Immunoglobulin (Ig)G purified from human sera mirrors intravenous Ig human leucocyte antigen (HLA) reactivity and recognizes one's own HLA types, but may be masked by Fab complementarity-determining region peptide in the native sera.

Intravenous immunoglobulin (IVIg) reacted with a wide array of human leucocyte antigen (HLA) alleles, in contrast to normal sera, due possibly to the purification of IgG from the pooled plasma. The reactivity of IgG purified from normal sera was compared with that of native sera to determine whether any serum factors mask the HLA reactivity of anti-HLA IgG and whether IgG purified from sera can recognize the HLA types of the corresponding donors. The purified IgG, unlike native sera, mirrored IVIg reactivity to a wide array of HLA-I/-II alleles, indicating that anti-HLA IgG may be masked in normal sera - either by peptides derived from soluble HLA or by those from antibodies. A < 3 kDa peptide from the complementarity-determining region (CDR) of the Fab region of IgG (but not the HLA peptides) masked HLA recognition by the purified IgG. Most importantly, some of the anti-HLA IgG purified from normal sera - and serum IgG from a few donors - indeed recognized the HLA types of the corresponding donors, confirming the presence of auto-HLA antibodies. Comparison of HLA types with the profile of HLA antibodies showed auto-HLA IgG to the donors' HLA antigens in this order of frequency: DPA (80%), DQA (71%), DRB345 (67%), DQB (57%), Cw (50%), DBP (43%), DRB1 (21%), A (14%) and B (7%). The auto-HLA antibodies, when unmasked in vivo, may perform immunoregulatory functions similar to those of therapeutic preparations of IVIg.

Induction of mouse monocyte Ia expression by a mesangial cell-derived product.

Previous studies in many laboratories have shown that macrophage Ia expression is not constitutive but under regulation. We provide data which demonstrate that product(s) of mouse mesangial cell cultures induce blood monocyte Ia expression as demonstrated by immunofluorescence. This process is time-related and is also dependent on novel protein synthesis, being abrogated when the monocytes are pretreated with cycloheximide. Preliminary characterization shows the mesangial cell product to be sensitive to heating at 100 degrees C x 30 min, to be resistant to digestion by trypsin at a concentration of 4 x 10(-6) M, and to have a molecular size of 10-100 kD as established by Amicon ultrafiltration. The substance is not interferon-gamma (IFN-gamma) since cultured mesangial cells had no contaminating T cells, mesangial cell supernatant had no detectable levels of IFN-gamma, and the Ia-inducing activity of the mesangial cell product was not abrogated by incubation of monocytes with mesangial cell supernatant which had been immunoprecipitated with anti-IFN-gamma. Similarly, experiments using anti-CSF-1 have excluded the possibility that the substance is CSF-1. The results of the study have relevance to the mechanisms by which monocytes which take up residence in the glomerular mesangium acquire Ia positivity, and also provide a potentially novel pathway by which a tissue product may induce monocytes to express Ia.

[Effects of steroid therapy in IgA nephropathy].

In order to estimate the effects of corticosteroid therapy in IgA nephropathy cases with daily urinary protein excretion of 1.0 g/day or more. 26 patients (8 men and 18 women, aged 32.6 +/- 14.0 years old) were subjected to this study. The results obtained were as follows: Urinary protein excretion after 1 year from the beginning of steroid therapy (1.56 +/- 1.14 g/day) was significantly (p less than 0.05) lower than that at the beginning of the therapy (4.61 +/- 6.01 g/day). In serum creatinine levels, there was no statistically significant difference with them between at the beginning (1.15 +/- 0.48 mg/dl) of steroid therapy and at the time of 1 year after (1.05 +/- 0.34 mg/dl) the therapy. As for the outcome at the end of this study setting (mean follow-up duration: 3.7 +/- 2.6 years), complete remission was attained in 7 cases, improvement in 5 cases, unchanged condition in 11 cases, increased urinary protein excretion in 2 cases and aggravated renal function in 1 case. In clinical findings at the renal biopsy, duration of the disease (3.4 +/- 1.6 months) in complete remission cases before biopsy was significantly (p less than 0.01) shorter than that in unchanged cases (65.0 +/- 40.0 months). In histological findings, rate of global sclerosing glomeruli (2.6 +/- 4.6%) in complete remission cases was significantly (p less than 0.05) lower than that (24.6 +/- 23.1%) in unchanged cases. These results suggest that steroid therapy in IgA nephropathy with persistent proteinuria of 1.0 g/day or more is beneficial, especially in cases that are in early stage of the disease with lower rate of global sclerosing glomeruli.

[A case of familial lecithin: cholesterol acyltransferase deficiency].

