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Biomedical subjects

D J Prieur

Publications and source records attributed to D J Prieur.

At least 73 records · Page 4Linked to original sources

Ocular melanin pigmentation anomalies in cats, cattle, mink, and mice with Chediak-Higashi syndrome: histologic observations.

The Chediak-Higashi syndrome (CHS) is a hereditary disorder of man, with the homologous condition reported in five animal species. Multiple defects, including oculocutaneous hypopigmentation, are present in individuals with this syndrome. Giant cytoplasmic granules, including melanosomes and lysosomes, are characteristic. In this study, eyes from CHS affected and control cats, cattle, mink, and mice were examined histologically to determine: 1) degree of pigmentation; 2) structure and distribution of melanin granules; and 3) morphology of cells and tissues containing melanin. The CHS cattle were found to be the most ocularly hypopigmented species, whereas CHS mouse eyes contained considerably more melanin than those of the other species. Melanin granules of abnormal sizes and shapes were present in neuroepithelial and uveal tissues of CHS animals of all four species. Depigmentation apparently had occurred in the CHS eyes, since less melanin was present in eyes of old CHS animals of each species than was present in eyes of young animals. In addition, melanin containing macrophages were common in CHS eyes, and the numbers of melanocytes and pigmented epithelial cells were decreased in older CHS eyes.

Animals↗

Auricular chondritis in fawn-hooded rats. A spontaneous disorder resembling that induced by immunization with type II collagen.

A spontaneous apparently unique auricular chondritis in the pinna of fawn-hooded rats is described. The chondritis was bilateral, with adult onset, and resulted in a marked thickening of the auricular cartilage. Microscopically, islands of proliferative cartilage were present, and at the margins between the normal cartilage and the thickened abnormal cartilage a marked cellular inflammatory response was present. The condition was familial in rats of the fawn-hooded strain and appeared to be unrelated to the platelet storage pool deficiency in this strain of rats. Biochemically no increased synthesis of pinna cartilage was detected. No histopathologic lesions were detected in other cartilaginous tissues of affected rats. The lesions in the pinna bore a striking resemblance to those induced in rats by immunization with Type II collagen. The spontaneous condition described herein may, therefore, represent a unique model of relapsing polychondritis of human beings, a disease with auricular chondritis associated with antibodies to Type II collagen.

Animals↗

Familial canine dermatomyositis. Initial characterization of the cutaneous and muscular lesions.

Familial canine dermatomyositis is a recently identified disease of collie dogs that resembles human juvenile dermatomyositis. The lesions in the skin and muscles obtained by biopsy from two litters of dogs were characterized for the purpose of determining the similarity of the lesions to those of human dermatomyositis. The cutaneous lesions began between 7 and 11 weeks of age and were present on the face, lips, ears, and skin over bony prominences of the limbs, feet, sternum, and tip of the tail. Histologically the cutaneous lesions frequently consisted of vesicles, pustules, and ulcers on the lips, face, and ears. Neutrophils, lymphocytes, mast cells, and macrophages were present throughout the dermis. Neutrophils and lymphocytes were also present in and around vessels. Between 13 and 19 weeks of age generalized muscle atrophy was noted. The muscle lesions consisted of interstitial lymphocyte, plasma cell, macrophage, and neutrophil accumulation; myofiber degeneration, regeneration, and atrophy; and fibrosis. Perivascular neutrophils, lymphocytes, and plasma cells were also seen. Histologically, the lesions resembled those present in human juvenile dermatomyositis; and these observations, coupled with clinical, immunologic, and clinical pathologic observations presented elsewhere, suggest that familial canine dermatomyositis is an appropriate and potentially useful model for human juvenile dermatomyositis.

Animals↗

Pathogenesis of feline gastric chlamydial infection.

Studies were conducted to determine whether the gastric chlamydiae that have been observed recently in cats are of pathologic significance. Chlamydiae were isolated in mouse L cell cultures from the homogenized pooled gastric mucosa of 3 cats that had been identified, by histopathologic examination, to have gastric chlamydiosis. Ten specific-pathogen-free kittens were exposed by aerosol and oral inoculation to the harvested feline gastric chlamydiae cell-culture media. In general, the clinical signs and lesions were conjunctivitis, rhinitis, and mild gastritis. The clinical signs and lesions were most severe in 2 chlamydia-infected kittens that had received methylprednisolone acetate (50 mg/kg of body weight). Chlamydiae were demonstrated in epithelial cells of conjunctival and nasal smears in 10 of 10 infected kittens from postexposure days 7 through 35. In addition, chlamydiae were isolated in L cell cultures from a variety of antemortem and postmortem specimens from infected kittens. The present study provided evidence that feline gastric chlamydiae, under appropriate conditions, were capable of inducing, in cats, clinical signs and lesions similar to those induced by the feline pneumonitis agent.

