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At least 1,513 records · Page 84Linked to original sources
PubMed2001

Cochlear outer-hair-cell efferents and complex-sound-induced hearing loss: protective and opposing effects.

Centrifugal crossed and uncrossed medial olivocochlear systems (CMOCS and UMOCS) terminate on cochlear outer hair cells (OHCs) and exercise effects through a nicotinic cholinergic receptor. Hence their cochlear effects have not been differentiated. Recent work on protection from loud-sound-induced temporary threshold shifts (TTSs) in hearing sensitivity suggest the two OHC efferent systems may act differently. This was tested, using traumatic complex sound, to determine if such sound could activate both MOCS components and then reveal whether they exerted different effects on TTSs to such stimuli. Traumatic noise bands activated crossed and uncrossed MOCS efferents. Two different CMOCS effects were observed. For frequencies in the noise (within-band frequencies), it protected hearing sensitivity as expected. Novel findings were that at frequencies higher than the noise band range (high-side frequencies), it acted to worsen hearing sensitivity and that this was opposed by a UMOCS effect generally targeted to these frequency regions. It is proposed that the two crossed MOCS actions are extensions of a contrast-enhancement action for low-level noise bands. It is also proposed that the UMOCS plays a state-restoration role to prevent an undesired CMOCS side-effect of exacerbation of high-side TTSs to high-level noise bands.

Acoustic Stimulation↗
PubMed1999

Experimental infection of cotton rats with three naturally occurring Bartonella species.

The kinetics of infection and humoral immune response of laboratory-bred cotton rats (Sigmodon hispidus) challenged with three Bartonella spp. recovered from the blood of naturally infected cotton rats captured in Georgia (USA) are described. Bartonella spp. infection, as determined by bacteremia, occurred in all 18 cotton rats inoculated with live Bartonella of each species at either a low dose, 10(3) colony-forming units (CFU's), or high dose, 10(7) CFU. Cotton rats inoculated with lower doses of Bartonella spp. developed higher bacteremia that persisted for longer periods than in those inoculated with high doses. Peak bacteremia varied among Bartonella spp, ranging from 10(4) to 10(6) CFUs per 1.0 ml of blood. Antibody measured by immunofluorescence assays using species-specific antigens indicated more rapidly rising and higher antibody titers in cotton rats challenged with high doses vs. low doses and with inactivated bacteria vs. live bacteria. Each group of rats produced high IgG titers to the homologous challenge antigen; low or unmeasurable cross-reactivity was detected to heterologous Bartonella antigens. Exposure of cotton rats to a specific Bartonella sp. resulted in protection, as measured by detectable bacteremia, in eight of nine animals challenged with the same Bartonella sp. used initially; no evidence of resistance to secondary challenge with different Bartonella spp. was obtained. Cross-protection between Bartonella spp., isolated from the same rodent species, may not occur.

Animals↗
PubMed1994

Analysis of C-terminally truncated dengue 2 and dengue 3 virus envelope glycoproteins: processing in insect cells and immunogenic properties in mice.

We constructed two recombinant Autographa californica nuclear polyhedrosis baculoviruses. Spodoptera frugiperda (Sf9) cells containing these constructs produce carboxy-terminally truncated envelope E proteins representing dengue (DEN) virus serotypes 2 and 3. The two recombinant proteins contained their homologous signal sequences at the N terminus and were truncated by 71 and 74 amino acids at the C terminus, respectively. This allowed the translocation of the recombinant proteins to the endoplasmic reticulum followed by glycosylation processing and secretion into the extracellular medium. An additional unglycosylated form which was not secreted was detected inside the infected Sf9 cells. Sera from Swiss mice immunized with the infected Sf9 cell lysates gave a DEN cross-reactive response in ELISA and substantial amounts of neutralizing antibodies to the homologous virus. Similar antibody titres were obtained when the two recombinant proteins were inoculated concomitantly. BALB/c mice were vaccinated with three doses of the recombinant E proteins, taken as monovalent or bivalent immunogens, and challenged with mouse-adapted DEN-2 virus. DEN-2 E protein induced a good protection (90%) against lethal encephalitis and recombinant DEN-3 E protein gave a substantial cross-protection (54%). Eighty-two percent of the mice immunized with a mixture of both recombinant E proteins survived the DEN-2 virus challenge.

Animals↗
PubMed1993

Inhibition of lipid A- and lipopolysaccharide-induced cytokine secretion, B cell mitogenesis, and lethal shock by lipid A-specific murine monoclonal antibodies.

