Preweaning experience in the control of mating preferences by genes in the major histocompatibility complex of the mouse.
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Animals↗
Biomedical subjects
J Bard
Publications and source records attributed to J Bard.
Mechanism of class switching.
We have documented the action of unequal sister chromatid exchange on antibody genes, and our studies provide the first molecular description of an unequal sister chromatid exchange event. We delineated the sequences that mediate class switch recombination in normal B cells through genomic Southern analysis of five IgG2-producing hybridomas. Successive subclass switching was documented in two of eight maps and may possibly account for interposed DNA in three additional maps, implying that subclass switching may be a relatively frequent occurrence in normal B cells. As in most other myelomas and hybridomas, the 5' breakpoint of switch recombination in our panel of hybridomas falls 5' to Cmu-associated tandem repeats, whereas the 3' breakpoint falls within C gamma-associated tandem repeats. We consider various hypotheses in the text, the most interesting of which is that deletion of Cmu-associated tandem repeats is a necessary first step before class switch recombination in mature B cells. This hypothesis suggests that Cmu-associated tandem repeats may be a separately regulated DNA element.
Animals↗
Chlamydia trachomatis (L2 serovar) can be bound, ingested and destroyed by differentiated but not by undifferentiated human promyelocyte cell line HL-60.
As a model system for analysing interactions between chlamydiae and myeloid cells and their precursors, we have studied binding, ingestion and destruction of Chlamydia trachomatis (L2 serovar) by the human promyelocytic cell line HL-60. HL-60 cells were induced by phorbol myristate acetate (PMA) and dimethyl sulphoxide (DMSO) to differentiate along either the macrophage or the granulocyte pathway, respectively. Using an immunofluorescence assay and electron microscopy, we have shown that induced (differentiated) HL-60 cells, but not uninduced (undifferentiated) HL-60 or other cell lines treated with PMA or DMSO, exhibit increased binding, ingestion and elimination of C. trachomatis; these activities are associated with specific histochemical and antigenic markers of myeloid differentiation. These results suggest that myeloid cells acquire the ability to interact with and kill chlamydiae during cell development.
Cell Differentiation↗
[Abnormal movements in migraine: a new case].
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Female↗
Both species of chlamydia and two biovars of Chlamydia trachomatis stimulate mouse B lymphocytes.
We have investigated the ability of both species of chlamydiae (C. trachomatis and C. psittaci), two major biovars of C. trachomatis (lymphogranuloma venereum and trachoma), and the two developmental forms of chlamydia (reticulate and elementary bodies) to stimulate murine spleen lymphocytes. All of these forms of the bacteria induce potent proliferation and differentiation to plaque-forming cells by B lymphocytes in vitro. Chlamydiae induce a broad antibody response, suggesting that stimulation is polyclonal in nature. Although all chlamydiae possess a lipopolysaccharide (LPS) genus-specific molecule similar to LPS found on Re mutant enterobacteria, polyclonal B cell stimulation is likely caused by molecules other than LPS, since i) polymyxin B failed to inhibit chlamydia-induced immunostimulation and ii) C3H/HeJ mice (LPS nonresponders) produced normal numbers of PFC after culture with chlamydia (but not LPS). Thus, a cross-species moiety that is not LPS is responsible for polyclonal stimulation by chlamydia. Because these bacteria can exist in latent forms in an animal, and all forms are immunostimulatory, the question of whether these bacteria can alter immune responses if released during other infections or immunizations has been raised.
Animals↗
Binding, ingestion, and growth of Chlamydia trachomatis (L2 serovar) analyzed by flow cytometry.
We have developed a method for quantitatively assessing binding, ingestion, and growth of Chlamydia trachomatis (L2 serovar) in several mammalian cell lines using fluorescence staining and flow cytometry. Cells were incubated with chlamydia at 4 degrees C to monitor binding; ingestion was determined by raising the temperature to 37 degrees C for 1-4 h and removing extracellular bacteria with pronase. Growth of bacteria was measured by assessing brightly stained intracellular inclusions. Fixation with methanol prior to fluorescent staining provided the most intense specific staining with minimal background, as well as preserving cell morphology. Our data reveal relatively slow ingestion of L2 by McCoy fibroblasts (maximum ingestion by 4 h) and a sizeable population of McCoy cells (30-40% of total cells) that ingest L2 but do not permit its growth under certain infectious conditions. It was possible to correlate specific histogram patterns on the flow cytometer with fluorescent microscope observations. This system provides a means of analyzing quantitative interactions between chlamydia and individual host cells.
Animals↗
Chlamydia trachomatis (L2 serovar) binds to distinct subpopulations of human peripheral blood leukocytes.
