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Biomedical subjects

R J Nelson

Publications and source records attributed to R J Nelson.

At least 145 records · Page 8Linked to original sources

Intraoperative angioscopy for coronary bypass surgery.

Despite advances in coronary artery surgery, technical abnormalities remain a significant cause of early graft closure. The development of small fiberoptic angioscopes now allows direct intravascular magnified examination. Seventy-five distal anastomoses and vein grafts, and five selected coronary arteries were examined with 0.8- to 2.5-mm diameter angioscopes introduced through the proximal vein graft while irrigating with clear cardioplegia. Angioscopic findings were correlated with angiographic data, vessel morphology, graft flow, and postoperative course. Satisfactory images were obtained in 72 of 75 anastomotic inspections. Each examination took less than 2 minutes and required less than 100 cc of flush. Angioscopic abnormalities that did not require revision were noted in 17 of 72 anastomoses; intimal flaps in 9, thrombus on posterior wall plaque in 4, intimal irregularities in 4, bucking of posterior wall in 3, and valve near anastomoses in 1. No outflow obstruction nor misplaced sutures were noted. Average flow rate through the grafts with anastomotic angioscopic abnormalities was 33 cc/min versus 40 cc/min in the remaining grafts. However, regression analysis revealed that low-graft flow was correlated with vessel size and runoff but was not with angioscopic findings. Intracoronary angioscopy revealed discrepancy with angiographic findings in 4 of the 5 examinations. No complications occurred as a result of angioscopy. No graft closure has occurred during early follow-up. Intraoperative angioscopy can be done with minimal alteration of the usual routine. The 24% occurrence of minor angioscopic abnormalities did not appear to compromise graft flow or early patency.

Angioscopy↗

The influence of season, photoperiod, and pineal melatonin on immune function.

In addition to the well-documented seasonal cycles of mating and birth, there are also significant seasonal cycles of illness and death among many animal populations. Challenging winter conditions (i.e., low ambient temperature and decreased food availability) can directly induce death via hypothermia, starvation, or shock. Coping with these challenges can also indirectly increase morbidity and mortality by increasing glucocorticoid secretion, which can compromise immune function. Many environmental challenges are recurrent and thus predictable; animals could enhance survival, and presumably increase fitness, if they could anticipate immunologically challenging conditions in order to cope with these seasonal threats to health. The annual cycle of changing photoperiod provides an accurate indicator of time of year and thus allows immunological adjustments prior to the deterioration of conditions. Pineal melatonin codes day length information. Short day lengths enhance several aspects of immune function in laboratory studies, and melatonin appears to mediate many of the enhanced immunological effects of photoperiod. Generally, field studies report compromised immune function during the short days of autumn and winter. The conflict between laboratory and field data is addressed with a multifactor approach. The evidence for seasonal fluctuations in lymphatic tissue size and structure, as well as immune function and disease processes, is reviewed. The role of pineal melatonin and the hormones regulated by melatonin is discussed from an evolutionary and adaptive functional perspective. Finally, the clinically significance of seasonal fluctuations in immune function is presented. Taken together, it appears that seasonal fluctuations in immune parameters, mediated by melatonin, could have profound effects on the etiology and progression of diseases in humans and nonhuman animals. An adaptive functional perspective is critical to gain insights into the interaction among melatonin, immune function, and disease processes.

Androgens↗

Genetic Diversity of Xanthomonas oryzae pv. oryzae in Asia.

