Biomedical subjects

M W Miller

Publications and source records attributed to M W Miller.

At least 73 records · Page 4Linked to original sources

PubMed1999

Expression of nerve growth factor, p75, and the high affinity neurotrophin receptors in the adult rat trigeminal system: evidence for multiple trophic support systems.

We hypothesize that discrete trigeminal structures have the components required for autocrine regulation as well as redundant neurotrophin support systems. We examined the expression of nerve growth factor (NGF) and the low affinity (p75) and high affinity (trkA, trkB, and trkC) neurotrophin receptors in the trigeminal system of adult rats. Four sites were examined; the trigeminal ganglion, mesencephalic nucleus, principal sensory nucleus (PSN), and trigeminal motor nucleus. NGF was expressed by more than 60% of neurons in each area studied. NGF immunolabeling may have resulted from exogenous protein incorporated from the microenvironment or from NGF synthesized by the neuron per se. To resolve this issue, in situ hybridization for NGF mRNA was performed. The mRNA was expressed by 2/3 to 7/8 of neurons in trigeminal structures. Moreover, double-labeling studies showed that virtually every ganglion cell that was NGF-immunoreactive also expressed the NGF transcript. Neurotrophin receptors (p75 and trk isoforms) were expressed by more than 60% of the neurons in each trigeminal structure. The only exception was the PSN, where the receptors were expressed by fewer than half of the neurons. Taken together, these data imply that NGF must be elaborated by neurons that co-express both p75 and trkA. Therefore, each trigeminal structure has the machinery for autocrine/paracrine regulation, as well as the capacity for retrograde and/or anterograde trophic support. Furthermore, the co-expression of the specific trk isoforms indicates that trigeminal neurons are sensitive to more than one neurotrophin.

Animals↗

PubMed1999

A longitudinal study of the effects of prenatal ethanol exposure on neuronal acquisition and death in the principal sensory nucleus of the trigeminal nerve: interaction with changes induced by transection of the infraorbital nerve.

The present study determines (1) whether ethanol-induced microencephaly results from reductions in neuronal acquisition (i.e., cell proliferation and neuronal migration) and/or increases in neuronal death and (2) whether ethanol exacerbates death by the same mode as that for naturally occurring or lesion-induced neuronal death. Pregnant rats were exposed to a diet containing 6.7% (v/v) ethanol or an isocaloric control diet during the last two weeks of gestation. At birth, the right infraorbital nerves of the pups were transected. The numbers of neurons in the principal sensory nucleus of the trigeminal nerve (PSN) on both sides of the pons were examined at various prenatal and early postnatal timepoints. The numbers of pyknotic and argyrophilic PSN cells were also counted. Ethanol delayed and reduced (19.9%) the prenatal acquisition of PSN neurons. The postnatal decline in neuronal number (indicative of neuronal death) was significantly increased (10.6%) by ethanol. Likewise, the numbers of pyknotic and silver-stained cells were significantly higher in ethanol-treated rats. Lesion of the infraorbital nerve induced significant transsynaptic neuronal death in the control rats. Ethanol increased the amount of death caused by the lesion; however, it altered neither the timing of the neuronal loss nor the incidence of pyknosis or silver-staining. Therefore, ethanol affects both neuronal acquisition and survival; the greater effect being on neuronal acquisition. The timing and morphology of dying cells indicate that regardless of the cause (natural processes, ethanol-induced, or lesion-induced), neurons die in the developing PSN by the same mode.

Age Factors↗

PubMed1999

Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knock-in mice.

