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Biomedical subjects

N J Millichamp

Publications and source records attributed to N J Millichamp.

At least 19 recordsLinked to original sources
PubMed1999

New form of X-linked dominant hereditary nephritis in dogs.

OBJECTIVE: To determine features of a new form of hereditary nephritis (HN) in dogs. ANIMALS: Parents and 16 first-generation offspring (8 males, 8 females). PROCEDURE: Adolescent dogs that developed renal failure were euthanatized and necropsied. Unaffected dogs were monitored until they were at least 2 years old. Studies included light and electron microscopy of kidneys obtained from affected and unaffected dogs and immunolabeling for collagen-IV chains in renal and epidermal basement membranes (BM). The nucleotide sequence of a portion of exon 35 of the COL4A5 gene was determined in genomic DNA isolated from affected and unaffected males. RESULTS: 7 of 8 male and 2 of 8 female offspring had proteinuria and juvenile-onset chronic renal failure, which progressed more rapidly in the males. Labeling for alpha3-alpha6(IV) chains was completely absent in renal BM of affected males and segmentally absent in affected females. Expression of alpha1-alpha2(IV) chains in glomerular BM (GBM) of affected dogs was increased. Labeling for alpha5-alpha6(IV) chains in epidermal BM was absent in affected males and segmental in affected females. Ultrastructural changes characteristic of HN were observed in GBM of affected dogs. The sequence of exon 35 of COL4A5 was normal in affected dogs. CONCLUSIONS: This renal disease is an example of X-linked dominant HN, with typical abnormalities of GBM ultrastructure and alpha(IV) chain expression. CLINICAL RELEVANCE AND IMPLICATIONS FOR HUMAN MEDICINE: Dogs with this naturally acquired progressive renal disease can be used to investigate the pathogenesis and treatment of similar disorders in human beings and dogs.

Animals↗
PubMed1998

A model of autosomal recessive Alport syndrome in English cocker spaniel dogs.

BACKGROUND: Dogs with naturally occurring genetic disorders of basement membrane (type IV) collagen may serve as animal models of Alport syndrome. METHODS: An autosomal recessive form of progressive hereditary nephritis (HN) was studied in 10 affected, 3 obligate carrier, and 4 unaffected English cocker spaniel (ECS) dogs. Clinical, pathological, and ultrastructural features of the disease were characterized. Expression of basement membrane (BM) proteins was examined with an immunohistochemical technique using monospecific antibodies. RESULTS: Affected dogs had proteinuria and juvenile-onset chronic renal failure. Glomerular basement membrane (GBM) thickening and multilamellation typical of HN were observed in all renal specimens obtained from proteinuric dogs, and severity of GBM ultrastructural abnormalities varied with the clinical stage of disease. Expression of alpha3(IV) and alpha4(IV) chains was totally absent in the kidney of affected dogs. Expression of alpha5(IV) and a6(IV) chains was normal in Bowman's capsule, collecting tubular BM and epidermal BM of affected dogs. The alpha5(IV) chain was not expressed in distal tubular BM of affected dogs. Expression of alpha5(IV) chains was markedly reduced but not absent, and expression of alpha6(IV) chains was present in GBM of affected dogs. Expression of alpha1-alpha2(IV) chains in GBM of affected dogs was increased. Features of obligate carriers were similar to those of unaffected dogs. CONCLUSIONS: We conclude that HN in ECS dogs is a naturally occurring animal model of autosomal recessive Alport syndrome. However, it differs from human disease in the persistence of alpha5(IV) chains in GBM and in the appearance of a6(IV) chains in GBM.

Animals↗
PubMed1994

Experimental microsporidiosis in immunocompetent and immunodeficient mice and monkeys.

