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Biomedical subjects

M A Miller

Publications and source records attributed to M A Miller.

At least 37 records · Page 2Linked to original sources

Melan A and S100 protein immunohistochemistry in feline melanomas: 48 cases.

Immunohistochemistry, using a monoclonal antibody to Melan A and a polyclonal antibody to S100 protein, was applied to 48 formalin-fixed, paraffin-embedded specimens of feline melanoma. Forty-two cutaneous, three oral, one mucocutaneous, and two metastatic melanomas comprised the tumors. Thirty-two tumors (67%) were positive for Melan A and 42 (87.5%) were positive for S100. All but one of the tumors that were positive for Melan A were also positive for S100. S100 was detected in 11 of 16 tumors that were negative for Melan A. Seventy-five percent (9 of 12) of amelanotic melanomas were negative for Melan A. Normal adrenal cortex, the cerebellum, and the skin had cells that were positive for Melan A. Sebaceous adenoma was the only nonmelanocytic tumor examined that reacted with antibody to Melan A. Although less sensitive than S100 protein, Melan A is more specific for melanoma and is useful in differentiating feline cutaneous melanoma from the more common pigmented basal cell tumor.

Animals↗

Immunohistochemical detection of thyroid transcription factor-1, thyroglobulin, and calcitonin in canine normal, hyperplastic, and neoplastic thyroid gland.

Immunohistochemistry for thyroid transcription factor-1 (TTF-1), thyroglobulin, and calcitonin was done in normal, hyperplastic, and neoplastic canine thyroid glands that had been fixed in formalin and embedded in paraffin. Prolonged fixation did not significantly alter the immunostaining for TTF-1. Staining for TTF-1 was always nuclear and usually strong. One of two C-cell adenomas, five of five follicular cell adenomas, 5 of 11 C-cell carcinomas, 38 of 42 follicular cell carcinomas, two of five cases of C-cell hyperplasia, two of two cases of follicular epithelial hyperplasia, one of two metastatic C-cell carcinomas, and three of four metastatic follicular carcinomas were positive for TTF-1. One follicular carcinoma that was positive for TTF-1 was negative for thyroglobulin. Thirty-nine of 42 follicular cell carcinomas were positive for thyroglobulin, including two cases that were negative for TTF-1. All C-cell lesions were positive for calcitonin. Of a variety of normal canine tissues and 278 nonthyroid tumors, only normal lung (airway and alveolar epithelial cells) and four of five pulmonary carcinomas were positive for TTF-1. TTF-1 is a good marker of thyroid differentiation and can be used in conjunction with thyroglobulin and calcitonin to increase the detection and differentiation of thyroid tumors and their metastases.

Adenoma↗

Bronchitis and bronchiolitis in a cat with cilia-associated respiratory bacillus-like organisms.

A 10-year-old male domestic shorthair cat died during anesthesia. Grossly, the lungs had multiple nodules corresponding to inflamed airways (bronchitis and bronchiolitis). Microscopically, cuffs and nodular aggregates of lymphocytes and plasma cells surrounded airways. Peribronchiolar fibrosis was also common. Globule leukocytes infiltrated the respiratory epithelium of noninflamed or mildly inflamed bronchi. Argyrophilic and filamentous organisms, consistent with cilia-associated respiratory bacillus-like organisms (CLO), were intermixed with cilia of respiratory epithelium. Ultrastructurally, CLO were longer and thinner than cilia and had a distinct trilaminar membrane, central electron-lucent areas, and no specialized external structures. Silver stained lung sections from 18 additional feline airways revealed similar bacilli in 2/9 normal lungs, 1/7 lungs with bronchitis and bronchiolitis, and 1/2 lungs with pneumonia. The significance of CLO in the pulmonary lesions was not determined.

Animals↗

Evaluation of an indirect fluorescent antibody test (IFAT) for demonstration of antibodies to Toxoplasma gondii in the sea otter (Enhydra lutris).

