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.     

Expression of measles virus nucleocapsid protein in osteoclasts induces Paget's disease-like bone lesions in mice.

We targeted the MVNP gene to the OCL lineage in transgenic mice. These mice developed abnormal OCLs and bone lesions similar to those found in Paget's patients. These results show that persistent expression of MVNP in OCLs can induce pagetic-like bone lesions in vivo. INTRODUCTION: Paget's disease (PD) of bone is the second most common bone disease. Both genetic and viral factors have been implicated in its pathogenesis, but their exact roles in vivo are unclear. We previously reported that transfection of normal human osteoclast (OCL) precursors with the measles virus nucleocapsid (MVNP) or measles virus (MV) infection of bone marrow cells from transgenic mice expressing a MV receptor results in formation of pagetic-like OCLs. MATERIALS AND METHODS: Based on these in vitro studies, we determined if the MVNP gene from either an Edmonston-related strain of MV or a MVNP gene sequence derived from a patient with PD (P-MVNP), when targeted to cells in the OCL lineage of transgenic mice with the TRACP promoter (TRACP/MVNP mice), induced changes in bone similar to those found in PD. RESULTS: Bone marrow culture studies and histomorphometric analysis of bones from these mice showed that their OCLs displayed many of the features of pagetic OCLs and that they developed bone lesions that were similar to those in patients with PD. Furthermore, IL-6 seemed to be required for the development of the pagetic phenotype in OCLs from TRACP/MVNP mice. CONCLUSIONS: These results show that persistent expression of the MVNP gene in cells of the OCL lineage can induce pagetic-like bone lesions in vivo.     

Time trends of the prevalences of hepatitis B e antigen positives among hepatitis B virus carriers in Japan

In order to examine time trends of the prevalences of HBeAg positives among HBV carriers in Japan, we analysed data on HBeAg of HBsAg positive voluntary blood donors (23,560 males, and 8659 females) at the Osaka Red Cross Blood Centre between January 1977 and March 1984. Age-specific prevalences of HBeAg positives decreased year by year for both sexes, especially for those in their teens and twenties. The prevalences of HBeAg positives decreased with age, but at any given age it was lower for the later than for the earlier birth cohorts. Although reasons for the secular declines are unknown, the findings suggest that the prevalence of HBeAg positives among HBV carriers will continue to decrease in Japan. This, together with the immunization programme implemented this year, may lead to a future reduction in the risk of HBV related liver diseases in Japan.     

Characteristics of rhabdomyosarcoma cell lines derived from uterine carcinosarcomas

 Rhabdomyosarcoma (RMS) is occasionally found in the female genital tract, and mostly appears as one of the heterologous mesenchymal components in uterine carcinosarcoma designated as malignant mixed müllerian tumour (MMMT). We examined the biological properties of a pure rhabdomyosarcoma (RMS) cell line designated FU-MMT-3, which was newly established from a surgical specimen taken from a patient with uterine MMMT. We also evaluated c-myc and MYCN gene amplification in three RMS cell lines (including FU-MMT-3) derived from three MMMTs by Southern blot analysis. FU-MMT-3 cells were propagated continuously for 57 serial passages over a 2-year period in vitro. FU-MMT-3 was able to produce tumours demonstrating pure RMS in athymic nude mice. Cytogenetically, FU-MMT-3 showed a triploidy pattern, with complex karyotypic abnormalities including trisomy of chromosome 8. All three RMS cell lines, including FU-MMT-3, showed amplification of the c-myc gene (approximately fourfold to eightfold), while no cell lines demonstrated MYCN gene amplification. FU-MMT-3 is considered to provide a useful system for the study of the biological behaviour of RMS in MMMTs. Extra copies of chromosome 8 and c-myc gene amplification may be associated with the rhabdomyoblastic differentiation in MMMT. Received: 7 January 1997 / Accepted: 2 May 1997     

Reduction of infarct size and infiltration of polymorphonuclear leukocytes by a thromboxane synthetase inhibitor. Studies in a rabbit ischemic heart model.

The effect of sodium 6-(2-(1-(1H)-imidazolyl)methyl-4,5-dihydrobenzo(b) thiophene)carboxylate (RS-5186), a potent and long acting thromboxane synthetase inhibitor in vitro and in vivo, on infarct size and on the infiltration of polymorphonuclear leukocytes (PMNs), was studied in a rabbit coronary artery occlusion (1 h)--reperfusion (0.5 h or 3 h) model. The infarcted region was stained with triphenyltetrazolium, and the ratio of infarcted area/left ventricular area was calculated. The infiltration of PMNs into the infarcted region was determined by measuring the PMNs specific enzyme, myeloperoxidase (MPO) activity. In the vehicle treated group, infarct size and MPO activity were increased with increased reperfusion time from 0.5 h to 3 h (infarct size: 15.3 +/- 2.7 to 25.2 +/- 3.2%; MPO activity: 255 +/- 51 to 825.3 +/- 169.4 units/g wet weight). There was also a significant correlation (r = 0.90, p less than 0.01) between the infarct size and MPO activity. In contrast, in the RS-5186 treated group (2 mg/kg i.v.), both infarct size and MPO activity did not increase with prolongation of the reperfusion period (infarct size: 12.8 +/- 5.5 to 10.3 +/- 3.6%; MPO activity: 318.8 +/- 36.7 to 381.2 +/- 72.6 units/g wet weight). In 0.5 h reperfused samples, there was no significant difference in infarct size or in MPO activity between the vehicle treated group and RS-5186 treated group.(ABSTRACT TRUNCATED AT 250 WORDS)     

