Biomedical subjects

F Xu

Publications and source records attributed to F Xu.

At least 199 records · Page 11Linked to original sources

PubMed1998

Radiation fields backscattered from material interfaces: I. Biological effectiveness.

Confluent cultures of CHO-K1 and CHO-xrs5 cells were irradiated attached to 6 microm Mylar with 137Cs gamma rays and 200 kVp X rays adjacent to scattering materials consisting of polystyrene, glass, aluminum, copper, tin and lead. The absorbed dose in cell nuclei was estimated from measurements of backscattered dose made with a parallel-plate ion chamber with a 5-microm Mylar window and a gas volume whose thickness was equivalent to approximately 2.6 microm of cells or tissue. Cell inactivation after various doses was measured by clonogenic assays after trypsinization and enumeration. Survival curves constructed from data pooled from at least two independent experiments were best fitted to a linear-quadratic (LQ) or a linear equation for CHO-K1 and CHO-xrs5 cells, respectively. An average distance of 9.3+/-1.9 microm from the scattering surfaces to the midline of nuclei for both the cell lines was estimated from electron micrographs of fixed cell sections. The major differences in biological effect observed when the cells were irradiated adjacent to these materials could be largely explained by the differences in the physical dose. Further analyses using the LQ equation suggested additional biological effects with implications for the mechanisms involved. CHO-K1 cells showed a small but consistent increase in the low-dose (alpha-inactivation coefficient) mechanism for both radiations scattered from high-Z material. An increased value of the alpha coefficient suggests an increase in RBE which could be associated with a higher proportion of low-energy and track-end electrons in these fields. The radiation fields which produced maximum single-hit killing in CHO-K1 cells also produced less killing by the quadratic (beta-inactivation coefficient) mechanism. In contrast, when similarly irradiated, CHO-xrs5 cells exhibited significantly lower alpha coefficients of inactivation. The mechanistic basis for this opposite effect of backscattered radiations in these cell lines is as yet unknown.

Animals↗

PubMed1997

Expression and mutational analysis of the DCC, DPC4, and MADR2/JV18-1 genes in neuroblastoma.

Loss of heterozygosity (LOH) on chromosome 18q21 is found frequently in various human cancers. Three candidate tumor suppressor genes, DCC (deleted in colorectal carcinomas), DPC4 (deleted in pancreatic carcinomas, locus 4), and MADR2/JV18-1 (MAD-related gene 2), have been cloned and identified from this chromosome region. We have reported recently that LOH on chromosome 18q is observed frequently in neuroblastoma. Alterations of DCC are involved in many human tumors. DPC4 and MADR2/JV18-1 are recently demonstrated to be altered in pancreatic and colorectal cancers, respectively. To confirm if inactivation of the DCC, DPC4, and MADR2/JV18-1 genes is involved in the pathogenesis of neuroblastoma and to clarify the mechanism of inactivation, we analyzed the expression of DCC, DPC4, and MADR2/JV18-1 in neuroblastoma cell lines and primary tumors by reverse transcription-PCR and investigated the mutations in the coding regions of these genes by PCR/reverse transcription-PCR single-strand conformation polymorphism. We found that 12 of 25 (48%) cell lines and 14 of 32 (44%) primary tumors, including 3 with 18q LOH, had absent or reduced expression of DCC mRNA. Expression was more likely to be reduced in advanced (67%) than in early stage neuroblastomas (24%) (P = 0.036), suggesting that inactivation of the DCC gene plays an important role in the progression of neuroblastoma. Altered expression of DPC4 was found in six (24%) cell lines and six (19%) tumors. MADR2/JV18-1 expression was reduced or absent only in four (16%) cell lines and three (9%) tumors. Mutations of the DCC genes were examined in 25 of 29 exons in neuroblastoma cell lines, and those exons in which mutations were found were further examined in primary tumors. We found missense mutations of AAC (Asn) to AGC (Ser) at DCC codon 176 in one cell line and ACC (Thr) to ATC (Ile) at codon 1105 in one cell line and tumor, respectively; polymorphisms of CGA (Arg) to GGA (Gly) at codon 201 and TTT (Phe) to TTG (Leu) at codon 951 in most of the cell lines and tumors; and a silent mutation of GAG (Glu) to GAA (Glu) at codon 118 in four cell lines and five primary tumors. We did not identify any mutations in the DPC4 and MADR2/JV18-1 genes in neuroblastoma. Our results suggested that mutations of the DCC gene may be involved in the pathogenesis of neuroblastomas but failed to account for the relatively high frequency of the altered expression, implying that other mechanisms are responsible for the inactivation of the DCC gene in neuroblastoma. Low frequency of reduced or absent mRNA expression and lack of mutations in DPC4 and MADR2/JV18-1 genes suggested a limited role for these two genes in neuroblastoma.