Microsporidia cause opportunistic infections in AIDS patients and commonly infect laboratory animals, as well. Euthymic C57B1/6 mice experimentally infected with intraperitoneal injections of 1 x 10(6) Encephalitozoon cuniculi Levaditi, Nicolau et Schoen, 1923, Encephalitozoon hellem Didier et al., 1991, or Nosema corneum Shadduck et al., 1990 displayed no clinical signs of disease. Athymic mice, however, developed ascites and died 8-16 days after inoculation with N. corneum, 21-25 days after inoculation with E. cuniculi, and 34-37 days after inoculation with E. hellem. All athymic mice displayed hepatomegaly, dilated intestine and accumulation of ascites fluid. Granulomatous lesions are primarily located in the liver, lung, pancreas, spleen, and on serosal surfaces of abdominal organs. The murine microsporidiosis model also was used to examine immune response that inhibit microsporidia growth in vitro. Recombinant murine interferon-gamma (mIFN-gamma, 100 mu/ml) alone or in combination with lipopolysaccharide (LPS; 10 ng/ml) could activate thioglycollate-induced peritoneal murine macrophages to destroy E. cuniculi. The production of the nitrogen intermediate, NO2-, correlated with parasite destruction. Inhibition of NO2- generation by addition of the L-arginine analogue, NG-monomethyl L-arginine (NMMA), inhibited microsporidia killing, as well. Since microsporidiosis is becoming an important opportunistic infection in AIDS patients, a microsporidiosis model is being developed using SIV/DeltaB670-infected rhesus macaque monkeys (Macaca mulatta). SIV-infected immunocompetent monkeys given E. cuniculi or E. hellem per os developed specific antibodies, and microsporidia could be detected sporadically by calcofluor or antibody fluorescence staining of stool and urine sediment smears. As immunodeficiency progressed, monkeys developed diarrhoea, cachexia, and anorexia, and organisms were detected in urine and stool with greater frequency. Immunodeficient SIV-infected monkeys died approximately 27 days after receiving E. hellem by intravenous inoculation, and approximately 110 days after receiving E. hellem per os. Lesions typical for SIV-infection were observed in both groups of monkeys and microsporidia were detected in kidney and liver of the intravenously-injected monkeys. The murine microsporidiosis model provides an efficient means for studying protective immune responses to microsporidiosis, and may prove useful for screening immunological and chemotherapeutic agents. The pathogenesis of Encephalitozoon microsporidiosis in SIV-infected monkeys appears to parallel encephalitozoonosis in AIDS patients, suggesting that simian microsporidiosis may provide a useful model for evaluating diagnostic methods and therapeutic strategies during various stages of progressing immunodeficiency.

Animals↗
PubMed1992

Comparison of applanation tonometers in dogs and horses.

Two Mackay-Marg tonometers and 2 Tono-Pen tonometers were evaluated in eyes in which intraocular pressure (IOP) had been altered and measured by use of a manometer. Eyes of anesthetized dogs and enucleated horse eyes were used. Compared with the manometer, none of the tonometers accurately measured IOP over the range between 0 and 100 mm of Hg. However at manometer measurements from 0 to 30 mm of Hg, several of the tonometers accurately measured IOP. In addition, significant differences were observed when the measurement accuracy of one tonometer was compared with that of another, especially at high IOP. Coefficient of determination (r2) values for a linear model ranged from 0.979 to 0.991 in dogs, and from 0.982 to 0.996 in horse eyes.

Animals↗
PubMed1992

Ocular trauma.

Horses with ocular trauma frequently present as emergency cases. This article provides a succinct review of various adnexal and globe injury issues. Accurate case assessment, management, prognosis, and follow-up considerations are presented.

Animals↗
PubMed1992

Effects of prostaglandin F2 alpha and leukotriene D4 on pupil size, intraocular pressure, and blood-aqueous barrier in dogs.

In each of 5 groups of dogs, 0.05 ml of 1 of the following solutions was injected into the anterior chamber of both eyes: phosphate-buffered saline solution, 0.001 microgram of prostaglandin F2 alpha (PGF2 alpha), 0.01 microgram of PGF2 alpha, 0.1 microgram of leukotriene D4 (LTD4), and 1 microgram of LTD4. A 10% solution of sodium fluorescein was injected IV (14 mg/kg of body weight) at the same time, and pupil size, intraocular pressure, and anterior chamber fluorescence were measured for 1 hour after injections. In a dose-dependent manner, PGF2 alpha was a potent miotic. A significant effect on intraocular pressure was not detected when the groups given PGF2 alpha were compared with the control group. When compared with LTD4, PGF2 alpha significantly (P less than 0.05) increased the breakdown of the blood-aqueous barrier, as evidenced by increased fluorescein leakage into the anterior chamber. Leukotriene D4 caused a decrease in pupil size only at 5 minutes, compared with that of the control group. Intraocular pressure was greater (but not significantly) in the group given 1 microgram of LTD4.

