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Biomedical subjects

J C Schuh

Publications and source records attributed to J C Schuh.

At least 19 recordsLinked to original sources
PubMed2000

Biochemical characterization of endogenously formed eosinophilic crystals in the lungs of mice.

Crystals seldom form spontaneously within tissues of mammals, except in the urinary tract or in association with eosinophil-rich diseases in humans (Charcot-Leyden crystals). Endogenously formed eosinophilic crystals have been reported in respiratory tract and other tissues of several strains of mice, but the biochemical characterization of these crystals has not been reported. In this study, eosinophilic crystal formation was examined in homozygous C57BL/6J viable motheaten mice, lung-specific surfactant apoprotein C promoter/soluble human tumor necrosis factor p75 receptor type II fusion protein transgenic mice (C57BL/6NTac x Sv/129), and CD40L-deficient mice with spontaneous Pneumocystis carinii infection. In viable motheaten but not wild type mice, rapidly developing crystals represented a major feature of the fatal lung injury induced by macrophage dysregulation. Conversely, eosinophilic crystals did not form until 4-8 months of age in transgenic and CD40L-deficient mice and were present in 10-30% of age-matched wild type controls. Mass spectrometry analysis of proteins from bronchoalveolar lavage fluid identified the crystals as Ym1, sometimes referred to as T-lymphocyte-derived eosinophil chemotactic factor. The Ym1 sequence was homologous to chitinase, and enzymatic assays indicated a 3-5-fold increase in chitinase activity compared with control mice. Intracellular and extracellular crystals associated with epithelial damage suggested that the crystals may contribute to lung inflammation through mechanical damage and enzymatic degradation.

Amino Acid Sequence↗
PubMed2000

Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice.

C57BL/6 mice genetically deficient in interleukin 15 (IL-15(-/-) mice) were generated by gene targeting. IL-15(-/-) mice displayed marked reductions in numbers of thymic and peripheral natural killer (NK) T cells, memory phenotype CD8(+) T cells, and distinct subpopulations of intestinal intraepithelial lymphocytes (IELs). The reduction but not absence of these populations in IL-15(-/-) mice likely reflects an important role for IL-15 for expansion and/or survival of these cells. IL-15(-/-) mice lacked NK cells, as assessed by both immunophenotyping and functional criteria, indicating an obligate role for IL-15 in the development and functional maturation of NK cells. Specific defects associated with IL-15 deficiency were reversed by in vivo administration of exogenous IL-15. Despite their immunological defects, IL-15(-/-) mice remained healthy when maintained under specific pathogen-free conditions. However, IL-15(-/-) mice are likely to have compromised host defense responses to various pathogens, as they were unable to mount a protective response to challenge with vaccinia virus. These data reveal critical roles for IL-15 in the development of specific lymphoid lineages. Moreover, the ability to rescue lymphoid defects in IL-15(-/-) mice by IL-15 administration represents a powerful means by which to further elucidate the biological roles of this cytokine.

Animals↗
PubMed1999

Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo.

To evaluate the utility of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a cancer therapeutic, we created leucine zipper (LZ) forms of human (hu) and murine (mu) TRAIL to promote and stabilize the formation of trimers. Both were biologically active, inducing apoptosis of both human and murine target cells in vitro with similar specific activities. In contrast to the fulminant hepatotoxicity of LZ-huCD95L in vivo, administration of either LZ-huTRAIL or LZ-muTRAIL did not seem toxic to normal tissues of mice. Finally, repeated treatments with LZ-huTRAIL actively suppressed growth of the TRAIL-sensitive human mammary adenocarcinoma cell line MDA-231 in CB.17 (SCID) mice, and histologic examination of tumors from SCID mice treated with LZ-huTRAIL demonstrated clear areas of apoptotic necrosis within 9-12 hours of injection.

Animals↗
PubMed1997

Flt3 ligand induces tumor regression and antitumor immune responses in vivo.

Daily treatment of mice with recombinant human Flt3 ligand (huFlt3L) results in a dramatic numerical increase in the number of dendritic cells (DCs) in vivo. Since DCs are pivotal in the induction of immune responses, we tested whether Flt3L treatment of mice challenged with a syngeneic methylcholanthrene (MCA)-induced fibrosarcoma would augment the generation of effective antitumor immune responses in vivo. Flt3L treatment not only induced complete tumor regression in a significant proportion of mice, but also decreased tumor growth rate in the remaining mice. A preliminary characterization of the cellular mechanisms involved suggests that Flt3L may be important in the treatment of cancer in situ through the generation of specific antitumor immune responses.

Animals↗
PubMed1995

Secondary retinoschisis in a dog.

Retinoschisis, an extreme form of cystic degeneration of the retina, was identified as a diffuse, bilateral microscopical change in an 8-month-old, male, English springer spaniel dog with a clinical history of blindness, retinal detachment and glaucoma. The absence of any material in the cystic spaces and the spectrum of intraocular degenerative changes indicated that the retinal change was a secondary retinoschisis, probably due to retinal detachment. Separation of retinal layers without disruption of the blood supply probably plays a part in the aetiology of retinoschisis. The pathogenesis and natural history of intraretinal cystic changes and retinoschisis in animals are poorly understood.

Animals↗
PubMed1992

Development and immunophenotyping of the pharyngeal tonsil (adenoid) in cattle.

