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Biomedical subjects

J Gordon

Publications and source records attributed to J Gordon.

At least 469 records · Page 26Linked to original sources

N4-Acetylcytidine. A previously unidentified labile component of the small subunit of eukaryotic ribosomes.

The nucleoside content of 18 S rRNA from rat liver is determined under conditions known to prevent the destruction of chemically labile modified nucleosides. Two base-modified nucleosides, not completely identified before, are shown to be N6-methyladenosine and 7-methylguanosine. The results further demonstrate the presence of a hitherto unidentified component of 18 S rRNA whose spectra and chromatographic properties are identical with that of N4-acetylcytidine. In addition, this compound is not detectable in 28 S rRNA nor in 16 S rRNA derived from the small ribosomal subunit of Escherichia coli. However, it appears to be conserved in the small ribosomal subunit of eukaryotes, since it is also present in yeast 17 S rRNA and chicken liver 18 S rRNA.

Animals↗

Epithelioid granulomas associated with Hodgkin's disease: clinical correlations in 55 previously untreated patients.

Non-caseating sarcoid-like epithelioid granulomas associated with Hodgkin's disease have been found in 55 patients initially staged and treated at the Stanford University School of Medicine. These patients are compared to 553 concurrent patients not having granulomas associated with their Hodgkin's disease. Pre-treatment parameters of the two groups are presented and found not to be different. Patterns of relapse in granuloma patients are presented and no relationship between location of granulomas and subsequent relapse is found. Survival and relapse-free survival curves are significantly different in favor of the granuloma group (p = 0.005 and p = 0.03, respectively). Correlation with skin test data has been attempted using a matched control analysis and no difference is found in reaction to intradermal antigens between the two groups.

Adult↗

Blastogenic factor: its role in the mixed leukocyte culture reaction.

The MLC-CML reaction depends on cooperation between different subsets of T lymphocytes in which soluble mediators may play a critical role. Evidence is presented that cell-free supernatants from mixed cultures, containing blastogenic factor (BF) activity can, together with solubilized membrane preparations, induce a primary cell-mediated lympholysis (CML) reaction of the same order of magnitude as intact allogeneic stimulating cells. Furthermore, BF alone can induce secondary mixed leukocyte culture (MLC) and CML reactions very efficiently. The results described suggest that BF is produced in response to activation by LD determinants, probably by helper T cells, and that the target of BF is the cytotoxic lymphocyte. It would appear that regulation of CML activity may be mediated by BF, and exhaustion of the mediator may be responsible for the decline of cell proliferation and effector function in the MLC reaction.

Cytotoxicity, Immunologic↗

Regulation of the mixed leukocyte culture reaction by suppressor cells.

Regulation of the mixed leukocyte culture (MLC) reaction by suppressor cells raised and tested in MLC has been evaluated. The experiments described suggest that suppressors are distinct from cytotoxic T lymphocytes (CTL), both in terms of conditions optimal for their activation, as well as through demonstration of efficient suppression in the total absence of cytotoxic activity. Suppressor cells inhibit the activation of the precursors of CTL, and may also prevent the production of the lymphokine blastogenic factor; they do not appear to interfere with the reaction of primed cells. It is suggested that suppressor cells may regulate the MLC reaction by preventing recruitment of fresh competent cells, and by limiting the duration of the reaction of cells already activated.

Cytotoxicity, Immunologic↗

Ureteroneocystostomy in the treatment of reflux in neurogenic bladders.

There were 15 patients with neurogenic bladders, representing 23 renal units with reflux, who underwent reimplantation with the Politano-Leadbetter technique. The over-all success rate was 30 per cent. Failures, including persistent reflux or obstruction, were demonstrated on at least 1 side of all bilateral reimplantations and 3 of 7 unilateral procedures. These results are compared to those in the recent literature. We conclude that case selection, limiting the operation to only those patients with balanced bladders, will ensure uniformly good results. External sphincterotomy in patients with reflux may alter the clinical course, either obviating the need for reimplantation or creating a balanced bladder. Other forms of therapy, such as urinary diversion, are indicated only in those patients who persist with markedly abnormal bladders and renal deterioration.

Adolescent↗

Two chromatographically separable forms of Escherichia coli elongation factor Tu.