Animals↗
PubMed1992

Comparison of prednisolone and RMI-1068 in the ocular irritative response in dogs.

Ocular inflammation was induced in 36 dogs by performing an anterior capsulotomy with a Nd:YAG laser. All dogs were pretreated with topical atropine. Dogs were then divided into three groups: (1) control, with no other pretreatment; (2) pretreatment with the topical dual cyclooxygenase/lipoxygenase inhibitor RMI-1068; and (3) pretreatment with topical prednisolone acetate. Dogs were studied 1-3 hours after lasering. RMI-1068 maintained mydriasis and raised intraocular pressure compared to the control and prednisolone groups. An ocular fluorophotometer used to measure anterior chamber fluorescence after IV injection of sodium fluorescein showed that RMI-1068 decreased anterior chamber fluorescein concentration compared to the control and prednisolone groups. RMI-1068 decreased PGF2 alpha concentrations in the aqueous at 1 and 3 hours compared to the control and prednisolone groups. Prednisolone decreased PGF2 alpha concentrations compared to the control group at 1 h. Concentrations of LTB4 in the aqueous at 1 hour were lower in the RMI-1068 group than in the control and prednisolone groups.

Animals↗
PubMed1991

Use of phacofragmentation for cataract removal in horses: 12 cases (1985-1989).

The medical records of 12 horses that had cataracts removed by use of phacofragmentation were reviewed. Cataracts were removed from 16 eyes in horses ranging in age from 2 months to 15 years. Complications after surgery included corneal ulcers in 13 eyes, diffuse corneal edema in 5 eyes, and uncontrollable uveitis in 3 eyes. Follow-up information was obtained in all horses from 1 month to 3.5 years after surgery. Visual results were judged good by owners or veterinarians in 10 of the horses.

Animals↗
PubMed1991

Acute effects of anti-inflammatory drugs on neodymium:yttrium aluminum garnet laser-induced uveitis in dogs.

Dogs were treated with flunixin meglumine, a cyclooxygenase inhibitor; L-651,896, a 5-lipoxygenase inhibitor; and matrine, a herbal anti-inflammatory drug. Acute inflammation was induced in the eyes by disruption of the anterior lens capsule, using a neodymium:yttrium aluminum garnet laser. Intraocular pressure, pupil diameter, and eicosanoid production in the aqueous humor were measured. Statistically significant effects were seen in the eyes of flunixin meglumine-treated dogs where mydriasis was maintained and aqueous prostaglandin E2 concentration was reduced.

Alkaloids↗
PubMed1991

Effect of flurbiprofen on facility of aqueous outflow in the eyes of dogs.

Aqueous outflow from cannulated canine eyes was determined, using a constant-pressure perfusion technique. The effect of topically applied flurbiprofen, a cyclo-oxygenase inhibitor, on outflow in eyes with or without neodymium:yttrium aluminum garnet laser-induced inflammation was measured. Flurbiprofen caused decrease in aqueous outflow that was more marked in the inflamed eyes.

Animals↗
PubMed1991

Comparison of flunixin meglumine and flurbiprofen for control of ocular irritative response in dogs.

Dogs were treated with the cyclo-oxygenase inhibitors flunixin meglumine IV or flurbiprofen topically. Acute inflammation was induced in the eyes by disruption of the anterior lens capsule, using a neodymium:yttrium aluminum garnet laser. Pupil diameter and intraocular pressure were measured before and after inducing ocular inflammation. Both drugs maintained mydriasis and increased intraocular pressure in the inflamed eyes, compared with untreated controls.

Animals↗
PubMed1990

Nonulcerative keratouveitis in five horses.

