Three Consecutive Cases of Familial Hemophagocytic Lymphohistiocytosis, Including a Case Due to Maternal Uniparental Disomy.

We have experienced 3 consecutive cases of familial hemophagocytic lymphohistiocytosis (FHL). All affected infants had mutations in exon 3 of the perforin gene. The first had a homozygous mutation, c.1168C>T (p.R390*), caused by maternal uniparental isodisomy. The second and third had compound heterozygous mutations: c.781G>A (p.E261K) and c.1491T>A (p.C497*); c.1724G>T (p.C242G) and p.R390*, respectively. FHL is very rare in Northern Japan but should be suspected if infants exhibit prolonged fever. This is the first report of a relationship of p.R390* with FHL caused by uniparental isodisomy, and the second reported case of FHL type 2 with this form of inheritance.

Molecular screening of canine GM1 gangliosidosis using blood smear specimens after prolonged storage: detection of carriers among shiba dogs in northern Japan.

Molecular screening of GM1 gangliosidosis in Shiba dogs was carried out in northern Japan using blood smear specimens after prolonged storage. Of 125 specimens obtained from 3 veterinary teaching hospitals for this screening, 68 specimens (54%) were adequate for direct amplification in a polymerase chain reaction (PCR)-based DNA test, and the percentage of adequacy was different at each hospital (34%, 73%, and 100%), suggesting that the amount of blood on the smear and the storage condition of specimens may affect adequacy. Of the 68 dogs examined, 2 dogs (2.9%) were heterozygous carriers for this disease and the other dogs were all genotypically normal. The results suggest blood smear specimens can be useful for PCR testing after prolonged storage provided specimens contain a generous amount of blood and have been adequately stored. The study also suggests that GM1 gangliosidosis may be widely prevalent in the Shiba dog population in northern Japan.

Anaplastic atypical myeloma with extensive cutaneous involvement in a dog.

A 7-year-old, male, mixed breed dog was referred to the Veterinary Teaching Hospital at Kitasato University because of anorexia, lameness and multiple cutaneous lesions. Observation of bone marrow plasmacytosis, osteolytic bone lesions, serum myeloma protein and cutaneous infiltration of myeloma cells led us to a diagnosis of multiple myeloma (MM) with cutaneous involvement. Polymerase chain reaction and sequence analysis for the rearranged genes of immunoglobulin and T-cell receptor demonstrated that the neoplastic cells found in skin lesions or bone marrow are of B-lymphocyte lineage and share a common original precursor cell. The dog was treated with UW-Madison protocol or melphalan/prednisone protocol and survived 175 days. This is rare case of anaplastic MM with cutaneous involvement in dog.

Protective effects of wheat bran against diquat toxicity in male Fischer-344 rats.

After injection with 0.1 mmol diquat/kg body weight, survival time was markedly shorter in Fischer-344 rats fed a purified diet than in rats fed a regular diet, and much more severe hepatotoxicity and nephrotoxicity were observed in the former than in the latter. The longer the feeding period on the purified diet, the shorter the survival time after diquat administration. These results indicate that the purified diet lacked components present in the regular diet that had protective effects against diquat toxicity. These two diets had nearly the same composition and content of vitamins and minerals. We tested the ingredients of the regular diet to determine which ones reduce diquat toxicity. We found that wheat bran had a protective effect, but that rice bran and bean-curd refuse (okara) did not.

Relationship between body iron stores and diquat toxicity in male Fischer-344 rats.

The effects of body iron stores on diquat (DQ)-induced toxicity were examined in male Fischer-344 rats, which are sensitive to this herbicide. The rats (5 weeks old) were fed diets containing 40 (lower iron storage [LIS] group) or 320 ppm iron (higher iron storage [HIS] group) for 5 weeks. The concentrations of nonheme iron and ferritin in the liver and kidney were significantly higher in the HIS group than in the LIS group (P<0.0001), although there was no significant differences between the HIS and LIS groups in hematological parameters, including red blood cell count, hemoglobin concentration, and mean corpuscular volume. Three hours after administration of 0.1 mmol DQ/kg, serum alanine aminotransferase and urea nitrogen were significantly higher than in controls (saline injection) for both the LIS and HIS groups (P<0.01), and, after DQ injection, these parameters were significantly higher in the HIS group than in the LIS group (P<0.01). When the rats were injected with 0.075 or 0.1 mmol DQ/kg, the survival time was significantly shorter in the HIS group than in the LIS group (P<0.05). These findings suggest that higher body iron stores result in more severe DQ toxicity in Fischer-344 rats.

Psychological distress among evacuees of a volcanic eruption in Japan: A follow-up study.

Psychological distress in 248 evacuees from a volcanic eruption was evaluated using a 30-item General Health Questionnaire (GHQ-30) at four time points after evacuation: 6 months, 12 months, 24 months and 44 months. The proportion of evacuees with psychological distress (defined as a GHQ score >/= 8) significantly decreased from 66.1% (6 months) to 45.6% (44 months). The GHQ mean score significantly improved from 12.6 to 8.9. Investigation of each factor on the GHQ showed progressive improvement over time in 'anxiety, tension and insomnia' and 'anergia and social dysfunction'. However, 'depression' began to improve only after 44 months and 'interpersonal dysfunction' started to worsen after 12 months. The dysfunction in interpersonal relationships continued at 44 months. Examination of the relation between GHQ mean scores and age group showed that recovery from psychological distress was more difficult in middle-aged and older evacuees than in younger evacuees.