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Biomedical subjects

J D Watson

Publications and source records attributed to J D Watson.

At least 235 records · Page 13Linked to original sources
PubMed1983

Genetic control of scrapie and Creutzfeldt-Jakob disease in mice.

Genetic control of experimental scrapie and Creutzfeldt-Jakob disease (CJD) was studied in inbred strains of mice by measuring the times from intracerebral inoculation with the agents to the onset of neurological dysfunction. Every strain of mice examined was susceptible to infection; however, a wide range of incubation times was found for both scrapie and CJD. New Zealand (NZ) mice, which eventually develop an autoimmune disorder, were inoculated intracerebrally with 10(6) ID50 units of the scrapie agent in a Chandler isolate. NZW mice showed incubation periods of less than 95 days; this is the shortest period recorded for any murine host with scrapie. In NZB and NZB X W F1 mice, the incubation periods were approximately 130 days and were similar to those in BALB/c and C57BL mice. Male and female NZ mice exhibited scrapie incubation periods of the same length. Similar results were obtained when B10.Q and C57BL/6J mice were inoculated intracerebrally with 10(4) ID50 units of the CJD agent in a K.Fu. isolate. These observations define a genetic locus or loci controlling the length of scrapie and CJD incubation periods; alleles coding for longer incubation times appear to be autosomal dominant. When congenic mice with a C57BL/10J background differing only in their H-2 haplotypes were studied, the results showed that the D subregion of the H-2 complex played a central role in controlling the length of the CJD incubation period. The q allele at the D subregion resulted in shorter incubation times, whereas the d allele resulted in long incubation times. The p, s, b, and k alleles gave intermediate incubation times. We propose the symbol PID-1 for designating this genetic locus which is located within the D subregion of the major histocompatibility (H-2) complex on murine chromosome 17. In addition, observations on congenic mice provide evidence for the influence of sex on CJD incubation periods. In some strains of inbred mice, males showed significantly shorter incubation periods compared with those for females with experimental CJD. These studies with inbred mice have defined previously unrecognized genes that control the length of scrapie and CJD incubation periods.

Animals↗
PubMed1983

Molecular characterization of interleukin 2.

The isolation of specific T cell growth factors termed interleukin 2 (IL 2) is changing the approach to understanding T cell function. This class of growth factors has allowed te establishment of a number of human and murine T cell lines. We summarize the biochemical properties of human and murine IL 2. Studies have been initiated to isolate mRNA encoding for IL 2. Such RNA can be translated in rabbit reticulocyte lysates yielding IL. 2. This RNA may be useful for the development of probes to isolate lymphokine genes.

Animals↗
PubMed1983

Biology and biochemistry of T cell-derived lymphokines. I. The coordinate synthesis of interleukin 2 and colony-stimulating factors in a murine T cell lymphoma.

Two cloned murine T cell lymphomas of identical lineage exhibit coordinate control of the synthesis of two lymphokines. One line, LBRM-33 5A4, growing in culture can be activated by phytohemagglutinin (PHA) to secrete Interleukin 2 (IL 2), a T cell growth factor, and colony-stimulating factor (CSF), a granulocyte/macrophage growth factor. In the absence of PHA, 5A4 cells do not produce IL 2 or CSF. The second line, LBRM-33 1A5, is incapable of IL 2 and CSF production after treatment with PHA. Stimulation of 1A5 cells with Interleukin 1 (IL 1) converts these cells to a state in which subsequent treatment with PHA leads to the production of IL 2 and CSF. When the 5A4 cell line is recloned, variant subclones can be isolated that do not produce IL 2 or CSF upon stimulation with PHA. The frequency of occurrence of nonproducing variants from 5A4 cells is approximately 1 in 20. Such clones appear to retain a stable nonproducer phenotype. Treatment of a number of these variant subclones with IL 1 prior to exposure to PHA results in the secretion of both IL 2 and CSF from cells. Thus, cell lines derived from cloned LBRM-33 tumor cells either produce both IL 2 and CSF upon stimulation with PHA or they do not produce either lymphokine. These results indicate that the synthesis of IL 2 and CSF in T cells may share common regulatory mechanisms. Further, the LBRM cells appear to be capable of oscillation between two phenotypes representing different states of lymphokine-producing cells.

Animals↗
PubMed1983

Constitutive production by the WEHI-3 cell line of B cell growth and differentiation factor that co-purifies with interleukin 1.

