Encephalomyocarditis (EMC) virus-induced orchitis in Syrian hamsters.

Testes of 8-week-old male Syrian hamsters which were inoculated intraperitoneally with 10(5) plaque-forming units of the D variant of encephalomyocarditis virus (EMC-D) were examined virologically and histologically. Viral replication was detected from 1 day post inoculation (1 DPI), became more prominent 3 DPI, and was no longer demonstrated 7 DPI. The weight of testis decreased in course of time and it was about 2% of that of control 6 weeks post inoculation (6 WPI). Histopathologically, degeneration and/or necrosis of germinal cells and spermatogonia were observed in many seminiferous tubules of all hamsters 3 DPI. At 7 DPI, luminal obstruction by cellular debris and subsequent replacement of them by mesenchymal cells were common in mildly atrophic tubules surrounded with inflammatory cells. Thereafter, atrophy of seminiferous tubules became severer with the lapse of time and, in addition to plasma cell infiltration, apparent increase in the number of Leydig cells was found in the interstices. No regenerative signs of germinal epithelia were detected by 6 WPI. This is the first report of EMC virus-induced orchitis.     

Electrophysiological comparison between patients with Binswanger's encephalopathy and Alzheimer's disease

Short-latency somatosensory (SSEPs), brainstem auditory evoked potentials (BAEPs) and event-related potentials (ERPs) were studied in 7 patients with Binswanger's encephalopathy, 12 patients with Alzheimer's disease and 17 normal subjects. Patients with Binswanger's encephalopathy showed significantly prolonged central conduction time (CCT) and P300 latency, and prolonged tendency of I-V IPL compared to those of normal subjects. In particular, CCT showed significant prolongation compared to that of patients with Alzheimer's disease. In patients with Alzheimer's disease, I-V IPL and P300 latency were significantly prolonged compared to those of normals although there was no significant difference in CCT between Alzheimer's disease and normal subjects. These results indicate some difference between Binswanger's encephalopathy and Alzheimer's disease from the electrophysiological aspects although both of these entities are characterized by progressive mental deterioration.     

Two Cases of Peritoneal Serous Papillary Adenocarcinoma

Two cases of peritoneal papillary carcinoma are reported. The patient in the first case was a 71-year-old woman with symptoms of obstructive ileus. Laparotomy revealed a tumor in the omentum involving the transverse colon, and several small tumors in the peritoneum and pelvic wall. However, no primary site of the tumor was seen in the ovary, pancreas, or gastrointestinal tract. The patient in the second case was a 44-year-old woman with carcinomatous peritonitis. Postmortem examination revealed multiple tumors in the peritoneum, omentum, and pelvic wall. Tumors were also found in the cortex with mild invasion of the underlying parenchyma of the bilateral ovaries, although these lesions were thought to be metastatic. The histologic features of the tumor in both cases were those of tubulopapillary adenocarcinoma containing scattered psammoma bodies. The cells were positive with the PAS D technique, but negative with alcian blue staining. In both cases, the serum levels of CA-125 were considerably elevated, and the tumor cells showed positivity for CA-125, S 100 protein, cytokeratin and EMA by im-munohistochemistry. The present cases were most likely peritoneal serous papillary adenocarcinoma derived from extraovarian peritoneal mesothelium with miillerian potential, being different from the usual type of diffuse malignant mesothelioma. Acta Pathol Jpn 41: 642-646, 1991.     

Adhesion dependent release of hepatocyte growth factor and interleukin-1 receptor antagonist from human blood granulocytes and monocytes: Evidence for the involvement of plasma IgG,complement C3 and β2 integrin

Objective:Evolving evidence of anti-inflammatory effects is observed in patients with rheumatoid arthritis or ulcerative colitis following periodic adsorptive granulocyte and monocyte (GM) apheresis with a column containing cellulose acetate (CA) beads as apheresis carriers. This study was undertaken to obtain insights into mechanisms of anti-inflammatory actions of adsorptive GM apheresis with CA beads. Methods:In a series of in-vitro experiments, we investigated the effects of plasma proteins and the leucocytes 2 integrin (CD18) on granulocyte adsorption to CA beads. Results:Granulocyte adsorption to CA beads required plasma IgG, the complement C3 and was inhibited by an antibody to leucocytes CD18. Further, hepatocyte growth factor (HGF) and interleukin-1 receptor antagonist (IL-1ra) which have strong anti-inflammatory actions were released by granulocytes that adhered to CA beads. Conclusions:Plasma IgG, C3 derived complement activation fragments and leucocytes CD18 are involved in granulocyte adhesion to CA beads and hence the release of HGF and IL-1ra.Received 27 October 2003; returned for revision 16 December 2003; accepted by M. J. Parnham 8 January 2004     

Metabolism of senile amyloid precursor and amyloidogenesis. Age-related acceleration of apolipoprotein A-II clearance in the senescence accelerated mouse.

Serum clearance kinetics of murine senile amyloid-related high-density lipoprotein (HDL) apoprotein A-II (apo A-II) was examined in the senescence-accelerated mouse, prone (SAM-P/1) and resistant (SAM-R/1), with 125I-HDL purified from both strains. In SAM-R/1, with 125I-HDL purified from both strains. In SAM-R/1, the serum half-life of apo A-II was not altered with increasing age and was practically identical to that of apo A-I. In 2-month old SAM-P/1, the serum half-life of both apo A-I and apo A-II was generally the same as observed in SAM-R/1. However, at age 6 and 12 months, in SAM-P/1, the serum half-life of apo A-II decreased significantly and was less than that of apo A-I. These age-related changes in apo A-II clearance kinetics were observed regardless of the HDL donor. The authors also examined the tissue distribution of injected apo A-II, using 125I-apo A-II reconstituted HDL, and found that several organs trapped more 125I radioactivity in old SAM-P/1 than in young mice. This evidence strongly suggests that age-related changes in the metabolic environment of apo A-II might affect senile amyloidogenesis in SAM-P/1.     

