[A case of antimitochondrial antibody (AMA) negative primary biliary cirrhosis (PBC) associated with Sjögren's syndrome and arthropathy].
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Autoantibodies↗
Biomedical subjects
H Kanno
Publications and source records attributed to H Kanno.
Hepatic resection under in situ hemihepatic hypothermic perfusion with hepatoprotective agents.
Hepatectomy was performed under in situ right lobar hypothermic perfusion combined with hepatoprotective agents in six patients who had hepatocellular carcinoma and coexisting liver disease. Following occlusion of the right hepatic vein and the right portal pedicle, in situ cold perfusion was initiated using chilled Ringer's lactate infused through a cannula placed in the right main portal vein. The right superior segments were resected in a bloodless field. The liver was cooled to 22-26 degrees C for 40 to 80 minutes with no significant changes in systemic hemodynamics or body temperature. Postoperative liver functions showed no marked derangement; the mean peak GPT was 221 U and the mean peak total bilirubin 2.3 mg d/l. Local cooling minimizes the risk of ischemia/reperfusion injury in this very vulnerable population, yet gives the surgeon adequate time to perform a challenging resection in a bloodless field.
Aged↗
Role of Epstein-Barr virus in pleural lymphomagenesis.
Longstanding inflammation in chronic pyothorax (CP) plays a role in the development of pleural lymphoma; therefore, in 1987, the term pyothorax-associated lymphoma (PAL) was proposed. A recent study showed in the tumor cells of a limited number of patients, the presence of the Epstein-Barr virus (EBV) genome together with the expression of latent infection genes in the tumor cells of PAL. The purpose of the present study is to evaluate an association of EBV with PAL in a large number of patients. In addition, the presence of the EBV genome was examined in cases with CP without PAL. Histologic, immunohistochemical studies, and analyses by polymerase chain reaction (PCR) and in situ hybridization method for EBV were performed on 34 PAL and 16 CP collected by nationwide study. Median age of the patients in both diseases was approximately 70 years with a marked preponderance in men. Mean duration of CP in patients with CP alone and with CP complicated with PAL was 33 and 37 years, respectively. Histologically all PAL were non-Hodgkin's lymphoma, with immunoblastic type being the most common. Immunohistochemistry revealed 28 of 34 PAL to be B-cell type. Combined PCR, in situ hybridization method, and immunohistochemistry showed that the EBV genome was detected in lymphoma cells in 85% of PAL with almost constant expression of latent membrane protein-1. The EBV genome was detected by PCR in only one of 16 CP.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Red cell enzymopathies as a model of inborn errors of metabolism.
The molecular abnormalities of erythroenzymopathies associated with hereditary hemolytic anemia have been determined using molecular techniques. Pyruvate kinase (PK) deficiency is the most common and well-characterized enzyme deficiency involving the glycolytic pathway and causing hereditary hemolytic anemia. We have identified six distinct missense mutations and a form of splicing mutation in 11 unrelated families with homozygous PK deficiency. Mutations located near the substrate binding site may change the conformation of the active site, resulting in a drastic loss of activity and severe clinical symptoms. Up to now, including these genetic defects, 21 missense, 1 nonsense and 2 splicing mutations, 2 insertions, and 3 deletions have been determined. G6PD deficiency is the most common metabolic disorder, and is associated with chronic and drug- or infection-induced hemolytic anemia. To date, sixty different mutations have now been identified. Except for three kinds of variants with small gene deletions or three nucleotide substitutions, all of those were found to be produced by one or two nucleotide substitutions. Molecular studies disclosed that all the class 1 variants associated with chronic hemolysis have the mutations surrounding either the substrate or the NADP binding site. Among rare enzymopathies, missense mutations have been determined in glucosephosphate isomerase deficiency, aldolase deficiency, triosephosphate isomerase (TPI) deficiency, phosphoglycerate kinase deficiency, and adenylate kinase deficiency. Compound heterozygous cases with missense mutation/nonsense mutation and missense mutation/decreased mRNA have been reported in TPI deficiency and diphosphoglyceromutase deficiency, respectively. In phosphofructokinase (PFK) deficiency, three kinds of 5'-splice junction mutations resulting in abnormally spliced PFK-M mRNA were identified. An exception is a hemolytic anemia due to increased adenosine deaminase activity. The basic abnormality appears to result from overproduction of structurally normal enzyme.
Anemia, Hemolytic↗
Hereditary hemolytic anemia caused by diverse point mutations of pyruvate kinase gene found in Japan and Hong Kong.
