Search PubMed⌕ Search

Biomedical subjects

R J Nelson

Publications and source records attributed to R J Nelson.

At least 91 records · Page 5Linked to original sources
PubMed1999

Influence of social factors on immune function and reproduction.

Animals are presented with continuous energy demands that vary seasonally. For example, during the winter many small mammals and birds inhibit reproduction and growth and funnel energy into thermogenesis or cellular maintenance. As energy shortages become more severe, survival may become compromised because processes such as immune function and thermogenesis are impaired. Thus, there are trade-offs between energetically expensive processes such as reproduction and immune function. In this review, the immune function and reproduction of seasonally breeding species are evaluated in relation to social interactions. It is proposed that individuals maintain the highest degree of immune function that is energetically possible within the constraints of other survival needs, as well as growth and reproduction, in habitats in which energy requirements and availability often fluctuate. It is hypothesized that extrinsic factors, such as social environment, modulate energy allocation to reproductive and immune function and that hormonal mechanisms underlie the partitioning of energy to various physiological components.

Animals↗
PubMed1998

Neurobehavioral deficits in mice lacking the erythrocyte membrane cytoskeletal protein 4.1.

The erythrocyte membrane cytoskeletal protein 4.1 (4.1R) is a structural protein that confers stability and flexibility to erythrocytes via interactions with the cytoskeletal proteins spectrin and F-actin and with the band 3 and glycophorin C membrane proteins. Mutations in 4.1R can cause hereditary elliptocytosis, a disease characterized by a loss of the normal discoid morphology of erythrocytes, resulting in hemolytic anemia [1]. Different isoforms of the 4.1 protein have been identified in a wide variety of nonerythroid tissues by immunological methods [2-5]. The variation in molecular weight of these different 4.1 isoforms, which range from 30 to 210 kDa [6], has been attributed to complex alternative splicing of the 4.1R gene [7]. We recently identified two new 4.1 genes: one is generally expressed throughout the body (4. 1G) [8] and the other is expressed in central and peripheral neurons (4.1N) [9]. Here, we examined 4.1R expression by in situ hybridization analysis and found that 4.1R was selectively expressed in hematopoietic tissues and in specific neuronal populations. In the brain, high levels of 4.1R were discretely localized to granule cells in the cerebellum and dentate gyrus. We generated mice that lacked 4.1R expression; these mice had deficits in movement, coordination, balance and learning, in addition to the predicted hematological abnormalities. The neurobehavioral findings are consistent with the distribution of 4.1R in the brain, suggesting that 4.1R performs specific functions in the central nervous system.

Animals↗
PubMed1998

Melatonin, immunity and cost of reproductive state in male European starlings.

The effects of reproductive condition and exogenous melatonin on immune function were investigated in castrated European starlings, Sturnus vulgaris. Photorefractory and photostimulated starlings exposed to long days were implanted with melatonin or with blank capsules. Photostimulated starlings with blank capsules exhibited reduced splenocyte proliferation in response to the T-cell mitogen, concanavalin A, compared with the other long-day birds. Exogenous melatonin prevented the suppression of immune function by photostimulation. Photorefractory starlings, with or without melatonin implants, exhibited enhanced immune function compared with photostimulated starlings implanted with blanks. This enhancement was not mediated by endogenous melatonin, but appeared to be related to changes in reproductive state. In addition to the traditional costs of reproduction in birds (e.g. raising of young), there may be a cost of the reproductive state of starlings (i.e. whether they are photorefractory or photostimulated). These data are, we believe, the first to indicate a direct effect of reproductive state on immune function that is independent of both photoperiod (i.e., changes in the duration of melatonin secretion) and gonadal steroids.

Animals↗
PubMed1998

Targeted reduction of oxytocin expression provides insights into its physiological roles.

