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Biomedical subjects

R J Miller

Publications and source records attributed to R J Miller.

At least 37 records · Page 2Linked to original sources
PubMed2001

Attenuation coefficient estimates of mouse and rat chest wall.

Attenuation coefficients of intercostal tissues were estimated from chest walls removed postmortem (pm) from 41 6-to-7-week-old female ICR mice and 27 10-to-11-week-old female Sprague-Dawley rats. These values were determined from measurements through the intercostal tissues, from the surface of the skin to the parietal pleura. Mouse chest walls were sealed in plastic wrap and stored at 4 degrees C until evaluated, and rat chest walls were sealed in Glad-Lock Zipper sandwich bags, and stored at -15 degrees C. When evaluated, chest wall storage time ranged between 1 and 2 days pm for mice and between 41 and 110 days pm for rats. All chest walls were allowed to equilibrate to 22 degrees C in a water bath prior to evaluation. For both mouse and rat intercostal tissues, the estimated frequency normalized attenuation coefficient was 1.1 dB/cm-MHz. In order to determine if there was an effect of storage time on estimates of attenuation coefficient, an independent experiment was conducted. The intercostal tissues from six mouse chest walls were evaluated at three time points (1, 22, and 144 days pm), and from six rat chest walls were evaluated at four time points (1, 22, 50, and 125 days pm). There was no difference in the estimated intercostal tissue attenuation coefficient as a function of time postmortem.

Animals↗
PubMed2001

Use of an allele-specific polymerase chain reaction assay to genotype pyrethroid resistant strains of Boophilus microplus (Acari: Ixodidae).

A polymerase chain reaction-based assay was developed to detect the presence of a pyrethroid resistance-associated amino acid substitution in Boophilus microplus (Canestrini). The assay uses a simple method for the extraction of genomic DNA from individual larvae and genotypes individuals for the presence of a Phe-->Ile amino acid substitution in the S6 transmembrane segment of domain III of the para-like sodium channel, clearly distinguishing heterozygotes from homozygotes. High frequencies for this amino acid substitution were found in the Corrales and San Felipe strains, which have target site insensitivity mechanisms for pyrethroid resistance. The Caporal resistant strain contained lower yet substantial numbers of amino acid-substituted alleles. Low amino acid substitution frequencies were found in the susceptible reference Gonzales strain and the Coatzacoalcos strain, which has metabolic esterase-mediated pyrethroid resistance. The amino acid substitution was not found in six other strains that were susceptible to pyrethroids.

Alleles↗
PubMed2001

Characterization of acaricide resistance in Rhipicephalus sanguineus (latreille) (Acari: Ixodidae) collected from the Corozal Army Veterinary Quarantine Center, Panama.

Rhipicephalus sanguineus (Latreille) were collected from the Corozal Army Veterinary Quarantine Center in Panama and characterized for resistance to five classes of acaricides. These ticks were highly resistant to permethrin, DDT, and coumaphos; moderately resistant to amitraz; and not resistant to fipronil when compared with susceptible strains. Resistance to both permethrin and DDT may result from a mutation of the sodium channel. However, synergist studies indicate that enzyme activity is involved. The LC50 estimate for permethrin was lowered further in the Panamanian strain then in susceptible strains with the addition of triphenylphosphate (TPP), but not with the addition ofpiperonyl butoxide (PBO). This suggests that esterases and not oxidases are responsible for at least some pyrethroid resistance. Elevated esterase activity and its inhibition by TPP were confirmed by native gel electrophoresis. The LC50 estimate obtained for coumaphos in the Panamanian strain was not lowered further than what was observed for susceptible strains by the addition of TPP or PBO. This indicates that enzyme activity might not be involved in coumaphos resistance. Resistance to amitraz was measured through a modification of the Food and Agriculture Organization Larval Packet Test. All tick strains were found to be susceptible to fipronil.

Animals↗
PubMed2000

The status of voltage-dependent calcium channels in alpha 1E knock-out mice.

It has been hypothesized that R-type Ca currents result from the expression of the alpha(1E) gene. To test this hypothesis we examined the properties of voltage-dependent Ca channels in mice in which the alpha(1E) Ca channel subunit had been deleted. Application of omega-conotoxin GVIA, omega-agatoxin IVA, and nimodipine to cultured cerebellar granule neurons from wild-type mice inhibited components of the whole-cell Ba current, leaving a "residual" R current with an amplitude of approximately 30% of the total Ba current. A minor portion of this R current was inhibited by the alpha(1E)-selective toxin SNX-482, indicating that it resulted from the expression of alpha(1E). However, the majority of the R current was not inhibited by SNX-482. The SNX-482-sensitive portion of the granule cell R current was absent from alpha(1E) knock-out mice. We also identified a subpopulation of dorsal root ganglion (DRG) neurons from wild-type mice that expressed an SNX-482-sensitive component of the R current. However as with granule cells, most of the DRG R current was not blocked by SNX-482. We conclude that there exists a component of the R current that results from the expression of the alpha(1E) Ca channel subunit but that the majority of R currents must result from the expression of other Ca channel alpha subunits.

