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Biomedical subjects

P A Nelson

Publications and source records attributed to P A Nelson.

At least 19 recordsLinked to original sources

Errors in two-point sound reproduction.

This paper deals with the problem of reproducing two signals at two points in space by using two acoustic sources. While much is now known about the techniques available for the design of matrices of inverse filters that enable this objective to be achieved in practice, it is still the basic physics of the sound field produced that controls the effectiveness of such systems and which ultimately dictates their design. The basic physical processes involved in producing the cross-talk cancellation that enables the reproduction of the desired signals is revisited here by using a simple two source/two field point free field model. The singular value decomposition is used to identify those frequencies where the inversion problem becomes ill-conditioned and to explain physically the origin of the ill-conditioning. As observed previously, it is found that cross-talk cancellation becomes problematic when the path length difference between the two sources and one of the field points becomes equal to one half the acoustic wavelength. The ill-conditioned frequencies are also found to be associated with a limited spatial region of cross-talk cancellation and with large source outputs manifested in the time domain by responses of long duration.

Acoustics↗

Ontogenetic changes and environmental effects on ocular transmission in four species of coral reef fishes.

Filtration by the humors, cornea and lens limits the spectrum of light available for vision as blocking compounds prevent some wavelengths from reaching photo-sensitive cells of the retina. The visual ecology of fishes is dependent upon factors changing with size and/or habitat. We predicted that ontogeny and habitat depth would affect ocular transmission for four fishes, Mulloidichthys flavolineatus, Parupeneus multifasciatus, Acanthurus triostegas, and Naso lituratus. We measured ocular transmission in specimens from a range of sizes (juvenile-adult) and capture depths (<3-37 m), and used the wavelength (nm) where transmission was reduced 50% as our comparative measure (T(50)). We modeled lens transmission varying pigment concentrations and pathlength, and compared predicted versus measured results. P. multifasciatus, M. flavolineatus, and N. lituratus showed a significant increase in short-wavelength blocking with size. A. triostegas were constant across sizes, and showed a slight but significant effect with depth. Comparisons of predicted versus observed transmission values suggest that pigment concentrations are held constant with age for all species, but species- and family-level differences emerge. The accumulation of blocking compounds in ocular tissues is a contributing means for balancing the costs and benefits of admitting short-wavelength radiation to the retina.

Age Factors↗

Antipsychotic drug treatment alters expression of mRNAs encoding lipid metabolism-related proteins.

Using an automated PCR-based genomics approach, TOtal Gene expression Analysis (TOGA), we have examined gene expression profiles of mouse striatum and frontal cortex in response to clozapine and haloperidol drug treatment. Of 17 315 mRNAs observed, TOGA identified several groups of related molecules that were regulated by drug treatment. The expression of some genes encoding proteins involved in neurotransmission, signal transduction, oxidative stress, cell adhesion, apoptosis and proteolysis were altered in the brains of both clozapine- and haloperidol-treated mice as recognized by TOGA. Most notable was the differential expression of those genes whose products are associated with lipid metabolism. These include apolipoprotein D (apoD), the mouse homolog of oxysterol-binding protein-like protein 8 (OSBPL8), a diacylglycerol receptor (n-chimerin), and lysophosphatidic acid (LPA) acyltransferase. Real-time PCR analysis confirmed increases in the RNA expression of apoD (1.6-2.2-fold) and OSBPL8 (1.7-2.6-fold), and decreases in the RNA expression of n-chimerin (1.5-2.2-fold) and LPA acyltransferase (1.5-fold) in response to haloperidol and/or clozapine treatment. Additional molecules related to calcium homeostasis and signal transduction, as well as four sequences of previously unidentified mRNAs, were also confirmed by real-time PCR to be regulated by drug treatment. While antipsychotic drugs may affect several metabolic pathways, lipid metabolism/signaling pathways may be of particular importance in the mechanisms of antipsychotic drug action and in the pathophysiology of psychiatric disorders.

Acyltransferases↗

Malignant glioma cells use MHC class II transactivator (CIITA) promoters III and IV to direct IFN-gamma-inducible CIITA expression and can function as nonprofessional antigen presenting cells in endocytic processing and CD4(+) T-cell activation.

