Movement disorders in encephalitis induced by Rhodococcus aurantiacus infection relieved by the administration of L-dopa and anti-T-cell antibodies

Mice injected with Rhodococcus aurantiacus by the intravenous (i.v.) route show neurological disorders, hemiparesis, vertical headshake and turn-round gait after day 7 postinfection (p.i.). Neurological symptoms caused by i.v. inoculation of R. aurantiacus were relieved by treatment with levodopa (l-dopa). R. aurantiacus was isolated from the brain and was found to be completely eliminated at day 7 p. i. Focal encephalitis was mainly observed in the brain stem, and T cells could be isolated from the brain after day 7 p.i. Administration of both an anti-CD4 monoclonal antibody (mAb) and an anti-CD8 mAb suppressed neurological symptoms. These results suggest that R. aurantiacus induces movement disorders in mice, and that the symptoms are mediated by T cells infiltrating the brain, rather than directly by the bacterium.     

Posthepatectomy hepatitis shortens tumor-free intervals in hepatitis C virus-associated hepatocellular carcinoma patients

In hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC), serum alanine aminotransferase (ALT) is frequently sustained on a high level after hepatectomy, with the formation of recurrent HCC tumors during follow-up periods. We investigated whether or not postoperative serum ALT level affects the interval before recurrence in hepatitis C virus-associated HCC. The subjects studied were 50 hepatectomized HCC patients who were HCV-Ab(+), and underwent a curable surgery in our Hospital from June 1990 to December 1999. We assessed the significance of the postoperative serum ALT level affecting tumor-free survival rates, as compared with other clinicopathological parameters, using univariate and multivariate Cox proportional hazard analysis. Thereafter, tumor-free and overall survival rates after hepatectomy were compared between high and low ALT groups, using Kaplan-Meier plotting and a log-rank test. The factor of ALT levels (a high or low ALT group) was most strongly associated with a tumor-free survival rate. Both tumor-free and overall survival rates were significantly poorer in the high ALT group than in the low ALT group among HCV-associated HCC cases (p<0.05). The results in this study suggest that postoperative hepatitis, which is indicated by sustained high ALT levels, may shorten the interval before recurrence in HCV-associated HCC. We should take care to control postoperative hepatitis to improve the prognoses of HCV-associated HCC cases.     

An Autopsy Case Combined With So-called Masson Bodies of Lung, Necrotizing Angitis of Gall Bladder and Subacute Glomerulonephritis—Pathologic and Histochemical Studies on the'Bourgexons Conjonctifs' (Masson,—

The Masson body termed by Masson, Riopelle and Martin in 1937, and periarteritis nodosa termed by Kusmaul and Maier in 1866 are both diseases recongnized as representing an allergic reaction.
I have studied an autopsy case of subacute glomerulonephritis, which also represents an allergic reaction, associated with Masson body and periarteritis nodosa.     

IL-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response

IL-1 is a pro-inflammatory cytokine consisted of two molecular species, IL-1alpha and IL-1beta, and the IL-1 receptor antagonist (IL-1Ra) is a natural inhibitor of both molecules. Although it is suggested that IL-1 potentiates immune responses mediated by T(h)2 cells, the role of IL-1 in asthma still remains unclear. In this study, we demonstrate that the ovalbumin (OVA)-induced airway hypersensitivity response (AHR) in IL-1alpha/beta-deficient (IL-1alpha/beta(-/-)) mice was significantly reduced from the levels seen in wild-type mice, whereas the responses seen in IL-1Ra(-/-) mice were profoundly exacerbated, suggesting that IL-1 is required for T(h)2 cell activation during AHR. OVA-specific T cell proliferation, IL-4 and IL-5 production by T cells, and IgG1 and IgE production by B cells in IL-1alpha/beta(-/-) mice were markedly reduced compared with these responses in wild-type mice; such responses were enhanced in IL-1Ra(-/-) mice. Using IL-1alpha(-/-) and IL-1beta(-/-) mice, we determined that both IL-1alpha and IL-1beta are involved in this reaction. Both IgG1 and IgE levels were reduced in IL-1beta(-/-) mice, while only IgE levels were affected in IL-1alpha(-/-) mice, indicating a functional difference between IL-1alpha and IL-1beta. These observations indicate that IL-1 plays important roles in the development of AHR.     

