-13-acetate (TPA), but the effect was much more striking with nocodazole. By contrast, induction of cytoplasmic maturation, as judged by beta-thromboglobulin production and platelet factor 4 expression, was more prominent in TPA-treated cells than in nocodazole-treated cells. Nocodazole and TPA could act synergistically to increase ploidy and to enhance the expression of mature phenotypes. Human thrombopoietin induced functional maturation but not polyploidization in UT-7 cells and also acts synergistically with nocodazole. Cyclin-dependent kinase inhibitor p21 was upregulated at the early stage of megakaryocytic differentiation, and overexpression of p21 resulted in an increase in ploidy of UT-7 cells. This suggests that p21 is implicated in polyploidization via suppression of CDC2 activity at mitosis. UT-7 but not HL-60 cells could incorporate [3H]thymidine in the presence of TPA, indicating the presence of megakaryocyte-specific licensing factor to allow DNA replication during differentiation. Taking these data together, we propose that megakaryocytic differentiation consists of two distinct processes, polyploidization and functional maturation, and that these two processes are independently regulated.

Carcinogens↗

Monocytes modulate the fibrinolytic balance of endothelial cells.

Cultured endothelial cells (ECs) produced a constitutive plasminogen activator inhibitor-I (PAI-1), whereas primary culture of monocytes from blood did not produce a detectable amount of PAI-1. Addition of monocytes to ECs caused the accumulation of a large amount of PAI-1 in the supernatant in a dose- and time-dependent manner. Having almost no effect on the production of tissue-type plasminogen activator (t-PA), monocytes decreased the potential fibrinolytic activity of ECs. The 6 hours conditioned medium obtained from the coculture system between monocytes and either ECs or paraformaldehyde-fixed ECs had almost the same effect on the other ECs to produce PAI-1 and t-PA as monocytes that were direct contact with ECs. In addition, this effect was specifically inhibited by using two antibodies against interleukin-1 beta and tumor necrosis factor-alpha. These results indicate that interleukin-1 beta and tumor necrosis factor-alpha induced by the coculture are mostly responsible for decreasing the fibrinolytic activity of ECs.

Cells, Cultured↗

Instrumentation of a handy microscopic probe for concurrent observation and measurement of active sweat secretion, and its applications.

Instrumentation for the concurrent, dynamic monitoring of active sweat glands and perspiration volume is described. A device for the measurement of the rate of sweat secretion was installed on the head part of a microscope. The combined apparatus (microscopic probe) is handy for use and its weight is very light (ca. 300 g). The microscopic probe is easily attached to the surface of human skin. The dynamic activities of the sweat glands on the forehead and nose and under the nose were observed and measurement when thermal, mental and physical stimuli were applied. The activities of individuals sweat glands were asynchronous when observed in units of a few seconds or less; however, they worked synchronously in a unit period of several seconds. The latter were recorded as fine peaks by a strip chart recorder. The proposed system may be useful for the study of the sympathetic nervous system, the skin sympathetic reflex and the working of sudomotor nerves.

Adult↗

A kinetic analysis of the effects of beta-phenylethylamine on the concentrations of dopamine and its metabolites in the rat striatum.

The purpose of this investigation was to determine whether the increase in the dopamine (DA) concentration in the rat striatum after a rapid iv injection of beta-phenylethylamine (PEA) can be quantitatively explained by the alteration of the striatum PEA concentration using a constructed DA metabolism model and to examine whether the time courses of the striatum DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentration can be described by this DA metabolism model. The time courses of PEA concentration in plasma and the striatum were determined by gas chromatography-mass spectrometry. The plasma PEA concentration was described by a two-compartment model with nonlinear elimination kinetics. The striatum PEA concentration was about 10 times higher than the plasma PEA concentration. The time course of the striatum PEA concentration was described by a diffusion-limited model including a Michaelis-Menten type transport system from plasma to the striatum and nonlinear elimination from the striatum. The DA concentration in the striatum increased immediately after PEA injection. In contrast, the DOPAC concentration in the striatum decreased immediately. HVA concentration in the striatum increased gradually. Assuming that the enhancement of DA concentration in the striatum after PEA injection is caused by the competitive inhibition of PEA on the reuptake of DA into DA neuronal terminals (and the metabolism from DA to DOPAC is then competitively inhibited by PEA in the DA neuronal terminals), the relationship between the enhancement of DA concentration and PEA concentration in the striatum was analyzed using a constructed DA metabolism model. The enhancement of the DA concentration in the striatum was described quantitatively by this model. Thus, it was clarified that a quantitative relationship between PEA concentration and the enhancement of DA concentration in the striatum is present after PEA injection. However, the time courses of the striatum DOPAC (lower dose) and HVA (time delay) concentrations could not be described by this model. These results indicated that other factors might be necessary to explain the time courses of the DOPAC and HVA concentrations in the striatum after PEA injection, such as the separate evaluation of the effect of PEA on the reuptake of DA into DA neuronal terminals and on the monoamine oxidase-B (MAO-B) activity in the DA neuronal terminals, and the metabolic pathway from DOPAC to HVA.