Malignant gliomas (MGs), lethal human central nervous system (CNS) neoplasms, contain tumor infiltrating lymphocytes (TIL). Although MHC class II molecules are frequently detected on MG cells, suggesting that they may be capable of antigen (Ag) presentation to CD4(+) T cells, deficiencies in CD4(+) T-cell activation are associated with these nonimmunogenic tumors. We evaluated regulation of the MHC class II transactivator (CIITA), the key intermediate that controls class II expression, in MG cells and tested whether MG cells could process native Ag. After interferon-gamma (IFN-gamma) stimulation, MG cells upregulated CIITA and class II molecules. IFN-gamma-inducible CIITA expression in MG cells, as well as primary human astrocytes, was directed by two CIITA promoters, pIV, the promoter for IFN-gamma-inducible CIITA expression in nonprofessional antigen-presenting cells (APC), and pIII, the promoter that directs constitutive CIITA expression in B cells. Both pIII and pIV directed CIITA transcription in vivo in MGs and ex vivo in IFN-gamma-activated primary MG cultures. We also demonstrate for the first time that MG cells can process native Ag for presentation to CD4(+) MHC class II-restricted Th1 cells, indicating that MG cells can serve as nonprofessional APC. CIITA may be a key target to modulate MHC class II expression, which could augment immunogenicity, Ag presentation, and CD4(+) T-cell activation in MG therapy.

Adult↗

Serological analysis of patients treated with a new surgical hemostat containing bovine proteins and autologous plasma.

A randomized, controlled clinical study of the management of diffuse bleeding with CoStasis surgical hemostat, a new hemostat containing bovine thrombin and collagen with the patient's own plasma, included patients undergoing cardiac, hepatic, iliac, and general surgery. Sera from 92 patients treated with CoStasis and 84 control patients were collected preoperatively and at a post surgical follow-up of 8 weeks. Among the control group, 57 patients were treated with Instat collagen sponge in noncardiac indications. Results showed that antibody responses in the CoStasis clinical study were similar to the reported literature for all antigens screened and were not associated with any adverse reactions. The bovine thrombin preparations in CoStasis and other commercially available thrombins were compared with the use of SDS-PAGE and Western blot analyses. Within this clinical study, CoStasis was shown to be a safe and effective hemostatic product containing bovine thrombin and bovine collagen and no pooled human blood products.

Animals↗

Clozapine increases apolipoprotein D expression in rodent brain: towards a mechanism for neuroleptic pharmacotherapy.

In contrast to typical neuroleptic drugs, which have high affinities for dopamine D2 receptors, clozapine binds to multiple neurotransmitter receptors. The mechanisms responsible for its superior clinical efficacy over typical neuroleptics remain unknown. Using an automated genomics approach, total gene expression analysis (TOGA), we found an approximately threefold increase in the accumulation of the mRNA encoding apolipoprotein D (apoD) in mouse striatum in response to chronic treatment with clozapine. While in control animals, apoD is expressed predominantly in astrocytes, in situ hybridization and immunohistochemical studies indicated a substantial increase in apoD expression in neurons of the striatum, globus pallidus and thalamus after 2 weeks of clozapine treatment. Clozapine-induced increases in apoD expression were also observed in some white matter regions. These results suggest that apoD is a mediator in the mechanisms of clozapine and thus that deficiencies in aspects of lipid metabolism may be responsible for psychoses.

Animals↗

Robustness to head misalignment of virtual sound imaging systems.

When binaural sound signals are presented with two loudspeakers, the listener's ears are required to be in the relatively small region which is under control of the system. Misalignment of the head results in inaccurate synthesis of the binaural signals. Consequently, directional information associated with the acoustic signals is inaccurately reproduced. When the two loudspeakers are placed close together, the spatial rate of change of the generated sound field is much smaller than that generated by two loudspeakers spaced apart. Therefore, the performance of such a system is expected to be more robust to misalignment of the listener's head. Robustness of performance is investigated here with respect to head displacement in three translational and three rotational directions. A comparison is given between systems consisting of two loudspeakers either placed close together or spaced apart. The extent of effective control with head displacement and the resulting deterioration in directional information is investigated in the temporal and spectral domain by analyzing synthesized binaural signals. Subjective localization experiments are performed for cases in which notable differences in performance are expected from the previous analysis. It is shown that the system comprising two loudspeakers that are close together is very robust to misalignment of the listener's head.