PEUTZ‐JEGHERS SYNDROME ASSOCIATED WITH RENAL AND GASTRIC CANCER THAT DEMONSTRATED AN STK11 MISSENSE MUTATION

A 75‐year‐old male was admitted to the gastroenterology unit of Nagoya City University Hospital due to epigastralgia after surgical treatment for right renal cancer. Endoscopy revealed advanced type 1 gastric cancer in the corpus of the stomach and multiple polypoid lesions in the stomach and duodenum. X‐ray examination of the small intestine using barium showed multiple polyps in the upper jejunum. Faint pigmentation on the palm was also detected. Peutz‐Jeghers syndrome (PJS) was diagnosed, despite a lack of family history. Total gastrectomy, resection of part of the upper jejunum and intraoperative endoscopic polypectomy of duodenal polyps was performed. This is the second reported case of PJS associated with renal cancer. We also detected a missense mutation in the tumor suppressor gene STK11 that, when mutated, is causative for PJS.     

Intravesical combination chemotherapy with mitomycin C and doxorubicin for superficial bladder cancer: a randomized trial of maintenance versus no maintenance following a complete response

Between November 1986 and April 1989, 101 patients with superficial bladder cancer were treated with intravesical instillations of mitomycin C on day 1 and doxorubicin on day 2 of each week for 5 consecutive weeks. Of 61 complete responders, 23 patients with carcinoma in situ and 28 with papillary cancer were randomly assigned to a non-maintenance group or to a group receiving maintenance therapy consisting of monthly instillations of the same drugs for 12 months. The 2-year non-recurrence rate calculated for patients with carcinoma in situ was significantly better in the maintenance group than in the non-maintenance group. A similar tendency was observed for patients with papillary cancer, although the difference was not significant. Side effects were considerable, with moderate to severe bladder irritation occurring in approximately half of the patients. In addition to our previous findings, the present results indicate that this intravesical combination chemotherapy is effective in eliminating superficial bladder cancers and that since the effect is not durable, even in complete responders, maintenance therapy is necessary to reduce subsequent tumor recurrence.Presented at the 4th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 16–17 November 1990, Osaka, Japan     

Anti-Candida albicans activity of essential oils including Lemongrass (Cymbopogon citratus) oil and its component, citral]

The effects of 12 essential oils, popularly used as antifungal treatments in aromatherapy, on growth of Candida albicans were investigated. Mycelial growth of C. albicans, which is known to give the fungus the capacity to invade mucosal tissues, was inhibited in the medium containing 100 micro g/ml of the oils: lemongrass (Cymbopogon citratus), thyme (Thymus vulgaris), patchouli (Pogostemon cablin) and cedarwood (Cedrus atlantica). Not only lemongrass oil but also citral, a major component of lemongrass oil (80%), in the range of 25 and 200 micro g/ml inhibited the mycelial growth but allowed yeast-form growth. More than 200 micro g/ml of citral clearly inhibited both mycelial and yeast-form growth of C. albicans. These results provide experimental evidence suggesting the potential value of lemongrass oil for the treatment of oral or vaginal candidiasis.     

Oxidative stress induced by iron released from transferrin in low pH peritoneal dialysis solution

Background. Transferrin binds extracellular iron and protectstissues from iron-induced oxidative stress. The binding of ironand transferrin is pH dependent and conventional peritonealdialysis (PD) solutions have unphysiologically low pH values.Herein, we investigated whether conventional PD solution releasesiron from transferrin and if the released iron causes oxidativestress. Methods. Effects of PD solutions on iron binding to transferrinwere examined with purified human transferrin and transferrinin dialysates drained from PD patients. Oxidative stress inducedby iron released from transferrin was evaluated in terms ofthe formation of thiobarbituric acid reactive substance (TBARS)and protein carbonylation in the human red blood cell (RBC)membrane. The iron deposition in peritoneal tissue from PD patientswas evaluated by Perls' staining with diaminobenzidine intensification. Results. Low pH PD solution released iron from transferrin.This iron release occurred within 1 min. Iron release was notobserved in neutralized PD solution. Iron released from transferrinin low pH PD solution increased TBARS formation and proteincarbonylation in the human RBC membrane. Iron deposition, whichis prominent in the fibrotic area facing the peritoneal cavity,was observed in the peritoneum of PD patients. Conclusions. Iron released from transferrin in low pH PD solutioncan produce oxidative stress in the peritoneum of a PD patient.Neutralizing PD solution can avoid this problem. Iron depositionin the peritoneum may participate in the pathogenesis of peritonealfibrosis in PD patients.