H9N2 influenza viruses from Israeli poultry: a five-year outbreak.

Since 2000, hundreds of H9N2 viruses have been isolated from all types of domestic birds. Although H9N2 is a low-pathogenicity virus, disease has been observed in all types of poultry in the field. Clinical signs ranged from very mild disease to high morbidity and mortality when the virus was associated with a secondary pathogen. Because of the wide range of the virus and the great losses it caused, initially a local vaccination program was implemented, but mass vaccination was quickly authorized. A local strain, isolated in 2002 was selected and is currently in use as an inactivated vaccine. An intensive operation is in progress to characterize the isolates. Several genes (hemagglutinin [HA], neuraminidase, nonstructural protein, nucleoprotein, and matrix) were sequenced, revealing three main groups: the first group included two isolates from 2000, the second group included isolates from 2001 to the beginning of 2003, and the third group included all isolates from 2003 to date. The differences between the second and third groups, in a part of the HA gene, ranged from 3.49% to 6.97% (average 4.57%) of the nucleotides. Similar differences were recorded in the other tested genes. These data could indicate the probable introduction of distinct progenitor viruses into the Israeli poultry population. Furthermore, sequencing of the HA protein of some Israeli isolates revealed the presence of L216 in the binding site; this finding was typical of the H9N2 viruses isolated from humans, which raises the possibility of an influence on host specificity and virulence.

Ecology and molecular epidemiology of H9N2 avian influenza viruses isolated in Israel during 2000-2004 epizootic.

The first two isolates of H9N2 influenza virus were picked up from turkey and chicken hosts in May 2000, but the actual epizootic of the low pathogenicity avian influenza (LPAI) H9N2 virus started in December 2001, following a 1.5-year period of silence, during which the H10N7 and H6N3 influenza viruses were isolated sporadically. The outbreak of the H9N2 influenza began in northern Israel, from where the epizootic spread all over the country. Damage was relatively limited because of the widespread use of an inactivated vaccine. Single isolates were recorded in commercial ostrich and goose flocks, and in a wild pigeon. Apart from the routine serological tests, the diagnostics used the RT-PCR (reverse transcription polymerase chain reaction) test with type-specific primers related to the M and nucleoprotein (NP) genes, and a set of subtype-specific primers related to all the haemagglutinin (HA) and neuraminidase (NA) subtypes. All the primers were specially constructed. The part coding for N-terminus of the H chain of the HA gene of 61 out of 400 isolates was sequenced. The isolates showed a high rate of mutability, and differed distinctly from the H9 prototype strain; they belong to the same phylogenetic lineage divided into three sublineages, one of which exhibited a unique cleavage-site motif RSKR. The result indicates that two parallel evolutionary trends originated from the same local "prototype" isolate.

Lethally irradiated normal strains of mice radioprotected with SCID bone marrow develop sensitivity to low doses of staphylococcal enterotoxin B.

Normal strains of mice are rendered sensitive to small amounts (3-10 micrograms) of staphylococcal enterotoxin B (SEB) by transplanting bone marrow cells of SCID donor mice to lethally irradiated recipients. Four to 12 weeks post-transplantation, SEB induces 56-100% lethality. Transplantation of normal mouse bone marrow cells, either alone or with the SCID mouse selected bone marrow cells, does not confer SEB sensitivity. These data imply that either irradiation ablates certain cell population(s), that confer resistance to SEB in normal mice (populations that are absent in the SCID donor mice) or that the donor cells selectively repopulate recipients with SEB-sensitive cells. This model will help elucidate the cells, cytokines and the SEB peptide fragments responsible for SEB toxicity and will be useful in identifying promising vaccine candidates and in developing preventive medicines to protect against this potent toxin.

Effects of the accidental feeding of lasalocid sodium to broiler breeder chickens.

Lasalocid sodium was accidentally introduced into the feed of several broiler breeder chicken farms at levels between 115 and 150 ppm. On one farm, leg weakness and ataxia were observed in a few cockerels. A reduction in egg production and a sharp decrease in fertility and hatchability were observed in all the flocks receiving the contaminated feed. Many piping chicks were unable to hatch and there was an increase in the number of weak ataxic chicks at the hatchery. Histological examination of the muscle tissues of the affected cockerels, the piping chicks unable to hatch and the one-day-old chicks with leg weakness and ataxia revealed severe muscle damage. Increasing levels of lasalocid were detected in the yolk of eggs collected from the affected flocks.