Three murine hybridomas secreting IgM monoclonal antibodies (MAbs) to lipid A (LA) of Salmonella minnesota R595 were generated. These MAbs serologically cross-reacted with LA and lipopolysaccharide (LPS) of unrelated gram-negative bacterial species. All three MAbs significantly suppressed the ability of LA and LPS from various gram-negative bacteria to induce tumor necrosis factor (TNF)-alpha (36%-67%) and interleukin-1 (30%-98%) in murine peritoneal macrophages and to stimulate B lymphocytes (37%-78%). Lipid A-induced TNF alpha production was also suppressed in mice (86%-88%). All three antibodies protected adrenalectomized mice against lethal shock induced by LA of S. minnesota R595. Optimal protection was achieved with one of the antibodies (MLA-1), if it was administered 2 h before injection of lipid A, and full protection persisted < or = 24 h. Moreover, MLA-1 was able to protect adrenalized or D(+)-galactosamine-sensitized mice against lethal shock induced by LPS derived from various gram-negative bacteria. This cross-protection could be predicted on the basis of serologic cross-reactivity and cross-neutralization by MLA-1 of the bioactivity of the heterologous LA or LPS in vitro.

Animals↗
PubMedDate not supplied

Syntheses of DNA duplexes containing a C-C interstrand cross-link.

Short DNA duplexes that contain a N4C-ethyl-N4C interstrand cross-link were prepared on controlled pore glass supports using a DNA synthesizer. The C-C cross-link was introduced via a convertible nucleoside on the support or by using a protected C-C cross-link phosphoramidite. An orthogonal protection scheme allowed selective chain growth in either a 3'-->5' or 5'-->3' direction. The cross-linked duplexes were purified by HPLC and characterized by MALDI-TOF mass spectrometry and/or by enzymatic digestion.

Cross-Linking Reagents↗
PubMed1978

Voluntary movement control and adaptation to cross-coupled stimulation.

The rates at which protective adaptation was acquired to an incremental cross-coupled stimulus were compared under three conditions of movement control: 1) a passive condition in which the 45 degree lateral tilts of the subject's chair were controlled entirely by the experimenter (N = 12); 2) an active condition in which the same movements were achieved directly through the subject's own muscular effort (N = 12); and 3) an active-passive condition in which control was exercised indirectly through microswitches located on the chair arms (N = 12). Adaptation was measured by the rate of neutralization of the oculogyral illusion, as estimated from the apparent motion of a small, dimly illuminated target. The results supported the prediction that the passive condition would be the least effective mode for acquiring adaptation. An unexpected finding was that the active-passive condition proved to be the most efficient for the development of adaptation.

Adaptation, Physiological↗
PubMed1988

Mouse hepatitis virus and host determinants of vertical transmission and maternally-derived passive immunity in mice.

Transmission of mouse hepatitis virus (MHV) in utero following oronasal inoculation of pregnant mice was found to depend upon MHV strain and host genotype. Virulent, polytropic MHV-JHM was recovered from multiple maternal tissues, including liver and uterus, as well as placenta and fetus in susceptible BALB/cByJ mice. Fetuses were infected during all 3 trimesters of pregnancy. Low virulence, polytropic MHV-S infected fetuses in a low percentage of susceptible BALB/cByJ dams. Infection of resistant CD-1 mice with MHV-JHM was limited, with no fetal infection. Enterotropic MHV-Y was largely restricted to intestine of BALB/cByJ and CD-1 dams, with minimal dissemination and no fetal infection. Maternally-derived MHV IgG antibody was detectable in pup sera through 4 weeks of age. Antibody titers were generally lower in second litters of the same dam. Cross-fostering experiments showed that antibody was transferred via colostrum and not in utero, and that pups were capable of absorption through 2 weeks of age. Pups nursing immune dams were protected against MHV challenge at 1 and 2 weeks of age, compared to pups nursing naive dams. Immunity to MHV challenge was cross-protective against both antigenically homotypic and heterotypic strains of MHV.

Animals↗
PubMed1993

tRNA-guanine transglycosylase from Escherichia coli. Overexpression, purification and quaternary structure.