Excitotoxicity, a form of neuronal injury in which excessive activation of glutamate receptors results in cellular calcium overload, has been implicated in the pathogenesis of Alzheimer disease (AD), although direct evidence is lacking. Mutations in the presenilin-1 (PS1) gene on chromosome 14 are causally linked to many cases of early-onset inherited AD (refs. 5,6). We generated PS1 mutant mice (PS1M146VKI) that express the PS1 M146V targeted allele at normal physiological levels. Although PS1M146VKI mice have no overt mutant phenotype, they are hypersensitive to seizure-induced synaptic degeneration and necrotic neuronal death in the hippocampus. Cultured hippocampal neurons from PS1M146VKI mice have increased vulnerability to death induced by glutamate, which is correlated with perturbed calcium homeostasis, increased oxidative stress and mitochondrial dysfunction. Agents that suppress calcium influx or release and antioxidants protect neurons against the excitotoxic action of the PS1 mutation. These findings establish a direct link between a genetic defect that causes AD and excitotoxic neuronal degeneration, and indicate new avenues for therapeutic intervention in AD patients.

Animals↗

PubMed1999

Increased vulnerability of hippocampal neurons from presenilin-1 mutant knock-in mice to amyloid beta-peptide toxicity: central roles of superoxide production and caspase activation.

Many cases of early-onset inherited Alzheimer's disease (AD) are caused by mutations in the presenilin-1 (PS1) gene. Overexpression of PS1 mutations in cultured PC12 cells increases their vulnerability to apoptosis-induced trophic factor withdrawal and oxidative insults. We now report that primary hippocampal neurons from PS1 mutant knock-in mice, which express the human PS1M146V mutation at normal levels, exhibit increased vulnerability to amyloid beta-peptide toxicity. The endangering action of mutant PS1 was associated with increased superoxide production, mitochondrial membrane depolarization, and caspase activation. The peroxynitrite-scavenging antioxidant uric acid and the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone protected hippocampal neurons expressing mutant PS1 against cell death induced by amyloid beta-peptide. Increased oxidative stress may contribute to the pathogenic action of PS1 mutations, and antioxidants may counteract the adverse property of such AD-linked mutations.

Alzheimer Disease↗

PubMed1999

Transforming growth factor beta1-regulated cell proliferation and expression of neural cell adhesion molecule in B104 neuroblastoma cells: differential effects of ethanol.

The expression and activity of factors influencing early neuronal development are altered by ethanol. Such factors include growth factors, for example, platelet-derived growth factor and basic fibroblast growth factor (for cell proliferation), and cell adhesion molecules (for neuronal migration). One agent, transforming growth factor beta1 (TGFbeta1), may affect both events. We tested the hypothesis that ethanol alters myriad TGFbeta1-mediated activities [i.e., cell proliferation and neural cell adhesion molecule (N-CAM) expression] using B104 neuroblastoma cells. TGFbeta1 inhibited the proliferation of B104 cells as evidenced by decreases in cell number and [3H]thymidine ([3H]dT) incorporation. TGFbeta1 induced sustained activation of extracellular signal-regulated kinases (ERKs), which are part of the family of mitogen-activated protein kinases (MAPKs). Treatment with PD98059 (a MAPK kinase blocker) abolished TGFbeta1-regulated inhibition of [3H]dT incorporation. TGFbeta1-mediated growth inhibition was potentiated by ethanol exposure. Ethanol also produced prolonged activation of ERK, an effect that was partially eliminated by treatment with PD98059. On the other hand, TGFbeta1 up-regulated N-CAM expression, and this up-regulation was not affected by treatment with PD98059. Ethanol inhibited the TGFbeta1-induced up-regulation of N-CAM expression in a concentration-dependent manner. Thus, TGFbeta1 affects ERK-dependent cell proliferation and ERK-independent N-CAM expression in B104 cells. Both activities are sensitive to ethanol and may underlie the ethanol-induced alterations in the proliferation and migration of CNS neurons.

Animals↗

PubMed1999

Chronic survival of calves implanted with the DeBakey ventricular assist device.

