Increased procollagen type III peptide in serum of rabbits exposed to diesel engine exhaust.
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Biomedical subjects
Publications and source records attributed to T Kanoh.
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We have previously reported that the beta-glucuronidase-treated urine of mice injected intraperitoneally with pyrene during exposure to NO2 contained highly mutagenic compounds such as nitropyrene metabolites when tested by the Ames assay using Salmonella typhimurium strain TA98. In the present study, we found that the formation of these mutagens was dose-dependent between 10 and 200 mg of pyrene per kg of body weight at 5 and 10 ppm of NO2. Further, to elucidate the substrate of nitration in vivo, we injected 1-hydroxypyrene, which is the metabolite of pyrene, to mice intraperitoneally during exposure to NO2. Since the results were the same as those obtained by injection with pyrene, we suggest that the pyrene was not nitrated directly but after its hydroxylation.
A long asymptomatic period is one of the characteristics of human immunodeficiency virus (HIV) infection, despite its fatal consequences. Antiviral defense in HIV-infected individuals controls viral replication during this period. In the present study, we demonstrate that peripheral blood leukocytes (PBL) of asymptomatic HIV-1 carriers, following exogenous HIV-1 infection in vitro, do not support viral replication. These cells do not produce detectable amounts of reverse transcriptase or accumulate unintegrated proviral DNA. This is a striking contrast to the behavior of HIV-1-infected PBL of seronegative individuals, which produce large amounts of RT and unintegrated DNA. Such resistance to HIV-1 replication is not seen in PBL of patients with advanced disease. Since the binding of HIV-1 to CD4 molecule is not impaired in PBL of asymptomatic carriers, the interference with HIV replication must occur after the stage of virus binding. PBL lose their resistance when CD8+ lymphocytes are removed. In addition, these PBL are not resistant to an exogenous infection with HIV-2. These observations suggest that certain populations of CD8+ lymphocytes of asymptomatic HIV-1 carriers operate on the target cells in PBL to block viral replication in an HIV-1-specific manner. Such CD8+ lymphocyte-mediated interference with HIV replication could play an important role in the maintenance of the period of disease latency.
Serum albumin concentrations and albumin metabolism were assessed in 150 patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and healthy subjects. Hypoalbuminemia was more marked in RA patients than in SLE patients. There was no correlation in RA patients between albumin levels and either disease activity or glucocorticosteroid administration; however, hypoalbuminemia in RA patients significantly correlated with juxta-articular erosions or with the incidence of peptic ulcer. The incidence of peptic ulcer was higher in RA patients with the combination of hypoalbuminemia and corticoid therapy, and reduced by the injection of anabolic steroid. In contrast, anabolic steroid did not improve hypoalbuminemia and bony erosions in the patients. The fractional catabolic rate of albumin was similarly elevated in both RA and SLE, while the absolute catabolic rate was increased to a greater extent in SLE patients. This explains the differences in serum albumin concentration between the patients with RA and SLE.
We have recently observed an unusual case of multiple myeloma with double Bence Jones proteinuria. Immunofixation clearly demonstrated monoclonal light chains of both kappa and lambda type in the urine. By double immunofluorescence staining, 11% of myeloma cells were found to be double producers. The marginal portion of cytoplasmic Russell bodies was stained with anti-lambda, while the core was diffusely stained with anti-kappa. Our results indicated that cells of common clonal origin produced Bence Jones proteins of both kappa and lambda type. No reference is found in the literature to such a finding in double Bence Jones proteinuria. In this article, in addition to the summary of nine cases of double Bence Jones proteinuria, possible explanations for this rare phenomenon are described to give a better understanding of this entity.
This article provides an overview of the clinical presentations of human immunodeficiency virus (HIV) infection, including some of the early and less severe diseases, such as acute HIV infection, persistent generalized lymphadenopathy (PGL) and acquired immunodeficiency syndrome (AIDS) related complex (ARC), and full-blown AIDS. The salient features of 24 cases of AIDS reported in Japan were summarized. There was no difference in clinical features between hemophiliacs (16 cases) and homosexual males (8 cases), except for a preponderance of cases of cytomegalovirus infection in the latter group. The new prognostic staging system, based on physiologic deficits, for AIDS was applicable to Japanese patients with AIDS. In addition, a three-year follow-up study on two of HIV-infected homosexuals was presented.