Acoustics↗

Diphyllobothriasis: update on human cases, foci, patterns and sources of human infections and future considerations.

Diphylobothriasis is a well documented disease of humans. On a world scale new infections are reported regularly, especially from Russia and parts of Japan. Globally, new species have been discovered and the etiology of the disease may be changing. Human infections appear to be in decline but it is not clear if the sources of infection are also in decline or if public health awareness has improved. In North America there has been a decline in human cases while in South America an increase in reports from fish, especially salmonids suggests high levels in these fish species. The history of human infections of Diphyllobothrium latum is primarily associated with the consumption of the northern circumpolar distributed pike and percids and is often considered a parasite of humans only. Indeed some researchers believe that D. latum was introduced to North America by northern European immigrants. The more benign human infections of D. dendriticum appears to be primarily associated with salmonids and coregonid fishes and fish eating birds. Although the early cases of diphyllobothriasis in the 1930s in North America came from fish originating in Lake Winnipeg, Manitoba, there was general belief that it was declining in fish populations and therefore of little significance to humans in the area. However, high levels of a plerocercoid in the flesh of walleyes and pike led to rejection of commercially harvested walleye and pike in Manitoba and northern Ontario, Canada, and a financial loss to Aboriginal fishers. D. latum is widely distributed in fishes of Manitoba and is infective to humans where it is not pathogenic and has a life span up to 4.5 years. The distribution and potential infection routes has not changed in a century and is still well established in natural hosts in the boreal regions of North America. Evidence is building for an old pre-European presence in North America, involving the Beringian land bridge and later involvement of susceptible hosts (northern European immigrants).

Animals↗

Resolution of front-back confusion in virtual acoustic imaging systems.

A geometric model of the scattering of sound by the human head is used to generate a model of localization cues based on interaural time delay (ITD). The ITD is calculated in terms of the interaural cross-correlation function (IACC) for sources placed at a series of azimuthal angles in the horizontal plane. This model is used to simulate the pressures generated at the ears of a listener due to real sources and due to a two-channel and a four-channel virtual source imaging system. Results are presented in each case for the variation of ITD with head rotation. The simulations predict that the rate of change of the ITD with head rotation produced by a real source and replicated by the four-channel virtual source imaging system, cannot be replicated by the two-channel system. These changes to the ITD provide cues which allow resolution of front-back confusion. The results of subjective experiments are also presented for the three cases modeled. These results strongly support the findings from the modeling work indicating that, for the systems described here, front-back confusion is resolved through changes to the ITD arising from head motion.

Attention↗

Redescription of Crepidostomum opeongoensis Caira, 1985 (Trematoda: Allocreadiidae) from fish hosts Hiodon alosoides and Hiodon tergisus (Osteichthyes: Hiodontidae).

Crepidostomum opeongoensis Caira, 1985 (Trematoda: Allocreadiidae) is redescribed from fish hosts Hiodon alosoides and Hiodon tergisus in southern Manitoba. The redescription adds details regarding the surface morphology and reproductive structures of the parasite not described previously. These include the characteristic tegumental papillae around the oral opening, paired papillae on the ventral and dorsal surfaces of the body, and tegumental bosses on the dorsal surface of the forebody. Crepidostomum opeongoensis co-occurred with its hypothesized sister species. Crepidostomum illinoiense, in all host individuals harboring the former, and both species are characteristic of hiodontids. The association of C. opeongoensis with hiodontids and the absence of hiodontids in Lake Opeongo where C. opeongoensis was originally reported indicate that the Algonquin Park region may have had hiodontids in the past and that the life cycle may be completed at present without the original fish host.

Animals↗

Locus of control, sex, and attitudes toward suicide.

A sample of 191 college students were administered the Suicide Opinion Questionnaire and the Rotter Locus of Control Scale. Significant differences in endorsement were obtained on 2 of the 8 Suicide Opinion Questionnaire scales with respect to sex and locus of control.

Adolescent↗

Lissorchis macropharynx n. sp. (Digenea: Lissorchiidae) from the shorthead redhorse, Moxostoma macrolepidotum (LeSueur) (Osteichthyes: Catostomidae).

