Activation of mRNA expression of collagen,collagenase and its inhibitor on renal biopsy specimens in patients with IgA nephropathy

Summary: In situ hybridization of mRNA for collagen IV, collagen VI, stromelysin (MMP-3) and TIMP1 was examined in renal biopsy specimens from patients with IgA nephropathy (IgAN) or diabetic nephropathy with various degrees of tissue damage. The majority of cells in the glomeruli expressed these mRNA almost simultaneously, but a few cells demonstrated positive expression for only one of these probes. There was a parallel relationship between the degree of tissue damage and that of mRNA expressions of these probes in patients with IgAN, while patients with diabetic nephropathy showed a reverse relationship between these two parameters. It is concluded that patients with mesangial proliferative glomerulonephritis expressed mRNA for collagen collagenase and its inhibitor in the glomeruli in parallel with the progress of tissue damage. In contrast, glomerular samples from patients with diabetic nephropathy showed that there was an inverse relationship between tissue damage and expression of mRNA. It is concluded that expression of collagen, collagenase and its inhibitor parallels the progression of glomerular changes in IgAN, but such parallel expression was not observed in patients with diabetic nephropathy.     

Cerivastatin inhibits fetal calf serunvinduced DNA synthesis in cultured rat mesangial cells

SUMMARY: Inhibition of mevalonate synthesis by several statins has been shown to suppress DNA synthesis in glomerular mesangial cells. In the present study, we investigated the effect of a new statin, cerivastatin, on fetal calf serum (FCS)-induced DNA synthesis of cultured rat mesangial cells. Cultured rat mesangial cells were stimulated by 10% FCS in the presence or absence of cerivastatin and mevalonate. 5-bromo-2-deoxyuridine (BrdU) incorporation was used to assess DNA synthesis. the present study showed that 10% FCS caused marked stimulation of DNA synthesis in the mesangial cells. Cerivastatin inhibited FCS-stimulated BrdU incorporation in a dose-dependent manner. IC₅₀ was approximately 1 umol/L. Exogenous mevalonate, farnesyl pyrophosphate and geranylgeranyl pyrophosphate significantly prevented the inhibitory effect of cerivastatin on DNA replication. It appears that cerivastatin, by inhibiting the synthesis of mevalonate, may suppress DNA synthesis in the mesangial cells.     

Effects of hydrocortisone and adrenaline on natural killer cell activity

We have studied the effects of hydrocortisone and adrenalineon natural killer (NK) cell activity and on the distributionof circulating lymphocyte sub-populations in 30 patients undergoingelective partial laminectomy under general anaesthesia. Thepatients were allocated to receive adrenaline (group 1, n =11), hydrocortisone and adrenaline (group 2, n = 11) or neitherhydrocortisone nor adrenaline (group 3, n = 8). Group 1 andgroup 2 patients received local adrenaline infiltration duringoperation to reduce bleeding. The mean dose of adrenaline administeredwas 2.1 (SD 0.2) µg kg^–1 Group 2 received hydrocortisone10 mg kg^–1 i.v. after premedication. In groups 1 and 2,adrenaline produced an instantaneous increase in NK cell activityaccompanied by a selective increase in circulating NK cells.The measurements returned to pre-infiltration levels within120 min of administration of adrenaline. The effect of adrenalinein causing increased NK cell activity was not blocked by pre-administrationof hydrocortisone. There was a significant decrease in the ratioof T helper/inducer cells (CD4) to T-suppressor/ cytotoxic cells(CD8) in all patients after induction of anaesthesia. In groups1 and 3, the CD4/CD8 cell ratio did not change significantlyduring operation. However, compared with groups 1 and 3, group2 showed a significantly reduced CD4/CD8 cell ratio during operation.Therefore, these results suggest that even in cases of suchsevere stress that the immune response was depressed by increasedserum cortisol concentrations, adrenaline-induced NK cell activityenhancement was preserved.     

Specific immunotherapy with tumour-draining lymph node cells cultured with both anti-CD3 and anti-CD28 monoclonal antibodies

For providing costimulatory signals, we utilized anti-CD28 monoclonal antibody (mAb) for the in vitro culture of tumour-draining lymph node (LN) cells. The proliferation of B16 melanoma-draining LN cells in the culture with anti-CD3 mAb was remarkably enhanced by the addition of anti-CD28 mAb. In culture with both anti-CD3 and anti-CD28 mAb, the B16-draining LN cells produced a higher level of interferon-γ, but not interleukin-4, than with anti-CD3 mAb alone. The B16-draining LN cells efficiently expanded in the culture with both anti-CD3 and anti-CD28 mAb and subsequently with a low dose of IL-2 (anti-CD3 plus anti-CD28/IL-2). The expanded cells consisted predominantly of CD8⁺ T cells and showed a specific cytolytic activity, in a major histocompatibility complex (MHC) class I-restricted manner, even without in vitro restimulation. In addition, the adoptive transfer of the B16-draining LN cells, expanded in the culture protocol of anti-CD3 plus anti-CD28/IL-2, showed a significant anti-tumour effect against metastatic B16 melanoma in combination with IL-2. The cured mice thus acquired a specific protective immunity. Moreover, this protocol was also moderately effective against poorly immunogenic 3LL carcinoma. Overall, our results suggest the potential for another immunotherapeutic strategy based on ‘the costimulatory theory’ other than vaccination with B7-transfected tumour cells.     

