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P H Patterson

Publications and source records attributed to P H Patterson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cytokine and growth factor involvement in schizophrenia--support for the developmental model.

Medical treatment with various cytokines can provoke psychiatric symptoms. Conversely, psychiatric patients can display abnormalities in cytokine and neurotrophic factor expression. Such observations have pointed to the potential contribution of cytokines and growth factors to schizophrenic pathology and/or etiology. The cellular targets of the relevant factors and the nature of their actions remain to be explored in mental illness, however. Recent physiological studies demonstrate that cytokines and neurotrophic factors can markedly influence synaptic transmission and plasticity upon acute or chronic application. Moreover, many of the molecular alterations observed in the schizophrenic brain are consistent with abnormalities in cytokine and neurotrophic factor regulation of these molecules. In this review, we summarize these molecular pathology findings for schizophrenia and highlight the neurodevelopmental activities of cytokines and neurotrophic factors that may contribute to the etiology or pathology of this illness.

Animals↗
PubMed2000

Leukaemia inhibitory factor is required for normal inflammatory responses to injury in the peripheral and central nervous systems in vivo and is chemotactic for macrophages in vitro.

The cytokine leukaemia inhibitory factor (LIF) is up-regulated in glial cells after injury to the peripheral and central nervous systems. In addition, LIF is required for the changes in neuropeptide expression that normally occur when the axons of sympathetic and sensory neurons are transected. We investigated whether LIF is also necessary for the initial inflammatory response that follows mechanical injury to the sciatic nerve and cerebral cortex of adult mice. We find that inflammatory cell infiltration into crushed sciatic nerve is significantly slower in LIF knock-out (KO) mice compared with wild-type (WT) mice. Similarly, the microglial and astroglial responses to surgical injury of the cortex are significantly slower in LIF KO mice compared with WT mice. Consistent with these in vivo results, LIF is chemotactic for peritoneal macrophages in a microchamber culture assay. Thus, LIF is a key regulator of neural injury in vivo, where it is produced by glia and can act directly on neurons, glia and inflammatory cells. We also find that the initial inflammatory response to cortical injury is diminished in interleukin (IL)-6 KO mice. Surprisingly, however, the inflammatory response in LIF-IL-6 double KO mice is very similar to that of the single KO mice, suggesting that these cytokines may act in series rather than in parallel in this response.

Animals↗
PubMed2000

Nutritional value of enzyme- or sodium hydroxide-treated feathers from dead hens.

Two feather digestion processes to remove the feathers from the carcasses of dead hens were evaluated for their impact on the nutritional quality of the resulting feather meal. There were three treatments: control (untreated feathers), a feather-digesting enzyme, and NaOH treatment. Both enzyme- and NaOH-treated feathers were easily separated from the hen carcasses. The CP level of enzyme-treated feathers after autoclaving (49.90%) was significantly less than the control and NaOH-treated feathers (94.48 and 87.31%, respectively) because of elevated ether extract levels resulting from skin and abdominal fat release during the 12-h enzyme incubation. Before autoclaving, pepsin digestibilities of enzyme- and NaOH-treated feathers were significantly higher than the control. However, after autoclaving, no significant difference was found in pepsin digestibility between the control and enzyme treatments or control and NaOH treatments. The typical limiting amino acids, methionine, lysine, and histidine, in feathers were present at greater levels in the resulting enzyme-feather meal (E-FM) compared with the NaOH-feather meal (N-FM) or control-feather meal (C-FM) on a percentage of CP basis. Cystine levels, however, were significantly lower in the E-FM and N-FM compared with that of the C-FM. In chick bioassays, no significant differences were found in protein efficiency ratio (PER) and net protein ratio (NPR) among C-FM, E-FM, and N-FM. The AMEn of E-FM (4.52 kcal/g) was significantly higher than the C-FM (3.58) or N-FM (2.79). These findings indicated that although enzyme treatment could improve the nutritional quality of feathers from dead hens, NaOH treatment was a more rapid means of separating feathers from the carcass.

Animal Feed↗
PubMed2000

Recycling dead hens by enzyme or sodium hydroxide pretreatment and fermentation.