Immunoperoxidase staining and electron and light microscopy were used to characterize the development of the pharyngeal tonsil in 98 cattle aged between 30 days of gestation and 12 years. The rugae of the pharyngeal tonsil were poorly formed before 95 days of gestation. Microvillous (M) cells associated with intra-epithelial leucocytes (lympho-epithelium) were scattered among ciliated and goblet cells covering most of the surface in post-natal animals. Intra-epithelial leucocytes were rare in fetuses, but ciliated and M cells could be distinguished. Leucocytes of the lamina propria started to accumulate at approximately 120 days of gestation. A loose accumulation of mononuclear cells progressed into a B-cell rich upper and T-cell rich lower layer, with typical lymphoid tissue organization in post-natal animals and lymphoid involution in aged cattle. Primary lymphoid follicles formed at 5 months of gestation, but germinal centres did not form until 2 to 4 weeks after birth. Except for null cells, the relative number of cells staining for each leucocyte phenotype or MHC class II antigen increased with age, especially during the neonatal period. The early development, strategic location and specialized structure of the pharyngeal tonsil suggest an important role in modulating inhaled antigens in cattle. Fetal and neonatal calves had minimal lymphoid tissue priming, as indicated by lack of secondary follicles, low MHC class II expression and few intra-epithelial leucocytes. The phenotypic differences may be relevant to the increased susceptibility of calves to infectious diseases shortly after birth.

Animals↗
PubMed1992

Bovine herpesvirus-1-induced pharyngeal tonsil lesions in neonatal and weanling calves.

The potential involvement of the pharyngeal tonsil in the pathogenesis of bovine herpesvirus-1 (BHV-1) infection was examined in neonatal and weanling calves infected by intranasal aerosol. Calves were monitored from days 1 to 5, and on day 6 (neonates) or 8 (weanlings) and, in a second trial at day 4.5, by histology, electron microscopy, immunocytochemistry and virus isolation. Mucosal lesions of neonates were similar to, but less extensive than, those of weanling calves. Loss of microvilli and goblet cells, with minimal epithelial erosions as early as day 1, progressed to necrosis of epithelium and adjacent lymphoid tissue, and leucocyte exudation. Lesions and clinical disease were progressive up to and including day 6 in neonates, but resolving in weanlings on days 5 and 8. By transmission electron microscopy, the physical characteristics of the phagocytic cells appeared similar in both age groups, and viral replication was not identified in leucocytes. Virus was isolated from, or found by immunocytochemistry in, the pharyngeal tonsil of all calves examined, except for two weanlings on days 1 and 8. Virus as detected by immunocytochemistry was restricted to epithelium and superficial lymphoid tissue in neonates, but was found in deep lymphoid tissue around germinal centres in weanlings. The study showed that the pharyngeal tonsil is readily infected with BHV-1 and may be an important lymphoid tissue for early anti-viral responses. The delayed inflammatory response and reduced viral clearance may contribute to the increased susceptibility of neonatal calves to fatal BHV-1 infections.

Animals↗
PubMed1989

Congenital intraocular melanoma in a calf.

A congenital benign intraocular melanoma was the cause of extreme buphthalmos in the enucleated right eye of a 7-day-old Charolais-cross calf. The tumour was well differentiated with rare mitotic figures and no evidence of extrascleral nor vascular invasion. Congenital intraocular tumours occur rarely in animals and man. There was no evidence of malignancy when the calf was slaughtered 9 months after the enucleation.

Animals↗
PubMed1989

Bilateral colobomas in a horse.

Bilateral true colobomas with retrobulbar cysts located over the optic nerves are described in an 8-year-old Quarterhorse mare with a history of progressive blindness. Colobomas result from the failure of an embryonic fissure to close and retrobulbar cysts result from eversion of the neuroectoderm through the colobomas. It could not be determined whether the small optic nerves and the scars, rosettes and disorganization of the cell layers in the retina were the result of concurrent dysplasia or were secondary to degeneration.

Animals↗
PubMed1987

Hepatic nodular myelolipomatosis (myelolipomas) associated with a peritoneo-pericardial diaphragmatic hernia in a cat.

Multiple hepatic myelolipomas were found in a domestic cat with a concurrent congenital peritoneopericardial diaphragmatic hernia. Histological features of the myelolipomas consisted of unencapsulated nodules composed of adipocytes interspersed with islands of haemopoietic tissue. The myelolipomas probably originated as metaplastic change within the liver, initiated by chronic hypoxia caused by entrapment of the affected liver within the pericardial sac. Nodular myelolipomatosis is suggested as a more accurate term for the non-neoplastic nodules referred to as myelolipomas.

Animals↗
PubMed1987

Equine basal cell tumors.

Basal cell tumors from 11 horses were examined histologically. Distinct patterns identified in the order of frequency are adenoid (six), solid (three), and medusoid (two). A minor component of most of these neoplasms was a ribbon pattern and cystic spaces. Hyalinized connective tissue and clear cells reminiscent of hair follicle glassy membranes and outer root sheath were present in a solid and the medusoid tumors. Heavy melanin pigmentation was present in one solid basal cell tumor. In eight cases for which information was available, the tumors had not recurred 3 to 8 years after excision.

Animals↗
PubMed1986

Inclusion body disease of cranes: comparison of pathologic findings in cranes with acquired versus experimentally induced disease.

Inclusion body disease of cranes was the cause of death in 17 immature and mature cranes of 5 different species in Wisconsin. A herpesvirus of unknown origin was the apparent cause. An isolate of this herpesvirus was used to experimentally infect 3 species of cranes. Macroscopic and microscopic lesions associated with naturally acquired and experimentally induced disease were essentially identical. Multifocal hepatic and splenic necrosis was found in all cranes evaluated. Necrosis of the gastrointestinal tract, thymus, and bursa of Fabricius also was seen in some of the cranes. Eosinophilic intranuclear inclusion bodies often were commonly associated with hepatic lesions, sometimes with the splenic lesions, and rarely with the thymic or gastrointestinal tract lesions. The lesions of this inclusion body disease were similar to those reported for cranes in Austria from which a crane herpesvirus was isolated.

Animals↗