Restriction fragment length polymorphism and virulence analyses were used to evaluate the population structure of Xanthomonas oryzae pv. oryzae, the rice bacterial blight pathogen, from several rice-growing countries in Asia. Two DNA sequences from X. oryzae pv. oryzae, IS1112, an insertion sequence, and avrXa10, a member of a family of avirulence genes, were used as probes to analyze the genomes of 308 strains of X. oryzae pv. oryzae collected from China, India, Indonesia, Korea, Malaysia, Nepal, and the Philippines. On the basis of the consensus of three clustering statistics, the collection formed five clusters. Genetic distances within the five clusters ranged from 0.16 to 0.51, and distances between clusters ranged from 0.48 to 0.64. Three of the five clusters consisted of strains from a single country. Strains within two clusters, however, were found in more than one country, suggesting patterns of movement of the pathogen. The pathotype of X. oryzae pv. oryzae was determined for 226 strains by inoculating five rice differential cultivars. More than one pathotype was associated with each cluster; however, some pathotypes were associated with only one cluster. Most strains from South Asia (Nepal and India) were virulent to cultivars containing the bacterial blight resistance gene xa-5, while most strains from other countries were avirulent to xa-5. The regional differentiation of clusters of X. oryzae pv. oryzae in Asia and the association of some pathotypes of X. oryzae pv. oryzae with single clusters suggested that strategies that target regional resistance breeding and gene deployment are feasible.

Journal Article↗

Extracerebral absorption of near infrared light influences the detection of increased cerebral oxygenation monitored by near infrared spectroscopy.

The detection of increased cerebral oxygenation secondary to cerebral hyperaemia, induced by hypercapnia has been studied in anaesthetised patients using a near infrared, reflectance mode, cerebral oxygenation monitor (Invos 3100 Somanetics, Troy, Michigan, USA). Two studies were performed, with and without a pneumatic scalp tourniquet, to distinguish between extracranial and intracranial changes in tissue oxygenation. In the control study a mean increase in end tidal CO2 of 23.1 mm Hg was accompanied by a mean increase in middle cerebral artery flow velocity of 116%. Regional cerebral oxygen saturation (rSO2) measured transcutaneously in the frontal distribution of the middle cerebral artery increased significantly from 70.5% to 74.6% (p = 0.001). During the second study with a scalp tourniquet inflated to maintain the extracranial tissues in a state of stable ischaemia a mean increase in end tidal CO2 of 22.3 mm Hg was accompanied by a mean increase in middle cerebral artery flow velocity of 121%. The change in rSO2 from 62.6% to 64.5% was not significant (p = 0.085). There was no correlation between the change in middle cerebral artery flow velocity and rSO2 in the control or scalp ischaemia group. This study shows that the Invos 3100 monitor is sensitive to tissue oxygenation but does not reliably detect changes in cerebral oxygenation as a result of profound cerebral hyperaemia. The contribution of extracerebral tissue to the attenuation of near infrared light and the lack of spatial resolution remain major problems to be overcome before this or other near infrared spectroscopy instruments can be introduced into clinical practice.

Adult↗

Posttranslational mitochondrial protein import in a homologous yeast in vitro system.

Posttranslational import of preproteins into mitochondria has been reported to be inefficient in a homologous yeast in vitro system, suggesting a requirement for coupling of protein synthesis and import. We have characterized a homologous yeast in vitro system which allows posttranslational mitochondrial import of preproteins. The efficiency is comparable to that of the heterologous system with rabbit reticulocyte lysate and isolated yeast mitochondria. Import in the homologous system depends on mitochondrial surface receptors, a membrane potential and the matrix heat shock protein Hsp70. Import is not blocked by the protein synthesis inhibitor cycloheximide, but is impaired by induction of stable folding in preproteins. Our studies demonstrate a posttranslational translocation mechanism in the homologous system, strongly supporting the validity of conclusions drawn from the widely used heterologous import system.

Animals↗

Protection from endotoxic shock in mice by pharmacologic inhibition of phosphatidic acid.

Certain phosphatidic/plasmanic/plasmenic acid (PA) species function as lipid intermediates in cell activation and may function directly as intracellular signaling molecules. PA can also be dephosphorylated to 1,2-diradyl-sn-glycerol by phosphatidate phosphohydrolase. Treatment of various cell types, including murine P388 monocytic leukemia cells, with bacterial lipopolysaccharide rapidly stimulates large increases in PA and PA-derived diradylglycerol. Pentoxifylline, 1-(5-oxohexyl)-3,7-dimethylxanthine, inhibits lipopolysaccharide-stimulated formation of PA in P388 cells at high concentrations (IC50 = 500 microM). Lisofylline [1-(5R-hydroxyhexyl)-3,7-dimethylxanthine] is a unique metabolite of pentoxifylline in humans and is > 800-fold more active as an inhibitor of PA formation than pentoxifylline (IC50 = 0.6 microM). Lisofylline does not inhibit lipopolysaccharide-induced activation of phosphatidylinositol-specific phospholipase C and generation of phosphatidylinositol-derived diradylglycerol. Lisofylline but not pentoxifylline protects BALB/c mice from endotoxin lethality when administered 4 hr after lipopolysaccharide. This protective effect is independent of either agent's effect on suppression of plasma tumor necrosis factor alpha. These data suggest that inhibitors of PA formation may have significant clinical potential in the treatment of sepsis and septic shock.

