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Biomedical subjects

K Masuda

Publications and source records attributed to K Masuda.

At least 379 records · Page 21Linked to original sources

Liposteroid against refractory pulmonary haemorrhage in idiopathic pulmonary haemosiderosis.

We describe two Japanese children with idiopathic pulmonary haemosiderosis (IPH), whose refractory haemorrhages were treated with an intravenous lipid emulsion containing dexamethasone (liposteroid). A 22-month-old boy and a 14-month-old girl have been observed with similar symptoms; periodic bouts of anaemia, reticulocytosis, diffuse infiltrates on chest X-ray and the finding of siderophages in sputum or gastric lavage fluid. The MRI of the lung was useful for the diagnosis. Methylprednisolone pulse therapy was successful in treating acute massive bleeding. Subsequent oral prednisolone could not prevent chronic recurrent haemorrhages. However, the intermittent administration of liposteroid (0.05 mg/kg/dose IV) led to a cessation of bleeding; the haemoglobin concentration rose to normal levels. This observation emphasizes the usefulness of liposteroid in the management of refractory IPH.

Dexamethasone↗

Striatal 18F-dopa uptake and brain glucose metabolism by PET in patients with syndrome of progressive ataxia.

Striatal 18F-Dopa uptake and brain glucose metabolism were studied by PET with 6-L-[18F]flurodopa and [18F]fluorodeoxyglucose in 11 patients with syndrome of progressive ataxia. Five of the 11 patients were diagnosed as having cerebellar cortical degeneration (CCD), including 3 with late cerebellar cortical atrophy and 2 with Holmes type hereditary ataxia while 6 demonstrated olivopontocerebellar atrophy (OPCA). The caudate and putaminal 18F-Dopa uptake ratios to the occipital cortex in CCD showed no significant difference from those in the controls. On the other hand, those with OPCA decreased as compared to the controls. In addition, the cerebellar glucose metabolism in CCD decreased as compared to the controls, while that in the brainstem showed no significant decrease from the controls. The glucose metabolic rates both in the cerebellar hemisphere and in the brainstem in the OPCA patients decreased compared to the controls. The cerebral cortical, striatal and thalamic glucose metabolisms were normal in both the CCD and OPCA in groups. The appearance of a decreased glucose metabolism in the cerebellum is considered to be relevant in the genesis of cerebellar ataxia, even though their underlying diseases were different from each other. The differences in the glucose metabolism of the brainstem and in the nigrostriatal presynaptic dopaminergic function between CCD and OPCA as assessed by PET may be caused by differences in the pathophysiological mechanism between CCD and OPCA, and those differences appear to be useful when making a differential diagnosis of CCD and OPCA.

Adult↗

Metabolic pathway of 2-deoxy-2-[18F]fluoro-D-talose in mice: trapping in tissue after phosphorylation by galactokinase.

To make clear the metabolic fate of 2-deoxy-2-[18F]fluoro-D-talose ([18F]FDT) in animals, the in vivo and in vitro metabolism of non-radioactive 2-deoxy-2-fluoro-D-talose (FDT) was investigated by 19F-NMR spectroscopy. Based on the 19F-NMR spectral analyses, 2-deoxy-2-fluoro-alpha-D-talose-1-phosphate (FDT-1-P) was identified as a single metabolite in the organs of tumor-bearing mice after FDT administration (60 mg/kg). In the liver, almost all FDT was converted to FDT-1-P within 10 min after FDT injection and the phosphate form remained unchanged for at least 3 h. FDT was well converted to FDT-1-P by galactokinase in vitro. The FDT-1-P formed, however, failed to convert to a uridylate derivative by treatment with galactose-1-phosphate uridyltransferase. The observed low affinity of galactose-1-phosphate uridyltransferase for the FDT-1-P could account for the accumulation mechanism of FDT-1-P in vivo. Similar metabolic studies of [18F]FDT with radio-TLC demonstrated the [18F]FDT-1-P as a single metabolite of [18F]FDT in the mouse liver. These results indicate that [18F]FDT enters a D-galactose metabolic pathway and undergoes a metabolic trapping in the [18F]FDT-1-P form by galactokinase in the tissues such as liver and tumor. Consequently, [18F]FDT is expected to be a new radiopharmaceutical for the measurement of galactokinase activity by positron emission tomography.