Animals↗

Secondary amyloidosis in a bull with Chediak-Higashi syndrome.

A ten year old Hereford bull with Chediak-Higashi syndrome was examined at necropsy after a lifelong history of recurrent bacterial infections. Amyloidosis, which has not been previously reported in Chediak-Higashi, was identified in liver, spleen and kidney.

Amyloidosis↗

Natural killer cell activity in fawn-hooded rats.

Fawn-hooded (FH) rats were shown to lack the genetically conditioned defect of natural killer (NK) activity hypothesized to be present by analogy with the Chediak-Higashi syndrome (CHS) in mice and human beings. In 4-h 51Cr release assays, splenic NK cells from FH rats killed YAC-1, RL male l and G1-TC tumor targets without deficiency based upon comparison with cells from BD-IV, BD-IX and NBR inbred rat strains. Progeny of BD X FH F1 rats backcrossed to FH failed to reveal a correlation of reduced NK activity and dilute coat color. From these, and other data presented, it is concluded that despite similarities in coat color dilution and platelet storage pool deficiency. FH rats do not closely resemble CHS mice or human beings in having deficient NK activity and cannot be considered the rat homolog of the CHS.

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Animal models.

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Animals↗

[3H]-imipramine binding sites in fawn-hooded rats.

The existence of high-affinity [3H]-imipramine recognition sites was demonstrated in membranes prepared from the cerebral cortex, hypothalamus and platelets obtained from fawn-hooded rats. The Bmax and Kd values for [3H]-imipramine binding to cerebral cortical membranes were virtually identical to those obtained with cortical membrane preparations of Sprague-Dawley rats. An NBR strain of rats, genetically related to fawn-hooded rats, was found to have significantly higher levels of [3H]-imipramine binding sites in cerebral cortical membranes when compared to fawn-hooded and Sprague-Dawley rats. All four strains of rats examined possessed extremely high densities of [3H]-imipramine binding sites in a purified platelet membrane fraction. These results do not support the finding of others that the cerebral cortex and platelets of fawn-hooded rats are virtually devoid of [3H]-imipramine binding sites.

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Prevalence, lesions, and differential diagnosis of Ollulanus tricuspis infection in cats.

Ollulanus tricuspis were found in the stomachs of 26 of 201 cats which were mainly from Washington and Idaho. Twenty-four of the cats were from research or commercial breeding colonies (catteries) and two were pets. Twenty-seven percent of colony cats were infected with O. tricuspis, whereas only 2% of the pet cats were infected. No consistent clinical signs were seen. Histologically there was a significant increase in fibrous connective tissue in the lamina propria and in the number of lymphoid follicles and globule leukocytes in the gastric mucosa of infected cats. Histologic examination revealed no parasites in 13 of the 26 infected cats. The 26 infected cats were identified by examination of stomach washings. An additional 21 cats had larvae of other nematodes in their stomachs. These nematode larvae need to be differentiated from O. tricuspis.

Animals↗

Chlamydial infection of the gastric mucosa in twelve cats.

Twelve cats, all from research or commercial breeding colonies, had unidentified, intracellular organisms in the gastric mucosa. Histochemical staining and ultrastructural features provided the basis for identification of the organism as a Chlamydia sp. Ultrastructural observations were restricted to one of the 12 infected cats. There was no consistent association of gastric chlamydial infection and clinical disease. The infection was present in apparently healthy cats as well as those with a variety of clinical signs and lesions, especially weight loss of undetermined origin. None of the cats with gastric chlamydial infection had lesions compatible with feline pneumonitis. The significance of gastric chlamydial infection has yet to be established.

Animals↗

Abnormal retinal projections in cats with the Chediak-Higashi syndrome.

The Chediak-Higashi syndrome (CHS) occurs in mammals, including humans and cats. The CHS is characterized by decreased oculocutaneous pigmentation, enlarged cytoplasmic granules, increased susceptibility to infections, and a hemorrhagic tendency. Ocular anomalies include pale irides and albinotic or subalbinotic fundi. Cats with CHS also have photophobia and prolonged postrotatory nystagmus. Since hypopigmentation of the pigment epithelium is correlated with misrouting of retinal ganglion cells in mammals, visual projections of CHS cats were examined by autoradiographic techniques to determine whether they exhibit abnormal retinogeniculate projections. In CHS cats, misrouted optic projections fragment layer A1 of the dorsal lateral geniculate nucleus into several islands, similar to the disruption of this lamina reported in the Siamese cat.

Animals↗

Ultrastructure of resting and activated storage pool deficient platelets from animals with the Chédiak-Higashi syndrome.