Oxytocin is a nonapeptide hormone that participates in the regulation of parturition and lactation. It has also been implicated in various behaviors, such as mating and maternal, and memory. To investigate whether or not oxytocin (OT) is essential for any of these functions, we eliminated, by homologous recombination, most of the first intron and the last two exons of the OT gene in mice. Those exons encode the neurophysin portion of the oxytocin preprohormone which is hypothesized to help in the packaging and transport of OT. The homozygous mutant mice have no detectable neurophysin or processed oxytocin in the paraventricular nucleus, supraoptic nucleus or posterior pituitary. Interestingly, homozygous mutant males and females are fertile and the homozygous mutant females are able to deliver their litters. However, the pups do not successfully suckle and die within 24 hours without milk in their stomachs. OT injection into the dams or rescue with the rat OT gene restores the milk ejection in response to suckling. OT is also needed for post-partum alveolar proliferation. These results indicate an absolute requirement for oxytocin for successful milk ejection, but not for mating, parturition and milk production, in mice. Furthermore, homozygous mutant mice show reduced aggression in some tests.

Aggression↗
PubMed1998

Short-day enhancement of immune function is independent of steroid hormones in deer mice (Peromyscus maniculatus).

The effects of photoperiod and steroid hormones on immune function were assessed in male and female deer mice (Peromyscus maniculatus). In experiment 1, male deer mice were castrated, castrated and given testosterone replacement, or sham-operated. Half of each experimental group were subsequently housed in either long (LD 16:8) or short days (LD 8:16) for 10 weeks. Short-day deer mice underwent reproductive regression and displayed elevated lymphocyte proliferation in response to the T-cell mitogen concanavalin A, as compared to long-day mice. In experiment 2, female deer mice were ovariectomized, ovariectomized and given estrogen replacement, or sham-operated. Animals from each of these experimental groups were subsequently housed in either LD 16:8 or LD 8:16 for 10 weeks. Short-day deer mice underwent reproductive regression and displayed reduced serum estradiol concentrations and elevated lymphocyte proliferation in response to concanavalin A, as compared to long-day mice. Surgical manipulation had no effect on lymphocyte proliferation in either male or female deer mice. Neither photoperiod nor surgical manipulation affected serum corticosterone concentrations. These results confirm that both male and female deer mice housed in short days enhance immune function relative to long-day animals. Additionally, short-day elevation in splenocyte proliferation appears to be independent of the influence of steroid hormones in this species.

Animals↗
PubMed1998

Chemotherapy for spinal cord astrocytoma: can natural history be modified?

Standard treatment of spinal cord astrocytomas is based upon surgery, followed by radiotherapy when resection is incomplete or when histology is of high grade. Owing to the major consequences of radiotherapy on the spine in childhood, alternative therapies must be explored. The potential role of chemotherapy in the management of spinal cord astrocytoma remains to be defined. Two patients are described. The first was a 19-month-old child with an anaplastic astrocytoma of the cervical spinal cord that progressed rapidly after initial partial resection. Chemotherapy was begun according to the UKCCSG Baby Brain Protocol, with marked clinical improvement. Reassessment by MRI at 4 months showed improvement, and at the end of treatment no evaluable disease remained. The second was a 4-year-old child with a recurrent low-grade astrocytoma. Chemotherapy according to the SIOP Protocol for Low Grade Gliomas was administered for 3 months, after which marked tumour regression was seen, with neurological recovery. These patients demonstrate the potential value and low morbidity of chemotherapy in spinal cord astrocytoma. The management of this rare tumour is discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Behavior in mice with targeted disruption of single genes.

The use of mice with targeted deletion, or knockout, of specific genes provides a relatively new approach to establish the molecular bases of behavior. As with all ablation studies, the interpretation of behavioral data may be limited by the technique. For example, indirect effects of the missing gene may affect behavior, rather than the missing gene per se. Also, because the missing gene might affect many developmental processes throughout ontogeny and because up-regulation or compensatory mechanisms may be activated in knockouts, behavioral data from mice with targeted gene deletions should be interpreted with caution. The development of conditional knockouts, in which a specific gene can be inactivated any time during ontogeny, should allow investigators to avoid these conceptual shortcomings associated with behavioral data from knockouts in the near future. The behavioral alterations reported in knockout mice are reviewed here. Many dramatic changes in complex motivated behaviors including aggression, sexual, ingestive, and parental behaviors, have been reported for knockouts. There have also been many reports of alterations in sensorimotor abilities and spontaneous activity, as well as impairments in balance, coordination, and gait. Impaired learning and memory have also been reported for mice with targeted disruption of specific genes. Taken together, the use of knockouts will provide an important new tool to understand the mechanisms underlying behavior.

Animals↗
PubMed1998

Impaired spatial working and reference memory in segmental trisomy (Ts65Dn) mice.

