Roles of type II pneumocytes in macrophage (Mphi)-mediated host resistance to pulmonary Mycobacterium tuberculosis (MTB) and M. avium complex (MAC) infections were studied. Electron microscopy of the lung sections of mice given intratracheal infection indicated that the organisms invaded both Mphis and type II pneumocytes. When Mono-Mac-6 Mphis(MM6-Mphis) and A-549 type II pneumocytes (A-549 cells) were cocultivated, bacterial growth in MM6-Mphis was reduced by A-549 cell-derived soluble factors, indicating the roles of type II pneumocytes in Mphi-mediated host resistance to mycobacteria. MTB- or MAC-infected A-549 cells showed increased mitochondrial RNA expression of cytokines and surfactant proteins (SPs), in the order tumor necrosis factor-alpha (TNF-alpha) > or = granulocyte-Mphi colony-stimulating factor (GM-CSF) > Mphi chemoattractant protein > or = interleukin-8 > SP-D. Anti-TNF-alpha and anti-GM-CSF antibodies attenuated A-549 cell-dependent inhibition of intramacrophage mycobacteria, indicating their crucial roles in A-549 cell-mediated potentiation of Mphi antimycobacterial activity.

To examine whether simple f3-carbolines induce parkinsonian-like symptoms in vivo via N-methylation, the simple~3-carbolines norharman (NH), 2-mono-N-methylated norharmanium cation (2-MeNH~), and 9-mono-N '-methylnorharman (9-MeNH) were systematically administered to C57BL/6 mice for 7 days. These substances induced bradykinesia with reduction of locomotion activity. NH or 2-MeNH + decreased dopamine (DA) contents to 50-70% of values in controls in the striatum and midbrain. 9-MeNH potently decreased not only DA but also serotonin content in various regions. Immunohistochemical examination revealed that the numbers of tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta of NH-and 9-MeNHtreated mice were diminished to 76 and 66% of values in control mice, respectively. The formation of a toxic metabolite, 2,9-di-N,N'-methylated norharmanium cation (2,9-Me 2NH~), was 14 and eight times higher in the brain of mice receiving 9-MeNH than that in NH-and 2-MeNH + -treated mice, respectively. In cultured mesencephalic cells from rat embryo, 2,9-Me2NH~selectively killed TH-positive neurons only at a lower dose but was toxic to all neurons at higher doses. Thus, the excess formation of 2,9-Me2NH + would induce nonspecific neurotoxicity. These results indicated that 9-indole nitrogen methylation should be the limiting step in the development of the toxicity. NH, a selective dopaminergic toxin precursor, is sequentially methylated to form 2,9-Me2NH~,which could be an underlying factor in idiopathic Parkinson's disease. Key Words: /~-Carboline-Parkinsonism-Animal model-Dopamine-Nigrostriatal degeneration-Bradykinesia-N-Methylation.

A new, spontaneously occurring diabetic syndrome has been observed in the aged males of an inbred strain of Wistar rats, WBN/Kob. The main clinical sign, glycosuria, was first detected at about 60 weeks of age, and thereafter some animals developed hyperlipidaemia and gradual emaciation. Prior to the onset of glucosuria, male rats showed impaired glucose tolerance after a glucose load at 21 weeks of age. The histopathologic lesions of the pancreas in the diabetic males consisted of multifocal fibrosis, decrease in number and size of islets and atrophy of exocrine tissue. Multifocal inflammatory foci of varying stages were the main pancreatic lesion in prediabetic male rats. This inflammatory change was detected even in 12-week-old rats and tended to occur around the islets. Therefore focal fibrosis and the decrease in the number and size of islets were considered to result from post-inflammatory scarring. The maturity-onset of this syndrome and the impaired glucose tolerance in younger animals suggested that diabetes mellitus of this rat strain is insulin-independent type II. However, the histological lesions of the pancreas were somewhat different from previous reports of both type I and II diabetes mellitus in man and animals.

: Aims/Background: The mammalian liver receives both sympathetic and parasympathetic nerves that contain aminergic, cholinergic and peptidergic components. The intrahepatic distribution of nerve fibers are highly species‐dependent; and also, even within one species, there are notable variations. To reveal the pattern and type of hepatic innervation in different species, we examined the distribution and density of these nerve fibers. Methods: The livers of rats, golden hamsters, guinea pigs, dogs and humans were used. Aminergic and peptidergic nerve fibers were identified by immunohistochemistry for tyrosine hydroxylase (TH), neuropeptide Y (NPY), substance P (SP), vasoactive intestinal polypeptide (VIP), calcitonin gene‐related peptide (CGRP), and galanin (GAL), and cholinergic fibers were identified by the acetylcholinesterase (AChE) neurohistochemistry method. Results: AChE‐, TH‐, NPY‐, CGRP‐, VIP‐, and SP‐positive nerves were observed in the connective tissue of the portal region, and they were in close contact with hepatic arteries, portal veins and bile ducts in all five species. Within the parenchyma of guinea pig, dog and human livers, TH‐, NPY‐ and SP‐positive fibers were observed, but no AChE‐ and CGRP‐positive fibers were observed. In rat and hamster livers, no parenchymal nerve fibers could be demonstrated, but CGRP‐, NPY‐ and SP‐positive fibers were observed in the border of periportal areas. The density of CGRP‐positive nerve fibers were slightly higher around bile ducts than around hepatic arteries and portal veins. GAL‐positive fibers were not detected in any animal. Conclusions: These data indicate that there were differences in the patterns of hepatic innervation among rats, golden hamsters, guinea pigs, dogs and humans. The data also show that: 1) in rat and hamster livers, hepatic functions may be regulated by both sympathetic and parasympathetic nerves in the portal region; 2) in guinea pig, dog and human livers they may be regulated by these fibers both in the interlobular region (parasympathetic and sympathetic systems) and in the intraparenchymal region (sympathetic system); and thus, 3) in the latter three species, hepatocytes and sinusoidal cells may be innervated by sympathetic nerves.

1. Phytoncides are volatile substances released mainly from trees. We studied whether phytoncides can reduce stress responses in stroke-prone spontaneously hypertensive rats (SHRSP). 2. Under the restraint stress, SHRSP exposed to phytoncides showed lower blood pressure than those without the exposure (186.8 +/- 3.9 vs 207.7 +/- 3.4 mmHg, respectively, P < 0.01 by Student's t-test). 3. Consistent with the observation above, the plasma concentration of catecholamines under the restraint stress was lower in the phytoncides group than in the control group. 4. Based on these results, we concluded that phytoncides reduced the cardiovascular response to restraint stress in SHRSP.