This study was conducted to evaluate the recycling of whole dead hens into feed ingredients by enzyme or sodium hydroxide pretreatment and fermentation. Evaluation criteria included nutrient preservation, pathogenic microorganism elimination, and assays of nutritional quality. The pH levels of enzyme- and NaOH-treated hen carcasses decreased from 6.01 and 7.66 to 4.18 and 4.24, respectively, during the 21-d fermentation. Hydrogen sulfide levels were not detected on Days 1 and 3 from the enzyme treatment; however, high levels (800 ppm) were measured from the NaOH treatments. By Day 21, H2S levels of both treatments had decreased to 78 ppm. The control, enzyme, and NaOH treatments before fermentation contained high levels of Escherichia coli and Staphylococcus aureus; however, after fermentation, these potential pathogens were eliminated in the enzyme and NaOH treatments. Levels of CP, EE, and ash of the control product were higher than either the enzyme or NaOH treatment. NaOH reduced pepsin digestibility by 11% compared to the enzyme treatment. In a bioassay, the chicks fed control autoclaved hen meal (CHM) had higher (P < 0.05) feed intake, weight gain, protein efficiency ratio (PER), and net protein ratio (NPR) than enzyme-treated, fermented, and autoclaved hen meal (EHM) or NaOH-treated, fermented, and autoclaved hen meal (NHM). However, the AMEn of the CHM and EHM were higher than the NHM (P < 0.05) when evaluated using mature cockerels. These results indicated that fermentation processing of dead hens reduced the concentration of some nutrients and depressed growth performance when hen meals were fed to young chicks.

Amino Acids↗
PubMed1999

An endothelin receptor B antagonist inhibits growth and induces cell death in human melanoma cells in vitro and in vivo.

Activation of the endothelin receptor B (ETRB) in cultured melanocyte precursors promotes cell proliferation while inhibiting differentiation, two hallmarks of malignant transformation. We therefore tested whether ETRB has a similar role in malignant transformation of melanoma. When tested in culture, we find that the selective ETRB antagonist BQ788 can inhibit the growth of seven human melanoma cell lines, but not a human kidney cell line. This inhibition often is associated with increases in pigmentation and in the dendritic shape that is characteristic of mature melanocytes. In three cell lines we also observe a major increase in cell death. In contrast, the endothelin receptor A (ETRA) antagonist BQ123 does not have these effects, although all the cell lines express both ETRA and ETRB mRNA. Extending these studies in vivo, we find that administration of BQ788 significantly slows human melanoma tumor growth in nude mice, including a complete growth arrest in half of the mice treated systemically. Histological examination of tumor sections suggests that BQ788 also enhances melanoma cell death in vivo. Thus, ETRB inhibitors may be beneficial for the treatment of melanoma.

Animals↗
PubMed1999

Morphological domains of Lewis-X/FORSE-1 immunolabeling in the embryonic neural tube are due to developmental regulation of cell surface carbohydrate expression.

The Lewis-X (LeX) carbohydrate epitope, recognized by the FORSE-1 monoclonal antibody (mAb), shares expression boundaries with neural regulatory genes and may be involved in patterning the neural tube by creating domains of differential cell adhesion. The present experiments focus on the question of what determines the expression pattern of LeX in embryonic rat brain. Comparisons of FORSE-1-positive glycolipid and protein antigens in embryonic, early postnatal, and adult tissues show that the LeX epitope is carried primarily by glycolipids during embryonic development and by a proteoglycan and glycoproteins in postnatal and adult tissue. Immunohistochemistry using FORSE-1 and an antibody to the proteoglycan phosphacan, which carries LeX, shows that the distribution of LeX is more restricted than phosphacan. These observations suggest that the precise spatial regulation of FORSE-1 binding in the embryonic forebrain is due to the expression pattern of the LeX carbohydrate on glycolipids, rather than to the transcriptional regulation of a carrier protein.

Animals↗
PubMed1999

Leukemia inhibitory factor augments neurotrophin expression and corticospinal axon growth after adult CNS injury.