Lecithin: cholesterol acyltransferase (LCAT) is an enzyme that catalyzes the esterifying reaction of cholesterol in plasma high density lipoprotein (HDL). Deficiency of LCAT is a rare hereditary disease characterized by several clinical symptoms such as proteinuria, corneal opacity, and anemia due to a shortened life span of erythrocytes. In this communication, we report a case of 40 year-old female patient of LCAT deficiency. She visited a hospital for work-up of proteinuria, corneal opacity and anemia. Activity of her serum LCAT was found to be extremely low, and characteristic changes in plasma lipids due to deficiency of LCAT was observed: those were marked decreases in HDL-cholesterol, degree of esterification in serum cholesterol, and apoprotein A-I, A-II, B and C-II levels. The diagnosis of LCAT deficiency was finally made. We studied about histopathological changes in the patient's kidney, and erythrocyte membrane lipid composition and fluidity. Histopathological findings in renal biopsy were follows: a) Light microscopy showed spherical deposits stained with periodic acid-Schiff in mesangial matrix and adjacent capillary loops, and hyaline deposits in arterioles, b) Electron microscopy showed vacuoles in mesangial matrix and along the glomerular basement membranes. In erythrocyte membrane lipids, increase of cholesterol to phospholipid molar ratio was evident, being accompanied by changes in phospholipid fractions: increase of phosphatidylcholine, and decreases of phosphatidylethanolamine, sphingomyelin and lysophosphatidylcholine. In phospholipid acyl chains, increase of C18:2 and decreased of C18:1 were evident in the patient. Erythrocyte membrane fluidity was found to be decreased in the patient in a measurement by pyrene, probably being related to the changes in membrane lipid composition.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence that mouse mesangial cells produce colony-stimulating factor-1.

The contractile mesangial cell has previously been shown to be a metabolically active cell capable of producing a variety of substances. In this communication, we report that the contractile mouse mesangial cell produces a factor which induces the replication of blood monocytes and splenic macrophages but not of peritoneal macrophages. This factor has an isoelectric pH of 4 as determined by chromatofocusing, a molecular weight of 68,000 daltons as determined by gel chromatography, and is reactive to anti-CSF-1 as assessed by experiments showing inhibition of function by the antibody. These physiological, physico-chemical and immunological characteristics indicate that the substance is most likely colony-stimulating factor-1 (CSF-1).

The biology of mesangial cells in glomerulonephritis.

It is likely that a complex bidirectional interaction occurs between mesangial cells and the immune cells which infiltrate the mesangium during nephritis. Macrophages and other immune cells liberate a series of mediators, including substances such as IL-1, beta-endorphin, TNF, and PDGF--all of which promote the growth of mesangial cells. The end result is mesangial cell proliferation and increased matrix production, both of which are seen in nephritis. The proliferating mesangial cells liberate autocoids such as IL-1 and PDGF, thereby setting up an amplifying loop. Simultaneously, suppressive factors such as TGF-beta are released which antagonize the actions of these growth-promoting substances. The proliferating mesangial cells also produce immunomodulatory peptides, which will in turn act on the infiltrating macrophages to stimulate their replication and activation. Such activated macrophages continue to amplify the inflammatory lesion and also promote the phagocytosis of localized antigen-antibody complexes. The net effect of all of these interactions will depend on the dominance of substances which persist and override the roles of other molecules. Studies of the controls which regulate the production of these growth factors/immune modulators will yield insights into the fundamental mechanisms which determine the outcome in glomerulonephritis.

[The removal efficiency of beta 2-microglobulin, alpha 1-microglobulin and alpha 1-acid glycoprotein by using dialyzers in the bloodstream and transference of endotoxin through membranes].

Retention of beta 2-microglobulin (beta 2-MG) has been indicated as one of the causes of hemodialysis-associated amyloidosis. Membranes with higher permeability (high-performance membrane) have recently been developed accordingly. Several dialyzers were tested by us in an attempt to study their removal efficiency of beta 2-MG and higher molecular substances of alpha 1-microglobulin (alpha 1-MG) and alpha 1-acid glycoprotein (alpha 1-AG), as well as transferring of endotoxin (ET) through membranes into bloodstream. The membranes subjected to our study were PMMA, CTA, PS, EVAL-C and CA. Removal efficiency of beta 2-MG through EVAL-C and CA was lower as compared with that through other membranes (P less than 0.05), while the EVAL-C showed relatively higher removal efficiency for alpha 1-MG and alpha 1-AG. Permeability for ET was not observed with all membranes studied herein.

[A case of acute potassium bromate intoxication].

