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J D Kemp

Publications and source records attributed to J D Kemp.

At least 73 records · Page 4Linked to original sources

Evidence that 5-HT agonist-induced rotational behaviour in the rat is mediated via 5-HT1 receptors.

The rotational behaviour induced by 5-HT agonists has been investigated in rats with lesions of the dorsal raphe' nucleus (DRN). We have previously reported that 5-methyoxy-N,N-dimethyl-tryptamine (5-MeODMT) caused dose-related contralateral rotation in rats with 5,7-dihydroxytryptamine (5,7-DHT) lesions of the DRN. Similar findings are now presented for the 5-HT1 agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-3 (1,2,3,6-tetrahydropyridin-4-yl) (1H indole) (RU24969). In this model, in agreement with the behavioural studies, both agonists were shown to have a greater affinity for the 5-HT1 binding site when compared with the 5-HT2 binding site. Antagonist studies using selective 5-HT2 antagonists (ketanserin and pirenperone) at non-sedative doses failed to inhibit this behaviour. In contrast, the classical 5-HT antagonist methysergide caused significant inhibition of the rotational behaviour. These results suggest that 5-HT agonist-induced rotation in the rat is mediated via 5-HT1 receptors, probably located in the substantia nigra.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Large cell lymphoma complicating acute lymphoblastic leukemia.

Non-Hodgkin's lymphoma (NHL) is a very rare complication of acute lymphoblastic leukemia (ALL). We present the pathologic, clinical, immunologic, and ultrastructural features of the third reported example of NHL following successfully treated ALL. This white girl developed ALL with predominantly L1 cells at 3.5 yr of age. The lymphoblasts were terminal deoxynucleotidyl transferase (TdT) positive and were non-B, non-T cells. She achieved a complete remission with standard induction therapy and has remained in continuous complete remission. Four and one-third years after the onset of ALL, she developed multifocal, pleomorphic large cell lymphoma of the small bowel, which resulted in episodes of intussusception and obstruction. These pleomorphic and frequently multinucleated lymphoma cells lacked TdT, common ALL antigen, and all tested markers of B cell, T cell, and histiocyte differentiation. Following three small bowel resections, systemic multiagent chemotherapy, and abdominal irradiation, she is currently free of disease.

Bone Marrow↗

Enhancement of B lymphocyte secretory differentiation by a Ly 1+,2-,Qa-1+ helper T cell subset that sees both antigen and determinants on immunoglobulin.

The question of how many helper T cells are required for producing optimal antibody responses and what function each of the candidate helper cells performs are subjects of intense interest (and controversy) to the majority of immunologists. Our manuscript directly demonstrates for the first time that B cell clone growth and secretory differentiation are controlled by two distinct classes of helper T cells which can be discriminated from one another by profiles of their expressed cell surface alloantigens. There is a significant amount of inferential evidence that two types of helper T cells are required to interact with B cells and antigen in order to induce maximal antibody responses. In all reports, classical MHC-restricted, carrier-specific helper T cells (TH 1) had to interact with hapten-specific B cells via carrier-hapten bridges before the second helper cell (TH 2) could act. In contrast to the TH 1 cells, TH 2 cells have been reported neither to be MHC-restricted nor to require carrier-hapten bridges in their interaction with hapten-specific B cells. That certain isotype-, allotype-, or idiotype-expressing portions of the antigen-induced antibody response are preferentially enhanced in the presence of and depleted in the absence of the appropriate TH 2 cells has led to the suggestion that such TH 2 cells interact with B cells through receptors specific for determinants expressed on B cell surface immunoglobulin molecules. That TH 2 cells recognize autologous immunoglobulin determinants is also indirectly supported by their reported absence in appropriately immunized mice which were deficient in the relevant immunoglobulin during ontogeny [e.g. all TH 2 cells in anti-mu-treated mice; T15-specific TH 2 cells in (CBA/N X BALB/c)F1 male Xid mice which lack T15+ B cells]. It has been suggested that TH 2 cells recognize not only autologous immunoglobulin determinants but also "nominal" antigen since they have been reported to be dependent on antigen priming and reexposure to the priming antigen. However, to establish firmly that a TH 2 cell expresses receptors for both antigen and Ig determinants, one must isolate that helper cell by virtue of its receptor for one of these two moieties and show that the isolated cell has receptors for the other. We have done this, as well as showing that the Ig-recognizing, carrier-immune T cell selectively enhanced B cell secretory differentiation while having no effect on clonal expansion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

T-DNA of pTi-15955 from Agrobacterium tumefaciens is transcribed into a minimum of seven polyadenylated RNAs in a sunflower crown gall tumor.

