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P H Patterson

Publications and source records attributed to P H Patterson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Enhanced survival and neuronal differentiation of adrenal chromaffin cells cografted into the striatum with NGF-producing fibroblasts.

Although adrenal medullary chromaffin cells have been used extensively for intracerebral grafting, their survival has generally been poor. Improved survival of the implanted cells has been achieved by exposing the chromaffin cells to NGF in vivo. Culture studies have shown, however, that chromaffin cells are converted into sympathetic neurons when NGF is included in the medium. The degree to which such a transdifferentiation may occur in vivo has not been determined. We assessed the effects of cografting chromaffin cells with primary fibroblasts genetically engineered to express NGF. Chromaffin cells from 10 d old rats were implanted with NGF-producing or beta-galactosidase-producing primary fibroblasts (control fibroblasts) into the striatum of 6-hydroxydopamine treated adult rats of the same strain. Eight weeks postgrafting, chromaffin cells cografted with NGF-producing fibroblasts displayed many of the features of mature sympathetic neurons such as large somata, long processes, transmitter vesicles similar to those found in neurons, and positive immunolabeling for the neuronal markers neurofilament, MAP2 and SCG10. Chromaffin-derived neuron number was also significantly enhanced in the presence of NGF-producing fibroblasts. While control fibroblasts were also found to increase chromaffin cell number above that of chromaffin cells grafted alone, the control fibroblasts did not induce neuronal transdifferentiation. These results demonstrate that chromaffin cells cografted with NGF-producing fibroblasts undergo transdifferentiation in vivo and express many characteristics of mature sympathetic neurons. The consequences of this transdifferentiation on the long term survival and function of the transplanted cells in vivo remain to be clarified.

Adrenal Glands↗
PubMed1995

Regionalization of the developing forebrain: a comparison of FORSE-1, Dlx-2, and BF-1.

The FORSE-1 monoclonal antibody (mAb) was generated using a strategy designed to produce mAbs against neuronal cell surface antigens that might be regulated by regionally restricted transcription factors in the developing CNS. To determine whether FORSE-1 has a labeling pattern similar to that of known transcription factors, the expression of BF-1 and Dlx-2 was examined by in situ hybridization on sections serial to those labeled with FORSE-1. We find a striking overlap between BF-1 and FORSE-1 in the telencephalon; both are expressed in the lateral but not the medial walls of the telencephalon, and the boundaries of expression are apparently identical. FORSE-1 staining is detected prior to BF-1 expression in the neural tube, however. FORSE-1 and Dlx-2 have very different patterns of expression in the forebrain, suggesting that regulation by Dlx-2 cannot by itself explain the distribution of FORSE-1. However, they share some sharp boundaries in the diencephalon. In addition, FORSE-1 identifies some previously unknown boundaries in the developing forebrain. These results indicate that a new cell surface marker can be used to subdivide the embryonic telencephalon and diencephalon into regions smaller than previously described, providing necessary complexity to the developmental patterning in the forebrain.

Animals↗
PubMed1994

Major changes in the expression of the mRNAs for cholinergic differentiation factor/leukemia inhibitory factor and its receptor after injury to adult peripheral nerves and ganglia.

The neuropoietic cytokine cholinergic differentiation factor/leukemia inhibitory factor (CDF/LIF) acts as a trophic factor, enhancing neuronal survival, and as a differentiation factor, altering neuronal gene expression. There is also evidence that its plays a role in the response of adult neural tissue to injury. We have examined this possibility further in rats by analyzing changes in the levels of mRNAs for CDF/LIF and its two receptor subunits in response to peripheral nerve damage in culture and in vivo. Using a quantitative RNase protection assay, we find that CDF/LIF mRNA increases dramatically (176-fold) in adult, but not neonatal, sympathetic ganglia and in adult dorsal root ganglia and sciatic nerve after organ culture for 24 hr. This mRNA is clearly detectable by in situ hybridization only in the nonneuronal cells of these structures. When the sciatic nerve is transected in vivo, CDF/LIF mRNA increases significantly in the regions immediately proximal and distal to the lesion site. The mRNA for the ligand binding subunit of the CDF/LIF receptor complex decreases somewhat upon culture and nerve section. The dramatic rise in CDF/LIF mRNA after nerve injury is further evidence that this cytokine is involved in the response to damage, a function that overlaps with its postulated role in wounding or infection in several nonneural tissues.

Animals↗
PubMed1994

Neuropoietic cytokines and activin A differentially regulate the phenotype of cultured sympathetic neurons.

