Immune complex-mediated glomerulonephritis and interstitial pneumonia simulating Goodpasture's syndrome

An autopsy case of what was clinically considered to be Goodpasture's syndrome was investigated. The lung had hemorrhagic interstitial pneumonia, showing granular patterns of IgG and C3 along the alveoli by the immunofluorescent method and electron-dense subepithelial deposits by electron microscopy. The kidney had crescentic and segmental necrotizing glomerulonephritis associated with membranous nephropathy. Uneven, continuous patterns of immunofluorescent IgG and C3 along the GBM were noted. Electron microscopy showed numerous subepithelial deposits, and immunoelectron microscopy revealed that IgG was not present in the GBM itself but present in the subepithelial deposits. Anti-GBM antibody activity was not detected in the serum or the kidney eluate. It was suggested that renal and pulmonary lesions occurred through the same mechanism and in association with immune deposits. We propose that there is a disease having immune complex-mediated deposits. We propose that there is a disease having immune complex-mediated renal and pulmonary lesions which clinically resembles the conventional Goodpasture's syndrome.     

Association of the insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients of migraine with aura

Recently, several angiotensin I-converting enzyme (ACE) inhibitors and an angiotensin II receptor blocker were demonstrated to have a clinically important prophylactic effect in migraine. ACE is one of the key enzymes in the rennin-angiotensin-aldosterone system, which modulates vascular tension and blood pressure. In humans, serum ACE levels are strongly genetically determined. Individuals who were homozygous for the deletion (D) allele showed increased ACE activity levels. To investigate the role of ACE polymorphism in headache, we analyzed the ACE insertion (I)/deletion (D) genotypes of 54 patients suffering from migraine with aura (MwA), 122 from migraine without aura, 78 from tension-type headache (TH), and 248 non-headache healthy controls. The ACE D allele were significantly more frequent in the MwA than controls (p<0.01). The incidence of the D/D genotype in MwA (25.9%) was significantly higher than that in controls (12.5%; p<0.01; odds ratio=5.26, 95% confidence interval: 1.69-16.34, adjusted for age and gender). No differences in the remaining groups were found. Our results support the conclusion that the D allele and the D/D genotype in the ACE gene is a genetic risk factor for Japanese MwA. There seems to be a possible relationship between ACE activity and the pathogenesis of migraine.     

Alterations of 3-nitrotyrosine concentration in the cerebrospinal fluid during aging and in patients with Alzheimer's disease

To investigate the significance of nitric oxide (NO)-mediated neuron death in aging and Alzheimer's disease (AD), the 3-nitrotyrosine concentration in the cerebrospinal fluid (CSF) was investigated in neurologically normal controls and patients with AD. The 3-nitrotyrosine concentration and the 3-nitrotyrosine/tyrosine ratio significantly increased with advancing age, whereas the tyrosine concentration was unaltered. In patients with AD, the 3-nitrotyrosine concentration and the 3-nitrotyrosine/tyrosine ratio increased significantly (>six-fold) compared with controls of similar age, and increased significantly with decreasing cognitive functions, whereas the tyrosine concentration did not change. These findings suggest that an activation of tyrosine nitration, increase in nitrated tyrosine-containing proteins, and/or its degradation may be involved in brain aging and play an important role in the pathogenesis of AD.     

Increase in oxidized NO products and reduction in oxidized glutathione in cerebrospinal fluid from patients with sporadic form of amyotrophic lateral sclerosis

To determine the role of free radical mechanisms in the pathogenesis of amyotrophic lateral sclerosis (ALS), cerebrospinal fluid concentrations of oxidized nitric oxide (NO) products (nitrite and nitrate) and reduced and oxidized forms of glutathione (GSH and GSSG, respectively) were compared between patients with the sporadic form of ALS (SALS) and controls. In the SALS patients, the nitrate levels were significantly higher (by 73%) in contrast to remarkably lower GSSG/GSH ratio, approximately 3-fold, compared to controls. These results suggest that NO production or oxidation is activated in SALS patients, leading to a decrease in superoxide radicals to oxidize GSH. The subsequent generation of a highly reactive anion, peroxynitrite, may play a causal role in the pathogenesis of SALS.     