Cell Adhesion Molecules↗

PubMed1997

Reduction of metastatic properties of BL6 melanoma cells expressing terminal fucose(alpha)1-2-galactose after alpha1,2-fucosyltransferase cDNA transfection.

We reported previously that transfection of BL6 melanoma cells that do not express the alpha1,3-galactosyltransferase (alpha1,3GT) gene with the alpha1,3GT cDNA resulted in synthesis and expression of alpha-galactosyl epitopes (Gal(alpha)1-3Gal(beta)1-4GlcNAc-R) and an impairment of their metastatic potentials. It was of interest to test whether inhibition of metastatic properties of BL6 melanoma cells is specifically associated with the appearance of the terminal alpha-Gal or whether capping N-acetyllactosamine with another oligosaccharide would also affect the metastatic properties of BL6 melanoma cells. For this purpose, BL6-2 clone isolated from B16BL6 melanoma was transfected with the alpha1,2-fucosyltransferase (alpha1,2FT) cDNA. The alpha1,2FT catalyzes a transglycosylation reaction, resulting in syntheses of the Fuc(alpha)1-2Gal(beta)1-4GlcNAc-R structure, which is known as the H antigen of O blood group in humans and is also synthesized in some cells of mice. Transfection of BL6 melanoma cells with the alpha1,2FT cDNA resulted in the appearance of the terminal Fuc(alpha)1-2Gal(beta)1-4GlcNAc-R epitopes reacting with the Ulex europaeus agglutinin lectin. In parallel, the transfected cells showed a decrease in N-acetyllactosamine sialylation. Decline in sialylation of the transfected cells is likely to be the result of competition between alphal,2FT and alpha2,3- or alpha2,6-sialyltransferases for the common substrate N-acetyllactosamine (Gal(beta)1-4GlcNAc-R) on N-linked carbohydrate chains of glycoproteins and glycolipids. The alpha1,2FT-transfected BL6-2 cells showed an increase in homotypic aggregation. In parallel, metastatic ability of the alpha1,2FT-transfected BL6-2 cells was reduced significantly in the immunocompetent as well as immunosuppressed (X-irradiated) mice. Thus, these data imply that capping N-acetyllactosamine with alphaGal or alphaFuc and the corresponding reduction in sialylation of BL6-2 melanoma cells were associated with reduction of their metastatic potential.

Animals↗

PubMed1997

Effects of redox potential and hydroxide inhibition on the pH activity profile of fungal laccases.