To evaluate the cognitive phenotype of the segmental trisomy 16 (Ts65Dn) mouse, a model of Down Syndrome (DS, trisomy 21), we assessed spatial working and reference memory using a 12-arm radial maze (RAM). Ts65Dn mice made a greater number of reference memory errors across trials compared to control mice. Both genotypes showed improvement across trials, although improvement was slower in Ts65Dn mice. Ts65Dn mice also made a greater number of working memory errors on the RAM, and in contrast to control mice, did not improve across trials, always performing at near-chance levels. These results provide evidence for both spatial working and reference memory deficits in Ts65Dn mice, characteristics of cognitive dysfunction.

Animals↗
PubMed1998

Sensitivity of near infrared spectroscopy to cerebral and extra-cerebral oxygenation changes is determined by emitter-detector separation.

OBJECTIVE: To examine the effect of two emitter-detector separations (2.7 and 5.5 cm) on the detection of changes in cerebral and extra-cerebral tissue oxygenation using near infrared spectroscopy (NIRS). METHODS: Two NIR detectors were placed on the scalp 2.7 and 5.5 cm from a single NIR emitter. Changes in deoxyhaemoglobin (HHb), oxyhaemoglobin (O2Hb),oxidised cytochrome C oxidase (Cyt) and total haemoglobin (tHb) were recorded from each detector during the induction of cerebral oligaemia (transition from hypercapnia to hypocapnia) and scalp hyperaemia (following release of a scalp tourniquet). RESULTS: Cerebral oligaemia (mean decrease in middle cerebral artery blood flow velocity of 44%) induced by a mean reduction in end tidal CO2 of 18 mmHg was accompanied by a significant increase in the spectroscopic signal for HHb and a decrease in the O2Hb signal. The signal change per unit photon path length detected at 5.5 cm was significantly greater for HHb (p = 0.007) than that detected at 2.7 cm. In contrast, the increase in all chromophores detected at 5.5 cm during scalp hyperaemia was significantly less than that detected at 2.7 cm (p<0.001). CONCLUSIONS: The differing sensitivity of the proximal and distal channels to changes in cerebral and extracerebral oxygenation is compatible with theoretical models of NIR light transmission in the adult head and may provide a basis for spatially resolving these changes. The optimal emitter-detector separation for adult NIRS requires further investigation and may differ between individuals.

Adult↗
PubMed1998

Simultaneous encoding of tactile information by three primate cortical areas.

We used simultaneous multi-site neural ensemble recordings to investigate the representation of tactile information in three areas of the primate somatosensory cortex (areas 3b, SII and 2). Small neural ensembles (30-40 neurons) of broadly tuned somatosensory neurons were able to identify correctly the location of a single tactile stimulus on a single trial, almost simultaneously. Furthermore, each of these cortical areas could use different combinations of encoding strategies, such as mean firing rate (areas 3b and 2) or temporal patterns of ensemble firing (area SII), to represent the location of a tactile stimulus. Based on these results, we propose that ensembles of broadly tuned neurons, located in three distinct areas of the primate somatosensory cortex, obtain information about the location of a tactile stimulus almost concurrently.

Action Potentials↗
PubMed1998

Ejaculatory abnormalities in mice with targeted disruption of the gene for heme oxygenase-2.

Nitric oxide (NO) is well established as a neurotransmitter in the central and peripheral nervous systems. More recently, another gas, carbon monoxide (CO) has also been implicated in neurotransmission. In the nervous system CO is formed by a subtype of heme oxygenase (HO) designated HO2. HO2 is localized to discrete neuronal populations in the brain resembling localizations of soluble guanylyl cyclase, which is activated by CO. CO may also function in the peripheral autonomic nervous system, in conjunction with NO. The majority of ganglia in the myenteric plexus possess both HO2 and neuronal NO synthase (NOS). Defects in myenteric plexus neurotransmission occur both in mice with targeted deletion of genes for HO2 and neuronal NOS. HO2 also occurs in other autonomic ganglia including the petrosal, superior cervical and nodose ganglia. Neuronal NOS is localized to neurons regulating male reproductive behavior, such as penile erection, and NOS inhibitors prevent erection. Because of the other parallels between NO and CO, we speculated that CO may play a role in male reproductive behavior. In the present study we describe HO2 localization in neuronal structures regulating copulatory reflexes. Reflex activity of the bulbospongiosus muscle, which mediates ejaculation and ejaculatory behavior, is markedly diminished in mice with targeted deletion of the gene for HO2 (HO2-).

