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H Li

Publications and source records attributed to H Li.

At least 883 records · Page 49Linked to original sources
PubMed1999

Determining the molecular-growth mechanisms of protein crystal faces by atomic force microscopy.

A high-resolution atomic force microscopy (AFM) study has shown that the molecular packing on the tetragonal lysozyme (110) face corresponds to only one of two possible packing arrangements, suggesting that growth layers on this face are of bimolecular height [Li et al. (1999). Acta Cryst. D55, 1023-1035]. Theoretical analyses of the packing also indicated that growth of this face should proceed by the addition of growth units of at least tetramer size, corresponding to the 43 helices in the crystal. In this study, an AFM linescan technique was used to measure the dimensions of individual growth units on protein crystal faces as they were being incorporated into the lattice. Images of individual growth events on the (110) face of tetragonal lysozyme crystals were observed, shown by jump discontinuities in the growth step in the linescan images. The growth-unit dimension in the scanned direction was obtained from these images. A large number of scans in two directions on the (110) face were performed and the distribution of lysozyme growth-unit sizes were obtained. A variety of unit sizes corresponding to 43 helices were shown to participate in the growth process, with the 43 tetramer being the minimum observed size. This technique represents a new application for AFM, allowing time-resolved studies of molecular processes to be carried out.

Animals↗
PubMed1999

Determining the molecular-packing arrangements on protein crystal faces by atomic force microscopy.

Previous atomic force microscopy (AFM) studies and periodic bond-chain (PBC) analyses of tetragonal lysozyme crystals have suggested that the (110) face consists of chains of molecules related to one another by 43 axes parallel to the crystal face. In this study, high-resolution AFM images of the (110) face were obtained and analyzed in order to verify this prediction. A computer program was employed which constructs the theoretical AFM image corresponding to a specific crystallographic molecular-packing arrangement and AFM tip shape. The packing arrangement and tip shape were varied in order to obtain the maximum possible correlation between experimental and theoretical images. The prediction from PBC analysis of an arrangement involving 43 helices was confirmed in this manner, while the alternate arrangement, consisting of molecules related to one another by 21 axes, was not observed. However, the surface structure was found to differ significantly even from this crystallographic arrangement. The molecules were found to pack slightly closer about what will become the 43 axes within the interior of the crystal, suggesting the occurrence of surface reconstruction or rearrangement on the tetragonal lysozyme (110) face. This study represents a new approach for more precise determination of the molecular-packing arrangements on protein crystal faces employing AFM.

Crystallization↗
PubMed1999

Pressure response of protein backbone structure. Pressure-induced amide 15N chemical shifts in BPTI.

The effect of pressure on amide 15N chemical shifts was studied in uniformly 15N-labeled basic pancreatic trypsin inhibitor (BPTI) in 90%1H2O/10%2H2O, pH 4.6, by 1H-15N heteronuclear correlation spectroscopy between 1 and 2,000 bar. Most 15N signals were low field shifted linearly and reversibly with pressure (0.468 +/- 0.285 ppm/2 kbar), indicating that the entire polypeptide backbone structure is sensitive to pressure. A significant variation of shifts among different amide groups (0-1.5 ppm/2 kbar) indicates a heterogeneous response throughout within the three-dimensional structure of the protein. A tendency toward low field shifts is correlated with a decrease in hydrogen bond distance on the order of 0.03 A/2 kbar for the bond between the amide nitrogen atom and the oxygen atom of either carbonyl or water. The variation of 15N shifts is considered to reflect site-specific changes in phi, psi angles. For beta-sheet residues, a decrease in psi angles by 1-2 degrees/2 kbar is estimated. On average, shifts are larger for helical and loop regions (0.553 +/- 0.343 and 0.519 +/- 0.261 ppm/2 kbar, respectively) than for beta-sheet (0.295 +/- 0.195 ppm/2 kbar), suggesting that the pressure-induced structural changes (local compressibilities) are larger in helical and loop regions than in beta-sheet. Because compressibility is correlated with volume fluctuation, the result is taken to indicate that the volume fluctuation is larger in helical and loop regions than in beta-sheet. An important aspect of the volume fluctuation inferred from pressure shifts is that they include motions in slower time ranges (less than milliseconds) in which many biological processes may take place.