We identified four distinct point mutations in homozygous pyruvate kinase (PK) variants in Japanese and Chinese patients with chronic nonspherocytic hemolytic anemia. All gene abnormalities were missense mutations that caused single amino acid substitutions. 1261A (Q421K) and 1436A (R436H), which were identified in PK Sendai and PK Shinshu, had been found in unrelated Japanese and Amish PK variants, respectively. The clinical severity and extremely low residual erythrocyte PK activity of PK Shinshu as well as of the Amish PK might be caused partly by aberrant splicing, because the 1436A mutation changes a nucleotide at the last nucleotide in the exon 10. Recently, we diagnosed a 42-year-old Japanese woman with chronic nonspherocytic hemolytic anemia as having a homozygous PK deficiency. DNA sequencing of the variant PK gene showed a homozygous missense mutation at 1403GCT-->GTT, resulting in a single amino acid substitution from 468la-->Val. The gene mutation is likely to impair the allostericity of this enzyme, speculated from the tertiary structure. A homozygous missense mutation in PK Hong Kong, a boy of a non-Han southern Chinese minority group, was identified in exon 7 of the human L-PK gene, 941ATT-->ACT, resulting in a single amino acid substitution from 314lle-->Thr. The R-PK activity is expected to be severely affected, because the mutated amino acid residue is located between the 313 Lys and the 315 Glu, which are very important for acid-base catalysis and magnesium binding, respectively. Both the R- and M2-type PK were shown by polyacrylamide gel electrophoresis of the PK Hong Kong erythrocyte lysate, and this is the first report of a homozygous individual whose erythrocytes contain the immature (M2)-type isozyme.
Adult↗
Somatic mutations of the von Hippel-Lindau tumor suppressor gene in sporadic central nervous system hemangioblastomas.
Hemangioblastoma is one of the benign tumors in the central nervous system. It is often associated with the von Hippel-Lindau (VHL) disease, a well known hereditary tumor syndrome. It is believed that inactivation of both alleles of VHL tumor suppressor gene is essential in the tumorigenic processes in hemangioblastomas associated with VHL disease. The molecular basis for the development of sporadic hemangioblastomas is not known. Here, we analyzed 13 cases of primary sporadic hemangioblastomas for somatic mutations of VHL gene with single strand conformational polymorphism analyses of the tumor DNAs. We detected abnormal single strand conformational polymorphism pattern in 7 tumors (54%). Of these 7 possibly mutated tumors, we successfully characterized 3 tumors by direct sequencing. We were unable to sequence 4 tumors because of the poor quality of DNA obtained from paraffin blocks. Somatic mutations in the 3 tumors were 2 missense mutations and 1 microdeletion. These mutations were observed in 1 tumor in exon 1 and 2 tumors in exon 2. Our results suggest that mutations of VHL tumor suppressor gene are involved in the development of at least 20% of sporadic central nervous system hemangioblastomas.
Base Sequence↗
Molecular abnormality of erythrocyte pyruvate kinase deficiency in the Amish.
We describe the cellular and molecular biologic studies of the erythrocyte pyruvate kinase (PK) deficiency of the Amish deme in Pennsylvania. Nucleotide sequencing of the patient's PK gene showed a point mutation, CGC to CAC, corresponding to no. 1436 from the translational initiation site of the R-type PK (R-PK) mRNA, and it caused a single amino acid substitution from Arg to His at the 479th amino acid residue of the R-PK. The substituted Arg residue is located in the C domain of PK subunit, that is essential for both the intersubunit contact and the allosteric regulation. Because this enzyme shows the catalytic activity only as a dimer or tetramer, it is rational that the structural alteration would result in severe PK deficiency. To elucidate the effect of the PK deficiency on red blood cell (RBC) membrane, we performed the cellular studies of the patients' RBCs. Ouabain-insensitive K+ efflux was increased to 142% to 145% of normal controls and not inhibited by furosemide, as previously observed in HbSC disease RBCs.
Adult↗
Molecular recognition of the identity-determinant set of isoleucine transfer RNA from Escherichia coli.