Animals↗
PubMed2000

Selective regulation of N-type Ca channels by different combinations of G-protein beta/gamma subunits and RGS proteins.

We examined the effects of G-protein beta and gamma subunit heterodimers on human alpha(1B) (N-type) Ca channels expressed in HEK293 cells. All of the known beta subunits (beta1-beta5) produced voltage-dependent inhibition of alpha(1B) Ca channels, depending on the gamma subunit found in the heterodimer. beta1-beta4 subunits inhibited Ca channels when paired with gamma1-gamma3. However, beta5 subunits only produced inhibition when paired with gamma2. In contrast, heterodimers between beta5 subunits and RGS (regulators of G-protein signaling) proteins containing GGL domains did not produce inhibition of Ca channels. However, GGL domain-containing RGS proteins (e.g., RGS6 and RGS11) did block the ability of Gbeta5/gamma2 heterodimers to inhibit Ca channels. Because all of the G-protein beta subunits are found in the nervous system, we conclude that they may all potentially participate in Ca channel inhibition. The interaction of GGL-containing RGS proteins with Gbeta5gamma2 suggests a novel way in which Ca channels can be regulated.

Analysis of Variance↗
PubMed2000

Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival.

Recent in vitro and in vivo studies have shown that the chemokine fractalkine is widely expressed in the brain and localized principally to neurons. Central nervous system expression of CX(3)CR1, the only known receptor for fractalkine, has been demonstrated exclusively on microglia and astrocytes. Thus, it has been proposed that fractalkine regulates cellular communication between neurons (that produce fractalkine) and microglia (that express its receptor). Here we show, for the first time, that hippocampal neurons also express CX(3)CR1. Receptor activation by soluble fractalkine induces activation of the protein kinase Akt, a major component of prosurvival signaling pathways, and nuclear translocation of NF-kappaB, a downstream effector of Akt. Fractalkine protects hippocampal neurons from the neurotoxicity induced by the HIV-1 envelope protein gp120(IIIB), an effect blocked by anti-CX(3)CR1 antibodies. Experiments with two different inhibitors of the phosphatidylinositol 3-kinase, a key enzyme in the activation of Akt, and with a phospholipid activator of Akt demonstrate that Akt activation is responsible for the neuroprotective effects of fractalkine. These data show that neuronal CX(3)CR1 receptors mediate the neurotrophic effects of fractalkine, suggesting that fractalkine and its receptor are involved in a complex network of both paracrine and autocrine interactions between neurons and glia.

Animals↗
PubMed2000

Cryosurgery for prostate cancer: new technology and indications.

Patients diagnosed with prostate cancer who elect to pursue active treatment of their disease must choose among the many available treatment alternatives. Several treatment options now exist for similar-stage disease (clinical T1-3N0M0), including radical prostatectomy, external beam radiation, prostate brachytherapy (PB), and cryosurgical ablation of the prostate (CSAP). This article reviews the current role of CSAP in the treatment of clinically localized prostate cancer. CSAP has a role in the primary treatment of men with high-risk, clinically localized prostate cancer (defined as PSA >10, Gleason score >or=7, or clinical stage >or= cT2B). CSAP (occasionally followed by external beam radiotherapy) appears to offer improved rates of cancer control over other types of single or combination therapies for this high-risk prostate cancer, and it is associated with an acceptable side-effect profile. CSAP should also be the treatment of choice for men with recurrent local disease who have undergone external beam radiotherapy or PB.

Cryosurgery↗
PubMed2000

More mysteries of opium reveal'd: 300 years of opiates.

This year is the 300th anniversary of the publication of one of the first books written about opiates and their subjective effects. Since that time the influence of opiates in Western society has grown enormously, as has our knowledge of the mechanisms by which these drugs produce their effects. Wars have been fought over the use of opiates and the economies of several countries depend on their production. In this article, some aspects of the history and effects of opiates on the arts in particular are explored.

History, 17th Century↗
PubMed2000

The selective toxicity of 1-methyl-4-phenylpyridinium to dopaminergic neurons: the role of mitochondrial complex I and reactive oxygen species revisited.

