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Biomedical subjects

T Fujisawa

Publications and source records attributed to T Fujisawa.

At least 217 records · Page 12Linked to original sources

[Theophylline reduces serum levels of ECP in vitro].

Measurement of serum levels of ECP has been widely used for monitoring airway inflammation in bronchial asthma and recently been applied to measure anti-inflammatory effect of theophylline. However, reduced levels of ECP in theophylline-administered patients may express not only in vivo effect of theophylline but also in vitro effect after sampling because serum ECP measures released ECP during coagulation and theophylline has been reported to inhibit eosinophil degranulation in vitro. In order to answer the question, we tested whether theophylline added to blood after sampling reduces measured levels of serum ECP. Various concentrations of theophylline were added to SST tube, to which venous blood from atopic patients was drawn. Serum was, then, obtained by centrifugation after 15 min to 6 hours of incubation at room temperature. Theophylline significantly reduced serum ECP in a concentration-dependent manner. Percent reduction of ECP levels at 1 hour of incubation were 11.9%, 18.7%, 22.8%, and 51.7% at theophylline levels of 5, 12.5, 22.5, and 120 micrograms/ml, respectively. Kinetics of serum ECP release was also inhibited in the presence of theophylline. These results suggest that in vitro effect of theophylline on serum ECP levels should be considered when data of serum ECP in patients who take theophylline are interpreted.

Adult↗

The long-term effect of occlusal therapy on self-administered treatment outcomes of TMD.

Because of a lack of substantial scientific data, the efficacy of occlusal therapy for the management of temporomandibular disorders (TMD) is still controversial. Of a total of 1405 consecutive TMD patients examined over the last 10 years, 369 (26.3%) were determined to have completed treatment at least 1 year before the present survey. A sample questionnaire was mailed to each patient in this sample population. The questionnaire failed to reach 46 patients; of the 323 patients who received the questionnaire, 260 (80.5%) responded. The mean duration of time between their last visit and this survey was 3.7 years. The questionnaire elicited information on treatment outcomes, present treatment needs, and current signs and symptoms. Participants were divided into two treatment groups: (a) those who underwent some occlusal therapies (Phase II) following successful reversible therapies (Phase I) (20 men and 114 women); and (b) those who underwent reversible therapy only (33 men and 93 women). Participants were further differentially diagnosed into five diagnostic subgroups of TMD, based on the clinical examination at the initial visit, tomography, and, for some patients, magnetic resonance imaging. The subgroups included myalgia, arthralgia, anterior disc displacement with an without reduction, and osteoarthritis/osteoarthrosis. Only 12.3% of the total population surveyed reported lack of improvement to an acceptable level and further need for treatment. The remaining patients reported satisfactory results in the reduction of TMD symptomatology and no further need for treatment, because their symptoms had either disappeared or improved to an acceptable level. Regardless of treatment groups and diagnostic subgroups, the current subjective signs and symptoms were negligible in most patients, and mean mouth openings were in the normal range. No particular diagnostic subgroups seemed to have significantly better outcome following Phase II occlusal therapy. These results suggest that the majority of TMD signs and symptoms improve to an acceptable level with only reversible therapy, and the long-term value of additional occlusal therapy following reversible therapy is minimal. Therefore, permanent occlusion-changing therapies apparently are not generally needed to maintain TMD symptom reduction over time.

Activities of Daily Living↗

Tyrosinemia type I-like disease: a possible manifestation of 3-oxo-delta 4-steroid 5 beta-reductase deficiency.

BACKGROUND: It has been suggested that quantitative analysis of urinary bile acids may help to distinguish primary 3-oxo-delta 4-steroid 5 beta-reductase deficiency from the excretion of 3-oxo-delta 4 bile acids that occurs as a result of liver damage. METHODS: Urinary bile acids were quantitatively analyzed by gas chromatography-mass spectrometry in four Japanese patients with severe neonatal cholestasis associated with hypertyrosinemia without urinary succinylacetone (i.e. tyrosinemia type I-like disease). These four patients represented sporadic cases. RESULTS: Large amounts of 3-oxo-delta 4 bile acids were detected, which comprised greater than 80% of the total urinary bile acids. Small amounts of allo-bile acids and primary bile acids were also detected, comprising less than 1% and 15% of the total urinary bile acids, respectively. CONCLUSIONS: It was suspected that these four patients had a primary 3-oxo-delta 4-steroid 5 beta-reductase deficiency. However, it is possible that some patients in this study may have had a secondary 3-oxo-delta 4-steroid 5 beta-reductase deficiency, caused by idiopathic neonatal cholestatic liver failure.