A number of different combination regimens including high-dose corticosteroids (HDCS) have been widely used in an attempt to achieve better results for relapsed or alkylating agent-resistant multiple myeloma (MM). A major complication of these regimens is commonly said to be infection. In addition, we have had occasion to point out that a rapid progression of systemic amyloidosis can be one of serious complications of HDCS therapy in MM. The patient, born in 1940, was diagnosed of having Bence Jones (BJ) type MM in 1987. The conventional therapy including alkylating agents and interferon-alpha induced a partial remission of 22 months' duration. After the relapse, 2 courses of vincristine, adriamycin plus high-dose dexamethasone resulted in a reduction of the excreted amount of urinary BJ proteins with symptomatic improvement. However, the following clinical features indicating systemic amyloidosis occurred in succession within 2 months after beginning the therapy: submandibular swelling, giant tongue, shoulder pad sign, carpal tunnel syndrome, low voltage on ECG and recurrent diarrhea. The biopsy specimens from the submandibular gland revealed amyloid deposition. In the present case, a rapid progression of systemic amyloidosis is supposed to be attributable to the HDCS therapy. The possible mechanism of enhancement of amyloidosis by HDCS therapy is discussed.
The term, "monoclonal gammopathy of undetermined significance (MGUS)" is used because it is not known at the time of recognition whether the M-component will remain stable or will develop into multiple myeloma (MM) or related disorders. Recently, we have encountered a case of MGUS in which a diagnosis of primary amyloidosis (PA) was made more than 10 years after the recognition of an M-component in the serum. A 64-year-old man presented in 1979 for evaluation of monoclonal gammopathy. The level of M-component (IgG-lambda) in the serum was 1.6 g/dl. The urinary Bence Jones proteins (BJP) were negative. Bone marrow aspirate contained 9.8% plasma cells. Skeletal surveys were normal. A diagnosis of MGUS was made. In 1982, a trace amount of BJP was detected in the urine. Since 1988, carpal tunnel syndrome, angina pectoris and congestive heart failure developed in succession. In November 1989, the patient was admitted to Kyoto University Hospital for examination. Serum electrophoretic pattern remained unchanged. The excreted amount of urinary BJP was less than 0.3 g/day. Bone marrow aspirate contained 5.4% plasma cells. Histologic studies of bone marrow biopsy specimens revealed amyloid deposition. An echocardiogram was thought to reveal amyloidosis. Significant uptake of Tc-99m (V) DMSA was found in carpal regions, kidneys and heart. A diagnosis of PA was made. It is noteworthy that the development of PA did not accompany an increase in the serum M-component. An early diagnosis of PA as well as MM should be kept in mind in the follow-up study of patients with MGUS.
Elastolytic cutaneous lesions were the initial manifestation of amyloidosis in two patients with multiple myeloma. The skin of the fingertip was noticeably soft, loose, and redundant. The skin of the fingers was depressed with pressure and remained depressed for an abnormally long period of time. Amyloid deposition in the dermis was demonstrated in both cases. In addition, fragmentation and a decrease of elastic fibers in the dermis were observed. Possible explanations for the pathogenesis of such skin lesions were also discussed.
A 55-year-old man, who has been on follow-up observation with chronic atrial fibrillation, came in with a sudden onset of chest pain on July 31, 1986. He was diagnosed as having acute myocardial infarction indicated by abnormal ECG, elevated serum enzyme and characteristic signs of echocardiography. Emergency coronary angiography was performed 2 hours after the onset of chest pain, and it was reported as showing total obstruction of the distal left anterior descending artery. Percutaneous transluminal coronary recanalization using 1,200,000 units of urokinase was unsuccessful. The repeated angiography performed 40 days later, showed normal coronary arteriogram, but left ventriculogram revealed akinesis of the apical segment. Furthermore, left atrium opacified in the levophase of pulmonary arteriogram indicated left atrial thrombus. The cause of the myocardial infarction was considered to be coronary embolism from the left atrial thrombus with atrial fibrillation. It must be the first report documented by coronary angiography, of coronary thrombo-embolism due to chronic atrial fibrillation without any underlying disease.
To assess the effect of aging on neutrophil (PMN) functions and the parameters related to reactive oxygen species (ROS), we measured the following in blood samples from 166 asymptomatic aged individuals: PMN activities including chemotaxis, phagocytosis and generation of ROS; the activity of superoxide dismutase (SOD) of blood cell; and serum lipid peroxide levels. Compared with non-aged adults, the older individuals showed markedly attenuated PMN chemotaxis, and slightly elevated serum lipid peroxide levels. Other parameters were not significantly different between the two aged groups. In contrast both to the elderly group as a whole and to the subgroup 65 to 79 years old, the subjects over greater than or equal to 80 years old showed normal PMN chemotaxis and serum lipid peroxide levels, as defined by the young adult control group. Thirty-two subjects who entered the study at ages 69 to 72 years were followed with serial assays for seven years; twenty-one of these subjects died during this observation period. There was a striking and significant difference between the survivors and nonsurvivors with regard to PMN chemotaxis and serum lipid peroxide levels; even when asymptomatic upon initial examination, the nonsurvivors showed diminished PMN chemotaxis and elevated lipid peroxide levels. It seems from both the cross-sectional and longitudinal parts of our study that PMN chemotaxis and serum lipid peroxide levels correlate with survival to advanced age.
