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Biomedical subjects

K Kanazawa

Publications and source records attributed to K Kanazawa.

At least 199 records · Page 11Linked to original sources

Cytotoxic antibody against trophoblast and lymphocytes present in pregnancy with intrauterine fetal growth retardation and its relation to anti-phospholipid antibody.

To elucidate immunological mechanisms involved in the genesis of intra-uterine fetal growth retardation (IUGR), an in vitro cytotoxicity assay against normal trophoblast and lymphocytes was performed. The data demonstrated the existence of cytotoxic antibody directed against trophoblast exclusively in the IgG fraction of the sera of 9 out of 15 mothers with IUGR, but in none of the sera from normal pregnant women. This antibody showed differential reactivity patterns that may be indicative women. This antibody showed differential reactivity patterns that may be trophoblast in common. Out of 9 IUGR mothers with this cytotoxic antibody, in 6 cases (66.7%) chronic villitis was evident upon microscopic examination of the placenta, the frequency being significantly higher than that in IUGR mothers without cytotoxicity or in control mothers (P less than 0.02). It is suggested that in situ inflammatory change triggered by this antibody might lead to IUGR through chronic villitis. This antibody showed cross-reactivity with anti-negatively charged phospholipid antibody, as confirmed by an absorption experiment, indicating that the trophoblast antigenic stimuli in pregnancy can induce the production of various autoantibodies including anti-phospholipid antibodies. These results are of interest in relation to the pathogenesis of autoimmune diseases.

Adult↗

Discrepancy in the diagnoses of hydatidiform mole by macroscopic and microscopic findings and the deoxyribonucleic acid fingerprint method.

Ten cases of hydatidiform mole were analyzed by the deoxyribonucleic acid fingerprint method. Deoxyribonucleic acid samples were prepared from hydatidiform mole tissue of hydatidiform mole and maternal and paternal blood. A case of partial hydatidiform mole diagnosed by histologic findings was revealed to be complete hydatidiform mole by deoxyribonucleic acid fingerprinting.

Chorionic Gonadotropin↗

In vitro IgG rheumatoid factor production by CD5-negative murine B cells in response to immune complexes of lipopolysaccharide.

We studied the in vitro production of rheumatoid factor (RF) by spleen cells of normal adult mice. IgG RF cross-reactive with rabbit IgG was produced in response to immune complexes of TNP-lipopolysaccharide (LPS) with murine IgG anti-TNP antibody in an Fc-specific manner, but not to a mixture of IgG and LPS. Antibody-uncomplexed LPS induced little IgG RF production, but suppressed the subsequent IgG RF response to antibody-complexed LPS, whereas IgM RF was induced by either LPS or antibody-complexed LPS. The IgG RF production followed as rapid a time course as IgM RF production; the rate of IgG RF production reached its maximum soon after a lag period of 1 day and declined after 5 days. Treatment of splenic B cells from BALB/c mice with anti-Ly-1.2 antibody and rabbit complement resulted in a selective reduction of IgM RF production by 90%, with little effect of IgG RF production. These results suggest that IgG RF is derived primarily from CD5- memory B cells which have been developed in normal mice by an unknown mechanism. Unlike the CD5+ precursor cells for IgM RF, these memory cells are unresponsive to polyclonal stimulation by LPS but are activated by simultaneous stimulation by aggregated Fc epitopes and the mitogenic stimulus from LPS.

Animals↗

IgG isotype and isotype specificity of murine monoclonal IgG rheumatoid factors.

Immune complexes of lipopolysaccharide (LPS) with homologous IgG antibody induces rheumatoid factor (RF) predominantly of the IgG class in normal mice, while LPS alone induces mostly IgM RF directed to homologous IgG1. In this study, IgG monoclonal RFs (mRF) were prepared from hybridomas derived from spleen cells of BALB/c mice which were immunized with complexes of TNP-LPS with anti-TNP mouse IgG and their specificity to mouse IgG subclasses was assessed by analysing dissociation kinetics of the ligands due to RF-specific and non-specific interactions. Of the 19 IgG mRFs (11 IgG1, five IgG2a, one IgG2b and two IgG3 types) tested, 14 were directed to either IgG3 or IgG2b or both, while only one exhibited a significant binding capacity to IgG1. Other mRFs, although reactive to rabbit IgG, exhibited little homophilic activity. None of these mRFs reacted strongly with their own isotypes. The results suggest that the IgG RF producing cells are not direct progenies of the IgG1-directed IgM RF-producing cells but may have developed via a rigorous selection process to eliminate clones that produce self-reactive RF.

