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Biomedical subjects

N Endo

Publications and source records attributed to N Endo.

At least 127 records · Page 7Linked to original sources

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↗

[Prophylactic use of DDAVP in a patient with von Willebrand disease during labor: a case report and a review].

A Case of delivery in a 23-year-old woman after a prophylactic infusion of DDAVP is described. She had a life-long history of easy bruising and frequent epistaxis, with the diagnosis of vWD being made when she was 14 years old. A hemostatic examination showed a prolonged bleeding time, a moderate reduction in the factor VIII level (VIII: C) and von Willebrand Factor Antigen (vWF: Ag), decreased platelet aggregation by ristocetin, and depletion of platelet retention. In April, 1988, in the 34th week of pregnancy, she was admitted to our clinic in order to avoid abnormal bleeding during labor. On admission, the level of factor VIII, ristocetin aggregation, and platelet retention were normal, but the bleeding time remained prolonged. The diagnosis of vWD type I was made on the normal multimeric structure. The DDAVP infusion test revealed a shortening of the bleeding time and an increase in the vWF: Ag. In the 41st week of pregnancy, labor was induced, accompanied by infusion of DDAVP, she gave birth to an infant without any abnormal bleeding. Since conventional treatments with human plasma derivatives may cause complicating viral infections, we propose the infusion of DDAVP is one of the treatments to prevent the abnormal bleeding of the patient with vWD during labor.

Adult↗

Preparation and in vitro cytotoxicity of a methotrexate-anti-MM46 monoclonal antibody conjugate via an oligopeptide spacer.

A method was developed by which conjugates of methotrexate (MTX) with antibody were prepared via an oligopeptide spacer which, after internalization of the conjugates into the target cells, would be cleaved by lysosomal enzymes to liberate MTX or its derivative(s) for entry of the drug into the cytoplasm through the lysosomal membrane. The conjugate of MTX with a monoclonal antibody (MAb) (aMM46) to mouse mammary carcinoma MM46 cells prepared by this method via Leu-Ala-Leu-Ala showed potent, antibody-directed cytotoxicity through lysosomal degradation of the conjugate, most likely at the tetrapeptide spacer. This was supported by the following observations: (a) the cytotoxicity of the aMM46 conjugate was more potent than that of the corresponding normal gamma-globulin conjugate, the antibody alone not being cytotoxic; (b) the conjugate retained its potent cytotoxicity to MM46 cells even after removal, by hydroxylamine treatment, of a less stably bound MTX derivative which might have been released extracellularly and have caused non-specific cytotoxicity by entering the cells via the membrane active transport system for MTX; (c) the cytotoxicity was not inhibited by thiamine pyrophosphate, an inhibitor of the MTX transport system; (d) the cytotoxicity was inhibited significantly with ammonium chloride, which inactivates lysosomal enzymes by raising the pH; and (e) the cleavability of the Leu-Ala-Leu-Ala spacer by the lysosomal enzymes was verified by using bio-undegradable poly(D-lysine) and biodegradable poly(L-lysine) as the lysosomotropic macromolecular carriers: unlike the poly(L-lysine) counterpart, the direct MTX-poly(D-lysine) conjugate showed very weak cytotoxicity while the tetrapeptide-mediated conjugate of MTX with poly(D-lysine) exhibited potent cytotoxicity.

Animals↗

[Isolation and characterization of proteoglycan in bovine periodontal ligament].

Proteoglycan, one of the major non-collagenous protein in the connective tissue, is bound with fibronectin and other cell adhesion proteins, and has a role in the formation of the tissue and the organ. Although the glycosaminoglycan components in various tissue have been widely investigated, the molecular structure of periodontal ligament proteoglycan (PDL-PG) was rarely reported. In present study, proteoglycans of bovine periodontal ligament were purified by chromatography from material adsorbed by DEAE-Sephacel from a guanidium HCl extract. The sequential chromatographic steps consisted of ion-exchange chromatography on DEAE-Sephacel in 4M urea and gel filtration on Sepharose CL-4B in 4M guanidium HCl. The preparation contained a relatively small proteoglycan (Mr = 132,000 dalton) and a free glycosaminoglycan chain (Mr = 88,000 dalton). A Mr = 58,000 dalton core protein was shown by gradient SDS gel electrophoresis after chondroitinase ABC or chondroitinase AC II treatment. The glycosaminoglycan chains after chondroitinase AC II hydrolysis were seen on gel as polydispersed, broad alcian blue staining material (Mr = 20,000-60,000 dalton) while chains were totally hydrolyzed by chondroitinase ABC. These indicate a chondroitin sulfate/dermatan sulate (CS/DS) hybrid glycosaminoglycan chain. Papain digestion of the proteoglycan resulted in a single glycosaminoglycan chain after SDS gel electrophoresis with no protein band. These results suggest that the PDL-PG is slightly larger than that of bone and contains a single chondroitin sulphate/dermatan sulphate chain attached to a 58 K core protein. Antisera raised against PDL-PGs cross-reacted with PDL-PGs but not with other PDL proteins or bone PGs. It has been shown that during biosynthesis of dematan sulfate, L-iduronic acid is formed by epimerization of D-glucuronic acid, and sulfation. The degree of epimerization and sulfation may be related to the function of PDL in buffering the mechanical force applied to the tooth.