The ultrastructural of platelets from Chédiak-Higashi (CH) and normal cattle, mink, and cats at rest was studied. Platelets from CH animals had a virtual absence of platelet dense granules. Alpha granules, amorphous membrane-surrounded structures, mitochondria, and microtubules of CH bovine platelets were similar in number and appearance to those in normal bovine platelets. Giant CH granules, present in other cells and considered diagnostic of the syndrome, could not be identified in platelets from CH animals. The open canalicular system and dense tubule system were not readily identifiable in resting bovine platelets. The ultrastructure of normal and CH cattle platelets was evaluated at various stages of ADP-induced aggregation. After platelets changed shape during the first phase of aggregation, the ultrastructural appearance of CH platelets was similar to that of normal platelets. The CH platelets composing the aggregates during irreversible aggregation did not appear as activated as did normal platelets, even though the aggregation tracings were similar. Normal and CH cattle platelets treated with thrombin appeared morphologically similar and were characterized by centrifugal movement of granules.

Adenosine Diphosphate↗

A gastric nematode (Ollulanus tricuspis) in cats in the Pacific Northwest.

Ollulanus tricuspis, a minute gastric nematode not previously documented in the United States, was identified by histologic examination and by dissecting microscopic examination of stomach contents of 7 cats from 3 breeding colonies in the Pacific Northwest. The nematode may have contributed to chronic weight loss and undernutrition in part by causing gastric irritation, with resultant vomiting. The findings suggest that infection with Ollulanus parasites may be more widespread in the United States than realized.

Animals↗

Evaluation of the platelet storage pool deficiency in the feline counterpart of the Chediak-Higashi syndrome.

Cats with the Chediak-Higashi (CH) syndrome have abnormal hemostasis with prolonged bleeding times and normal coagulation times. Platelet aggregation induced by serotonin, ADP, and collagen was impaired. Platelets from normal and CH cats were incubated with 14C-adenine and then gel-filtered. Gel-filtered platelets (GFP) from CH cats contained 63% of the ATP, 38% of the ADP, 100% of the Ca2+, and 75% of the Mg25 of normal platelets. Serotonin could not be detected in CH platelets. Acid hydrolase and total platelet protein of CH platelets was similar to normal platelets. Gel-filtered platelets were treated with thrombin to induce maximal secretion. Secretion of ATP, Ca2+, and Mg2+ was 1.9%, 12.4%, and 16% respectively of normal platelets. ADP secretion by CH platelets was not detectable. The ATP/ADP ratio in the 14C-labeled metabolic pool of normal platelets was similar to that of total measured nucleotide pool of CH platelets. These findings suggest that in feline CH platelets, as in platelets from CH mink and cattle, there is storage pool deficiency that is virtually complete, and the virtual absence of ADP and 5HT may in part account for the abnormal hemostasis. Aggregation of platelets from CH cats was impaired, but these platelets did aggregate to arachidonate, serotonin-induced biphasic aggregation, and the aggregation response to ADP and collagen varied according to the amount of serotonin-induced TxB2 formed. These findings support a major role for arachidonate in platelet activation.

Adenine Nucleotides↗

Role of NK cells in tumour growth and metastasis in beige mice.

Although natural killer (NK) cells are thought to give the host a spontaneous resistance against tumours and have been postulated to act in vivo as surveillor cells, definitive data in support of these hypotheses has not been obtained. Recently the beige (bg) mouse, a morphological homologue of the human Chediak-Higashi (CH) syndrome, was shown to be deficient in NK activity. Specifically, spleen cells of bg mice were demonstrated to be incapable of in vitro natural cytotoxicity against tumour cells. We report here that a tumour line, modified to be sensitive to NK cytotoxicity by in vitro culture, demonstrated in vivo an increased growth rate, faster induction time and an increased metastatic capability in bg compared to control mice. This was not found with a tumour line insensitive to NK activity (without in vitro culture). In vivo activation of NK cells in bg and control mice resulted in a decrease in tumour growth rate and metastatic frequency. These results demonstrate that NK cells have an important function in the host's control of tumour growth and metastasis.

Animals↗

Role of natural killer cells in tumor growth and metastasis: C57BL/6 normal and beige mice.

The role of natural killer (NK) cells in tumor growth and metastasis was studied in syngeneic normal and beige inbred C57BL/6 mice. Mice with the beige point mutation have been shown to be deficient in nonstimulated NK activity. Tumor-passaged B16 malignant melanoma cells were refractory to NK activity as determined by in vitro assay, but after in vitro culture they became sensitive to NK activity. The NK-insensitive B16 tumor grew and metastasized similarly in normal and beige mice. However, the NK-sensitive B16 tumors grew more slowly and produced fewer metastases in normal mice than in NK-deficient beige mice. Activation of NK cells by lymphocytic choriomeningitis virus infection decreased the rate of growth and number of metastases of both NK-sensitive and NK-insensitive tumors in both normal and beige mice. These results suggest the importance of NK cells as a determinant of tumor growth and metastasis.

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