Amides↗
PubMed1999

Morphological and physiological characteristics of discontinuous linear atrial ablations during atrial pacing and atrial fibrillation.

INTRODUCTION: Linear atrial ablations are thought to be necessary to accomplish successful catheter ablation of atrial fibrillation. In order to investigate the conduction characteristics of atrial myocardium in regions of linear lesion discontinuity (gaps), we performed activation sequence mapping in gap regions during atrial pacing and atrial fibrillation. METHODS AND RESULTS: In seven dogs, a linear epicardial ablation was created on the right atrial free wall with a discontinuous segment (gap) in the mid-portion of the lesion. A plaque electrode was used to measure conduction across the gap. Conduction was assessed during (1) atrial pacing from the edge of the plaque electrode during sinus rhythm, and (2) during atrial fibrillation. After each series of measurements, the lesion gap was decreased by creating additional radiofrequency ablations and repeat conduction maps were obtained. The process was repeated until conduction block was observed during atrial pacing. Gap lengths ranged from 0 to 25 mm. During atrial pacing, gaps as narrow as 2 mm demonstrated normal conduction and gaps as large as 5 mm demonstrated block during pacing. Although conduction block was never present across gaps greater than 5 mm, the ability to predict conduction block as a function of gap width was difficult for lesions < or = 5 mm due to a significant degree of overlap between normal conduction and conduction block in this gap range. During atrial fibrillation, 1/175 (0.6%) mapped wavelets conducted across gaps that demonstrated block during pacing; whereas, 411/600 (68.5%; P < 0.0001) wavelets conducted across gaps that did not demonstrate block during pacing (P = NS compared to preablation measurements). Histologically normal atrial myocytes were observed within gaps exhibiting conduction block. CONCLUSIONS: Visible gaps > 5 mm rarely demonstrate conduction block during atrial pacing and atrial fibrillation; whereas, gaps < or = 5 mm in length may demonstrate block. Lesion gaps that do not demonstrate conduction block during atrial pacing have no higher rate of functional conduction block during atrial fibrillation than fibrillating atria without ablation lesions.

Animals↗
PubMed1999

Clinical significance of TT virus infection in patients with chronic hepatitis C.

OBJECTIVE: The TT virus (TTV) is a novel DNA virus that has recently been identified. The clinical significance of TTV infection in patients with chronic hepatitis C has not been determined. The aim of this study was to determine the prevalence and possible role of TTV in a well characterized population with chronic hepatitis C infection. METHODS: Ninety patients with chronic HCV and known time of HCV acquisition were selected from approximately 250 patients followed at our institution. Characteristics including age, sex, histology, and length of disease were recorded. Direct sequencing of the NS5 region was used for HCV genotyping. TTV DNA detection was based on PCR. RESULTS: TTV infection was present in 24 of 90 (27%) HCV patients. Patients were divided into four groups based on stage of disease; chronic hepatitis (CH, 29 patients), compensated cirrhosis (CC, 17 patients), decompensated cirrhosis (DC, 28 patients), and hepatocellular carcinoma (HCC, 16 patients). TTV was present in 2/29 (7%), 2/17 (12%), 11/28 (39%), and 9/16 (56%) in those with CAH, CC, DC, and HCC respectively. TTV was significantly more prevalent among those with advanced disease (DC and HCC) compared to those with stable disease (CH and CC; p = 0.001). Mean age, sex, and the time from exposure to HCV to development of complications were similar in TTV-positive and -negative patients. TTV infection was more common in patients infected with HCV genotype 1b. Univariate analysis showed that length of HCV infection, HCV genotype 1b, and TTV infection were important in predicting the stage of liver disease in HCV patients. However, after adjusting for length of HCV infection, TTV but not HCV genotype was important in predicting the stage of liver disease. CONCLUSIONS: We conclude that 1) TTV infection is common in patients with chronic HCV; 2) TTV infection is more prevalent among patients with advanced HCV-associated liver disease (DC and HCC) than in those with stable disease (CH and CC); and 3) TTV infection is more common in patients with HCV genotype 1b but is independent from genotype in predicting the stage of HCV-associated liver disease.