An indirect fluorescent antibody test (IFAT) for detection of Toxoplasma gondii infection was validated using serum from 77 necropsied southern sea otters (Enhydra lutris nereis) whose T. gondii infection status was determined through immunohistochemistry and parasite isolation in cell culture. Twenty-eight otters (36%) were positive for T. gondii by immunohistochemistry or parasite isolation or both, whereas 49 (64%) were negative by both tests. At a cutoff of 1:320, combined values for IFAT sensitivity and specificity were maximized at 96.4 and 67.3%, respectively. The area under the receiver-operating characteristic curve for the IFAT was 0.84. A titer of 1:320 was used as cutoff when screening serum collected from live-sampled sea otters from California (n = 80), Washington (n = 21), and Alaska (n = 65) for T. gondii infection. Thirty-six percent (29 out of 80) of California sea otters (E. lutris nereis) and 38% (8 out of 21) of Washington sea otters (E. lutris kenyoni) were seropositive for T. gondii, compared with 0% (0 out of 65) of Alaskan sea otters (E. lutris kenyoni).

Alaska↗

Measurement of the high energy two-body deuteron photodisintegration differential cross section.

The first measurements of the d(gamma,p)n differential cross section at forward angles and photon energies above 4 GeV were performed at the Thomas Jefferson National Accelerator Facility (JLab). The results indicate evidence of an angular dependent scaling threshold. Results at straight theta(cm) = 37 degrees are consistent with the constituent counting rules for E(gamma) greater, similar 4 GeV, while those at 70 degrees are consistent with the constituent counting rules for E(gamma) greater, similar 1.5 GeV.

Journal Article↗

Oxidative responses of human and murine macrophages during phagocytosis of Leishmania chagasi.

Leishmania chagasi, the cause of South American visceral leishmaniasis, must survive antimicrobial responses of host macrophages to establish infection. Macrophage oxidative responses have been shown to diminish in the presence of intracellular leishmania. However, using electron spin resonance we demonstrated that murine and human macrophages produce O2-during phagocytosis of opsonized promastigotes. Addition of the O2- scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl to cultures resulted in increased infection, suggesting that O2- enhances macrophage leishmanicidal activity. The importance of NO. produced by inducible NO synthase (iNOS) in controlling murine leishmaniasis is established, but its role in human macrophages has been debated. We detected NO. in supernatants from murine, but not human, macrophages infected with L. chagasi. Nonetheless, the iNOS inhibitor N(G)-monomethyl-L-arginine inhibited IFN-gamma-mediated intracellular killing by both murine and human macrophages. According to RNase protection assay and immunohistochemistry, iNOS mRNA and protein were expressed at higher levels in bone marrow of patients with visceral leishmaniasis than in controls. The iNOS protein also increased upon infection of human macrophages with L. chagasi promastigotes in vitro in the presence of IFN-gamma. These data suggest that O2- and NO. each contribute to intracellular killing of L. chagasi in human and murine macrophages.

Animals↗

Testosterone regulates alpha-synuclein mRNA in the avian song system.

Alpha-synuclein is a small, highly conserved protein in vertebrates that has been linked to several neurodegenerative diseases. The avian song control system is one of the model systems in which the protein was independently discovered. Alpha-synuclein is dynamically regulated in the song system during song learning, a process in which sex steroids play a central role. We compared alpha-synuclein mRNA expression in the brains of 12 adult male chipping sparrows (Spizella passerina) treated with either testosterone or blank s.c. implants. We saw pronounced upregulation of alpha-synuclein mRNA in, as well as an increase in the volume of, the song control nucleus area X in response to exogenous testosterone. To our knowledge this is the first report of steroid regulation of synuclein gene expression in any model system.

Animals↗

Mammary duct ectasia in dogs: 51 cases (1992-1999).

