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.     

The experimental pharmacotherapy of the liver lesion induced by indomethacin

In experiments on albino rats it was established that three administrations of indomethacin in a dose of 0.01 g/kg body weight induced a severe damage of the liver characterized by disturbances of hepatocytic membranes, bile-producing and protein-producing functions of the liver, an enhancement of lipid peroxidation, a decrease of reduced glutathione pool. Antioxidants (tocopherol acetate, essentiale, legalon, flacumin) limit manifestations of indomethacin, hepatotoxicity, as a result of which tha functional-biochemical disorders in the liver show up to a lesser degree. During the combined use of antioxidants in indomethacin-induced lesions of the liver their hepatoprotective activity increases.     

Reduction of reticulata neuronal activity by zolpidem and alpidem, two imidazopyridines with high affinity for type I benzodiazepine receptors

Zolpidem and alpidem, two imidazopyridines with high affinity for the type I benzodiazepine recognition site, have recently been proposed as preferential hypnotic (zolpidem) and anxiolytic (alpidem) drugs notable for the minor incidence of side-effects. To further characterize the molecular mechanism involved in the action of these drugs, we studied their effects in comparison with those of diazepam on the spontaneous electrical activity of substantia nigra pars reticulata (SNR) neurons. These cells have been shown to be extremely sensitive to various positive and negative modulators of GABAergic transmission. All three drugs consistently produced a dose-dependent (0.03-8.0 mg/kg i.v.) inhibition of the firing of SNR cells when administered as a single bolus. However, zolpidem was more potent and efficacious than diazepam or alpidem. The ID50s were 0.076, 0.492 and 0.821 mg/kg, respectively. When the drugs were injected in exponentially (ratio 2) increasing doses up to 8.0 mg/kg, the rank order for tachyphylaxis was zolpidem much greater than diazepam greater than alpidem. Since the effects of the drugs were abolished and prevented by a small dose (0.5 mg/kg i.v.) of flumazenil (Ro 15-1788), it is likely that the effects were mediated through activation of benzodiazepine receptors. The results indicate that the hypnotic, zolpidem, has a more potent inhibitory action on SNR cell activity than the anxiolytics, alpidem and diazepam.     

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.     

Juvenile hypocalcemia provokes persistent electroencephalographic change in renally compromised rats

In view of the putative involvement of calcium in uremic encephalopathy and the critical importance of this element in juvenile development, we examined the effect of temporary restriction of dietary calcium intake on serum chemistry and the quantitative electroencephalogram (Q.EEG) in unilaterally 3/4 nephrectomized juvenile male Sprague-Dawley rats. Animals were renally infarcted at 22-26 days of age (50-74 g) and placed on one of two isocaloric dietary regimens: powdered normal rat diet (ND, n = 25) or low calcium diet (LCD, n = 8) for 30 days. At this time, ND animals showed normal serum chemistries, whereas LCD rats were hypocalcemic and azotemic with significantly elevated blood urea nitrogen (BUN) and serum creatinine concentrations and reduced renal creatinine clearance values. All animals thereafter received ND for 25-34 further days, during which time chronic Q.EEG electrodes were implanted. At the end of the common ND feeding period, serum chemistry values were equal and normal in both groups. The average theta/alpha ratio (TAR) of the overnight Q.EEG was assessed for 3 days. We found that the TAR of previously LCD animals was significantly elevated compared with ND rats. This indicates an encephalopathic slowing of the background rhythm of these animals. We conclude that, following restoration of a transient uremic and hypocalcemic episode induced by LCD feeding, the Q.EEG background frequency of juvenile renally impaired rats was abnormally slow after 30 days of ND feeding.     

Polyploidization and centrosome hyperamplification in inflammatory bronchi

OBJECTIVE AND DESIGN: Inflammatory and tumorous bronchi were screened in order to obtain new tumor relevant cytogenetic parameters. MATERIAL OR SUBJECTS: Bronchial cells of 32 patients were cultivated by standard cell culture procedures. METHODS: Tetraploidy and aneuploidy was determined by enumeration of chromosome 7 and 8 versus the number of centrosomes. The resulting data were correlated with histopathological data. RESULTS: Tetra- and aneuploidy of epithelial cells were detectable in 76% of tumor cell cultures, 75% of high grade inflammatory tissues and 40% of non- and low grade-inflammatory tissues. Additionally, we observed centrosome hyper-amplification and multipolar mitoses not only in the tumor but also in the early stages of inflammation. CONCLUSION: Inflammatory bronchi already show tumor-specific features and may consequently represent the preliminary genetic stage of cancer development in bronchi.     

Modelling debonded stem-cement interface for hip implants: effect of residual stresses.

OBJECTIVE: To assess the effect of the residual stresses due to cement curing on the load transfer of cemented hip implants. DESIGN: The load transfer at the stem-cement interface of an idealized hip stem surrounded by cortical bone was investigated using a three-dimensional finite element analysis. A debonded stem-cement interface was considered to simulate a highly polished stem in contact with cement; Coulomb friction at the stem-cement interface was considered. BACKGROUND: Numerical analyses on the load transfer of cemented hip implants do not include residual stresses due to cement curing at the stem-cement interface. METHODS: The magnitude of the residual stresses was determined experimentally. In the finite element model, non-linear contact elements modelled the debonded stem-cement interface. In particular, the compressive radial residual stresses that are generated at the interface, due to the cement expansion during curing, were treated similar to a press-fit problem. RESULTS: The cement stress distributions were affected by the magnitude of the residual stresses. Failing to include residual stresses underestimated the cement stresses at the interface, mainly affecting the radial and hoop stresses. The load was transferred from the stem to the cement more uniformly along the interface once residual stresses were included. CONCLUSIONS: Because there is no chemical bond at the interface between the stem and cement, the interface resistance depends on friction thus radial residual compressive stresses developed by the cement curing play a direct role. RELEVANCE: Implant loosening of cemented hip implants is one of the major causes of late failure of the arthroplasty. The load is transferred from the stem to the bone primarily across the interfaces, consequently modelling accurately the interface is essential in predicting the load transfer.