A number of cytokines sharing limited sequence homology have been grouped as a family because of partially overlapping biological activities, receptor subunit promiscuity, and the prediction of a shared secondary structure. Since several of these cytokines regulate gene expression and cell number in the nervous and hematopoietic systems, this specific group is termed the neuropoietic cytokine family. Using a reverse transcription-polymerase chain reaction-based assay system for monitoring the expression of multiple phenotypic markers in cultured sympathetic neurons, we present further evidence that, in addition to cholinergic differentiation factor/leukemia inhibitory factor and ciliary neurotrophic factor, oncostatin M, growth promoting activity, interleukin 6, and interleukin 11 belong in this family. In addition, one member of the transforming growth factor beta superfamily, activin A, shares a selective overlap with the neuropoietic family in the spectrum of neuropeptides that it induces in sympathetic neurons. The particular neuropeptides induced by activin A, however, demonstrate that the activity of this cytokine is distinct from that of the neuropoietic family. Twenty-six other cytokines and growth factors were without detectable activity in this assay.

Activins↗
PubMed1994

The molecular basis of retinotectal topography.

Over 50 years have passed since Roger Sperry formulated a simple model of how visual space, as seen by the retina, can be projected onto the brain in a two-dimensional, topographic map during development. Sperry posited a set of two orthogonal gradients in the retina that gives each cell a positional identity. He further suggested that these molecules could be used to match up with complementary gradients in the target field of the retinal projection, the tectum. While some investigators hold that the existence of such molecules may not be necessary to establish retinotectal maps, recent work has identified several cell surface proteins whose distributions are of the type predicted by Sperry. An unexpected twist comes from culture assays demonstrating that inhibitory activities on tectal membranes can guide the growth of processes from retinal neurons. Moreover, the expression patterns of several enzymes and three transcription factors suggest that these proteins are candidates for regulatory agents in the determination of cell position in the retina. In addition, results from perturbation experiments support the candidacy of two of the enzymes, and a new mutant screen has uncovered several as yet unidentified genes that are required for establishment of the proper retinotectal map. A number of these results were presented at a recent meeting on neurospecificity held in Cargese, Corsica and sponsored by NATO and NSF.

Animals↗
PubMed1994

Energy metabolism in isolated chick (Gallus domesticus) gastrocnemius and tilapia (Tilapia mossambica) epaxial muscle at various temperatures in vitro.

Muscle respiration experiments on inhibitor dosage (experiment 1), muscle preparation (tendons removed vs. unstretched vs. stretched muscles; chick muscle only; experiment 2) and media temperature (26.5, 32, 37, 42 degrees C; experiment 3) were conducted on chick (Gallus domesticus) gastrocnemius and tilapia (Tilapia mossambica) epaxial muscle in vitro. Experiment 1: The dosage of cycloheximide and ouabain required for maximum inhibition of protein synthesis and Na+,K+ ATPase, respectively, in chick and tilapia muscle was approximately 6 x 10(-5) M. Experiment 2: Removing the tendons of chick muscle decreased (% inhibition, P = 0.05) cycloheximide-sensitive respiration compared to stretched and unstretched muscles (tendons intact). However, muscle preparation had little influence on ouabain-sensitive respiration. Experiment 3: Cycloheximide-sensitive respiration tended to increase (microliter O2/mg DNA.hr, P = 0.054) with media temperature in tilapia muscle. Chick muscle was less responsive in this respect. Ouabain-sensitive respiration increased at lower temperature in chick muscle (% inhibition, cubic relationship, P = 0.001) and at higher temperature in tilapia muscle (% inhibition, quadratic relationship, P = 0.0002).

Animals↗
PubMed1994

Depolarization differentially regulates the effects of bone morphogenetic protein (BMP)-2, BMP-6, and activin A on sympathetic neuronal phenotype.

As a first step in defining the role of the transforming growth factor-beta (TGF-beta) superfamily in the development of the sympathetic nervous system, we analyzed effects of several members of this family on neuronal gene expression in dissociated cell culture using a reverse transcription-polymerase chain reaction method. We found that, in addition to activin A, bone morphogenetic protein (BMP)-2 and BMP-6 also induce mRNAs for distinct sets of neuropeptides and neurotransmitter synthetic enzymes in sympathetic neurons. TGF-beta 1 and TGF-beta 3 are, however, without detectable effect in this assay. Surprisingly, we find that the patterns of neuropeptide genes induced by activin A, BMP-2, and BMP-6 are each affected differently by neuronal depolarization. Depolarization can either promote or block the effects of different cytokines on the same neuropeptide gene, and depolarization can either promote or block the effects of a given cytokine on different neuropeptide genes. This evidence suggests that neuronal activity may be a key mediator of cytokine modulation of neuronal gene expression.

Activins↗
PubMed1994

Intratracheal injection of LPS and cytokines. V. LPS induces expression of LIF and LIF inhibits acute inflammation.

