Biomedical subjects

Y Hamashima

Publications and source records attributed to Y Hamashima.

At least 19 recordsLinked to original sources

PubMed1991

Analysis of IgG immune complexes in sera from patients with membranous nephropathy: role of IgG4 subclass and low-avidity antibodies.

The levels of circulating immune complexes (CIC) were determined using an anti-C3d binding assay in patients with various types of glomerulonephritis (GN). It was found that IgG class CIC were positive in 20% (7/35) of patients with idiopathic membranous nephropathy (MN) and in 80% (8/10) of patients with lupus glomerulonephritis (LN). Of these patients, IgG4 subclass CIC were observed more frequently in 29% of MN and 60% (3/5) of minimum change nephrotic syndrome, and, with less amounts, in 10% (1/10) of membranoproliferative GN (MPGN) and 20% (2/10) of IgA nephropathy. On the other hand, the patients with LN showed a lower positivity (30%) of IgG4-CIC as compared with that of IgG-CIC. In the comparison of mean levels, only MN patients showed significantly higher value than normal individuals (p less than 0.05). In patients with MN, the CIC of the other IgG subclasses (IgG1, IgG2, IgG3) were not significantly elevated and their positivities were low (9-11%). The study on the salt-dependent dissociability of CIC, which is considered to reflect the avidity of antibodies in CIC, showed that the IgG-CIC of 11 of 15 patients with MN were dissociable to various extents even at the physiological concentration. These findings suggested that IgG4 subclass specificity and low avidity may be pathogenic characteristics of IgG-CIC in certain populations of patients with MN.

Antibody Affinity↗

PubMed1990

Allogeneic bone marrow-plus-liver transplantation in the C57BL/KsJ spm/spm mouse, an animal model of Niemann-Pick disease.

The C57BL/KsJ spm/spm mouse, an animal model of Niemann-Pick disease, shows defective sphingomyelinase activity resulting in accumulation of sphingomyelin in various organs. To replace the defective enzyme, allogeneic bone marrow-plus-liver transplantation was performed. Bone marrow transplantation with or without concomitant liver grafting in C57BL/KsJ spm/spm mice at the age of 2-9 weeks led to an amelioration of the hepatosplenomegaly. The treatment, however, neither prevented the development of neurological signs nor increased the life-span. The sphingomyelin and cholesterol contents of the liver decreased, while sphingomyelinase activity in the liver increased after bone marrow transplantation. Foam cells disappeared from the bone marrow, liver, spleen, thymus, and lymph nodes, but depletion of Purkinje cells was not prevented. These results suggest that bone marrow transplantation either alone or with liver transplantation may become a useful strategy for the treatment of Niemann-Pick disease provided the central nervous system is not involved.

Animals↗

PubMed1989

Autoimmune abnormalities in a murine model of accelerated senescence.

Immunopathological abnormalities in senescence-accelerated mice (SAM) were studied by comparison of senescence-prone (SAM-P/1) and senescence-resistant (SAM-R/1) mice. Sera from SAM-P/1 mice contained a number of autoantibodies, including natural thymocytotoxic autoantibody (NTA), anti-nuclear antibodies (ANA) and IgG anti-single-stranded and anti-double-stranded (ss and ds) DNA antibodies. Furthermore, an earlier increase in serum IgG2 levels and an earlier appearance of IgG circulating immune-complexes (CIC) associated with low C3 levels, were observed in SAM-P/1 mice. These serological findings were distinctive features in SAM-P/1 mice, which could almost discriminate these mice from SAM-R/1 mice. In addition, age-associated glomerular mesangial and capillary lesions with granular IgG and C3 deposition were frequently observed in SAM-P/1 mice, whereas SAM-R/1 mice even at 10 months of age showed only mild mesangial lesions. These findings suggest that autoimmune abnormalities may contribute to the accelerated senescence in these mice.

Aging↗

PubMed1989

Lectin histochemistry in ulcerative colitis and Crohn's disease.

