Type-specific evolution of amyloid plaque and angiopathy in APPsw mice

To clarify how Aβ deposits start in the brain, we examined the early to late stages of senile plaques and amyloid angiopathy in APPsw mice. All types of human senile plaques were observed in the mouse brains. The premature forms of cored plaques appeared first in the cerebral cortex of mice at 7–8 months old. Then, amyloid angiopathy emerged, followed by diffuse plaques consisting of Aβ1–42. Modifications of the N-terminus of Aβ were late phase phenomena. The premature forms of cored plaques were composed of central Aβ1–40 amyloid cores, surrounding amorphous Aβ1–42 deposits, and accumulation of Aβ1–42 in some peripheral cells. These cells were incorporated in amyloid cores, and these plaques developed to large cored plaques composed of Aβ1–40 and Aβ1–42. The size and number of cored plaques were increased with age. These findings indicate different evolution paths for cored plaques and diffuse plaques, and suggest the presence of a pathway that initiates with the intracellular accumulation of Aβ1–42 and leads to the development of classic plaques in human brain tissues.     

Use of real-time PCR to monitor human herpesvirus 6 reactivation after allogeneic bone marrow transplantation

Reactivation of human herpesvirus 6 (HHV-6) is common following allogeneic marrow transplantation, however, little is known about the immune control and pathogenic potential of HHV-6 infection after transplantation. In order to determine whether reactivation of HHV-6 plays an important role in the development of complications in patients undergoing allogeneic bone marrow transplantation or not, we developed a very rapid quantification of viral DNA using a LightCycler. The amount of viral DNA was determined using a supernatant of a chronically infected cell line [TaY(OK)] which contains a known amount of viral DNA. Peripheral blood cells were collected from 5 patients undergoing allogeneic bone marrow transplantation once before transplant and once per week after transplant for 8-24 weeks. The real-time PCR system revealed that there was a linear correlation in the range of 101 to 105 molecules of reference. Using this system, we have found the presence of non-diagnosed HHV-6 reactivation as well as symptomatic infection, indicating the potential for routine implementation of this technology for laboratory diagnosis of HHV-6 infection. Our study shows that this method of rapid quantification of HHV-6 genomes by the real-time PCR using a LightCycler may be useful not only to understand the reconstitution of the immune system following marrow transplantation but also to manage the care of patients.     

Newcastle disease virus evolution. I. Multiple lineages defined by sequence variability of the hemagglutinin-neuraminidase gene

We compared the hemagglutinin-neuraminidase gene sequence among 13 strains of Newcastle disease virus (NDV) isolated over the last 50 years. Although overall homology was remarkably high, the sequence variability demonstrated the existence of at least three distinct lineages, which must have co-circulated for considerable periods. The sequence variability also appears to reflect some accumulation of mutations over time. Strictly correlating with the lineages, the translation products could be classified into three size classes. One class lacked the interchain disulfide bond, and another represented unusual precursor protein of biologically inactive form. The lineages correlated to some extent with virulence and place of isolation of the strains. However, antigenic variations, which were neither cumulative nor progressive, did not correlate with the lineages. These analyses showing multiple lineages were greatly facilitated by a precise calculation of synonymous substitutions, which had been largely free from selective pressures and had occurred frequently and evenly throughout the coding region.     

Expression of highly polysialylated neural cell adhesion molecule in rat subventricular zone with exposure to repeated kindled seizures

Immunoreactive highly polysialylated neural cell adhesion molecule (PSA-NCAM) expression was examined in the rat with repeated exposure to amygdaloid kindled generalized seizures (GS). In the sham control brain, PSA-NCAM staining was slightly observed in the subventricular zone (SVZ) of the striatum. The number of PSA-NCAM positive cells increased four times in the bilateral SVZ after three consecutive GS, with a further increase after 30 consecutive GS. As PSA-NCAM is involved in neural plasticity as well as migration of neural stem cells (NSC), expression of PSA-NCAM in the SVZ suggests that the recurrent GS may mainly contribute to reconstruction of synaptic network and could also contribute to NSC migration after kindling.     

