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Biomedical subjects

J C Howard

Publications and source records attributed to J C Howard.

At least 91 records · Page 5Linked to original sources
PubMed1983

Intercalative and nonintercalative binding of large cationic porphyrin ligands to polynucleotides.

The interactions of two positional isomers and one analogue of meso-tetra (4-N-methylpyridyl) porphine, with the synthetic polynucleotides poly[d(A-T)] . poly[d(A-T)] and poly[d(G-C)] . poly[d(G-C)] have been investigated by circular dichroism. All four porphyrins were found to bind to the polynucleotides as shown by the induction of circular dichroism in their Soret bands. Furthermore, the sign of the induced ellipticity reflects selective occupation of binding sites by the porphyrin ligands. The conformational lability of poly[d(A-T)] X poly[d(A-T)] was found to be appreciable as micromolar amounts of meso-substituted 4-N-methylpyridyl, 3-N-methylpyridyl, and p-N-trimethylanilinium porphines induced a CD spectrum similar but not identical to that of DNA in the Z-form, i.e. a negative band at 280 nm and a positive band at 259 nm. The effect of porphyrin binding to poly[d(G-C)] X poly[d(G-C)] was less pronounced and dissimilar to that seen in the AT polymer.

Chemical Phenomena↗
PubMed1983

The mechanism of synergistic complement-mediated lysis of rat red cells by monoclonal IgG antibodies.

The mechanism of synergistic complement-mediated lysis of rat red cells was investigated using rat monoclonal antibodies against class I RT1Aa antigens. The increased lytic activity when using two antibodies simultaneously is due to the increase in the number of activated C1 molecules on the cell surface and this results from (a) an increase in the number of binding sites for C1q, (b) an increase in the functional affinity constant for C1q binding and (c) an increase in the rate of activation of C1. Complete lysis of red cells was only achieved if one member of the synergistic pair was of the gamma 2b isotype, and this isotype was the only one to which binding of 125I-labeled C1q could be detected. A partial synergistic effect was seen using an F(ab')2 fragment of antibody. Increased uptake and activation of C1 probably results both from the presence of two antibodies attached to each antigen molecule and from the formation of antigen-antibody catenars.

Animals↗
PubMed1983

The major histocompatibility complex of the rat: a partial review.

The major histocompatibility complex of the rat is now called RT1, and this name is becoming widely accepted. In the past five years many recombinants have been reported within RT1 that enable distinct functional regions to be identified and located relative to each other. RT1 does not at present look particularly like its closest known relative, H-2. No doubt the genetic relationship will become apparent at the DNA level. The spontaneous diabetes mellitus of the BB rat line is associated with RT1. The data so far suggest that RT1u supplies a dominant susceptibility that becomes apparent only if protection conferred by a dominant gene mapping outside the MHC is withdrawn. It seems likely that the BB rat carries a recessive mutation at this "protective" locus.

Alleles↗
PubMed1982

Immune response genes controlling responsiveness to major transplantation antigens. Specific major histocompatibility complex-linked defect for antibody responses to class I alloantigens.

We have identified two major histocompatibility complex (MHC)-linked Ir genes that control the antibody response made by rats against class I major alloantigens. We have named these genes Ir-RT1Aa and Ir-RT1Ac. These Ir genes determine responsiveness of the immunized animal in a typical codominant fashion. There is no evidence so far for trans-complementation between low-responder haplotypes. Detailed studies of Ir-RT1Aa indicate that it controls the antibody response to at least two distinct alloantigenic determinants on RT1Aa molecules. These class I molecules thus behave like hapten-carrier conjugates when the response against the carrier is under Ir gene control. Analysis of the origin of alloantibody-forming cells in tetraparental radiation chimeras indicates that Ir-RT1Aa must control the provision of effective help to B cells. In many respects therefore, the properties of Ir-RT1Aa are broadly similar to those described for Ir genes controlling antibody responses to conventional antigens. The existence of apparently conventional Ir genes controlling the antibody response to major alloantigens strongly suggest that the processing of these transmembrane molecules by host antigen-presenting cells is a prerequisite for immune induction, and that it is the MHC of the responder rather than that of the allograft to which T helper cells are restricted in alloimmune responses in vivo.

Animals↗
PubMed1982

The influence of drugs on the overflow of noradrenaline and the identification of receptors in guinea-pig atria.

1 Salbutamol (1.0 microM) and isoprenaline (1.2 nM) significantly increased the fractional release of tritiated noradrenaline from driven left atria but phentolamine (10 microM) failed to do so. Butoxamine (4.0 microM) blocked the increase in overflow produced by isoprenaline. Isoprenaline (1.2 nM), phentolamine (10.0 microM) and salbutamol (1.0 microM) failed to increase the overflow of tritiated noradrenaline from spontaneously beating atria. 2 Spontaneously beating atria were therefore used to identify the receptors mediating chronotropism and inotropism. 3 There was no clear relationship between inotropism and chronotropism. 4 The inotropic effects of both dobutamine (0.04-4.0 microM) and isoprenaline (0.11-9.0 nM) were inhibited by practolol (4.0 microM) and by butoxamine (4.0 microM). The chronotropic effects were inhibited only by practolol (4.0 microM). 5 Both inotropic and chronotropic effects of noradrenaline (3.0-200 nM) were antagonized by practolol (4.0 microM), but not by butoxamine (4.0 microM). Thus both functions appeared to be mediated by beta 1-adrenoceptors when noradrenaline was the agonist. 6 Inotropic responses to salbutamol (0.45-7.5 microM) were inhibited by both practolol (4.0 microM) and by butoxamine (4.0 microM), but chronotropic responses were antagonized only by butoxamine (4.0 microM), Thus salbutamol acts on both beta 1-and beta 2-adrenoceptors to produce an inotropic response but only on beta 2-adrenoceptors to produce its chronotropic response. 7 It is concluded that both beta 1- and beta 2-adrenoceptors can mediate chronotropism and inotropism in guinea-pig isolated atria. Determination of the postsynaptic effects of drugs should be carried out on spontaneously beating rather than driven atria to obviate modification of the responses by noradrenaline release from sympathetic neurons.