We experienced a case of a 44 year old man who had ingested potassium bromate solution for suicide attempt. Soon after the ingestion, nausea, vomiting, abdominal pain and diarrhea developed in him. Several hours later, he began to complain of auditory disturbance and, in addition, anuric acute renal failure occurred. Direct hemoperfusion and hemodialysis was performed on the patient for the treatment purpose. Five weeks later, he was released from hemodialysis procedure. Gradually, on the other hand, progressing anemia was observed until 90th hospital day, which slowly improved thereafter. Further, pruritus, lower leg pain, headache, tinnitus and loss of sense of taste, etc. were observed in the clinical course. Renal biopsy was performed on the 119th hospital day and the specimen showed the regenerative stage of acute tubular necrosis. In our case, acute renal failure was reversible and, many other clinical manifestations were observed. However slight anemia and irreversible severe auditory disturbance remained unimproved.

[A case of Fabry's disease detected by renal biopsy findings].

A 39 year-old man was found to have mild proteinuria by urinary examination since one year ago. He was for the first time diagnosed as having Fabry's disease by histopathological and electronmicroscopic findings of the renal biopsy specimens, which showed the presence of numerous vacuolated cells and electron dense bodies inside the cells. The level of WBC alpha-galactosidase was significantly lower than normal level. The pedigree of this patient showed a familial history of various types of renal disease. One of the patient's brothers also showed decreased level of WBC alpha-galactosidase, who has been treated by maintenance hemodialysis for 2 years. It is concluded that early diagnosis of this disease through renal biopsy and WBC alpha-galactosidase level is important to manage the future course of patients with Fabry's disease.

IgD multiple myeloma with renal involvement: case report.

IgD multiple myeloma is a unique type of multiple myeloma which is characterized by increased serum IgD and IgD type M-component in immunoelectrophoresis. It frequently shows renal involvement but it is a rare form of myeloma. The distinctive features of IgD myeloma are the dominance in males, high frequency in younger persons, and the uncertain appearance of M-component in serum electrophoresis. We experienced 3 cases of IgD multiple myeloma with renal failure which required hemodialysis before IgD myeloma was diagnosed. It is important to consider IgD myeloma when treating the patients with renal involvement of unknown origin.

[A case of blue rubber-bleb nevus syndrome with CAPD].

The first case of blue-rubber-bleb nevus syndrome treated with CAPD in Japan was presented. As operation for A-V fistula construction could not be performed due to the skin lesions, she was obliged to have CAPD treatment. She has been visiting our hospital for regular check-ups.

[Disturbance of the autonomic nerve system in patients with chronic renal failure--represented by variation coefficient of R-R intervals in the ECG as a parameter].

Autonomic nerve dysfunction in patients with chronic renal failure has of late become an issue to be investigated. R-R intervals in resting electrocardiograms were measured to evaluate activities of the cardiac parasympathetic nerve system. A total of 140 patients with chronic renal failure were studied to be compared with 20 normal controls (cont.) and 39 with diabetes mellitus (DM). Of these patients 15 were subjected to conservative treatment (CRF), while 125 patients were undergoing hemodialysis due to chronic renal failure-100 of them derived from chronic glomerulonephritis (HD) and 25 from diabetes mellitus (DM.HD). The variation coefficient of the R-R interval (CVRR) was measured after the subject patients had rested for over 15 minutes before a dialysis session. The mean CVRR were 2.15 +/- 1.25% in CRF group, 2.36 +/- 1.37% in HD and 1.37 +/- 0.99% in DM.HD. These values were significantly lower than in control group (4.70 +/- 2.64%). On the other hand, the value in DM.HD group, as shown above, was significantly lower than in HD. In CRF group the CVRR values lowered as residual renal functions decreased. No significant correlations between CVRR S and the duration of hemodialysis treatment were noted among the groups. In HD group the CVRR S were significantly lower in patients with hypotensive tendency during hemodialysis than in those who enjoyed good control of blood pressure. These results suggest that the measurement of CVRR S can be of help in evaluating autonomic nerve dysfunction in patients with chronic renal failure.

Lupus nephritis with adult T cell leukemia.

A 64-year-old Japanese male patient with lupus nephritis associated with adult T cell leukemia (ATL) is described. Percutaneous renal biopsy demonstrated findings consistent with membranous lupus nephritis. To our knowledge, this is the first case of lupus nephritis complicated by ATL, suggesting that human T cell leukemia virus type I may be correlated not only to outbreaks of ATL but also to lupus nephritis/systemic lupus erythematosus.

The effect of transforming growth factor-beta on mouse mesangial cell proliferation.