Amino Acid Metabolism, Inborn Errors↗

Small-angle X-ray scattering study on CEL-III, a hemolytic lectin from Holothuroidea Cucumaria echinata, and its oligomer induced by the binding of specific carbohydrate.

Hemolytic lectin CEL-III from a marine invertebrate Cucumaria echinata forms an oligomer upon binding of specific carbohydrate such as lactose at high pH values and in the presence of high concentrations of salt. In this study, using small-angle X-ray scattering, we characterized CEL-III and its oligomer induced by the binding of lactose. The molecular mass of the oligomer was determined as 1019 kDa from its forward scattering value, compared with 47,490 Da for the monomer. This oligomer size is much larger than that estimated using SDS-polyacrylamide gel electrophoresis (SDS-PAGE, 270 kDa). The monomer has a 24.6 A radius of gyration and can be approximated by a rod which has a 20 A radius and a height of 75 A, while the oligomer has a 101.4 A radius of gyration. Together with the comparison of the radii of gyration and the forward scattering of the cross-section of the monomer and oligomer, it is suggested that in aqueous solution the oligomer comprises three or four molecules of a smaller unit which was observed by SDS-PAGE (270 kDa), held by a relatively weak interaction. The scattering profile also suggests that the oligomer has a hole in its central axis which might be associated with the formation of ion-permeable pores in the erythrocyte membrane by CEL-III during the hemolytic process.

Animals↗

Coexistence of a graft with the preserved native liver in auxiliary partial orthotopic liver transplantation from a living donor for ornithine transcarbamylase deficiency.

BACKGROUND: Auxiliary partial orthotopic liver transplantation (APOLT) has recently been performed in patients with noncirrhotic metabolic liver diseases. However, long-term outcomes for the preserved native liver and the transplanted liver graft have not been clearly established yet. METHODS: The recipient was a 36-month-old girl with ornithine transcarbamylase deficiency. She underwent APOLT, using her father's left lateral segment. RESULTS: Liver function was normalized soon after APOLT and the patient was able to ingest a normal diet without medication. Coexistence of the well-functioning native liver and graft was demonstrated in a computed tomography scan, Doppler ultrasonography, scintigraphy, and histological examination, during a relatively long-term follow-up period. CONCLUSIONS: APOLT seems to be most useful for the treatment of noncirrhotic metabolic liver diseases.

Biopsy↗

Insulin gene region contributes to genetic susceptibility to, but may not to low incidence of, insulin-dependent diabetes mellitus in Japanese.

In the Caucasian population, it has been demonstrated that the insulin gene (INS) region contains the insulin-dependent diabetes mellitus locus (IDDM2). In the Japanese population, however, there has been no report demonstrating the contribution of IDDM2 to the pathogenesis of IDDM. We conducted an association study of IDDM in a large number of Japanese subjects with multiple polymorphisms in INS region. We found a significant association of the INS region with IDDM. Alleles positively associated with IDDM in INS region were the same as those positively-associated with IDDM in Caucasian population, although positively-associated alleles are very common (allele frequencies > 0.9) in the Japanese general population. These data suggest that IDDM2 is involved in the genetic susceptibility to IDDM in Japanese. The high frequencies of disease-associated alleles in the general population suggest that IDDM2 locus is not responsible for the low incidence of IDDM in Japanese.

DNA, Satellite↗

Systematic isolation of peptide signal molecules regulating development in hydra: LWamide and PW families.

To isolate new peptide signal molecules involved in regulating developmental processes in hydra, a novel screening project was developed. Peptides extracted from the tissue of Hydra magnipapillata were systematically purified to homogeneity using HPLC. A fraction of each purified peptide was examined by differential display-PCR for its ability to affect gene expression in hydra. Another fraction was used to determine the tentative structure using an amino acid sequence analyzer and/or a mass spectrometer. Based on the results, peptides of potential interest were selected for chemical synthesis, followed by confirmation of the identity of the synthetic with the native peptides using HPLC. Using this approach, 286 peptides have been isolated, tentative amino acid sequences have been determined for 95 of them, and 19 synthetic peptides identical to native ones were produced. The 19 synthetic peptides were active in a variety of biological tests. For example, Hym-54 stimulated muscle contraction in adult polyps of hydra and sea anemone, Anthopleura fuscoviridis, and induced metamorphosis of planula, the larval stage, into polyps in a marine hydrozoan species, Hydractinia serrata. Another peptide, Hym-33H, inhibited nerve cell differentiation in hydra and induced tissue contraction in planula of Hydractinia serrata. The evidence obtained so far suggests that hydra contains a large number (>350) of peptide signal molecules involved in regulating developmental or other processes in cnidaria. These peptides can be isolated and their functions examined systematically with the new approach developed in this study.

