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J Dodd

Publications and source records attributed to J Dodd.

At least 73 records · Page 4Linked to original sources
PubMed1988

Markers shared between dorsal root and enteric ganglia.

Although the bowel is known to contain intrinsic primary afferent neurons with mucosal projections these cells have not been identified. The current study was undertaken to determine whether carbohydrate differentiation antigens or enzymatic markers common to primary sensory neurons could be found in enteric neurons. Subpopulations of sensory neurons of rat dorsal root ganglia (DRG) can be identified by the immunocytochemical detection of lactoseries and globoseries carbohydrate differentiation antigens with monoclonal antibodies (MAbs) and by the histochemical demonstration of carbonic anhydrase (CA)- or fluoride-resistant acid phosphatase (FRAP) activities; therefore, these markers, and their coincident expression with neuropeptides, were studied in neurons of the rat small intestine. Subsets of enteric neurons were demonstrated by a MAb (1B2/1B7) recognizing greater than 45%, and by a MAb (alpha-SSEA-1) recognizing less than 0.1%, of DRG neurons, as well as by CA, but not FRAP activity. 1B2/1B7+ neurons were found in both the submucosal (approximately 46% of neurons) and myenteric plexuses (approximately 2% of neurons). Submucosal 1B2/1B7+ neurons with mucosal projections also displayed vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY) but not substance P (SP) or calcitonin-gene-related peptide (CGRP) immunoreactivities. SSEA-1+ neurons were only found in the myenteric plexus, did not project to the mucosa (and thus are unlikely to be primary afferents), and were SOM+ or ENK+ but VIP- and NPY-. CA activity was intense in approximately 39% of the neurons of the submucosal plexus and in mucosal nerve fibers. Some (approximately 20%) of the submucosal CA neurons were also CGRP+, but VIP- and NPY-; therefore, MAb 1B2/1B7 and CA activity mark different nonoverlapping sets of submucosal neurons. Following the neonatal administration of capsaicin (50 mg/kg), 1B2/1B7 immunoreactivity was lost from all submucosal neurons; however, VIP immunoreactivity was not depleted from the cell bodies. Although it cannot yet be concluded that the MAb 1B2/1B7 or CA markers demonstrate the intrinsic sensory neurons of the gut, the presence in the bowel of both is consistent with the supposition that sensory neurons related to those of DRG are also found in the intestine. The functional and possible developmental significance of this relationship remains to be defined.

Acid Phosphatase↗
PubMed1988

Spatial regulation of axonal glycoprotein expression on subsets of embryonic spinal neurons.

The identification of surface proteins restricted to subsets of embryonic axons and growth cones may provide information on the mechanisms underlying axon fasciculation and pathway selection in the vertebrate nervous system. We describe here the characterization of a 135 kd cell surface glycoprotein, TAG-1, that is expressed transiently on subsets of embryonic spinal cord axons and growth cones. TAG-1 is immunochemically distinct from the cell adhesion molecules N-CAM and L1 (NILE) and is expressed on commissural and motor neurons over the period of initial axon extension. Moreover, TAG-1 and L1 appear to be segregated on different segments of the same embryonic spinal axons. These observations provide evidence that axonal guidance and pathway selection in vertebrates may be regulated in part by the transient and selective expression of distinct surface glycoproteins on subsets of developing neurons.

Animals↗
PubMed1988

Isolation and characterization of temperature-sensitive mutations in RPA190, the gene encoding the largest subunit of RNA polymerase I from Saccharomyces cerevisiae.

The isolation and characterization of temperature-sensitive mutations in RNA polymerase I from Saccharomyces cerevisiae are described. A plasmid carrying RPA190, the gene encoding the largest subunit of the enzyme, was subjected to in vitro mutagenesis with hydroxylamine. Using a plasmid shuffle screening system, five different plasmids were isolated which conferred a temperature-sensitive phenotype in haploid yeast strains carrying the disrupted chromosomal RPA190 gene. These temperature-sensitive alleles were transferred to the chromosomal RPA190 locus for mapping and physiology experiments. Accumulation of RNA was found to be defective in all mutant strains at the nonpermissive temperature. In addition, analysis of pulse-labeled RNA from two mutant strains at 37 degrees C showed that the transcription of rRNA genes was decreased, while that of 5S RNA was relatively unaffected. RNA polymerase I was partially purified from several of the mutant strains grown at the nonpermissive temperature and was shown to be deficient when assayed in vitro. Fine-structure mapping and sequencing of the mutant alleles demonstrated that all five mutations were unique. The rpa190-1 and rpa190-5 mutations are tightly clustered in region I (S.S. Broyles and B. Moss, Proc. Natl. Acad. Sci. USA 83:3141-3145, 1986), the putative zinc-binding region that is common to all eucaryotic RNA polymerase large subunits. The rpa190-3 mutation is located between regions III and IV, and a strain carrying it behaves as a mutant that is defective in the synthesis of the enzyme. This mutation lies within a previously unidentified segment of highly conserved amino acid sequence homology that is shared among the largest subunits of eucaryotic nuclear RNA polymerases. Another temperature-sensitive mutation, rpa190-2, creates a UGA nonsense codon.