The electronic absorption spectrum, susceptibility to fluoride inhibition, redox potential, and substrate turnover of several fungal laccases have been explored as a function of pH. The laccases showed a single spectrally detectable acid-base transition at pH 6-9 and a fluoride inhibition that diminished by increased pH (indicating a competition with hydroxide inhibition). Relatively small changes in the redox potentials (< or = 0.1 V) of laccase were observed over the pH 2.7-11. Under the catalysis of laccase, the apparent oxidation rates (kcat and kcat/Km) of two nonphenolic substrates, potassium ferrocyanide and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid), decreased monotonically as the pH increased. In contrast, the apparent oxidation rates (kcat and kcat/Km) of three 2,6-dimethoxyphenols (whose pKa values range from 7.0 to 8.7) exhibited bell-shaped pH profiles whose maxima were distinct for each laccase but independent of the substrate. By correlating these pH dependences, it is proposed that the balance of two opposing effects, one generated by the redox potential difference between a reducing substrate and the type 1 copper of laccase (which correlates to the electron transfer rate and is favored for a phenolic substrate by higher pH) and another generated by the binding of a hydroxide anion to the type 2/type 3 coppers of laccase (which inhibits the activity at higher pH), contributes to the pH activity profile of the fungal laccases.

Fungi↗

PubMed1997

Is OVX1 a suitable marker for endometrial cancer?

The single most common cause leading to the diagnosis of endometrial cancer is postmenopausal bleeding. Although most patients with early-stage disease (FIGO stage I and II) can be cured, prognosis worsens considerably with increasing stage. While serum CA 125 levels are elevated only in a significant proportion of patients with advanced disease, recently a new serum marker (OVX1) for the detection of early-stage endometrial cancer was reported. Serum OVX1 levels were measured using an OVX1 radioimmunoassay (RIA) or enzyme immunoassay (EIA) in 192 patients with endometrial cancer. CA 125 levels were measured in 112 patients using the CIS ELSA CA 125 kit. Apparently healthy females had mean serum OVX1 levels measured with the OVX1-EIA of 1.34 +/- 0.74 U/ml, while patients with endometriosis had mean OVX1 serum levels of 3.15 +/- 2.45 U/ml. The mean OVX1 serum level for endometrial cancer patients was 2.00 +/- 1.32 U/ml. These values were 2.76 +/- 1.62, 6.10 +/- 4.66, and 5.37 +/- 3.49, respectively, using the OVX1-RIA assay. Applying a cutoff value of 2.8 U/ml, serum OVX1-EIA levels in endometrial cancer patients were increased in 25 of 127 patients (19.7%) with stage I disease, 5 of 17 patients with stage II (29.4%), 5 of 22 patients (22.7%) with stage III, and 4 of 11 patients (36.4%) with stage IV disease. Using the OVX1-RIA and a cutoff of 7.2 U/ml, serum levels were increased in 22 of 127 (17.3%) stage I, 6 of 17 (35.3%) stage II, 5 of 22 (22.7%) stage III, and 6 of 11 (54.5%) stage IV patients. Serum CA 125 levels, determined in a total of 112 patients, were elevated above 35 U/ml in 12 of 79 patients (15.2%) with stage I, 4 of 12 patients (33.3%) with stage II, 8 of 13 patients (61.5%) with stage III, and all of 8 patients (100%) with stage IV disease. While a good correlation between serum CA 125 levels and the clinical stage of the disease was found, no correlation could be detected for OVX1 and stage.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1997

Protein stability and conformational rearrangements in lipid bilayers: linear gramicidin, a model system.

The replacement of four tryptophans in gramicidin A by four phenylalanines (gramicidin M) causes no change in the molecular fold of this dimeric peptide in a low dielectric isotropic organic solvent, but the molecular folds are dramatically different in a lipid bilayer environment. The indoles of gramicidin A interact with the anisotropic bilayer environment to induce a change in the molecular fold. The double-helical fold of gramicidin M, as opposed to the single-stranded structure of gramicidin A, is not compatible with ion conductance. Gramicidin A/gramicidin M hybrid structures have also been prepared, and like gramicidin M homodimers, these dimeric hybrids appear to have a double-helical fold, suggesting that a couple of indoles are being buried in the bilayer interstices. To achieve this equilibrium structure (i.e., minimum energy conformation), incubation at 68 degrees C for 2 days is required. Kinetically trapped metastable structures may be more common in lipid bilayers than in an aqueous isotropic environment. Structural characterizations in the bilayers were achieved with solid-state NMR-derived orientational constraints from uniformly aligned lipid bilayer samples, and characterizations in organic solvents were accomplished by solution NMR.