Animals↗

Characteristics of ceftibuten uptake into Caco-2 cells.

The characteristics of ceftibuten uptake into Caco-2 cells grown in a collagen-coated dish were examined. Ceftibuten showed stereoselective and pH-dependent uptake. The pH-dependency of ceftibuten was more marked than that of cefaclor or cephalexin, but all three antibiotics showed maximal uptake at pH 5.5. Ceftibuten uptake was linear for the initial 1 hr and then reached a plateau. The initial uptake (15 min) was markedly reduced by the addition of 2,4-dinitrophenol or FCCP (a protonophore), or by lowering the incubation temperature. The uptake of ceftibuten into the brush-border membrane vesicles prepared from cultured Caco-2 cells showed an overshoot in the presence of an H(+)-gradient. These findings indicated that the uptake of ceftibuten was energy-dependent, especially H(+)-gradient-dependent. Uptake inhibition by various compounds was compared using Caco-2 cells. Amino acids and a tetrapeptide did not inhibit uptake, whereas di- or tri-peptides were effective inhibitors. These observations suggest that ceftibuten is taken up by a carrier-mediated transport system(s) for dipeptides. Various antibiotics differed in their ability to inhibit uptake, with cyclacillin showing maximum inhibition. Differences in the inhibitory effect may be accounted for by the heterogeneity (multiplicity) of the transport systems.

2,4-Dinitrophenol↗

Lidocaine hydrochloride and acetylsalicylate kill bacteria by disrupting the bacterial membrane potential in different ways.

Lidocaine hydrochloride (LH), a local anesthetic, and acetylsalicylate (AcSAL), show antibacterial activity for both gram-negative and gram-positive bacteria. Kinetic studies indicated that antibacterial activity of LH was different from that of AcSAL. A subinhibitory concentration of LH and AcSAL enhanced the sensitivity of Escherichia coli, Salmonella typhimurium, and Pseudomonas aeruginosa to novobiocin and nalidixic acid. The synergistic effect of AcSAL with novobiocin and nalidixic acid was higher than that of LH. The effect of both drugs on the membrane potential of inner membrane was also studied using inverted membrane vesicles of bacteria. Both LH and AcSAL depolarized the membrane potential after the vesicles were energized with nicotinamide adenine dinucleotide. However, unlike AcSAL, pre-treatment of vesicles with LH had no effect on the generation of membrane potential. These results suggest that depolarization of the cytoplasmic membrane, preceded by the permeabilization of the outer membrane for gram-negative bacteria, is associated with antibacterial activity of LH and AcSAL. The difference in actions of LH and AcSAL was discussed.

Anti-Bacterial Agents↗

Bactericidal action of tachyplesin I against oral streptococci.

Tachyplesin I, a polycationic antimicrobial peptide isolated from hemocytes of horseshoe crabs, kills bacteria by disrupting the membrane potential of the cytoplasmic membrane. The present study shows that, among 36 oral streptococcal strains, 12 of 21 Streptococcus sanguis, 3 Streptococcus mutans, 9 Streptococcus salivarius and 3 Streptococcus milleri strains were susceptible to tachyplesin I, whereas 9 S. sanguis strains were resistant. Interestingly, these resistant strains include the clinical isolates from both Kawasaki disease and Behçet patients. According to the time-kill study, tachyplesin I inhibited irreversibly the growth of S. sanguis, S. mutans and S. salivarius strains within 20 min and an S. milleri strain within 80 min. Although it has been suggested that Escherichia coli cultured in rich media were more susceptible to tachyplesin I, the present results show that only 3 S. milleri strains were more sensitized to tachyplesin I in a glucose-supplemented medium, and other tested strains were not. Similarly, only 4 strains were more resistant to tachyplesin I in saline than these were in a rich medium.