The cytokine leukemia inhibitory factor (LIF) modulates glial and neuronal function in development and after peripheral nerve injury, but little is known regarding its role in the injured adult CNS. To further understand the biological role of LIF and its potential mechanisms of action after CNS injury, effects of cellularly delivered LIF on axonal growth, glial activation, and expression of trophic factors were examined after adult mammalian spinal cord injury. Fibroblasts genetically modified to produce high amounts of LIF were grafted to the injured spinal cords of adult Fischer 344 rats. Two weeks after injury, animals with LIF-secreting cells showed a specific and significant increase in corticospinal axon growth compared with control animals. Furthermore, expression of neurotrophin-3, but not nerve growth factor, brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor, or ciliary neurotrophic factor, was increased at the lesion site in LIF-grafted but not in control subjects. No differences in astroglial and microglial/macrophage activation were observed. Thus, LIF can directly or indirectly modulate molecular and cellular responses of the adult CNS to injury. These findings also demonstrate that neurotrophic molecules can augment expression of other trophic factors in vivo after traumatic injury in the adult CNS.

Animals↗
PubMed1999

Leukemia inhibitory factor, Interleukin 6, and other cytokines using the GP130 transducing receptor: roles in inflammation and injury.

Inflammation refers to a complex set of mechanisms by which tissues respond to injury and infection. Among the many soluble mediators associated with this process, cytokines are known to be crucial in regulating a variety of cellular and molecular events. Leukemia inhibitory factor (LIF), interleukin 6 (IL-6), IL-11, and possibly other members of this cytokine family are key mediators in various inflammatory processes such as the acute-phase reaction, tissue damage, and infection. These cytokines can act in both pro-inflammatory and anti-inflammatory ways, depending on a number of variables. We emphasize here recent work utilizing knockout mice, which has highlighted the roles of LIF and IL-6, particularly in interactions between the immune and nervous systems.

Animals↗
PubMed1999

Differential regulation of cytokine expression following pilocarpine-induced seizure.

While the pathological changes that occur in the brain following seizure have been well characterized, the molecular mechanisms underlying these events are poorly understood. Cell death, reactive gliosis, and axonal sprouting are among the best studied alterations in the epileptic brain. Previous work in both the peripheral and the central nervous systems suggests that cytokines are capable of affecting each of these processes. To better understand the role of cytokines in seizures and their sequelae, we have characterized cytokine expression in an animal model of epilepsy. Using pilocarpine to chemically induce seizures, and RNase protection assays to assess mRNA levels, we have quantified changes in expression of several members of the neuropoietic cytokine family following a single, prolonged seizure. Levels of oncostatin M (OSM), leukemia inhibitory factor (LIF), cardiotrophin-1, and ciliary neurotrophic factor were all increased in the hippocampus after seizure, though to differing extents and with markedly different time courses. Cells expressing the most dramatically up-regulated cytokines, LIF and OSM, were identified by combined in situ hybridization and immunohistochemistry. The majority of LIF(+) cells in the hippocampus were glial fibrillary acidic protein(+) astrocytes, while the majority of OSM(+) cells had the morphology of interneurons and were occasionally colabeled with neurofilament markers. Both the time course and the localization of cytokine up-regulation following seizure suggest possible roles for these intercellular signaling molecules in epilepsy.

Animals↗
PubMed1999

Cytokine and growth factor involvement in long-term potentiation.

Hippocampal long-term potentiation (LTP) is one of the best-studied models of learning and memory at the molecular level. While it has long been known that tetanic stimulation causes changes at the synapse within seconds to minutes, recent research has begun to focus on factors that may affect synaptic plasticity on a longer time scale. One group of factors with many of the characteristics predicted for both short- and long-term actions at the synapse is the cytokines and growth factors. In vitro, these proteins can alter neuronal morphology, gene expression, and proliferation, and many cytokines and their receptors are present in the adult CNS. Because brain-derived neurotrophic factor (BDNF) is the best-studied synaptic modulator of this class, we begin by discussing the experimental evidence linking BDNF to LTP. Ten cytokines and growth factors that have been examined in the context of hippocampal LTP are then considered. We discuss the effects of LTP on the expression of the cytokines and explore the regulation of synaptic plasticity by exogenous application or antagonist perturbation of these proteins. The available evidence strongly supports a role for these factors in synaptic modulation and should prompt further exploration of their functions at the synapse.