Base Sequence↗
PubMed1999

Characterization of a novel methyl-accepting chemotaxis gene, dmcB, from the oral spirochete Treponema denticola.

Immediately downstream from the previously isolated Treponema denticola ATCC 35405 prtB gene coding for a chymotrypsinlike protease activity, an open reading frame, ORF3, was identified which shared significant homology with the highly conserved domains (HCDs) of bacterial methyl-accepting chemotaxis proteins (MCPs). Nucleotide sequencing of this ORF revealed that the gene would code for a protein with a size of approximately 41 kDa. In addition, this sequence contained a domain which was virtually identical to the HCD of a recently characterized MCP, DmcA, of strain 35405. Therefore, this ORF was named dmcB. Northern blot analysis suggested that dmcB was part of an operon structure containing prtB. Insertional inactivation of dmcB utilizing an ermF-ermAM cassette resulted in a mutant with decreased chemoattraction toward nutrient supplements. In addition, the mutant displayed an altered pattern of methylated proteins under conditions of chemotaxis. Inactivation of the dmcB gene also attenuated the methylation of the DmcA protein. These results suggest that the dmcB gene codes for an MCP in T. denticola which may interact with other MCPs in these organisms.

Amino Acid Sequence↗
PubMed1999

The periplasmic murein peptide-binding protein MppA is a negative regulator of multiple antibiotic resistance in Escherichia coli.

MppA is a periplasmic binding protein in Escherichia coli essential for uptake of the cell wall murein tripeptide L-alanyl-gamma-D-glutamyl-meso-diaminopimelate. We have found serendipitously that E. coli K-12 strains carrying a null mutation in mppA exhibit increased resistance to a wide spectrum of antibiotics and to cyclohexane. Normal sensitivity of the mppA mutant to these agents is restored by mppA expressed from a plasmid. As is observed in the multiple antibiotic resistance phenotype in E. coli cells, the mppA null mutant overproduces the transcriptional activator, MarA, resulting in expression of the membrane-bound AcrAB proteins that function as a drug efflux pump. Reduced production of OmpF similar to that observed in the multiple antibiotic resistance phenotype is also seen in the mppA mutant. These and other data reported herein indicate that MppA functions upstream of MarA in a signal transduction pathway to negatively regulate the expression of marA and hence of the MarA-driven multiple antibiotic resistance. Overproduction of cytoplasmic GadA and GadB and of several unidentified cytoplasmic membrane proteins as well as reduction in the amount of the outer membrane protein, OmpP, in the mppA null mutant indicate that MppA regulates a number of genes in addition to those already known to be controlled by MarA.

ATP-Binding Cassette Transporters↗
PubMed1999

Cellular motor protein KIF-4 associates with retroviral Gag.

Previously we demonstrated that murine retroviral Gag proteins associate with a cellular motor protein, KIF-4. Using the yeast two-hybrid assay, we also found an association of KIF-4 with Gag proteins of Mason-Pfizer monkey virus (MPMV), simian immunodeficiency virus (SIV), and human immunodeficiency virus type 1 (HIV-1). Studies performed with mammalian cell systems confirmed that the HIV-1 Gag protein associates with KIF-4. Soluble cytoplasmic proteins from cells infected with recombinant vaccinia virus expressing the entire Gag-Pol precursor protein of HIV-1 or transfected with HIV-1 molecular clone pNL4-3 were fractionated by sucrose gradient centrifugation and further separated by size-exclusion and anion-exchange chromatographies. KIF-4 and HIV-1 Gag cofractionated in both chromatographic separations. Immunoprecipitation assays have also verified the KIF-4-Gag association. KIF-4 binds mainly to the Gag precursor (Pr55 Gag) and a matrix-capsid processing intermediate (Pr42) but not to other processed Gag products. The binding of Gag is mediated by a domain of KIF-4 proximal to the C terminus. These results, and our previous studies, raise the possibility that KIF-4 may play an important role in retrovirus Gag protein transport.