In vivo characteristics of low molecular weight copoly (D,L-lactic acid) formulations with controlled release of LH-RH agonist

Amorphous and crystalline copolymers with a relatively low molecular weight of 1800 were synthesized by direct copolycondensation of D-lactic acid and L-lactic acid in the absence of a catalyst, to evaluate their in vivo capabilities as biodegradable carriers for drug delivery systems. A luteinizing hormone-releasing hormone agonist, des-Gly10-(D-Leu6)-LH-RH ethylamide, was incorporated in a fine cylindrical copolymer formulation, under melt-pressing technique, a mild heat-pressure condition. This formulation was implanted subcutaneously in the back of male rats. The rate of in vivo degradation of amorphous copolymer was much faster than that of crystalline copolymer. Contrary to this tendency, the in vivo release of the drug from this amorphous formulation was held constant over a longer period, compared with the crystalline formulation. This can be closely related to the difference in dispersion of the drug in the formulation.     

Release of non-glycosylated polymeric immunoglobulin receptor protein

Using a recombinant vaccinia virus containing the T7 RNA polymerase, we have established a system for the transient expression of human polymeric immunoglobulin receptor (pIgR) in baby hamster kidney cells, a baby hamster-derived fibroblastic cell line. This transfection system resulted in the successful expression of pIgR in these cells, and Western blot analysis showed that human pIgR was expressed as two different molecular weight forms of 92 and 107 kDa. Treatment with endoglycosidase H showed that the difference between these two forms was due to the glycosylation status of the protein. In order to examine the functional role of glycosylation, we treated the transfected cells with tunicamycin, which prevents a core glycosylation step in the endoplasmic reticulum. Non-glycosylated pIgR was released into the culture medium of the transfected cells, albeit with extremely low efficiency. Taking these results together, we conclude that the glycosylation of pIgR may play a positive role in the efficient transport or release of free pIgR.     

Adult-onset type II citrullinemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle

Citrin is a mitochondrial aspartate glutamate carrier primarily expressed in the liver, heart, and kidney. We found that adult-onset type II citrullinemia is caused by mutations in the SLC25A13 gene that encodes for citrin. In this report, we describe the frequency of SLC25A13 mutations, the roles of citrin as a member of the urea cycle and as a member of the malate-aspartate shuttle, the relationship between its functions and symptoms of citrin deficiency, and therapeutic issues.     

Balanced complex rearrangement involving chromosomes 8, 9, and 12 in a normal mother,derivative chromosome 9 with recombinant chromosome 12 in her daughter with minor anomalies

We report on a 19-month-old girl with a derivative chromosome 9 and a recombinant chromosome 12 resulting from a maternal balanced complex rearrangement involving chromosomes 8, 9, and 12. The karyotype of the phenotypically normal mother was 46,XX,t(8;12) (9;12) (8qter→8p23::12q12→12q15::9q32→9qter;9pter→9q32::12q15→12qter;12pter→12q12::8p23→8pter). The child's karyotype was 46,XX,?9,?12, +der(9) (9pter→9q32::12q15→12qter),+rec(12) (12pter→12q15::9q32→9qter) mat. The child had severe growth retardation, minor anomalies including trigonocephaly, hypertelorism, broad nasal root, apparently low-set and posteriorly angulated ears, triangular face, pectus carinatum, clinodactyly of fifth fingers, and almost normal psychomotor development. To the best of our knowledge, there have been only 3 previous reports of recombination derived from parental complex chromosome rearrangements. In the recombination products, the chromosomes were apparently balanced and the offspring had no clinical abnormalities. The present case exhibited abnormalities and may have a submicroscopic aberration of 12q arising from crossing over during maternal meiotic pairing, although her chromosomes appeared to be balanced. © 1993 Wiley-Liss, Inc.