A Study on HL—A System in Japanese

Two hundred unrelated Japanese individuals were HL-A typed with UCLA Research Tray T3 (Terasaki's Tray), which contains specificities added after the Fifth International Workshop. Phenotype, gene and haplotype frequencies were calculated with standard errors and delta values. HL-A9, HL-A5 and W10 had a higher frequency and HL-A1, 3 and 8 had a lower frequency in Japanese than in Caucasians. The frequent haplotypes were HL-A9-HL-A5, HL-A9-HL-A7 and HL-A2W10. HL-A9-HL-A5 showed very positive high linkage disequilibrium parameter (delta value) and HL-A9-W10 showed negative high value. The sera designated as anti-HL-A, W5 and W15 in the T3 Tray which react identically in Caucasians showed different patterns of reaction when tested in the Japanese population. Five hundred Japanese parous women's sera were tested for cytotoxic antibodies. Some Japanese antisera showed high correlation coefficient values on HL-A2, HL-A9, HL-A10, HL-A11 and HL-A12. The women providing the anti-HL-5 complex sera and their immunizing persons were HL-A typed. These complex sera reactions were compared with the antisera in the T3 Tray. A new group of sera (SN-1), "operationally monospecific" and cross-reacting with W22, was found in the present study. Population and family studies suggested that the sera SN-1 are third in frequency within the second series (phenotypic frequency 17-22%) and show high delta values with HL-A11 in the Japanese population.     

RELATIONSHIP BETWEEN GENETIC POLYMORPHISM OF CYP2E1 AND ALDH2, AND POSSIBLE SUSCEPTIBILITY TO ALCOHOLISM

In 45 healthy Japanese volunteers, it was found that personsheterozygous for ALDH2 (ALDH2^*1/ALDH2^*2), and also either heterozygousor mutant homozygous for CYP2E1 (C₂/C₂ or C₁/C₂ can drink muchmore alcohol, even with (slight) flushing, than persons heterozygousfor ALDH2 (ALDH2^*1/ALDH2^*2) and normal homozygous for CYP2E1(C₁/C₁)     

Contact pressure distribution features in Down syndrome infants in supine and prone positions, analyzed by photoelastic methods

BACKGROUND: Local force distribution supporting the bodyweight of infants with Down syndrome (DS) appears to be different from that of healthy controls. The purpose of the present study was to establish methods to assess this force distribution and to allow therapeutic evaluation of neurological development in DS infants prior to walking. METHODS: Contact pressure distribution patterns in supine and prone positions were measured by photoelastic methods and were compared between DS infants and healthy controls. The DS group included eight subjects, seven with regular trisomy 21, and one with a Robertson translocation. The controls consisted of 14 neonates, four 4-month-old infants and eight 7-month-old infants. RESULTS: In both groups, head loading ratio decreased as age advanced but the decrement was less in the test group than in the control group. When the bodyweight loading ratios were measured in two different lying positions, that is, prone and supine, the ratios for prone generally tended to be smaller than those for supine in the controls. This kind of difference between prone and supine was not seen in the DS group. The bodyweight is somewhat sustained with limbs and the limbs loading ratios in the DS group were always significantly lower than in the controls. CONCLUSION: Coordinated development of weight-supporting limbs seems to be poor in the DS group.     

Altered intrahepatic pathway of para-umbilical vein in portal hypertension

The object of this study was to determine the frequency and characteristics of altered paraumbilical vein in the hepatic parenchyma, developed from portal hypertension, using computed tomography (CT). Two hundred and ninety-two patients who presented with portal hypertension from 1986 to 1996 were studied retrospectively. The pathway of the dilated para-umbilical vein was demonstrated by contrast-enhanced CT. Thirty-one (11%) patients had a dilated para-umbilical vein arising from the left portal vein into the falciform ligament. In 24 (77%) of these patients, the para-umbilical vein followed the expected route, passing through the fissure of ligamentum teres hepatis. The remaining seven patients (23%) displayed the unusual pathway, with the vein arising from the left branch of the portal vein and passing into the hepatic parenchyma. In these seven patients, four had one collateral vein, and three patients had two collateral veins in the liver parenchyma. The dilated para-umbilical vein frequently passes through the hepatic parenchyma in patients with portal hypertension.