The factors which regulate mesangial cell growth are of importance in determining the cellular lesions of nephritis. In this communication, we report that transforming growth factor-beta (TGF-beta) exerts a suppressive effect on mesangial cell 3H-thymidine uptake. Furthermore, TGF-beta antagonizes the mitogenic effect of epidermal growth factor (EGF) on DNA synthesis. The concomitant presence of TGF-beta in the cell cultures is not required for its effect since cells pretreated with the substance and rinsed of it showed suppressed 3H-thymidine uptake and did not respond to EGF. The effect of TGF-beta can also be demonstrated on cells committed to proliferate by the prior addition of EGF. The results of the study have relevance to the mechanisms underlying the histologic lesions of immune-mediated nephritis.

[Graves' disease complicated with systemic lupus erythematosus (SLE): a case report].

A 25 year old man had been subjected to subtotal thyroidectomy under the diagnosis of Graves' disease. About a year later the patient developed systemic lupus erythematosus (SLE). Reports on cases of Graves' disease complicated with SLE have barely been observed so far. Consequently, the authors reckoned, with reference to the other literatures on the subject, our case worth reporting.

[Anemia in patients on continuous ambulatory peritoneal dialysis (CAPD)].

Inhibitors of erythropoiesis found in the blood of uremic patients have been implicated as some of the causes of anemia in chronic renal failure. As a treatment to remove the inhibitors, continuous ambulatory peritoneal dialysis (CAPD) is thought to be more effective than hemodialysis. Some researchers have reported that CAPD has improved anemic state in hemodialysis patients. However, there have been some cases of severe anemia seen in CAPD patients. To access the effect of the CAPD, we have performed serial examination on hemoglobin (Hb) and hematocrit (Ht) in 5 uremic patients under CAPD treatment. Hb levels in 4 and Ht in 3 of 5 patients have been known to be increased. One patient was shown to have no increment on the levels of Hb and Ht. On the other hand, further investigation has been down to access the effect of the recombinant human erythropoietin (r-HuEPO: Chugai pharmaceutical) on anemic patients, in whom no effect was noticed by treatment of CAPD. One severe anemic patient, who had been undergoing the treatment of CAPD for two years, was given r-HuEPO intravenously. The patient showed the increment on the levels of Hb and Ht, and the decreases on the levels of serum iron and ferritin. However, the patient has developed hypertension. In conclusion, CAPD was known to be not always effective for the increment of Hb and Ht, while r-HuEPO was very effective for the improvement of severe anemia in CAPD patients which enabls them to lead better social life for them.

[Investigation on antibodies to human T cell leukemia virus type I in patients with primary glomerulonephritis].

We investigated on antibodies to human T cell leukemia virus type I (anti HTLV-I) in 101 patients with primary glomerulonephritis in Kagoshima prefecture, an endemic area of HTLV-I in Japan. The positive rate in patients with primary glomerulonephritis was 17.8%, which was not significantly higher than in healthy residents 4741 persons of 11.9% in the same area. Classified by renal biopsy findings, the positive rate in patients with membranous nephropathy was 21.4% (9/42), minimal change nephrotic syndrome 14.3% (2/14), IgA nephropathy 15.4% (2/26), and others 15.8% (3/19) respectively, which were not significantly differed from that in healthy residents. Positivity of aged patients (60 years or over) in membranous nephropathy on the contrary was significantly higher than that in healthy residents (p less than 0.01). Further study is required to clarify the relationship between HTLV-I infection and glomerulonephritis.

1,25-Dihydroxyvitamin D3 and rat vascular smooth muscle cell growth.

Recent studies from several laboratories have shown perturbations of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] metabolism in hypertension. While these perturbations may exert their effect on blood pressure via their actions on calcium metabolism, it is possible that this vitamin D metabolite may have direct effects on vascular smooth muscle cell (VSMC) physiology. To examine this, we studied the effect of 1,25(OH)2D3 on VSMC growth and found that this substance suppressed VSMC [3H]thymidine uptake; furthermore, this vitamin D metabolite also suppressed the stimulatory effect of epidermal growth factor (EGF) on VSMC proliferation. The concomitant presence of this substance appeared to be required for its action on VSMC growth since cells pretreated with the vitamin D metabolite for up to 72 hours and then washed of the substance grew normally and responded to EGF. Studies were also done to determine if 1,25(OH)2D3 had any effect on the function of EGF receptors on VSMC. Experiments using Iodine-125-labeled EGF showed no differences in the binding of this ligand to VSMC, either untreated or treated with 1,25(OH)2D3, which indicates the effect of the vitamin D metabolite on VSMC growth (when exposed to EGF) was not mediated by an alteration of EGF receptor function. The results of these studies have implications for the pathogenesis of vascular diseases such as hypertension and atherosclerosis.