Acyltransferases↗

Proenkephalin transgenic mice: a short promoter confers high testis expression and reduced fertility.

The regulation and possible function of the preproenkephalin gene in testis were studied in vivo in transgenic mice containing: (1) bases -193 to +210 of the human proenkephalin gene and an additional one kilobase of 3' proenkephalin flanking sequence driving expression of bacterial chloramphenicol acetyltransferase (CAT), and (2) the same promoter and flanking sequences driving expression of a rat proenkephalin cDNA. Five lines of mice, designated HEC1-5, expressed the first construct and 10, HER1-10, the second. Each HEC male and many HER males showed dramatic expression of the transgene in the testis, although much lower expression was observed in the brain and other enkephalin-producing tissues. High levels of expression in testis can thus be achieved with a very short promoter region and do not require intron A sequences previously considered necessary. Altered enkephalin expression may affect testicular function. One founder, HER8, displayed grossly abnormal testicular morphology and was completely infertile. A second founder, HER6, had low sperm motility. Two offspring from other lines also displayed subnormal fertility. These studies support a role for specific promoter sequences in testis expression and may further support a significant role for proenkephalin in testicular function.

Animals↗

Day length influences proceptive behavior of female prairie voles (Microtus ochrogaster).

Prairie voles typically do not breed during the winter; instead, they typically confine breeding to the spring and summer. One proximate cue contributing to this seasonal change in breeding among males is photoperiod. However, photoperiod does not appear to affect female fecundity. Female prairie voles are induced into estrus by chemosensory cues in the urine of male conspecifies. Females are exposed to these cues when they groom the ano-genital region of males. Females that do not groom the ano-genital region of males rarely become estrus. Ano-genital grooming can be considered a proceptive behavior because the onset of estrus is dependent upon females exhibiting this behavior. This study addressed whether or not photoperiod influenced the proceptive behavior of female prairie voles. The results indicated that females maintained in a long photoperiod groomed the ano-genital region of anesthetized stimulus males more frequently than females maintained in a short photoperiod. This change in proceptive behavior may contribute to the seasonal changes in breeding exhibited by prairie voles.

Animals↗

Near-infrared spectroscopy in adults: effects of extracranial ischaemia and intracranial hypoxia on estimation of cerebral oxygenation.

We have studied the effects of extracranial ischaemia and intracranial hypoxia on measurement of cerebral oxygenation using near-infrared, reflectance-mode, cerebral oximetry (Invos 3100 cerebral oximeter) in healthy adult subjects. Under stable systemic conditions, scalp ischaemia induced by a pneumatic tourniquet caused an apparent reduction in mean regional cerebral oxygenation (rSO2) from mean 72 (SD 6)% to 59 (7)% (n = 8, P < 0.001). rSO2 returned to control values within 1 min of release of the tourniquet. Local scalp ischaemia induced by rapid frontalis muscle exercise caused a significant reduction (4.5 (2)% in rSO2 (n = 12, P < 0.001). The effect of systemic hypoxia on rSO2 was examined during controlled scalp ischaemia. A decrease in mean SpO2 from 98 (2)% to 66 (6)% was associated with a decrease in mean rSO2 from 57 (4)% to 41 (6)%. There was a significant correlation between the percentage reduction in rSO2 and SpO2 during hypoxia (r = 0.81, P < 0.001). We conclude that the Invos cerebral oximeter was capable of detecting tissue hypoxia deep to the scalp under carefully controlled conditions but that it also was affected significantly by changes in extracranial blood flow and oxygenation which may affect its reliability in clinical practice. Further work is necessary to define those situations in which cerebral oximetric monitoring is useful and valid.