Animals↗
PubMed1998

Social, but not photoperiodic, influences on reproductive function in male Peromyscus aztecus.

Nontropical rodents rely on environmental factors to restrict breeding to a specific time of the year. Among these factors, photoperiod appears to be the primary environmental cue used for predicting optimal breeding conditions. The purpose of the present study was to characterize reproductive function, as well as photoperiodic and social responsiveness in male Peromyscus aztecus, which occupy low-latitude, high-altitude habitats. In experiment 1, adult male P. aztecus were individually housed in either long (16L:8D) or short days (8L:16D) for 10 wk. Short-day mice did not differ from long-day mice on any reproductive or nonreproductive parameter. Comparisons to related Peromyscus species suggested that relative reproductive organ size and function were reduced in both long- and short-day males. Because ad libitum food and water were available, we reasoned that males in both photoperiodic conditions lacked social stimuli. To test this hypothesis, adult male P. aztecus were housed in long days either individually or with a female conspecific in experiment 2. Mice housed with females had significantly larger relative paired testes and epididymal masses, and higher testicular sperm counts and serum testosterone levels compared to those of individually housed mice. Taken together, these results suggest that social factors may play a more prominent role than photoperiod in stimulating reproductive development in laboratory-housed P. aztecus. These results are consistent with the results found for other low-latitude rodent species and suggest that P. aztecus uses a flexible rather than obligatory breeding strategy.

Animals↗
PubMed1998

Short photoperiod affects reproductive function but not dehydroepiandrosterone concentrations in male deer mice (Peromyscus maniculatus).

Cessation of breeding is central among the suite of winter-coping strategies used by small rodents to survive energy-demanding winter conditions. Animals use photoperiod to predict the onset of winter and initiate, well in advance of deteriorating conditions, seasonal adaptations. Exposure to short photoperiod leads to regression of the reproductive system in long-day breeding animals. Likewise, exposure to short days leads to enhanced immune function among several rodent species studied. Because dehydroepiandrosterone (DHEA) increases immune function in virtually all studies reported to date, we sought to determine if DHEA concentrations might be influenced by photoperiod, thereby suggesting a mechanism whereby short photoperiod may enhance immune function. Male deer mice (Peromyscus maniculatus) were exposed to either short or long days for 10 weeks. Short photoperiods caused significant reduction in all reproductive organs measured relative to animals housed in long days. However, DHEA concentrations did not differ between short- and long-day mice. Taken together, these data suggest that short-day enhancement of immune function in deer mice is independent of DHEA concentrations.

Adipose Tissue↗
PubMed1998

Exogenous melatonin enhances cell-mediated, but not humoral, immune function in adult male deer mice (Peromyscus maniculatus).

Many nontropical rodent species display seasonal changes in reproductive physiology and metabolism, as well as in immune function. Field studies of seasonal changes in immune function typically report decreased immune function in the short days of winter compared to summer; presumably, reduced immunity in winter reflects increased glucocorticoid secretion in response to environmental stressors. In contrast, laboratory studies of photoperiodic changes in immunity invariably demonstrate increased immune function in short compared to long days. Although the precise mechanisms regulating short-day enhancement of immune function are not known, it is hypothesized that increased immunity is due to the increased duration of melatonin secretion in short compared to long days. However, melatonin can act both directly (i.e, via melatonin receptors located on lymphatic tissue) and indirectly (i.e., via alterations in gonadal steroids) to affect immune function. The present study examined the effects of exogenous melatonin administration on both cell-mediated and humoral immune function in adult male deer mice (Peromyscus maniculatus), as well as the role of gonadal steroid hormones in mediating these effects. Mice either were castrated to remove circulating androgens or received sham operations and were implanted with empty capsules or capsules containing melatonin. Individual mice implanted with melatonin underwent reproductive regression and displayed enhanced splenocyte proliferation to the T-cell mitogen concanavalin A; antigen-specific serum immunoglobulin M production was unaffected by melatonin treatment. Castration had no effect on either cell-mediated or humoral immune function. Taken together, these results suggest that exogenous melatonin enhances cell-mediated, but not humoral, immune function in adult male deer mice and that this effect is independent of gonadal steroid hormones. These results are consistent with a direct effect of melatonin on immunity.