Animals↗
PubMed1999

An Epstein-Barr virus that expresses only the first 231 LMP1 amino acids efficiently initiates primary B-lymphocyte growth transformation.

An Epstein-Barr virus (EBV) recombinant (MS231) that expresses the first 231 amino acids (aa) of LMP1 and is truncated 155 aa before the carboxyl terminus transformed resting B lymphocytes into lymphoblastoid cell lines (LCLs) only when the infected cells were grown on fibroblast feeder cells (K. M. Kaye et al., J. Virol. 69:675-683, 1995). Higher-titer MS231 virus has now been compared to wild-type (WT) EBV recombinants for the ability to cause resting primary B-lymphocyte transformation. Unexpectedly, MS231 is as potent as WT EBV recombinants in causing infected B lymphocytes to proliferate in culture for up to 5 weeks. When more than one transforming event is initiated in a microwell, the MS231 recombinant supports efficient long-term LCL outgrowth and fibroblast feeder cells are not required. However, with limited virus input, MS231-infected cells differed in their growth from WT virus-infected cells as early as 6 weeks after infection. In contrast to WT virus-infected cells, most MS231-infected cells could not be grown into long-term LCLs. Thus, the LMP1 amino-terminal 231 aa are sufficient for initial growth transformation but the carboxyl-terminal 155 aa are necessary for efficient long-term outgrowth. Despite the absence of the carboxyl-terminal 155 aa, MS231- and WT-transformed LCLs are similar in latent EBV gene expression, in ICAM-1 and CD23 expression, and in NF-kappaB and c-jun N-terminal kinase activation. MS231 recombinant-infected LCLs, however, require 16- to 64-fold higher cell density than WT-infected LCLs for regrowth after limiting dilution. These data indicate that the LMP1 carboxyl-terminal 155 aa are important for growth at lower cell density and appear to reduce dependence on paracrine growth factors.

B-Lymphocytes↗
PubMed1999

The serine protease and RNA-stimulated nucleoside triphosphatase and RNA helicase functional domains of dengue virus type 2 NS3 converge within a region of 20 amino acids.

NS3 protein of dengue virus type 2 has a serine protease domain within the N-terminal 180 residues. NS2B is required for NS3 to form an active protease involved in processing of the viral polyprotein precursor. The region carboxy terminal to the protease domain has conserved motifs present in several viral RNA-stimulated nucleoside triphosphatase (NTPase)/RNA helicases. To define the functional domains of protease and NTPase/RNA helicase activities of NS3, full-length and amino-terminal deletion mutants of NS3 were expressed in Escherichia coli and purified. Deletion of 160 N-terminal residues of NS3 (as in NS3del.2) had no detrimental effect on the basal and RNA-stimulated NTPase as well as RNA helicase activities. However, mutagenesis of the conserved P-loop motif of the RNA helicase domain (K199E) resulted in loss of ATPase activity. The RNA-stimulated NTPase activity was significantly affected by deletion of 20 amino acid residues from the N terminus or by substitutions of the cluster of basic residues, 184RKRK-->QNGN, of NS3del.2, although both mutant proteins retained the conserved RNA helicase motifs. Furthermore, the minimal NS3 protease domain, required for cleavage of the 2B-3 site, was precisely defined to be 167 residues, using the in vitro processing of NS2B-NS3 precursors. Our results reveal that the functional domains required for serine protease and RNA-stimulated NTPase activities map within the region between amino acid residues 160 and 180 of NS3 protein and that a novel motif, the cluster of basic residues 184RKRK, plays an important role for the RNA-stimulated NTPase activity.

Acid Anhydride Hydrolases↗
PubMed1999

Predicting deterioration in patients with lobar haemorrhages.

