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Biomedical subjects

M D McGavin

Publications and source records attributed to M D McGavin.

At least 19 recordsLinked to original sources

Transgenic mouse model of AA amyloidosis.

AA amyloidosis can be induced in mice experimentally through injection of certain chemical or biological compounds. However, the usefulness of this approach is limited by its dependence on exogenous inflammatory agents that stimulate cytokines to increase the synthesis of precursor serum amyloid A (SAA) protein and the transitory nature of the pathological fibrillar deposits. We now report that transgenic mice carrying the human interleukin 6 gene under the control of the metallothionein-I promoter had markedly increased concentrations of SAA and developed amyloid in the spleen, liver, and kidneys by 3 months of age. At the time of death about 6 months later, organs obtained from these animals had extensive amyloid deposits. This disease process was apparent radiographically using small-animal computer axial tomography and magnetic resonance imaging equipment. The AA nature of the amyloid was evidenced immunohistochemically and was unequivocally established by sequence analysis of protein extracted from the fibrils. The availability of this unique in vivo experimental model of AA amyloidosis provides the means to assess the therapeutic efficacy of agents designed to reduce or prevent the fibrillar deposits found in AA and other types of amyloid-associated disease.

Amino Acid Sequence↗

Bilateral renal metastases of nasal chondrosarcoma in a dog.

Chondrosarcoma is the most common nonepithelial sinonasal neoplasm in the dog, and metastasis is considered rare. A 7-year-old Irish Setter had bilateral renal enlargement 17 months following surgery and radiotherapy for a primary nasal chondrosarcoma. Histologic evaluation revealed chondrosarcoma metastases in both kidneys. A diagnosis of nasal chondrosarcoma with bilateral renal metastasis was made. The clinical importance of this report is that routine recommendations for the evaluation of regional and/or distant metatasis in a dog with a dignosis of nasal chondrosarcoma, namely routine whole body physical examination and thoracic radiography, failed to demonstrate the presence of abdominal metatases, which ultimately led to the demise of this dog. The biologically aggressive nature of this chondrosarcoma of the nasal cavity indicates that additional information is needed before a prognosis can be reliably established for dogs with this tumor type.

Animals↗

Simultaneous exposure to nicotine and hyperoxia causes tumors in hamsters.

BACKGROUND: We have shown that the nicotine-derived nitrosamine 4-(methyl-nitrosamino)-3-(pyridyl)-1-butanone (NNK) causes a high incidence of neuroendocrine lung tumors in male Syrian golden hamsters when administered to animals maintained in an atmosphere of 60% hyperoxia. In vitro studies with fetal hamster pulmonary neuroendocrine cells (PNE cells) and human neuroendocrine lung cancer cell lines revealed that nicotine and NNK are both potent mitogens for normal and neoplastic PNE cells when the cells were maintained in an atmosphere of high CO2. These effects were completely inhibited by antagonists of nicotinic acetylcholine receptors (nAChR). NNK displaced 3H-(-)L-nicotine from the nAchR in radioreceptor assays with cell membrane fractions from hamster lungs enriched in PNE cells. We therefore hypothesized that NNK acts as an agonist of the nAchR in PNE cells and that stimulation of this receptor in an environment of impaired pulmonary oxygenation is an important molecular event leading to the development of lung tumors with a neuroendocrine phenotype. EXPERIMENTAL DESIGN: To test this hypothesis, we exposed male Syrian golden hamsters maintained in 60% hyperoxia to s.c. injections of nicotine for the duration of their life. To allow for a survival time long enough to assess a potential carcinogenic effect of this treatment, animals demonstrating symptoms of respiratory distress were returned to ambient air for 24 hours throughout the experiment. RESULTS: A low but significant number of the animals exposed to hyperoxia and nicotine developed tumors of the nasal cavity, lungs, and adrenal glands. All of the tumor-bearing animals had survived 40 weeks or longer. The lung tumors demonstrated focal areas of positive immunoreactivity to neuron-specific enolase (NSE) and 5-hydroxy-tryptamine (5-HT, serotonin), both of which are markers of neuroendocrine differentiation. Hamsters maintained in ambient air and receiving identical injections with nicotine as well as animals maintained in hyperoxia and injected with saline did not develop tumors in any organs. All hamsters exposed to hyperoxia and surviving more than 12 weeks had thickened alveolar walls and emphysema. CONCLUSIONS: Our data support the hypothesis that chronic stimulation of the nAChR in an environment of impaired pulmonary oxygenation contributes to the carcinogenic burden associated with exposure to cigarette smoke and provides selective growth advantage for lung tumors with a neuroendocrine phenotype.