Spontaneous uterine granular cell tumour in a Fischer 344 rat.

The microscopic features of a spontaneous uterine granular cell tumour in a Fischer 344 rat are described. The location of the tumour is novel for the rat. The neoplasm is characterized by the presence of cells with cytoplasmic granules which were PAS positive and diastase resistant. Electron microscopy and immunohistochemistry results are presented and the origin of the tumour is discussed.

Spontaneous rete testis adenocarcinoma in a Fischer 344 rat: a cytomorphological and ultrastructural study.

The report consists of a cytomorphological and ultrastructural description of a spontaneous rete testis adenocarcinoma observed in a 108-week-old Fischer 344 rat. This tumour is considered to be very rare in rats. Crucial evidence for the malignancy of this tumour was the penetration of a neoplastic gland into the tunica albuginea.

Gingival hyperplasia in rats induced by oxodipine--a calcium channel blocker.

Oxodipine, a new calcium channel blocker, induced gingival hyperplasia in rats. This is the first time that a calcium channel blocker has been documented as resulting in gingival hyperplasia in rats. In contrast to diphenylhydantoin, the hyperplastic changes induced by oxodipine were not precipitated by any prior irritation. The histology consisted of purely fibroblastic proliferation without infiltrate of inflammatory cells.

The renal carcinogenic effect of Merpafol in the Fischer 344 rat.

Three groups of Fischer 344 rats were fed Merpafol (Makhteshim, Israel), an agricultural fungicide, in increasing concentrations for a period of 2 years. A control group was maintained under identical conditions, but without the addition of the fungicide in the diet. A range of nonneoplastic and neoplastic lesions were observed in the kidneys of rats fed Merpafol. The histogenesis of the renal tumors is discussed in relation to chemical-induced epithelial hyperplasia and cystic tubular dilation. Comparative aspects of renal cyst development and carcinoma in humans are also discussed.

Quantitative evaluation of chlortoluran-induced splenic hemosiderosis by means of an image analyzer.

This study investigated a technique for the quantification of hemosiderin layed down in the spleen. The model used was the rat to which the urea-based herbicide chlortoluran was fed for 90 days. There was good correlation between hematological, biochemical, histological and image analytical techniques when splenic hemosiderosis was of a moderate to severe degree. Where hemosiderosis was of a slight nature, only the technique of image analysis was able to detect the on-going changes.

Toxicity study in rats of a tellurium based immunomodulating drug, AS-101: a potential drug for AIDS and cancer patients.

Male and female Sprague Dawley rats were injected intraperitoneally for 4 weeks with ammonium trichloro (dioxyethylene-0-0'-) tellurate, an immunomodulating drug at doses ranging from 3 to 24 mg/kg/week. Routine laboratory examinations included body weight, food consumption, clinical chemistry and hematological examinations. At termination of the experiment, all rats were sacrificed and subjected to a detailed necropsy. Few mortalities were recorded during the course of the study. Clinical signs included hind limb paresis and paraphimosis. A garlic odor pervaded the room. Body weight and food consumption were adversely affected in a dose-related manner. Effects were elicited on the hematological system; changes being noted in the platelet and leukocyte counts as well. Clinical chemistry evaluation revealed signs of hepatoxicity, especially in the female treated groups. The level of beta-globulin was increased. At necropsy organs were found to have a grayish-blue discoloration. Tellurium related histopathological changes were observed in the eyes, liver, thymus, bone marrow, heart and kidneys. An attempt has been made to compare the toxicity of this drug with other tellurium-containing compounds. A good correlation was found. Novel effects of the drug were retinopathy and replacement of bone marrow by bony or fibrous tissue. The possibility that some of the effects may have been elicited due to selenium-vitamin E deficiency has been considered.

Efficacy of antibodies to epidermal growth factor receptor against KB carcinoma in vitro and in nude mice.