The glycoconjugate composition of intestinal goblet cell mucin was characterized according to the anatomical distribution of lectin-binding sites in surgically resected intestinal tissues and mucosal biopsy specimens obtained from 38 control subjects, and from 32 patients with the active phase of ulcerative colitis, and 12 with Crohn's disease. Immunoperoxidase labeling studies found that in control tissues binding by Soybean Agglutinin (SBA), Dolichos Biflorus Agglutinin (DBA), Wheatgerm Agglutinin (WGA), and Ricinus Communis Agglutinin-120 (RCA-120) was consistently higher than that of Peanut Agglutinin (PNA), Ulex Europaeus Agglutinin-1 (UEA-1), Concanavalin A (ConA) and Helix Pomatia Agglutinin (HPA). Tissues from ulcerative colitis and Crohn's disease patients, showed increases in DBA and SBA binding, a reduction in HPA binding, and changes in the distribution of PNA, UEA-1, RCA-120, and HPA labeling sites. These results demonstrated that the expression of lectin-binding sites on human intestinal goblet mucin was specifically altered in ulcerative colitis and Crohn's disease, thus possibly providing another approach to the assessment of neoplastic risk on these diseases.

Adolescent↗

PubMed1988

Immunohistochemical examination of Peyer's patches in autoimmune mice.

The distribution of T-cells and B-cells in Peyer's patches was examined in three autoimmune model mice, MRL/Mp-lpr/lpr, BXSB, NZBWF1/J mice and normal BALB/c mice, between one and ten months old. A multiple layering technique was used for immunohistochemical detection of lymphocyte surface antigens of T-cells (Thy1.2, Lyt1, Lyt2) and B-cells (surface IgM) and peanut agglutinin receptor for germinal center cells. The T-cell population of female MRL/Mp-lpr/lpr mice increased markedly with age, and the B-cell population of the male BXSB mouse tended to increase. However, little change was observed with age in the NZBWF1/J mice. The immunohistochemical properties of the Peyer's patches in the three autoimmune model mice were different.

Animals↗

PubMed1988

Comparative studies on immunoglobulins, complement component (C3), albumin, and immunoglobulin A-containing circulating immune complexes in serum and bile of patients with biliary obstruction.

We measured the concentrations of IgA, IgG, IgM, secretory IgA, albumin, complement component (C3), and IgA-containing circulating immune complex (IgA-CIC) in the serum and bile of patients with biliary obstruction. The bile-to-serum (BS) ratio of the concentrations of albumin and IgG increased with the increase in total serum bilirubin. This indicates that the permeability from blood to bile increases with the degree of biliary obstruction, and the blood-bile barrier function breaks down. The BS ratios of IgA and IgM, which are selectively secreted into bile, did not show a significant correlation with total serum bilirubin. The index of the BS ratio to the BS ratio of albumin (BS/BS-Alb index) of IgA and IgM was significantly larger than that of IgG. This indicates that the selective transport of IgA and IgM into bile is present even in patients with obstructive jaundice. Since the BS/BS-Alb index of C3 is larger than that of IgG, and the SGOT correlated directly with the BS ratio of C3, some of the C3 in bile may come from damaged hepatocytes.

Albumins↗

PubMed1988

Circulating immune complex, endotoxin, and biliary infection in patients with biliary obstruction.

Immunoglobulin A-containing circulating immune complexes, immunoglobulin G-containing circulating immune complexes, and endotoxin were measured in the sera of patients with obstructive jaundice. The bile of patients with percutaneous transhepatic biliary drainage was also cultured for bacteriologic studies. There was a significantly positive correlation between the endotoxin levels and both immunoglobulin A-containing circulating immune complex and immunoglobulin G-containing circulating immune complex. The endotoxin levels of the patients with gram-negative infections were significantly increased compared with those of the patients with sterile cultures. The immunoglobulin G-containing circulating immune complex levels of the patients with bacteria in bile were significantly increased compared with those of the patients with sterile cultures. The immunoglobulin A-containing circulating immune complex levels of the patients with bacteria in bile were slightly increased, but the difference did not reach statistical significance. These results indicate that one of the causes of increased circulating immune complex levels may be endotoxemia in combination with biliary infection in patients with biliary obstruction.

