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The amount of monoclonal immunoglobulin (M protein) distinguishes multiple myeloma (M) from mono- clonal gammopathy of undetermined significance (MGUS) and indicates the effectiveness of treatment for MM. It should be calculated by serum total protein (g/dL) and M peak ratio (%) on the densitometry of se- rum electrophoresis. However, the ordinary method possibly overestimates the amount of M protein, be- cause this method utilizes the area from the baseline of the M peak (baseline method). For the more accu- rate measurement of M protein, in this study, we evaluated a capillary electrophoresis system that enables to extract the proper area of M peak by manual operation (peak method). Three serum samples with positive M protein were mixed with M protein negative serum at various ratio, and the measured values of M protein were compared with the theoretical values for both baseline and peak methods. All the results showed that the peak method gave the values close to the theoretical values compared with the baseline method. Espe- cially, the less M protein positive serum was mixed, the further the values by the baseline method parted from the theoretical one. In conclusion, the peak method using a capillary electrophoresis system should be introduced for the accurate quantification of M protein. [Original].

Amyloidosis is one of the most well-known protein-misfolding diseases caused by the deposition of insolu- ble amyloid fibrils in extracellular spaces. At least 31 amyloid fibril proteins have been identified. To elu- cidate the pathogenesis and diagnose the type of amyloidosis, mass spectrometric techniques, including liquid chromatography/tandem mass spectrometry and matrix-assisted laser desorption/ionization time of flight mass spectrometry, have been widely used for the analysis of biological samples, such as serum, urine, and tissues. We review new insights into the diagnosis and pathogenesis of amyloidosis using several mass spectrometric methods. [Review].

Serum IgG, IgA, and IgM are routinely measured by turbidimetric immunoassay (TIA), nephelometric immunoassay (NIA), and latex agglutination turbidimetric immunoassay (LATIA) while IgD and IgE, which are present in low concentrations, are usually measured by LATIA and other sensitive assays. There were some differences between LATIA and TIA in the values obtained from lyophilized serum, and sera with monoclonal proteins. We successfully solved the problem by dissociated and/or aggregated immunoglobulins treated with a newly prepared reagent. The difference caused a remarkable improvement thus realizing a coincidence in the measured values on LATIA and TIA.

Since the immunoglobulin levels of survey samples for the survey of Japanese Association of Medical Tech7ologists in 2003, especially the IgA and IgM, became different by the immunological methods (LAIA [latex agglutination immunoassay] and TIA [turbidimetric immunoassay]), the cause of difference was investigated. From the results of gel filtration and immunoblotting analysis, it was suggested that profiles of the reaction of purified IgA and IgM polymers in survey samples were different on each method. In the case of M protein, also, there were higher levels of IgM and IgA type M protein by TIA and SRID methods than other methods even though the precipitation curve was obscure. Similarly, several samples from patients with M protein demonstrated higher values by SRID method than that of other methods. When these samples were analyzed by gel filtration and immunoblotting, they did not indicate the presence of the polymeric IgM. It will be suggested that non-specific reactions on TIA (weak reaction) and SRID (unusual precipitin line) methods were present. Furthermore, in a case of IgM type M protein, IgM level was twice higher by LAIA than that by TIA. However, it did not indicate any polymer or fragment of IgM by gel filtration and immunoblotting. Accordingly, it was assumed that the difference in measured values between the methods was attributable to the difference of the reaction to the samples.

Two cases with abnormal laboratory data due to interaction between immunoglobulins and other serum proteins are described. Case 1 was a patient with lactate dehydrogenase (LD) -IgG3 complex whose serum LD value was moderately elevated. Case 2 were nondiabetic patients with IgA type M-proteinemia who had significantly increased serum fructosamine (FRA). The IgG3 in Case 1 was found to be conjugated to LD by immunoprecipitation assay. The LD-IgG3 complex was easily dissociated by affinity chromatography on 5'-AMP or Cibacron Blue F3G-A. The relative molecular weights of the patient's gamma3 chains and light chains were 67,000 and 28,000, respectively, by Western blotting, which corresponded to the expected values. However, the patient's IgG3 did not react to the anti-kappa and anti-lambda light chain antibodies in Immunofixation electrophoresis. Serum FRA concentrations were higher in patients (Case 2) with IgA type M-proteinemia or polyclonal hyper-IgA than those with the IgG type or IgM type. The sera from the patients with IgG or IgM type M-proteinemia had FRA only at the position of albumin, but 11 of 13 sera with IgA type M-proteinemia stained for glycoprotein at the position of the M-protein band as well as the albumin band. The abnormal precipitin arcs of IgA-albumin complex were observed in 11 of 13 sera from patients with IgA type M-proteinemia that were glycosylated at the position of M-protein band.

