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.     

A case of parathyroid hormone-related peptide producing gallbladder carcinoma presenting humoral hypercalcemia of malignancy]

Humoral hypercalcemia of malignancy (HHM) in neoplastic syndrome has been most commonly reported in squamous cell carcinoma. Gallbladder carcinoma with HHM is uncommon. In this report, we describe a male case of gallbladder carcinoma with marked hypercalcemia and a high level of serum parathyroid hormone-related peptide (PTHrP). An immunohistochemical examination using PTHrP was also positive.     

Regeneration of the hamstring tendons after harvesting for arthroscopic anterior cruciate ligament reconstruction: a histological study in 11 patients

The purpose of our study is to evaluate whether the hamstring tendons can regrow after harvesting for anterior cruciate ligament (ACL) reconstruction and whether the regenerate tissue can be histologically characterized as tendinous. Eleven of the patients (eight female and three male; mean age, 23 years; range 17–37 years) consented to participate in this study. One year after the ACL reconstruction, surgical biopsy was done. Regeneration of the tendon was detected macroscopically in 9 of the 11 patients. Histologically and immunohistochemically, the regenerated tendons closely resembled normal ones. The results of this study show the hamstring tendons can regenerate after harvesting for the ACL reconstruction.     

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)     

A novel murine model of pharyngeal candidiasis with local symptoms characteristic of pharyngeal thrush produced by using an inhaled corticosteroid.

We established a novel murine model of pharyngeal candidiasis maintaining stable yeast population and local symptoms characteristic of pharyngeal thrush. The persistent Candida-infection was prolonged by inhalation of beclomethasone dipropionate corticosteroid. The severity of infection lesions was evaluated by determining viable cell number of Candia albicans and scores representing symptomatic curd-like white patch on pharyngeal tissue. The utility of this model was shown by the disappearance of lesions and fungal cells after treatment with fluconazole (FLCZ). The model would be useful for evaluating new chemotherapeutic or immunotherapeutic approaches against pharyngeal candidiasis, as well as in pathological studies.     

Amlodipine-induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats.

Amlodipine is a dihydropyridine calcium channel blocker that is widely used for the treatment of hypertensive patients and has an antioxidant effect on vessels in vitro. The aim of the present study was to examine whether treatment with amlodipine reduced oxidative stress in the brains of stroke-prone spontaneously hypertensive rats (SHRSP). The animals received amlodipine, nicardipine or hydralazine for 30 days in their drinking water. Levels of thiobarbituric acid-reactive substances (TBARS) in the brain (cortex, cerebellum, hypothalamus, and brainstem) were measured before and after each treatment. Systolic blood pressure decreased to similar levels in the amlodipine-, nicardipine-, and hydralazine-treated groups. Urinary norepinephrine excretion was significantly reduced in SHRSP after treatment with amlodipine, but not with nicardipine or hydralazine. Levels of TBARS in the cortex, cerebellum, hypothalamus, and brainstem were significantly higher in SHRSP than in Wistar-Kyoto rats (WKY), and were reduced in amlodipine-treated, but not in nicardipine- or hydralazine-treated, SHRSP. Electron spin resonance spectroscopy revealed increased levels of reactive oxygen species in the brains of SHRSP, which were reduced by treatment with amlodipine. Intracisternal infusion of amlodipine also reduced systolic blood pressure, urinary norepinephrine excretion, and the levels of TBARS in the brain. These results suggested that oxidative stress in the brain was enhanced in SHRSP compared with WKY rats. In addition, antihypertensive treatment with amlodipine reduced oxidative stress in all areas of the brain examined and decreased blood pressure without a reflex increase in sympathetic nerve activity in SHRSP.