Glomerulonephritis with fibrillary deposition in a transgenic mouse carrying the human prototype c-Ha-ras gene (rasH2 mouse)

Glomerulonephritis was observed in a 34-week-old transgenic CB6F1 mouse carrying the human prototype c-Ha-ras gene (rasH2 mouse) from a medium-term carcinogenicity study of N-methyl-N-nitrosourea (MNU). Lesions were characterized by severe diffuse enlargement and prominent hyalinization of glomeruli. The hyaline material was positive for periodic acid-Schiff but negative for amyloid by the Congo red method. Immunohistochemically, affected glomeruli were positive for polyclonal anti-mouse IgG. Ultrastructurally, there were characteristic subendothelial and mesangial deposits composed of fibrils showing a fingerprint pattern. Lamellae were 7.5-14.3 nm in diameter and formed multilayered structures. In addition to the renal lesions, a lymphoma was observed in the thymus, with metastasis to the spleen and some lymph nodes. However, there was no glomerulonephritis in 32 other mice bearing thymic lymphomas and in more than 40 males and females given MNU in the same study. Thus, the lesions in this mouse may have been spontaneous. Glomerulonephritis was not found in more than 120 other male and female rasH2 mice in our facility. This is the first report of glomerulonephritis in a rasH2 mouse, a promising candidate for medium-term carcinogenicity risk assessment.     

Glycogen storage disease type III with muscle involvement: reappraisal of phenotypic variability and prognosis.

A review of the case histories of 19 Japanese patients with enzymatically proven glycogen storage disease (GSD) III who developed muscular symptoms at various ages illustrates the phenotypic variability of this disease. There seem to be 4 subgroups of GSD III with muscle involvement according to the clinical symptoms. The first group of patients is characterized by the childhood onset of muscle weakness and hepatic disorders. The second group of patients develops muscular symptoms in adult years while the liver symptoms start in childhood. The third group includes the patients whose muscle weakness started in adult years long after liver symptoms in childhood had disappeared. The fourth group shows only muscular symptoms as adults without any sign or history of liver dysfunction since childhood. The prognosis for each subgroup seems to be different; however, none of them appears to be better than that for GSD I, as has been suggested previously.     

Immunohistochemical evaluation of the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on dopaminergic nigrostriatal neurons of young adult mice using dopamine and tyrosine hydroxylase antibodies

The recovery of dopamine (DA) neurons in young adult mice from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damage was analyzed at various times after MPTP treatment with DA and tyrosine hydroxylase (TH) immunohistochemistry and also by chemical DA assay. A remarkable discrepancy in the recovery rate of DA and TH reactivities of the nigral neurons was observed: the TH immunoreactivities of both cell bodies in the substantia nigra and terminals in the neostriatum were markedly reduced 4 days after MPTP. However, these reactivities progressively improved and almost fully recovered after 25 days, while the DA immunoreactivities were maximally depleted 10 days after, and the depletion continued even through the 25th day. The alteration of DA levels was correlated with that of DA immunoreactivity. These findings suggest that a major effect of MPTP on the DA neurons of young adult mice is a transient neurotoxicity, and that the TH content improves more promptly than that of DA.     

Can Mycobacterium tuberculosis infection prevent asthma and other allergic disorders?

It is generally considered that tuberculosis (TB) is a disease which upregulates Th1 cell function. There is a hypothesis that infection of Mycobacterium tuberculosis may prevent allergic disorders such as bronchial asthma. However, our clinical experience of patients with TB somewhat conflicts this hypothesis. Hence, we investigated Th1/Th2 balance in the peripheral blood of patients with active TB by measuring serum levels of IgE antibody and by intracellular cytokine assay. We found that serum levels of IgE in the patients with active TB were significantly higher than in those with lung cancer or with COPD. In the TB patients, titers of IgE tended to correlate with disease severity. Intracellular cytokine assay demonstrated that IFN-gamma-positive cells were significantly decreased in the patients with active TB compared to normal controls. The ratio of IFN-gamma-positive (Th1-like)/IL-4-positive (Th2-like) cells was remarkably reduced in the TB patients (p < 0.0001). This ratio showed a significant negative correlation with erythrocyte sedimentation rate and with C-reactive protein. Therapy against TB for 2-3 months did not result in significant changes of the Th1/Th2 ratio. These findings suggest that infection of M. tuberculosis does not systematically upregulate Th1 cells in some patients, and is unlikely to prevent allergic disorders like asthma.     