Adrenal Gland Neoplasms↗

Bacterial epididymitis in two stallions.

Two stallions had unilateral bacterial epididymitis attributable to S zooepidemicus infection. Diagnosis was based on bacterial isolation, WBC in the semen, higher than normal blood fibrinogen concentration, and leukocytosis with regenerative left shift. One horse had high seminal pH. Ultrasonography of the involved epididymides revealed changes consistent with the appearance of abnormal accumulation of exudate in the tail of the epididymis. Treatment included unilateral orchiectomy and antibiotic administration. In stallion 1, the infection persisted despite treatment. Treatment result was not available for stallion 2.

Animals↗

X-ray computed tomography-aided diagnosis of nasal adenocarcinoma, with extension to the skull and central nervous system, in a dog.

A dog with tonoclonic seizures, disorientation, and tetraparesis was evaluated by use of skull radiography. An advanced, highly aggressive process was centered within the caudal portion of the right nasal cavity. X-ray computed tomography further defined the mass to be occupying the caudal portion of the nasal cavity and frontal sinuses, with concurrent involvement of the adjacent turbinates and frontal, maxillary, and palatine bones. Despite the aggressive nature of the process, no alteration to the external contour of the cranium or nose was observed. Histologic examination revealed well-differentiated adenocarcinoma.

Adenocarcinoma↗

Factors limiting the usefulness of histopathologic examination of skin biopsies in the diagnosis of large animal dermatoses.

Skin biopsy for histologic, immunofluorescent, parasitologic, and bacteriologic examination is a common procedure, but for maximum effectiveness the clinician must realize the importance of precautions to select the correct stage of lesion of different diseases; avoiding creating artifacts during removal and fixation; and give full details of history, clinical diagnosis, and differential diagnoses on the laboratory request sheet. Pathology reports describing the subtleties of histologic changes are difficult to write, particularly if the lesions are not specific. Overly long histologic reports without a definitive diagnosis may frustrate a clinician who is unfamiliar with the significance of histologic lesions. For these reasons, clinician and pathologist must develop a rapport and empathy for the other's difficulties and adequately communicate to allow each to make a maximum contribution toward the final diagnosis. Histopathologic examination of skin lesions may not produce a specific diagnosis but is frequently useful in the elimination of other suspected diagnoses.

Animals↗

Death of an African elephant from probable toxemia attributed to chronic pulpitis.

A 31-year-old captive male African elephant (Loxodonta africana) of 5,000-kg body weight died suddenly in ventral recumbency. Lesions seen at necropsy were bilateral purulent pulpitis and periodontitis of both tusks, serous atrophy of coronary groove fat, Grammocephalus cholangitis, myocardial and skeletal lipofuscinosis, and scattered segmental necrosis in the pectoral muscles. Nonhemolytic streptococci, Corynebacterium sp, Peptostreptococcus anaerobius, Fusobacterium nucleatum, and Bacteroides sp, were recovered from the exudate around one or both tusks. We postulated that the elephant died of hypoxia from prolonged ventral recumbency because of weakness and inability to rise secondary to toxemia from bilateral pulpitis and periodontitis.

Animals↗

Age-related changes in percentage of fiber types and mean fiber diameters of the ovine quadriceps muscles.