Animals↗

Result of immunotherapy on patients with unexplained recurrent abortion: a beneficial treatment for patients with negative blocking antibodies.

Thirty-nine unexplained recurrent aborters underwent vaccination using husband's lymphocytes according to the previously reported protocol. No mixed lymphocyte culture reaction-blocking antibodies (MLR-BAbs) were observed in these patients prior to vaccination. Of 35 newly pregnant patients after vaccination(s), pregnancy successfully continued in 28 (80.0%) and have already been terminated with a liveborn offspring. Pregnancy outcome was also analyzed in unexplained recurrent aborters who revealed positive MLR-BAbs without immunotherapy. In this group, out of eight pregnancies in seven patients, five (62.5%) continued beyond their critical period of 14 wks of gestation. Three infants born from these pregnancies, however, presented severe abnormalities. Furthermore, outcome of 14 pregnancies in 12 unexplained recurrent aborters with negative MLR-BAbs was analyzed since they had become pregnant without immunotherapy; pregnancy was successfully continued in only four cases (28.6%). Thus, vaccination using husband's lymphocytes on unexplained recurrent aborters with negative MLR-BAbs is suggested to be effective. In addition, it is suggested that immunotherapy for patients with positive MLR-BAbs should be carefully followed.

Abortion, Habitual↗

[Decubitus].

Since decubitus, one of the common lesions, is not yet fully under medical control, it still offers serious problems. The incidence of this lesion once comprised about 12% of the patients hospitalized in a geriatric institution, and was responsible for the development of sepsis in about 20% of those cases. Although the incidence of this lesion has been declining, it still debilitates many geriatric patients, especially with neurological or malignant diseases. Care being necessary to disperse the pressure on the skin adjacent to the bone, many devices have been invented. The air-fluidized bed is especially effective in preventing and alleviating decubitus. However, a simple device utilizing polyvinyl sponge plates is worthy to try from the standpoint of cost-performance. Several surgical reparative manoeuvres as well as newly developed medicines, such as prostaglandin E1, etc. now promote favourable outcomes. However, the importance of basic preventive care, such as postural change with massage, local hygiene, nutrition, etc. cannot be ignored.

Aged↗

Differential expression of human leukocyte antigen-A, -B, and -C locus specific genes in trophoblast and embryonic cells.

Research on the escape mechanism of the fetoplacental unit has focused on the placental trophoblast, which is though to play an important role in the survival of the fetus. There are two major findings in the present study: (a) The expression of human leukocyte antigen (HLA)-A, -B, and -C locus specific genes is greatly reduced in trophoblast cells compared to embryonic cells by Northern blot analysis using locus specific oligonucleotide probes. This is true even though the transcripts detected by a complementary DNA probe, which contains a very conserved sequence present in all members of the HLA gene family, are equally abundant in trophoblast and embryonic cells. (b) When trophoblast cells or embryonic cells are cocultured with peripheral blood lymphocytes from the corresponding female in the presence of recombinant interleukin 2, allogeneic cytotoxic T lymphocytes are generated only in cultures with embryonic cells, and trophoblast cells express the resistance to lysis by the allogeneic cytotoxic T lymphocytes. These results strongly suggest that the reduction in expression of transplantation antigens (HLA-A, -B, and -C) might address the question why maternal tissue does not reject trophoblast cells.

Base Sequence↗

[Cytomorphological reappraisal of choriocarcinoma cells--a proposal of a four cell pattern].