Adult↗

RFLP mapping of genes conferring complete and partial resistance to blast in a durably resistant rice cultivar.

Moroberekan, a japonica rice cultivar with durable resistance to blast disease in Asia, was crossed to the highly susceptible indica cultivar, CO39, and 281 F7 recombinant inbred (RI) lines were produced by single seed descent. The population was evaluated for blast resistance in the greenhouse and the field, and was analyzed with 127 restriction fragment length polymorphism (RFLP) markers. Two dominant loci associated with qualitative resistance to five isolates of the fungus were tentatively named Pi-5(t) and Pi-7(t). They were mapped on chromosomes 4 and 11, respectively. To identify quantitative trait loci (QTLs) affecting partial resistance, RI lines were inoculated with isolate PO6-6 of Pyricularia oryzae in polycyclic tests. Ten chromosomal segments were found to be associated with effects on lesion number (P < 0.0001 and LOD > 6.0). Three of the markers associated with QTLs for partial resistance had been reported to be linked to complete blast resistance in previous studies. QTLs identified in greenhouse tests were good predictors of blast resistance at two field sites. This study illustrates the usefulness of RI lines for mapping a complex trait such as blast resistance and suggests that durable resistance in the traditional variety, Moroberekan, involves a complex of genes associated with both partial and complete resistance.

Chromosome Mapping↗

Reproductive and nonreproductive responsiveness to photoperiod in laboratory rats.

Laboratory rats (Rattus norvegicus) have been traditionally considered nonphotoperiodic because reproductive function is unaffected by day length. However, at least three experimental manipulations of rats--perinatal androgen injection, peripubertal androgen implants, and peripubertal olfactory bulbectomy--have been reported to unmask reproductive responsiveness to photoperiod. The physiological means by which early testosterone treatment or olfactory bulbectomy affect the expression of photoperiodism were hypothesized to operate through similar underlying mechanism(s) that involved gonadotropin and prolactin blood levels. Short day lengths reduce blood levels of gonadotropins in so-called photoperiodic rodent species. Reduced prolactin levels result in virtually all reproductively photoperiodic species housed in short day lengths. In Experiment 1, male weanling rats either were olfactory-bulbectomized or received a sham-procedure and housed for 10 weeks in long (LD 16:8) or short (LD 8:16) days. Short-day rats reduced body mass, testicular sperm counts, and the size of their reproductive systems; olfactory bulbectomy amplified this inhibitory effect for some parameters including testicular and epididymal sperm counts. However, neither short days nor olfactory bulbectomy affected blood titers of follicle stimulating hormone (FSH) or prolactin. Pelage density was also unaffected by photoperiod, but rats retained their juvenile fur color; i.e., short-day rats remained white, but long-day rats became yellowish. In Experiment 2, male rats were injected with testosterone at 3 days of age, then housed in long or short days until 10 weeks of age. Day length alone did not affect any experimental parameter measured in Experiment 2 except fur color; again, short-day rats retained their juvenile fur color.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Relationship between Phylogeny and Pathotype for the Bacterial Blight Pathogen of Rice.

Several transposable elements were isolated from the genome of Xanthomonas oryzae pv. oryzae. These elements and an avirulence gene isolated from X. oryzae pv. oryzae were used as hybridization probes for a collection of X. oryzae pv. oryzae strains from the Philippines. Each of the sequences was present in multiple copies in all strains examined and showed distinct patterns of hybridizing bands. Phenograms were derived from the restriction fragment length polymorphism data obtained for each of the individual probes and for pooled data from multiple probes. The phenograms derived from the different probes differed in topology and, on the basis of bootstrap analysis, were not equally robust. For all of the probes, including the avirulence gene, some groups (even some haplotypes) consisted of multiple races. The strains were grouped into four major clusters on the basis of the two probes giving the highest bootstrap values. These groups were inferred to represent phylogenetic lineages. Three of the six races of X. oryzae pv. oryzae appeared in more than one of the lineages, and another was present in two sublineages. For three of the races, strains representing different phenetic groups were inoculated on rice cultivars carrying 10 resistance genes. Two new races were differentiated, corresponding to pathogen lineages identified by DNA typing. On the basis of DNA and pathotypic analyses, together with information on the spatial and temporal distribution of the pathogen types from this and other studies, a general picture of X. oryzae pv. oryzae evolution in the Philippines is presented.