Mean fiber diameters and percentages of each fiber type of the vastus lateralis, vastus medialis, rectus femoris, and vastus intermedius muscles from 15 sheep, ranging from 1 day to 5 years of age, were determined. Myosin adenosine triphosphatase and nicotinamide adenine dinucleotide-tetrazolium reductase stained sections were used. The vastus lateralis, vastus medialis, and rectus femoris contained 3 fiber types (I, IIA, and IIB). The vastus intermedius was composed almost entirely of type I fibers. From birth to 5 years of age, mean fiber diameters of type I fibers increased from 15.8 to 47.0 micron in the vastus lateralis, 15.6 to 50.7 micron in the vastus medialis, 17.5 to 46.5 micron in the rectus femoris, and 26.7 to 51.8 micron in the vastus intermedius. Means of fiber diameters of type II fibers increased from 16.1 to 44.6 micron in the vastus lateralis, 19.8 to 44.0 micron in the vastus medialis, and 17.0 to 44.5 micron in the rectus femoris. The percentage of type II fibers in the vastus lateralis, vastus medialis, and rectus femoris decreased from 85% to 90% at birth to approximately 72% at 5 years of age. The vastus intermedius consisted of only type I fibers in sheep 2 years and older.

Adenosine Triphosphatases↗

Pathological changes in calves injected intradermally with Mycobacterium intracellulare serotype Davis and M. avium serotype 2.

Three strains of the M. intracellulare-M. avium complex were injected intradermally into 12 calves. M. intracellulare serotype Davis (M. avium complex serotype 8) was injected into five calves. One calf died with disseminated caseous granulomas at 79 days; three calves killed between 56 and 82 days after inoculation had widely disseminated caseous or caseous or caseocalcareous granulomas. One calf killed at 173 days had only encapsulated granulomas at the injection site and its regional lymph node. Two strains of M. avium serotype 2 (M. avium complex serotype 2) were injected intradermally into seven calves. Six had disseminated granulomas when killed 54-170 days after inoculation. One calf killed at 55 days had granulomas confined to the inoculation sites and their regional lymph nodes. Lesions induced by both M. avium serotype 2 and M. intracellulare serotype Davis were initially caseocalcareous granulomas which became encapsulated and nonprogressive after about 112 days. Two calves inoculated with similar doses of M. bovis and killed in extremis at 37 and 65 days after inoculation had disseminated progressive lesions without encapsulation.

Animals↗

Hepatic midzonal necrosis in a pig fed aflatoxin and a horse fed moldy hay.

A 35-kg Duroc pig died 3 days after eating a ration containing aflatoxin B1, B2, G1, and G2. It had hemorrhagic enteritis and extensive midzonal necrosis in the liver. A 13-year-old Quarterhorse that died 2 days after eating moldy hay had hemorrhagic enteritis, fatty degeneration of the myocardium and renal tubules, and extensive total midzonal necrosis of the liver.

Animal Feed↗

Scanning electron microscopy of ruminal papillae in calves fed various amounts and forms of roughage.

Twenty neonatal calves were fed milk plus 1 of 4 rations ad libitum: pelleted concentrates plus alfalfa hay, pelleted concentrates plus ground alfalfa hay, pelleted concentrates alone, or pelleted concentrates containing whey. Eight calves were killed at 4 weeks of age, and 12 calves at 6 weeks. The ruminal mucosa was examined grossly, by light microscopy, and by scanning electron microscopy. Well-developed differences among groups were evident in calves at 6 weeks of age; changes at 4 weeks were similar, but less developed. In 6-week-old calves fed concentrates plus alfalfa hay ad libitum, papillae were flattened and tongue shaped on the ventral floor of the atrium ruminis (cranial sac). Calves fed concentrates plus ground alfalfa had tongue shaped, rounded, and finger-like papillae. Calves fed concentrates alone or concentrates plus whey developed small, nodular, branched papillae which were cauliflower shaped and severly parakeratotic and were arranged on transverse folds on the floor of the atrium ruminis and on zigzag folds elsewhere in the rumen, except on the dorsal wall in contact with the gas bubble. The transition from tongue-shaped to nodular-shaped papillae under the influence of ration occurred last on the floor of the atrium ruminis. At least in 6-week-old calves, that site generally is not typical of changes in most ruminal papillae.

Age Factors↗