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In two cases of vacuolated plasma cells, one of which was associated with primary macroglobulinemia and the other was with kappa-chain Bence Jones multiple myeloma, we examined the immunopathological features of the vacuoles in order to know whether the Ig-secreting system or the lysosomal system is of importance in the process of vacuole formation. Immunofluorescent studies detected no Ig in the vacuoles. Detection of intracellular Ig by immunoelectron microscopic technique revealed that Ig was localized only in a small portion of the vacuoles but not in most vacuoles. Even when Ig was included in the vacuoles, only the contents of the vacuoles were positive for Ig but their demarcating membrane was negative for Ig. In contrast, electron microscopic studies of acid phosphatase activity revealed the presence of its activity in all vacuoles. These findings suggest that the lysosomal system but not the Ig-secreting system may play a major role in vacuolation of these myeloma cells.
A 70-year-old man, diagnosed to have multicentric giant lymph node hyperplasia (MGLNH) of the plasma cell type by postmortem examination, had double cancers of the thyroid and kidney, as well as a large amount of ascites and persistent serositis. Serum immunoelectrophoresis showed monoclonal IgG (lambda). Using the paired immunofluorescent technique, monoclonal plasma cell proliferation was observed on the section of a lymph node. The cause of the ascites was speculated to be the combined influence of peritonitis, renal dysfunction and obstruction of abdominal lymphatic ducts. Occurrence of double cancers and persistent peritonitis suggest the long-standing faulty immune regulation in MGLNH.
A case of large granular lymphocyte (LGL) leukemia with ascites and CNS involvement was reported. A 39-year-old Japanese female was admitted to our hospital in March, 1987 because of high fever. Her clinical and hematological features were characterized by generalized lymphadenopathy, marked hepatosplenomegaly, high serum LDH level (3,257 mU/ml), marked leukocytosis (71,000/microliters) with 74% LGLs and bone marrow infiltration with 57% LGLs. Despite of chemotherapy, ascites, retroperitoneal mass and CNS involvement developed and she died of sepsis after three months. LGLs from the patient's blood, marrow and ascites, stained positively for acid phosphatase. These LGLs were E rossete+ and Fc (IgG) receptor+ and were positive for CD2, OKM1, HLA-DR and Leu11, but were negative for CD1, CD3, CD4, CD8 and Leu7 as well as for terminal deoxynucleotidyl transferase activity. The natural killer activity against K562 target cells was high and was significantly augmented after stimulation by recombinant human interleukin 2. These LGLs also demonstrated normal antibody-dependent cytotoxicity activity. Cytogenetic study on bone marrow cells and ascitic cells revealed clonal chromosomal abnormalities. These clinical, hematological, immunological and cytogenetic findings suggest that this patient had a neoplastic proliferation of natural killer cells.
A 62-year-old woman with chronic neutrophilic leukemia (CNL) is described. She presented in February 1988 for evaluation of leukocytosis of 3 years' duration with no complaint. Physical examination was normal. The leukocyte count was 20,100/microliters with 70% segmented neutrophils and 12% band forms. A myelogram showed marked myeloid hyperplasia and plasmacytosis (5.9%). Neutrophil alkaline phosphatase score, serum lysozyme and vitamin B12 levels were elevated. Cytogenetic analysis of the marrow aspirate showed normal karyotype, with no Philadelphia chromosome. Total serum protein (TP) was 7.5 g/dl with increased beta-globulin (23.5%), identified as monoclonal IgA kappa (3.3 g/dl) on immunoelectrophoresis. No activity of G-CSF was detected in the serum. A retrospective study revealed that the beta-globulin level was normal (6.3%, TP 6.9 g/dl) in 1980 and that it was slightly increased (11.6%, TP 7.0 g/dl) without leukocytosis (5,900/microliter) in 1981. In 1985, when leukocytosis obviously existed (9,900/microliter), the percentage of beta-globulin was increased to 17.5% (TP 7.2 g/dl). The possibility that monoclonal gammopathy preceded the leukocytosis must be admitted. On the basis of our observation, it is assumed that CNL and monoclonal gammopathy may be blood dyscrasias derived from a common precursor cell or that the immunological abnormality associated with monoclonal gammopathy may be implicated in the development of CNL.