Antigen-Antibody Complex↗

PubMed1988

The effect of splenectomy on antibody response to lipopolysaccharide (E. coli) immunization.

The influence of splenectomy on the antibody response to lipopolysaccharide (LPS: E. coli 0128:B12) was investigated in mice. Splenectomy had little effect on the primary response to the LPS. However, the level of IgG anti-LPS antibodies of splenectomized mice was significantly lower than that of sham-operated mice when the mice were immunized 1, 3, and 7 days after the operation and reimmunized 7 days after the first immunization. There was no significant difference in those immunized 30 days after the operation and reimmunized 7 days later. In mice immunized before splenectomy and reimmunized 30 days after splenectomy, the level of IgG anti-LPS antibodies was low, even in the mice splenectomized 30 days after primary immunization. Our results indicate that splenectomy impairs the antibody response to lipopolysaccharides.

Animals↗

PubMed1988

Pathogenesis of lupus dermatoses in autoimmune mice. X. Evaluation of histamine-N-methyltransferase activity in the skin of autoimmune.

We measured histamine concentration and its metabolizing enzymes in the skin of MRL/Mp-lpr/lpr (MRL/l) and BXSB mice to clarify the contribution of histamine metabolism to the mechanisms of the development of lupus dermatoses. The concentration of histamine seemed to differ with the mouse strain. The activity of histamine-N-methyltransferase (HMT), one of two major metabolizing enzymes, was significantly lower in the tail and back skin of MRL/l mice at the age of 5 months than in the control MRL/Mp-+/+(MRL/n) mice, although there were no characteristic differences among several mouse strains of 1 mo of age. In the back skin of MRL/l mice, an age-dependent decrease of HMT activity was observed along with a corresponding decrease in histamine concentration, whereas an age-dependent increase of both HMT activity and histamine concentration was demonstrated in BXSB mice and other control mouse strains. Autoimmune-prone male BXSB mice and non-autoimmune female BXSB mice at 5 mo of age showed similar HMT activity. Corticosteroid treatment restored HMT activity in the skin of MRL/l mice but not in MRL/n mice. In addition, the change in HMT activity in MRL/l mice treated with corticosteroid appeared earlier than changes in clinicopathological examinations including skin eruptions, dermatopathology and proteinuria. Diamine oxidase (DAO) activity, another major metabolizing enzyme, was not detected in the skin of any autoimmune or control mouse strains. These findings suggest that the low activity of HMT in the skin of MRL/l mice plays a significant pathological role in the development of spontaneous lupus-like eruption. In other mouse strains, it is assumed that HMT activity is regulated by genetic factors.

Abdomen↗

PubMed1988

Immunological status of nude mice engrafted with allogeneic or syngeneic thymuses.

Restoration of T-cell functions and changes in autoantibody production were studied in BALB/c nu/nu (nude) mice engrafted with syngeneic (BALB/c) or allogeneic (C57BL/6J) thymuses across major histocompatability barriers. T-cell functions, including mitogen responses and antibody production to sheep red blood cells (SRBC), were restored in nude mice engrafted with either allogeneic or syngeneic thymuses. Alloreactivity was evaluated by analysis of the pattern of skin allograft rejection, generation of alloreactive cytotoxic T-lymphocytes (CTLs), or quantitation of mixed-lymphocyte reaction (MLR). BABL/c nude mice engrafted with thymuses from newborn C57BL/6J mice accepted the skin from either thymus donor-type mice or from host-type mice. By contrast, such thymic chimeras rejected skin grafts from a third-party donor. CTLs from nude mice engrafted with C57BL/6J thymuses were cytotoxic to target cells of the third party but not to target cells of the host-type or of the thymus-type. In the MLR assay, spleen cells of nude mice engrafted with C57BL/6J thymuses responded vigorously to third party cells and only slightly to cells of the thymus-type. Low levels of serum IgG and high titers of IgM antibodies to nuclear antigens (but not dsDNA) or skin basal cells were also found in nude mice. Antibodies to both nuclear antigens and skin basal cells disappeared after transplantation of syngeneic thymuses, but not after transplantation of allogeneic thymuses. By contrast, serum IgG levels were restored to normal in nude mice engrafted with either syngeneic or allogeneic thymuses. These results suggest that either HLA-matched or HLA-mismatched thymus grafts may become a viable treatment for certain patients with T cell deficiencies associated with deficient development or maintenance of thymic structure and/or function.

