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Biomedical subjects

T Fujisawa

Publications and source records attributed to T Fujisawa.

At least 289 records · Page 16Linked to original sources
PubMed1994

Fetal bile acid metabolism during infancy: analysis of 1 beta-hydroxylated bile acids in urine, meconium and feces.

Fetal bile acids (1 beta-hydroxylated, 6 alpha-hydroxylated and unsaturated bile acids), especially 1 beta, 3 alpha,7 alpha, 12 alpha-tetrahydroxy-5 beta-cholan-24-oic acid (CA-1 beta-ol), have been detected in urine and feces early in life. To investigate whether a fetal pathway of bile acid synthesis exists in infancy, we measured the concentrations of bile acids in the urine, meconium and feces from normal newborns and infants by means of gas chromatography-mass spectrometry. The mean ratio of total bile acids to creatinine in urine increased between birth and 7 days and then gradually decreased; however, the concentration of total bile acids in urine remained significantly higher than that in adult urine until 3 mo of age. The main urinary bile acid was CA-1 beta-ol, and substantial amounts of fetal bile acids were detected in urine until 3 mo of age. The ratio of cholic acid to chenodeoxycholic acid was abnormally low in meconium (mean, 0.44; range, 0.19 to 0.74), and hyocholic acid constituted 19.3% of total bile acids. The mean total bile acid content of feces decreased between birth and 7 days of age and thereafter increased. The mean percentage of fetal bile acids in feces decreased after birth, but substantial amounts were present in feces until 1 mo of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Absence of association of TAP and LMP genes with type 1 (insulin-dependent) diabetes mellitus.

Although one of the major genes which cause type 1 (insulin-dependent) diabetes mellitus is located in the class II HLA region in humans, its precise location is still unknown. In order to investigate whether TAP (Transporter associated with Antigen Processing) and LMP (Low Molecular Weight Polypeptide) genes, which are located in the class II HLA region, are HLA-linked diabetogenic genes, the association of TAP1, TAP2 and LMP2 genes with type 1 diabetes was analyzed in the Japanese population. No difference in allele frequencies of these genes was detected between diabetic patients and control subjects. On the other hand, DQA1 and DQB1 genes showed significant association with type 1 diabetes. These data suggest that the diabetogenic gene in the class II HLA region may be located near the DQA1 and DQB1 loci, rather than the TAP and LMP loci.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Assessment of eosinophil and neutrophil participation in atopic dermatitis: comparison with the IgE-mediated late-phase reaction.

We hypothesized that repeated IgE-mediated late-phase reactions are critical in the pathogenesis of atopic dermatitis (AD). Prior studies have shown that extracellular deposition of eosinophil granule major basic protein (MBP) occurs in lesional AD skin, despite a paucity of infiltrating eosinophils, and that deposition of both neutrophil and eosinophil granule proteins occurs in the IgE-mediated late-phase reaction. We evaluated the participation of both eosinophil and neutrophil granule proteins in AD. Cutaneous biopsy specimens and serum and urine samples were obtained from 22 patients with AD. Lesional tissue was examined by means of immunofluorescence for neutrophil elastase and lactoferrin and for eosinophil granule MBP, eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP). Serum levels of elastase, MBP, EDN, and ECP and urine levels of MBP, EDN, and ECP were measured. Marked extracellular deposition of at least one of the eosinophil granule proteins was present in the dermis of 15 of the 22 AD skin specimens, but minimal or no extracellular neutrophil elastase or lactoferrin deposition was observed in any specimens. Serum and urine levels of MBP, EDN, and ECP in the patients were elevated when compared with those of normal controls, whereas serum levels of neutrophil elastase were not elevated. Serum MPB levels correlated with extent of body surface involvement. These results suggest that eosinophil degranulation occurs in AD but that neutrophil degranulation does not. Although eosinophil degranulation is prominent in both the late-phase reaction and in AD, the lack of neutrophil degranulation in AD demonstrates differences in the inflammatory reactions.

Adolescent↗
PubMed1994

Early-onset type 2 (non-insulin-dependent) diabetes mellitus is associated with glucokinase locus, but not with adenosine deaminase locus, in the Japanese population.