Anti-Bacterial Agents↗

S-antigen specific T cell clones from a patient with Behçet's disease.

The isolation and characterisation of T cell clones or lines specific to retinal antigens are valuable tools to clarify the underlying mechanisms of autoimmunity to retinal antigens as a contributing factor in ocular inflammation. Patients with Behçet's disease have been reported to be sensitised to S-antigen (S-Ag). In the present study, four T cell clones established from the peripheral blood of a patient with Behçet's disease were analysed. A CD4+ T cell clone (clone 2) and a CD8+ T cell clone (clone 10) proliferated specifically to bovine S-Ag. Although these S-Ag specific T cell clones proliferated vigorously to the intact antigen, their responses to S-Ag derived synthetic peptides M and G were weak, suggesting that the sites of human T cell recognition of S-Ag may be different from those established in the experimental model. The proliferative responses of both clones (2 and 10) were inhibited by anti-HLA-DR monoclonal antibody but not by anti-HLA-class 1 monoclonal antibody. The other two clones studied, clones 6 and 30, were CD3+, CD4-, CD8-, and they did not proliferate specifically to S-Ag. Clone 6 expressed gamma delta T cell receptors (TCR) and showed non-specific cytotoxic activity toward K562 and Daudi cell lines. Clone 30 expressed alpha beta TCR, and was devoid of cytotoxic activity. Human T cell lines and clones specific to retinal antigens will provide the framework necessary to examine the events that lead to ocular inflammation.

Adult↗

Colonic submucosal tumors: comparison of endoscopic US and target air-enema CT with barium enema study and colonoscopy.

PURPOSE: To compare the imaging characteristics of colonic submucosal tumors at endoscopic ultrasound (US) and target air-enema computed tomography (TACT) with those at conventional double-contrast barium enema study and colonoscopy. MATERIALS AND METHODS: Twenty consecutive patients with suspected colonic submucosal tumors at barium enema study and colonoscopy underwent endoscopic US, TACT, or both. Morphologic features and posture-related change in shape of tumor were evaluated with barium enema study, color and consistency of tumor with colonoscopy, internal echogenicity of tumor and layer of origin in normal colonic wall with endoscopic US, and CT attenuation number with TACT. RESULTS: Eight lipomas, seven carcinoids, three leiomyomas, four lymphangiomas, and one hemangioma were found at histologic examination. Lipomas and lymphangiomas had characteristic findings at endoscopic US and TACT. The differential diagnosis of the other submucosal tumors was facilitated by using endoscopic US. CONCLUSION: Endoscopic US and TACT may play a valuable role in the evaluation of colonic submucosal tumors.

Adult↗

Selective antitumor effect of thioether-linked immunotoxins composed of gelonin and monoclonal antibody to alpha-fetoprotein or its F(ab')2 fragment.

Two thioether-linked conjugates composed of monoclonal antibody (MoAb) to alpha-fetoprotein (AFP), 80G or its F(ab')2 fragment, and a type 1 ribosome-inactivating protein (RIP), gelonin, were prepared as potent immunotoxins [80G-CS-GL(IT) and F(ab')2-CS-GL(IT)]. Each conjugate contained one gelonin per 80G or its F(ab')2 fragment. The binding activity of these conjugates was as high as that of intact 80G or F(ab')2. The in vitro cytotoxic effect of F(ab')2-CS-GL(IT) on AFP-producing HuH-7 cells was approximately 100-fold more potent than that of 80G-CS-GL(IT). Also, F(ab')2-CS-GL(IT) showed slight cytotoxicity against non-AFP-producing HuH-13 cells, while 80G-CS-GL(IT) did not. On the other hand, both conjugates had similar selective antitumor activity against HuH-7N cells in nude mice, possibly due to their similar distribution in the tumor. The results suggest that our MoAb 80G is a suitable carrier for delivering type 1 RIP such as gelonin into AFP-producing hepatoma cells and that its F(ab')2 fragmentation does not enhance targeting efficiency.

Animals↗

Fibroblast attachment to Arg-Gly-Asp peptide-immobilized poly(gamma-methyl L-glutamate).