Lipopolysaccharide (LPS) injected into the trachea of rats was found to induce the secretion of leukemia inhibitory factor (LIF) into bronchoalveolar lavage (BAL) fluid with a maximum expression of LIF after 2-12 h. The acute pulmonary neutrophilic inflammation caused by the intratracheal injection of bacterial endotoxin (LPS) could be inhibited by the intratracheal coinjection of recombinant LIF. Compared with intratracheal injection of LPS alone, intratracheal coinjection of LIF and LPS decreases the number of BAL neutrophils obtained 6 h later by approximately 50% (P < 0.0001). LIF decreased the amount of the proinflammatory cytokine tumor necrosis factor (TNF), but not the amount of the anti-inflammatory cytokine interleukin (IL)-6, in the BAL fluid of LPS-injected rats. Similarly, intravenous LIF was found to decrease TNF expression, but increase IL-6 expression, in the serum of rats receiving intravenous LPS. Intravenous LIF, even in the absence of LPS, was found to cause IL-6 expression. In conclusion, intratracheal LPS initiates the secretion of endogenous LIF into the alveolar space where LIF may contribute to the downregulation of LPS-initiated acute neutrophilic inflammation by downregulating expression of TNF. LIF may down-regulate LPS-initiated TNF expression at least in part indirectly by upregulating expression of IL-6, a cytokine known to downregulate LPS-initiated TNF expression.

Acute Disease↗
PubMed1994

Feeding value of poultry by-products extruded with cassava, barley, and wheat middlings for broiler chicks: the effect of ensiling poultry by-products as a preservation method prior to extrusion.

In one experiment, six treatment diets including two levels of cassava meal, barley, or wheat middlings extruded with poultry by-products (PBP; a 3:1 ratio of broiler offal and condemned carcasses) were compared with a corn and soybean meal control diet for broiler performance from 1 d to 3 wk of age. No treatment differences in body weight (P > .05) were observed, and all chicks averaged 166, 421, and 788 g at 1, 2, and 3 wk of age, respectively. Weight gain and feed consumption were not affected by the experimental diets (P < .05). Birds fed the control diet had better overall feed conversion (1.24) than birds fed the diet containing 20% extruded barley and PBP (1.37) (P < .05). Feeding PBP extruded with cassava (10 and 20%) or barley (10%) resulted in equal broiler performance at less cost than birds fed the control diet. In a second experiment, 10% sucrose was mixed with PBP by weight and ensiled for 7 d at ambient temperatures in an anaerobic vessel. Diets containing cassava extruded with fresh and ensiled PBP (FR-PBP and EN-PBP, respectively) were compared with control diets (CON) for broilers to 6 wk of age. No differences in body weight were observed by 6 wk. Feed conversion of the CON birds was poorer than the birds fed the FR-PBP (P < .05). Chilled carcass yield was better for the CON compared with the EN-PBP treatment; however, dietary treatment had no effect on the percentage breast meat, thigh, drumstick, wing, or cage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1994

Comparison of freeze-dried and extruded Spirulina platensis as yolk pigmenting agents.

Experiment 1 was an 8-wk study with Japanese quail fed 0, .5, 1.0, 2.0, and 4.0% of freeze-dried spirulina or the dry equivalent of fresh spirulina extruded with corn. Experiment 2 was a 16-wk repeat of Experiment 1 using levels of 0, .25, .5, 1.0, and 2.0% spirulina. In the third experiment, corn, barley, and cassava were extruded with fresh spirulina equal to 1% of the dried product, and each feedstuff fed with 1% freeze-dried spirulina. Four replicates of five quail were assigned to each treatment. Yolk color increased with increasing dietary levels of spirulina in Experiment 1. There also was a consistent increase in yolk color with freeze-dried spirulina compared with the extruded spirulina. This pattern was also seen in Experiment 2. In addition, eggs from quail fed the extruded corn control diet had markedly lower yolk scores than those from quail fed the untreated corn control diet. The mean Roche yolk color score of eggs from quail fed corn, barley, or cassava extruded with spirulina was 5.91, 3.55, and 6.70, respectively. These values were respectively 1.41, 1.89, and 4.06 units greater than the corresponding control values.

Animals↗
PubMed1993

A modified method for obtaining large amounts of high titer polyclonal ascites fluid.

When limited amounts of antigens are available, it is often difficult to obtain large quantities of polyclonal antisera. Although antisera can be raised in small rodents, yields are usually small. To circumvent these problems, we have designed a modified method for generating polyclonal ascites fluid (AF). Using the appropriate strain of mice and adjuvant, we generated high serum titers by injection of 1-100 micrograms of protein. Following i.p. injection of compatible sarcoma cells, 13-19 ml of high titer (1:1000-1:20,000), polyclonal ascites fluid were obtained from each mouse. Similar results were obtained using nine different antigens.

Adjuvants, Immunologic↗
PubMed1993

Distribution of CD9 in the developing and mature rat nervous system.