tRNA-guanine transglycosylase (TGT) is the enzyme responsible for the posttranscriptional modification of specific tRNAs (Asn, Asp, His and Tyr) with queuine. In E. coli this modification occurs via a two-step reaction: (1) TGT-catalyzed base exchange of guanosine-34 with preQ1 (7-aminomethyl-7-deazaguanine) and (2) addition of a cyclopentenediol moiety to the preQ1-34 tRNA. E. coli TGT is normally expressed at very low levels (approximately 1 mg from 500 g cells). The sequence of the queuine operon of E. coli has recently been reported by Reuter et al. (1991). We have cloned the tgt gene into an overexpressing vector in order to provide a more efficient preparation of TGT. A simple, four-step purification scheme yields 78 mg of homogeneous TGT per liter of cell culture (A600 = 5 to 6). Amino-terminal protein sequencing confirms the identity of the recombinant protein and indicates that the initiator methionine is retained in the mature form. Native-PAGE of TGT and SDS-PAGE of cross-linked TGT are most consistent with a hexameric quaternary structure for the enzyme. The cross-linking data also suggests that the enzyme exists as a dimer of trimers of identical 42.5 kDa subunits (total M(r) = 255 kDa. The enzyme is inactivated by cross-linking with the bisimidoester, dimethylsuberimidate. Substrate (tRNA) protects the enzyme against cross-linking and inactivation by dimethylsuberimidate and against inactivation by modification with ethylacetimidate, a monofunctional, imidoester. This indicates that the enzymic residues (presumably lysines) that are involved in cross-linking and the inactivation are in the active site of the enzyme.

Amino Acids↗
PubMed2006

Immunization with live Neisseria lactamica protects mice against meningococcal challenge and can elicit serum bactericidal antibodies.

Natural immunity against Neisseria meningitidis is thought to develop following nasopharyngeal colonization with this bacterium or other microbes expressing cross-reactive antigens. Neisseria lactamica is a commensal of the upper respiratory tract which is often carried by infants and young children; epidemiological evidence indicates that colonization with this bacterium can elicit serum bactericidal activity (SBA) against Neisseria meningitidis, the most validated correlate of protective immunity. Here we demonstrate experimentally that immunization of mice with live N. lactamica protects animals against lethal meningococcal challenge and that some, but not all, strains of N. lactamica elicit detectable SBA in immunized animals regardless of the serogroup of N. meningitidis. While it is unlikely that immunization with live N. lactamica will be implemented as a vaccine against meningococcal disease, understanding the basis for the induction of cross-protective immunity and SBA should be valuable in the design of subunit vaccines for the prevention of this important human infection.

Animals↗
PubMed1993

Regional adenosine attenuates postischemic spinal cord injury.

PURPOSE: Operations on the thoracic and thoracoabdominal aorta are associated with postoperative paraplegia rates as high as 20% to 30%. Attempts to reduce this complication have focused on decreasing the energy needs of the spinal cord with protective agents such as hypothermia and barbiturates or on increasing blood flow with various shunts. This study explores the hypothesis that perfusion of the spinal cord with hypothermic solutions or with adenosine will prevent or ameliorate paraplegia. METHODS: New Zealand white rabbits underwent 40 minutes of infrarenal aortic isolation. The infrarenal aorta is the primary source of spinal cord blood supply in the New Zealand white rabbit. Control rabbits sustained aortic occlusion without any protective measures. The remaining animals were randomized into three groups that underwent aortic cross-clamping with various protective adjuncts. Group I received regional aortic hypothermia perfusion, group II received systemic adenosine, and group III received regional aortic perfusion with high-dose adenosine. RESULTS: Neurologic function was graded according to the Tarlov scale (0 = no movement, 1 = slight movement, 2 = sits with assistance, 3 = sits alone, 4 = weak hop, 5 = normal hop). After 96 hours animals were euthanized, and spinal cords were harvested for histologic examination. The nonparaplegic animals in group I had a mean Tarlov score of 1.5, whereas those in group III had a mean score of 3.4. Histologic studies on spinal cord tissue revealed no significant differences between the study groups. CONCLUSIONS: These data demonstrate that administration of regional adenosine attenuates ischemic injury associated with aortic occlusion in this experimental model.

Adenosine↗
PubMed1992

Immunization against geographical isolates of Trichinella spiralis in mice.

Partially purified antigen preparations from six isolates of Trichinella spiralis were used to immunize mice. Immunogenicity of the antigens was assessed in terms of antibody and lymphocyte responses and ability to stimulate protective immunity against challenge. Isolate antigens showed considerable cross-reactivity, and all elicited protective responses. Two major patterns of immunizing ability could be distinguished: (a) isolates that immunized well against heterologous challenge and elicited good immunity in London isolate-immunized mice (C-76 and Laso), and (b) isolates that immunized poorly against heterologous challenge and were least effective in London isolate-immunized mice (GM-1 and Mad-83). The immunogenicity of one isolate (C-76) was markedly greater than the others, inducing rapid loss in unvaccinated mice, almost complete protection in London isolate-immunized mice, and immunity in London isolate-challenged mice equivalent to the homologous antigen. These variations in immunogenicity, cross-reactivity and immunizing ability are discussed in terms of constraints that may operate against the development and use of vaccines against parasites that are widely distributed geographically.