Dimerization↗

PubMed1997

Knockout of the vesicular monoamine transporter 2 gene results in neonatal death and supersensitivity to cocaine and amphetamine.

Vesicular monoamine transporters are known to transport monoamines from the cytoplasm into secretory vesicles. We have used homologous recombination to generate mutant mice lacking the vesicular monoamine transporter 2 (VMAT2), the predominant form expressed in the brain. Newborn homozygotes die within a few days after birth, manifesting severely impaired monoamine storage and vesicular release. In heterozygous adult mice, extracellular striatal dopamine levels, as well as K+- and amphetamine-evoked dopamine release, are diminished. The observed changes in presynaptic homeostasis are accompanied by a pronounced supersensitivity of the mice to the locomotor effects of the dopamine agonist apomorphine, the psychostimulants cocaine and amphetamine, and ethanol. Importantly, VMAT2 heterozygous mice do not develop further sensitization to repeated cocaine administration. These observations stress the importance of VMAT2 in the maintenance of presynaptic function and suggest that these mice may provide an animal model for delineating the mechanisms of vesicular release, monoamine function, and postsynaptic sensitization associated with drug abuse.

Amphetamine↗

PubMed1997

Cardiolipin remodeling in a Chinese hamster lung fibroblast cell line deficient in oxidative energy production.

The metabolism of cardiolipin was investigated in a Chinese hamster lung fibroblast cell line CCL16-B2 deficient in oxidative energy metabolism and its parental cell line CCL16-B1. Mitochondrial enzyme activities involved in de novo cardiolipin biosynthesis were elevated in CCL16-B2 cells compared with CCL16-B1 cells, indicating initially an elevation in cardiolipin biosynthesis. Content of all phospholipids, including cardiolipin and its precursors, and high energy nucleotides were unaltered in CCL16-B2 cells compared to CCL16-B1 cells. When cells were incubated with [1,3-(3)H]glycerol for up to 4 h radioactivity incorporated into cardiolipin in CCL16-B2 cells did not differ compared with CCL16-B1 cells. In contrast, radioactivity incorporated into phosphatidylglycerol, the immediate precursor of cardiolipin, was elevated over 2-fold in CCL16-B2 cells compared with CCL16-B1 cells. Analysis of the fatty acid molecular species in cardiolipin revealed alterations in the level of unsaturated but not saturated fatty acids in B2 compared with B1 cells. In vivo cardiolipin remodeling, that is, the deacylation of cardiolipin to monolysocardiolipin followed by reacylation back to cardiolipin, with [1-(14)C]palmitate and [1-(14)C]oleate and in vitro mitochondrial phospholipid remodeling with [1-(14)C]linoleate were altered in CCL16-B2 cells compared to CCL16-B1 cells. Since both the appropriate content and molecular composition of cardiolipin is required for optimum mitochondrial oxidative phosphorylation, we suggest that the difference in CL molecular species composition observed in CCL16-B2 cells, mediated by alterations in in vivo cardiolipin remodeling, may be one of the underlying mechanisms for the reduction in oxidative energy production in CCL16-B2 cells.

Animals↗

PubMed1997

Plant-derived vaccine protects target animals against a viral disease.

The successful expression of animal or human virus epitopes on the surface of plant viruses has recently been demonstrated. These chimeric virus particles (CVPs) could represent a cost-effective and safe alternative to conventional animal cell-based vaccines. We report the insertion of oligonucleotides coding for a short linear epitope from the VP2 capsid protein of mink enteritis virus (MEV) into an infectious cDNA clone of cowpea mosaic virus and the successful expression of the epitope on the surface of CVPs when propagated in the black-eyed bean, Vigna unguiculata. The efficacy of the CVPs was established by the demonstration that one subcutaneous injection of 1 mg of the CVPs in mink conferred protection against clinical disease and virtually abolished shedding of virus after challenge with virulent MEV, demonstrating the potential utility of plant CVPs as the basis for vaccine development. The epitope used occurs in three different virus species-MEV, canine parvovirus, and feline panleukopenia virus- and thus the same vaccine could be used in three economically important viral hosts-mink, dogs, and cats, respectively.