Amino Acid Sequence↗
PubMed1987

Physical characteristics of ribosomal protein S4 from Escherichia coli.

A hydrodynamic study of protein S4 from Escherichia coli 30 S ribosomal subunits indicates that this protein is moderately asymmetric. A sedimentation coefficient of 1.69 S and a diffusion coefficient of 7.58 X 10(-7) cm2/s suggest that S4 has an axial ratio of about 5:1 using a prolate ellipsoidal model. This structure should give a radius of gyration of about 29-30 A from small-angle neutron or small-angle x-ray scattering studies. This study has utilized quasi-elastic light scattering as an analytical tool to obtain a diffusion coefficient as well as a method to monitor sample quality. Using quasi-elastic light scattering in this manner allows an assessment of problems associated with protein purity which may be responsible for the many disparate results reported for ribosomal proteins and especially protein S4.

Chemical Phenomena↗
PubMed1987

Production of pregnancy-associated plasma protein-A (PAPP-A) by cultured tumour granulosa cells.

Ten ovarian and 2 cervical tumour cell lines were analysed for the production of pregnancy-associated proteins. Pregnancy-associated plasma protein-A (PAPP-A) was detected by radioimmunoassay in culture media of 2 out of 4 (50%) tumour granulosa cell lines (mean = 104 microIU/10(5) cells/24 h) but not in any ovarian (n = 6) or cervical (n = 2) tumour cell lines. By contrast, human chorionic gonadotrophin (hCG), pregnancy specific beta 1-glycoprotein and alpha-fetoprotein (AFP) were not detected in any of the PAPP-A positive media. Only two cell lines produced hCG (58.5 and 25.5 mIU/10(5) cells/24 h). No AFP was produced by any of these 12 cell lines, whereas placental protein 5 was positive in 7. None of these proteins were detected in the culture media of 4 cell lines. In vitro derived PAPP-A was immunologically indistinguishable from either pregnancy or ovarian follicular PAPP-A. All PAPP-A species interacted reversibly with immobilised heparin and were determined by molecular sieve chromatography to have an apparent molecular weight of 820,000 daltons. Cultured tumour granulosa cells specifically synthesised and secreted a large protein which was immunologically and physicochemically indistinguishable from in vivo (pregnancy and ovarian follicular) derived PAPP-A.

Female↗
PubMed1986

Selective expression of endogenous lactose-binding lectins and lactoseries glycoconjugates in subsets of rat sensory neurons.

Cell-surface glycoconjugates and endogenous lectins have been implicated in cellular interactions that contribute to embryonic development. Functional subsets of primary sensory neurons in mammalian dorsal root ganglia (DRG) have been shown recently to express specific cell-surface oligosaccharide structures. We report here that endogenous lectins with affinity for sensory neuron glycoconjugates are also synthesized by subsets of DRG neurons and are present in the dorsal horn of the developing spinal cord. The distribution of two endogenous lactose-binding lectins, RL-14.5 and RL-29 (subunit Mrs of 14,500 and 29,000, respectively), was examined by immunoblotting and by immunocytochemistry in embryonic and postnatal rat DRG and spinal cord. The two lectins appear soon after the formation of the DRG and are present in the cell bodies and terminals of subsets of DRG neurons that also express cytoplasmic and cell-surface lactoseries glycoconjugates. RL-14.5 and RL-29 are present in overlapping, but not coincident, subsets of DRG neurons that project to the superficial dorsal horn of the spinal cord. In addition, RL-14.5, but not RL-29, is expressed in spinal motoneurons from embryonic day 14. The preferential localization of lactoseries glycoconjugates and lactose-binding lectins in the DRG and the dorsal horn of the spinal cord suggests that these complementary molecules contribute to the development and function of primary sensory neurons.

Animals↗
PubMed1986

A comparison of circulating immune complexes, pregnancy associated beta 1-macroglobulin and galactosyltransferase as tumour markers for ovarian cancer.

