Melanocyte lysis by cytotoxic T lymphocytes recognizing the MART-1 melanoma antigen in HLA-A2 patients with Vogt Koyanagi Harada disease

The MART-1/Melan-A melanoma antigen recognized by the majorityof HLA-A2-restricted tumorinfiltrating lymphocytes is a selfantigen expressed on melanocytes and the retina. We have investigatedwhether Vogt–Koyanagi–Harada (VKH) disease and sympatheticophthalmia (SO), systemic inflammatory disorders affecting variousorgans containing melanocytes, are autoimmune diseases directedtoward the MART-1 antigen. In two of three patients with VKHdisease and one patient with SO, CD8⁺ T cell clones (TCC) fromintraocular fluid of HLA-A2⁺ patients lysed T2 cells when pulsedwith a HLA-A2-binding MART-1 peptide, but not a HLA-A2-bindingpMel-17 or tyrosinase peptide, in a HLA-A2-restricted manner.These CD8⁺ TCC lysed both melanocytes and melanoma cells ina HLA-A2-restricted manner. In addition, CD8⁺ TCC recognizinga HLA-A2-binding MART-1 peptide were also established from peripheralblood mononuclear cells of a patient with VKH disease. In contrast,either CD4⁺ TCC from these patients or CD8⁺ TCC from the intraocularfluid of HLA-A2⁺ patients with uveitis associated with Behcet'sdisease or HTLV-I uveitis did not show this cytotoxicity. Theresults demonstrate that the MART-1 peptide-specific cytotoxicT lymphocytes lyse melanocytes in the eye of patients with VKHdisease or SO, suggesting that these diseases are autoimmunediseases directed toward the MART-1 antigen in HLA-A2⁺ patients.     

Analysis of three compartments of extracellular fluid in dog

The distribution kinetics of an extracellular volume tracer 51Cr-EDTA was analysed from the results of continuous monitoring of plasma radioactivity. 51Cr-EDTA was injected intravenously into spleno-nephrectomized dogs by a single injection, and the radioactivity of circulating blood and physiological parameters were continuously monitored for 150 min. The dilution curve of radioactivity was resolved into 4 components, and expressed as c(t) = Ae-alpha t + Be-beta t + Ce-gamma t + D. The half-times of each term were 0.51, 2.41, and 19.26 min, respectively. Based on this result, 51Cr-EDTA space was divided into 3 compartments--plasma volume (V0), rapidly diffusing interstitial fluid (V1), and slowly diffusing interstitial fluid (V2). To explain the distribution of the tracer among these fluid spaces, two possible models were proposed. In the "tandem model" the volume of each compartment was calculated as 59.2, 121.7, and 101.7 ml/kg of body weight, respectively, and the mobility index of the tracer from V0 to V1 was 5.1 times as great as that from V1 to V2. In the "parallel model" the volumes were 59.2, 72.3, and 151.1 ml/kg of body weight and the mobility index of the tracer from V0 to V1 was 3.3 times as great as that from V0 to V2. The characteristics of each model were discussed in relation to the properties of the interstitial space.     

Role of N-methyl-D-aspartate receptors and the nitric oxide pathway in nociception/hyperalgesia elicited by protease-activated receptor-2 activation in mice and rats

Activation of the peripheral protease-activated receptor-2 (PAR-2) triggers nociceptive behaviour and thermal hyperalgesia in rats. The present study created a novel mouse model for PAR-2-triggered nociception, and then examined the roles of NMDA receptors and the nitric oxide (NO) pathway in nociceptive processing by PAR-2. Intraplantar administration of the PAR-2 agonist SLIGRL-NH(2) elicited nociceptive responses in mice, an effect being more specific in mast cell-depleted mice. This PAR-2-triggered nociception was abolished by the NMDA receptor antagonist MK-801, but not the neuronal NO synthase inhibitor 7-nitro indazole. In contrast, the PAR-2-triggered thermal hyperalgesia in rats was blocked by both agents. Our study thus provides a novel mouse model for PAR-2-mediated nociception, and suggests that NMDA receptors are involved in PAR-2-triggered nociception and hyperalgesia, while NO contributes only to the latter.     

Polyarteritis Nodosa with Atrophy of the Left Hepatic Lobe

A 73-year-old Japanese man with a history of partial gastrectomy due to gastric cancer 4 years previously was admitted because of intermittent fever. The patient developed abdominal pain, erythema, and myalgia in addition to the fever during the final clinical course, and died of acute heart failure. Autopsy disclosed atrophy of the left lobe of the liver and acute myocardial infarction. Neither metastasis nor recurrence of the cancer was observed. Small and medium-sized arteries of the visceral organs showed various stages of necrotizing vasculitis with narrowing of the lumina. The vasculitis was most prominent in the left lobe of the liver and in the heart. Narrowing of the portal vein due to portal tract inflammation in addition to vasculitis of the hepatic arteries may have induced ischemia and infarction, which had resulted in atrophy of the left hepatic lobe. Acta Pathol Jpn 42: 662–666, 1992.     