OBJECTIVE: To evaluate the clinical and pathologic characteristics of mammary duct ectasia in dogs. DESIGN: Retrospective study. ANIMALS: 51 dogs with mammary duct ectasia. PROCEDURE: Information regarding body condition, history, number and location of affected mammary glands, appearance of lesions, surgical treatment, nonsurgical treatment, and evidence of recurrence or development of mammary neoplasia was obtained from surveys sent to referring veterinarians. Results of information from examination of histologic sections and referring veterinarians were evaluated for all mammary duct ectasia biopsies performed between 1992 and 1999. RESULTS: Duct ectasia was the primary diagnosis in 51 of 1,825 (2.8%) mammary biopsy specimens and comprised 48% of nonneoplastic mammary diseases. Affected dogs were evenly distributed over a range of 1 to 13 years of age, with a mean age at the time of diagnosis of 6.1 +/- 3.1 years. All dogs were female (31 sexually intact, 20 spayed); 10 of 26 had whelped. Duct ectasia was described as nodular (26 dogs), cystic (13), and multiglandular (11) and located in caudal (31) more often than cranial (14) or middle glands (10). Ectasia recurred in 3 dogs. One dog had a history of previously excised mammary adenocarcinoma; another subsequently developed mammary carcinoma. CONCLUSIONS AND CLINICAL RELEVANCE: Duct ectasia affected mature, sexually intact and spayed female dogs over a wide age range. Certain breeds were affected more commonly than expected. Increased risk for mammary neoplasia was not evident. Duct ectasia should be considered as a cause for mammary enlargement, especially in young dogs or when its cystic nature is evident. Mastectomy is usually curative, and neoplasia should be ruled out in dogs with ectasia.

Age Distribution↗

A sperm cytoskeletal protein that signals oocyte meiotic maturation and ovulation.

Caenorhabditis elegans oocytes, like those of most animals, arrest during meiotic prophase. Sperm promote the resumption of meiosis (maturation) and contraction of smooth muscle-like gonadal sheath cells, which are required for ovulation. We show that the major sperm cytoskeletal protein (MSP) is a bipartite signal for oocyte maturation and sheath contraction. MSP also functions in sperm locomotion, playing a role analogous to actin. Thus, during evolution, MSP has acquired extracellular signaling and intracellular cytoskeletal functions for reproduction. Proteins with MSP-like domains are found in plants, fungi, and other animals, suggesting that related signaling functions may exist in other phyla.

Amino Acid Sequence↗

Evidence for a three-nucleon-force effect in proton-deuteron elastic scattering.

Developments in spin-polarized internal targets for storage rings have permitted measurements of 197 MeV polarized protons scattering from vector polarized deuterons. This work presents measurements of the polarization observables A(y), iT11, and C(y,y) in proton-deuteron elastic scattering. When compared to calculations with and without three-nucleon forces, the measurements provide further evidence that three-nucleon forces make a contribution to the observables. This work indicates that three-body forces derived from static nuclear properties appear to be crucial to the description of dynamical properties.

Journal Article↗

Regulation of GP63 mRNA stability in promastigotes of virulent and attenuated Leishmania chagasi.

GP63 is a 63-kDa glycoprotein that is abundantly expressed on the surface of all Leishmania species and is involved in several steps of promastigote infection of host cells. Leishmania chagasi has at least 18 haploid msp (major surface protease) genes encoding GP63 that are divided into three classes, mspS, mspL or mspC, according to their unique 3' UTR sequences and differential expression. All three msp classes are constitutively transcribed during virulent promastigote growth in vitro, although mspL mRNA is most abundant during logarithmic phase and mspS mRNA predominates in stationary phase. Thus, the steady state levels of the mspL and mspS mRNAs are post-transcriptionally regulated. Using Actinomycin D to arrest transcription, we found that in virulent promastigotes the half-life (t(1/2)) of mspL mRNA is coordinately modulated with growth phase, decreasing from a mean of 84 min during early logarithmic growth to a mean of 17 min at a stage intermediate between logarithmic and stationary phase. However, in attenuated promastigotes, the t(1/2) of mspL RNA remains the same throughout parasite growth. In contrast to mspL RNA, the t(1/2) of mspS and mspC RNA is constant throughout all growth phases of both virulent and attenuated promastigote growth. The presence of the translation inhibitor cycloheximide increases the t(1/2) of mspL RNA 4-6-fold in both virulent and attenuated promastigotes at all growth phases. These results indicate that the t(1/2) of mspL RNA is maintained by at least two distinct mechanisms - one activated during growth to stationary phase and the other dependent on a labile negative regulatory protein factor(s).