IgE antibody to fish gelatin (type I collagen) in patients with fish allergy

BACKGROUND: Most children with anaphylaxis to measles, mumps, and rubella vaccines had shown sensitivity to bovine gelatin that was included in the vaccines. Recently, it was found that bovine type I collagen, which is the main content in the gelatin, is a major allergen in bovine gelatin allergy. Fish meat and skin also contain type I collagen. OBJECTIVE: The present study was designed to investigate IgE antibody to fish gelatin in children with fish allergy. METHODS: Serum samples were taken from patients in 3 groups: (1) 10 patients with fish allergy and specific IgE to fish meat; (2) two patients with allergies to both fish meat and bovine gelatin and specific IgE to fish meat and bovine gelatin; and (3) 15 patients with atopic dermatitis and specific IgE to fish meat. Various fish gelatins (type I collagen) were prepared from fish skin. IgE antibody to fish gelatin was analyzed by using ELISA and immunoblotting. RESULTS: Of 10 patients with fish allergy, 3 had specific IgE to fish gelatin. Of two patients with fish allergy and bovine gelatin allergy, all had specific IgE to fish gelatin. Of 15 patients with atopic dermatitis and specific IgE to fish meat, 5 had specific IgE to fish gelatin. Furthermore, IgE from pooled serum of the patients reacted with both the alpha1 and alpha2 chains of fish type I collagen in immunoblots. There is cross-reactivity among gelatins from various fishes, but there is little cross-reactivity between fish and bovine gelatins. CONCLUSION: Some fish-sensitive patients possessed IgE antibody to fish gelatin. Fish gelatin (type I collagen) might be an allergen in subjects with fish allergy.     

Cytokine production profile of splenocytes derived from zymosan A-treated SKG mice developing arthritis

Objective SKG mice have a point mutation of the zeta-associated protein of 70 kD (ZAP-70) and spontaneously develop a severe polyarthritis in the conventional condition, whereas they are healthy under the specific pathogen free (SPF) condition. The purpose of this study was to investigate the cytokine production from splenocytes in SKG mice developing arthritis under the SPF condition. Material SKG and BALB/c mice were intraperitoneally injected with zymosan A under the SPF condition. Spleen was isolated 1, 2 or 8 weeks after the intraperitoneal injection of saline or zymosan A. Splenocytes were cultured with concanavalin A. Cytokine production and proliferation were measured 48 and 72 h after the culture. Results An intraperitoneal injection of zymosan A induced severe polyarthritis with increased levels of rheumatoid factor and interleukin 6 (IL-6) only in SKG mice. Splenocytes from SKG mice did not proliferate well maybe because of less productivity of IL-2. The IL-4 production from splenocytes of SKG mice was higher, while interferon-γ production was lower than those of BALB/c mice. An injection of zymosan A reduced the IL-4 production only in SKG mice. Conclusions SKG mice do not develop arthritis under the SPF condition possibly because of a low proliferative activity of T cells and Th2-predominance. Received 27 December 2005; returned for revision 7 February 2006; accepted by A. Falus 10 March 2006     

Regional assignment of human protooncogenec-myb to 6q21→qter

Using human-mouse somatic cell hybrids containing different parts of chromosome 6 and a DNA probe of the oncogene (V-myb) of avian myeloblastosis virus (AMV), we regionally mapped by Southern blot techniques the human cellular myb (cmyb) protooncogene to 6q21qter.     

Polymorphous low-grade adenocarcinoma of submandibular gland origin

A case of polymorphous low-grade adenocarcinoma (PLGA) in the submandibular gland is reported. A 72 year old woman presented with a 5 year history of a gradually expanding tumor in the submandibular region. The surgical specimen revealed a relatively well demarcated tumor, 35 × 35 × 20 mm in size. Macroscopically, necrosis and hemorrhage were not seen in the solid tumor. Histologically, the tumor growth pattern was variable, composed of tubular, papillary, solid, trabecular and cribriform structures. Immunohistochemically, some tumor cells were positive for epithelial membrane antigen (EMA), S-100 protein, keratin, and carcino-embryonic antigen (CEA). Electron microscopically, prominent microvilli projected into the luminal spaces, and basal lamina and hemidesmosomes were seen in the tumor cells adjacent to the connective tissues. The submandibular gland is an extremely rare location for PLGA. To the authors' knowledge, this is the first case of its kind reported in the English literature.