OBJECTIVE: To study the clinical course and determine predictors of deterioration in patients with lobar haemorrhages). METHODS: A comprehensive review of 61 consecutive patients with lobar haemorrhages was performed. Neurological deterioration was defined as (1) decrease in Glasgow coma sum score by 2 points, (2) new neurological deficit, or (3) clinical signs of brain herniation. A univariate logistic regression was performed and expressed in odds ratios. RESULTS: Sixteen of 61 (26%) patients with lobar haemorrhages deteriorated after admission. In a univariate analysis, only a Glasgow coma score <14 predicted deterioration (75% of deteriorators v 24% who did not deteriorate; p<0.0001). Initial CT characteristics predictive of deterioration included haemorrhage volume >60 ml (63% v 16%, p< 0.0001), shift of the septum pellucidum (75% v 36%, p<0.01), effacement of the contralateral ambient cistern (33% v 0%, p<0.0001), and widening of the contralateral temporal horn (50% v 0%, p<0.0001). Patients presenting and deteriorating within 12 hours of ictus declined due to enlargement of the haemorrhage. Those who deteriorated more than 12 hours after initial neurological symptoms, showed increased mass effect secondary to oedema. CONCLUSION-Patients with lobar haemorrhages presenting immediately after ictus are at risk for deterioration from enlargement of the haemorrhage and predictors of deterioration may be absent. Patients with large volume lobar haemorrhages presenting to the emergency department with decreased level of consciousness and shift on CT are at risk for further deterioration from worsening oedema. These patients require close observation and early aggressive management may be warranted.

Brain↗
PubMed1999

The structural basis of T cell activation by superantigens.

Superantigens (SAGs) are a class of immunostimulatory and disease-causing proteins of bacterial or viral origin with the ability to activate large fractions (5-20%) of the T cell population. Activation requires simultaneous interaction of the SAG with the V beta domain of the T cell receptor (TCR) and with major histocompatibility complex (MHC) class II molecules on the surface of an antigen-presenting cell. Recent advances in knowledge of the three-dimensional structure of bacterial SAGs, and of their complexes with MHC class II molecules and the TCR beta chain, provide a framework for understanding the molecular basis of T cell activation by these potent mitogens. These structures along with those of TCR-peptide/MHC complexes reveal how SAGs circumvent the normal mechanism for T cell activation by peptide/MHC and how they stimulate T cells expressing TCR beta chains from a number of different families, resulting in polyclonal T cell activation. The crystal structures also provide insights into the basis for the specificity of different SAGs for particular TCR beta chains, and for the observed influence of the TCR alpha chain on SAG reactivity. These studies open the way to the design of SAG variants with altered binding properties for TCR and MHC for use as tools in dissecting structure-activity relationships in this system.

Amino Acid Sequence↗
PubMed1999

Stimulation of cystine uptake by nitric oxide: regulation of endothelial cell glutathione levels.

Nitric oxide (NO) is known to produce some of its biological activity through modification of cellular thiols. Return of cellular thiols to their basal state requires the activity of the GSH redox cycle, suggesting important interactions between NO signaling and regulation of cellular redox status. Because continuous exposure to NO may lead to adaptive responses in cellular redox systems, we investigated the effects of NO on cellular GSH levels in vascular endothelial cells. Acute exposure (1 h) of cells to >1 mM S-nitroso-N-acetyl-penicillamine (SNAP) led to depletion of GSH. On the other hand, chronic exposure to lower concentrations of SNAP (</=1 mM) led to a progressive increase in cytosolic GSH, reaching fourfold above basal by 16 h. The mechanism may involve an increase in GSH biosynthesis through effects on biosynthetic enzymes or through increased supply of cysteine, the limiting substrate. In this regard, we report that chronic exposure to SNAP led to a concentration-dependent increase in cystine uptake over a time course similar to that seen for elevation of GSH. The effect of SNAP on cystine uptake was inhibitable by either cycloheximide or actinomycin D, suggesting a requirement for both RNA and protein synthesis. Furthermore, uptake was Na+ independent and was blocked by extracellular glutamate. Extracellular glutamate also blocked SNAP-mediated elevation of cytosolic GSH. Finally, in a coculture model, NO produced by cytokine-pretreated RAW 264.7 cells increased both GSH levels and cystine uptake in naive endothelial cells. These findings strongly suggest that NO leads to adaptive induction of the x-c amino acid transport system, increased cystine uptake, and elevation of intracellular GSH levels.