Five horses with severe nonulcerative keratouveitis had corneal lesions characterized by a pink stromal infiltrate that initially appeared in the stroma near the limbus. Unremitting iridocyclitis also was evident. In 3 horses, microscopic lesions consisted of marked corneal stromal fibrosis, with mild to severe inflammatory cellular infiltration. Corticosteroids and mydriatic/cycloplegics applied topically and corticosteroids and nonsteroidal anti-inflammatory medications administered parenterally were used with varying degrees of success to control pain and retain vision.

Animals↗
PubMed1990

Retinal degeneration in the dog and cat.

Retinal degenerations in the dog and cat are an important cause of blindness in these species. Particularly in the dog, many retinal degenerations, collectively called progressive retinal atrophy, seen in clinical practice are inherited. The clinical signs, electrophysiological findings, pathology, and underlying biochemical defects in the retina vary from breed to breed. Specific categories of inherited retinal degeneration are now recognized, and classified into early onset photoreceptor dysplasias, late-onset retinal degenerations, or retinal degenerations secondary to primary RPE dystrophy. As new inherited retinal degenerations are reported in different breeds they can generally be assigned to one these categories. Other causes of retinal degeneration include nutritional deficiencies, glaucoma, inflammation, ischemia, and toxins. Idiopathic retinal degeneration occurs in the dog with some frequency.

Animals↗
PubMed1989

Effects of lipoxygenase inhibitors in a model of lens-induced uveitis in dogs.

Uveitis was induced in dogs by intracameral injection of canine lens protein. The lipoxygenase inhibitors phenidone and norhydroguaiaretic acid, and dimethyl sulfoxide decreased fibrin production at 0.5 and 1 hour after induction of uveitis. Phenidone and norhydroguaiaretic acid also inhibited the initial increase in intraocular pressure early in the course of inflammation. Leukotriene B4 in the aqueous was measured by use of radioimmunoassay at 1 hour after inflammation. In control dogs, 230 to 1,700 pg of leukotriene B4/ml was measured; in dogs treated with phenidone, leukotriene B4 was not measured.

Animals↗
PubMed1989

Transretinal mass receptor potentials recorded from the canine retina in vitro.

A transretinal method for recording the summed potentials generated by photoreceptors of the isolated canine retina in vitro is reported. Pieces from 10 retinas of 5 clinically and visually normal dogs were maintained in a recording chamber and superperfused with a modified cell culture medium. Sodium glutamate added to the medium eliminated electrical responses from retinal glia and allowed the summed receptor potentials to be recorded. The response to flashes of light consisted of a negative potential, which increased in amplitude in a graded manner and in complexity with increased stimulus intensity. The response was similar in waveform to that reported in other vertebrate species, using intracellular and extracellular techniques. This method of recording the mass transretinal receptor potentials in vitro will be of value for investigating abnormal photoreceptor functions in dogs in the early stages of inherited retinal degeneration.

Action Potentials↗
PubMed1988

Progressive retinal atrophy in Tibetan terriers.

Progressive retinal atrophy was studied in 17 Tibetan Terriers. The diagnosis was made on the basis of clinical signs of the disease, retinal histopathologic findings, or both. Affected dogs were the progeny of matings of affected or ophthalmoscopically normal dogs. Results of the mating supported a simple autosomal recessive mode of inheritance. The disease initially could be diagnosed by findings of night blindness and ophthalmoscopic signs of tapetal hyperreflectivity in affected dogs that were approximately 1 year old. Electroretinograms recorded from affected dogs, compared with those of clinically normal dogs of the same age, did not reveal appreciable abnormalities until affected dogs were 10 months old, at which time a reduction in the amplitude of the b wave was seen in response to a Ganzfeld white-light stimulus. The peak times of the response were unaffected. With progression of the disease, the electroretinographic b-wave amplitude was gradually reduced, and the electroretinographic response was extinguished in affected dogs by the time they were 30 months old. Early in the disease, rod and cone functions were affected equally, with more rapid loss of rod function developing only later in the disease. Fluorescein angiography of affected dogs did not reveal abnormalities earlier than could be detected by ophthalmoscopy. Despite the electroretinographic findings, histopathologic findings included patchy disorientation and disorganization of the outer segments of rods and cones in affected dogs as young as 9 weeks. With progression of the disease, rods were lost at a faster rate than cones, and atrophy of the inner retinal layer was observed.

Animals↗