Neuronal histamine inhibits methamphetamine-induced locomotor hyperactivity in mice

Mianserin (5-20 mg/kg), like chlordiazepoxide (2.5-10 mg/kg), inhibits the shock-induced suppression of drinking (SSD) in rats. However, in contrast to chlordiazepoxide, the effect of mianserin is not blocked by the benzodiazepine antagonist, Ro 15-1788 (10 mg/kg). Although mianserin does not inhibit [3H]diazepam binding in vitro it has now been found to enhance [3H]flunitrazepam binding to mouse whole brain in vivo at 10-100 mg/kg p.o. These results suggest that mianserin does influence central benzodiazepine receptors, but the mechanism by which it does so differs from that of chlordiazepoxide.     

Interaction of cholecystokinin with vasoactive intestinal peptide in body shaking response to ice-water immersion in rats

Interaction of cholecystokinin (CCK) with vasoactive intestinal peptide (VIP) in body shaking response to ice-water immersion was observed in pentobarbital-anesthetized rats. Although CCK itself had no influence on the response, VIP suppressed it and this effect of VIP was antagonized by simultaneous administration of sulfated octapeptide of CCK, but not by non-sulfated CCK.     

Topographical projections from the thalamus to the putamen in the cat

Thalamic projections to the putamen (Put) in the cat were studied by the retrograde horseradish peroxidase method. Major thalamic projections to the Put originate from the midline and intralaminar nuclear regions including the centre médian-parafascicular complex (CM-Pf). The other thalamic projections to the Put arise mainly from the suprageniculate nucleus (Sg), magnocellular division of the medial geniculate nucleus (MGm), caudomedial part of the lateroposterior nucleus (LP) and ventrolateral part of the ventromedial nucleus (VM). The VM projects to the rostral Put, while the posterior thalamic regions (Sg, MGm, LP) project to the caudal Put.     

Enzyme-linked immunosorbent assay (ELISA) for detecting antisperm antibodies in mice with testicular autoimmunity

We developed an ELISA for measuring antisperm antibodies in the mouse by using serum samples obtained from mice immunized with murine testicular antigens in complete Freund's adjuvant (CFA) as well as from mice rendered vasectomized. Sperm antigens used were syngeneic epididymal spermatozoa and two types of soluble, murine testicular antigens prepared in our laboratory. This study deals with a) the sequential changes of antisperm antibody levels following immunization; b) determination of immunoglobulin classes of these antibodies; c) a correlation between the absorbance values and the endpoint titers of antisperm antibodies; and d) comparison of endpoint titers of antisperm antibodies detected by ELISA with those by immunoperoxidase staining method in immune and nonimmune sera. It is suggested that serum dilution as high as 1/800 or more is required for detecting antibody titers of immune sera, because nonimmune mouse sera reveal a definite, although low, level of absorbance value at a serum dilution of 1/400 or less.     

CHONDROID SYRINGOMA (MIXED TUMOR OF THE SKIN)

The clinicopathology of 13 cases of chondroid syringoma were examined. The ages of the patients ranged from 26 to 86 years, with an average of 48 years. There were eight males and five females. Ten tumors out of the thirteen appeared on the face. Only one patient out of ten was suspected of recurrence in follow-up information. Histologically, all tumors consisted of epithelial cells, chondroid or myxoid matrix, and other strumal elements. The tumors were histologically classified into two types; twelve tumors had tubular and cystic lumina lined by two layers of epithelial cells, and only one case had small lumina lined by only a single layer. By an immunohistochemical study with a PAP method, positive stainings of keratin were observed in all cases, and S-100 protein in all but one. Ultrastructurally, the tumor cells showed features of an epithelial cell. Some ultrastructural differences were noted between two types of chondroid syringoma. Type I tumor cells had many tonofilaments in cytoplasm, but cytoplasmic filaments in type II were of the intermediate-type.     

Kappa-type light chain crystal storage histiocytosis.

An autopsy case of systemic histiocytosis with excessive deposition of kappa-type light chain crystals was reported in a 58 year-old man who had consistently showed kappa-type light chain paraproteinemia, Bence Jones proteinuria and hypogammaglobulinemia for about 10 years until his death. However, no bony destruction was found by repeated X-ray examinations. At autopsy, extensive hyperplasia of crystal-storing histiocytes was observed in the bone marrow, spleen, liver, lymph nodes, interstitial tissues of visceral organs and loose connective tissues. In the bone marrow and some other tissues, mild proliferation of plasmocytoid cells containing small crystals were found. Histochemically the crystals positively stained with various methods for amino acids and proteins, especially with Weigerts' method for fibrin. Ultrastructurally intralysosomal crystal deposition was confirmed in the storage histiocytes and derivation of the crystals from Golgi's sacculi in the plasmocytoid cells was suggested. Biochemically the crystals were regarded as mainly consisting of dimers of a variable half of light chain immunoglobulin and immunochemically and immunohistochemically reacted to anti-kappa type light chain serum. Such a generalized storage histiocytosis may be secondarily induced by immunoglobulin synthesized in plasmocytoid cells.