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.     

Disposition of [3H]flobufen and its active metabolite in rats

The present authors investigated the excretion, distribution and pharmacokinetics of the novel potential antirheumatic agent flobufen and its active metabolite after p.o. and i.v. doses of 2, 10 and 50 mg/kg administered to rats. The drug is resorbed well from the digestive tract and mostly it is metabolized to the principal metabolite M, which is only slowly excreted from the organism mainly by renal clearance. Within the whole dose range the kinetics of the drug is linear. Binding of flobufen and M to proteins is high (95-99%). The highest concentrations of radioactive metabolites (mostly M) were found in the plasma, liver, lungs, kidneys, connective tissue and inflammatory foci. The penetration of metabolites through the placenta and excretion in human milk are relatively important.     

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.     

Penetration and distribution of three lipophilic probes in vitro in human skin focusing on the hair follicle.

Fluorescent model substances of increasing lipophilicity (Oregon Green) 488, Bodipy, FL C5 and Bodipy 564/570 C5) were selected to enable the visualization in the skin using confocal laser scanning microscopy. After measuring the penetration for 18 h, the nonfixed human scalp skin was imaged from the bottom parallel to the stratum corneum and in a cross-section view perpendicular to the skin surface. The images were evaluated by calculating relative accumulation values for different penetrants. The studies indicate that the penetrated amount is highest for Bodipy FL C5 (medium lipophilicity) and lowest for Bodipy 564/570 C5 (high lipophilicity) whereas Bodipy 564/570 C5 (high lipophilicity) reveals the highest relative accumulation in parts of the hair follicle compared to Oregon Green 488 (low lipophilicity). The addition of 30% (v/v) ethanol to the donor phase of substance with a low lipophilicity increases the follicular delivery. From our results we conclude that delivery to the hair follicle can be improved by increasing the drugs lipophilicity and optimizing the composition of the donor phase. However, no conclusion can be drawn about the actual route of transport to the hair follicle.     

Babinski-Nageotte syndrome on magnetic resonance imaging

A 70-year-old woman developed left hypoglossal nerve palsy, a right hemiparesis sparing the face, and a typical left Wallenberg's syndrome. These symptoms resulted from a lesion in the left half of the medulla oblongata, suggesting Babinski-Nageotte syndrome, a rare cerebrovascular disease. This is the first case of ischemic infarction in the territory of the left vertebral artery and posterior inferior cerebellar artery demonstrated on magnetic resonance imaging. Severe bilateral lesions of the distal vertebral arteries demonstrated on digital subtraction angiography may have contributed to the development of this syndrome.     

Cytochrome P-45011 beta in rat brain

The presence of cytochrome P-45011 beta in rat brain was studied by immunohistochemistry using polyclonal rabbit antibodies raised against purified bovine adrenocortical P-45011 beta, which is involved in the steroid 11 beta-hydroxylation and glucocorticoid formation. The results showed that cytochrome P-45011 beta immunoreactivity is selectively localized to the tracts of myelinated fibers throughout the brain. The specificity of immunohistochemical stainings with P-45011 beta antibodies was established by control tests including nonimmune rabbit immunoglobulin Gs and P-45011 beta antibodies absorbed with purified antigen. Western immunoblots of homogenates from different brain areas with P-45011 beta antibodies, together with biochemical enzymatic assays for cytochrome P-45011 beta monooxygenase activity in these homogenates, confirmed the selective localization of this enzyme observed with immunohistochemistry. Cytochrome P-45011 beta and 11 beta-hydroxylase activity were detected in a homogenate from the cortical white matter (brain area rich in myelinated fibers) as in that from the rat adrenal, but were not detectable in a homogenate from the cerebral cortex (brain area poor in myelinated fibers). Furthermore, quantitation of the P-45011 beta bands on the immunoblots by the areal density revealed that the cortical white matter contains approximately 1.4 pmol of cytochrome P-45011 beta/mg of tissue protein, the value of which was about one sixth of the corresponding value estimated in the rat adrenal. This relatively high content of cytochrome P-45011 beta was also reflected in a relatively high level of 11 beta-hydroxylase activity measured in a homogenate of this brain area by biochemical enzymatic assays using [4-14C]-11-deoxycorticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recurrence, progression and survival in bladder cancer. A retrospective analysis of 232 patients with greater than or equal to 5-year follow-up

A retrospective study of 232 bladder tumours with minimum follow-up 5 years is presented. The carcinoma was superficial in 66%, muscle-invasive in 31% and could not be staged in 3%. Primary treatment was mainly transurethral resection for superficial tumour, but was cystectomy or radiotherapy in 22 of 29 T1 G3. Of the superficial tumours, 71% recurred. Progression to higher T stage occurred in 15% of Ta and 29% of T1 tumours, and half of these patients died of bladder cancer. The corrected 5-year survival rates in grades 1, 2A, 2B and 3-4 were 96, 84, 64 and 43%, and in stages Ta, T1, T2 and T3 they were 94, 69, 40 and 31%. All patients with T4 tumour died within 4 years. Among the 45 patients with 40 Gy irradiation + cystectomy, the corrected 5-year survival rate was 83% in superficial and 64% in muscle-invasive tumours, and among the 38 with radical radiotherapy the rates in T1-3 were 46, 36 and 13%. Transurethral resection was successful in most Ta cases. Most T1 tumours were, like T2-4, of higher grade than Ta. Prognosis was worse in T1 than in Ta. After progression to muscle-invasive disease, even during close follow-up the outlook was poor, as poor as for patients with primary muscle-invasive disease.     

Renal growth after neonatal urinary tract infection

This study presents the result of 12–21 years' follow-up in a group of children with neonatal urinary tract infection (onset within 1 month after birth) in whom early renal growth retardation was noted without concomitant classical renal scarring. In all cases the neonatal infection was diagnosed and treated within a few days of onset and the patients were closely supervised thereafter. Renal length, parenchymal thickness and area were measured at urography. At first follow-up (22 children, mean age 4.1 years) a significant reduction of renal parenchymal thickness was noted. Long-term follow-up (18 patients, mean age 17 years) demonstrated a normalization of renal size in the entire group, although less complete in the subgroup with reflux. There were two major findings in the present study. Firstly, renal growth retardation was seen after neonatal infection, both with and without reflux. Secondly, normalization of renal size in previously small kidneys was demonstrated, suggesting that growth retardation can be a reversible phenomenon. The tendency for such normalization was slightly more marked in children without reflux. Reduction of parenchymal thickness without calyceal deformity, therefore, does not necessarily mean irreversible damage, and differentiation between permanent scarring and temporary growth retardation can thus only be made at later follow-up, possibly not until after puberty. The demonstration of renal growth retardation in spite of early diagnosis and treatment emphasizes the great vulnerability of the kidney in the newborn.