Amino Acid Sequence↗

Autologous tumor killing activity as a prognostic factor in primary resected nonsmall cell carcinoma of the lung.

BACKGROUND: Cytotoxic activity of peripheral blood lymphocytes obtained during surgery against autologous fresh tumor cells has been reported. However, the role of lymphocyte autologous tumor killing or natural killer activity during the postoperative period remains obscure. In this article, the authors describe the importance of postoperative autologous tumor killing activity as a prognostic factor in patients with primary resected nonsmall cell lung carcinoma (NSCLC) after long term follow-up. METHODS: Forty-two patients who had resection of NSCLC, with primary culture of autologous tumor cells taken successfully, were studied. Cytotoxic activity against autologous, allogenic NSCLC and K562 leukemia cells was examined using peripheral blood lymphocytes obtained during the 2 weeks immediately following surgery. Factors related to prognosis were analyzed by univariate and multivariate analyses. RESULTS: The overall 5- and 10-year survival rates for the NSCLC patients were 40.5% and 27.5%, respectively. Statistical analysis of survival curves revealed a significant difference with regard to T classification (P = 0.025), N classification (P = 0.0015), stage (P = 0.028), and postoperative autologous tumor killing activity (P = 0.0008); there were no significant differences in relation to age, gender, histology, differentiation, visceral pleural invasion, resectability, surgical method, allogeneic tumor killing activity, or natural killer activity. Multivariate analysis demonstrated a significant correlation between disease recurrence and N classification (P = 0.0003), T classification (P = 0.023), stage (P = 0.001), and autologous tumor killing activity (P = 0.007), indicating independent prognostic significance. The phenotypes of the effector cells involved in autologous tumor killing activity were CD3(+), CD4(-), CD8(+), and CD11b(-). Autologous tumor killing activity was inhibited by competing unlabeled autologous tumor cells. CONCLUSIONS: Autologous tumor killing activity during the 2 weeks immediately following surgery is an important prognostic factor in resected NSCLC.

Adult↗

Pathology of chronic hepatitis C in children. Child Liver Study Group of Japan.

Limited information is available regarding the histology of hepatitis C virus infection in children. The aim of this study was to determine the histological pattern of chronic hepatitis C (CHC) in children, and liver biopsy specimens from 109 pediatric patients with CHC were examined. Each biopsy specimen was evaluated based on a numerical scoring system for the stage of fibrosis (1-4), the grade of portal/periportal necroinflammation (0-4), the grade of lobular necroinflammation (0-4), and their sum (final grade). The histological lesions considered to be characteristic of chronic hepatitis were also evaluated. None of the children had liver cirrhosis, and 105 cases (97%) were stage 1 or 2. Only 4 children were stage 3. Two of these 4 cases showed hemosiderosis. A significant correlation was observed between the staging score and the final grade in the pediatric patients (r = .59; P < .0001). The histological characteristics of adult CHC, such as lymphoid aggregate, bile duct injury, and fatty changes, were also observed in the children. In conclusion, the majority of children with CHC presented with mild fibrosis, but a few showed CHC with lobular distortion and hemosiderosis. Frequent blood transfusion may aggravate hepatic lesions in pediatric CHC.

Adolescent↗

Atypical MRI features of Wilson's disease: high signal in globus pallidus on T1-weighted images.

Most reports of MRI in Wilson's disease have been of abnormal low-signal lesions on T1-weighted images and high signal intensity on T2-weighted images. In contrast, we report three patients who had high-signal lesions in the globus pallidus on T1-weighted images, a finding seen in patients with portal-systemic encephalopathy. The possible causes include the paramagnetic effect of copper or iron and accumulation of Alzheimer type II glial cells.