1-Methyl-4-phenylpyridinium (MPP(+)) is selectively toxic to dopaminergic neurons and has been studied extensively as an etiologic model of Parkinson's disease (PD) because mitochondrial dysfunction is implicated in both MPP(+) toxicity and the pathogenesis of PD. MPP(+) can inhibit mitochondrial complex I activity, and its toxicity has been attributed to the subsequent mitochondrial depolarization and generation of reactive oxygen species. However, MPP(+) toxicity has also been noted to be greater than predicted by its effect on complex I inhibition or reactive oxygen species generation. Therefore, we examined the effects of MPP(+) on survival, mitochondrial membrane potential (DeltaPsim), and superoxide and reduced glutathione levels in individual dopaminergic and nondopaminergic mesencephalic neurons. MPP(+) (5 microM) selectively induced death in fetal rat dopaminergic neurons and caused a small decrease in their DeltaPsim. In contrast, the specific complex I inhibitor rotenone, at a dose (20 nM) that was less toxic than MPP(+) to dopaminergic neurons, depolarized DeltaPsim to a greater extent than MPP(+). In addition, neither rotenone nor MPP(+) increased superoxide in dopaminergic neurons, and MPP(+) failed to alter levels of reduced glutathione. Therefore, we conclude that increased superoxide and loss of DeltaPsim may not represent primary events in MPP(+) toxicity, and complex I inhibition alone is not sufficient to explain the selective toxicity of MPP(+) to dopaminergic neurons. Clarifying the effects of MPP(+) on energy metabolism may provide insight into the mechanism of dopaminergic neuronal degeneration in PD.

1-Methyl-4-phenylpyridinium↗
PubMed2000

Trust and disclosure of sexual orientation in gay males' mother-son relationships.

This study explored the possibility that changes in feelings of trust for mother are associated with gay males' decisions to disclose (or withhold) their sexual orientation in their mother-son relationships. Fifty gay and bisexual males completed a questionnaire about their coming out experiences in the context of their relationships with their mothers. As part of this questionnaire, they completed a retrospective graphical trust history task that involved plotting the degree of trust they felt for their mothers over time and across important events (such as disclosure). Results are discussed in terms of gay men's expectations about their mothers' responses to disclosure, the evidence for stability versus change in their memories regarding the nature of their feelings of maternal trust over time, the complexity of the trust histories participants drew, similarity between disclosers and non-disclosers in the shape of their trust curves, and the types of events and experiences that constituted the timeline or "plot" in the stories participants told about their mother-son relationships. This study offers the first empirical evidence to support speculations linking disclosure of sexual orientation to the climate of trust that exists in the relationship between discloser and target (e.g., Holtzen, Kenny & Mahalik, 1995).

Adolescent↗
PubMed2000

Pupation site selection of cat fleas (Siphonaptera: Pulicidae) in various carpet types and its influence on insecticide efficacy.

Pupation sites of cat flea, Ctenocephalides felis (Bouché), larvae were determined in three styles of nylon and one style of wool carpet. Nylon saxony carpet had 59.3% of pupae at the top of the pile and 40% at the base of the pile. In nylon contract carpet, 55.2% of pupae were found at the top, 42.6% in the middle, and only 2.2% at the base of the pile. Nylon loop carpet contained 59.2% of pupae at the base, 25.5% in the middle, and 15.3% in the top of the pile. Wool loop carpet had 92.4% at the base and 3.8% both in the middle and top of the pile. Bioassays comparing the control of pupae manually placed at the base of carpets to that in carpets with natural pupation showed that control of pupae in the latter was 39-68% higher. Pupal control after natural pupation was greatest in nylon saxony and nylon contract carpets and lowest in nylon loop and wool loop carpets. Additional studies demonstrated that vacuuming provided the same level of pupal control on nylon saxony carpet as a spray application of permethrin to the carpet surface. Therefore, pupae that survived chemical and mechanical control treatments in nylon saxony carpet probably pupated away from the surface of the pile. Application of permethrin to the base of nylon saxony carpet did not significantly increase control. Future bioassays with cat flea pupae in carpet should be performed after natural pupation and consider carpet make and style.

Animals↗
PubMed2000

Involvement of regions in domain I in the opioid receptor sensitivity of alpha1B Ca(2+) channels.