The attachment of MRC-5 human fibroblasts was investigated on poly(gamma-methyl L-glutamate) (PMLG), and upon cell adhesion peptides Arg-Gly-Asp-Ser (RGDS)- and Gly-Arg-Gly-Asp-Ser (GRGDS)-immobilized PMLG (RGDS-PMLG and GRGDS-PMLG). The peptides were immobilized by their N-terminal amine to activated PMLG surfaces. Prior to peptide immobilization, the aminolysis of PMLG surfaces was performed with hydrazine hydrate (HA), ethylenediamine (EDA), and hexamethylenediamine (HMDA) and was followed by the activation with hexamethylene diisocyanate. Surface characterization of these films was carried out by means of a Fourier transform IR (FT-IR) spectrometer equipped with an attenuated total reflectance (ATR) attachment. The amount of immobilized RGDS could be controlled by the reaction time of the aminolysis. The effects of HA, EDA, and HMDA as a spacer on the cell attachment were also investigated, and it was suggested that a longer spacer promoted the cell attachment via specific receptor-ligand interaction.

Amino Acid Sequence↗

In vivo 19F NMR comparative study of 5-fluorouracil, 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) and an FT-uracil coadministration system in mouse tumors.

The suppression of alpha-fluoro-beta-alanine (FBAL) formation from 5-fluorouracil (FU) is an important subject in relation to tumor chemotherapy. This is the first comparative study of FU, 1-(2-tetrahydrofuryl)-5-fluorouracil (FT, a prodrug of FU) and of FT+uracil as a coadministration system (UFT) under an oral dose using the in vivo 19F NMR method. The slow release of FU from FT and the suppression of the catabolism of FU to FBAL in mouse livers and tumors by the coadministration of uracil with FT were demonstrated using consecutive NMR measurements. The applicability of the in vivo 19F NMR method to the drug evaluation in tumors and livers of small animals was successfully tested.

Animals↗

Suppressive effects of polygonati rhizoma on hepatic glucose output, GLUT2 mRNA expression and its protein content in rat liver.

The intraperitoneal administration of the methanol extract of Polygonati Rhizoma (OM) into normal rats caused a significant decrease in the blood glucose level at 4 h after its administration of 800 mg/kg (P < 0.01), but not the serum insulin level. Using the perfused rat liver in vitro, a significant decrease of the hepatic glucose output was observed by the infusion of OM (P < 0.05 at 250 micrograms/ml OM). In addition, the hepatic content of facilitative glucose transporter isoform 2 (GLUT2) mRNA and its protein content in the total membrane fraction from rat liver significantly decreased in the intraperitoneally OM-treated rats when compared to that in the controls (mRNA P < 0.01, protein P < 0.001). On the other hand, OM (500 micrograms/ml) exhibited no apparent stimulatory effect on the insulin secretion from the isolated rat pancreatic islets. These results suggest that the hypoglycemic effect of OM is derived, at least in part, from the decrease in hepatic glucose output, due presumably to the reduction of GLUT2 mRNA expression and its protein content in total membrane of the liver, and that because of its unique therapeutic mechanism, OM could be a new category of therapeutic agent for non-insulin-dependent diabetes mellitus.

Animals↗

Hind III site causing Proinsulin Kyoto and Pst I site polymorphism of the insulin gene in Japanese: its lack of association with either IDDM or NIDDM.

The gene encoding Proinsulin Kyoto has been isolated and characterized by DNA sequencing, indicating that the molecular basis of the disorder is a G-T point mutation in the insulin gene which creates a Hind III site. In addition, in the 3'-untranslated region of the mutant insulin gene, a Pst I site negative, alpha type allele was found, and in the normal gene, a Pst I site positive, beta type allele was found. In order to clarify the frequency of the mutation and to determine whether this mutation is associated with diabetes mellitus or not, we have investigated Hind III polymorphism in 91 normal Japanese subjects and patients with IDDM and NIDDM. No cases with the Proinsulin Kyoto gene were found among the subjects examined. Secondly, to determine whether this alpha type allele is associated with DM in Japanese, we investigated Pst I polymorphism in the same subjects. The frequencies of the alpha type and beta type alleles were 92% and 8%, respectively. No significant difference in genotypic frequency was found among normal, NIDDM, and IDDM. We conclude that the Proinsulin Kyoto gene is not a common cause of DM and the occurrence of the alpha type insulin gene in Japanese diabetes is more frequent than in other races, so this Pst I polymorphism is not a marker for diabetes mellitus in Japanese.