Molecular recognition of Escherichia coli tRNA(Ile) by the cognate isoleucyl-tRNA synthetase (IleRS) was studied by analyses of chemical footprinting with N-nitroso-N-ethylurea and aminoacylation kinetics of variant tRNA(Ile) transcripts prepared with bacteriophage T7 RNA polymerase. IleRS binds to the acceptor, dihydrouridine (D), and anticodon stems as well as to the anticodon loop. The "complete set" of determinants for the tRNA(Ile) identity consists of most of the nucleotides in the anticodon loop (G34, A35, U36, t6A37 and A38), the discriminator nucleotide (A73), and the base-pairs in the middle of the anticodon, D and acceptor stems (C29.G41, U12.A23 and C4.G69, respectively). As for the tertiary base-pairs, two are indispensable for the isoleucylation activity, whereas the others are dispensable. Correspondingly, some of the phosphate groups of these dispensable tertiary base-pair residues were shown to be exposed to N-nitroso-N-ethylurea when tRNA(Ile) was bound with IleRS. Furthermore, deletion of the T psi C-arm only slightly impaired the tRNA(Ile) activity. Thus, it is proposed that the recognition by IleRS of all the widely distributed identity determinants is coupled with a global conformational change that involves the loosening of a particular set of tertiary base-pairs of tRNA(Ile).
Anticodon↗
Importance of anti-siphon devices in the treatment of pediatric hydrocephalus.
The effects of an anti-siphon device (ASD) on shunt flow and intracranial pressure (ICP) in 16 children with hypertensive hydrocephalus were examined using quantitative radionuclide shuntography (99mTc) with the children in supine and sitting positions. The average age of these patients was 9.5 years. Results were compared with those recorded in 36 patients with adult normal-pressure hydrocephalus (NPH). The closing pressure levels of shunt valve used were low in 8 cases, medium in 7 and high in 1. Half the children (8) had shunt systems with, and the other 8 without, ASD. In the children who had the shunt system without ASD, sitting shunt flow was significantly greater than supine shunt flow, which indicated overdrainage. Conversely, in children who had the shunt system with ASD, supine shunt flow was greater than sitting shunt flow. Because ASD prevented overdrainage, ICP was higher with the shunt system with ASD than with the shunt system without ASD. Without ASD, sitting shunt flow of children was lower than that of adult patients with NPH because of the lower hydrostatic pressure, which correlated with their height. Conversely, in the presence of a shunt system with ASD, sitting shunt flow of children was greater than that of adults, because of the higher ICP and lower hydrostatic pressure. The effect of ASD was smaller in children than in adults, because positive pressure over the ASD was greater (hypertension vs normal pressure) and negative pressure under the ASD was less (short vs tall) in children than in adults. Thus, in children the ASD was effective in preventing overdrainage.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Acute simultaneous bilateral vestibulocochlear impairment in neuro-Behçet's disease: a case report.
The central nervous system (CNS) is often a preferential target of Behçet's disease and diverse neurological manifestations have been described. Isolated hearing impairment or disequilibrium is also known to occur, but the simultaneous bilateral impairment of both vestibular and cochlear functions has been only rarely documented in Behçet's disease. A 52-year-old Japanese woman with neuro-Behçet's disease had meningoencephalitis, a profound thrombocytopenia, and bilateral vestibulocochlear impairment during the acute exacerbation. Although the CNS involvement was apparent, the clinical history and neuro-otological findings pointed to bilateral inner ear involvement rather than the brainstem or the 8th nerve lesions. She has made an excellent clinical response to pulse-dose methylprednisolone therapy with improvement in her neurological symptoms and in arresting the acute deterioration of hearing loss, but repeated audiograms failed to maintain the improvement with a modest dose of oral prednisolone. Since the bilateral vestibulocochleopathy can be as incapacitating as oculopathy in Behçet's disease, an early detection and prompt instillation of adequate corticosteroid therapy may be mandatory, although not curative.
Acute Disease↗
Immune complex-degradation ability of macrophages in MRL/Mp-lpr/lpr lupus mice and its regulation by cytokines.
Impaired clearance of circulating and/or deposited immune complexes (IC) by the mononuclear phagocytic system is one of the major factors in the pathogenesis of IC diseases. MRL/Mp-lpr/lpr (MRL/lpr) lupus mice spontaneously develop a lethal glomerulonephritis associated with IC deposition. The ability of macrophages to degrade phagocytozed IC and regulation of this degradation in MRL/lpr mice were examined. In 4-month-old MRL/lpr mice, macrophages accumulated in the affected glomeruli and these macrophages contained many phagosomes containing electron-dense bodies. When culture supernatant of human T cell line HUT102 was administered intraperitoneally into disease-bearing MRL/lpr mice, degradation of these electron-dense bodies in the macrophages in glomeruli was noted. We developed a quantitative in vitro assay for IC degradation activity of MRL/lpr resident peritoneal macrophages (RPM) using peroxidase-labelled IC derived from MRL/lpr mouse sera. The ability of the RPM to degrade IC was remarkably enhanced by the pretreatment with HUT102 cell products and the related human recombinant cytokines, lymphotoxin and IL-1 alpha. Moreover, pretreatment of RPM from non-diseased MRL/Mp-+/+ mice with the culture supernatant of spleen cells from diseased MRL/lpr mice reduced their IC degradation activity. These results suggested that the ability of macrophages to degrade IC in MRL/Mp strains of mice is under the regulation of cytokines, and the impaired ability in the disease-bearing mice may be the result of abnormalities in the cytokine system in these mice.