The myelomonocytic cell line WEHI-3 produces constitutively a factor that affects the growth and differentiation of murine B cells in culture. This cell line also secretes colony-stimulating factors (CSF), interleukin 1 (IL 1) but not interleukin 2. Sequential purification through AcA54 gel filtration, DEAE-Sephacel ion exchange chromatography, and buffer electrofocussing clearly resolved the B cell growth and differentiation factor (BGDF) from the CSF activities but failed to separate BGDF from IL 1. The WEHI-3-derived material responsible for BGDF/IL 1 activity, however, exhibited different behavior on DEAE chromatography (elution at 175 mM NaCl) to that reported for IL 1 from the P388D1 cell line (elution at 50 mM NaCl). B cell growth and differentiation could be induced by WEHI-3 BGDF/IL 1 in cultures of normal spleen cells depleted of T cells and adherent cells but not in cultures of spleen cells from B cell-deficient CBA/N mice, even though thymocytes from such mice displayed a normal response to IL 1. Significant B cell proliferation induced by BGDF/IL 1 was apparent only in the presence of submitogenic concentrations of anti-mouse IgM antibodies, but under these conditions few antibody-forming cells (AFC) were generated. In contrast, B cell differentiation to AFC occurred in the presence of the factor alone, and this response was inhibited by anti-IgM. Thus there appeared to be a reciprocal relationship between B cell proliferation and differentiation induced by BGDF/IL 1. The significance of these results is discussed in the light of other recent studies of BGDF.

Animals↗
PubMed1983

In-vivo modulation of thymus-derived lymphocytes with monoclonal antibodies in mice. I. Effect of anti-Thy-1 antibody on the tissue distribution of lymphocytes.

A procedure is described for the in vivo removal of all detectable T lymphocytes from spleen and lymph nodes in mice. A single intraperitoneal injection of monoclonal anti-Thy-1 antibody into mice leads to rapid depletion of functional T cells from peripheral lymphoid organs, but not thymus. The extent of T-cell depletion is dependent on the cytotoxic titre of the anti-Thy-1 antibody used. Antibody with a median cytotoxic titre greater than 10(6) causes the complete removal of cells bearing Thy-1, Lyt-1 and Lyt-2 surface antigens from peripheral lymphoid populations in 3 days. Eight days after treatment Thy-1+, Lyt-1+ and Lyt-2+ cells begin to reappear in these organs. Splenic B cells, assayed by the expression of surface immunoglobulin (sIg) and by mitogenic responsiveness to bacterial lipopolysaccharide (LPS), are not affected by this treatment. The monoclonal anti-Thy-1 antibody does not appear to penetrate thymus tissue and bind to thymocytes. Anti-Thy-1 antibody, but not F(ab')2 is required for in-vivo T-cell depletion. These findings indicate that anti-Thy-1 antibody causes the removal of Thy-1+ cells from peripheral lymphoid tissue, and as the circulating levels of anti-Thy-1 antibody decrease, cells from the thymus repopulate the thymus-dependent areas of the depleted lymphoid organs.

Animals↗
PubMed1982

Forehead reconstruction using a bi-pedicled bone flap.

The forehead can be reconstructed using a bi-pedicled bone flap based on the temporalis muscles. The technique is illustrated by the description of a patient in whom post-operative radio-isotope scanning was used to demonstrate the viability of the transposed bone. The technique is useful when there has been previous infection.

Forehead↗
PubMed1981

Action of vibration on the response of cat muscle spindle Ia afferents to low frequency sinusoidal stretching.

1. A study has been made of the effect of continuous vibration, at 150 Hz, upon the response of muscle spindle afferents to low frequency sinusoidal stretching (1 and 8 Hz). Using the soleus muscle of the anaesthetized cat, with severed ventral roots, recordings were made of single Ia afferents and of the massed Ia afferent discharges in the main bulk of the cut L7 dorsal root. 2. When the amplitude of vibration was large (50 micrometers, short pulses) and that of the sinusoidal stretching was not too great (50-100 micrometers, peak-to-peak) the discharge of the afferents was largely locked 1:1 to the vibration and the response to the sinusoidal stretching was abolished. 3. When the amplitude of the vibration was reduced to below that eliciting continuous afferent driving, then the response to sinusoidal stretching of any amplitude was often markedly increased. This arose through the vibration having a much more powerful excitatory action during the rising phase of the sinusoidal stretch than it did during the falling phase. 4. Averaged over a full cycle, the phase of the response to the sinusoidal stretching tended to be delayed during the vibration in comparison with the normal. This was largely dependent upon the afferents continuing to respond maximally to the vibration around the peak of the sinusoidal stretch, at which stage their unvibrated response is declining, rather than to a phase lag of the whole pattern of response. 5. The results are discussed in relation to the effects of vibration on tremor and the human stretch reflex, and on the determination of the frequency-response of spindle afferents.

Action Potentials↗
PubMed1981

Effect of vibrating agonist or antagonist muscle of the reflex response to sinusoidal displacement of the human forearm.