Albuterol↗
PubMed1982

Clinical application of the bivariate plotting procedure in the prediction of hearing loss.

This study examined the utility of the bivariate plotting approach to reflex-based hearing loss prediction, and introduced a modification to the method which accounts for the effects of mild and high frequency hearing losses. The effect of pure tone sensitivity at 3,000 Hz was found to be of particular importance in the predictive accuracy of the method. When 3,000 Hz is considered, the original concept of the bivariate graph can be further refined into three regions. Here, normal ears and those with substantial hearing loss can be identified with considerable success. A "grey area" between these correctly identifies some degree of loss with 89% accuracy.

Adult↗
PubMed1981

The consequences of intravenous clofibrate and its implications in the treatment of fat embolism.

Intravenously administered clofibrate has previously been used in treating experimental fat embolism. In the present study, this procedure was found to produce a syndrome identical to classical experimental fat embolism syndrome. Following the intravenous injection of clofibrate, and the lungs of rats became hemorrhagic and edematous (increased weight) and contained fat globules (clofibrate emboli) when observed microscopically. Dosages of 100 to 0.88305 mul/100 gm body weight produced symptoms ranging from acute death due to massive embolism of lungs to a subclinical fat (clofibrate) embolism syndrome.

Animals↗
PubMed1981

Induction of DNA damage by porphyrin photosensitizers.

The photosensitizing effects of hematoporphyrin derivative, meso-tetra(p-sulfonatophenyl)porphine, meso-tetra(p-carboxyphenyl)porphine, and meso-tetra(4-N-methylpyridyl)-porphine on ColE1 supercoiled DNA were studied using agarose gel electrophoresis. Photoinduced single- and double-strand breaks were observed to form under neutral conditions. Singlet oxygen was shown to predominate in the mechanism of the induction of these lesions in the case of hematoporphyrin derivative, meso-tetra(p-sulfonatophenyl)porphine, and meso-tetra(p-carboxyphenyl)porphine and to play a significant role in the case of meso-tetra(4-N-methylpyridyl)porphine. The results suggest the possibility that the risk of photodynamic carcinogenesis may accompany photochemotherapy and fluorescence endoscopic procedures involving porphyrin photosensitizers.

Cocarcinogenesis↗
PubMed1980

Heterogeneity of the tolerant state in rats with long established skin grafts.

Tolerance in rats with long established allogeneic skin grafts brought about by the neonatal inoculation of hybrid lymphomyeloid cells is immunologically heterogeneous because 2 states of tolerance may be defined operationally as fully and partially tolerant. T cells from fully tolerant donors transfer tolerance and are unresponsive in MLC, but T cells from partially tolerant donors do not transfer tolerance and are modestly responsive in MLC. A state of tolerance may exist without detectable suppression. Therefore, tolerance, traditionally defined as the permanent acceptance of an allogeneic skin graft, does not reflect a uniform immunologic state.

Animals↗
PubMed1980

Isolation of six monoclonal alloantibodies against rat histocompatibility antigens: clonal competition.

We describe the isolation of six clones and some variant derivatives of rat x mouse hybrid myelomas secreting alloantibody against antigens of the rat major histocompatibility complex. Very large numbers of active hybrids were obtained but many were lost early in the post-fusion period; evidence is presented for rapid selective processes operating in uncloned complex hybrid cultures. The results suggest that the secretion of specific immunoglobulin chains is as stable a function in rat x mouse hybrid myelomas as in mouse x mouse hybrid myelomas.

Animals↗
PubMed1979

Effectiveness of antihistamines in the symptomatic management of the common cold.

A multicentric trial compared the effect of chlorpheniramine maleate with a placebo on the signs and symptoms of the common cold. Two hundred seventy-one patients were domiciled for 48 hours and evaluated during this period and for four days afterwards. Evaluations by both patients and physicians showed that chlorpheniramine maleate was superior to placebo in lessening the degree of symptoms of the common cold. Statistically significant differences were found both on the first day and as late as the seventh day. Significant differences and trends were shown in such measures as total objective score, physicians' evaluation of symptoms. The overall incidence of side effects other than drowsiness did not differ between the treatment groups.

Adolescent↗
PubMed1979

Interaction of DNA with a porphyrin ligand: evidence for intercalation.

The porphyrin photosensitizer, meso-Tetra (4-N-methylpyridyl) porphine tetraperchlorate binds to calf thymus DNA by intercalation and by external electrostatic association. This was concluded from the results of measruements involving Scatchard analysis, viscometry, thermal denaturation, and circular dichroism.

Animals↗