To investigate the possible contribution of glucokinase (GCK) and adenosine deaminase (ADA) loci to the genetic susceptibility to type 2 (non-insulin-dependent) diabetes mellitus, we studied the association of these loci with type 2 diabetes in the Japanese population. Fifty patients with type 2 diabetes and 50 control subjects were analyzed for microsatellite polymorphism 3' to the GCK gene and PstI polymorphism in the ADA gene by polymerase chain reaction. The frequency of the most common GCK allele (Z) was significantly lower in type 2 diabetic patients than that in control subjects and a longer Z + 2 allele was more common in type 2 diabetic patients (26% vs. 15%, P = 0.053), particularly in those with younger age of onset (33% vs. 15%, younger onset type 2 diabetes vs. control, P = 0.014). The frequency of genotypes containing at least one Z + 2 allele was significantly more common in type 2 diabetic patients (46% vs. 28%, P < 0.05), particularly in those with younger age of onset (61% vs. 28%, relative risk 4.00, P < 0.01). In contrast, there was no difference in allelic or genotypic frequencies of PstI polymorphism in the ADA gene between the two groups. Despite the association between the GCK locus and type 2 diabetes, none of the patients had known mutations (Glu265-->AM265, Glu279-->AM279, Gly299-->Arg299, Glu300-->Gln300, Leu309-->Pro309). These results suggest that the GCK locus, but not the ADA locus, contributes to the genetic susceptibility to type 2 diabetes in Japanese.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Deaminase↗
PubMed1994

Histologic activity of the liver in children with transfusion-associated chronic hepatitis C.

Adults with chronic hepatitis C develop cirrhosis over a period of 6 to 20 years, but there are few reports of this disorder in children. To determine the histologic activity of chronic hepatitis C in children, we examined 31 biopsy specimens from 25 children (age range 3-16 years) with this disease. All patients were seropositive for antibody to hepatitis C virus by second-generation testing, and for HCV-RNA by the polymerase chain reaction. All cases were transfusion-associated. Patients were divided into two groups according to underlying disease: malignant disease or aplastic anemia (Group A, 17 cases) and non-malignant disease (Group B, eight cases). All patients in Group A, but only one in Group B, had received multiple transfusions. All patients in Group A had received intensive courses of cytotoxic and immunosuppressive agents. The histologic diagnosis was made using the standard criteria and Knodell's histology activity index. Chronic persistent hepatitis was more common in Group B (six patients) than in Group A (three patients). Chronic aggressive hepatitis 2B was found only in Group A (five patients). The mean histology activity index score was higher in Group A than in Group B (8.5 vs. 5.7). Six patients (four in Group A and two in group B) subsequently had a liver biopsy. The pathological diagnosis did not change after the second biopsy in any patient in Group B, while two patients in Group A showed a rapid progression of hepatitis. In each category of the histology activity index, periportal necrosis and intralobular necrosis were more severe in Group A than in Group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

The hydration of Ras p21 in solution during GTP hydrolysis based on solution X-ray scattering profile.

The small-angle X-ray scattering technique was used to characterize the structure in solution of wild type ras p21 as well as the oncogenic proteins mutated at residue 12, 59, or 61. In the presence of GDP, the radius of gyration, Rg, determined for wild type ras p21 was 16.89 +/- 0.01 A, while the wild type ras p21 bound to the GTP analogue GDPNHP (5'-guanyl imido diphosphate beta-gamma-imidoguanosine 5'-triphosphate) showed an Rg value of 17.46 +/- 0.01 A, which is 3.3% larger. The result shows that ras p21 expands upon GTP binding. The Rgs of mutated proteins were 17.04 +/- 0.01, 16.98 +/- 0.01, and 17.03 +/- 0.01 A for the Gly-12 to Val, Ala-59 to Thr, and Gln-61 to Leu mutants, respectively. The scattering profiles were analyzed by simulation of hydrated ras p21, based on the crystal atomic coordinates, and it was concluded that the ras p21 molecule incorporates 20% more bulk water upon GTP binding. The increase of bulk water is especially conspicuous around the interface between switch I (residues 32-40) and switch II (residues 60-66) regions. This suggests that hydration plays an important role in the interaction with GAP.

Computer Simulation↗
PubMed1994

The capacity of dog lung to release prostaglandin I2 as a biochemical parameter for evaluating lung damage during preservation.

The release of prostaglandin I2 (PGI2) from the vasculature is thought to reflect damage to the vessels. Basal and bradykinin (BK)-stimulated release of PGI2 from isolated dog lungs after 6-hr preservation were investigated to evaluate lung damage after preservation. Maximal PGI2 release induced by BK decreased significantly after preservation at 24 degrees C (room temperature), but not after hypothermic preservation at 4 degrees C, although basal PGI2 release without BK stimulation did not change in either group of lungs after preservation. The function of allotransplanted lungs assessed by arterial oxygen tension was impaired by preservation at room temperature but not by hypothermic preservation. No differences were observed by light microscopy in either group in the pulmonary tissues, including the pulmonary artery, after preservation. In summary, damage to the lung after preservation may be reflected by the maximal PGI2 release from the lung after BK infusion. Therefore the maximal PGI2 releasing capacity induced by BK may be a useful biochemical parameter for estimating the viability of preserved lungs.