Animals↗
Immunoreactivity of neoplastic and non-neoplastic monocytoid B lymphocytes for DBA.44 and other antibodies.
AIMS--To evaluate the immunoreactivities of neoplastic and non-neoplastic monocytoid B cells (MBC) and compare them with hairy cell leukemia (HCL) and mantle cell lymphoma (MCL). METHODS--An immunohistochemical study of paraffin wax embedded sections was done on surgically resected specimens of spleens with MBC clusters from patients with gastric cancer (14 cases), tonsils (five cases), and lymph node (two cases) showing lymphoid follicular hyperplasia (LFH), submandibular lymph nodes containing MBC in Sjögren's syndrome (one case). Extranodal organs affected by MCL (three cases) and monocytoid B cell lymphoma (MBCL) (seven cases), and spleens from HCL (four cases) were also studied. These specimens were fixed in 10% formalin and routinely processed for paraffin wax embedding. Fresh spleen specimens from patients with liver cirrhosis (one case) and gastric cancer (seven cases) were snap frozen. RESULTS--Mantle zone lymphocytes were DBA.44, CD74 positive and showed a weaker reaction for CDw75 than marginal zone lymphocytes and MBC, which were almost DBA negative. In neoplastic diseases tumour cells in MCL were DBA.44, CD74, and CDw75 positive. MBCL showed a positive reaction for CD74 and CDw75, but positivity for DBA.44 was observed in only one of seven cases. The HCL specimens, all positive for DBA.44, showed a weaker reaction for CD74 and a stronger reaction for CDw75 than either MCL and MBCL specimens. CONCLUSION--These results show that mantle zone lymphocytes and MCL more closely matched HCL for reactivity to DBA.44 than MBC and MBCL. Reactivities for DBA.44 and CDw75 were greater in MBCL compared with its non-neoplastic counterpart, MBC.
Adult↗
Aleutian mink disease: puzzles and paradigms.
Aleutian mink disease (AD) is a naturally occurring persistent virus infection of mink caused by the Aleutian mink disease parvovirus (ADV). The classical form of AD, which occurs in adult mink, is notable for high titers of antiviral antibodies, hypergammaglobulinemia, plasmacytosis, and immune complex disease. In addition, there is a progressive renal disease characterized by mesangial proliferative glomerulonephritis and severe interstitial nephritis. Development of AD depends on both host and viral factors, and mink of certain genotypes fail to develop progressive disease when inoculated with low-virulence strains of virus. In newborn mink kits, ADV causes a fatal, acute interstitial pneumonitis associated with permissive viral replication in alveolar type 2 cells, but treatment of newborn kits with anti-viral antibody aborts the acute disease and converts into one resembling the persistent infection observed in adults. In infected adult mink, ADV is sequestered as immune complexes in lymphoid organs, but actual viral replication is restricted at the level of the individual cell and can be detected in only a small population of macrophages and follicular dendritic cells. ADV infection of mink primary macrophages and the human macrophage cell line U937 is antibody dependent and leads to the production of the cytokine interleukin-6. Furthermore, levels of interleukin-6 are increased in lymph node culture supernatants from infected mink. Chronic production of interleukin-6 may promote development of the immune disorder characteristic of AD.
Aleutian Mink Disease↗
Angiosarcoma developing from chronic pyothorax.