The DeBakey ventricular assist device (VAD) is a miniaturized, electromagnetically driven axial flow pump capable of generating in excess of 10 L/min output. The VAD was evaluated in 19 calves during experiments designed to test iterative modifications in the system and to determine the safety of the DeBakey VAD for intermediate to long-term implant. Five of the animals died or were euthanized during the perioperative period (i.e., Days 1-5) due to complications associated with bleeding (n = 3), sudden cardiac arrest (n = 1), or pump occlusion due to a muscle remnant associated with coring (n = 1). The remaining 14 animals survived from 7-145 days. Ten of the 14 animals survived 30 or more days, and 2 animals survived 93 and 145 days before elective euthanasia. Pump function was evaluated in the 14 calves that survived beyond the perioperative period. Pump output at implantation averaged 3 L/min while output at 100 days (n = 2) averaged 4.22 L/min. The electrical current did not change across time during the study, indicating normal operation of the bearings. Pumps consumed less than 10.5 W of power for all support durations. Hemolysis did not occur; the average daily plasma free hemoglobin varied from 2.0 to 8.0 mg/dl. Evaluation of serum biochemical data showed that implantation of the DeBakey VAD in calves with normal hearts did not impair end organ function; BUN, creatinine, and total bilirubin varied minimally within the normal range. The white blood cell count of implanted animals remained within the normal range throughout the study.

Animals↗

PubMed1999

PrP genotypes of captive and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease.

The PrP gene encodes the putative causative agent of the transmissible spongiform encephalopathies (TSEs), a heterogeneous group of fatal, neurodegenerative disorders including human Creutzfeldt-Jakob disease, bovine spongiform encephalopathy, ovine scrapie and chronic wasting disease (CWD) of North American deer and elk. Polymorphisms in the PrP gene are associated with variations in relative susceptibility, pathological lesion patterns, incubation times and clinical course of TSEs of humans, mice and sheep. Sequence analysis of the PrP gene from Rocky Mountain elk showed only one amino acid change (Met to Leu at cervid codon 132). Homozygosity for Met at the corresponding polymorphic site (Met to Val) in humans (human codon 129) predisposes exposed individuals to some forms of Creutzfeldt-Jakob disease. In this study, Rocky Mountain elk homozygous for PrP codon 1 32 Met were over-represented in both free-ranging and farm-raised CWD-affected elk when compared to unaffected control groups.

Animals↗

PubMed1999

Folate and folate-dependent enzymes associated with rat CNS development.

Folic acid and its derivatives are important mediators in growth-related cellular processes. The concentration of folate and two folate-dependent enzymes, 10-formyltetrahydrofolate synthetase (10-FTHFS) and 10-formyltetrahydrofolate dehydrogenase (10-FTHFDH), was determined in brain regions over the early period of rat development. Folate concentrations determined at birth were high in all brain regions studied. During the first 2 weeks, folate concentrations declined steadily, followed by a period of significant increase. High and invariant activity of 10-FTHFS was found throughout the period of study. Low amounts of 10-FTHFDH were seen for the first 2 weeks, but increased significantly from postnatal days 14 to 28. These changes correlated with changes determined in the concentration of folate, supporting the idea that this protein is involved with folate uptake and/or storage. Furthermore, immunohistochemical expression of 10-FTHFDH in different rat brain regions revealed glial cells as a preferential cellular location for this folate-binding protein.

Aging↗

PubMed1999

Utility of produce ratios to track fruit and vegetable consumption in a rural community, church-based 5 A Day intervention project.

Previous research suggests that grocery store characteristics may be useful in evaluating community-based dietary interventions. We undertook a study to determine whether produce ratios (ratios of produce sales to total grocery sales) were a useful indicator of fruit and vegetable (F & V) consumption in a church-based, community intervention trial that promoted 5 A Day guidelines within 10 rural counties of North Carolina. Produce ratios were collected from stores identified by participants in the Black Churches United for Better Health Project. Baseline and study period data for 21 stores in intervention counties and 18 stores in nonintervention counties were compared using repeated-measures analysis of variance. Produce ratios were significantly associated with seasonality (p < 0.0001), but no differences were seen between the two groups of stores. These findings do not support data from individual telephone surveys, which showed significant differences in F & V consumption between participants in the two groups. Our inability to detect differences at the store level may have been due to 1) the incapacity of produce ratios to capture F & V purchases that were juice, frozen, or canned products; 2) shifts in procuring F & Vs from grocery stores to other sources (i.e., gleaning and produce cooperatives); 3) the modest proportion of shoppers that received the full intervention dose; and 4) a general lack of power to detect differences at the store level. Therefore, although produce ratios did not serve as a valid measure for this project, if their limitations are recognized and compensated for, they may have applicability for future investigations that monitor F & V consumption.