Two forms of the elongation factor Tu from Escherichia coli have been separated by chromatography on DEAE-Sephadex A50. Obvious chromatographic artifacts have been ruled out by investigation of the elution profile of GDP (a component of the column buffer as well as a ligand of Tu) and by rechromatography of the two components, either separately to give the component peaks or together to give a double peak. The two components have been confirmed as Tu by the poly(uridylic)-dependent polyphenylalanine synthesis and by the distribution of the Tu protein as quantitated from sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Complexes with the elongation factors Ts and G have also been ruled out by activity profiles and by quantitation of the protein distribution, again on gels. The distribution of the two forms between ribosomal and supernatant fractions has been examined: one is bound preferentially to the ribosomal fraction and the other is found in the supernatant fraction. The possible significance of this is discussed.

Bacterial Proteins↗

The eel retina. Receptor classes and spectral mechanisms.

Light and electron microscopy revealed that there are both rods and cones in the retina of the eel Anguilla rostrata. The rods predominate with a rod to cone ratio of 150:1. The spectral sensitivity of the dark-adapted eyecup ERG had a peak at about 520 nm and was well fit by a vitamin A2 nomogram pigment with a lambdamax = 520 nm. This agrees with the eel photopigment measurements of other investigators. This result implies that a single spectral mechanism--the rods--provides the input for the dark-adapted ERG. The spectral sensitivity of the ERG to flicker in the light-adapted eyecup preparation was shifted to longer wavelengths; it peaked at around 550 nm. However, there was evidence that this technique might not have completely eliminated rod intrusion. Rod responses were abolished in a bleached isolated retina preparation, in which it was shown that there were two classes of cone-like mechanisms, one with lambdamax of 550 nm and the other with lambdamax of less than 450 nm. Ganglion cell recording provided preliminary evidence for opponent-color processing. Horizontal cells were only of the L type with both rod and cone inputs.

Animals↗

The eel retina. Ganglion cell classes and spatial mechanisms.

We have been able to separate optic fibers in the eye of the eel Anguilla rostrata into two distinct classes on the basis of spatial summation properties. X fibers, the first class, are like X ganglion cells in the cat: they have null positions for contrast reversal sine gratings; they respond at the modulation frequency; and many have a strong surround mechanism. X fibers, the second class, respond with an "on-off" response to local stimulation, to diffuse light modulation, to coarse drifting gratings, and to contrast reversal gratings. We have put forward a model for the receptive field of X fibers which involves two subunits, with rectification before the subunits add their signals. This model accounts for many of the quirks of X fibers.

Animals↗

Free immunoglobulin light chain synthesis by lymphocytes from patients with hypogammaglobulinaemia.

Lymphocytes from six individuals with reduced or deficient serum immunoglobulins of one or more class were assessed for immunoglobulin production in vitro. There was no clinical evidence of a secondary cause for hypogammaglobulinaemia and three of the cases were receiving immunoglobulin therapy. The predominant immunoglobulin product in the culture supernatants form four cases was free light chain. In contrast, peripheral lymphocytes from two cases with partial IgA deficiency and from normal individuals exhibited a balanced synthesis of heavy and light chains. These findings are discussed with particular reference to free light chain synthesis by immature neoplastic B lymphocytes and to normal B lymphocyte differentiation.

Adolescent↗

Anti-tumor immunity in B lymphocyte-deprived mice. I. Immunity to a chemically induced tumor.

Immunity to a syngeneic methylcholanthrene-induced tumor was studied in (C57BL/6 X C3H)F1 males, treated continuously from birth with a rabbit anti-mouse IgM serum. Such mice have been shown to be selectively depleted of Ig-bearing lymphocytes and incapable of synthesizing antibodies. In the experiments reported, a heightened resistance of these mice to the syngeneic fibrosarcoma was demonstrated. This resistance was manifest in significantly slower tumor growth at the site of injection, as well as a lower incidence of spontaneous pulmonary metastasis.

Animals↗

Free light chain synthesis by neoplastic cells in chronic lymphocytic leukaemia and non-Hodgkin's lymphoma.

Cell populations from twenty-two cases of B-cell neoplasia reflecting various stages of B-lymphocyte maturation were investigated for their ability to synthesise immunoglobulin (Ig) in vitro. All surface Ig positive neoplasms studied synthesised labelled Ig of the same light chain class as that expressed at the cell surface. Immature B-cell neoplasms, chronic lymphocytic leukaemia (CLL) and CLL-type lymphoma, synthesised only a minor proportion of their total protein as Ig; labelled free light chain was the only detectable secreted Ig product in thirteen cases and was in excess in the remaining four. Labelled heavy chain was detected in cell lysates in all but one case. Follicular centre cell lymphomas, neoplasms of more mature B-lymphocyte types, synthesised more of their total protein as Ig and showed a more balanced synthesis of heavy and light chains compared to the other neoplasms studies. The Ig synthesis patterns and, in particular, free light chain production, are discussed in relation to normal B-lymphocyte maturation.

