Biomedical subjects

S L Klein

Publications and source records attributed to S L Klein.

At least 19 recordsLinked to original sources

PubMed2007

A survey of zoonotic pathogens carried by Norway rats in Baltimore, Maryland, USA.

Norway rats (Rattus norvegicus) carry several zoonotic pathogens and because rats and humans live in close proximity in urban environments, there exists potential for transmission. To identify zoonotic agents carried by rats in Baltimore, Maryland, USA, we live-trapped 201 rats during 2005-2006 and screened them for a panel of viruses, bacteria, and parasites. Antibodies against Seoul virus (57.7%), hepatitis E virus (HEV, 73.5%), Leptospira interrogans (65.3%), Bartonella elizabethae (34.1%), and Rickettsia typhi (7.0%) were detected in Norway rats. Endoparasites, including Calodium hepatica (87.9%) and Hymenolepis sp. (34.4%), and ectoparasites (13.9%, primarily Laelaps echidninus) also were present. The risk of human exposure to these pathogens is a significant public health concern. Because these pathogens cause non-specific and often self-limiting symptoms in humans, infection in human populations is probably underdiagnosed.

Animals↗

PubMed2001

Sex differences in immune responses and viral shedding following Seoul virus infection in Norway rats.

In the field, male rodents are more frequently infected with hantaviruses than females. This study examined whether patterns of immune responses against hantavirus differed between the sexes. Male and female Long Evans rats (Rattus norvegicus) were inoculated with Seoul virus, and antibody and cytokine responses, as well as virus shedding were assessed. Males were more likely to shed virus in saliva, to shed virus through multiple routes (saliva, urine, and feces), and to have viral RNA in the spleen than females. Anti-Seoul virus IgG responses were higher in males than females. In both sexes, splenic IFNgamma and IL-4 production increased following infection. After infection, males had higher Th1 immune responses (i.e., IgG2a, IFNgamma, and IL-2) than females; in contrast, Th2 immune responses (i.e., IgG1, IL-4, and IL-10) were similar between the sexes. These data suggest that immune responses to Seoul virus differ between the sexes.

Animals↗

PubMed2000

The effects of hormones on sex differences in infection: from genes to behavior.

Males of many species are more susceptible than females to infections caused by parasites, fungi, bacteria, and viruses. One proximate cause of sex differences in infection is differences in endocrine-immune interactions. Specifically, males may be more susceptible to infection than females because sex steroids, specifically androgens in males and estrogens in females, modulate several aspects of host immunity. It is, however, becoming increasingly more apparent that in addition to affecting host immunity, sex steroid hormones alter genes and behaviors that influence susceptibility and resistance to infection. Thus, males may be more susceptible to infection than females not only because androgens reduce immunocompetence, but because sex steroid hormones affect disease resistance genes and behaviors that make males more susceptible to infection. Consideration of the cumulative effects of sex steroid hormones on susceptibility to infection may serve to clarify current discrepancies in the literature and offer alternative hypotheses to the view that sex steroid hormones only alter susceptibility to infection via changes in host immune function.

Animals↗

PubMed2000

In vitro melatonin treatment enhances splenocyte proliferation in prairie voles.

The seasonal effects of photoperiod on reproduction are mediated by melatonin, and it is hypothesized that increased immune function in short days is due to the increase in the duration of nightly melatonin secretion. Melatonin can act both directly and indirectly on target tissue within the immune system. The present study sought to tease apart the direct and indirect effects of melatonin on one aspect of immune function by examining the influence of in vitro melatonin on splenocyte proliferation in female prairie voles held in long (LD 16:8) or short (LD 8:16) days. Splenocyte proliferation in response to the T-cell mitogen concanavalin A was enhanced by the addition of melatonin in vitro, as compared to cultures receiving no melatonin. Body mass increased in short-day housed prairie voles, indicating that the animals were responsive to photoperiod. However, photoperiod did not affect splenocyte proliferation in the present study. These results support the hypothesis that melatonin exerts a direct effect on splenocyte proliferation, potentially via high-affinity melatonin receptors localized on splenocytes. The findings also indicate that, irrespective of photoperiod, melatonin exerts direct effects on splenocytes to enhance immune function.

Animals↗

PubMed2000

Sex differences in Seoul virus infection are not related to adult sex steroid concentrations in Norway rats.

