Tadashi Kanoh

Neutrophil chemotaxis, phagocytosis and parameters of reactive oxygen species in human aging: Cross-sectional and longitudinal studies

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.

Selective IgA deficiency in Japanese blood donors: frequency and statistical analysis.

Abstract. The incidence of selective IgA deficiency (SIgAD) was determined in a healthy adult population of 222,597 Japanese volunteer blood donors. Of the blood donors screened, only 0.007% (1:14,840) were found to be IgA‐deficient (less than 10 mg/dl) by means of the double diffusion method, while 0.005% (1:18,500) were less than 5 mg/dl, and 0.003% (1:31,800) were less than 1 mg/dl by means of the single radial immunodiffusion method. Statistical analysis of the results clearly showed that the incidence of SIgAD in Japanese blood donors is very much lower than that in blood donors of European ancestry. The Japanese population may occupy a unique position in the ethnical peculiarities. Anti‐IgA antibodies were found in 3 (25.0%) of 12 IgA‐deficient blood donors whose IgA levels were less than 5 mg/dl, a prevalence rate comparable to that in donors of European ancestry. Although it is difficult to develop a suitable file of IgA‐deficient donors in Japan, the establishment of a Rare Donor Registry System on IgA deficiency is a matter of urgency.

The ratio of lipidperoxides to superoxide dismutase activity in the skin lesions of patients with severe skin diseases: An accurate prognostic indicator

We studied 35 patients with active inflammatory skin diseases, measuring the levels of lipidperoxides and of the oxygen radical scavenging enzyme superoxide dismutase (SOD) in biopsy specimens of skin lesions. Lipidperoxide levels were markedly elevated in all patients. In fifteen patients with disease that was severe and highly resistant to therapy, SOD activity was only slightly increased, in comparison with normal controls. In contrast, in the twenty patients with mild disease that responded well to therapy, SOD activity was markedly elevated. The ratio of lipidperoxide levels to SOD activity was thus an accurate prognostic indicator, being elevated only in the group not responding to treatment. These findings suggest that the severity of allergic inflammatory skin disease and/or the response to treatment may in part be governed by the degree to which the patients SOD activity is up-regulated in response to the generation of tissue-damaging substances such as lipidperoxides. Interestingly, our studies revealed the SOD activities of both normal and inflamed skin to be unexpectedly high; our data suggest that SOD plays a critical role in protecting the skin from the effects of oxygen radicals and ultraviolet light.

Fulminant clonal expansion of large granular lymphocytes: Characterization of their morphology, phenotype, genotype, and function

A 39‐year‐old woman exhibited abrupt malignant transformation of the large granular lymphocytes (LGL) after a chronic course of Tγ‐lymphoproliferative disease (Tγ7‐LPD). The Tγ‐lymphocytes were CD2+, CD3‐, CD8‐, CD16+, Leu7‐, and Leul9+ with morphologic characteristics of LGL. Newly appearing LGL were much larger and had more prominent azurophilic granules. Although fundamentally they had the same phenotype as the LGL in chronic stage, they showed increased la‐like antigen and decreased CD16 antigen expressions. Immunoglobulin (Ig) G‐kappa type monoclonal component was detected in the patients serum. The LGL showed a germ‐line configuration for T‐cell receptor (TCR) beta and gamma chain genes, whereas the clonal chromosomal abnormalities indicated the neoplastic nature of the LGL. The LGL exhibited competent natural killer (NK), interleukin 2 (IL2) activated killer (AK), and antibody‐dependent cell‐mediated cytotoxicity (ADCC) activities. The LGL may have derived from NK cells at their mature stage with prethymic phenotype and may have influenced the homeostasis of the patients humoral immune response.

The effect of aging on cutaneous lipid peroxide levels and superoxide dismutase activity in guinea pigs and patients with burns

Cutaneous lipid peroxide levels and superoxide dismutase (SOD) activity in non-aged and aged guinea pigs were measured between 15 min and 7 days after experimental infliction of burns. Skin burns on non-aged and aged patients were also subjected to these assays. In non-aged guinea pig skin burns, lipid peroxide levels increased from 24 hr to the fourth day after the burn infliction, while SOD activity did not increase but showed a slight decrease 12 hr and 24 hr post-burn. On the other hand, while the aged group showed a more increase in skin lipid peroxide levels compared to that seen in non-aged mice, skin SOD activity began to decrease from 30 min post-burn, the maximum decrease being reached on the second day. The activity did not return to normal by the 7th day. In non-aged patients skin burns showed increases in both lipid peroxide levels and SOD activity, while in aged patients, though they showed a marked increase in lipid peroxide levels, SOD activity remained unchanged. The present study indicated that, although in our recent study, skin SOD activity of healthy elderly people was found to be comparable to that in non-aged individuals, the capacity for induction of SOD activity under oxygen stress differed with age in both guinea pig and human burn sufferers. Furthermore, this induction capacity seemed to vary from species to species.