Black or African American↗

PubMed1999

Immunologic responses of domestic and bighorn sheep to a multivalent Pasteurella haemolytica vaccine.

The efficacy of a Pasteurella haemolytica vaccine (serotypes A1, A2, and T10) to induce humoral antibodies and alter colonization of the upper respiratory tract by related P. haemolytica spp. strains was evaluated in 10 bighorn (Ovis canadensis canadensis) and 10 domestic (Ovis aries) sheep. Sheep of each species were divided into five pairs based on age and history of respiratory disease. One sheep in each pair was vaccinated twice 2 wk apart with 2 ml of vaccine (VAC group) and the remaining animals (NV group) were injected with 2 ml of sterile saline. Mild, transient lameness was the only observed adverse effect. Blood sera from the sheep were tested for agglutinating antibodies against whole cells of A1, A2, and T10 and for leukotoxin neutralizing antibodies. Antibody titers were expressed as the reciprocal log2 of the highest reactive dilutions. Domestic sheep > 1-yr-old and two bighorn sheep with a history of A1 infection had higher titers throughout the study against A1 cells than domestic sheep < 1-yr-old and bighorns without a history of A1 infection. Both domestic and bighorn sheep had log2 titers of 8 to 12 against A2 cells and 6 to 12 against T10 cells during this time. Bighorn sheep in the VAC group had 2 to 32 fold titer increases for A1 cells by 2 wk post-vaccination (PV) compared to 0 to 2 fold increases in VAC domestic sheep. Two to 16 and 0 to 8 fold increases in antibodies titers to A2 and T10 cells, respectively, were detected in sera of both VAC groups. Sera of bighorn sheep with a history of respiratory disease and all domestic sheep had log2 leukotoxin neutralizing antibody titers of 4 to 14 in contrast to < or = 2 in sera of bighorn sheep without a history of respiratory disease. Neutralizing antibody titers of two bighorns without a history of respiratory disease in the VAC group increased from log2 0 to 5 in one and from 0 to 9 in the other 2 wk PV. Antibody increases in these animals were no longer evident at 16 wk PV while titers of animals with histories of disease remained relatively stable. The types and numbers of Pasteurella spp. isolated from nasal and pharyngeal swabs varied throughout the study without conclusive evidence of suppression of colonization. Although the animals were not experimentally challenged to determine the efficacy of the vaccine, one VAC and one NV bighorn sheep died following introduction of an A2 P. haemolytica strain when leukotoxin neutralizing antibodies had returned to pre-vaccination levels. This vaccine appeared to be safe for use in bighorn sheep and stimulated moderate but transient increases in antibody levels which should provide some protection against naturally occurring disease. A vaccine which would induce production of high and maintained antibodies against multiple strains of P. haemolytica would be valuable for use in bighorn sheep maintained in captivity or when captured for relocation.

Agglutination Tests↗

PubMed1999

Polymerase chain reaction techniques for differentiating cytotoxic and noncytotoxic Pasteurella trehalosi from Rocky Mountain bighorn sheep.

OBJECTIVE: To evaluate 2 polymerase chain reaction (PCR)-based methods for differentiating cytotoxic and noncytotoxic Pasteurella trehalosi from Rocky Mountain bighorn sheep (Ovis canadensis canadensis). SAMPLE POPULATION: 23 isolates of P. trehalosi from bighorn sheep in Colorado, including 18 from free-ranging herds and 5 from a captive herd. PROCEDURE: Using a sequence of the leukotoxin gene region of P. haemolytica serotype 1, 7 PCR primers were designed. A PCR amplification was performed on a sample of bacterial cell suspensions from pure cultures of P. trehalosi with known in vitro cytotoxic effects. The 2 most promising primer pairs were used in a study of 23 P. trehalosi isolates. Results were analyzed for association with cytotoxicity and 3 distinct ribotypes (Eco, Aco, and Bco). RESULTS: Significant associations were observed between in vitro cytotoxicity and PCR results for coding region, between ribotype Eco classification and PCR results for coding region, and between ribotype Eco classification and PCR results for promoter region. There was a negative association between ribotype Aco classification and PCR results for coding and promoter regions. CONCLUSIONS AND CLINICAL RELEVANCE: The PCR for the leukotoxin A coding region may be useful in differentiating cytotoxic from noncytotoxic P. trehalosi isolates recovered from bighorn sheep. It may be useful for studying epidemiologic features of pasteurellosis in bighorn sheep and for designing vaccines to protect wild sheep against pneumonia caused by P. trehalosi and P. haemolytica.