CD9 is a cell surface protein implicated in intercellular signaling that has been identified in selected cell types of the hematopoietic system. To begin a study of the role of CD9 in the developing and adult nervous system, we used the anti-rat CD9 monoclonal antibody ROCA2 to determine the distribution of this protein. The identity of the antigen in these tissues was confirmed by immunoblotting and peptide sequencing. Early embryonic sympathetic and dorsal root ganglion sensory neurons and adrenal chromaffin cells all express CD9. ROCA2 also labels the somas, axons, and growth cones of cultured sympathetic and sensory neurons. In the central nervous system (CNS), CD9 is transiently and specifically expressed in embryonic spinal motoneurons. In the adult, central and peripheral glia intensely express CD9. Thus, CD9 is developmentally regulated in a variety of peripheral and central neurons and glia, including proliferating progenitors as well as mature cells. These findings suggest that CD9 may have diverse roles in the nervous system.

Animals↗
PubMed1993

Leukemia inhibitory factor mediates an injury response but not a target-directed developmental transmitter switch in sympathetic neurons.

Leukemia inhibitory factor (LIF; also known as cholinergic differentiation factor) is a multifunctional cytokine that affects neurons, as well as many other cell types. To examine its neuronal functions in vivo, we have used LIF-deficient mice. In culture, LIF alters the transmitter phenotype of sympathetic neurons, inducing cholinergic function, reducing noradrenergic function, and altering neuropeptide expression. In vivo, a noradrenergic to cholinergic switch occurs in the developing sweat gland innervation, and changes in neuropeptide phenotype occur in axotomized adult ganglia. We find that the gland innervation of LIF-deficient mice is indistinguishable from normal. In contrast, neuropeptide induction in ganglia cultured as explants or axotomized in situ is significantly suppressed in LIF-deficient mice. Thus, LIF plays a role in transmitter changes induced by axotomy but not by developmental interactions with sweat glands.

Animals↗
PubMed1993

A novel approach to screen for cytokine effects on neuronal gene expression.

We describe an assay based on reverse transcription-polymerase chain reaction to detect the expression of mRNAs for a variety of transmitter synthetic enzymes and neuropeptides present at low levels in primary neuronal cultures. The assay is specific for mRNA-derived templates and is not affected by the presence of genomic DNA. Using this method, we demonstrate that cholinergic differentiation factor/leukemia inhibitory factor (CDF/LIF) and ciliary neurotrophic factor (CNTF) induce mRNAs for choline acetyltransferase, somatostatin, substance P, vasoactive intestinal polypeptide, cholecystokinin, and enkephalin. The induction of cholecystokinin and enkephalin by CDF/LIF and CNTF had not been shown previously. These data illustrate that the assay can reproduce findings obtained with other methods, as well as provide the sensitivity necessary to produce new results. These results also extend the overlap of CDF/LIF and CNTF in controlling gene expression in cultured sympathetic neurons, supporting the idea that these cytokines may share receptor subunits and signal transduction pathways.

Animals↗
PubMed1993

Surface and cytoskeletal markers of rostrocaudal position in the mammalian nervous system.

To identify cell surface molecules that define position in the mammalian nervous system, we previously characterized the binding of two monoclonal antibodies, ROCA1 and ROCA2, to adult rat sympathetic ganglia and intercostal nerves. The binding of ROCA1 is highest in rostral ganglia and nerves and declines in a graded manner in the caudal segments. ROCA2 labels the same cells in ganglia and nerves as ROCA1, but not in a position-selective manner. We now show by immunoblot analysis that ROCA1 recognizes two antigens in membrane/cytoskeletal fractions of peripheral nerves and ganglia: (1) a Triton X-100-insoluble, 60 kDa protein and (2) a Triton x-100-insoluble, 26 kDa protein. The 60 kDa protein is expressed at higher levels in rostral than in caudal intercostal nerves, and is identified as the intermediate filament protein peripherin. In contrast, it is the ROCA1 epitope on the 26 kDa protein, and not the protein itself, that is preferentially visualized immunohistochemically in rostral nerves and ganglia. We suggest that the ROCA1 epitope on the 26 kDa protein is masked in sections of caudal nerves and ganglia. Amino acid sequence data obtained from the affinity-purified 26 kDa protein indicate significant homology with human CD9, a cell surface protein implicated in intercellular signaling in hematopoietic cells. These results suggest that intermediate filament gene expression and epitope masking on the cell surface may be involved in functions related to position in the nervous system.

Amino Acid Sequence↗
PubMed1993

Cytokines and the function of the mature nervous system.

In addition to the role that cytokines (growth factors, interleukins, instructive factors) play in regulating neuronal survival, growth and gene expression during development, recent evidence suggests that these intercellular signals can also control similar functions in the normal, as well as the injured, adult nervous system. Some of this evidence is summarized here, with particular emphasis on the potential role of cytokines in synaptic function and plasticity.

Adult↗