It is generally accepted that choriocarcinoma is composed of two cell types: syncytiotrophoblast (ST)-like cells and cytotrophoblast (CT)-like cells. In normal and molar pregnancy, there is another population of trophoblast in the cell column, the decidua and so forth. They are designated intermediate trophoblast (IT) and multinuclear IT. It remains to be clarified whether IT-like cells and multinuclear IT-like cells are observed in choriocarcinoma. In the present study, choriocarcinoma cells were reappraised cytomorphologically in three cases of uterine choriocarcinoma and additional three cases of metastatic choriocarcinoma. The results were as follows: 1. Choriocarcinoma cells could be classified into four cell types: ST-like cells, CT-like cells, IT-like cells and multinuclear IT-like cells. 2. IT-like cells predominated in metastatic lesions as compared with primary lesions. It seemed that choriocarcinoma shows both differentiations which take place in villous and extravillous trophoblasts of normal and molar pregnancy. IT-like cells were found to infiltrate into vessel walls, which, together with the predominance of IT-like cells in metastatic lesions, suggests that IT-like cells contribute greatly to the hematogenous metastasis in choriocarcinoma. The presence of ST-like cells, CT-like cells and multinuclear IT-like cells in metastatic lesions may indicate a germinative nature of IT-like cells.

Cell Nucleus↗

[Analysis of GM2 and anti-GM2 antibody in normal pregnancy].

Oncofetal antigen immunogenic (OFA-I), an antigen common to the fetal brain and some malignant tumors (derived from ectoderm), is immunogenic in man, and anti-OFA-I antibody appears in the sera of not only malignant patients but also pregnant women. Biochemical analysis revealed that OFA-I is ganglioside GM2 and GD2. In the present study, GM2 and anti-GM2 antibody were investigated as to the kinetics in pregnant sera and the tissue localization in placenta and decidua. The results obtained were as follows: 1. The concentration of GM2 was 76.7 pmol/ml (mean) in pregnant sera and 10.8 pmol/ml (mean) in cord sera. GM2 was not measurable in the sera of non-pregnant women. 2. GM2 was detected by thin layer chromatogram-immunostaining methods in the gangliosides extracted from decidua and term placenta. GM2 was, however, undetected from villi at an early stage. 3. In immunohistological analysis for GM2, positive findings were observed in decidua and in villous stroma of term placenta. In contrast, no distinct positive findings were observed in trophoblast at any stage. 4. Anti-GM2 antibody appeared in pregnant sera at an early stage and was detectable up to the 5th day postpartum.

Adult↗

Preparation and characterization of des-C-terminal tubulin.

Tubulin, from which the C-terminal peptide had been removed by limited proteolysis was compared to intact native tubulin. Des-C-terminal tubulin (with a nominal molecular weight of 48,000) was prepared by digestion with 1% subtilisin carlsberg at 25 degrees C for 16 min, and the product was purified by ion-exchange chromatography on cellulose DE-52 followed by Sephadex G-50 chromatography. The purified product was composed of the cores of both the alpha- and beta-subunits of tubulin and was free from other proteins and peptides containing the COOH-terminal moiety as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) Sephadex G-50 and ion exchange DE-52 cellulose chromatographies, and ultracentrifugation analysis. The ultraviolet (UV) absorption and fluorescence spectra of des-C-terminal tubulin were the same as those of native tubulin. The sedimentation coefficient of des-C-terminal tubulin (5.9S) was slightly higher than that of native tubulin reflecting a decrease in axial ratio. The change in circular dichroism in the far UV indicated a decrease of alpha-helical contents by 10-15%. These optical properties of des-C-terminal tubulin indicate that the elimination of the COOH-terminal region from tubulin did not change the conformation of the core tubulin molecule significantly, the decrease in alpha-helix being due to the elimination of the C-terminal peptide. des-C-terminal tubulin bound 2 moles/mole of GTP and 1 mole/mole of cholchicine, just as intact tubulin, but its binding ability of ruthenium red was reduced.

Animals↗

Perioperative fluctuation in plasma levels of granulocyte elastase and alpha-1-antitrypsin: the influence of the severity of surgical intervention and their effect on the respiratory index.