Animals↗

PubMed1987

Immunohistochemical localization of a new thiamine diphosphate-binding protein in the rat nervous system.

The neurophysiological roles of thiamine-binding proteins have lately attracted considerable attention. We purified a new thiamine diphosphate-binding protein (ThDP-BP) prepared from rat livers and produced an antiserum against it. We examined the immunohistochemical distribution of ThDP-BP in the rat nervous system by the avidin-biotin complex technique. Immunoreactivity for ThDP-BP was found in several groups of neurons, and other neuronal tissues including glial cells, ependymal cells and Schwann cells. In neurons, the cytoplasm and processes were stained, but the nucleus was scarcely stained. In glial cells, the nucleus was stained, but the cytoplasm was not stained.

Animals↗

PubMed1987

Frequency and size of coronary arterial aneurysm at necropsy in Kawasaki disease.

The diameter of the largest coronary arterial aneurysm was examined in 61 autopsied children with Kawasaki disease. Thirty children died during the acute stage: The largest diameter of the coronary aneurysm was 6 mm or more in 23 who died of coronary heart disease and 4.5 mm or less in 7 who died of myocarditis. Thirty-one children died during the healed stage: The diameter of the largest coronary aneurysm was 8 mm or more in 26, to 8 mm in 3, and 2.5 mm or less (normal) in 2. Two patients without coronary aneurysms died of bacterial infections or accidents. Twenty-nine patients with a coronary aneurysm 6 mm or more in diameter died of coronary heart disease. Twenty-three of 26 children with a coronary aneurysm 8 mm or larger had multivessel coronary aneurysms.

Autopsy↗

PubMed1987

T-cell acute lymphoblastic leukemia relapsing as acute myelomonocytic leukemia and terminating possibly as chronic myelocytic leukemia.

A 9-year-old boy suffering from T-cell acute lymphoblastic leukemia (T-ALL) with a mediastinal mass had a complete remission as a result of treatment. Ten months later, he developed a typical acute myelomonocytic leukemia (AMMoL) pattern. Two months after a second relapse, he showed a clinical picture that was indistinguishable from chronic myelocytic leukemia (CML). At autopsy, massive infiltration of CML-like cells was observed even in the thymus (190 g). These observations suggest that the leukemia in this child arose in a pluripotent stem cell capable of differentiation into both T-lymphocytic and myelomonocytic lineages.

Antibodies, Monoclonal↗

PubMed1987

Plasma levels of secretory IgA in patients with gastric cancer.

The levels of plasma secretory IgA were measured in patients with gastric cancer and found to be slightly higher (9.6 +/- 6.2 micrograms/ml) than those in healthy controls (7.0 +/- 2.6 micrograms/ml, 0.05 less than P less than 0.1). Secretory IgA levels in those with hepatic metastases (19.7 +/- 12.2 micrograms/ml) were significantly higher than those in patients without hepatic metastases (P less than 0.001). In the latter, there was no significant relationship between plasma secretory IgA levels and the deepest layer of cancerous invasion or lymph node metastases. The secretory IgA levels in cases of well differentiated tubular adenocarcinoma were significantly higher than those with poorly differentiated adenocarcinoma (P less than 0.05). Although there is small diagnostic value in the detection of gastric cancer by measuring the levels of secretory IgA, high levels of secretory IgA in gastric cancer patients may be indicative of the presence of hepatic metastases.