Analysis of Variance↗
PubMed1998

Photoperiod, ambient temperature, and food availability interact to affect reproductive and immune function in adult male deer mice (Peromyscus maniculatus).

Winter is often stressful. Increased energetic demands in winter and concurrent reductions in energy availability can lead to an energetic imbalance and compromise survival. To increase the odds of surviving winter, individuals of some nontropical rodent species have evolved mechanisms to enhance immune function in advance of harsh winter conditions. Short day lengths provide a proximate cue for enhancement of immune function, an adaptive functional response to counter environmental stress-induced reduction in immune function. In the present study, photoperiod, ambient temperature, and food availability were manipulated and reproductive function and cell-mediated immunity were assessed in adult male deer mice (Peromyscus maniculatus). Mice maintained in short days regressed their reproductive systems and displayed enhanced immune function compared to long-day animals. Reduced food availability elevated corticosterone concentrations and suppressed reproductive and immune function, whereas ambient temperature alone had no effect on cell-mediated immunity. The suppressive effect of food restriction on reproductive and immune function was overcome by maintaining animals in short days. However, short-day, food-restricted mice maintained at low ambient temperatures displayed reduced reproductive and immune function compared to animals maintained at mild temperatures. Taken together, these results suggest that short-day enhancement of immune function can counteract some, but not all, of the immunosuppressive effects of winter stressors. These data are consistent with the hypothesis that immune function is enhanced in short days to counteract stress-mediated immune suppression occurring during winter.

Adipose Tissue↗
PubMed1998

Reversible snaring for proper prosthetic seating during valve replacement.

A method of reversible suture snaring is described for evaluating the final valve seating and positioning before knot tying of valve sutures. This allows for alteration of the operative plan before investing substantial ischemic time in a nonfunctional result. The procedure has been used in 577 consecutive prosthetic valve replacements in the past 5 years. The technique maintains proper seating while the valve is permanently anchored in place.

Heart Valve Diseases↗
PubMed1998

Impaired ovulation in mice with targeted deletion of the neuronal isoform of nitric oxide synthase.

BACKGROUND: Nitric oxide (NO) plays an important role in numerous reproductive processes. To date, most studies have assessed the role of NO by using nonspecific pharmacological inhibitors of the precursor to NO, nitric oxide synthase (NOS). These pharmacological NOS inhibitors suppress all isoforms of NOS; thus, the precise contribution of each isoform to female reproductive physiology is unknown. The purpose of this study was to determine the specific role of neuronal NOS (nNOS) in the regulation of ovulation in female mice lacking the gene that encodes for nNOS (nNOS-/-). MATERIALS AND METHODS: Ovulation was assessed in wild-type (WT) and nNOS-/- female mice by examining the number of ovarian rupture sites and number of oocytes recovered from the oviducts following mating or exposure to exogenous gonadotropins (i.e., 5 IU pregnant mares serum gonadotropin [PMSG] and 5 IU human chorionic gonadotropin [hCG]). Ovulatory efficiency was determined as the number of ovulated oocytes per number of ovarian rupture sites. To examine whether ovulatory deficits in nNOS-/- mice were due to alternations in central mechanisms, plasma luteinizing hormone (LH) concentrations were assessed in WT and nNOS-/- mice that were challenged with 25 ng of gonadotropin-releasing hormone (GnRH). To determine whether ovulatory deficits in nNOS-/- mice were due to local ovulation processes, nerves innervating the reproductive tract of WT and nNOS-/- females were examined for the presence of nNOS protein. RESULTS: There were substantial fertility deficits in nNOS-/- female mice; the nNOS-/- mice had fewer oocytes in their oviducts following spontaneous and gonadotropin-stimulated ovulation. Pituitary responsiveness to exogenous GnRH challenge was intact in nNOS-/- mice. Dense nNOS protein staining was observed in nerves innervating the reproductive tracts of WT mice. CONCLUSIONS: The reproductive deficits in nNOS-/- females are most likely due to alternations in the transfer of oocytes from the ovaries to the oviducts during ovulation. These results suggest that defects in neuronally derived NO production may contribute to female infertility.

Animals↗