Field studies of hantavirus infection in rodents report that a higher percentage of infected individuals are males than females. To determine whether males were more susceptible to hantavirus infection than females, adult male and female Long Evans rats (Rattus norvegicus) were inoculated with doses of Seoul virus ranging from 10(-4) to 10(6) PFU. The 50% infective doses (ID(50)) were not significantly different for male and female rats (10(0.05) and 10(0.8) PFU, respectively). To determine whether sex differences in response to infection were related to circulating sex steroid hormones, sex steroid concentrations were manipulated and antibody responses and virus shedding were assessed following inoculation with the ID(90). Regardless of hormone treatment, males had higher anti-Seoul virus immunoglobulin G (IgG) and IgG2a (i.e., Th1) responses than females and IgG1 (i.e., Th2) responses similar to those of females. Males also shed virus in saliva and feces longer than females. Manipulation of sex steroids in adulthood did not alter immune responses or virus shedding, suggesting that sex steroids may organize adult responses to hantavirus earlier during ontogeny.

Animals↗

PubMed1999

Reproductive function in female mice lacking the gene for endothelial nitric oxide synthase.

Nitric oxide (NO) acts as a neuronal messenger in both the central and peripheral nervous systems and has been implicated in reproductive physiology and behavior. Pharmacological inhibition of nitric oxide synthase (NOS) with the nonspecific NOS inhibitor, l-N(G)-nitro-Arg-methyl ester (l-NAME), induced deficits in both the number of ovarian rupture sites and the number of oocytes recovered in the oviducts of mice. Female neuronal NOS knockout (nNOS-/-) mice have normal numbers of rupture sites, but reduced numbers of oocytes recovered following systemic injections of gonadotropins, suggesting that NO produced by nNOS accounts, in part, for deficits in ovulatory efficiency observed after l-NAME administration. Additionally, endothelial NOS knockout (eNOS-/-) mice have reduced numbers of ovulated oocytes after superovulation. Because endothelial NOS has been identified in ovarian follicles, and because of the noted reduced breeding efficiency of eNOS-/- mice, the present study sought to determine the role of NO from eNOS in mediating the number of rupture sites present after ovulation. Estrous cycle length and variability were consistently reduced in eNOS-/- females. The number of rupture sites was normal in eNOS-/- mice under natural conditions and after administration of exogenous GnRH. After exogenous gonadotropin administration, eNOS-/- females displayed a significant reduction in the number of ovarian rupture sites. Female eNOS-/- mice also produced fewer pups/litter compared to WT mice. These data suggest that NO from endothelial sources might play a role in mediating rodent ovulation and may be involved in regulation of the timing of the estrous cycle.

Animals↗

PubMed1999

Activation of the immune-endocrine system with lipopolysaccharide reduces affiliative behaviors in voles.

In Experiment 1, individually housed male meadow voles (Microtus pennsylvanicus) and prairie voles (Microtus ochrogaster) were injected with lipopolysaccharide (LPS) and exhibited the expected decrease in testosterone and increase in corticosterone and interleukin-1beta concentrations 3 hr later, indicating activation of the endocrine and immune systems. In Experiment 2, LPS- and saline-injected males were tethered in a 3-chamber partner preference apparatus. The time females spent in each chamber with a male, as well as the amount of time spent in social contact, was monitored. Female prairie voles, but not meadow voles, spent more time in the chamber with saline- than with LPS-injected males. LPS-injected male prairie and meadow voles engaged in less social contact with female conspecifics than did saline-injected males. These data suggest that LPS modifies physiology and behavior in male voles and that females may use these changes to discriminate healthy from potentially infected males.

Animals↗

PubMed1999

Role of steroid hormones in Trichinella spiralis infection among voles.

Males are generally more susceptible to parasite infection than females. This sex difference may reflect the suppressive effects of testosterone and enhancing effects of estradiol on immune function. This study characterized the role of circulating steroid hormones in sex differences after infection with the nematode Trichinella spiralis. Because testosterone suppresses immune function and because polygynous males have higher circulating testosterone concentrations than monogamous males, sex differences in parasite burden were hypothesized to be exaggerated among polygynous meadow voles compared with monogamous prairie voles. As predicted, sex differences in response to T. spiralis infection were increased among meadow voles; males had higher worm numbers than females. Male and female prairie voles had equivalent parasite burden. Overall, prairie voles had higher worm numbers than meadow voles. Contrary to our initial prediction, differences in circulating estradiol concentrations in females, testosterone concentrations in males, and corticosterone concentrations in both sexes were not related to the observed variation in T. spiralis infection. Taken together, these data suggest that not all sex differences in parasite infection are mediated by circulating steroid hormones and that adaptive-functional explanations may provide new insight into the causes of variation in parasite infection.

Animals↗

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

A comparison by burst testing of three types of vascular anastomosis.