Adult↗

PubMed1987

Immunohistochemical distribution of vitamin B12 R-binder in renal cell carcinoma.

Renal cell carcinomas and normal kidney tissues were examined for the expression of vitamin B12 R-binder by the indirect immunoperoxidase method. In normal kidney tissue, the presence of the vitamin B12 R-binder was shown to be confined to the straight portion (pars recta) of proximal tubules. Seven of the 38 cases of renal cell carcinoma (18%) expressed the vitamin B12 R-binder antigen. This provides a further evidence of the proximal tubular nature of renal cell carcinoma, and suggests that a small proportion of renal cell carcinomas originate from the straight portion of the renal proximal tubules.

Carcinoma, Renal Cell↗

PubMed1987

Clonotypic comparison of IgG anti-DNA antibodies of healthy subjects and systemic lupus erythematosus patients: studies on heterogeneity and avidity.

Qualitative characteristics of IgG anti-ssDNA antibodies were studied and compared by isoelectric focusing (IEF) and enzyme-linked immunosorbent assay (ELISA) between normal human sera (NHS) and systemic lupus erythematosus (SLE) sera. In NHS, IgG anti-ssDNA spectrotypes were observed in a high alkaline pH range (7.5 to 8.5) at physiological NaCl concentrations (0.15 M). In SLE sera the spectrotypes were found to a more intensified extent in the alkaline pH range as compared to those in NHS. With regard to avidity, analyzed by salt-dependent changes of anti-ssDNA activities, NHS showed strong ssDNA-binding bands in a wide range of pH 7.0-8.5 comparable to those in SLE sera. However, these bands became extremely weak and/or faint in pH 7.5-8.5 as the NaCl concentration was raised to 0.15 M and 0.20 M. On the other hand, SLE sera still exhibited thick binding bands at higher NaCl concentrations. This salt-dependency of these antibodies was-also demonstrated by ELISA of serum samples adjusted to contain comparable antibody levels. These findings suggest that clonotypes of IgG anti-ssDNA antibodies both in NHS and in SLE sera are essentially oligoclonal and highly cationic, and that the distinctive characteristics of these antibodies in NHS may be of low avidity, in contrast to SLE sera which exhibit high avidity.

Adult↗

PubMed1987

Unusual renal sarcoma in a young adult: its similarities to clear cell sarcoma of the kidney.

We report an unusual case of renal sarcoma in a young adult. Histological examination demonstrated many similarities to the histopathological features of clear cell sarcoma of the kidney. Immunohistochemically, none of the intrinsic tumor cells showed positive staining with the antibodies against the intermediate filament proteins, epithelial membrane antigen, S100 protein, neuron-specific enolase, Leu-7 or myoglobin. The clinical course of this tumor was that of high grade malignancy, resulting in death with generalized metastases 13 months after tumor resection.

Adult↗

PubMed1987

Treatment of type 1 diabetes mellitus in non-obese diabetic mice by transplantation of allogeneic bone marrow and pancreatic tissue.

Non-obese diabetic (NOD) mice provide a model for type 1 diabetes mellitus. We previously showed that allogeneic bone marrow transplantation (ABMT) can prevent and treat insulitis and overt diabetes in NOD mice. However, ABMT alone could not be used to treat overt diabetes in NOD mice whose islets had been completely destroyed. To provide insulin-producing cells, pancreatic tissue from newborn mice was grafted under the renal capsules in combination with ABMT. The aims of concomitant ABMT are as follows. (i) It induces immunological tolerance to the donor-type major histocompatibility complex determinants and permits the host to accept subsequent pancreatic allografts from the bone marrow donor. (ii) ABMT replaces abnormal stem cells with normal stem cells. After transplantation of bone marrow plus newborn pancreas, NOD mice showed reduction of the glycosuria and a normal response in the glucose-tolerance test. Immunohistological study revealed the presence of clustered insulin-containing beta cells in the grafted pancreatic transplants. ABMT may become a viable treatment of established type 1 diabetes mellitus in humans.

Animals↗