Base Sequence↗

CT of intraabdominal desmoid tumors: is the tumor different in patients with Gardner's disease?

OBJECTIVE: A retrospective study of abdominal CT scans of patients with proved intraabdominal desmoid tumors was done to determine if any objective characteristics exist to differentiate desmoids related to Gardner's syndrome from isolated desmoids. Because the desmoid tumors of Gardner's syndrome can predate the diagnosis of Gardner's syndrome, it would be helpful to know which patients with desmoids need careful follow-up studies as well as initial workup for Gardner's syndrome and all its ramifications. Also, it would be important to differentiate benign from malignant desmoids associated with Gardner's syndrome. It was hoped that the location, enhancement characteristics, and/or the presence or absence of infiltration might be of value. We were interested in noting if, over time, the growth characteristics of desmoids found in Gardner's syndrome were different from those of isolated desmoids. MATERIALS AND METHODS: We reviewed 101 abdominal CT scans obtained in 23 patients during a 13-year period. Forty desmoid tumors were intraabdominal, including 30 lesions associated with Gardner's syndrome in 13 patients and 10 desmoids of the idiopathic form in 10 patients. These tumors were studied to define location; whether they were single or multiple; and whether they had any specific CT characteristics regarding margins, attenuation numbers, or contrast enhancement. RESULTS: Desmoid tumors associated with Gardner's syndrome were more likely to be multiple (38%, five of 13 patients) and to involve the mesentery (60%, 18 of 30 tumors) and the abdominal wall (40%, 12 of 30 tumors), whereas isolated desmoid tumors were singular (all 10 patients) and were located in the retroperitoneum (six cases), pelvis (three), and anterior wall (one). Desmoids related to Gardner's syndrome also tended to be smaller (mean diameter, 4.8 cm) than idiopathic desmoids (mean diameter, 13.8 cm). No differentiating CT characteristics regarding margins, attenuation numbers, or response to contrast material were ascertained. Ten new lesions (seven intraabdominal, three mesenteric) developed in three patients with Gardner's syndrome, whereas no new intraabdominal lesions developed in patients with idiopathic desmoids. Follow-up data on 16 surgically resected desmoids in nine patients (seven with Gardner's syndrome and two with isolated desmoids) revealed seven local recurrences (two in the two patients with isolated desmoids and five in two patients with Gardner's syndrome). CONCLUSION: No CT characteristics, such as attenuation values, margins, and response to the contrast material, were found that would enable differentiation between isolated intraabdominal desmoids and those associated with Gardner's disease. Desmoid tumors associated with Gardner's syndrome tend to occur in the mesentery and abdominal wall, whereas isolated desmoids involve the retroperitoneum and pelvis. When studying CT scans obtained over time, new lesions were noted to develop in a few of the patients with Gardner's syndrome (three of 13), whereas no new lesions were found in patients with isolated desmoids.

Adult↗

Diagnosis of inflammatory pseudotumor of the liver: value of CT.