Animals↗

PubMed1998

An evaluation of sialation of the nucleoporin p62.

Many nuclear and cytosolic proteins are modified by single residues of O-linked N-acetyl-D-glucosamine. These include many proteins found in nuclear pore complexes required for transport of macromolecules between the nucleus and the cytoplasm. The best characterized pore glycoprotein, p62, mediates its function as one component of a protein complex essential for nuclear transport. Although p62 sugar residues are not essential for nuclear transport, they appear to oppose protein phosphorylation occurring at sites predicted to destabilize protein-protein interactions of the p62 complex. Recently, a p62-like protein isolated from mouse neuroblastoma cells was reported to be modified by both GlcNAc and sialic acid. As there is little precedent for nucleoplasmic sialation, the finding that a characterized nuclear pore protein is sialated is significant because it may regulate pore function. To assess the biological importance of p62 sialation, GlcNAc and sialic acid-specific lectins were used to examine the state of p62 glycosylation in cells commonly used to study nuclear transport: frog eggs and normal rat kidney and HeLa fibroblasts. In addition, four mouse neuroblastoma cell lines derived from the same tumor were examined. The glycosylation of p62 in these cells appears to involve only single O-linked GlcNAc moieties; no significant sialation was detected.

Animals↗

PubMed1998

Nuclear glycogen and glycogen synthase kinase 3.

Glycogen is the principal storage form of glucose in animal cells. It accumulates in electron-dense cytoplasmic granules and is synthesized by glycogen synthase (GS), the rate-limiting enzyme of glycogen deposition. Glycogen synthase kinase-3 (GSK-3) is a protein kinase that phosphorylates GS. Two nearly identical forms of GSK-3 exist: GSK-3 alpha and GSK-3 beta. Both are constitutively active in resting cells and their activity can be modulated by hormones and growth factors. GSK-3 is implicated in the regulation of many physiological responses in mammalian cells by phosphorylating substrates including neuronal cell adhesion molecule, neurofilaments, synapsin I, and tau. Recent observations point to functions for glycogen and glycogen metabolism in the nucleus. GSK-3 phosphorylates several transcription factors, and we have recently shown that it modifies the major nuclear pore protein p62. It also regulates PK1, a protein kinase required for maintaining the interphase state and for DNA replication in cycling Xenopus egg extracts. Recently, glycogen was shown to be required for nuclear reformation in vitro using ovulated Xenopus laevis egg lysates. Because neither glycogen nor GSK-3 has been localized to the nuclear envelope or intranuclear sites, glycogen and GSK-3 activites were measured in rat liver nuclei and nuclear reformation extracts. Significant quantities of glycogen-like material co-purified with the rat-liver nuclear envelope. GSK-3 is also highly enriched in the glycogen pellet of egg extracts of Xenopus that is required for nuclear assembly in vitro. Based on the finding that enzymes of glycogen metabolism copurify with glycogen, we propose that glycogen may serve a structural role as a scaffold for nuclear assembly and sequestration of critical kinases and phosphatases in the nucleus.

Animals↗

PubMed1998

Chronic Trypanosoma cruzi infection in dogs: 11 cases (1987-1996).