In order to examine whether granulocyte elastase is related to surgical stress and postoperative respiratory function, the perioperative plasma levels of granulocyte elastase and alpha 1-antitrypsin were periodically measured in 49 patients who underwent various operations and the correlation between these levels and the respiratory index was examined. A strong correlation between elevated plasma levels of granulocyte elastase and the degree of aggressiveness of surgery was quite conspicuous; as the operative intervention became more severe, the plasma levels of granulocyte elastase were higher. The plasma level of alpha 1-antitrypsin was in inverted relation to granulocyte elastase. Moreover, marked and prolonged elevation of plasma granulocyte elastase levels induced postoperative pulmonary complications. A highly significant positive correlation was found between the plasma level of granulocyte elastase and the respiratory index. Elevated granulocyte elastase and/or decreased alpha 1-antitrypsin may therefore be implicated in the etiology of postoperative respiratory dysfunction. Thus, an abnormal elevation of plasma granulocyte elastase may allude the existence of postoperative respiratory dysfunction.

Adult↗

Transient carnitine-responsive medium-chain dicarboxylic aciduria in an infant with cholestasis, hypoglycemia and cardiac failure.

In a cholestatic infant showing hypoglycemia and cardiac failure, non-ketotic medium-chain dicarboxylic aciduria was disclosed by urinary organic acid analysis. As urinary excretion of long-chain fatty acids was also increased, a defect in beta-oxidation of long-chain fatty acids appeared likely. To try to improve this abnormality, carnitine supplements were given, which led to the complete resolution of clinical and laboratory abnormalities. This is the first reported case of a cholestatic infant who responded to carnitine supplementation. Deficiency of carnitine palmitoyl transferase was suspected as the underlying cause.

Carnitine↗

Is immunotherapy for habitual aborters an immunologically hazardous procedure for infants?

Physical development and tests of immunologic function are reported from the first year of life for 13 infants born to mothers who were habitual aborters and who had undergone subcutaneous vaccination with their husband's lymphocytes. The mean weight of the infants at birth was 2,975 +/- 540 g, including one infant who was small for dates. Physical development parameters for the first year were all within normal range. Immunologic studies were performed at ages 0, 1, 3, 6, 9, and 12 months. The studies included the following: (1) serum levels of immunoglobulins and complement components; (2) the number of peripheral blood lymphocytes (PBL) and their subpopulations; and (3) proliferative responses by PBL against unrelated lymphocytes and some mitogens (pokeweed, phytohemagglutinin, and concanavalin A). All were normal when compared with studies of infants of nonimmunized mothers. These observations suggested that subcutaneous vaccination of women with their husband's lymphocytes did not result in any adverse effects on their infants' physical or immunologic development.

Abortion, Habitual↗

MLR-blocking antibodies are directed against alloantigens expressed on syncytiotrophoblasts.

In this study, the reactivity of mixed lymphocyte reaction-blocking antibodies toward trophoblasts was investigated. Nineteen sera that had a significant level of MLR-blocking effect were obtained from normal pregnant women and from primary habitual aborters after immunotherapy. The blocking effects of these sera were studied before and after absorption with syncytiotrophoblast plasma membrane (STPM) from the respective mothers' placenta (autologous) as an experimental group and from unrelated mothers' placenta (allogeneic) as a control. The HLA types of cord blood lymphocytes corresponding to ten of these STPM were then determined. In the study with the 11 normal pregnancy sera, the blocking effect of every serum was partially removed by autologous STPM absorption. This revealed a significant difference between the preabsorption and postabsorption MLR-blocking effect. Nevertheless, absorption by the allogeneic STPM either partially removed or did not remove the blocking effect. Furthermore, there was a statistically significant difference in the elimination of the MLR-blocking effect between the autologous STPM and the allogeneic STPM. Studies with the sera from the immunized aborters revealed similar results. There was no statistically significant difference in the elimination of the antibodies between absorption with autologous and with allogeneic STPM. In these habitual aborters' sera, comparison of paternal stimulator and cord blood lymphocytes HLA types showed that the positive allogeneic STPM absorptions could not be explained sufficiently by coincidence of HLA types. Further studies are needed to determine whether the alloantigens are HLA-linked or not.

