Verminous vasculitis, pneumonia and pulmonary infarction in a cynomolgus monkey after treatment with ivermectin

An apparently healthy cynomolgus monkey (Macaca fascicularis) died 2 hours after routine inhalation anesthesia and implantation of a femoral catheter. Gross necropsy findings included patchy raised areas of severe pulmonary hemorrhage and consolidation. Filarioid nematodes (Edesonfilaria malayensis) were located in pulmonary blood vessels and in numerous 0.1-2 cm fibrous cysts on the pleural surfaces of the lungs, pericardium, diaphragm, retroperitoneum, and in the urinary bladder wall. Microscopic lesions included verminous vasculitis, pulmonary infarcts and pneumonia. Many of the nematodes were more necrotic than the surrounding host tissue. During quarantine, 17 days before surgery, the monkey had been given a single dose of ivermectin (200 micrograms/Kg, intramuscular) as an anthelminthic for gastrointestinal nematodes. It is postulated that many of the filarioid nematodes were killed by this treatment. These parasitic emboli caused pulmonary infarction and the severe inflammatory reaction. The resulting pulmonary disease compromised pulmonary function and contributed to death after anesthesia. This complication should be considered if monkeys possibly harboring filarioid nematodes are treated with ivermectin.     

Spontaneous hypertension and its sequelae in woolly monkeys (Lagothrix lagotricha)

Arteriolar nephrosclerosis was observed at necropsy in 26 of 38 woolly monkeys (Lagothrix lagotricha). This lesion is the earliest histologic change associated with hypertension in humans. Seventeen of the monkeys had died of congestive heart failure, renal failure or acute cardiovascular accident, complications similar to those seen in human hypertension. All monkeys known to be over 4 years of age were affected. Direct blood pressure measurements in nine otherwise healthy woolly monkeys revealed systolic pressures of 194 +/- 20 mmHg. Our physiologic, clinical and pathologic studies suggest that woolly monkeys develop hypertension spontaneously and could be a useful model for the study of human hypertension.     

Post-stenotic core flow behavior in pulsatile flow and its effects on wall shear stress

Arteries of several species, including man, tend to adjust their diameters such that the mean wall shear stress is in the range of 10-20 dynes cm-2. Additionally, intimal thickening in the human carotid bifurcation correlates well with the reciprocal of wall shear stress as determined in model studies. The correlation indicates that wherever the local mean wall shear stress exceeds approximately 10 dynes cm-2, the artery tends to be spared from intimal thickening. However, it is not known whether mean shear stress, i.e. the time-averaged value, or the instantaneous shear stress is the appropriate correlative variable. Each of these variables suggests different mechanisms for the reaction of the artery wall to its hemodynamic environment. It is therefore important to devise means by which the effects of mean shear and pulsatile shear can be separated in the study of atherogenesis. The present investigation examines the post-stenotic flow field in Plexiglas models under pulsatile conditions approximating those in the aortas of the cynomolgus monkey, an animal often employed in atherogenesis research. Behavior of the core flow and its effects on wall shear stress are studied for stenoses of 75 and 90% area reductions using laser velocimetry. The results show that the post-stenotic field contains regions in which the mean wall shear stress is low, but the pulsatile excursions are large.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neoplasms in NIH type II athymic (nude) mice

Necropsy and histopathology were performed over an 18-month period on 173 NIH type II athymic (nude) mice and 53 NIH type II mice heterozygous at the nu locus. A total of 149 mice were used in studies of tumor transplantation while 77 mice were screened as part of the quality assurance program for the colony. Twenty-nine neoplasms were found in 173 nu/nu mice. Only one neoplasm, an ovarian granulosa cell tumor, was found in 53 nu/+ mice. In nu/nu mice, there were nineteen lymphosarcomas, nine ovarian granulosa cell tumors, and one transitional cell carcinoma of the urinary bladder. A greater number of lymphosarcomas occurred in mice greater than 6 months old. A greater number of tumors, particularly lymphosarcomas, were found in nu/nu mice than in nu/+ mice.     

Assemblage-level effects of the introduced peacock hind (<Emphasis Type="Italic">Cephalopholis argus</Emphasis>) on Hawaiian reef fishes

The peacock hind Cephalopholis argus (family Serranidae), locally known as ‘roi’, was introduced from French Polynesia to Hawaii in the mid-twentieth century as a food fish. However, because of its association with ciguatera fish poisoning, it is rarely fished for food. Previous research indicates that roi could have a negative impact on native reef fish assemblages because of their high densities and prey consumption rates. However, it is unclear whether roi add to the cumulative mortality of prey (predation hypothesis), or whether predation is instead compensatory (doomed surplus hypothesis). This study experimentally assessed the effects of roi on reef fish populations through a long-term (5.5 year) predator removal experiment. A Before-After-Control-Impact study design was used to assess changes in fish assemblages following the removal of roi on 1.3 ha of patch reef. Increases in the density of prey-sized fish (<15 cm TL) were observed 18 months after roi removal. However, those effects did not translate into sustained increases in prey. While increases in potential competitors, wrasses (family Labridae), particularly the piscivorous ringtail wrasse Oxycheilinus unifasciatus, were observed on roi-free reefs, the fish assemblage did not diverge substantially in composition. Native reef fish appeared to resist the potential negative impacts of predation by roi, possibly through a refuge in size for some fish families. Management to protect intact fish assemblage size-structure could serve to bolster native resistance to invading species. In considering the threats facing coral reefs, and the possible solutions, roi removal alone will not likely replenish native fishery resources.     