Animals↗

Xerostomia, xerophthalmia, and plasmacytic infiltrates of the salivary glands (Sjögren's-like syndrome) in a cat.

A 2.5-year-old domestic shorthair cat was evaluated because of dysphagia and weight loss of 4 weeks' duration. MIld blepharospasm and conjunctival hyperemia were evident in both eyes, oral mucous membranes were tacky on palpation, and salivary glands were enlarged. Results of a Schirmer tear test were 0 mm/min for both eyes. Administration of atropine did not cause salivation or caused secretion fo thick rope-like saliva. Examination of biopsy specimens of salivary glands revealed a plasmacytic infiltrate. Sjögren's syndrome (SS) was diagnosed. Oral administration of prednisone was instituted but was discontinued after a minimal positive response was evident 6 weeks after initiation of treatment. Palliative treatment with a 6% solution of pilocarpine 4 to 5 times/d, cyclosporine, hylan A, and neomycin-polymyxin-bacitracin ophthalmic ointment resulted in clinical improvement in the cat. Although reported rarely in animals, SS may be more common than currently is recognized. Most treatment regimens for SS are aimed at alleviating clinical signs.

Animals↗

Deceiving appearances: signaling by "dead" and "fractured" receptor protein-tyrosine kinases.

The mechanisms by which most receptor protein-tyrosine kinases (RTKs) transmit signals are now well established. Binding of ligand results in the dimerization of receptor monomers followed by transphosphorylation of tyrosine residues within the cytoplasmic domains of the receptors. This tidy picture has, however, some strange characters lurking around the edges. Cases have now been identified in which RTKs lack kinase activity, but, despite being "dead" appear to have roles in signal transduction. Even stranger are the cases in which genes encoding RTKs produce protein products consisting of only a portion of the kinase domain. At least one such "fractured" RTK appears to be involved in signal transduction. Here we describe how these strange molecules might function and discuss the questions associated with their evolution. BioEssays 23:69-76, 2001.

Animals↗

Isolation and characterization of Sarcocystis from brain tissue of a free-living southern sea otter (Enhydra lutris nereis) with fatal meningoencephalitis.

A protozoan was isolated in cell culture from the brain of a free-ranging sea otter with fatal meningoencephalitis. The biological history of this otter, a study animal being monitored via an intraperitoneal radio transmitter, is summarized. Histologically, protozoal parasites were associated with areas of brain inflammation and necrosis in the cerebrum and cerebellum. Morphology and measurements of fixed, Giemsa-stained protozoal zoites growing on coverslips were consistent with Sarcocystis. These parasites reacted only with polyclonal antisera raised against S. neurona on immunohistochemistry. Cell culture-derived zoites reacted strongly with polyclonal antiserum to S. neurona on indirect fluorescent antibody tests. Amplification of portions of the 18S ribosomal DNA and the adjacent first internal transcribed spacer were performed. The resulting sequences were compared with published sequences from similar apicomplexan protozoa. This isolate (SO SN1), was indistinguishable from S. neurona, based on parasite morphology, antigenic reactivity and molecular characterization.

Animals↗

Why is it so difficult to simulate entropies, free energies, and their differences?

The classical 19th century thermodynamic inequalities of Clausius and Helmholtz are applied to the calculation of entropy and free energy changes by computer simulation. The irreversibility of finite-time thermodynamic paths is exploited to obtain upper and lower bounds on these quantities. Schrödinger's microscopic interpretation of heat and work provides the basis for a literal implementation of the key historical concepts on the computer using the Monte Carlo algorithm of Metropolis. Coupling schemes, paths, and reference states are variationally optimized to improve the convergence of the simulated properties, and a newly introduced variational flexibility, metric scaling, is overviewed. Reasons for expecting limiting power laws for the convergence are outlined.

Chemistry↗