A new in vivo test for burst strength of arterial anastomoses was tested in 40 rats. Twelve had a severed right femoral artery reanastomosed by the traditional nine-suture technique. In a second group of 12, a modified telescoping sleeve method of reanastomosis was used. In a third group of 12, a laser-assisted anastomosis using four stay sutures was performed. Four rats had sham procedures. Immediately after reanastomosis three vessels from each group plus all four sham surgical vessels were subjected to burst testing. These tests were performed again on the repaired vessels at 1 week, 1 month, and 2 months. All the vessels were patent at burst testing. All repairs held at all times to greater than 160 mm mean arterial pressure. The four-suture telescopic anastomosis technique was consistently strongest over time, but all techniques showed adequate strength at all time intervals.

Anastomosis, Surgical↗

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

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↗

PubMed1997

Social environment and steroid hormones affect species and sex differences in immune function among voles.

Testosterone has bipotential effects on male fitness; that is, it both suppresses immune function and maintains characteristics important for reproductive success. Presumably, these effects of testosterone may be more pronounced among polygynous species because testosterone concentrations are generally higher among polygynous than monogamous males. The present study examined sex and species differences in cell-mediated immunity among four arvicoline rodents. The role of mating system and sex steroids in sex differences in immune function was examined in individually housed polygynous meadow (Microtus pennsylvanicus) and montane (M. montanus) voles and monogamous prairie (M. ochrogaster) and pine (M. pinetorum) voles in Experiment 1. No sex differences in splenocyte proliferation were observed among the four species and circulating testosterone concentrations did not correlate with immune function of individuals within each species. The contribution of social isolation to these results was examined in Experiment 2, in which meadow and prairie voles were housed individually, or with same- or opposite-sex conspecifics in either pairs or groups of four per cage for 28 days. Overall, prairie voles exhibited more robust immune responses than meadow voles when housed in pairs or in same-sex groups. Sex differences in immune function were also apparent; male meadow voles had higher immune responses than female conspecifics when housed in pairs, whereas female prairie voles had higher responses than male conspecifics when housed in same-sex pairs. Circulating sex steroid hormones and corticosterone appear to mediate some, but not all, of the changes in immune function evoked by differential housing conditions. Taken together, these results suggest that social factors have significant effects on immunity and should be considered in studies of sex differences in immunity at both proximate and ultimate levels.

Animals↗

PubMed1997

Urinary bladder-urethral sphincter dysfunction in mice with targeted disruption of neuronal nitric oxide synthase models idiopathic voiding disorders in humans.

Idiopathic voiding disorders affect up to 10-15% of men and women. We describe bladder abnormalities in mice with targeted deletion of the gene for neuronal nitric oxide synthase which model the clinical disorders. The mice possess hypertrophic dilated bladders and dysfunctional urinary outlets which do not relax in response to electrical field stimulation or L-arginine. The mice also display increased urinary frequency.

Animals↗

PubMed1997

Sex differences in immunocompetence differ between two Peromyscus species.

Males generally exhibit reduced immunocompetence and greater susceptibility to disease than females. The explanations for why males may be more susceptible to disease than females fall into two categories: 1) the proximate mechanisms mediating immunity, such as hormonal mechanisms, and 2) variation in reproductive success between the sexes. The present study examined the extent to which these factors contribute to sex differences in cell-mediated immune function in polygynous Peromyscus maniculatus and monogamous Peromyscus californicus. Prevailing hypotheses suggest that, because variation in male and female reproductive success is greater among polygynous than monogamous species, sex differences in immunocompetence should be greater among polygynous than monogamous species as well. In contrast to these predictions, sex differences in cell-mediated immunity and body mass were only observed among monogamous P. californicus, in which females exhibited higher splenocyte proliferation in response to the T cell mitogen, concanavalin A, and weighed less than male conspecifics. Male P. maniculatus had higher serum testosterone concentrations than male P. californicus, but females of the two species did not differ in circulating estradiol concentrations. Sex steroid concentrations were not correlated with either immunocompetence or body mass; however, large P. californicus males exhibited reduced immune responses. Taken together, these results do not support the hypothesis that sex differences in immunocompetence are more pronounced among polygynous compared with monogamous species. Furthermore, these data suggest that circulating testosterone does not mediate sex differences in immuno-competence or body mass in P. californicus.

Animals↗

PubMed1996

Reproductive and immune responses to photoperiod and melatonin are linked in Peromyscus subspecies.