Lissorchis macropharynx (Digenea: Lissorchiidae) is described from the shorthead redhorse, Moxostoma macrolepidotum (LeSueur) (Catostomidae) from the Assiniboine River drainage of southern Manitoba. The species is morphologically similar to Lissorchis hypentelii in possessing a similar body shape (widest at the ovarian region and a relatively long hindbody), a distinctly trilobed and relatively posteriorly situated ovary, and in the distribution of the vitellaria. It differs from L. hypentelii and all other lissorchiids in possessing a massive pharynx that is generally equal in length to or longer than the oral sucker and almost as deep as the cervical region of the body it occupies, a protruding acetabular region with an aspinose ridged/folded and grooved anterior surface, and a massive cirrus sac that reaches the level of the ovary. Museum specimens of Lissorchis spp. from M. macrolepidotum from other drainages in Manitoba and Wisconsin were also identified as L. macropharynx.

Animals↗

Alveolar bone loss of maxillary anterior teeth in adult orthodontic patients.

The purpose of this study was to evaluate prevalence and severity of alveolar bone loss in adult orthodontic patients, and to identify risk factors for such bone loss. Standardized periapical radiographs of maxillary anterior teeth and cephalograms made before (T-1) and after (T-2) treatment and treatment charts of 343 adults aged 20.0 to 70.1 years (mean 34.5, SD 9.0) before treatment, representing groups of consecutively treated patients from four orthodontic practices, were examined. Alveolar bone loss was calculated by subtracting the distance from the cementoenamel junction (CEJ) to the alveolar crest (AC) at each interproximal tooth surface from the mesial of one maxillary canine to the mesial of the other. Changes in bone level were calculated by subtracting the distance CEJ-AC at T-1 from the corresponding distance at T-2. Tooth movement was calculated from measurements of superimposed tracings of pretreatment and posttreatment cephalograms. Hygiene level was scored subjectively as adequate or inadequate on the basis of gingival appearance on posttreatment intraoral color slides. Sample means of averaged bone loss of all six anterior teeth and of the surface with the most severe bone loss per patient were 0.54 mm (SD 0.62) and 1.82 mm (SD 1.01), respectively. Only 2.5% of the patients had averaged bone loss of > or = 2 mm, whereas 36% of the patients had one or more surfaces with bone loss of > or = 2 mm. Multiple linear regression analyses revealed a positive relationship between age and bone loss, and a negative relationship between initial bone level and subsequent bone loss. No association was found between bone loss and length of treatment, posttreatment gingival appearance, amount of horizontal or vertical tooth movement, or treatment with maxillary osteotomy.

Adult↗

Tube feeding in children with end-stage renal disease.

Aggressive nutritional support and treatment with peritoneal dialysis (PD) have been advocated in the management of children with end-stage renal disease. In recent years, supplemental enteral feeding has been recommended by the majority of pediatric centers in the US and Europe since it has been shown to improve growth and neurologic development. Tube feeding, most commonly using a nasogastric (NG) or gastrostomy tube (G-tube) must be instituted when voluntary intake does not consistently meet the caloric and protein requirements or when there is poor growth. Recurrent emesis is the most common complication with NG feeds, while PD leak and exit site infection have been described with G-tube feeds. The early initiation of aggressive nutritional therapy to maximize growth potential must be emphasized.

Adolescent↗

Crepidostomum percopsisi n. sp. (Digenea: Allocreadiidae) from the trout perch (Percopsis omiscomaycus) of Dauphin Lake, Canada.

Crepidostomum percopsisi n. sp. is described from the small intestine of the trout perch (Percopsis omiscomaycus) in Dauphin Lake, Manitoba. It is morphologically similar to Crepidostomum isostomum, which has been reported from the trout perch and several other species of fish. It differs from C. isostomum based on the vitellaria confined to the hindbody of the worm, size and shape of the cirrus, size of the testes, and its greater body length. A comparison of our specimens with those illustrated and identified as C. isostomum from trout perch indicates that such specimens are identical to larger specimens of C. percopsisi recovered by us from trout perch in May. To date, C. percopsisi has only been reported from the trout perch of Dauphin Lake, Lake Winnipeg, and Oneida Lake, which suggests host specificity.

Animals↗

Decreased CNS inflammation and absence of clinical exacerbation of disease after six months oral administration of bovine myelin in diseased SJL/J mice with chronic relapsing experimental autoimmune encephalomyelitis.