Animals↗
PubMed2005

Dendritic cells cross-present exogenous fungal antigens to stimulate a protective CD8 T cell response in infection by Histoplasma capsulatum.

The contribution of CD8 T cells in host defense against histoplasmosis is minor in the CD4 T cell-intact mouse, as it has been shown that depleting CD8 T cells only marginally affects fungal clearance. However, it remains to be determined whether the CD8 T cells are protective in a host lacking functional CD4 T cells. In this study, MHC class II-deficient mice infected with Histoplasma capsulatum (Histoplasma) kept the fungus in check for up to 16 wk, indicating that CD8 T cells are able to limit fungal replication. Ex vivo studies showed that CD8 T cells from Histoplasma-infected mice expressed both intracytoplasmic IFN-gamma and granzyme B. Furthermore, CD8 T cells exhibited cytotoxic activity against macrophage targets containing Histoplasma. We demonstrated that the macrophage, being the primary host cell as well as the effector cell, can also serve as Ag donor to dendritic cells. Histoplasma-specific CD8 T cells are stimulated by dendritic cells that present exogenous Histoplasma Ags, either through direct ingestion of yeasts or through uptake of apoptotic macrophage-associated fungal Ags, a process known as "cross-presentation." Based on these results, we present a model detailing the possible sequence of events leading to a cell-mediated immune response and fungal clearance in Histoplasma-infected hosts.

Animals↗
PubMedDate not supplied

[Renal protection during surgical procedures on the infrarenal aorta].

INTRODUCTION: Despite the progress in surgical and anaesthetic management, decreased renal function is still observed after abdominal infrarenal aortic surgery and remains an important problem in postoperative period. Although data regarding the efficacy of perioperative renal protection are conflicting, it is widely believed that renal protection before aortic cross-clamping is beneficial and therefore is commonly used. The aim of this study was to evaluate the impact of renal protection in patients undergoing elective infrarenal aortic surgery (1ARS). PATIENTS AND METHODS: We have prospectively studied 80 patients undergoing elective infrarenal aortic surgery from October 1996 to May 1998 in the Clinical Centre of Serbia, because of aorto-occlusive disease or aortic aneurysm. Patients were excluded from the study for three reasons: prior renal dysfunction, suprarenal aortic cross-clamping and ruptured aortic aneurysm. We have randomized the patients in two groups: without renal protection--group A (n = 40) and with renal protection--group B (n = 40). Preanaesthetic medication consisted of midazolam (5 mg i.m.). Anaesthesia was induced with etomidat 0.3 mg/kg, fentanyl 0.05-0.1 mg and succinil-holin Img/kg. Ventilation was controlled using 50% of nitrous oxyde and oxygen. Supplemental anaesthesia consisted of isoflurane and fentanyl, in order to maintain the mean arterial pressure and heart rate +/- 20% regarding preoperative values. In all patients two peripheral vein and radial artery catheters were cannulated before anaesthesia. Central venous catheter and Foley urinary bladder catheter were inserted after the induction of anaesthesia. Two-lead electrocardiograms were recorded. All patients in group B were given intravenously mannitol (0.3 g/kg) before aortic cross-clamping (ACC). After aortic cross-clamping, these patients received furosemide (20-40 mg) or dopamine (1-3 micrograms/kg/min) to the end of surgery (Table 1). In 8 time points (preoperatively, after induction, during ACC, 2 and 8 hours after ACC, on day 1, 2 and 3 postoperatively) haemodynamic parameters (mean arterial and central venous pressure), volume load, urinary output, creatinine and free-water clearance, serum electrolytes, BUN, creatinine, plasma and urine osmolality and ACC time were analyzed in each patient. Renal complications were classified as transient or persistent. Transient renal dysfunction was defined as a greater rise than 20% rise in peak serum creatinine level over baseline serum creatinine level, with a peak of at least 168 mumol/L. Persistent renal insufficiency was defined as a greater rise than 20% rise in discharge serum creatinine level over baseline serum creatinine level, with a peak of at least 168 mumol/L. Moreover, renal insufficiency was defined as a free-water clearance greater than -15 ml/h. Aortic cross-clamping time was defined as a period in which the proximal inflow was occluded. The results were expressed as means +/- SD. Statistical difference detected with Student's t-test, with p < 0.05 being considered significant. RESULTS: Patients in groups A and B were similar regarding the age (64.32 vs. 62.00), sex (males 35, females vs. males 34, females 6) and preoperative diseases. (Tab. 2) No difference was found between groups regarding any of the parameters (BUN, serum creatinine, electrolytes, volume load, creatinine and free-water clearance, haemodynamic parameters, plasma and urine osmolality). Urinary output was higher in group B during and 2 hours after ACC. (Graph 1.) ACC time was similar in two groups (24.1 min vs 24.5 min). (Graph. 2) Only one patient in group B revealed transitory renal insufficiency, not requiring special treatment. These data indicate that renal protection did not influence renal function. Short ACC time may have impact on the obtained results. Our results suggest that renal protection should not be considered as mandatory for elective infrarenal aortic surgery. Because of the short ACC time observed in this study (in comparison to other studies), further studies of renal protection in patients with longer ACC time are needed.