Serial blood samples have been obtained from 12 patients with ovarian cancer who were treated by surgery and, generally, chemotherapy or radiotherapy. Some achieved clinical remission, but the majority relapsed after variable time interval. Three potential tumour markers (Circulating Immune Complexes, Pregnancy Associated beta 1-Macroglobulin and Galactosyltransferase) have been studied longitudinally in serum for clinical correlation, predictive value, and biochemical 'lead time' to clinically detectable progression. None of the 3 offered any signal advantage over the others, and each showed an inconsistent relationship to observed disease status, with high levels indicating a poor outlook and the converse not true. Thus, since the 'lead time' is short, and reliability low, none of the compounds can be strongly commended as individual markers for ovarian cancer.

Adenocarcinoma↗
PubMed1986

Cell surface glycoconjugates and carbohydrate-binding proteins: possible recognition signals in sensory neurone development.

Dorsal root ganglion (DRG) neurones transmit cutaneous sensory information from the periphery to the dorsal horn of the spinal cord. Subpopulations of DRG neurones that subserve distinct sensory modalities project to discrete regions in the dorsal horn. The formation of specific sensory connections during development may involve cell-surface interactions with spinal cord cells. Molecules that are expressed on the surface of functional subpopulations of DRG and dorsal horn neurones have therefore been identified. Distinct subsets of DRG neurones express globo- or lactoseries carbohydrate differentiation antigens. The expression of defined carbohydrate structures correlates with the embryonic lineage, peptide phenotype and the central termination site of DRG neurones. Similar or identical glycoconjugates have been implicated in cellular interactions that contribute to preimplantation embryonic development. Small-diameter DRG neurones that project to the superficial dorsal horn express N-acetyllactosamine backbone structures that are potential ligands for beta-galactoside-specific binding proteins (lectins). Two lectins have been identified that are expressed early in development in the superficial dorsal horn. These complementary molecules may contribute to the development of sensory afferent projections in the spinal cord.

Aging↗
PubMed1986

Nursing evaluation of the efficacy of analgesic delivery in post operative pain.

To evaluate nursing management of post-operative pain and nausea in adult patients. To ascertain patterns of pain medication and correlate these with the quality of pain relief achieved. The progress of 22 adult patients was recorded for three days post-operatively. Pain was assessed at rest and on activity three times a day using visual analogue scales. Nausea levels were assessed similarly. All analgesics and antiemetics administered were recorded. There was a wide range of variation in the administration of medications and consequently a wide range of effectiveness. A significant proportion of patients showed unacceptably high levels of pain indicating undertreatment. Patients and nurses had conflicting expectations of who should initiate the request for pain relief medication.

Administration, Oral↗
PubMed1985

Structure and expression of differentiation antigens on functional subclasses of primary sensory neurons.

Subpopulations of dorsal root ganglion neurons can be distinguished on the basis of their peripheral receptive properties, spinal terminal arbors and neuropeptide content. We have used monoclonal antibodies (MAbs) to define antigenic determinants on functional populations of DRG neurons projecting to the superficial dorsal horn of the spinal cord. Three MAbs recognize defined carbohydrate epitopes associated with lacto- and globo-series glycolipids that constitute the stage-specific embryonic antigens (SSEAs) 1, 3 and 4. SSEA-3 and SSEA-4 are present in the cytoplasm of about 10% of DRG neurons in adult rat. These neurons are distinct from those that contain substance P, somatostatin or the fluoride-resistant acid phosphatase enzyme, FRAP. SSEA-1 is present in a small percentage of DRG neurons. SSEAs are present on the surface of DRG neurons maintained in dissociated cell culture: 6% are SSEA-1+, 7% are SSEA-3+ and 10-15% are SSEA-4+. MAbs LD2, KH10, TC6 and TD10 identify epitopes expressed coincidently in 25% of small DRG neurons that project to lamina II of the dorsal horn. All somatostatin- but less than 1% of substance P-immunoreactive DRG neurons express these antigens. MAb LA4 labels a distinct population of small DRG neurons that also projects to lamina II. There is extensive overlap between LA4+ neurons and those that contain FRAP. Antigens recognized by these MAbs are expressed on the surface of 10-20% of DRG neurons in culture. Preliminary biochemical studies suggest that these antigens may be glycolipids. Molecules bearing carbohydrate differentiation antigens may be involved in the development and specification of sensory connections in the dorsal horn of the spinal cord.

ABO Blood-Group System↗
PubMed1985

Pregnancy-associated beta 1-macroglobulin: detection on the surface of ovarian cancer cell lines.