Murine chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE) is a model of inflammatory demyelinating disease of the central nervous system (CNS) with similarity to multiple sclerosis (MS) in humans. Mice with confirmed neurologic deficits from CR-EAE were treated by oral administration of whole bovine myelin to investigate the effect of long-term oral delivery of myelin antigens on clinical disease and on the inflammatory response in the CNS. EAE-positive mice were fed doses of 1 mg, 10 mg, or 20 mg of bovine myelin every other day for 6 months. We found that prolonged oral delivery of neuroantigen suppressed inflammatory and demyelination foci in the CNS of myelin-treated mice with no exacerbation of clinical disease status compared with the control group. Analysis of histologic sections of brain and spinal cords with hematoxylin-eosin (H&E) and Luxol fast blue (LFB) staining showed a decrease in the inflammatory cell infiltration and active centers of demyelination, respectively. Furthermore, after 6 months of treatment, there was no increased sensitization to myelin antigens seen, as measured by antimyelin basic protein (MBP) or anti-proteolipid apoprotein (PLP) antibodies. These results demonstrate that prolonged oral administration of myelin antigens in diseased animals has an ameliorating effect on the pathologic process and supports its potential long-term use in humans with MS.

Administration, Oral↗

Antigen-driven peripheral immune tolerance: suppression of experimental autoimmmune encephalomyelitis and collagen-induced arthritis by aerosol administration of myelin basic protein or type II collagen.

Antigen-driven tolerance is an effective method of suppressing cell-mediated immune responses. We have previously demonstrated that exposure of gut-associated lymphoid tissue to myelin basic protein (MBP) via oral administration suppresses experimental autoimmune encephalomyelitis (EAE). To further study presentation of antigen to the immune system by mucosal surfaces as a method of antigen-driven tolerance, the effect of inhalation of MBP was investigated. MBP was given as an aerosol to Lewis rats on Days -10, -7, -5, and -3 prior to immunization with MBP in Freund's adjuvant and on Days 0, 2, and 4 following immunization. Aerosolization of MBP completely abrogated clinical EAE in 100% of treated rats. Central nervous system inflammation and delayed-type hypersensitivity and antibody responses to MBP were also significantly reduced in aerosol-treated animals. Aerosolization of histone, a basic protein of similar weight and charge as MBP, had no effect. Disease was also suppressed with one aerosol treatment on Day -3 or by administering MBP nasally. Aerosolization was more effective than oral administration of MBP over a wide dose range (0.005-5 mg). Splenic T cells isolated from animals postaerosolization adoptively transferred protection to naive animals immunized with MBP. Aerosolization of MBP to animals with relapsing EAE after recovery from the first attack decreased the severity of a subsequent attack. Aerosol and oral MBP were equally effective at suppressing the in vitro immune response as measured by proliferation and interferon-gamma production. We then tested aerosolization of a different autoantigen in a different disease model and found that aerosolization of type II collagen was effective in suppressing collagen-induced arthritis. Thus, aerosolization of an autoantigen is a potent method to downregulate an experimental T cell-mediated autoimmune disease and suggests that exposure of antigen to lung mucosal surfaces preferentially generates immunologic tolerance.

Administration, Oral↗

Myelin basic protein in experimental allergic encephalomyelitis is not affected at the posttranslational level: implications for demyelinating disease.

The microheterogeneity of myelin basic protein, expressed as the ratio between the least cationic (C-8) charge isomer and the most cationic (C-1), was examined in experimental allergic encephalomyelitis (EAE) cases. These included acute EAE of 2 months' duration induced with bovine proteolipid protein in complete Freund's adjuvant (CFA), chronic EAE induced with mouse spinal cord homogenate in varying doses from 0.5 to 2.0 mg in CFA, and chronic relapsing EAE of 12 months' duration induced with synthetic peptide 139-151 of the proteolipid protein sequence. The C-8/C-1 ratio was within the normal range for all groups of animals. However, the C-8/C-1 ratio was six- to sevenfold increased in a spontaneously demyelinating transgenic model, ND4, which contains 70 copies of the cDNA for DM20 (Mastronardi et al.: 1996). Since an increase in the C-8/C-1 ratio was also observed in victims of multiple sclerosis but not other neurological diseases, the ND4 model may address primary changes prior to demyelination, while the EAE model addresses the autoimmune aspects of the disease.

Animals↗