Amino Acid Sequence↗

PubMed1997

Multiple myeloma cells are protected against dexamethasone-induced apoptosis by insulin-like growth factors.

Multiple myeloma cell lines express functional receptors for insulin-like growth factors (IGFs) and several cell types that make up the bone marrow microenvironment produce these cytokines. This suggests that IGFs may play a role in survival and/or expansion of the malignant clone within the marrow in patients with multiple myeloma. We tested the effects of these growth factors on myeloma cells challenged with dexamethasone. Dye exclusion and MTT assays demonstrated that both IGF-I and IGF-II protected the 8226 and dox-40 myeloma cell lines and three primary myeloma cultures from dexamethasone-induced cytotoxicity in a dose-dependent fashion. Morphologic studies of target cells and their nuclei as well as DNA electrophoresis confirmed the IGFs afforded protection against dexamethasone-induced apoptosis. Insulin also protected but was less impressive and required much higher concentrations. IGFs also protected against cycloheximide-induced apoptosis but were ineffective against serum starvation, topoisomerase II inhibitors, or anti-fas antibodies. IGF-induced protection against dexamethasone was not associated with any alteration in quantitative or qualitative expression of BCL-2, BAX or BCL-X proteins. These data indicate that insulin-like growth factors may play a role in maintenance of the malignant clone in patients with myeloma by protecting tumour cells from apoptotic death.

Animals↗

PubMed1997

Molecular cloning of a lobster G alpha(q) protein expressed in neurons of olfactory organ and brain.

We have isolated from an American lobster (Homarus americanus) olfactory organ cDNA library a clone, hG alpha(q), with >80% identity to mammalian and arthropod G alpha(q) sequences. In brain and olfactory organ, hG alpha(q) mRNA was expressed predominantly in neurons, including virtually all the neuronal cell body clusters of the brain. G alpha(q) protein was also expressed broadly, appearing on western blots as a single band of 46 kDa in brain, eyestalk, pereiopod, dactyl, tail muscle, olfactory organ, and aesthetasc hairs. These results suggest that hG alpha(q) plays a role in a wide variety of signal transduction events. Its presence in the olfactory aesthetasc hairs, which are almost pure preparations of the outer dendrites of the olfactory receptor neurons, the expression of a single hG alpha(q) mRNA species (6 kb) in the olfactory organ, and the localization of hG alpha(q) mRNA predominantly in the olfactory receptor neurons of the olfactory organ strongly suggest that one function of hG alpha(q) is to mediate olfactory transduction.

Animals↗

PubMed1997

Molecular cloning and characterization of a lobster G alphaS protein expressed in neurons of olfactory organ and brain.

We have isolated from an American lobster (Homarus americanus) olfactory organ cDNA library a clone, lobG alphaS, with >70% identity to mammalian and arthropod G alphaS sequences. In genomic Southern blots, a fragment of lobG alphaS detected only one band, suggesting the lobsters have a single G alphaS gene. In brain and olfactory organ, lobG alphaS mRNA was expressed predominantly in neurons, including many of the neuronal cell body clusters of the brain. G alphaS protein was also expressed broadly, appearing on western blots as a band of 51.8 kDa in brain, eyestalk, pereiopod, dactyl, tail muscle, olfactory organ, and aesthetasc hairs. These results suggest that lobG alphaS plays a role in a wide variety of signal transduction events. Its presence in the olfactory aesthetasc hairs, which are almost pure preparations of the outer dendrites of the olfactory receptor neurons, and the expression of lobG alphaS mRNA in the olfactory receptor neurons of the olfactory organ indicate that lobG alphaS may mediate olfactory transduction. That virtually all ORNs express lobG alphaS mRNA equally predicts that hyperpolarizing odor responses mediated by cyclic AMP are a property of all lobster olfactory receptor neurons.