Early evolution of metazoan serine/threonine and tyrosine kinases: identification of selected kinases in marine sponges

The phylum Porifera (sponges) was the first to diverge from the common ancestor of the Metazoa. In this study, six cDNAs coding for protein- serine/threonine kinases (PS/TKs) are presented; they have been isolated from libraries obtained from the demosponges Geodia cydonium and Suberites domuncula and from the calcareous sponge Sycon raphanus. Sequence alignments of the catalytic domains revealed that two major families of PS/TK, the "conventional" (Ca(2+)-dependent) protein kinase C (PKC), the cPKC subfamily, as well as the "novel" (Ca(2+)- independent) PKC (nPKC), form two separate clusters. In each cluster, the sequence from S. raphanus diverges first. To approach the question about the origin of protein-tyrosine kinases (PTK), which are found only in Metazoa, we analyzed two additional PS/TKs which have been cloned from S. domuncula: the stress-responsive protein kinase (KRSvSD) and the protein-kinase-C-related kinase (PRKvSD). The construction of the phylogenetic tree, comprising the eight PS/TKs and the PTK cloned previously from G. cydonium, revealed that the PTK derived from the branch including the KRSvSD kinase. These data facilitate the first molecular approach to elucidate the origin of metazoan PTK within the PS/TK superfamily.      

Analysis of lens cell fate and eye morphogenesis in transgenic mice ablated for cells of the lens lineage

Transgenic mice carrying the diphtheria toxin A gene driven by mouse gamma 2-crystallin promoter sequences manifest microphthalmia due to ablation of fiber cells in the ocular lens. Here we map ablation events in the lens by crossing animals hemizygous for the ablation construct with transgenic mice homozygous for the in situ lacZ reporter gene driven by identical gamma 2-crystallin promoter sequences. By comparing the spatial distribution of lacZ-expressing cells and the profile of gamma-crystallin gene expression in the lenses of normal and microphthalmic offspring, the contributions of specific cell types to lens development were examined. The results suggest that phenotypically and developmentally distinct populations of lens fiber cells are able to contribute to the lens nucleus during organogenesis. We also show that dosage of the transgene and its site of integration influence the extent of ablation. In those mice homozygous for the transgene and completely lacking cells of the lens lineage, we show that the sclera, cornea, and ciliary epithelium are reduced in size but, otherwise, reasonably well formed. In contrast, the anterior chamber, iris, and vitreous body are not discernible while the sensory retina is highly convoluted and extensively fills the vitreous chamber.     

Adenocarcinoma of Brunner's glands in a baboon (Papio cynocephalus)

A spontaneous neoplasm in an adult female baboon (Papio cynocephalus) was characterized by glandular formation, production of extracellular mucus, and focal invasion of the duodenal wall and pancreas. The tumor was diagnosed as a mucus-secreting adenocarcinoma of Brunner's glands.     

Regulation of rat ovarian cell growth and steroid secretion

A cultured rat ovarian cell line (31 A-F(2)) was used to study the effect of growth factors (epidermal growth factor [EGF] and fibroblast growth factor [FGF]), a survival factor (ovarian growth factor [OGF]), a hormone (insulin), and an iron-binding protein (transferring) on cell proliferation and steroid production under defined culture conditions. EGF and insulin were shown to be mitogenic (half-maximal response at 0.12 nM and 0.11 muM, respectively) for 31A-F(2) cells incubated in serum-free medium. EGF induced up to three doublings in the cell population, whereas insulin induced an average of one cell population doubling. FGF, OGF, and transferrin were found not to have any prominent effect on cell division when incubated individually with 31A-F(2) cells in serum-free medium. However, a combination of EGF, OGF, insulin, and transferrin stimulated cell division to the same approximate extent as cells incubated in the presence of 5 percent fetal calf serum. EGF or insulin did not significantly affect total cell cholesterol levels (relative to cells incubated in serum-free medium) when incubated individually with 31A-F(2) cells. However, cell cholesterol levels were increased by the addition of OGF (250 percent), FGF (370 percent), or a combination of insulin and EGF (320 percent). Progesterone secretion from 31A-F(2) cells was enhanced by EGF (25 percent), FGF (80 percent), and insulin (115 percent). However, the addition of a mitogenic mixture of EGF, OGF, insulin, and transferrin suppressed progesterone secretion 150 percent) below that of control cultures. These studies have permitted us to determine that EGF and insulin are mitogenic factors that are required for the growth of 31A-F(2) cells and that OGF and transferrin are positive cofactors that enhance growth. Also, additional data suggest that cholesterol and progesterone production in 31A-F(2) cells can be regulated by peptide growth factors and the hormone insulin.     

Genome sequence of the biocontrol strain Pseudomonas fluorescens F113

Pseudomonas fluorescens F113 is a plant growth-promoting rhizobacterium (PGPR) that has biocontrol activity against fungal plant pathogens and is a model for rhizosphere colonization. Here, we present its complete genome sequence, which shows that besides a core genome very similar to those of other strains sequenced within this species, F113 possesses a wide array of genes encoding specialized functions for thriving in the rhizosphere and interacting with eukaryotic organisms.