The structural basis of Ca(2+) channel inhibition by G proteins has received considerable attention recently, and multiple regions on Ca(2+) channels that interact with G protein subunits have been identified. We have demonstrated previously that a region extending from the N terminus to the I/II loop of the Ca(2+) channel is involved in determining the differences between alpha1B and alpha1E Ca(2+) channels with respect to inhibition by G proteins. Here we explore this region of the channel in greater detail in an effort to further define the regions involved in determining inhibition. Chimeric Ca(2+) channels constructed from alpha1B and alpha1E Ca(2+) channels revealed that the N terminus, the I/II loop, and domain I all play an important role in determining inhibition. We identified a 70-amino acid fragment from domain I that mediates the effects of domain I, and a 50-amino acid fragment from the I/II loop that mediates the effects of the I/II loop. When these regions from alpha1B were exchanged into alpha1E, inhibition identical with that of alpha1B was observed. The differences between alpha1B and alpha1E in the identified region of domain I involve residues that are predicted to be almost exclusively extracellular. Mutations to some of the high-affinity G protein binding regions of alpha1B (alpha interaction domain, CC14, and a C-terminal Galpha binding site) caused relatively little change in inhibition, which suggests that these sites are not necessary individually for G protein-mediated inhibition and may help to explain the small effects of exchanging these regions in isolation.

Amino Acid Sequence↗
PubMed2000

Counseling patients about cryotherapy for prostate cancer in the information age.

Patients diagnosed with prostate cancer who elect to pursue active treatment of their disease must choose among the many available treatment alternatives. Several treatment options now exist for similar stage disease (clinical T1-3N0M0), including radical prostatectomy, external beam radiotherapy, prostate brachytherapy, cryosurgical ablation of the prostate (CSAP), and various combination therapies. This article focuses principally on the authors' philosophy regarding the role of CSAP in the treatment of clinically localized prostate cancer and is written to aid patients in their treatment decision. There is limited information on CSAP in the standard resources, such as the Internet and books frequently used by patients to make their treatment decisions. This article can serve as a resource on the evolution, results, and complications of CSAP that are reported. Cryosurgical ablation of the prostate has a role in the primary treatment of men with high risk, clinically localized prostate cancer (defined as prostate-specific antigen >10, Gleason score > or =7, or clinical stage > or =cT2B). Cryosurgical ablation of the prostate (occasionally followed by external beam radiotherapy) appears to offer improved rates of cancer control over other types of single or combination therapies for this high risk prostate cancer, and is associated with an acceptable side effect profile. Cryosurgical ablation of the prostate should also be the treatment of choice for men with recurrent local disease after external beam radiotherapy.

Adult↗
PubMed1999

The role of beta-catenin stability in mutant PS1-associated apoptosis.

Most early onset cases of familial Alzheimer's disease (FAD) are caused by mutations in presenilin-1 (PS1) and presenilin-2 (PS2). These mutations lead to increased beta-amyloid formation and induce apoptosis when expressed in vitro. Recently, PS1 has been reported to associate with beta-catenin, an armadillo repeat protein. PS1 may regulate the function of beta-catenin, and mutant PS1 may disrupt this regulation. In the present study, we confirm that PS1-WT, as well as mutant PS1, associates with beta-catenin, and that mutant PS1 expression decreases the stability and/or enhances the degradation of beta-catenin. Most importantly, we correlate beta-catenin's destabilization with mutant PS1-associated apoptosis by administering drugs that alter the stability of beta-catenin. The application of LiCl and a proteasome inhibitor, N-acetyl-leu-leu-norleucinal (ALLN), increased the stability of cytosolic beta-catenin in mutant PS1-expressing cells leading to rescue of these cells from apoptosis. These studies suggest that beta-catenin is a key mediator of mutant PS1-associated apoptosis and FAD pathogenesis.

Alzheimer Disease↗
PubMed1999

Mutant presenilin-1 induces apoptosis and downregulates Akt/PKB.

Most early onset cases of familial Alzheimer's disease (AD) are caused by mutations in presenilin-1 (PS1) and presenilin-2 (PS2). These mutations lead to increased beta-amyloid formation and may induce apoptosis in some model systems. Using primary cultured hippocampal neurons (HNs) and rat pheochromocytoma (PC12) cells transiently transfected with replication-defective recombinant adenoviral vectors expressing wild-type or mutant PS1, we demonstrate that mutant PS1s induce apoptosis, downregulate the survival factor Akt/PKB, and affect several Akt/PKB downstream targets, including glycogen synthase kinase-3beta and beta-catenin. Expression of a constitutively active Akt/PKB rescues HNs from mutant PS1-induced neuronal cell death, suggesting a potential therapeutic target for AD. Downregulation of Akt/PKB may be a mechanism by which mutant PS1 induces apoptosis and may play a role in the pathogenesis of familial AD.

Adenoviridae↗