Iodine-125-labeled monoclonal antibody 108.4 (108.4 mAb), raised against the extracellular domain of the epidermal growth factor (EGF) receptor, was shown to visualize sc xenografts of human oral epidermoid carcinoma (KB) cells in nude mice. In vitro, although EGF caused an increase in the number of KB cell colonies (150% at a concentration of 160 mM), the anti-EGF receptor antibodies reduced clone formation. At a concentration at which EGF caused a 50% increase in colony number, the addition of a 100-fold molar excess of 108.4 mAb resulted in a decrease in the number of cell colonies to 20% of the original value. Therefore, the effect of antibody on the KB tumor was studied in vivo in three different modes of tumor transplantation. Antitumor activity was demonstrated first by retardation (versus controls) of the growth of tumor cells as sc xenografts (P greater than .017), then by prolongation of the life span of animals with the ip form of the tumor (P less than .001), and finally on an experimental lung metastasis by a reduction in the number and size of tumors (P less than .05). When the anti-EGF receptor antibodies were added together with cisplatin, the antitumor effect was greatly enhanced, suggesting that the toxic activity of these agents is synergistic (P less than .007). The antitumor effect persisted when animals were treated with the F(ab)'2 fragment of the antibody, although it was less efficient. The Fab fragment of the antibody, whose ability to bind to the cell-associated receptor was completely conserved, did not affect the growth of the tumor. The activity manifested by the F(ab)'2 fragment of the anti-EGF receptor antibodies suggested that the antitumor effect was not due to immune mechanisms requiring the Fc portion of the antibody.

Gingival hyperplasia in dogs induced by oxodipine, a calcium channel blocking agent.

Subchronic oral exposure of dogs to Oxodipine, a new calcium channel blocker of the dihydropyridine-type, resulted in dose-related gingival hyperplastic changes. The doses at which an effect was elicited were 24 and 73 times the intended therapeutic dose for man. The effects were first noted after 7 weeks of treatment, and were limited to the high and intermediate dose groups of both sexes. Macroscopically, a generalized enlargement of the maxillary and mandibular facial and lingual gingivae were noted. The histological changes were similar to those described in man for Nifedipine and hydantoin-related drugs. An increase in the activity of alkaline phosphatase and a decrease in alanine aminotransferase was demonstrated. This article is the first to describe gingival hyperplasia in dogs induced in a dose-dependent manner by a calcium channel blocker.

Epidermoid cysts in the central nervous system of mice.

Two epidermoid cysts are described in mice, one intracranial, in the fourth ventricle and the other in the thoracic spinal canal. They were lined by compressed squamous epithelium and contained keratinaceous squamae. These incidental findings suggest that such cysts might be detected more often if more extensive examinations of the CNS were carried out in group studies.

Excretion and reexcretion of thermosensitive and wild-type strains of infectious bovine rhinotracheitis virus after co-infection or two successive infections.

Twelve cattle were divided into 2 groups. The first was intranasally co-infected with 2 strains of infectious bovine rhinotracheitis virus (Bovine herpesvirus 1; BHV 1): the thermosensitive vaccine strain IBR/ts RLB106 and a Belgian field isolate IBR/Cu5. Reactivation of BHV 1 was induced by dexamethasone treatment 2 months later and again 5 months later for 3 animals that only reexcreted small quantities of virus during the first dexamethasone treatment. The second group was intranasally infected with IBR/Cu5. Two months later, an attempt to reinfect this group with IBR/ts RLB106 failed. Four months after the primary infection, these cattle were treated with dexamethasone. Except after reinfection and at the beginning or the end of the (re)excretion periods, excreted and reexcreted viruses replicated at 35, 37 and 40 degrees C, indicating the presence of the wild-type virus. Only one isolate, out of 116 cloned from the nasal exudates collected during the excretion and reexcretion periods, expressed the thermosensitive phenotype. This isolate was characterized by its mean plaque size as the IBR/ts RLB106 strain. The epizootiological significance of these findings is discussed, with emphasis on the weak spreading capacity of the ts vaccine strain and the possibility of emergence of recombinant viruses.