Monoclonal antibody analysis of glomerular, tubulo-interstitial infiltrating immune cells in various glomerulonephritis

To investigate the role of cell-mediated immunity (CMI) in glomerulonephritis (GN), we identified the infiltrating immune cells both within the glomerulus and in the interstitium. Frozen sections from 103 patients with various forms of GN: 10 with minor glomerular abnormality (MGA) as control, 10 with minimal change nephrotic syndrome (MCNS), 10 with membranous nephropathy (MN), 9 with focal glomerulosclerosis (FGS), 30 with IgA nephropathy (IgAN), 22 with acute post streptococcal glomerulonephritis (APSGN), and 2 with rapidly progressive glomerulonephritis (RPGN) were examined using monoclonal antibodies (MoAb) by indirect immunoalkaline-phosphatase labelling. In most glomerulonephritis, monocyte/M phi and helper/inducer T cells were predominantly infiltrating in the interstitium, but intraglomerular infiltration was rare, except for APSGN. This interstitial infiltration increased proportionally to the level of serum creatinine, and was most prominent in RPGN. Apparently different distribution was seen in APSGN, that is, prominent increase in total number of intra-glomerular monocyte/M phi infiltration with slightly increased T cells. The change was correlated with time after onset; namely the more leucocytic infiltration was observed when the tissue was taken earlier. These data suggest that in APSGN, monocyte/M phi accumulate in glomeruli via cell mediated immunity in addition to humoral immune mechanism resulting in glomerular hypercellularity, whereas in most chronic glomerulonephritis interstitial leucocyte infiltration, particularly helper T cells and monocyte/M phi may play an important role in the progression of glomerulonephritis.     

Pharmacological studies of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate. Effects on experimental pancreatitis

The effects of FUT-187 (6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate, CAS 103926-82-5), a novel synthetic protease inhibitor, were examined in experimental rat and canine models of pancreatitis. 1. FUT-187 significantly increased the survival of rats with trypsin- and phospholipase A2-induced pancreatitis in a dose-dependent manner (10-100 mg/kg, p.o.). 2. FUT-187 decreased plasma enzymatic activity reflecting the degree of pancreatitis in rats with ethionine-induced pancreatitis, and showed a tendency to ameliorate histopathological changes in the pancreas (10-100 mg/kg p.o.). 3. FUT-187 (10 mg/kg) produced an obvious improvement of various biochemical parameters of pancreatitis and also reduced histopathological changes in the pancreas in animals with experimental pancreatitis produced by the closed duodenal loop method. In addition, FUT-187 significantly increased the survival of dogs when given by direct administration into the lumen of the closed duodenal loop. The therapeutic effects of FUT-187 in experimental pancreatitis were nearly equal in most instances to those of camostat mesilate. Thus, FUT-187 would appear to be an effective new agent for the treatment of pancreatitis.     

A case of a small hepatoma with multicentric development in precirrhotic fibrosis

Multicentricity of hepatocellular carcinoma (HCC) is considered, especially in patients with liver cirrhosis. This paper describes an operative case of a male patient with probable multicentric development of HCC in precirrhotic fibrosis. The main tumors inside the capsule were completely necrotic due to transarterial embolization (TAE). Histologic examination disclosed discrete tiny nodules of HCC that were not detected grossly. They showed highly differentiated trabecular arrangements: Edmondson I. A scirrhous type was noted in the center of the tumors. At the borders of the tumors the carcinoma cells exhibited replacing growth patterns and it was thought that they developed multicentrically. Partial resection must be performed as extensively as possible in a case such as the present one.     

ACETALDEHYDE ADDUCTS WITH HAEMOGLOBIN: DETERMINATION OF ACETALDEHYDE RELEASED FROM HAEMOGLOBIN BY ACID HYDROLYSIS

Acetaldehyde, the first metabolite of ethanol, reacts with haemoglobinin vitro to produce acetaldehyde—haemoglobin adducts.Some clinical studies on the minor haemoglobins have suggestedthat these adducts may be formed in people abusing alcohol.Under hydrolysis of haemoglobin, with oxalic acid at 100°Cin sealed vials, some acetaldehyde was released and then specificallydetermined by HPLC. The kinetics of hydrolysis were studiedusing haemoglobin previously labelled with ¹⁴[C] acetaldehyde.The maximum liberation of ¹⁴[C] acetaldehyde was obtained after3 hr 30 min hydrolysis and this time factor was then utilizedin the analysis of alcoholic and control haemoglobin. Thus,we have confirmed the formation of acetaldehyde haemoglobinadducts in vivo. It must be noted that the released acetaldehydecorresponds only to an index of the stable adducts. The levelswere higher in alcoholics than in controls (1.417±0.171and 1.295±0.139 nmol/mg Hb, respectively, P<0.001).In conclusion, this marker is not a convenient tool for themonitoring of alcohol exposure levels because of the low differencesbetween alcoholic and control haemoglobins.     

Population screening and referral for hypercholesterolemia

To determine the potential effect of screening on referral patterns, an adult population sample (4,404 men, 5,164 women, 20-69 years of age) was systematically recruited and screened for hypercholesterolemia and then analyzed by different cholesterol referral recommendations. Using levels suggested by the Lipid Research Clinics Coronary Primary Prevention Trial (greater than or equal to 265 mg/dL), 7.3% of men and 5.8% of women would be referred for follow-up. With the suggested recommendations of the National Cholesterol Education Program (NCEP), (greater than or equal to 200 mg/dL), 49.2% of men and 40.2% of women would be referred. The use of age-related definitions of the NIH Consensus Conference on Lipid Lowering results in 28.0% referrals in men and 21.8% in women. From this population, hypercholesterolemia subjects (greater than or equal to 265 mg/dL at screening; n = 624) were invited for a second cholesterol determination (58% returned), which found 36% below the 265 mg/dL level. Population screening for cholesterol is likely to produce large numbers of patients for follow-up, with the actual numbers strongly dependent on cutoff levels and age-sex distributions. Referral and follow-up of these patients may place a significant load on an unprepared health care community.     

Development of traumatic retinal detachment

Post-traumatic retinal detachment occurs frequently as a late consequence of progressive vitreous changes, especially following penetrating injuries. Occasionally, it develops soon after the trauma, without preceding proliferative vitreoretinopathy, is based on posterior vitreous detachment and morphologically resembles an idiopathic retinal detachment. It is possible that the posterior vitreous detachment in these cases is encouraged by the presence of intravitreal hemorrhage.