Intensified IgA mesangial deposits after administration of sheep anti-type IV collagen serum in mice

Sheep anti-type IV collagen serum was intravenously administered to male mice of the BALB/c, C3H and ddY strains, and their kidneys were morphologically studied monthly for 10 months thereafter. By immunofluorescence, the sheep IgG was seen to have immediately become conjugated to the glomeruli, mainly in a mesangial pattern. Successively, autologous mouse C3 and IgG appeared with the same type of distribution. Within 3 to 4 months after the start of the experiment, mouse IgA also appeared in the mesangium, especially in ddY mice. The intensity and frequency of mesangial IgA deposition and the serum IgA level increased with time in this strain. BALB/c and C3H mice also showed the same tendency of mesangial IgA deposition, although to a lesser degree. In summary, it was concluded that mesangial IgA deposition was due to non-immunological local trapping, on the basis of the results obtained by ELISA analysis of the sera and renal eluate. Although the ddY mouse is known to show spontaneous mesangial IgA deposition associated with a high serum IgA level with aging, these characteristics were much accelerated and intensified by this antiserum treatment. The relation of this observation to the pathogenesis of human IgA nephritis is discussed.     

EXPERIMENTAL MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS IN RATS INDUCED BY INTRAVENOUS ADMINISTRATION OF ANTI-THYMOCYTE SERUM

Focal glomerulonephritis was induced in rats, by a single intravenous injection of anti-Thy-1.1 antibody (ATS). One hour after the administration, the glomeruli of affected rats developed necrotic changes of the mesangial cells while after two hours, mesangiolytic changes appeared. From six days onwards, focal segmental mesangial proliferation which persisted until 30 days, occurred. This is thought to be the first report of experimental nephritis induced by pure anti-mesangial antibody.     

Serum gamma-glutamyl transpeptidase levels and hypertension in non-drinkers: a possible role of fatty liver in the pathogenesis of obesity related hypertension

The relationships between increases in body mass index (BMI) and increases in hypertension were compared between non-drinkers with elevated serum gamma-glutamyl transpeptidase (gamma-GTP) levels (> or = 50 U/l) and those with normal levels, who comprised 10,952 men and 22,107 women aged 40-59 years recruited from an occupational health clinic. Hypertension was found in 16.1% and 13.5% of the men and women, and elevated serum g-GTP was found in 10.8% and 2.8% of the men and women, respectively. The prevalences of hypertension and elevated serum gamma-GTP levels were both increased with increased BMI. Hypertension was, however, shown to be 1.5 times more prevalent in the persons with elevated serum gamma-GTP levels than in those with normal levels in both sexes, even after adjusting for BMI by a multiple logistic analysis. It can be concluded that elevations of serum gamma-GTP, which are probably a reflection of fatty liver in the non-drinkers, are closely related to the development of hypertension associated with increased obesity.     

The relationship between waist-to-hip ratio and occupational status and life-style factors among middle-aged male and female Japanese workers.

As a marker of body fat distribution and therefore level of obesity, the waist-to-hip ratio (W:H) is a good indicator of coronary heart disease risk status. The present study investigated the association between occupational status and life-style factors, and W:H of middle-aged Japanese male (n = 2,550) and female (n = 1,283) workers in a metal-products factory. A higher W:H was observed in the management level males as compared with the other male workers and we suggest this was promoted by the sedentary aspect of their work, as well as their higher levels of alcohol consumption and lower levels of leisure-time physical activity. In contrast, a higher W:H was recorded in female labourers, whose work was typically less sedentary as compared with female managers. Life-style factors included in the study were not related to this observation. We conclude that other unmeasured psychosocial factors may be important in promoting higher W:H in female labourers.