When male rats were given single i.p. injection of 500 mg of L-arginine/100 g body weight, the pancreatic acinar cells were destroyed selectively, without any morphological change of Langerhans' islets. As early as 24 hours after the injection, loss of basophilia, zymogen degranulation, and vacuolar and necrotic changes of the acinar cells were noted. After 3 days, fibroblastic activity and atrophy of pancreatic lobuli were evident. Early electron microscopic findings were changes of the endoplasmic reticulum, such as partial dilatation or vacuolation of the cisternae, usually with loss of ribosomes attached to the membrane. The effect of arginine excess may be ascribed to imbalance of amino acids and subsequent to decrease of protein synthesis in the acinar cells. In the course of this study, fat necrosis with marked infiltration of leucocytes was observed in adipose tissues in peripancreatic, epididymal, omental and retroperitoneal areas. This change correlated closely with the marked necrosis of the pancreas. An increase in the level of lipase in the blood was also demonstrated.

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Cryptococcus neoformans causes infection in individuals with defective T cell function, such as AIDS, as well as without underlying disease. It has been suggested that humoral as well as cellular immunity might play an important role in the immune response to C. neoformans infection. We have recently shown, using immunoblotting, that the 70-kD hsp family of C. neoformans was the major target molecule of the humoral response in murine pulmonary cryptococcosis. In this study we also used immunoblotting to define the antibody responses in the sera of 24 patients with pulmonary cryptococcosis: 21 proven and three suspected diagnoses. Anti-C. neoformans hsp70 antibody was detected in 16 of 24 (66.7%) patients with pulmonary cryptococcosis. Fourteen of 17 (82.3%) patients with high antigen titres (> or = 1:8) and two of seven (28.6%) patients with low titres (< or = 1:4) had detectable levels of anti-hsp70 antibody. Sera from patients positive for anti-hsp70 antibody showed high titres in the Eiken latex agglutination test for the detection of serum cryptococcal antigen. Our results indicate that the 70-kD hsp family from C. neoformans appears to be a major target molecule of the humoral response, not only in murine pulmonary cryptococcosis, but also in human patients with pulmonary cryptococcosis.

We compared the specificities and sensitivities of four tests used for the serodiagnosis of candidemia in 39 patients with candidemia, including 10 patients with superficial Candida colonization, 10 patients with deep mycosis, and 20 healthy subjects. The results obtained by the dot immunoblotting assay for detecting the enolase antigen (48 kDa) were compared with those of assays for detecting mannan antigen, heat-labile antigen (a threshold titer of four times), and ␤-glucan (>60 pg/ml). Enolase antigen was detected in 28 (71.8%) patients with candidemia, while 30 (76.9%), 10 (25.6%), and 27 (84.4%) patients were positive for the heat-labile antigen by the Cand-Tec assay, the mannan antigen by the Pastorex Candida assay, and ␤-glucan by the limulus test, respectively. Ten patients with superficial Candida colonization, 5 patients with invasive pulmonary aspergillosis, 5 patients with cryptococcosis, and 20 healthy subjects were negative for both enolase antigen and mannan antigen. Two patients with superficial Candida colonization, one patient with invasive pulmonary aspergillosis, and two patients with cryptococcosis were positive by the Cand-Tec assay. The ␤-glucan concentration was more than 60 pg/ml in all patients with invasive pulmonary aspergillosis; however, it was less than 10 pg/ml in all patients with cryptococcosis. The specificity of enolase antigen in the serodiagnosis of candidemia was 100%, but the sensitivity was 71.8%. The specificity and sensitivity of Cand-Tec, the assay for mannan antigen, and the assay for ␤-glucan were 76.9 and 87.5%, 25.6 and 100%, and 84.4 and 87.5%, respectively. Our results demonstrated that antigen detection tests are useful for the diagnosis of candidemia; however, none is satisfactory for the serodiagnosis of candidemia. We suggest that a combination of two assays may increase the accuracy of diagnosis of candidiasis.

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