B-Lymphocytes↗

Free immunoglobulin light chain synthesis by neoplastic cells in leukaemic reticuloendotheliosis.

Neoplastic cell preparations from four patients with clinically and morphologically well-defined leukaemic reticuloendotheliosis (LRE) were investigated for their capacity to synthesize immunoglobulin in vitro. Neoplastic cells from all cases synthesized immunoglobulin of the same light chain class as expressed at their cell surface. Labelled IgM and IgD were identified in cell lysates while free light chain was the predominant labelled immunoglobulin product in the LRE culture supernatants. The capacity of LRE cells to synthesize immunoglobulin and free light chain was similar to that of neoplastic cells from patients with chronic lymphocytic leukaemia, and provides further evidence for the B-lymphocyte origin of the neoplastic cells in LRE.

Cells, Cultured↗

Evolutionary microdivergence of chick and rat liver ribosomal proteins.

We have set out to establish a nomenclature for ribosomal proteins which transcends, as far as is possible, the species from which the ribosomes were isolated. Initally, we identified individual proteins of rat liver by two-dimensional polyacrylamide gel electrophoresis and comparison with the classification system established by others (Sherton, C.C., and Wool, I.G. (1972) J. Biol. Chem. 247, 4460-4467). This was possible with minor modifications. We carried out a detailed comparison of the rat liver proteins with those of chick liver; parallel separate and mixed preparations of ribosomal subunits from the two species were made. Spots on the two-dimensional gels were carefully scrutinized for possible species differences. Proteins which gave congruent spots for the separate and the mixed preparations were tentatively assumed to be identical between the two species. For these proteins, a species-independent nomenclature was adopted. Contrary to earlier reports, a number of proteins were found which were not identical between the two species. These were assigned a species-specific nomenclature. In all, 7 proteins in the small subunit and 17 from the large subunit of the rat liver ribosome were found to be significantly different in the chick. The evolutionary implications of this are discussed.

Animals↗

Modification of pigmentation patterns in allophenic mice by the W gene.

Mouse embryos heterozygous at the W locus were combined with embryos which were wild type at this locus but homozygous for albino. The resulting allophenics displayed an unusual pigmentation phenotype consisting of entirely white fur and ruby-coloured eyes. Microscopic examination showed the eye pigment to be located exclusively in the retinal epithelium, which was a mosaic of black and white sectors. This ruby-eyed white pattern corresponds to what would have been expected for WWCC in equilibrium wwcc mosaics but not for WwCC in equlibrium wwcc mice. WW mice are black-eyed whites, but Ww mice have black eyes and black fur, except for a small ventral white spot. These results suggest that melanocytes of the Ww genotype, although capable of producting normally pigmented fur in Ww animals, fail to populate hair follicles when the competition with wwcc (albino) melanocytes that are wild type at the W locus. The genotype of these WwCC in equilibrium wwcc alophenes was proved by progeny testing. This is apparently the first report of a single gene change affecting the competitive ability of cells in allophenic mice, and suggests that such changes may play a significant role in the clonal selection of embryonic cells during development.

Animals↗

Estrogen and endometrial carcinoma. An independent pathology review supporting original risk estimate.

Initial evidence suggested that estrogen therapy increases the risk of endometrial carcinoma. It was then suggested that some studies may have exaggerated the hazard of estrogen therapy by including patients with atypical endometrial hyperplasia among those having endometrial carcinoma. Three internationally recognized pathologists reviewed the histology slides available from the Ziel and Finkle study, which originally reported a risk ratio of 7.6 for estrogen users. At least one of the pathologists concurred with the original diagnosis in all but one case. Furthermore, all pathologists aggreed that 74 per cent (66/89) were correctly diagnosed. In the 66 patients with unanimous diagnosis, 61 per cent (40/66) had used conjugated estrogens, versus 57 per cent (54/94) in the original study. On the basis of 66 patients and 132 matched controls, the revised risk-ratio estimate is 8.1 (with a one-sided 95 per cent lower confidence limit of 4.5), validating the original estimate.

Biopsy↗