Animals↗
PubMed1999

Fetal spinal cord tissue in mini-guidance channels promotes longitudinal axonal growth after grafting into hemisected adult rat spinal cords.

Solid fetal spinal cord (FSC) tissue, seeded into semipermeable mini-guidance channels, was tested for the ability to promote axonal growth across the gap created by a midthoracic (T8) hemisection in adult rats. Fetal thoracic spinal cords, at embryonic days 13 to 15, were harvested and gently aspirated into mini-guidance channels (1.25 mm in diameter and 3.0 mm in length). Care was taken to maintain the rostro-caudal orientation of the FSC. In control rats, the FSC-channel construct was exposed to 5 freeze/thaw cycles to produce non-viable grafts before implantation into the hemisected cord. All cases revealed intact tissue cables of various diameters spanning the rostro-caudal extent of the lesion cavity, with integration of host-graft tissues at both interfaces. Immunofluorescence results indicated that numerous neurofilament-positive axons were present within the FSC tissue cable. Double-labeling of a subpopulation of these axons with calcitonin gene-related peptide indicated their peripheral nervous system (PNS) origin. Descending serotonergic and noradrenergic axons were found in the proximity of the rostral host-graft interface, but were not observed to grow into the FSC-graft. Anterograde tracing of propriospinal axons with Phaseolus vulgaris-leucoagglutinin demonstrated that axons had regenerated into the FSC-graft and had traveled longitudinally to the distal end of the channel. Few axons were observed to cross the distal host-graft interface to enter the host spinal cord. Cross-sectional analysis at the midpoint of the tissue cable stained with toluidine blue demonstrated a significant increase (P < 0.01) in myelinated axons in viable FSC grafts (1455 +/- 663, mean +/- S.E.M.; n = 6) versus freeze-thaw control grafts (155 +/- 50; n = 5). In addition to the myelinated axons, many unmyelinated axons were observed in the tissue cable at the electron microscopic level. Areas resembling the PNS with typical Schwann cells, as well as those resembling the central nervous system with neurons and central neuropil, were also seen. In freeze-thaw control grafts, neither viable neurons nor central neuropil were observed. Retrograde tracing with Fast Blue and Diamidino Yellow demonstrated that neurons within the FSC graft extended axons into the host spinal cord at least for 2 mm from both the rostral and caudal host-graft interfaces. We conclude that viable FSC grafts within semipermeable guidance channels may serve both as a permissive bridge for longitudinally directed axonal growth and a potential relay for conveying information across a lesion site in the adult rat spinal cord.

Acrylic Resins↗
PubMed1999

Continuing postischemic neuronal death in CA1: influence of ischemia duration and cytoprotective doses of NBQX and SNX-111 in rats.