Aorta, Abdominal↗
PubMed1989

Monoclonal antibodies that cross-react with the E1 glycoprotein of different alphavirus serogroups: characterization including passive protection in vivo.

A panel of four monoclonal antibodies (mAb) were produced that cross-react with representatives of two different togavirus serogroups, namely sindbis (SIN) and Semliki Forest (SF) viruses, by ELISA and ADCMC assays. Three of these mAb, IgG2a and IgG2b isotypes, passively protected C3H/Hej mice against 10 and 100 LD50 of SF challenge and one, IgM, did not protect against either challenge dose, or even at 1 LD50. All these mAb were cross-reactive with the E1 glycoprotein of the viruses by immunoblotting in which three different patterns of reactivity were evident, suggesting that three epitopes were involved. The patterns depended upon whether the mAb recognized E1 extracted from purified virions or infected cells and whether SDS-PAGE and immunoblotting were done in the presence or absence of beta-mercaptoethanol. One mAb (IgM) reacted with nonreduced or reduced E1 from either virions or cells suggesting recognition of a linear epitope. The other three mAb reacted with nonreduced but not reduced E1 from virions suggesting that recognition depends upon conformational epitopes. These three mAb reacted also with nonreduced E1 extracted from SF-infected cells whereas only one reacted with nonreduced E1 extracted from SIN-infected cells.

Animals↗
PubMed1997

Protective effects of carnosine against malondialdehyde-induced toxicity towards cultured rat brain endothelial cells.

Malondialdehyde (MDA) is a deleterious end-product of lipid peroxidation. The naturally-occurring dipeptide carnosine (beta-alanyl-L-histidine) is found in brain and innervated tissues at concentrations up to 20 mM. Recent studies have shown that carnosine can protect proteins against cross-linking mediated by aldehyde-containing sugars and glycolytic intermediates. Here we have investigated whether carnosine is protective against malondialdehyde-induced protein damage and cellular toxicity. The results show that carnosine can (1) protect cultured rat brain endothelial cells against MDA-induced toxicity and (2) inhibit MDA-induced protein modification (formation of cross-links and carbonyl groups).

Animals↗
PubMed2005

Double hydrophilic block copolymer monolayer protected hybrid gold nanoparticles and their shell cross-linking.

This paper describes the syntheses of core/shell gold nanoparticles stabilized with a monolayer of double hydrophilic block copolymer and their stimuli responsiveness before and after shell cross-linking. The hybrid nanoparticles consist of gold core, cross-linkable poly(2-(dimethylamino)ethyl methacrylate) (PDMA) inner shell, and poly(ethylene oxide) (PEO) corona. First, diblock copolymer PEO-b-PDMA was prepared via the reversible addition-fragmentation chain transfer (RAFT) technique using a PEO-based macroRAFT agent. The dithioester end group of PEO-b-PDMA diblock copolymer was reduced to a thiol end group. The obtained PEO-b-PDMA-SH was then used to prepare diblock copolymer stabilized gold nanoparticles by the "grafting-to" approach. 1,2-Bis(2-iodoethoxy)ethane (BIEE) was utilized to selectively cross-link the PDMA residues in the inner shell. The stimuli responsiveness and colloidal stability of core/shell gold nanoparticles before and after shell cross-linking were characterized by laser light scattering (LLS), UV-vis transmittance, and transmission electron microscopy (TEM). At pH 9, the average hydrodynamic radius Rh of non-cross-linked hybrid gold nanoparticles starts to increase above 35 degrees C due to the lower critical solution temperature (LCST) phase behavior of the PDMA blocks in the inner shell. In contrast, Rh of the shell cross-linked gold nanoparticles were essentially independent of temperature. Core/shell gold nanoparticles before and after shell cross-linking exhibit reversible swelling on varying the solution pH. Compared to non-cross-linked core/shell gold nanoparticles, shell cross-linking of the hybrid gold nanoparticles leads to permanent core/shell nanostructures with much higher colloidal stability and physically isolates the gold core from the external environment.

Gold↗