Animals↗

[Importance of posterior discrepancy in the development of skeletal Class III malocclusion].

The purpose of this communication is to explain regarding with relationship between the development of skeletal Class III malocclusion and the tooth-to-denture base discrepancy especially those in the posterior part of dentition (posterior discrepancy). Four cases which had skeletal Class III malocclusion and had experienced unsuccessful orthodontic correction were presented to evaluate the causative factors of skeletal Class III malocclusion. The observation of serial cephalograms led us to the conclusion that the continuous forward displacement of the mandible was associated with superversion of maxillary and/or mandibular molars caused by the "squeezing out" effect of poterior discrepancy. Moreover, superversion of molar provides a less steep maxillary occlusal plane in the denture frame. Accordingly, a vertical expression of the posterior discrepancy may provide one of the best explanation for development of skeletal Class III malocclusion.

Humans↗

[The present status and problems in the treatment of biliary atresia with special reference to surgical and long-term results].

The surgical results are not satisfactory yet in Japan and only 46% of the patients are free of jaundice 3 years ago. However, we found many presentations which reported jaundice disappearance rate with more than 80% in the last several years. The main cause of death in jaundiced patients with the failed hepatic portoenterostomy was hepatic failure. Other causes of deaths in these patients, including those died within one month after operation, were peritonitis, cardiac and/or renal failure, hemorrhagic tendency and lung edema. The main cause of death in jaundice-free patients was rupture of the esophageal varices. We examined 48 long-term survivors ranging in age from 10 to 33 years. There were 41 cases without and 7 with jaundice. Thirty-seven (77%) of 48 cases were leading their normal lives. Among them, 6 cases were enjoying their lives after overcoming the sequelae, such as portal hypertension. The morbidities of the remaining 11 (23%) long-term survivors were jaundice in 7, portal hypertension in 5, encephalopathy after splenorenal shunt in 1 and so on. The cured states of most cases without jaundice are satisfactory and eventually these former patients can achieve a favorable quality of life.

Adolescent↗

Nature of linkage and mode of action of methotrexate conjugated with antitumor antibodies: implications for future preparation of conjugates.

The binding of methotrexate (MTX) to IgG in conjugates was examined by studies on a direct MTX conjugate with a monoclonal antibody (aMM46) to mouse mammary tumor MM46 cells and corresponding irrelevant antibody and normal gamma-globulin conjugates, all prepared by the active ester method with MTX N-succinimidyl ester (MTX-OSu). The binding was examined in terms of effects on the potency and selectivity of the cytotoxic activity of the aMM46 conjugate. The results obtained supported the following conclusions: (a) MTX-OSu reacts not only with the amino group of IgG to give an amide bond, but also with another group(s) to give a less stable bond(s) such as an ester bond; (b) in contrast to the amide bond-linked MTX, which is taken up by the cells by endocytic internalization, a substantial portion of the MTX linked by an ester or other less stable bond(s) is released from the conjugates extracellularly and enters the cells by the MTX active transport system, as revealed by the inhibitory effect of thiamine pyrophosphate on the cytotoxicity; (c) this MTX linked by a less stable bond(s) that causes nonspecific cytotoxicity can be removed by treatment with hydroxylamine; (d) the overall cytotoxicity of aMM46-MTX decreased on removal of this less stably linked MTX, suggesting that the lysosomal degradation of the conjugate carrying amide bond-linked MTX to liberate MTX derivatives of low molecular weight is insufficient; (e) the liberation of low-molecular-weight substances in the lysosomes is probably more important for efficient entry of active substances into the cytosol, than for inhibition of the activity of dihydrofolate reductase, because after hydroxylamine treatment, the amide bond-linked MTX showed greater decrease in drug cytotoxicity than in inhibitory activity against dihydrofolate reductase; (f) in combination with hydroxylamine treatment, insertion between MTX and IgG of a linkage capable of ready cleavage in lysosomes deserves exploitation as a method for making potent conjugates with less nonspecific activity.

Animals↗