3,4-Dihydroxyphenylacetic Acid↗

Activation of human monocytes for enhanced production of interleukin 8 during transendothelial migration in vitro.

Interleukin-8 (IL-8) is a chemokine for polymorphonuclear leukocytes (PMNs) and lymphocytes, which promotes the extravasation of these inflammatory cells. In this study, we investigated IL-8 synthesis induced by the adhesive interaction between monocytes and endothelial cells during transmigration and the capacity of transmigrated monocytes to produce IL-8. Cocultured human monocytes and human umbilical vein endothelial cell (HUVEC) monolayers induced the synergistic production of IL-8, compared with cultures of either monocytes or HUVEC monolayers alone. Coculture-induced IL-8 production almost doubled after HUVECs were stimulated with IL-1 beta. The induced IL-8 mRNA expression was consistent with the protein data, indicating the de novo synthesis of IL-8 by the coculture. Monoclonal antibodies (mAbs) against IL-8 inhibited the transendothelial chemotactic activity of the supernatants for PMNs by 55%. Immunohistochemistry revealed that both adherent and transmigrated monocytes and unstimulated HUVECs expressed IL-8 protein, whereas nonadherent monocytes did little. Transmigrated monocytes spontaneously secreted a 3.8-fold greater amount of IL-8 than the initial monocytes. Coculture-induced IL-8 production was inhibited about 30% by polyclonal Abs against IL-alpha, IL-1 beta, or tumor necrosis factor alpha, while it was not affected by mAbs against intercellular adhesion molecule 1 or vascular cell adhesion molecule 1. The results suggested that adhesive interaction during the transmigration of monocytes through HUVEC monolayers activates both cell types to produce IL-8 and that transmigrated monocytes are capable of producing ample IL-8.

Antibodies, Monoclonal↗

Characteristics of cefdinir uptake by rabbit small intestinal brush-border membrane vesicles.

Aminocephalosporins with peptide-like structures have been shown to be absorbed by the intestinal peptide carrier. We investigated the transport mechanism of cefdinir, an oral monocarboxylic acid cephalosporin, using rabbit small intestinal brush-border membrane vesicles. Transport of cefdinir showed a slow and almost linear uptake rate for concentrations up to 30 mM with and without and inward H+ gradient. No overshoot phenomenon was observed in the presence of an inward H+ gradient. The uptake rate increased only slightly with decreasing extravesicular pH, and a protonophore had little effect on the uptake. Aminocephalosporins such as cephalexin only slightly inhibited cefdinir uptake even in the presence of an inward H+ gradient, and vice-versa. Monocarboxylic acids such as acetic acid and salicylic acid had little effect on cefdinir uptake. These findings suggest that in contrast with other oral cephalosporins cefdinir uptake through the brush-border membrane is slow and involves a mechanism similar to passive diffusion.

Animals↗

Gastrointestinal submucosal tumors: evaluation with endoscopic US.

PURPOSE: To describe the endoscopic ultrasound (US) features of benign versus malignant submucosal tumors throughout the gastrointestinal tract. MATERIALS AND METHODS: One hundred nine patients aged 24-81 years suspected to have submucosal tumors (11 esophageal, 41 stomach, 24 duodenal, and 33 colorectal tumors) at barium studies or endoscopy underwent endoscopic US. The layer of origin, internal echo pattern, and lesion margin were analyzed by means of consensus and independent interpretation by three radiologists. RESULTS: Endoscopic US findings revealed several distinct patterns among various submucosal tumors. Sixteen (94%) of the 17 homogeneous lesions with histopathologic findings of malignancy were hypoechoic, although 29 (43%) of the 68 homogeneous lesions with histopathologic findings of benignity were similarly hypoechoic. Homogeneous lesions that were anechoic, of intermediate echogenicity, or hyperechoic were almost exclusively benign (39 [98%] of 40). In contrast, 23 (96%) of the 24 malignant lesions were heterogeneous (n = 7) or homogeneously hypoechoic (n = 16). The sizes of benign and malignant lesions were significantly different (P < .05). There was no significant difference in the echo pattern (i.e., homogeneous versus heterogeneous), but there was a significant difference in the proportion of hypoechoic versus nonhypoechoic lesions (anechoic, hyperechoic, or of intermediate echogenicity; P < .001). CONCLUSION: The differential diagnosis of gastrointestinal submucosal tumors is assisted with endoscopic US.