Electromagnetic wave emitting products and “Kikoh” potentiate human leukocyte functions

Tourmaline (electric stone, a type of granite stone), common granite stone, ceramic disks, hot spring water and human palmar energy (called “Kikoh” in Japan and China), all which emit electromagnetic radiation in the far infrared region (wavelength 4–14 µm). These materials were thus examined for effects on human leukocyte activity and on lipid peroxidation of unsaturated fatty acids. It was revealed that these materials significantly increased intracellular calcium ion concentration, phagocytosis, and generation of reactive oxygen species in neutrophils, and the blastogenetic response of lymphocytes to mitogens. Chemotactic activity by neutrophils was also enhanced by exposure to tourmaline and the palm of “Kikohshi” i.e., a person who heals professionally by the laying on of hands. Despite the increase in reactive oxygen species generated by neutrophils, lipid peroxidation from unsaturated fatty acid was markedly inhibited by these four materials. The results suggest that materials emitting electromagnetic radiation in the far infrared range, which are widely used in Japan for cosmetic, therapeutic, and preservative purposes, appear capable of potentiating leukocyte functions without promoting oxidative injury.

Methyltransferase and phospholipase A2 activity in the cell membrane of neutrophils and lymphocytes from patients with Behçet's disease, systemic lupus erythematosus, and rheumatoid arthritis

Phospholipid methylation and phospholipase A2 activation in the membrane of neutrophils and lymphocytes, which participate in the induction of cell activation, were assessed in patients with Behçets disease, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). [3H-methyl] incorporation and phospholipase A2 activity of neutrophils from active cases of Behçets disease and RA were significantly increased compared with normal controls. In lymphocytes from the patients with active Behçets disease and RA, a significant increase in methyltransferase activity and a marked enhancement of phospholipase activity were found. A modest increase in these two membrane phospholipid enzyme activities was observed in lymphocytes of patients with active SLE. In addition, these enzyme activities were significantly enhanced in normal leukocytes preincubated with serum from patients with active SLE and malignant RA. The potentiated functions of neutrophils and lymphocyte abnormalities in the patients tested thus seem to be at least partly due to an increase in these enzymatic activities in the cell membrane.

IgM-producing gastric plasmacytoma.

A case of gastric plasmacytoma is reported in an 81‐year‐old woman. Immunofluorescent and immunoelectrophoretic studies showed that the tumor cells produced IgM‐λ molecules, whereas no monoclonal immunoglobulin could be detected both in the serum and in the urine. Of more than 60 reported cases of gastric plasmacytoma, only a few reports referred to the production of monoclonal immunoglobulin by the tumor cells. This case is the first one of IgM‐producing gastric plasmacytoma. Moreover, the produced IgM was found to be 7S‐IgM. It is extremely rare that 7S‐IgM alone is detected in the absence of 19S‐IgM.

Soft-tissue uptake of technetium-99m MDP in multiple myeloma.

Abnormal accumulation of Tc-99m MDP in the lungs and stomach was observed in a patient with multiple myeloma and refractory hypercalcemia. There was no roentgenographic evidence of calcification. At postmortem examination, the presence of amyloid deposits was confirmed in both organs, while the corresponding metastatic calcification was demonstrated only in the gastric mucosa. It seems likely that, in our case, soft-tissue localization of bone-seeking agent was attributable to the presence of amyloid deposits rather than metastatic calcification. No cases showing the combined occurrence of amyloid deposition and metastatic calcification in soft-tissues have previously been demonstrated to concentrate bone-seeking agent.

Intracellular formation of amyloid fibrils in Myeloma. Cytochemical, immunochemical, and electron microscopic observations

Needle‐like, rod‐shaped, and rhomboid intracytoplasmic crystalline inclusions were found in myeloma cells from the bone marrow of a patient with IgA‐κ and Bence Jones‐κ type multiple myeloma. Cytochemical, immunochemical, and electron microscopic studies revealed that these inclusions consisted of at least three kinds of components: kappa light chain crystals, lysosomal enzymes, and amyloid fibrils. The coexistence of these three kinds of inclusions in one myeloma cell suggests an intracellular site for the formation of amyloid fibrils. From these observations, the authors postulated that the excessively produced light chains were transported to the Golgi apparatus where they were transformed into crystalline inclusions, and thereafter, digested by lysosomal enzymes to form amyloid fibrils. The demonstration of crystalline inclusions which reacted exclusively with antisera against free light chains indicates that the Bence Jones protein is a precursor of amyloid light chain.