Amino Acid Sequence↗

PubMed1997

Competition between adjacent meiotic recombination hotspots in the yeast Saccharomyces cerevisiae.

In a wild-type strain of Saccharomyces cerevisiae, a hotspot for meiotic recombination is located upstream of the HIS4 gene. An insertion of a 49-bp telomeric sequence into the coding region of HIS4 strongly stimulates meiotic recombination and the local formation of meiosis-specific double-strand DNA breaks (DSBs). When strains are constructed in which both hotspots are heterozygous, hotspot activity is substantially less when the hotspots are on the same chromosome than when they are on opposite chromosomes.

Alcohol Oxidoreductases↗

PubMed1997

Mapping of the target antigens of the rotavirus-specific cytotoxic T cell response.

The cytotoxic T cell (CTL) response in C57/B16 (H-2b) mice to rotavirus has been analysed using a cognate set of vaccinia virus recombinants covering the 12 primary gene products of the UKtc strain of bovine rotavirus. The gene products of RNA segments 5 (VP5/NSP-1) and 8 (VP7) both elicited a classic CD8+ Class I MHC restricted CTL response. Using L cells transfected with specific Class I MHC loci as targets the VP5/NSP-1 response was found to be restricted at Db and the VP7 response at Kb. Vaccinia virus recombinants expressing VP7 genes from seven G serotypes were used to show that the CTL response to this antigen is completely cross-reactive. By contrast, using the same strategy the CTL response to VP5/NSP-1 was found to be virus strain specific. A vaccinia virus recombinant carrying RNA segment 5 from the deletion mutant P9D delta 5 was used to localize at least one CTL epitope in VP5/ NSP-1 to the first 150 amino acids of the protein. The expression of a number of fragments of VP7 in vaccinia virus recombinants was used to show that the CTL epitope (amino acids 31-40) previously identified through the use of synthetic peptides is virus serotype specific rather than cross-reactive.

Animals↗

PubMed1997

Characterization of the gene encoding an extracellular laccase of Myceliophthora thermophila and analysis of the recombinant enzyme expressed in Aspergillus oryzae.

A genomic DNA segment encoding an extracellular laccase was isolated from the thermophilic fungus Myceliophthora thermophila, and the nucleotide sequence of this gene was determined. The deduced amino acid sequence of M. thermophila laccase (MtL) shows homology to laccases from diverse fungal genera. A vector containing the M. thermophila laccase coding region, under transcriptional control of an Aspergillus oryzae alpha-amylase gene promoter and terminator, was constructed for heterologous expression in A. oryzae. The recombinant laccase expressed in A. oryzae was purified to electrophoretic homogeneity by anion-exchange chromatography. Amino-terminal sequence data suggests that MtL is synthesized as a preproenzyme. The molecular mass was estimated to be approximately 100 to 140 kDa by gel filtration on Sephacryl S-300 and to be 85 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Carbohydrate analysis revealed that MtL contains 40 to 60% glycosylation. The laccase shows an absorbance spectrum that is typical of blue copper oxidases, with maxima at 276 and 589 nm, and contains 3.9 copper atoms per subunit. With syringaldazine as a substrate, MtL has optimal activity at pH 6.5 and retains nearly 100% of its activity when incubated at 60 degrees C for 20 min. This is the first report of the cloning and heterologous expression of a thermostable laccase.

Aspergillus oryzae↗

PubMed1997

Respiratory-related neurons of the fastigial nucleus in response to chemical and mechanical challenges.