We have previously shown that infants with pneumonitis caused by Chlamydia trachomatis, an obligate intracellular bacterium, possess increased percentages of B lymphocytes but not T lymphocytes in their peripheral blood. It was then demonstrated that chlamydiae induce proliferation in vitro of human peripheral blood B lymphocytes and, in the presence of T cells, differentiation of B cells to immunoglobulin-secreting cells. In this study, we show that C. trachomatis (L2 serovar) binds preferentially to 50% of human B lymphocytes from peripheral blood but only to a small percentage, if any, of T cells. Both monocytes and granulocytes bind and ingest chlamydiae. Despite chlamydial binding to B cells and ingestion by monocytes, no uptake by B cells and limited growth (fewer than 0.5% inclusion-containing cells) in monocytes occur. There is a dramatic decrease in the percentage of cells associated with the bacteria after culture. These results are the first demonstration of binding of C. trachomatis (L2 serovar) to lymphocytes and represent a direct step toward correlating physical interactions between bacteria and lymphocytes with specific immunostimulatory activities in vitro.
Adhesiveness↗
Participation of the murine X and Y chromosomes in genetically determined chemosensory identity.
The major histocompatibility complex of the mouse imparts to each mouse an odor that reflects its genetic constitution at this region of chromosome 17. Sensory recognition of these differential odors influences reproductive behavior and evokes neuroendocrine responses critical to the maintenance of pregnancy. To determine whether other parts of the mouse genome contribute to individual scent marking, and so may similarly exert a selective force on loci other than the major histocompatibility complex, mice differing genetically only in their X and/or Y chromosomes were tested for individuality of scent in the Y-maze system previously employed to investigate major histocompatibility complex-related scent distinctions. It is shown that the X and Y chromosomes each confer individually of scent related to genotype.
Animals↗
Influence of a genetic difference confined to mutation of H-2K on the incidence of pregnancy block in mice.
In mice, pregnancy is often terminated when the stud male is removed and the pregnant female is exposed to the presence or scent of an unfamiliar male. It is reported here that the incidence of such blocking of pregnancy was higher when the stud and unfamiliar male differed by mutation of the H-2K class I gene of the major histocompatibility complex than when the stud and unfamiliar males were genetically identical. Thus, the olfactory distinction of mice differing by mutation of the H-2K gene, previously demonstrated after training of mice in a Y maze, can spontaneously influence neuroendocrine communications affecting reproduction.
Abortion, Spontaneous↗
Growth regulation in multilayered cultures of human diploid fibroblasts: the roles of contact, movement and matrix production.
Early subcultures of human embryonic lung fibroblasts are exceptional, as they grow far beyond confluence before growth ceases: the stationary dish may well contain 3-10 monolayer equivalents. Maximal growth rates, however, occur at about one-sixth confluence when doubling times are 15-20 hr; a density at which cell contacts begin to become frequent. The fact that a slowing down of growth is first apparent at such low densities argues against this regulation being due to diffusion effects. Confirmation of the role of short-range or contact interactions in growth regulation comes from an experiment using mixed cultures of fibroblasts: this shows that growth inhibition is not carried by medium-borne influences but depends on short-range (less than 1 mm) interactions. Evidence that cells can escape the effects of such contact interactions and so divide comes from time-lapse studies of dense cultures: there is a burst of motility soon after a fresh-medium change, which is followed by a burst of mitosis approximately 20 hr later. A medium change to conditioned medium supplemented with 10% foetal calf serum leads to neither the burst of motility nor the subsequent burst of mitosis, although this medium is better able to support the growth of sparse cells than is fresh medium. Data are also presented to show that the amount of collagen deposited in superconfluent cultures affects their growth: the stimulation of collagen production with ascorbic acid leads to an unexpectedly low stationary cell density and rather less movement in the culture. This result suggests that the collagen stabilizes cell contacts that are responsible for growth inhibition. The question of why these cells grow more slowly as density increases cannot be answered directly by these experiments; nevertheless, the results suggest that cell contact affects the permeability of the cell membrane to medium.
Cell Communication↗
In vitro expression of chloroplast genes in lysates of higher plant chloroplasts.