The effects of photoperiod and melatonin treatment on reproductive and immune function were assessed in two subspecies of Peromyscus maniculatus from different latitudes of origin. In experiment 1, P. m. bairidii (latitude = 42 degrees 51' N) and P. m. luteus (latitude = 30 degrees 37' N) were housed in either long (LD 16:8) or short days (LD 8:16) for 8 weeks. Short-day P. m. bairdii displayed reproductive regression and elevated splenocyte proliferation in response to the T-cell mitogen concanavalin A, as compared to long-day mice. In contrast, P. m. luteus did not undergo reproductive regression or exhibit any increase in lymphocyte proliferation in short days. In experiment 2, individuals of both P. m. bairdii and P. m. luteus were implanted with empty capsules or capsules that contained melatonin. Individual P. m. bairdii implanted with melatonin underwent reproductive regression. Individuals of this subspecies also displayed elevated lymphocyte proliferation compared to control mice. Conversely, P. m. luteus implanted with melatonin did not undergo reproductive regression and displayed no significant changes in lymphocyte proliferation. These results suggest that reproductive responsiveness to melatonin mediates short-day enhancement of immune function in deer mice. These data also imply that melatonin may not possess universal immunoenhancing properties. Rather, the effectiveness of melatonin to influence immune responses may be constrained by reproductive responsiveness to this indole-amine.

Animals↗

PubMed1996

Characterization of sensorimotor performance, reproductive and aggressive behaviors in segmental trisomic 16 (Ts65Dn) mice.

In the present study, segmental trisomy 16 (Ts65Dn) mice, an animal model of Down Syndrome (DS), were examined for sensorimotor, reproductive, and aggression abnormalities associated with DS. The Ts65Dn mice exhibited no sensorimotor deficits in olfactory sensitivity, visual abilities, orientation reactions, forelimb strength, postural skills, balance/ coordination, climbing, or locomotion compared to genetically matched control B6EiC3HF1 mice. In mating tests, the percentage of Ts65Dn mice displaying intromissions when paired with estrous females was significantly less than that in controls. Although the percentage of Ts65Dn mice that mounted and ejaculated with an estrous female was marginally less than in controls, there were no significant differences on the other measures of reproductive behavioral performance. In aggression tests, Ts65Dn males showed increased offensive aggression in a neutral arena both when paired and among grouped males. Conversely, Ts65Dn mice exhibited less offensive aggression against an intruder in their home cage than control males. In sum, these mice possess some of the adaptive behavior abnormalities observed in DS patients; however, because the Ts65Dn mice do not have any observed sensorimotor deficits that could interfere with behavioral assessments, they may serve as a useful model for the study of behavioral impairments associated with DS.

Aggression↗

PubMed1996

Cerebral microregional oxygen balance during chronic versus acute hypertension in middle cerebral artery occluded rats.

This study was performed to compare microregional 0(2) supply and consumption balance in spontaneously hypertensive rats (SHR), normotensive Wistar Kyoto rats (WKY), and in phenylephrine-induced acutely hypertensive WKY (WKY + ph) rats. Under isoflurane anesthesia, a middle cerebral artery (MCA) of SHR (n = 7) and WKY (n = 14) rats was occluded. Seven of the WKY rats were infused with phenylephrine (WKY + ph) to keep the mean arterial pressure (MAP) at the same level as that of the SHR. In all animals, 1 h after MCA occlusion, regional cerebral blood flow (rCBF) was determined using an autoradiographic technique, and microregional arterial and venous 02 saturations were determined using microspectrophotometry. MAP was 76 +/- 4 (SD), 136 +/- 15, and 132 +/- 12 mm Hg for the WKY, WKY + ph, and SHR groups, respectively. All variables describing regional O2 balance and rCBF were similar between the SHR and the WKY groups in the ischemic cortex as well as in the contralateral cortex. With phenylephrine infusion, rCBF of both the ischemic cortex and the contralateral cortex were increased in the WKY group. The average 02 supply-to-consumption ratio in the ischemic cortex was higher in the WKY + ph than in the WKY or SHR group. In the ischemic cortex, heterogeneity of venous 02 saturation (SvO2), expressed as a coefficient of variation (CV = 100 X SD/mean), was significantly lower in the WKY + ph (18.3 +/- 2.4) group than in the SHR (30.5 +/- 11.8) or in the WKY (31.3 +/- 9.0) group. The number of veins with low 02 saturation (SvO2 < 40%) in the ischemic cortex was significantly lower in the WKY + ph than in the SHR or in the WKY group. Our data suggest that in chronically hypertensive animals, cerebrovascular adaptations enable the microregional 02 balance in focal ischemia to be maintained at a level similar to that of normotensive animals. However, in normotensive animals with focal cerebral ischemia, an acute increase of MAP improves microregional O2 balance.

Acute Disease↗