Animals↗
PubMed1994

Solid cell nests of the thyroid in medullary thyroid carcinoma.

Solid cell nests of the thyroid gland were studied in 44 patients with medullary thyroid carcinoma. In 10 (22.7%) patients, solid cell nests were revealed in the vicinity of tumour foci (five cases) or in the contralateral thyroid lobe and isthmus (four cases); in one case the location was indeterminate. In all seven cases in which immunohistochemical studies were carried out, solid cell nests showed negative staining for thyroglobulin, calcitonin and chromogranin A, findings which were distinct from those in medullary thyroid carcinoma. It is therefore suggested that solid cell nests of the thyroid are not precursors of this tumour.

Adolescent↗
PubMed1994

Alagille syndrome with a spontaneous appearance of the interlobular bile ducts.

We report a rare case of a 10 year old girl diagnosed as having Alagille syndrome on the basis of a characteristic face, posterior embryotoxon, cholestasis, peripheral pulmonary artery stenosis and the absence of interlobular bile ducts in a liver biopsy at 1.5 years of age. Since 1.5 years old, she had been in good health without medication and the serum biochemical liver function tests indicated no progression of cholestasis. A second liver biopsy at 9.5 years of age showed normal interlobular bile ducts confirmed by anti-keratin staining at each of the five examined portal areas. Alagille syndrome is usually associated with the progressive disappearance of interlobular bile ducts. The findings of interlobular bile ducts in the second liver biopsy were therefore rare and unique to this case.

Alagille Syndrome↗
PubMed1994

Evaluation of media for determining hemolytic activity and that of API Listeria system for identifying strains of Listeria monocytogenes.

Several media were used to evaluate the hemolytic activity of Listeria monocytogenes, and this property was used along with the API Listeria system to identify Listeria spp. All L. monocytogenes strains were identified correctly with this system, and blood agar base no. 2 and Columbia blood agar base supplemented with horse blood were suitable for detection of hemolytic activity.

Agar↗
PubMed1994

Mechanism of eosinophil infiltration in the patient with subcutaneous angioblastic lymphoid hyperplasia with eosinophilia (Kimura's disease). Mechanism of eosinophil chemotaxis mediated by candida antigen and IL-5.

Kimura's disease is a chronic granulomatous disease of unknown etiology. Although eosinophilia is one of the characteristic features in this disease, little is known about the mechanism of eosinophilia. In the present study it was demonstrated that interleukin-5 (IL-5) was produced and released from the site of a granuloma and lymph nodes after stimulation with candida antigen. It was also shown that peripheral blood eosinophils from patients with Kimura's disease contained a large proportion of hypodense eosinophils and that their viability was prolonged. These results strongly suggest that locally produced IL-5 induced by candida antigen contributes to the eosinophilia in this disease.

Adult↗
PubMed1994

Interferon-gamma induces interleukin-3 release from peripheral blood eosinophils.

Interferon-gamma (IFN-gamma) upregulates eosinophil effector functions and prolongs the in vitro survival of eosinophils. We examined the possible capacity of IFN-gamma to stimulate eosinophils to produce eosinophil-activating cytokines. Eosinophils purified from mild atopic volunteers were cultured with 100 U/ml IFN-gamma. Viability of eosinophils was counted and supernatants were tested for the presence of cytokines by neutralization of eosinophil viability-enhancing activity with specific antibodies to IFN-gamma, interleukin-5 (IL-5), IL-3, or granulocyte-macrophage colony-stimulating factor (GM-CSF). IFN-gamma-enhanced eosinophil viability was up to 95% on the 4th day of culture. Pretreatment with anti-IL-3 antibody partially blocked the IFN-gamma-enhanced eosinophil survival. IFN-gamma-stimulated eosinophil supernatants had eosinophil survival. IFN-gamma-stimulated eosinophil supernatants had eosinophil viability-enhancing activity that was blocked by pretreatment not only with anti-IFN-gamma but also with anti-IL-3. Antibodies to IL-5 or GM-CSF did not have the blocking effect. To further confirm the production of IL-3 by eosinophils, we performed reverse transcription polymerase chain reaction (RT-PCR) for IL-3 messenger RNA (mRNA) in IFN-gamma-stimulated eosinophils. Significant IL-3 mRNA expression in eosinophils was observed at 6 h of incubation with IFN-gamma. These results suggest that IFN-gamma stimulates the autocrine function of eosinophils and may play an important role in allergic inflammation.