Responses of cerebellar respiratory-related neurons (CRRNs) within the rostral fastigial nucleus and the phrenic neurogram to activation of respiratory mechano- and chemoreceptors were recorded in anesthetized, paralyzed, and ventilated cats. Respiratory challenges included the following: 1 ) cessation of the ventilator for a single breath at the end of inspiration (lung inflation) or at functional residual capacity, 2) cessation of the ventilator for multiple breaths, and 3) exposure to hypercapnia. Nineteen CRRNs having spontaneous activity during control conditions were characterized as either independent (basic, n = 14) or dependent (pump, n = 5) on the ventilator movement. Thirteen recruited CRRNs showed no respiratory-related activity until breathing was stressed. Burst durations of expiratory CRRNs were prolonged by sustained lung inflation but were inhibited when the volume was sustained at functional residual capacity; it was vice versa for inspiratory CRRNs. Multiple-breath cessation of the ventilator and hypercapnia significantly increased the firing rate and/or burst duration concomitant with changes noted in the phrenic neurogram. We conclude that CRRNs respond to respiratory inputs from CO2 chemo- and pulmonary mechanoreceptors in the absence of skeletal muscle contraction.

Animals↗

PubMed1997

Involvement of the fastigial nuclei in vagally mediated respiratory responses.

Previous studies have demonstrated that the cerebellum, especially the fastigial nucleus (FN), is capable of modulating respiratory responses to chemical and mechanical stimuli. Because there is evidence to show projections from vagal afferents to the FN, the goal of this study was to determine the role of the FN in the respiratory reflexes elicited by activation of vagal afferents. Experiments were performed in anesthetized (chloralose), paralyzed, and artificially ventilated cats with an occipital exposure of the cerebellum. Administration of capsaicin (Cap; 5-10 micrograms/kg) via the right external jugular vein at the end of inspiration and application of lung inflation (LI; 10 cmH2O) during inspiration were carried out to stimulate nonmyelinated and myelinated vagal afferents, respectively. The phrenic neurogram was recorded as an index of the respiratory motor output. Control cardiorespiratory variables [expiratory duration (TE), arterial blood pressure] and their immediate responses to stimuli were compared before and after bilateral lesions of the FN. The results showed the following. 1) Cap injection and LI resulted in a dramatic increase in TE (apnea). 2) FN lesions did not significantly alter the control TE; however, the apneic duration induced by Cap injection was prolonged. 3) Neither FN lesions nor cerebellectomy affected the apneic duration that resulted from application of LI. 4) Cold blockade of the vagi (6-8 degrees C) eliminated the respiratory responses elicited by LI but not Cap injection; vagotomy abolished the responses to both stimuli. 5) FN lesions did not change the control ABP or its responses to either LI or Cap injection. It is concluded that the FN is involved in vagally mediated respiratory reflexes elicited by activation of nonmyelinated (C-fiber) vagal afferents.

Animals↗

PubMed1997

Cerebellar modulation of cough motor pattern in cats.

Cerebellar modulation of cough motor pattern in cats. J. Appl. Physiol. 83(2): 391-397, 1997.-The cerebellum modulates respiratory muscle activity in part via its influence on the central respiratory pattern generator. Because coughing requires well-coordinated respiratory muscle activity, studies were conducted to determine whether the cerebellum influences the centrally generated cough motor pattern. Integrated phrenic and lumbar efferent neurograms (PN and LN, respectively) were monitored in decerebrated, paralyzed, and ventilated cats. Mechanical probing of the intrathoracic trachea was used to evoke fictive coughs; i.e., large increases in PN and LN amplitudes. Cerebellectomy resulted in a decrease in the number of coughs per trial (cough frequency) and LN peak amplitudes without any consistent change in PN peak amplitudes. Cerebellar nuclei [the rostral interposed nucleus (INr) and the rostral fastigial nucleus (FNr)] known to be involved in respiratory control were ablated to determine their potential role in the cough response. Control (eupneic) respiratory frequency was not affected by cerebellectomy or INr/FNr lesions. Cough frequency was depressed by lesion of the INr but not by ablation of the FNr. No significant changes in PN and LN amplitudes were observed after lesion of either the INr or FNr. These results suggest that the cerebellum, specifically the INr, is involved in modulation of the frequency of centrally generated coughing.

Animals↗