Phasically firing neurons in the supraoptic nucleus of the rat hypothalamus: immunocytochemical and electrophysiological studies

Relations between firing patterns and peptides in supraoptic neurons of rat hypothalamic slice preparations were studied by electrophysiology, intracellular fluorescent dye-marking and immunocytochemistry. Seven out of 10 magnocellular neurons which showed phasically firing patterns were identified by injections of Lucifer Yellow-CH (LY); these were also stained with an anti-vasopressin serum. This report presents direct evidence that most of the phasically firing neurosecretory neurons in the supraoptic nucleus contain vasopressin. This study demonstrates the feasibility of combining immunocytochemical and electrophysiological techniques to study the peptides contents of single mammalian neurons.     

FAMILIAL AMYLOID POLYNEUROPATHY WITH MARKED HYPERTROPHY OF THE PERIPHERAL NERVES

Autopsy findings in a 40-year-old male with heredofamilial amyloidosis and polyneuropathy are reported. He had been suffering from progressive autonomic as well as sensorimotor dysfunctions. Prominent amyloid deposit was found in the kidney, heart, thyroid, and testis, and less in the interstitium and small vessels of almost all organs. The peripheral nerves, some showing prominent hypertrophy, were most severely involved by amyloid deposit in a form of stellate mass, which ultrastructurally consisted of radially arranged amyloid filaments. In the hypertrophied nerves and ganglia, in addition to amyloid, massive accumulation of acid mucopolysaccharide (AMPS) was seen filling up the interstitial space, which was the cause of hypertrophy. Ultrastructurally, AMPS was seen as finely granular substance. An extracted amyloid from the kidney showed 8 nm filament on negative staining and was estimated of having a molecular weight of 14,000.     

Dynamic characteristics of carotid sinus pressure-nerve activity transduction in rabbits

The dynamic characteristics of the baroreflex neural arc from pressure input to efferent sympathetic nerve activity (SNA) reveal derivative characteristics in the frequency range of 0.01 to 0.8 Hz (i.e., the baroreflex gain augments with increasing frequency) and high-cut characteristics in the frequency range above 0.8 Hz (i.e., the baroreflex gain decreases with increasing frequency) in rabbits. The derivative characteristics accelerate the arterial pressure regulation via the baroreflex. The high-cut characteristics preserve the baroreflex gain against pulsatile pressure by attenuating the high-frequency components less necessary for arterial pressure regulation. However, to what extent the carotid sinus baroreceptor transduction from pressure input to afferent baroreceptor nerve activity (BNA) contributes to these characteristics remains unanswered. To test the hypothesis that the carotid sinus pressure-BNA transduction partly explains the derivative characteristics but not the highcut characteristics, we examined the dynamic BNA response to pressure input in the frequency range from 0.01 to 3 Hz by using a white noise analysis in 7 anesthetized rabbits. The transfer function from pressure input to BNA showed slight derivative characteristics in the frequency range from 0.01 to 0.3 Hz with approximately a 1.7-fold increase in dynamic gain, but it showed no high-cut characteristics. In conclusion, the carotid sinus baroreceptor transduction partly explained the derivative characteristics but not the high-cut characteristics of the baroreflex neural arc. The present results suggest the importance of the central processing from BNA to efferent SNA to account for the overall dynamic characteristics of the baroreflex neural arc.     

Intracerebroventricular injection of arginine-vasopressin V1 receptor antagonist attenuates the surge of luteinizing hormone and prolactin secretion in proestrous rats

Metamorphosis in the fly (Musca domestica) involves extensive lysis, neurogenesis and reorganization of neural tissue. Despite this, two experiments are reported which show aspects of larval memory persist into the adult form. Experimental larvae were reared in sawdust scented with aversive odours (mint or geraniol). Control larvae were reared on plain sawdust. In blind post-metamorphosis testing using a Y maze, adult flies showed a preference for the specific odour to which the larvae had been exposed. Control flies found both test odours aversive. A second experiment explores the possible role of cell survival through metamorphosis as a mechanism of the persistence of memory. Cells from trained donor flies when grafted into untrained recipients produced specific changes in recipient odour preference reflecting the donor larvae training.