OBJECTIVE: To determine whether prevalence of naturally developing chronic infection with Trypanosoma cruzi in dogs in Texas changed between 1987 and 1996 and to characterize clinical aspects of the disease. DESIGN: Retrospective study. ANIMALS: 11 dogs with chronic infection with T cruzi. PROCEDURE: Number of positive serologic test results for T cruzi obtained between 1987 and 1996 were compared with the number of tests for T cruzi performed during the same period. Survival time, signalment, and clinical signs of dogs and results of thoracic radiography, electrocardiography, and echocardiography were evaluated. The Mann-Whitney test was used to assess the association between age at time of initial examination and survival time. RESULTS: The proportion of positive test results increased, compared with the number of tests submitted, during the 9-year period. Clinical signs in affected dogs were consistent with right-sided cardiac disease. Results of thoracic radiography were nonspecific. Conduction disturbances and supraventricular and ventricular arrhythmias were evident. Echocardiographic abnormalities, including chamber enlargement and functional impairment, were detected. Dogs were characterized on the basis of survival time; group-1 dogs (n = 6) survived 0 to 5 months, and group-2 dogs (5) survived 31 to 60 months. Age at time of initial examination was associated with survival time. CLINICAL IMPLICATIONS: Clinical course of disease varied. Electrocardiographic and echocardiographic changes may be detected. Clinicians should be aware of the potential for T cruzi infection in dogs with clinical signs of right-sided cardiac dysfunction and unexplained conduction disturbances and arrhythmias. Prevalence of this disease may be increasing in some regions of Texas.

Animals↗

PubMed1998

Effect of ethanol on neurotrophin-mediated cell survival and receptor expression in cultures of cortical neurons.

The interaction of ethanol and neurotrophin-mediated cell survival was examined in primary cultures of cortical neurons. Cells were obtained from rat fetuses on gestational day 16 and maintained in a medium supplemented with either 10% or 1.0% fetal calf serum (FCS). Exogenous nerve growth factor (NGF; 20 ng/ml), brain-derived neurotrophic factor (BDNF; 20 ng/ml) or neurotrophin 3 (NT-3; 20 ng/ml) was added to the cultures alone, or in combination with ethanol (400 mg/dl). The number of viable neurons was determined after a 48 h treatment with a growth factor and/or ethanol. The effects of ethanol on the expression of high affinity neurotrophin receptors (trkA, trkB, and trkC) and the low-affinity receptor (p75), were analyzed using Western immunoblots. In untreated cultures, 22.7% and 26.3% of the cells raised in a medium containing 10% and 1.0% FCS, respectively, were lost. Only NGF prevented the death of the cultured cortical neurons. Ethanol was toxic; it caused a 23.5% and 16.7% loss of cells (for cells grown in a medium containing 10% and 1.0% FCS, respectively) beyond that occurring 'naturally' in an untreated culture. Ethanol completely blocked the NGF-mediated cell survival. In general, BDNF and NT-3 did not offset the toxic effect of ethanol. Immunoblotting studies showed that the expression of p75 was significantly (p < 0.05) lower (40%) in ethanol-treated cultures, but ethanol did not affect trk expression. Thus, ethanol has specific effects upon NGF-mediated cell survival and the effects on the low affinity receptor imply that p75 specifically plays an important role in NGF signaling.

Animals↗

PubMed1998

Multiple copies of the ALA-D gene are located at the Lv locus in Mus domesticus mice.

Incremental differences in delta-aminolevulinate dehydratase (ALA-D; the second enzyme of the heme biosynthetic pathway) activity among inbred mouse strains can be attributed to variation in the number of copies of the ALA-D gene. We have cloned and characterized the Lv locus from an inbred mouse strain (DBA/2J) that has three times the normal ALA-D activity levels. The entire 12-kb ALA-D gene plus 16 kb of flanking DNA are found in 28-kb tandemly repeating units. We used the derived nucleotide sequence surrounding the internal junction of the repeats to survey wild-caught mice and demonstrate that multiple copies of the ALA-D gene occur in 7 of 24 worldwide locations of Mus domesticus mice. Data are consistent with a model that high lead (Pb) in the environment may be providing a selective advantage to mice harboring multiple copies of the ALA-D gene, since the enzyme is potently inhibited by lead.