Animals↗
PubMed1998

Analysis of neuronal and glial phenotypes in brains of mice deficient in leukemia inhibitory factor.

Leukemia inhibitory factor (LIF) can regulate the survival and differentiation of certain neurons and glial cells in culture. To determine the role of this cytokine in the central nervous system in vivo, we examined the brains of young and adult mice in which the LIF gene was disrupted. Immunohistochemical staining of neurons for choline acetyltransferase, tyrosine hydroxylase, serotonin, parvalbumin, calbindin, neuropeptide Y, vasoactive intestinal polypeptide, and calcitonin gene-related peptide revealed no significant differences between null mutant and wild-type (WT) brains. In contrast, analysis of glial phenotypes demonstrated striking deficits in the LIF-knockout brain. Staining with several anti-glial fibrillary acidic protein (GFAP) antibodies showed that the number of GFAP-positive cells in various regions of the hippocampus in the female mutant is much lower than in the WT. The null male hippocampus also displays a significant, though less marked deficit. The number of astrocytes in the mutant hippocampus, as determined by S-100 staining, is not, however, significantly different from WT. In addition, quantification of immunohistochemical staining of female, but not male, mutants reveals a significant deficit in myelin basic protein content in three brain regions, suggesting alterations in oligodendrocytes as well. Thus, while overall brain histology appears normal, the absence of LIF in vivo leads to specific, sexually dimorphic alterations in glial phenotype.

Animals↗
PubMed1998

Leukemia inhibitory factor is an anti-inflammatory and analgesic cytokine.

The mRNA for leukemia inhibitory factor (LIF), a neuroimmune signaling molecule, is elevated during skin inflammation produced by intraplantar injection of complete Freund's adjuvant (CFA). Moreover, although LIF knock-out mice display normal sensitivity to cutaneous mechanical and thermal stimulation compared with wild-type mice, the degree of CFA-induced inflammation in mice lacking LIF is enhanced in spatial extent, amplitude, cellular infiltrate, and interleukin (IL)-1beta and nerve growth factor (NGF) expression. Conversely, local injection of low doses of recombinant LIF diminishes mechanical and thermal hypersensitivity as well as the IL-1beta and NGF expression induced by CFA. These data show that upregulation of LIF during peripheral inflammation serves a key, early anti-inflammatory role and that exogenous LIF can reduce inflammatory hyperalgesia.

Analgesics↗
PubMed1998

Effect of leukemia inhibitory factor (LIF) on the morphology and survival of cultured hippocampal neurons and glial cells.

Leukemia inhibitory factor (LIF) is a cytokine involved in the survival, differentiation and regeneration of sympathetic, sensory and motor neurons. Its effects in the brain are less well characterized. In a previous study, we found LIF transcripts to be predominantly expressed in neurons of the adult rat brain. Highest levels were observed in the hippocampus, particularly in granular neurons of the dentate gyrus and in hilar interneurons. Here we report the effects of LIF on survival and differentiation of postnatal rat hippocampal cells in vitro. We find that LIF minimally influences the survival and differentiation of dentate gyrus neurons, causing a slight reduction of the number of dendrites per neuron. In contrast, LIF induces a pronounced increase in the number of astrocytes. This increase does not appear to be due to enhanced proliferation but rather to increased cell survival. On the other hand, epidermal growth factor (EGF) induces astrocyte proliferation, and addition of LIF inhibits the EGF effect. In summary, LIF does not appear to be crucial for the survival or differentiation of cultured dentate gyrus neurons. This cytokine increases astrocyte survival but does not enhance astrocyte proliferation, and LIF is able to counteract the growth stimulation elicited by EGF.

Animals↗
PubMed1998

Sympathetic neurons can produce and respond to interleukin 6.

