Tartrate-resistant acid phosphatase-positive cells in the synovial–cartilage junction and bone marrow during the progression of collagen-induced arthritis in adult rats

We investigated the time-course changes in bone destruction in rats with collagen-induced arthritis (CIA). The synovial–cartilage junction (SCJ) and epiphyseal bone marrow of the femoral posteromedial condyle in CIA rats were evaluated histologically and immunohistologically at 2, 3, 4, 6, and 8 weeks after sensitization. Two weeks after sensitization, tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells formed resorption lacunae on the lateral side of the cortical bone under the SCJ. No resorption lacunae were observed in bone marrow. Three weeks after sensitization, resorption lacunae on the lateral side of the cortical bone expanded, but no bone marrow invasion by pannus was observed. In bone marrow, many TRAP-positive multinuclear cells appeared and formed resorption lacunae in subchondral bone. Four weeks after sensitization, cortical bone was destroyed, and pannus had invaded the bone marrow. After six weeks, trabecular bone and subchondral bone plate were extensively resorbed by TRAP-positive cells. Bone destruction in CIA began with the appearance of TRAP-positive cells on the lateral side of the cortical bone under the SCJ, followed by the TRAP-positive multinuclear cells in bone marrow, which were morphologically unconnected to the SCJ lesions. These histological findings suggested that bone destruction in the early stage of arthritis occurred in two anatomically different regions.     

Gonadotropin-inhibitory hormone neurons interact directly with gonadotropin-releasing hormone-I and -II neurons in European starling brain

Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic dodecapeptide (SIKPSAYLPLRF-NH(2)) that directly inhibits gonadotropin synthesis and release from quail pituitary. The action of GnIH is mediated by a novel G-protein coupled receptor. This gonadotropin-inhibitory system may be widespread in vertebrates, at least birds and mammals. In these higher vertebrates, histological evidence suggests contact of GnIH immunoreactive axon terminals with GnRH neurons, thus indicating direct regulation of GnRH neuronal activity by GnIH. In this study we investigated the interaction of GnIH and GnRH-I and -II neurons in European starling (Sturnus vulgaris) brain. Cloned starling GnIH precursor cDNA encoded three peptides that possess characteristic LPXRF-amide (X = L or Q) motifs at the C termini. Starling GnIH was further identified as SIKPFANLPLRF-NH(2) by mass spectrometry combined with immunoaffinity purification. GnIH neurons, identified by in situ hybridization and immunocytochemistry (ICC), were clustered in the hypothalamic paraventricular nucleus. GnIH immunoreactive fiber terminals were present in the external layer of the median eminence in addition to the preoptic area and midbrain, where GnRH-I and GnRH-II neuronal cell bodies exist, respectively. GnIH axon terminals on GnRH-I and -II neurons were shown by GnIH and GnRH double-label ICC. Furthermore, the expression of starling GnIH receptor mRNA was identified in both GnRH-I and GnRH-II neurons by in situ hybridization combined with GnRH ICC. The cellular localization of GnIH receptor has not previously been identified in any vertebrate brain. Thus, GnIH may regulate reproduction of vertebrates by directly modulating GnRH-I and GnRH-II neuronal activity, in addition to influencing the pituitary gland.     

A Superinfection of Salmonella typhi and Hepatitis E Virus Causes Biphasic Acute Hepatitis

A 47-year-old Japanese man was referred to our hospital because of a sustained high fever with diarrhea 12 days after a flight from India. Liver enzymes were elevated with rose spots, hepatosplenomegaly, relative bradycardia, and acute cholecystitis. A liver biopsy depicted the dense infiltration of lymphocytes and Kupffer cells in sinusoids and the granulomatous formation in the parenchyma. The liver damage was initially resolved with the administration of ceftriaxone for 16 days but flared up 1 week later. Laboratory tests yielded positive reactions for Salmonella typhi and hepatitis E virus RNA. The pathophysiological presentations of concurrent typhoid and type E hepatitis are discussed.     

A rare case of clear cell sarcoma with 4 types of EWSR1-ATF1 fusions detected not in primary site but in metastatic site

Clear cell sarcoma is a unique tumor which has EWSR1-ATF1 or EWSR1-CREB1 fusion. Several patterns of EWSR1-ATF1 fusion are observed in clear cell sarcoma. Since type 5–7 fusions were reported recently, they are classified as type 1–7. We examined EWSR1-ATF1 and EWSR1-CREB1 fusions in a single case of clear cell sarcoma with lung metastasis in a 36-year-old Japanese man. As a result, we found only type 1 EWSR1-ATF1 fusion in the primary site, but 4 types of EWS-ATF1 fusion (type 1, 2, 5, 6) were detected in the metastatic site. These 4 types of fusion were completely identical to the recent report, but the case had the same fusion patterns in both primary and metastatic sites. In our case, increased splicing activity in the EWSR1-ATF1 fusion might be acquired at the metastatic site. There is another possibility that metastasis might develop through the increased splicing activity in the fusion.     

Low-dose Interferon-α Treatment Improves Survival and Inflammatory Responses in a Mouse Model of Fulminant Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is accompanied by severe lung inflammation induced by various diseases. Despite the severity of symptoms, therapeutic strategies for this pathologic condition are still poorly developed. Interferon (IFN)-α is well known as an antiviral cytokine and low-dose IFN-α has been reported to show antiinflammatory effects. Therefore, we investigated how this cytokine affected ARDS in a mouse model. C57BL/6 mice received sequential intratracheal administration of α-galactosylceramide (α-GalCer) and lipopolysaccharide (LPS), which resulted in the development of fulminant ARDS. These mice were then treated intranasally with IFN-α and their survival, lung weight, pathological findings, and cytokine production were evaluated. Administration of low-dose IFN-α prolonged survival of fulminant ARDS mice, but higher doses of IFN-α did not. Histological analysis showed that low-dose IFN-α treatment improved findings of diffuse alveolar damage in fulminant ARDS mice, which was associated with reduction in the wet/dry (W/D) lung weight ratio. Furthermore, IFN-γ production in the lungs was significantly reduced in IFN-α-treated mice, compared with control mice, but tumor necrosis factor (TNF)-α production was almost equivalent for both groups. Low-dose IFN-α shows antiinflammatory and therapeutic effects in a mouse model of fulminant ARDS, and reduced production of IFN-γ in the lung may be involved in the beneficial effect of this treatment.