Northern blot hybridization analysis of polysomal polyadenylated RNA isolated from sunflower crown gall tumor PSCG-15955 demonstrated that a minimum of seven RNAs were transcribed from T-DNA of pTi-15955 from Agrobacterium tumefaciens. The sizes of the T-DNA transcripts were 1.8, 1.6, 1.5, 1.1, 1.0 kilo bases (kb) and two transcripts of 0.8 kb long. The relative abundance of these polyadenylated RNAs varied greatly, the 1.0 kb RNA being the most abundant and the 1.6 kb RNA being the least abundant. Assignment of map locations of the seven polyadenylated RNAs indicated that the conserved region of T-DNA which may play a central role in tumorigenesis contained four RNAs of 1.8, 1.1, 0.8(a) and a portion of 0.8(b) kb long.

DNA Restriction Enzymes↗

Octopine synthase mRNA isolated from sunflower crown gall callus is homologous to the Ti plasmid of Agrobacterium tumefaciens.

We have shown that the structural gene for octopine synthase (a crown gall-specific enzyme) is located in a central portion of the T-DNA that came from the Ti plasmid of agrobacterium tumefaciens and is expressed after it has been transferred to the plant cells. Polyadenylylated RNA was prepared from polysomes isolated from an octopine-producing crown gall callus and purified by selective hybridization to one of five recombinant plasmids. Each such plasmid contained a different fragment of T-DNA of pTi-15955 (octopine-type Ti plasmid). Purified mRNA was translated in vitro in rabbit reticulocyte lysates, and the translation products were immunoprecipitated with antibody against octopine synthase. Total and immunoprecipitated products were characterized by their molecular weights. A polypeptide of M(r) 40,000 (the same as authentic octopine synthase) was synthesized in vitro by crown gall mRNA selectively hybridized to three of the five fragments of T-DNA and precipitated with antibody against octopine synthase. This polypeptide was not immunoprecipitated with normal rabbit antibody nor was it synthesized when mRNA from the habituated callus was substituted. A mRNA 1500 bases long was detected when total mRNA was fractionated on an agarose gel, transferred to nitrocellulose, and used for hybridization to three of the five (32)P-labeled T-DNA fragments. This apparent mRNA for octopine synthase hybridized to the same three fragments of T-DNA as the mRNA for the M(r) 40,000 polypeptide and was not detected in the habituated callus.

Journal Article↗

Lyb3: a B cell surface antigen associated with triggering secretory differentiation.

The results discussed in this review show that the TNP-specific IgA lambda 2-secreting BALB/c plasmacytoma MOPC-315 is partially composed of small lymphocytoid, presecretory cells which express the Lyb3 determinant. It is shown that MOPC-315 cell secretory differentiation, but not clonal proliferation, can be modulated by anti-Lyb3. Anti-Lyb3 serum has been shown to: 1) augment secretory differentiation enhancement by suboptimal numbers of secretory differentiation-enhancing, IgA315-specific helper T cells; 2) replace this secretory differentiation-enhancing T cell population as long as clone growth helper T cells are present; and 3) block suppression of secretory differentiation mediated by carrier-immune Ts cells. These results demonstrate that whether anti-Lyb3 serum enhances immune responses by replacing or augmenting a helper signal or by counteracting suppressor signals, the effects are focused on secretory differentiation events and have no effect on clonal proliferation.

Antibodies, Monoclonal↗

Stereospecificity of behavioural effects of viloxazine in bulbectomized rats does not correlate with its 5-HT-releasing action in vitro.

The effects of the antidepressant drug viloxazine and its two optically active isomers on the passive avoidance learning deficit surgically induced in rats by bilateral bulbectomy have been determined. Fourteen consecutive daily injections of either the racemate or the S-isomer (2, 5 and 10 mg kg-1 i.p.) significantly improved the acquisition of avoidance behaviour. The R-isomer was devoid of such activity in this same dose range. The various isomeric species of viloxazine were also studied in vitro for their ability to induce a release of noradrenaline, dopamine and 5-hydroxytryptamine (5-HT) from rat brain slices. In agreement with previous reports, racemic viloxazine caused a concentration-dependent (10(-5)-10(-3 M) release of 5-MT without affecting any significant change in the release of either catecholamine. However, in contrast to the results of the behavioural studies, this phenomenon did not exhibit stereospecificity, all three isomeric forms being equally active. Thus, there is no simple relationship between viloxazine's behavioural activity in bulbectomized rats and its 5-HT releasing properties observed in vitro. The significance of these findings with respect to previously reported effects of the drug indicative of facilitation of central 5-HT mediated processes is discussed.

