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Biomedical subjects

N Endo

Publications and source records attributed to N Endo.

At least 19 recordsLinked to original sources

Hypoaminotransferasemia in patients undergoing long-term hemodialysis: clinical and biochemical appraisal.

BACKGROUND & AIMS: It has been reported that patients with chronic renal failure have low serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as a result of vitamin B6 deficiency. Chronic hepatitis C is common among patients undergoing hemodialysis, and low aminotransferase levels cause diagnostic problems. The aim of this study was to determine the cause of hypoaminotransferasemia. METHODS: Serum levels of vitamin B6 and its coenzyme were reassessed in relation to AST and ALT levels in patients undergoing long-term hemodialysis using high-performance liquid chromatography. RESULTS: The mean (+/- SD) serum AST and ALT levels in 304 patients negative for hepatitis B surface antigen and anti-hepatitis C virus were 9.2 +/- 2.4 and 7.4 +/- 1.7 IU/L, respectively. In 556 normal adults, they were 22.7 +/- 5.4 and 18.0 +/- 4.0 IU/L, respectively (P < 0.001). Mean serum vitamin B6 and pyridoxal-5'-phosphate levels in patients undergoing dialysis were not reduced compared with the control, although occasionally patients had low levels. The AST and ALT assay reagents in Japan do not contain added pyridoxal-5'-phosphate; addition of pyridoxal-5'-phosphate (0.1 mmol/L) to the reagent significantly increased measurements to similar extents in both groups. CONCLUSIONS: Serum AST and ALT levels in patients undergoing dialysis are very low, but they are not a result of vitamin B6 deficiency. The upper normal limits of AST and ALT levels in patients undergoing dialysis should be reduced considerably, and these levels should be interpreted with caution in the diagnosis of liver disease.

Adult

Predictive value of screening tests for persistent hepatitis C virus infection evidenced by viraemia. Japanese experience.

In November 1989, Japanese Red Cross Blood Centres started screening for hepatitis C virus (HCV) with enzyme-linked immunosorbent assay (Elisa) for the C100-3 viral peptide as the first such nationwide programme in the world. Thereafter post-transfusion non-A non-B hepatitis (PTNANBH) was reduced by 61-80%, but this was not as complete a success as our programme to prevent post-transfusion hepatitis B by screening for high titer hepatitis B core antibody, which we began in the same period. In order to acquire more effective control of PTNANBH, the HCV core-related antigen (GOR, N14) and second-generation Elisa (Ortho2, Abbott2) and second-generation antigen agglutination (PA, PHA) tests have been employed. Among 16,500 donors in 11 blood centers, 365 were serologically positive by at least one of these tests. Among these, HCV RNA was detected in 138 units and the remaining 227 were HCV RNA negatives. The effectiveness of these serological tests to detect HCV RNA-positive status were analyzed. Passive haemagglutination and particle agglutination (PHA and PA) tests were highly effective to predict HCV viraemia among blood donors. Also, these tests can easily determine antibody titre. By either PHA or PA, all units with > or = 2(12) agglutination titre (120 and 122 units) were HCV RNA positive and all agglutination-positive units with serum alanine aminotransferase level higher than 35 Karmen units were HCV RNA positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase

Enhancement of antigen-induced interleukin 4 and IgE production by specific IgG1 in murine lymphocytes.

Conalbumin (CA)-specific type 2 helper T cell (Th2) clone, D10G4.1 (D10) produces IL4 when stimulated with varying doses of TNP-CA in the presence of mitomycin C-treated C3H spleen cells or purified B cells as antigen-presenting cells (APC). The production of IL4 was assessed by bioassay and by expression of IL4 mRNA. IL4 production reached maximum at 100 micrograms/ml of TNP-CA, whereas 1 microgram/ml of the antigen induced less than 10% of the maximum level of IL4. This lower level of IL4 production was augmented to the maximum level when monoclonal anti-TNP IgG1 was added to the culture at 0.5-1 microgram/ml. Anti-TNP IgE, but not anti-TNP IgM, was also effective, though IgE was 1/10 as effective as IgG1. IgG1 with an irrelevant specificity and F(ab')2 of anti-TNP IgG1 did not show augmenting effects. Moreover, the enhancement by anti-TNP IgG1 was completely abolished by monoclonal antibody against murine Fc gamma RII, 2.4G2. These results suggest that a low dose of the antigen complexed with IgG1 is focused on APC by means of Fc gamma RII, processed, and presented efficiently to the Th2 clone. On the other hand, the co-culture of D10 with normal C3H B cells in the presence of 1-100 micrograms/ml TNP-CA resulted in polyclonal IgE production. Anti-TNP IgG1 markedly augmented the lower level of IgE production induced by a suboptimal dose of the antigen (1 microgram/ml). This augmentation was shown to be dependent on endogenous IL4 because the enhancement was abolished by monoclonal anti-IL4 (11B11).