Abortion, Habitual↗

Establishment and characterization of a subline predisposed to pulmonary metastasis from a human gestational choriocarcinoma cell line in nude mice.

A subline predisposed to pulmonary metastasis was successfully derived by repeating in vivo selection of GCH-1, a human gestational choriocarcinoma cell line, in nude mice. While the parent line GCH-1, transplanted subcutaneously to nude mice, induced pulmonary metastasis in a few of the host animals, the newly established subline GCH-1(m) successfully metastasized to the lungs in 100% of them. Compared with GCH-1, GCH-1(m) exhibited a higher degree of cell atypia, a lower capacity for cell growth and markedly higher productivity for human chorionic gonadotropin (hCG). Another characteristic of this subline was its enhanced growth after the addition of a pulmonary extract obtained from nude mice. The relationship of these findings to the mechanisms of metastasis of this cancer was discussed.

Animals↗

Depletion of hepatic coenzyme A derivatives is one of the markers of the toxicity of orally administered secondary autoxidation products of linoleic acid in rat.

When 400 mg/rat/day of secondary autoxidation products of linoleic acid was orally administered 3 times to rats, they died at 30-40 h after the third dose. To search the markers of the toxicity of secondary products in vivo, the rats were killed at 24h after the third dose, and conditions of their digestive tracts and liver were analyzed. In the stomach, macroscopically, inflation, retention of undigested food, and edema were seen. Slight congestions were detected in the small intestines. It was considered that these injuries led to reduction in food consumption and then depression of the growth, but did not lead to the death of the animals. The lipid peroxide levels in the liver and the activities of its detoxifying enzymes were increased as compared to those in the control groups. The hepatic lipid contents and unsaturated fatty acid compositions were also not changed. The endogenous lipid peroxidation, therefore, did not give the rats a severe stress. The activities of hepatic acetyl-CoA carboxylase and carnitine palmitoyltransferase were 20 and 35% lower than those of control, respectively. The levels of CoASH, acetyl-CoA, and long-chain acyl-CoA were 1/9, 1/2, and 1/4 of those in control, respectively. Thus, one of the markers of the toxicity of secondary products was the depletion of hepatic CoA derivatives. In rat, bio-energy was reduced by the decrease in the intestinal absorption of nutrients, and the depletion of hepatic CoA derivatives also failed to supply energy with beta-oxidation.

Animals↗

Succinate dehydrogenase and synthetic pathways of glucose 6-phosphate are also the markers of the toxicity of orally administered secondary autoxidation products of linoleic acid in rat liver.

In order to find the markers of the toxicity of the autoxidized lipids in the liver, rats were given a lethal amount of secondary autoxidation products of linoleic acid (400 mg/rat/day for 3 days) and then changes in the hepatic metabolic functions were analyzed. A decrease in acetyl-CoA level to half caused by the depletion of CoASH was reported in an associated paper (J. Nutr. Sci. Vitaminol., 35, 11-23, 1989). Citrate, isocitrate, and 2-oxoglutarate also decreased to half the level of those of the control group. Reduction in isocitrate dehydrogenase activity was only 25%, while NADH2 and ATP levels remained unchanged. Thus, the reduction in the citrate cycle activity was due to the decrease in acetyl-CoA. The activity of mitochondrial succinate dehydrogenase was decreased to 1/5. Other appreciable changes were depletion of glucose 6-phosphate and fructose 6-phosphate, accumulation of glucose 1-phosphate, reductions in hexokinase, phosphofructokinase, glucose-6-phosphatase, phosphoglucomutase, and phosphogluconate dehydrogenase activities, and decrease in the NADPH2 level. It was considered that these changes were caused by the depletion of glucose 6-phosphate whose synthetic pathways were abnormal. Therefore, the markers of the hepatotoxicity of secondary products were the changes in the CoASH level and the activities of succinate dehydrogenase and synthetic pathways for glucose 6-phosphate.

Animals↗