1. The mechanical resistance of the human forearm to imposed sinusoidal movements has been determined. By means of a visual monitor, subjects maintained a steady force (typically 100 N) by flexing the elbow so as to pull with the wrist against an isometric force transducer. This was mounted upon a stretcher which displaced the forearm sinusoidally at frequencies of 7-11 Hz with a peak-to-peak amplitude of movement of about 1 mm. The average mechanical resistance over 10-40 sec of stretching was analysed into its vector components at the fundamental of the stretching frequency. Observations were made of both the normal resistance and that obtained while applying continuous vibration at 100 Hz to the tendon of either the biceps (agonist) or triceps (antagonist).2. In confirmation of Joyce, Rack & Ross (1974), at frequencies around 10 Hz the normal (unvibrated) response sometimes showed a component of ;negative viscosity' (force increasing during muscle shortening), rather than the simple ;positive viscosity' attributable to muscle visco-elasticity; this effect is attributable to the stretch reflex being appropriately delayed and of sufficient magnitude to over-ride the inherent properties of muscle. Vibration of either agonist or antagonist usually increased the extent of the ;negative viscosity' (negative quadrature component of force), as well as changing the ;elastic' stiffness of the arm (in-phase component of force).3. More commonly, the component of viscosity was initially positive. It was then normally reduced by vibration; that is, the vibration had (in formal terms) again added a component of negative viscosity.4. The vibration did not produce these effects by acting directly upon the contractile system of muscle to reduce its ;visco-elasticity'. On increasing the frequency of stretching the effect of vibration systematically shifted from being the addition of a negative viscosity, as above, to being the addition of a positive viscosity. These effects may all be attributed to an action of vibration on the stretch reflex, with the precise action of the reflex determined by the relation between the cycle time and the delays round the reflex pathway.5. In some experiments the activity of the flexor muscles was sampled by surface electromyograms from biceps and from brachioradialis; these were rectified, smoothed and averaged. For biceps, the absolute depth of e.m.g. modulation in relation to the cycle of stretching was sometimes, but not always, increased by vibration; but for brachioradialis the modulation was always reduced. Thus vibration cannot invariably produce its effects on the mechanical resistance of the arm by increasing the size (gain) of the stretch reflex. However, in all subjects the phase of the electromyographic modulation of both muscles was significantly delayed during vibration, whether of biceps or of triceps. In comparison with the normal, vibration introduced a phase lag on average of 18 degrees . In qualitative terms, this can be shown to explain the typical augmentation of ;negative viscosity'.6. The findings are discussed in relation to the genesis of tremor and to the reflex regulation of muscle contraction. They support the classical idea that afferent activity from the antagonist is as crucially implicated as that from the agonist.

Adult↗
PubMed1980

Helper and killer T cells do not express B cell immunoglobulin joining and constant region gene segments.

We have analyzed four kinds of T cells for rearrangement and expression of immunoglobulin genes. These cells include: (a) whole thymus; (b) WEHI-22, a T-cell lymphoma; (c) HT-1, an major histocompatibility complex-restricted T helper line; and (d) CTLLi6, an H-2 alloreactive killer cell line. None of the B-cell joining and constant gene segments are rearranged in the T cells. The monoclonal cells do not express any C kappa, C lambda, Cmu or C alpha RNA species. Small amounts of C kappa, C alpha, and Cmu sequences are present in RNA prepared from the thymus, although the significance of this RNA for T-cell antigen receptor synthesis is uncertain. The data support the hypothesis that expression of B-cell joining and C gene segments is unnecessary for T-cell helper and T-cell killer activity.

Animals↗
PubMed1980

Genetic control of the immune response to collagen. I. Quantitative determination of response levels by multiple I-region genes.

The antibody response in mice to type I calf skin collagen is quantitatively determined by genes with map to the I region of the H-2 histocompatibility complex. The use of H-2 recombinant B10 congenic strains of mice reveals that a gene in the IA subregion and a gene to the right of the IA subregion affect responsiveness. To examine complementation patterns in the antibody response to collagen, five B10 congenic strains, each bearing an independent H-2 haplotype, were intercrossed to obtain nine hybrid strains heterozygous at the H-2 locus. In five combinations heterozygous progeny produced significantly greater antibody responses than those observed for the homozygous parental strains. Two low responder haplotypes, H-2k and H-2d, were shown to be qualitatively different. Mice of these haplotypes show a different dose--response pattern and a different phenotypic pattern of inheritance with respect to the high responder H-2b haplotype. Complementation effects found in F1 hybrid mice derived from H-2 recombinant parental strains indicate that high responsiveness, controlled by an IA6 subregion gene, can be influenced by an interaction between an IAk subregion gene and an ICd subregion gene on different chromosomes. These data are consistent with the possibility that there exist two or more I region genes that have distinct functions and can interact to affect the levels of immune responsiveness.

Alleles↗