Animals

[Kinetics of the complement subcomponent C1q production of peritoneal macrophages in NZB/W F1 female mice].

To clarify the role of local production (exohepatic) of complement on primary host defense mechanisms against microbial infections in the host who decreased the amount of complement in serum, the kinetics of the complement production by the complement-producing cells in exohepatic tissue was examined by measuring the amount of C1q, subcomponent of the first complement component, in cultured supernatant of the monolayer of peritoneal macrophages (PM phi) collected from 5, 15, 35, and 48 weeks-old female mice of NZB/W F1 (B/W F1). The C1q production of PM phi in B/W F1 mice showed remarkable decrease at 15 weeks-old. After that, however, the C1q producibility of PM phi recovered gradually and, at mice 48 weeks old, the complement produced finally exceeded the amount observed in mice 5 weeks-old, contrariwise the C1q values in serum were significantly lowering in the same aged mice. The increased production of C1q of PM phi was observed in both 35 and 48 weeks-old mice, of which the value corresponded with increase of anti-nuclear antibody titer in serum and of the amount of protein in urine. On female mice of ddY (control), the amount of C1q production of PM phi in 5 weeks-old mice was two-fold higher than that of 5 weeks-old B/WF1 mice. But at 15 weeks, the production showed a 1/2 decrease in that of mice 5 weeks-old and the decreased values were kept to 35 weeks-old.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids.

We have identified a novel member of the steroid hormone receptor superfamily by cDNA cloning from a human osteosarcoma SAOS-2/B10 cell library. Sequence analysis predicts a protein of 441 amino acids, which includes the conserved amino acid residues characteristic of the DNA- and ligand-binding domains of nuclear receptors. Amino acid sequence alignment and transcriptional activation experiments revealed that the new protein is closely related to the mouse peroxisome proliferator activated receptor. The overall homology is 62%, and the highest similarity is seen in the DNA- and ligand-binding domains, 86% and 71%, respectively. Northern blot analysis showed that in mature rats, the receptor is highly expressed in heart, kidney, and lung as a transcript of approximately 3500 nucleotides. In human cells, the size of the mRNA is approximately 4000 nucleotides. Transcription assays using hybrid receptors consisting of the ligand-binding domain of the new protein and the DNA-binding domain of the glucocorticoid receptor showed weak stimulation by the peroxisome proliferator activator WY14643, suggesting a relationship to that receptor. Similar stimulation was observed with arachidonic and oleic acid (100-250 microM).

Amino Acid Sequence

Fluorometric assay of rat tissue N-methyltransferases with nicotinamide and four isomeric methylnicotinamides.

Nicotinamide (NA) and its four isomeric methyl analogs [2-, 4-, 5- and 6-methylnicotinamides (MNs)] were tested as substrates for nicotinamide N-methyltransferase (NNMT) and amine N-methyltransferase (ANMT) using rat liver, kidney, spleen and brain 9000 x g supernatant fluids as model enzyme preparations. The N-methylated products were determined fluorometrically by their reaction with acetophenone or 4-methoxybenzaldehyde to form fluorescent 2,7-naphthyridine derivatives, and the lower limits of the determination were 8-30 pmol/100 microliters. N-Methyltransferase activities were detected in the liver with NA, 4-MN and 5-MN, and in the brain and spleen with 4-MN. On this basis, 5-MN is considered to be a selective substrate for NNMT in addition to NA, which is a known methyl acceptor for this enzyme. Although 4-MN appears to serve as a methyl acceptor for both ANMT and NNMT, it seems to be essentially a selective substrate for brain ANMT because of the absence of NNMT in brain. The fluorometric methods used here are also very useful because of their simplicity, sensitivity and selectivity.