In our previous study, we suggested that long-standing pleural inflammation might be an etiological factor for development of pleural soft-tissue sarcomas, especially malignant fibrous histiocytoma and angiosarcoma (AS). To study the etiological importance of chronic pyothorax for development of pleural AS, a nationwide study of AS in Japan was carried out. Histological and clinical findings in 99 collected cases with AS were reviewed. Six (6%) of the 99 cases were chronic pyothorax-associated AS. Another three cases of pyothorax-associated AS previously reported by us were also included. They were eight males and one female from 45 to 74 yr of age (median 65 yr). All patients had a 15- to 40- (mean 30) yr history of chronic tuberculous pyothorax. Histologically, the tumors contained irregular, occasionally dilated vascular channels, which were invested by tumor cells with an epithelioid appearance. From the statistical data reported previously, annual incidence of AS is probably 0.01 to 0.02 per 100,000 population. Meanwhile, there was an incidence rate of pyothorax-associated AS among chronic pyothorax patients of 0.036 per 100 patients. Thus, the frequency rate of pyothorax-associated AS is supposedly over 3600-fold higher than that in normal population. The present study shows that chronic tuberculous pyothorax is one of the causes of AS development.
Aged↗
Occurrence of monocytoid B-lymphocytes in Hodgkin's disease.
The nature and frequency of occurrence of monocytoid B-lymphocytes (MBL) was examined in 118 cases of Hodgkin's disease. Monocytoid cells were present in six cases (5%), four nodular sclerosis and two mixed cellularity. These cells were CD20+, CD3-, CD45RO-, KP-1-, PGM1-, with occasional positive reaction for MB-1 and CD74, indicating their B-cell nature, i.e., MBL. The MBL were distributed in the periphery of the nodules of nodular sclerosis accompanying centrally located Reed-Sternberg cells, although Reed-Sternberg cells were observed in some MBL clusters. In the mixed cellularity, MBL were located in the para-follicular area occasionally adjoining the lymph follicles. Because previous studies suggested depressed immune function in autoimmune diseases, acquired immune deficiency syndrome, and older persons to be responsible for the occurrence of MBL, it is possible that in some patients development of foci of MBL under immunodeficient conditions progresses to Hodgkin's disease.
Adult↗
[Two patients with positive anticentromere antibody showing different clinical features of CREST syndrome or primary biliary cirrhosis (PBC)].
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Autoantibodies↗
[The clinical effect of factor XIII on drug-induced hemorrhagic cystitis].
The therapeutic effects of Factor XIII (F XIII) concentrate against drug-induced hemorrhagic cystitis (HC) was investigated. HC occurred in 4 children with malignant disease during anti-cancer chemotherapy. Two (CML and T-ALL) of 4 patients developed HC after the administration of high dose cyclophosphamide as conditioning for allo bone marrow transplantation or peripheral blood stem cell autografts, and the other 2 patients (rhabdomyosarcoma, Wilm's tumor) developed HC after the administration of ifosfamide for relapse. When F XIII concentrate at a dose of 20 to 230 U/kg was administrated immediately after the onset of HC, the symptoms, i.e., bladder irritability and macrohematuria disappeared within a few days. The F XIII serum levels of those patients were low (27-57%), and the levels increased (63-230%) after administration of F XIII concentrate. The two patients with relapsed solid tumor showed no symptoms of HC during subsequent ifosfamide treatment when F XIII concentrate was administrated to maintain a normal F XIII range. These results suggest that the administration of F XIII concentrate may be useful for the prophylaxis and treatment of drug-induced HC in patients with a low F XIII level.
Adolescent↗
[Regulation of aromatase in human choriocarcinoma cells].
To examine the mechanism regulating trophoblastic aromatase, we studied the effects of various agents on aromatase activity and the aromatase cytochrome P-450 (P-450arom) concentration in human choriocarcinoma JEG-3 cells. Aromatase activity was assessed by radioassay with [1 beta-3H] androstenedione. The P-450arom concentration was determined by an enzyme-linked immunosorbent assay with specific antibodies to P-450arom. Human chorionic gonadotropin (hCG) stimulated aromatase activity and increased the P-450arom concentration in a concentration-dependent (0.1-100 IU/ml) manner. Cholera toxin (CT), an adenylate cyclase activator, stimulated aromatase activity and the P-450arom concentration in a concentration-dependent (0.1-10ng/ml) and a time-dependent (12-72h) manner. 12-O-tetradecanoyl phorbol 13-acetate (TPA) (0.1-100ng/ml), a protein-kinase C activator, also stimulated aromatase activity and increased the P-450arom concentration. On the other hand, Ca2+ ionophore A23187, an agent increasing intracellular Ca2+ accumulation, inhibited aromatase activity and reduced the P-450arom concentration. The effects of CT, TPA and Ca2+ ionophore were additive. Aromatase activity was correlated with the P-450arom concentration. These results suggest that in JEG-3 cells the signal transduction system modulates aromatase activity by changing the P-450arom concentration.
Aromatase↗