Animals↗

Genetic control of autoimmune disease: interactions between xid and Ipr.

A genetic experiment has been performed in mice to test the B cell "hyperactivity" hypothesis of autoantibody production. A backcross was designed such that some progeny carried both the sex-linked recessive gene xid, which markedly reduces the B cell hyperactivity and autoantibody production seen in NZB mice, and the autosomal recessive gene Ipr, which produces a severe lymphoproliferative/autoimmune disorder in the homozygous animal. The data indicate that although xid does not preclude any measured phenotypic expression of Ipr/Ipr disease, it may play a minor modulatory role. In addition, a background gene or genes in the CBA/N mouse, distinct from xid, modulates T cell proliferation in male backcross progeny. This experiment supports the view that autoimmune phenomena are fundamentally heterogeneous, and may involve complex cellular interactions.

Animals↗

The immune response to human type III and type V (AB2) collagen: antigenic determinants and genetic control in mice.

The genetic influences on the specific IgG antibody response to helical antigenic determinants of native soluble type III and V (AB2) human collagen have been studied in mice. H-2-linked Ir genes have been detected for each of these collagens, as have background effects. The alleles controlling high antibody responses can be distinguished from those previously described for bovine collagen type I and type I propeptide. Apparent two-gene complementation in the response to type V (AB2) may indicate that this antigen will be a useful probe in further studies of the complex nature of antigen presentation for T cell recognition. The present studies may facilitate the production of specific, high-affinity monoclonal antibodies for the human collagens which, in turn, will facilitate the study of connective tissue biology and pathology.

Animals↗

Characterisation of inhibitory 5-hydroxytryptamine receptors that modulate dopamine release in the striatum.

The effect of a series of indoleamines on the potassium-evoked tritium release of previously accumulated [3H]dopamine from rat striatal slices has been investigated. The indoleamines 5-hydroxytryptamine, 5-methoxytryptamine, 5-methoxy-N,N'-dimethyltryptamine and tryptamine (10(-7) to 10(-5) M) all reduced potassium-evoked release of tritium, to a maximum of 50%. The uptake of [3H]dopamine was unaffected by these compounds. A series of 5-hydroxytryptamine antagonists were examined for their ability to reduce the inhibition of potassium-evoked tritium release induced by 5-methoxytryptamine. The relative order of antagonist potency obtained was methysergide greater than metergoline greater than methiothepin greater than cinanserin greater than cyproheptadine greater than mianserin, and was consistent with an action on 5-hydroxytryptamine receptors. It is concluded that there are inhibitory 5-hydroxytryptamine receptors located on the terminals of dopaminergic neurones in the striatum.

Animals↗

Effect of breed, slaughter weight and sex on histological properties of ovine muscle.

Thirty-three wether and ewe lambs of two breed groups- Suffolk ram x Suffolk-Rambouillet ewe (Su x R) and Suffolk ram x Finnish Landrace-Southdown ewe (Su x F x So)-and two slaughter weight groups (32 and 41 kg) were studied. Carcass studies, including histological examinations of muscle fiber types, sarcomere lengths and fat cell, were made. The longissimus (LD) muscle at the 13th rib and a sample of the semimembranosus (SM) from the upper proximal location were used. Fibers in both muscles were classified as beta R, alpha R or alpha W. Su x F x So lambs had more alpha W fibers and fewer alphaR fibers in both muscles. Breed type appeared to cause a physiological shift from alpha R to alpha W fiber types. Furthermore, beta R fibers were larger in the SM of the Su x F x So lambs than in that of the Su x R lambs. beta Red fibers in the LD, and all three types fibers in the SM, increased in size with increased weight. Wethers had fewer alpha R fibers in the SM, while ewe lambs had larger alpha R and alpha W fibers in the SM. The more phasic LD muscle had fewer beta R fibers, more alpha W fibers and smaller alpha R and alpha W fibers than the more tonic SM. Su x F x So lambs were fatter, as indicated by larger fat cells in both muscles. In addition, as slaughter weight increased, there was a concurrent increase in fat cell diameters in both muscles. Fat cells were larger in the LD than in the SM. Sarcomere lengths were not affected by breed, slaughter weight or sex. However, sarcomeres were longer in the SM than in the LD. Fat cell size and beta Red cells size for the LD were positively correlated with carcass fat indices, while shear values were negatively correlated with fat cell diameters. There was also a positive relationship between sarcomere length and fat cell size in the SM.