Animals

Effect of interferon (IFN) on refractory idiopathic thrombocytopenic purpura: administration of 6 million units of recombinant IFN alpha-2b.

Five patients (six courses) with refractory idiopathic thrombocytopenic purpura (ITP) were given 6 million units of recombinant interferon (IFN) alpha-2b in 12 doses to achieve an improved response rate compared to previous studies using 3 million units. From the initial IFN administration, the platelet count increased from a pre-treatment level of 20.7 +/- 17.7 x 10(3)/microliters (mean +/- SD) and reached its first peak in weeks 2 or 3 of therapy (p < 0.05). In week 5, the platelet count made its second and maximum peak (66.5 +/- 57.9 x 10(3)/microliters; p < 0.05). A relatively good response of the platelet count (an increase to > 50 x 10(3)/microliters) was observed in three patients (four courses) out of five. These responses were not much faster or more improved than in previous reports, and a dose of 6 million units may be too large to treat some ITP patients. The platelet-associated IgG level showed a tendency to be reduced with IFN therapy. The mechanism for the increase of the platelet count may be the modification of platelet autoantibody production.

Adult

[Study of anti-idiotype antibodies to human monoclonal antibody].

A human monoclonal antibody, ll-50 (IgM, lambda), was generated, which reacted specifically with a major of glycolipid present in LS174T colon cancer cells. The glycolipid antigen which reacted with the ll-50 antibody was expected to four sugar residues from its TLC mobility, and it was ascertained that the glycolipid antigen which reacted with ll-50 antibody might be Lc4 antigen [Gal beta 1----3 GLcNAc beta 1----3 Gal beta 1----4 Glc beta 1----1 Cer] judging from TLC immunostaining and ELISA when the reactivity of ll-50 antibody was tested using various pure glycolipids in 3-5 sugar residues as an antigen. Sera in patients with malignant disorders and healthy individuals were analyzed by Sandwich assay of immobilized and biotinylated ll-50 antibody. The serum of the Lc4 antigen recognized by ll-50 antibody was significantly higher in patients with malignant disorders than that in healthy individuals (p less than 0.05). Three mouse monoclonal anti-idiotype antibodies, G3, B3 and C5 (all IgG1), were generated by the immunization of BALB/c mice with ll-50 antibody. These anti-idiotype antibodies specifically bound to to human monoclonal antibody, ll-50 and had a significant inhibitory activity towards the binding of ll-50 antibody to the Lc4 antigen. This indicated that these anti-idiotype antibodies, G3, B3, and C5, were paratope-related anti-idiotype antibodies. G3, B3, and C5 were expected to define the nearest idiotope because they could mutually inhibit ll-50 antibody. Sera in patients with malignant disorders and healthy individuals were analyzed by Sandwich assay of immobilized and biotinylated anti-idiotype antibodies, G3, B3, and C5. As to the ll-50 like antibodies defined by C5 (Id-C5+), the mean serum level in patients with malignant disorders was significantly higher than that in healthy individuals (p less than 0.05). As to the ll-50 like antibodies defined by B3 (Id-B3+), the mean serum level in patients with malignant disorders was significantly higher than that in healthy individuals.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure.

Studies of the mode of action of the bisphosphonate alendronate showed that 1 d after the injection of 0.4 mg/kg [3H]alendronate to newborn rats, 72% of the osteoclastic surface, 2% of the bone forming, and 13% of all other surfaces were densely labeled. Silver grains were seen above the osteoclasts and no other cells. 6 d later the label was 600-1,000 microns away from the epiphyseal plate and buried inside the bone, indicating normal growth and matrix deposition on top of alendronate-containing bone. Osteoclasts from adult animals, infused with parathyroid hormone-related peptide (1-34) and treated with 0.4 mg/kg alendronate subcutaneously for 2 d, all lacked ruffled border but not clear zone. In vitro alendronate bound to bone particles with a Kd of approximately 1 mM and a capacity of 100 nmol/mg at pH 7. At pH 3.5 binding was reduced by 50%. Alendronate inhibited bone resorption by isolated chicken or rat osteoclasts when the amount on the bone surface was around 1.3 x 10(-3) fmol/microns 2, which would produce a concentration of 0.1-1 mM in the resorption space if 50% were released. At these concentrations membrane leakiness to calcium was observed. These findings suggest that alendronate binds to resorption surfaces, is locally released during acidification, the rise in concentration stops resorption and membrane ruffling, without destroying the osteoclasts.