Immune responses in newly developed short-lived SAM mice. Selectively impaired T-helper cell activity in in vitro antibody response.

New short-lived strains of mice (SAM-P), which have been developed by Takeda et al. (1981), shows a defective antibody response to T dependent (TD) antigen in vitro, as demonstrated in the accompanying paper (see page 419). In the present study, we investigated the cellular site of the defect, using a cell culture system. In this paper, it is demonstrated that T-helper (Th) cell activity for the antibody response to TD antigen is impaired, while other cellular immune responses, e.g. mixed leucocyte reaction, cytotoxic T-lymphocyte response, and delayed-type hypersensitivity reaction, are normal. These results suggest that the defect in T-helper subset is limited in helper function for the antibody response, and that the helper function for the cell-mediated immune responses is intact. These two functions of the T-helper subset are apparently regulated in a different manner. The SAM-P strains of mice may thus serve as an appropriate model for studying functional heterogeneity in T-helper/inducer cell subsets.     

Spontaneous age-associated amyloidosis in senescence-accelerated mouse (SAM)

Morphological studies on spontaneous systemic amyloidosis were conducted on 222 senescence-accelerated mice (SAM) (P) and on 150 mice in the senescence-resistant series (R).Among the pathologic findings, amyloidosis showed the highest incidence in both SAM (79.7%) and R (32.7%) Although an extensive deposition of amyloid was evident in some aged mice in the R series, a more severe amyloidosis occurred with a higher incidence in the P series. There was a statistical significance between the incidence of amyloidosis and age, in both the P and R series. There were no differences in organ distribution and mode of amyloid deposition between the P and R series or between the sexes. In about 60% of the amyloid-positive cases in the 28 killed SAM and 7 mice in the R series, there were no signs of inflammation or neoplasm.The morphological features in SAM more closely resembled those seen in cases of murine spontaneous senile amyloidosis than the features seen in cases of experimentally induced amyloidosis. This model is expected to be a valuable tool with which to assess the relationship between amyloid deposition and the aging process or senescence, perhaps even cases of human senile amyloidosis.     

C-reactive protein levels in the serum of asthmatic patients.

BACKGROUND: Asthma is a chronic airway inflammatory disease caused by immune cells such as T lymphocytes and eosinophils. Recently, highly sensitive C-reactive protein (hs-CRP) assays have become available for detecting small changes in CRP levels within the reference range, allowing for the evaluation of clinical inflammation. OBJECTIVE: To investigate the relationship between hs-CRP levels and bronchial asthma. METHODS: We collected blood samples from 109 patients with bronchial asthma, with or without attacks, and measured serum eosinophil cationic protein levels, pulmonary function, and serum CRP levels using an hs-CRP assay. RESULTS: Mean serum hs-CRP levels were significantly higher in patients without attacks (0.473 mg/L) and with attacks (0.908 mg/L) (P < .001 for both) than in controls (0.262 mg/L). Serum hs-CRP levels were inversely correlated with forced expiratory volume in 1 second/forced vital capacity in asthmatic patients (r = -0.4915; P < .01). CONCLUSION: Serum hs-CRP levels may be related to the state of asthma exacerbation and allergic inflammation.     

WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production

WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors and is essential for resistance to Leishmania major infection. In the present study, we demonstrated that WSX-1 was also required for resistance to Trypanosoma cruzi. WSX-1-/- mice exhibited prolonged parasitemia, severe liver injury, and increased mortality over wild-type mice. WSX-1-/- splenocytes produced enhanced levels of Th2 cytokines, which were responsible for the prolonged parasitemia. Massive necroinflammatory lesions were observed in the liver of infected WSX-1-/- mice, and IFN-gamma that was overproduced in WSX-1-/- mice compared with wild-type mice was responsible for the lesions. In addition, vast amounts of various proinflammatory cytokines, including IL-6 and TNF-alpha, were produced by liver mononuclear cells in WSX-1-/- mice. Thus, during T. cruzi infection, WSX-1 suppresses liver injury by regulating production of proinflammatory cytokines, while controlling parasitemia by suppression of Th2 responses, demonstrating its novel role as an inhibitory regulator of cytokine production.     

A pedigree analysis with minimised ascertainment bias shows anticipation in Met30-transthyretin related familial amyloid polyneuropathy.

In type I familial amyloid polyneuropathy (FAP) caused by a variant Met30-transthyretin (TTR), genetic anticipation has been reported. To determine whether anticipation of the disease is a true biological phenomenon or the result of ascertainment bias, we compared age at onset of the affected child with that of the affected parent in 68 parent-child pairs (including data on assumed age at onset and on asymptomatic obligate heterozygotes and parents at obligate 50% risk) in 15 families. Excluding the parent-child pairs involving the proband and "bilineal pairs", onset occurred earlier in the child than in the transmitting parent in 60 out of 68 "unilineal pairs". After correction for ascertainment bias resulting from incomplete penetrance and reduced biological fitness in early onset patients, the number of anticipation pairs (60 pairs) was still significantly larger than that of non-anticipation pairs (29.7 pairs) (p < 0.05). When the children were sons, the difference in age at onset was significantly greater in the mother-son pairs than in the father-son pairs (p = 0.023). Although not all ascertainment biases could be eliminated, these data show strong evidence that anticipation in the transmission of Met30-TTR FAP is a true biological phenomenon.