Pregnancy-associated beta 1-macroglobulin (beta 1-PAM) is a serum protein which can be detected at elevated levels in the blood of many ovarian cancer patients. The presence of the antigen was investigated on the surface of 4 human ovarian cancer lines and 32 other human and rodent cell types and lines by means of immunofluorescent staining and anti-beta 1-PAM-enzyme conjugate. The antigen was detected only on the ovarian lines but no secretion of beta 1-PAM into the culture supernatants was observed. The ovarian cancer cells appeared to display the beta 1-PAM constantly during culture, and enzymic treatment of the cells indicated that detection of the cell-bound antigen with antiserum could be, at least partially, eliminated with proteases but not glycosidases or neuraminidase. The results serve to confirm the association of beta 1-PAM with ovarian cancer.

Antigens, Surface↗
PubMed1985

The value of the monoclonal antibody (cancer antigen 125) in serial monitoring of ovarian cancer: a comparison with circulating immune complexes.

The use of circulating immune complexes and a commercial monoclonal antibody to ovarian cancer (CA 125 kit) in monitoring progress in patients with ovarian cancer has been assessed. While changes in immune complexes were apparent in some patients with active progression of disease, the marked change in values and linear trend make the use of CA 125 a useful clinical marker.

Antigen-Antibody Complex↗
PubMed1985

The influence of pergonal on in vitro production of placental protein 5 (PP5) by ovarian tumour cells.

A radioimmunoassay for the measurement of placental protein 5 (PP5) has been developed using a second antibody-polyethyleneglycol method to separate free from bound ligand. PP5 immunoreactivity was detected in culture media from a cell line derived from a small cell carcinoma of the ovary (SCCWm2). The culture-derived PP5 shares immunological identity with pregnancy and ovarian follicular PP5. Affinity interactions between PP5 and matrices such as heparin or thrombin-Sepharose were similar and independent of the origin of PP5. PP5 was heterogeneous with two forms, a monomer (18k) and dimer (36k) being detected in all biological fluids examined. The dimer was predominant in ovarian follicles and the SCCWm2 cell line, while the monomer predominated in pregnancy serum. The basal rate of PP5 secretion by the SCCWm2 cell line was 0.61AU/24h/10(5) cells. Incubation of cells in the presence of 150mIU Pergonal stimulated PP5 production 20.6 fold and following removal of Pergonal the production rate was maintained at 18.0 times the basal rate. No choriconic gonadotrophin, pregnancy-specific beta 1-glycoprotein, pregnancy associated plasma protein-A or alpha fetoprotein was detected in the culture medium of the SCCWm2 cell line.

Carcinoma, Small Cell↗
PubMed1985

Lactoseries carbohydrates specify subsets of dorsal root ganglion neurons projecting to the superficial dorsal horn of rat spinal cord.

Cell surface carbohydrates are thought to play important roles in the development and differentiation of mammalian cells. In previous studies we have found that one population of dorsal root ganglion (DRG) neurons is specified by the expression of complex globoseries oligosaccharides (Dodd, J., D. Solter, and T. M. Jessell (1984) Nature 311: 469-472; Jessell, T. M., and J. Dodd (1985) Philos. Trans. R. Soc. Lond. (Biol.) 308: 271-281). We now report that monoclonal antibodies (MAbs) directed against backbone structures of lactoseries oligosaccharides define antigens present in the cytoplasm of a second, anatomically and functionally distinct subset of DRG neurons. Lactoseries carbohydrate structures identified by MAb A5 are restricted to small- and intermediate-diameter DRG neurons with central projections in the superficial dorsal horn of the rat spinal cord. The distribution of labeled terminals suggests that many of the DRG neurons that express lactoseries carbohydrates are likely to convey nociceptive information. More complex galactose- and fucose-substituted lactoseries structures recognized by MAbs LD2, KH10, TC6, TD10, LA4, and anti-Lewis a are segregated on subsets of DRG neurons that differ in their expression of substance P, somatostatin, and fluoride-resistant acid phosphatase and in their laminar termination in the superficial dorsal horn. The majority of lactoseries carbohydrate antigens identified in the cytoplasm of DRG neurons are also expressed on the surface of subsets of DRG neurons in culture. These studies establish that structurally defined carbohydrate differentiation antigens specify the majority of primary sensory neurons with cutaneous receptive fields. Moreover, lactoseries carbohydrate structures similar or identical to those expressed on neonatal DRG neurons in culture have been implicated in cell-cell interactions at early stages of preimplantation embryonic development. Our observations suggest strategies for testing the hypothesis that carbohydrates present on the surface of subsets of DRG neurons play a role in cell interactions that contribute to the laminar organization of sensory afferents in the developing spinal cord.

Acid Phosphatase↗