Cell Survival↗
PubMed1994

Increased expression of human 63-kD heat shock protein gene in Kawasaki disease determined by quantitative reverse transcription-polymerase chain reaction.

To investigate the possible role of heat shock protein (HSP) in the pathogenesis of Kawasaki disease (KD), we determined the expression of 63-kD HSP (P1 protein) gene in the leukocytes from the peripheral blood of 20 patients with KD, 20 patients with various other febrile diseases, and 10 healthy children using the quantitative reverse transcription-polymerase chain reaction technique. Although a low but constitutive expression of HSP was observed in the control patients and healthy children, the expression of HSP63 mRNA was significantly higher during the acute phase of KD. Because mycobacterial HSP65, a cognate of human HSP63, is a common immunogen in bacterial species, and because the major immunopathologic feature of KD is reportedly an abnormally activated immune system, it suggests that an increased level of HSP63 gene transcription may be associated with the pathogenesis of KD.

Base Sequence↗
PubMed1994

Purines. LXIII. Syntheses of azepinomycin, an antitumor antibiotic from Streptomyces species, and its 3-beta-D-ribofuranoside and their 8-imino analogues.

Three variants of a synthetic route to the antitumor antibiotic azepinomycin (3) from 1-substituted N'-alkoxy-5-formamidoimidazole-4-carboxamidine (type 10) are described. The synthesis started with the monocytes 10a-c and proceeded through the intermediates 11a-c, 12a-c, 13a-c, 14a-c, and 4a, b and 3-beta-D-ribofuranosylazepinomycin (4c). The benzyl version (series a), including the permutation 14a-->15-->3, was found to produce the antibiotic (3) most efficiently. The starting materials 10a-c were readily prepared from the 9-substituted adenines 7a-c via the N-oxides 8a-c and the 1-alkoxy derivatives 9a-c. The 8-amino analogues (17 and 18) of 3 and 4c were also synthesized from 12a and 12c, respectively.

Aminoglycosides↗
PubMed1994

[Inhibitory effect of TGF-beta 1 on cytokine-enhanced eosinophil survival].

TGF-beta 1 has many biological activities in various cell types and is regarded as a multifunctioning regulator of cell growth. We studied the effect of TGF-beta 1 on cytokine-enhanced eosinophil survival in vitro. Eosinophils were purified from patients with mild atopic dermatitis by Percoll density gradient centrifugation and the CD16 negative selection/immunomagnetic beads technique. Eosinophil purity was greater than 95%. The purified eosinophils were incubated in the presence of eosinophil-activating cytokines (IL-5, IL-3, GM-CSF, IFN-gamma) with and without TGF-beta 1 for 3 days. Eosinophil viability was determined by staining the cells with fluorescein diacetate and propidium iodide. Without cytokine, most eosinophils died by day 3 in culture, but human recombinant IL-5, IL-3, GM-CSF, and IFN-gamma enhanced eosinophil survival in a dose-dependent manner. To test the effect of TGF-beta 1 on enhanced eosinophil survival, eosinophils were cultured with activating cytokine and TGF-beta 1. TGF-beta 1 inhibited eosinophil survival in a dose-dependent manner. The inhibitory effects of TGF-beta 1 on IL-5 enhanced survival was partially reversed by high concentrations of IL-5 and was completely neutralized with anti-TGF-beta antibody. Moreover, the apoptosis of eosinophils induced by TGF-beta 1 was determined with the assay of DNA fragmentation on agarose gel electrophoresis. It is possible that TGF-beta 1 activates the pathway of apoptosis. The results suggest that TGF-beta 1 may play a crucial role in the regulation of allergic inflammation.

Apoptosis↗
PubMed1994

[Esophageal duplication with esophago-bronchial fistula].

In a case of 51-year-old woman with an esophago-bronchial fistula located in the right B2 bronchus, we found a tubular type of esophageal duplication communicating with the esophagobronchial fistula by examinations of esophagography and endoscopy. It was diagnosed as tubular type I double barreled type of esophageal duplication by Akaboshi's Classification. She successfully underwent resection of the accessory esophagus combined with the fistula and the adjacent pulmonary tissues. Squamous epithelium and smooth muscle tissue were observed in the resected esophageal specimen. Double barreled type of esophageal duplication is one of the rare malformation, and we have found 12 reported cases including our one case in the Japanese literatures. Moreover our case is the first one whose accessory esophagus were combined with an esophagobronchial fistula.

Bronchial Fistula↗