Adult↗

Establishment of internal-image anti-idiotype monoclonal antibodies to a human antibody to lung cancer.

Internal-image anti-idiotype antibodies are expected to enhance anticancer effector mechanisms in vivo. The objective of this study was to establish hybridomas producing anti-idiotype monoclonal antibodies against a human monoclonal antibody (hmAb) 4G12 that reacts strongly with lung squamous cell carcinomas. BALB/c female mice 6 weeks old were immunized with 4G12. Splenocytes were hybridized with P3U1 cells and hybrid cells secreting anti-4G12 hmAb were cloned. Two clones reacted with 4G12 hmAb but not with 3H12 IgM hmAb, human IgM, human serum or fetal calf serum. These two Ab2 antibodies (IgG1 kappa) 2B12 and 2H1 demonstrated 91.5% and 90.3% inhibition in their reactivity with radiolabelled 4G12 on PC10 cells, indicating that 2B12 and 2H1 antibodies were of the Ab2 beta type. In criss-cross inhibition assays, the binding of 2B12 or 2H1 to 4G12 was not inhibited by 2H1 or 2B12. Thus 2B12 and 2H1 were thought to recognize the different epitopes on the antigen-binding sites. Antisera against 2B12 and 2H1 demonstrated specific reactivity to PC10 cells. The two Ab2 beta antibodies, 2B12 and 2H1, express internal images of lung squamous cell carcinoma recognized by the 4G12 antibody and may be useful for cancer immunotherapy.

Animals↗

Spontaneous remission of chronic hepatitis C in children.

UNLABELLED: The clinical course of 48 children with chronic hepatitis C (33 boys, 15 girls; mean age: 12.2 years) was monitored for more than 3 years to clarify its natural course. All patients were positive for the second-generation antibody to hepatitis C virus (anti-HCV) and for serum hepatitis C virus (HCV) RNA. All but one patient had a history of blood transfusion. Serum levels of alanine aminotransferase (ALT) had been abnormal for more than 1.5 years. Spontaneous remission defined as a biochemical remission lasting more than 1 year in association with the disappearance of serum HCV RNA, occurred in 4 (8.3%), however, in 25%, HCV RNA was still detectable in the liver even after its disappearance from serum. In this patient, the level of antibody to HCV core antigen (anti-HCV core) did not decrease significantly and serum HCV RNA eventually reappeared. The serum titre of HCV RNA in the 4 children with spontaneous remission was lower than in the remaining 44 children. Spontaneous remission may occur in children with chronic hepatitis C in whom the serum titre of HCV RNA is low and serum level of anti-HCV core decreases significantly. Assessment of the intrahepatic HCV RNA is necessary to confirm complete remission. CONCLUSION: A low serum titre of HCV RNA and a significant decrease in the serum titre of anti-HCV core were associated with spontaneous remission in children with chronic hepatitis C. Intrahepatic HCV RNA assessment is necessary to confirm complete remission.

Adolescent↗

Trp64Arg mutation of beta3-adrenergic receptor in essential hypertension: insulin resistance and the adrenergic system.

A putative pathogenic mutation in the beta3-adrenergic receptor gene (Trp64Arg) has been reported to be associated with higher diastolic blood pressure as well as clinical features of the insulin resistance syndrome and an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM) in Pima Indians and Finns. Because essential hypertension is reported to be associated with insulin resistance, we studied the mutation in Japanese patients with essential hypertension to clarify associations of this mutation with hypertension, insulin resistance, and basal adrenergic state in hypertensive subjects. The allele frequency of the mutation (Arg) in patients with essential hypertension was similar to that in control subjects (35 of 202 alleles [17.3%] v 27 of 146 [18.5%], respectively, P > .7). Insulin sensitivity measured by hyperinsulinemic euglycemic glucose clamp and plasma norepinephrine and epinephrine levels were also similar in hypertensive subjects with and without the mutation. These data suggest that Trp64Arg mutation in the beta3-adrenergic receptor gene does not play a major role in susceptibility to essential hypertension or in insulin resistance and basal adrenergic state in hypertension.

Adult↗

Donor-specific cytotoxic lymphocyte activity from bronchoalveolar lavage during acute canine lung allograft rejection.