Alendronate

Shared human T cell receptor V beta usage to immunodominant regions of myelin basic protein.

Multiple sclerosis (MS) may be an autoimmune disease mediated by T cells specific for a myelin protein. Investigations have demonstrated myelin basic protein (MBP)-reactive T cells that were activated in vivo in MS patients, suggesting that MBP may be a target antigen in MS. The variable (V) region of the T cell receptor (TCR) beta chain was examined among 83 T cell lines from both MS patients and healthy subjects that were reactive with the immunodominant region of human MBP (residues 84 to 102) or with a second immunodominant region of MBP (143 to 168). V beta 17 and to a lesser extent V beta 12 were frequently used in recognition of MBP(84-102) among different individuals. In contrast, V beta 17 was very infrequent among lines reactive with MBP (143-168). These data demonstrate shared TCR V beta gene usage for the recognition of immunodominant regions of the human autoantigen MBP. Such TCR structures may be used as targets for specific immunotherapy in MS.

Amino Acid Sequence

Long-term follow-up after surgery for patients with biliary atresia.

Long-term results after surgery for biliary atresia (BA) in 48 patients, ranging in age from 10 to 33 years, were examined. There were 19 males and 29 females. Twelve had correctable type BA and 36 had the noncorrectable type. Forty-one cases had no jaundice; seven did. Thirty-seven of the 48 cases were leading normal lives. Among them, six cases were enjoying their lives after overcoming sequelae, such as portal hypertension. The main morbidities of the remaining 11 long-term survivors were jaundice and portal hypertension. The growth of most cases were comparable to those of the normal Japanese population. The data of liver function tests were variable and disclosed a moderate degree of abnormality in patients mainly complicated by cholangitis. Eleven cases, including six jaundice cases, required treatment for esophageal varices and/or hypersplenism. In conclusion, the cured states of most cases without jaundice are satisfactory and these former patients have achieved a favorable quality of life. Early operations are essential to obtain good short-term results as well as good long-term results.

Adolescent

Long-term effects of chincap therapy on skeletal profile in mandibular prognathism.

The purpose of this study was to investigate the long-term changes in the skeletal Class III profile subsequent to chincap therapy. The sample consisted of 63 Japanese girls who had skeletal Class III malocclusions before treatment. All underwent chincap therapy from the beginning of treatment. The duration of chincap therapy varied but averaged 4 1/2 years. The samples were divided into the following three groups according to their ages when chincap therapy was started: A group that started at 7 years of age (n = 23), a group that started at 9 years of age (n = 20), and one that started at 11 years of age (n = 20). The data were derived from lateral cephalometric head films, taken serially at the ages of 7, 9, 11, 14, and 17 years. Skeletal facial diagrams were constructed by X-Y coordinates of representative cephalometric landmarks. The data were analyzed statistically. The results of the present study were as follows: (1) The mandible showed no forward growth during the initial stages of chincap treatment in all three groups. (2) Patients who had entered treatment at 7 and 9 years of age appeared to show a catch-up manner of mandibular displacement in a forward and downward direction before growth was completed. (3) There was no statistical difference in the final skeletal profile between the group that had entered treatment at age 7 and the one that had entered at age 11. In conclusion, the skeletal profile was greatly improved during the initial stages of chincap therapy, but such changes were often not maintained thereafter. This finding indicated that chincap therapy did not necessarily guarantee positive correction of skeletal profile after complete growth.

Cephalometry

[Changes of frontal facial form occurred after correction of anterior reversed occlusion in children with TMJ dysfunction].