Journal Article↗

Day length affects immune cell numbers in deer mice: interactions with age, sex, and prenatal photoperiod.

The extent to which day length affects immune function was examined in the present study. Three goals were pursued: 1) to confirm and extend the observation that the immune systems of adult deer mice (Peromyscus maniculatus) are responsive to changes in photoperiod, 2) to examine the development of the photoperiod-associated changes in immune function, and 3) to discover whether photoperiodic information transmitted to the young during gestation influences immune function. In experiment 1, adult mice housed in short days had higher white blood cell and lymphocyte numbers than their long-day cohorts. Red blood cell and differential cell counts did not differ between long- and short-day animals. No sex differences were observed in the pattern of immune responses to photoperiod. The effect of photoperiod on immune cells in prepubertal animals was examined in experiment 2; a similar pattern of results was obtained as that for experiment 1, suggesting that the photoperiodic effect on the immune system is not mediated by sex steroid hormones. Prenatal and postnatal photoperiodic effects on immune cells were examined in experiment 3; pups gestated in one day length were cross-fostered to mothers in the same day length conditions or to mothers maintained in the alternative day length. The results of experiment 3 suggested that photoperiodic information transmitted from the mother to the young in utero subsequently affected immune systems of the pups. Animals gestated in short day lengths displayed higher immune status throughout life than mice gestated in long days. These results are discussed from an adaptive functional perspective.

Aging↗

Vibration-entrained and premovement activity in monkey primary somatosensory cortex.

1. Primary somatosensory cortical (SI) neurons exhibit characteristic activity before the initiation of movements. This premovement activity (PMA) may result from centrally generated as well as from peripheral inputs. We examined PMA for 55 SI neurons (10, 13, 28, and 4 in areas 3a, 3b, 1, and 2, respectively) with activity that was entrained to vibrotactile stimulation (i.e., was temporally correlated with the stimulus). We sought to determine whether the temporal characteristics of vibration-entrained discharges would change throughout the reaction time period, and, if they did, whether these changes might be accounted for by central inputs. 2. Monkeys made wrist flexions and extensions in response to sinusoidal vibration (27, 57, or 127 Hz) of their palms. Vibration remained on until the animal moved at least 5 degrees from the initial hold position. Mean firing rate (MFR), a measure of the level of activity, was derived from the number of spikes per vibratory cycle. The correlation between the vibration and the neuronal firing was described by the mean phase (MP) of the vibratory cycle at which spikes occurred. The degree of entrainment was quantified as synchronicity (Synch), a statistical parameter that could change from 0 for no entrainment to 1 for responses at a constant phase. 3. Premovement MFR increases (activation) and decreases (suppression) were observed. Moreover, two changes in MFR often were observed for the same neuron (2-event PMA). Many MFR shifts, especially the first in the two-event PMA, preceded electromyographic (EMG) onset. The pre-EMG MFR shifts more often had the same sign both for flexion and extension movements rather than having opposite signs. However, with equal frequency, post-EMG PMA events had the same or opposite sign for different movement directions. We suggest that the pre-EMG PMA has an origin different from movement-related peripheral reafference. 4. Premovement activation was accompanied by shifts of MP corresponding to earlier responses to the ongoing vibratory stimulus and by decreases of response Synch. Premovement suppression was not associated with consistent shifts of MP and Synch. We suggest that during premovement activation, asynchronous (uncorrelated with vibration) signals are integrated with the vibratory input. These asynchronous signals may make neurons more likely to discharge and to do so earlier with respect to the vibratory stimulus. The asynchronous component may also disrupt the vibration-entrained activity pattern.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