OBJECTIVE: We investigated the relationship between acute lung rejection and donor-specific cytotoxic activity (DSCA) in recipient's lymphocytes obtained from bronchoalveolar lavage (BAL). METHODS: A total of 26 mongrel dogs underwent left lung allotransplantation. Dogs received either no immunosuppressive treatment (group I), cyclosporine (group II), or cyclosporine and methylprednisolone for evidence of acute rejection (group III). DSCA was measured by a 51Cr release assay, using lymphocytes from BAL samples as effector cells and 51Cr-labeled donor skin fibroblasts as target cells. The pathologic findings of the transplanted lungs were classified according to the working formulation for classification and grading of pulmonary rejection. In addition, the degree of cellular infiltration in the perivascular, peribronchial, interstitial, and intraalveolar areas was determined based on an infiltration score. RESULTS: DSCA in BAL samples was elevated during mild, moderate and severe acute rejection. The accuracy of the diagnosis of mild or moderate rejection was 92.3% at effector:target (E:T) ratios of 100:1 and 50:1. The DSCA in the BAL fluid and the total infiltration score were correlated closely with correlation coefficients of 0.859 and 0.828 at E:T ratios of 100:1 in group I and group II dogs, respectively. Lung aeration improved and DSCA decreased with methylprednisolone therapy in three of four dogs with grade 2 rejection. CONCLUSION: There is a direct relationship between the DSCA in BAL fluid and the degree of tissue damage caused by acute rejection. The DSCA can be detected by a 51Cr release assay which may hold promise for future clinical applications.

Animals↗

Influence of various bile salts on beta-glucuronidase activity of intestinal bacteria.

While the decrease of the beta-glucuronidase activity of sonicated cells of Clostridium perfringens and Escherichia coli was obvious for sodium deoxycholate (DC), it was not so obvious for other bile salts (sodium glycocholate and sodium cholate). The enzyme activity of intact cells of these bacteria was significantly enhanced by the presence of DC, but not by the other bile salts in the buffer. These results suggest that the permeability of the bacterial cells is increased more by the presence of DC than by other bile salts.

Adult↗

Tissue-specific and glucose-dependent expression of receptor genes for glucagon and glucagon-like peptide-1 (GLP-1).

Both glucagon and glucagon-like peptide-1 (GLP-1) play an important role in the regulation of nutrient homeostasis. In this study, the tissue distributions of the expression of receptor genes for glucagon and GLP-1 were examined. Expression of glucagon receptor gene was detected in liver, kidney, ileum and pancreatic islets but not in brain. In contrast, expression of GLP-1 receptor gene was detected in brain, pancreas and pancreatic islets but not in liver, kidney, or ileum. To investigate the existence and characteristics of glucagon and GLP-1 receptors on pancreatic beta cells, expression of the receptor genes and translational regulation of the expression of the receptor genes by glucose were analyzed in a mouse pancreatic beta cell line, MIN6 cells. In the cDNA pool of MIN6 cells, both glucagon and GLP-1 receptor genes were identified and showed higher expression level in MIN6 cells cultured under high glucose condition than in those cultured under low glucose condition. These results suggest that glucagon and GLP-1 receptor genes are expressed in pancreatic beta cells and their expression is upregulated by glucose.

Animals↗

Insulin-dependent diabetes mellitus associated with autoimmune thyroiditis and rheumatoid arthritis.

A case associated with insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis (RA), and autoimmune thyroid disease (AITD) was reported. A high titer of anti-glutamic acid decarboxylase antibody (GAD) and a positive islet cell antigen were observed. The patient's human leukocyte antibody (HLA) haplotype was a homozygote of DQA1*0301, DQB1*0401, and DRB1*0405. Because this haplotype was in linkage disequilibrium with DPB1*0501, an allele associated with AITD in Japanese patients, the patient was homozygous for alleles susceptible to IDDM, RA, and AITD. A specific HLA haplotype susceptible to several autoimmune disease may result in the development of IDDM, RA, and AITD.

Alleles↗

The tannin-degrading species Streptococcus gallolyticus and Streptococcus caprinus are subjective synonyms.

The tannin-degrading species Streptococcus gallolyticus and Streptococcus caprinus have been shown to be subjective synonyms on the basis of their levels of 16S rRNA sequence similarity (98.3%) and DNA-DNA homology (> 70%) and the phenotypes of their type strains. S. gallolyticus has nomenclatural priority according to Rule 24b(2) of the International Code of Nomenclature of Bacteria.

Animals↗