The heterogeneities of tissue enzymes and the enzyme distribution patterns of organs, tissues and plasma have now been established by many findings in various cases and diseases. Based on these precise laboratory data, the fields of clinical enzymology has been developed so as to analyze the very specific pathophysiological state in specific disorders. The characteristics of tumor-producing enzymes and genetically modified enzymes were additionally clarified by advances in molecular technology. Enzyme linked immunoglobulins were newly categorized enzyme abnormalities found in plasma enzymes. Genetical abnormalities of plasma enzymes fully explained the clotting abnormalities, hyper coagulability and hyperlipidemia. Based on these advances, the roles and future of clinical enzymology will be presented shown and discussed in this symposium.

To evaluate chronic immune effects of endocrine disruptors, serum autoantibodies and immunoglobulin concentrations were studied in patients with Yusho. Autoantibodies were present in some patients of Yusho; 45.6% for antinuclear antibody, 12.7% for rheumatoid factor and 11.1% for thyroglobulin antibody. LE factor was not detected. Serum levels of immunoglobulin A(IgA), immunoglobulin G(IgG) and immunoglobulin M(IgM) were elevated in 12.7%, 24.1% and 8.9%, respectively. Thyroglobulin antibody was detected in 19.5% of Yusho patients with high PCB concentration(higher than 3.0 ppb), and in only 2.5% of patients with low PCB concentration (lower than 2.9 ppb). Furthermore, the mean absolute density of CD4 positive lymphocytes was higher in patients with high PCB concentration than in patients with low PCB concentration. We conclude that autoantibodies in patients with Yusho are frequent, and it may be associated with the increase of helper/inducer T cells. Effects of lactational exposure to chlorinated dioxins and related chemicals on lymphocyte subpopulations in Japanese babies were also studied. Estimated total TEQ intakes of chlorinated dioxins and related chemicals from the breast milk correlated negatively with the percentages of CD8 positive lymphocytes. It is showed that exposure to background levels of chlorinated dioxins and related chemicals through breast milk may cause some immunologic disorder.

To evaluate chronic immune effects of polychlorinated biphenyl (PCB), serum immunoglobulin concentrations and autoantibodies were studied in 79 patients with Yusho in 1997. Serum levels of immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) were elevated in 10 cases (12.7%), 19 cases (24.1%) and 7 cases (8.9%), respectively. Autoatibodies were present in some patients of Yusho; 10 cases (12.7%) for rheumatoid factor and 36 cases (45.6%) for antinuclear antibody. LE factor was not detected. There were no significant correlations between blood PCB concentrations and serum immunoglobulin concentrations, or presence of autoantibodies. We conclude that antinuclear antibody in patients with Yusho is frequent, although it may not be associated with blood PCB concentration.

An immunological study was carried out in 50 patients with etiology unknown sensorineural hearing loss, including the following: 12 low tone deafness, 7 sudden deafness, 8 unilateral deafness, 7 idiopathic bilateral progressive sensorineural hearing loss and 14 other bilateral sensorineural hearing loss. Twenty-five out of 50 of the cases demonstrated immunological abnormalities. A full array immunological tests were performed with the following results. High immnunoglobulin titers showed in 18 out of 50 cases. Six cases were positive for antinuclear antibody. The anti-DNA antibody assay revealed high titers in 2 cases. Also, anti-rheumatoid factor antibody assay showed high titers in 6 cases while abnormal values of complements in serum were detected in 6 cases, though an immune complex was demonstrated in only one case. Also, it was noted that six patients with immunological abnormalities have autoimmune diseases. The above results indicated that some cases of etiology unknown sensorineural hearing loss may have an immunological link.