Animals↗

PubMed1998

Prevalence of heartworm infection in cats with signs of cardiorespiratory abnormalities.

OBJECTIVE: To determine prevalence of heartworm infection in a population of pet cats with cardiorespiratory abnormalities and to determine relative usefulness of clinical signs and tests in diagnosis of heartworm disease. DESIGN: Prospective case series. ANIMALS: 100 client-owned cats with clinical signs of cardiorespiratory abnormalities. PROCEDURE: Cats were evaluated using CBC, modified Knott test, ELISA for serologic detection of heartworm antigen and antibodies to heartworms, thoracic radiography, and echocardiography. Cats were considered infected if they had circulating microfilaria, heartworm antigens in serum, or if heartworms were detected by echocardiography or on necropsy. Cats were considered suspicious for infection if they had 2 of the following: serum antibodies to heartworms, eosinophilia or basophilia, or indicative radiographic findings. RESULTS: 9 cats were infected with heartworms, resulting in a prevalence of 9%; 26 cats had evidence of heartworm exposure (i.e., serum antibodies to heartworms). Twenty cats were considered suspicious for heartworm infection. Some outdoor exposure was reported twice as often in heartworm-infected cats, compared with noninfected and suspicious cats. However, a third of infected cats were reportedly housed totally indoors. Cough and dyspnea were strong indicators of heartworm disease. Eight of 9 infected cats had serum antibodies to heartworms and heartworm antigen in serum. Thoracic radiography and echocardiography indicated heartworm infection in 6 and 7 of the 9 cats, respectively. CLINICAL IMPLICATIONS: Cough or dyspnea may indicate heartworm disease in cats; serologic tests, echocardiography, and radiography are most useful diagnostic procedures. Although living indoors is protective, it may not preclude heartworm infection in cats.

Animals↗

PubMed1998

Expression of p53 and ALZ-50 immunoreactivity in rat cortex: effect of prenatal exposure to ethanol.

Neuronal death is an active process that results in the upregulation of antigens recognized by ALZ-50 and p53. Since prenatal exposure to ethanol can induce the postnatal death of cortical neurons, we examined the effects of ethanol on the in vivo expression of both the ALZ-50-positive antigen and p53. Pregnant rats were fed one of three diets, a liquid diet containing ethanol (Et), an isocaloric and isonutritive diet (Ct), or chow and water (Ch). Segments of frontoparietal cortex from fetuses and pups were examined for ethanol-induced changes (a) in the expression of ALZ-50 and p53 immunoreactivity using a quantitative immunoblotting assay and (b) in the distribution of ALZ-50- and p53-positive cells using immunohistochemistry. In control rats, ALZ-50 identified a 56-kDa peptide that was transiently expressed postnatally and peak expression occurred on postnatal day (P) 6 to P12. In Et-treated rats, peak expression was attained earlier (on P3) and was about three times of that achieved in the controls. The anti-p53 antibody identified three proteins (28, 56, and 58 kDa). Peak expression in control rats occurred during the second postnatal week and only the 58-kDa protein was expressed in appreciable amounts in adult cortex. Each p53-positive protein was affected by ethanol exposure. The 28- and 56-kDa p53-positive proteins were affected by ethanol much in the same way as was the ALZ-50-positive antigen. That is, the timing and amount of peak expression were earlier and lower, respectively, in the Et-treated rats. The postnatal expression of the 58-kDa protein was halved following prenatal exposure to ethanol. Both ALZ-50 and anti-p53 immunoprecipitated proteins are p53- and ALZ-50-positive, respectively. Thus, ethanol alters the expression of the ALZ-50- and p53-positive proteins and presumably the timing of neuronal death in the developing cortex. The parallel effects of prenatal ethanol exposure on the 56-kDa ALZ-50-positive antigen and the 28- and 56-kDa p53-positive proteins and the coprecipitation of the proteins are consistent with the notion that ALZ-50 recognizes a form of p53.

Animals↗