Diagnosis, Differential↗

Inhibitory effects of angiotensin-converting enzyme inhibitor on cefroxadine uptake by rabbit small intestinal brush border membrane vesicles.

Effects of angiotensin-converting enzyme (ACE) inhibitors, captopril, enalapril maleate and quinapril, on the uptake of aminocephalosporin antibiotic, cefroxadine, by rabbit small intestinal brush border membrane vesicles were examined. These ACE inhibitors significantly inhibited the uptake of cefroxadine, which is transported by H+/dipeptide transporter in the membrane, in the order of captopril < enalapril < quinapril in the presence of an inward H+ gradient. Inhibitory effect of quinapril was more marked than that of aminocephalosporin cephradine, while in the absence of an inward H+ gradient inhibition by these ACE inhibitors was much less. Dixon plot analysis showed that the inhibition by enalapril and quinapril in the presence of an inward H+ gradient occurred in a competitive manner and estimated inhibition constants of these two drugs to be 5.3 mM and 0.46 mM, respectively. These results suggested the strong affinity of these ACE inhibitors, especially quinapril, on the H+/dipeptide transporter.

Angiotensin-Converting Enzyme Inhibitors↗

Skin permeation of parabens in excised guinea pig dorsal skin, its modification by penetration enhancers and their relationship with n-octanol/water partition coefficients.

Skin penetration of methyl, ethyl, propyl and butyl parabens through excised guinea pig dorsal skin was examined, and effects of the penetration enhancers, l-menthol plus ethanol itself and N-dodecyl-2-pyrrolidone, were observed. Permeability of coefficients of the parabens correlated with n-octanol/water partition coefficients. Addition of 1% l-menthol in 15% ethanol about sixteen times increased the permeability coefficient of methyl paraben, whereas this enhancer decreased that of butyl paraben to about one fifth of the control value. A similar, though weaker, tendency was observed for the effects of 15% ethanol itself. 0.025% suspension of N-dodecyl-2-pyrrolidone increased the permeability coefficient of methyl paraben about seven times, whereas it did not change that of butyl paraben significantly. Therefore, dependency of the permeability coefficients of the parabens on n-octanol/water partition coefficients almost disappeared in the presence of this compound. A spin label study with stratum corneum lipid liposomes revealed that increase of fluidity of the lipid bilayer by these penetration enhancers corresponded with their enhancement effects on skin penetration of methyl paraben. Perturbation of stratum corneum lipid lamella thus seems to be related with their enhancement of the absorption of hydrophilic paraben.

Animals↗

Studies on the constituents of Broussonetia species. II. Six new pyrrolidine alkaloids, broussonetine A, B, E, F and broussonetinine A and B, as inhibitors of glycosidases from Broussonetia kazinoki Sieb.

Six new pyrrolidine alkaloids called broussonetine A, B, E, F, and broussonetinine A and B were isolated from the branches of Broussonetia kazinoki Sieb. (Moraceae). Broussonetine A, B, E and F were formulated as 2 beta-hydroxymethyl-3 beta-hydroxy-5-alpha- (10-oxo-13-hydroxytridecyl)-pyrrolidine-4-O-beta-D-glucopyranoside (1), 2 beta-hydroxymethyl-3 beta-hydroxy-5 alpha-(9-oxo-13-hydroxytridecyl)-pyrrolidine-4-O-beta-D-glucopy ran oside (2), 2 beta-hydroxymethyl-3 alpha,4 beta-dihydroxy-5 alpha-(1,13-dihydroxy-10-oxo-tridecyl)-pyrrolidine (3), and 2 beta-hydroxymethyl-3 alpha,4 beta-dihydroxy-5 alpha-(1,13-dihydroxy-9-oxo-tridecyl)-pyrrolidine (4), respectively. Broussonetinine A and B (5 and 6) were also isolated and identified as the aglycones of 1 and 2. 3 and 4 exhibited a strong inhibition of alpha-glucosidase, beta-glucosidase, beta-galactosidase and beta-mannosidase, while 5 and 6 showed a strong inhibition of beta-galactosidase and alpha-mannosidase.

Alkaloids↗

Severe chest pain due to gastric anisakiasis.

We treated two cases of gastric anisakiasis presenting with severe chest pain. In both cases, there was a history of prior ingestion of raw saltwater fish. After endoscopic removal of larvae, the chest pain disappeared and never recurred. Other diseases causing chest pain were ruled out by symptoms, signs, blood tests, electrocardiography, chest radiograph, and ultrasonic examination of the heart and abdomen. Thus the chest pain was considered to be caused by gastric anisakiasis. Gastric anisakiasis should be included in the differential diagnosis of acute chest pain.

Adult↗