The purpose of this study was to investigate the facial pattern of early childhood patient with temporomandibular joint (TMJ) dysfunction (clicking) occurred after anterior cross-bite correction. Chin cap appliance was engaged in all cases, with or without minor intraoral mechano-therapy. Materials were consisted of postero-anterior cephalograms of 50 Japanese patients (6-9 years old), all showing anterior cross-bite with normal function of TMJ at pre-treatment stage. They were consisted of two groups, one was the group of 22 patients with TMJ dysfunction occurred after cross-bite correction and the other was the control group of 28 patients with no TMJ problem. Morphological measurements were done and compared between two groups at pre-treatment stage and after cross-bite correction stage. The results were as follows: 1. In many cases, the TMJ dysfunction was found at about 6 months later after anterior cross-bite correction. 2. It was cleared that the facial pattern of the TMJ dysfunction group showed asymmetry at pre-treatment stage and the same trend of asymmetry pattern continued after cross-bite correction. In conclusion, it was suggested that the TMJ dysfunction tends to occur in mandibular asymmetry patients after cross-bite correction stage because of the dynamic changes of occlusion and mandibular position.

Cephalometry

Method for the quantitative evaluation of the distribution pattern of nuclei in normal and malignant endometrial epithelia.

A quantitative method of evaluating the pattern of distribution of nuclei within a cell cluster was developed and applied to endometrial cytology. The distribution pattern (DP) is mathematically expressed using a "DP index," which can be determined as a product of the square root of the nuclear density, square root of n0, and the mean distance between the two nearest nuclei, r. The DP index has a limited range of decreasing values from 1.074 to 0.5 to 0, indicative of regular, random and aggregated patterns of nuclear distribution, respectively. The estimated DP index was 0.831 +/- 0.031 (mean +/- standard deviation) in the clusters of normal endometrial epithelial cells from 16 nonneoplastic cases, but 0.638 +/- 0.041 in malignant epithelia from 19 cases of well-differentiated adenocarcinoma. The index of normal epithelia was close to 0.877 of the regular hexagonal distribution pattern. Contrary to this, the DP index was significantly smaller in well-differentiated adenocarcinoma (P less than .001), approaching 0.5, the theoretical value of a random distribution pattern. These findings suggest that quantitative analysis of the distribution pattern of nuclei can be a useful aid in the cytodiagnosis of endometrial lesions.

Adenocarcinoma

[Bone marrow re-transplantation following a busulfan and cyclophosphamide regimen].

A 36-year-old man was diagnosed as having RAEB in 1986, and required blood transfusion regularly because of severe anemia. He received the first bone marrow transplantation following total-body irradiation and etoposide infusion in October 1987. He was found to be relapsed into RAEB on 106th day after BMT. And the second BMT was planned. According to the conditioning regimen of Tutschka, et al, we administrated busulfan and cyclophosphamide before re-transplantation. On 26th day after BMT, the WBC count exceeded 1,000/microliters and anemia was improved, while thrombocytopenia persisted until 50th day. Normal hematopoiesis in the bone marrow was confirmed on the 29th day. No severe side effect except for a little fevering and bleeding was found during the clinical course. Unfortunately he died of pneumonia following graft versus host disease on the 166th day after re-BMT. This new conditioning regimen is considered to be a choice for the high risk patients on re-transplantation.

Adult

Elevation by muroctasin of the serum level of the complement subcomponent C1q in mice and of its biosynthesis by cultured mouse peritoneal macrophages.

Augmentative effects of muroctasin (N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine, (MDP-Lys(L18] on the production of a subcomponent of the first complement component, C1q, in mice were examined. The serum level of C1q in mice treated subcutaneously with muroctasin was found to be elevated significantly at 24 h (p less than 0.1) and 48 h (p less than 0.01). At 24 h, samples of peritoneal macrophages were derived from mice, and incubated with Dulbecco's Modified Eagle Medium (MEM) at 37 degrees C for 24 h. At 19 h of incubation, the C1q concentration in the supernatant of the culture also increased significantly (p less than 0.05). Moreover, when the peritoneal macrophages from non-treated mice were cultured in MEM containing muroctasin (0.001 microgram/ml), the amount of C1q in the culture supernatants also increased significantly 3 h (p less than 0.01) after cultivation. These results indicate that muroctasin activated C1q generation by macrophages in mice through direct and/or indirect mechanisms.

Acetylmuramyl-Alanyl-Isoglutamine