Neuronal expression of cytokines is an area of active investigation in the contexts of development, disease, and normal neural function. Although cultured rat sympathetic neurons respond very weakly to exogenous interleukin 6 (IL-6), we find that addition of soluble IL-6 receptor (sIL-6R) and IL-6 enhances neuronal survival in the absence of nerve growth factor. Neutralizing monoclonal antibodies against IL-6 block these effects. Addition of IL-6 and sIL-6R also induces a subset of neuropeptide and transmitter synthetic enzyme mRNAs identical to that demonstrated for leukemia inhibitory factor, ciliary neurotrophic factor, and oncostatin M. Both of these effects are duplicated by addition of a highly active fusion protein of sIL-6R and IL-6, covalently linked by a flexible peptide chain, which is designated H-IL-6. In addition, we show that sympathetic neurons produce IL-6. In situ hybridization indicates a neuronal localization of IL-6 mRNA in superior cervical ganglia, and bioactive IL-6 protein is detected in ganglion culture supernatants. Interestingly, the IL-6 produced by sympathetic neurons does not lead to survival of these cells in culture unless sIL-6R is added. Thus, sympathetic neurons can produce IL-6 and may respond to it in an autocrine/paracrine manner if sIL-6R is present. Moreover, the prior findings of sIL-6R in serum and inflammatory fluids now have added interest in the context of neuro-immune interactions.

3T3 Cells↗
PubMed1998

Impact of cage density on pullet performance and blood parameters of stress.

The effects of cage density on pullet live performance and blood indices of stress were evaluated in two commercial White Leghorn strains housed at 38, 32, 26, and 20 birds per cage from Day 1 to 6 wk of age, and 19, 16, 13, and 10 birds per cage from 6 to 18 wk. Cage densities of 26 and 13 birds per cage represent a U.S. standard of 142 and 284 cm2 per bird that is often applied in commercial pullet rearing. Cage density treatments include confounding cage, feeder, and drinker spaces per bird as might be encountered in commercial practice when growing more pullets per cage. Body weight was significantly reduced at greater bird densities in both strains; however, one strain was affected as early as 6 wk of age, whereas in the other strain, body weight was not reduced significantly until 18 wk. Feed intake was increased by more than 13% in both strains at the lowest density treatment (20 birds per cage) from Day 1 to 2 wk but reduced by more than 9% by higher cage densities during the remainder of the study. Feed conversion (FC) ratio was similarly improved (i.e., reduced) when more pullets were housed per cage, and increased when fewer birds were placed per cage compared to the standard. Despite a significant reduction in feed intake and a corresponding loss of body weight, cage density treatments had no significant affect on hemagglutinin titers to sheep red blood cell antigen, percentage heterophils (H), lymphocytes (L), or the H:L ratio. However, pullet age and strain differences were observed for all blood parameters. Overall, treatments allowing more cage, feeder, and drinker spaces per bird than the U.S. commercial standard provided no body weight advantage, and allowed for greater feed intake and poorer FC at several ages.

Aging↗
PubMed1997

A more efficient and economical approach for monoclonal antibody production.

We describe here an efficient, economical way to produce monoclonal antibodies in tissue culture flasks. Hybridoma cells are cultured in horizontal tissue culture flasks until 90% confluent, and then the flasks are filled with culture medium and placed in a standing position and left in the incubator for 3-4 weeks until most of the cells have died. At this time, the culture fluid is harvested for antibodies. With this method, which involves only a single cell plating and one change of medium, the yield of antibodies from one tissue culture flask is 6- to 9-fold higher than is obtained by the usual method of sequential replating and harvesting of cells and media. This approach therefore saves labor as well as costly materials, and minimizes risk of contamination.

Animals↗
PubMed1997

Leukemia inhibitory factor (LIF) mRNA-expressing neuronal subpopulations in adult rat basal forebrain.

We have previously found leukemia inhibitory factor (LIF) mRNA in neurons of the adult rat brain. To identify which neuronal subpopulations are expressing LIF transcripts, non-radioactive in situ hybridization was combined with immunocytochemistry for various neuronal markers. Studying the rat basal forebrain and cerebral cortex, we find LIF mRNA is expressed in both cholinergic and GABAergic neurons. These data suggest a role for LIF in the function of these mature neurons.

Animals↗