OBJECTIVE: Inflammatory pseudotumor of the liver is a localized mass consisting of a fibrous stroma and chronic inflammatory infiltrate without anaplasia. Diagnosis of this rare disease is important to avoid surgery. The purpose of this study was to determine if CT is useful in the diagnosis of this lesion. SUBJECTS AND METHODS: CT scans of nine patients with a proved diagnosis of inflammatory pseudotumor of the liver were reviewed. Diagnosis was made by the surgical resection in three patients and by percutaneous biopsy in six patients. Six patients had symptoms and laboratory data suggesting active inflammation caused by the pseudotumor. The remaining three patients were asymptomatic. CT scans were performed with IV administration of the contrast material; scans were obtained in the portal venous and delayed phases in six patients and in the delayed phase in three patients. CT scans were analyzed for the number and size of the hepatic masses, and the degree and pattern of contrast enhancement on portal venous phase and delayed-phase images. RESULTS: Eight patients had a solitary hepatic mass, and one patient had two masses on the CT scan. The average size of the masses in the symptomatic patients (8.3 cm) was larger than that in the asymptomatic group (3.6 cm). CT scans in the portal venous phase showed a variable degree of contrast enhancement (seven masses). At least a part of seven masses, six of which were in symptomatic patients, showed greater contrast enhancement on delayed-phase CT scans than on the normal liver parenchyma. No constant pattern of enhancement was observed on delayed-phase CT scans in asymptomatic patients. CONCLUSION: Inflammatory pseudotumor of the liver should be included in a differential diagnosis in patients with a hepatic mass on a CT scan, especially when patients are symptomatic and the mass is fairly large and solitary showing contrast enhancement greater than that of liver parenchyma on delayed-phase CT scans. Percutaneous biopsy should be performed to obtain a histologic confirmation.

Adolescent↗

Immunotoxins composed of monoclonal antibody to alpha-fetoprotein and gelonin as a potent hepatoma-targeted drug delivery system.

This study was carried out to evaluate our monoclonal antibody (MoAb) to alpha-fetoprotein (AFP), 80G, as a carrier for targeting AFP-producing hepatoma. Pharmacokinetic analysis showed that the MoAb 80G was actively incorporated into AFP-producing HuH-7N cells (xenograft of human hepatoma cell line, HuH-7) in nude mice. Four conjugates composed of MoAb 80G, and a type 1 ribosome-inactivating protein, gelonin, were prepared. They involve two disulfide-linked and two thioether-linked conjugates. The binding activity of conjugates against AFP remained as high as that of intact 80G according to enzyme-linked immunosorbent assay. The in vitro cytotoxic effects of all the conjugates were specific against AFP-producing HuH-7 cells. Of these conjugates, two containing gelonin modified with 2-iminothiolane were more potent than the others. They showed significant antitumor activity upon AFP-producing HuH-7N cells in nude mice. However, the disulfide conjugate was more toxic to mice than the thioether conjugate judging from the loss in body weight and the liver damage. These results suggest that our MoAb 80G is a suitable carrier for targeting AFP-producing hepatoma cells, and that the noncleavable thioether conjugate is promising as an AFP-producing hepatoma-targeted drug delivery system.

Animals↗

[Diagnostic value of glass microfibre-based basophil histamine release test in food allergic children. Comparison with specific IgE antibody and skin scratch test].

We evaluated the diagnostic value of the glass microfibre-based histamine release test (HRT), which allows measurements to be performed using small amounts of whole blood, in 50 children with food allergy case histories. The patients were evaluated by radioallergosorbent tests (RAST), skin scratch tests (ST) and food challenge tests. Of the 50 patients, 39 had a confirmed clinical diagnosis of food allergy from food challenge tests and case histories, and were affected by a total of 60 positive allergens (egg 37, milk 11, soy beans 4, wheat 5, rice 3). The concordance, sensitivity, and specificity of HRT with the clinical diagnosis were 85.3%, 66.7% and 92.1%, those of RAST were 59.4%, 90.0% and 48.2%, and those of ST were 84.7%, 71.8% and 88.7%, respectively. The positive predictive values of HRT, RAST and ST were 75.5%, 38.8% and 66.7%. The false positive ratio of HRT (24.5%) was the lowest among all the tests. There was a significant correlation between HRT and RAST (r = 0.513, p < 0.001). However, the concordance of HRT with respect to RAST was 56.0%. The concordance and specificity of HRT in relation to the clinical diagnosis were higher than RAST and the same as ST. The sensitivity of RAST was higher than that of HRT. From these results, we concluded that RAST is good for the screening of allergens and that HRT is a useful diagnostic method for the confirmation of a clinical allergy.

Basophils↗