We compared clinical findings in 12 cases of systemic lupus erythematosus (SLE) in boys with those in 49 cases in girls. The age at which SLE developed in boys was consistent with that of infantile SLE and there was no age specificity. Momy cases in boys were diagnosed earlier as compared with cases in girls. Symptoms of infantile SLE, such as fever, arthalgia, butterfly rash, and urinary abnormalities, did not differ between boys and girls. However, a higher percentage of boys (58.3%) had central nervous system complications at onset than did girls (30.6%). Platelet counts tended to be higher in boys than in girls, a finding that suggests SLE tends to be more severe in boys than in girls. The incidence in the appiarance of LE cells, anti-Sm antibodies and immune complexes was higher in boys than in girls. Type IV or V renal pathologic changes (World Health Organization Histologic Classification) were present in 70% of boys. Our findings suggest that SLE in boys is more severe than that in girls and is more likely to be associated with central nervous system complications and severe renal complications.

Valve detachment or pseudoaneurysm is a well known complication of surgical treatment for cardiovascular disease due to aortitis syndrome. Although the preoperative management of inflammation by steroid therapy is very important, occasionally, the operation in active phase might be recommended because of progressive heart failure or impending rupture of aortic aneurysm. The pathology of aortitis syndrome is related to immunological abnormality, but there has been little information concerning the immunological factors. In order to evaluate the relationship between immunological factors and surgical results in patients with aortitis syndrome, immunological examination was obtained before surgery in 12 patients. Cardiovascular lesions due to aortitis syndrome were aortic regurgitation in 6 patients, annuloaortic ectasia in 1 patient, aortic arch aneurysm in 1 patient, mitral regurgitation in 2 patients, and coronary artery disease in 2 patients. Hospital mortality including initial operative death was not found. However, 6 late death (50%) occurred at late time with the mean of 23.8 months because of severe complications such as valve detachement or pseudoaneurysm after operation. In a comparison of the preoperative immunological values between survival group and late death group, immunoglobulins such as IgG, IgA, C3 and C4 were significantly higher in late death group. According to the recurrence of inflammation, the patients were divided into three groups. Group A included 3 patients who remains in active phase after initial operation in active phase. Group B included 3 patients who changed to active phase after initial operation in inactive phase. Group C included 6 patients who remains in inactive phase after initial operation. In a comparison among 3 groups, IgG and C4 showed no significant difference. However, IgA and C3 of group C were significantly lowest among three groups. This outcome is considered to be related to existence of latent inflammation. At operation, insertion of rigid prosthesis to fragile position due to latent inflammation may stimulate immunological reactions. We conclude that the preoperative values of the immunological factors, especially IgA and C3, are reliable predictors in postoperative prognosis.

In 79 RA patients treated with Bucillamine (Bu) we monitored IgG, A, M and total protein concentration x gamma-globulin% (Ig) before and after Bu. All of these four were lowered after Bu in both groups with and without adverse reaction. In the group with adverse reactions the serum level of IgG, A and Ig was significantly lower after Bu treatment than in the group without adverse reactions. The decreases of IgG and IgA were statistically significantly greater in the group with adverse reactions than those in the group without adverse reaction. The serum level of IgM after Bu in the effective group was significantly lower than that in the non-effective group. We also examined lymphocyte stimulation test (LST) in 44 RA patients treated with Bu. In the effective group Bu inhibited lymphocyte proliferative response to PPD more significantly than in the non-effective group. Bu also inhibited lymphocyte proliferative response after stimulation with PPD in the non-effective group doseresponsively. We concluded that the considerable decreases of IgG and IgA might correlate with the adverse reactions of Bu. The decrease of IgM and inhibition of LST with Bu might correlate with the efficacy of Bu.