Animals↗

Selectivity in the effects of indomethacin on BCG-activated suppressor cell populations.

Intravenous inoculation of BCG into C57 B1/6 mice activated natural suppressor cells in the bone marrow and induced suppressor cells in the spleen. The suppressor activity of these cell populations was determined by co-cultivating them with normal lymphocytes being immunized against allogeneic P815 cells in vitro. Six million cells from the spleen or bone marrow of BCG treated mice inhibited by more than 50% the alloimmunization of twenty million normal syngeneic lymphocytes. The suppressor cells were found in the nylon wool adherent population in spleen and in both the nylon wool adherent and non-adherent populations in bone marrow. Indomethacin, at a concentration of 10(-6)M, completely blocked the suppression generated by unfractionated spleen or adherent spleen from BCG treated mice. However, 10(-6)M and higher concentrations of indomethacin only partially blocked the suppression generated by unfractionated marrow or adherent marrow from BCG treated mice. The suppression generated by non-adherent marrow from BCG treated mice was completely insensitive to indomethacin.

Animals↗

Unilateral 5,7-dihydroxytryptamine lesions of the dorsal raphe nucleus (DRN) and rat rotational behaviour.

A unilateral lesion in the dorsal raphe nucleus (DRN) resulted in a decreased concentration of 5-hydroxytryptamine (5-HT) in the ipsilateral striatum (CS), anterior cortex and substantia nigra (SN), a loss of [3H]5-HT uptake sites in the cortex and striatum and a selective reduction in 5-HT turnover in the substantia nigra. The directly acting 5-HT agonist 5-methoxy-N,N-dimethyltryptamine induced contralateral turning behaviour in the lesioned animals, whilst the 5-HT releasing agent, p-chloroamphetamine, induced ipsilateral rotation. All rotational behaviour was blocked by haloperidol and the turning behaviour in response to 5-MeODMT was blocked by methysergide. The data presented suggest that the DRN innervates the SN and CS differentially and that nigral 5-HT receptors become supersensitive after denervation of the DRN-SN pathway.

5,7-Dihydroxytryptamine↗

Ly-1 inducer and Ly-1,2 acceptor T cells in the feedback suppression circuit bear an I-J-subregion controlled determinant.

An I-J-subregion controlled determinant is expressed on Ly-1 inducer and Ly-1,2 acceptor T cells in the feedback suppression circuit. Ly-1 T cells absorb the I-J antibody reactive with the Ly-1,2 acceptor T cell, suggesting that both inducer and acceptor T cells have the same I-J determinant. Since less than 10 percent of Ly-1 or Ly-1,2 T cells are killed by anti-I-J plus complement treatment, the I-J determinant demarcates functionally distinct subsets of both the Ly-1 and Ly-1,2 T-cell sets. This I-J determinant is not expressed on a detectable number of Ly-1 helper T cells which induce B lymphocytes to produce anti-sheep red cell antibody in tissue culture.

Animals↗

Purification and Characterization of the Crown Gall-specific Enzyme, Octopine Synthase.

A single enzyme catalyzes the synthesis of all four N(2)-(1-carboxyethyl)-amino acid derivatives found in a crown gall tumor tissue induced by Agrobacterium tumefaciens (E. F. Sm. and Town.) Conn strain B6 on sunflower (Helianthus annuus L.). This enzyme, octopine synthase, has been purified by ammonium sulfate fractionation and chromatography on diethylaminoethylcellulose, blue agarose, and hydroxylapatite. The purified enzyme has all the N(2)-(1-carboxyethyl)-amino acid synthesizing activities found in crude preparations, and the relative activities with six amino acids remain nearly constant during purification. Although the maximum velocities (V) and Michaelis constants (K(m)) differ, the ratio V/K(m) is the same for all amino acid substrates. Thus an equimolar mixture of amino acids will give rise to an equimolar mixture of products. The kinetic properties of the enzyme are consistent with a partially ordered mechanism with arginine (NADPH, then arginine or pyruvate). Octopine synthase is a monomeric enzyme with a molecular weight of 39,000 by gel filtration and 38,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Journal Article↗