BACKGROUND AND PURPOSE: Transient forebrain ischemia results in a 24- to 72-hour delayed loss of CA1 neurons. Previous work has not assessed whether insult durations can vary the degree and maturation rate of CA1 injury and whether there are different ultrastructural features of death after brief or severe ischemia. We also tested whether known cytoprotective drugs achieve permanent or transient neuroprotection. METHODS: In the first experiment, ischemia was induced for 5, 15, or 30 minutes with the use of the 4-vessel occlusion rat model with 1- to 28-day survival. Others subjected to 5 or 15 minutes of ischemia and allowed to survive for 14 or 7 days, respectively, were examined with electron microscopy. Finally, we determined whether NBQX (30 mg/kg x3 at 0 or 6 hours after ischemia), an AMPA antagonist, and SNX-111 (5 mg/kg at 6 hours after ischemia), an N-type Ca2+ channel antagonist, provided enduring CA1 protection against 10 minutes of ischemia. RESULTS: CA1 damage was not detected at 24 hours. Thirty minutes of ischemia produced 47% and 84% CA1 damage at 2 and 3 days, respectively. A 15-minute occlusion yielded 11%, 74%, and 86% loss at 2, 3, and 7 days, respectively. Five minutes of ischemia produced an even slower progression with 24%, 52%, and 59% loss at 3, 7, and 14 days, respectively. Ultrastructural examination after 5 and 15 minutes of ischemia revealed necrosis with no morphological evidence of apoptosis. Both NBQX (P<0.021) and SNX-111 (P<0.001) significantly reduced CA1 death at 7 days (</=35%) but not at 28 days (>/=80%) compared with saline treatment ( approximately 79%). CONCLUSIONS: Brief forebrain ischemia results in a slower progression of CA1 loss than more severe insults. Nonetheless, neuronal injury had necrotic, not apoptotic, morphology. NBQX and SNX-111 only postponed CA1 injury.

Animals↗
PubMed1999

Primary hypoxic tolerance and chemical preconditioning during estrus cycle in mice.

BACKGROUND AND PURPOSE: Exogenous application of estrogens or progesterone ameliorates hypoxic/ischemic cell damage. This study investigates whether values of primary and induced hypoxic tolerance vary endogenously during the estrus cycle in female mice. METHODS: Population spike amplitude (PSA) and NADH were measured during hypoxic hypoxia and recovery in hippocampal slices from untreated control animals (C slices) and slices prepared from animals pretreated in vivo with a single intraperitoneal injection of 3-nitropropionate (3NP) (3NP slices) or acetylsalicylate (ASA) (ASA slices). RESULTS: Posthypoxic recovery of PSA was dose dependent in 3NP slices from males, with maximal recovery on pretreatment attained with 20 mg/kg 3NP (82+/-32% [mean+/-SD]; C slices, 38+/-29%; P<0.01). PSA recovered to 17+/-12% in C slices during proestrus, 43+/-23% during estrus, and 63+/-44% during diestrus. In 3NP slices, recovery of PSA increased to 57+/-36% (P<0. 05) during proestrus. Hypoxic tolerance was not increased in other stages of the estrus cycle. Hypoxic NADH increase during proestrus declined from 212+/-76% in C slices to 133+/-11% in 3NP slices (P<0. 05). Recovery of PSA in ASA slices was 75+/-36% (P<0.01 versus control) in males and 48+/-34% during proestrus (P<0.05 versus ASA slices from males). CONCLUSIONS: Primary and induced hypoxic tolerance are endogenously modulated during the estrus cycle. Differences in hypoxic oxidative energy metabolism mediate part of the differential tolerance. Experimental and clinical therapeutic strategies against cerebral ischemia/hypoxia need to consider sex-related dependence.

Action Potentials↗
PubMed1999

Astrocyte reaction in the rat vestibular nuclei after unilateral removal of Scarpa's ganglion.

Unilateral vestibular ganglionectomy (UVG) results in a complete degeneration of vestibular nerve fibers and terminals in the ipsilateral vestibular nuclear complex (VNC). A subsequent glial reaction may affect the activities of VNC neurons and thereby influence compensation for lesion-induced vestibular disorders. Expression of glial fibrillary acidic protein (GFAP), a specific marker for reactive astrocytes, was demonstrated immunohistochemically in the rat VNC at 7, 14, and 35 days after UVG. An increased GFAP-positive astrocytic response was evident at 7 days after lesion in all the VNC regions on the lesioned side and in some regions on the unlesioned side and remained through 35 days. The glial response included hypertrophy, which was more prominent at 7 days than at 14 days or 35 days, and proliferation, more prominent at the later times, of GFAP-positive astrocytes. Astrocytic projections around VNC neuron somata and proximal dendrites increased in number and became thicker and more elongated, especially at 14 days, in the lateral vestibular nucleus. It is suggested that UVG results in a bilateral astrocytic reaction in the VNC that would affect the subsequent compensation.

Animals↗