To clarify the alteration of serum immunoglobulin levels with age, serum immunoglobulin and other parameters (age, symptoms, blood biochemical parameters, etc.) of inhabitants (213 persons; 63 men, 150 women) of a remote island in Shimane Prefecture were studied. Their subjective symptoms were collected by means of a questionnaire and various blood parameters were measured. These data were analyzed by t-test and multivariate analysis. The IgM level was decreased with age and each immunoglobulin level correlated with the total-protein level in serum. The IgG level of the subjects feeling fatigue was higher than that of the subjects not feeling fatigue.

Leukotriene B4 (LTB4), an arachidonic acid metabolite released by neutrophils, is involved in the regulation of the host immune response to antigenic stimulation. Furthermore, LTB4 affects the chemokinesis, aggregation, and enzyme release of neutrophils and stimulates activity of cytotoxic T cells, natural killer cells and suppressor T cells. On the other hand, smoking typically results in inflammatory stimulation of the lung, and long-term smoking can cause chronic stimulation. In this paper, we report the measurement of LTB4, IgG, IgA, IgM, IgD and IgE in sera of cigarette smokers who did not have an allergic reaction (group 1), non-smokers who also had no history of allergy (group 2) and non-smokers who had delicate allergic conditions (group 3). The mean LTB4 concentration in serum of group 1 was nearly 3.3-fold greater than in group 2 and 2-fold greater than in group 3, being 430 +/- 55 (Mean +/- S.D.), 130 +/- 22 and 220 +/- 14 pg/ml, respectively. Concentrations of IgG, IgA, IgM, IgD and IgE of all volunteers were in the normal healthy range. The mean concentration of IgE in the serum of group 1 did not change significantly within one day. It was 35 +/- 4 IU/ml in the morning, 34 +/- 4 IU/ml in the afternoon, 31 +/- 2 IU/ml in the evening and 32 +/- 4 IU/ml the next morning. But in group 3 the IgE concentration changed significantly within one day, being < 25 IU/ml in the morning, 97 +/- 7 IU/ml in the afternoon, 97 +/- 7 IU/ml in the evening and 25 +/- 14 IU/ml the next morning.(ABSTRACT TRUNCATED AT 250 WORDS)

In Japan, the isolation rate of HIV-1 has increased in recent years, and has become as high as 36.7% in 1991. In order to evaluate the onset of AIDS, we have collected various HIV markers, which were obtained from surveillance committee of Natural History. These data include a total of 1991 specimens (actual number 556 individuals) from Japanese hemophiliacs and non-hemophiliacs since 1985. The data analysed CDC stage, leucocyte counts, lymphocyte counts, CD4+ cell counts, CD8+ cell counts, CD4/CD8 ratio and immunoglobulins (IgA, IgG, IgM). The results indicate that in HIV-isolation positive patients, leucocyte counts, lymphocyte counts, CD4+ cell counts, CD8+ cell counts and CD4/CD8 ratio were significantly lower than those of HIV-isolation negative patients in both hemophiliacs and non-hemophiliacs. IgA value of the positive patients was significantly higher than that of the negative patients, while the IgM value showed converse results to the IgA, in hemophiliacs only. In general, the difference of each HIV marker in non-hemophiliacs was more conspicuous than those in hemophiliacs.

A case of cow's milk allergy related to type I and type III allergic reactions is reported. The patient is a one-month-old girl. She had watery diarrhea and abdominal distention soon after commencement of milk feeding two weeks after birth. She was cyanotic and floppy on admission. Intravenous complete hyperalimentation was tried to combat her diarrhea with good clinical effect. Then feeding with 605Z milk (enzyme digested cow's milk antigen, Meiji Milk Products Co., Ltd.) was started, and the diarrhea improved. Laboratory findings showed positive milk PK test, elevated IgE score, and positive milk specific RAST score, decreased serum complement, elevated levels of each immunoglobulin class of milk specific antibodies, especially milk specific IgG1 antibody and increased complement absorption test. She was diagnosed as having milk allergy related to both type I and type III allergies from the above-mentioned results. Specific antibodies were diminished after feeding with 605Z. Although her mother had not taken cow's milk over the past 10 years, she took a lot of milk during her pregnancy. But her serum milk specific antibodies were not elevated. It was suggested that the baby's antibodies were not derived from her mother but that the baby produced them by herself.