A DNA-dependent in vitro-coupled transcription-translation system has been prepared from lysates of isolated chloroplasts. These lysates are comparable to those of Escherichia coli in transcriptional and translational fidelity and efficiency in response to a given template DNA. When Nicotiana tabacum chloroplast DNA is used as template with chloroplast lysates (N. tabacum or spinach) or E. coli lysates, NaDodSO4 gel analysis reveals similar polypeptide patterns that are distinct from the patterns obtained with E. coli DNA. Genes in recombinant plasmids containing chloroplast DNA are also expressed in these in vitro systems. DNA . RNA hybridization experiments show that transcripts are synthesized from most of the chloroplast genome. Newly synthesized large subunit of ribulosebisphosphate carboxylase/oxygenate and a transcript of the large subunit gene (rbcL) are observed in chloroplast lysates using as template chloroplast DNA or cloned fragments of tobacco chloroplast DNA that contain the large subunit gene. Results suggest that differential expression of chloroplast genes occurs in vitro. By using cloned chloroplast DNA templates in this homologous system, it is possible to identify and map structural genes for chloroplast proteins.
Cell-Free System↗
Chlamydia trachomatis stimulates human peripheral blood B lymphocytes to proliferate and secrete polyclonal immunoglobulins in vitro.
Infectious Chlamydia trachomatis (LGV strain), obligate intracellular bacteria, stimulated human peripheral blood lymphocytes to proliferate and secrete immunoglobulins in vitro. In contrast, mock-infected preparations were unable to induce similar responses in peripheral blood lymphocytes. Although levels of immunoglobulin secreted into the media of LGV-stimulated cultures were greater than 10 micrograms/ml, we estimated that less than 1% of these molecules were directed against the bacteria itself, suggesting polyclonal antibody production. Since stimulation with Formalin-killed bacteria resulted in comparable numbers of plaque-forming cells (PFC) as infectious particles, we concluded that the polyclonal immunoglobulin response was not dependent on the in vitro chlamydial infectious process. The polyclonal PFC response induced by LGV was highly sensitive to monocyte inhibition. Although LGV induced proliferation of predominantly B cells, the numbers of generated PFC was increased by the addition of autologous T cells. Neither lymphocyte proliferation nor PFC responses of normal human volunteers correlated significantly with the presence or titer of antichlamydial antibodies in their sera.
Antibodies, Bacterial↗
SCH 370 (clotrimazole-betamethasone dipropionate) cream in patients with tinea cruris or tinea corporis.
The safety and efficacy of SCH 370 (1 percent clotrimazole/0.05 percent betamethasone dipropionate) cream was compared with each of its individual components in 331 patients with tinea cruris or tinea corporis. The study was a multicentered, randomized, double-blind, parallel-groups design. The patients received one of three treatments applied twice a day for two weeks and returned for a follow-up visit two weeks after the last application. Total signs and symptoms scores of infections were evaluated at baseline, once between days three to five, and after weeks one, two, and four. Culture and potassium hydroxide preparations were done at baseline and weeks two and four. SCH 370 cream demonstrated more rapid therapeutic activity than the antifungal agent alone, resulting in significantly better clinical results in early treatment and in midtreatment. As expected with a steroid, betamethasone dipropionate achieved relief of inflammatory signs and symptoms early in the course of treatment, but SCH 370 was superior from one week on in the patients with tinea cruris and at post-treatment in the patients with tinea corporis. Mycologically, SCH 370 cream and clotrimazole were comparable at the end of the study and results were significantly better than those for betamethasone dipropionate. All three treatments were safe with no reports of unexpected or serious adverse experiences.
Adult↗
Recognition of H-2 types in relation to the blocking of pregnancy in mice.
Inbred BALB/c females were mated and subsequently exposed in a divided cage to "stimulus" males or females whose H-2 type was similar or dissimilar to the stud male's. The incidence of pregnancy blocking was considerably higher when stud and stimulus males differed in H-2 type than when they did not. Similar results were obtained with urine samples of H-2 identical and nonidentical males. Females exposed after mating to other females whose H-2 type differed from the stud male, under the same experimental conditions, also showed an appreciable incidence of pregnancy block. It is therefore concluded that chemosensory recognition of H-2 types affects the reproductive hormonal status of the pregnant female.
Animals↗
[Cataplectic falls disclosing hypercalcemia].
Clinical manifestations of hypercalcaemic encephalopathy were heralded in three patients by isolated cataplexy-like falls without loss of consciousness. In one patient the falls with global hypotonia occurred every 5 to 10 seconds and were unaccompanied by changes in E.E.G. The falls disappeared after hypercalcaemia was corrected by excision of a parathyroid adenoma in two patients and by calcitonin injections in one. For this reason, there is little doubt that they were due to the hypercalcaemia, but their mechanism is poorly understood; it probably involves metabolic disturbances in the reticular systems of the brain stem. The connections between calcium metabolism and neuromediators in the brain stem are discussed.
Adenoma↗
Sensory distinction between H-2b and H-2bm1 mutant mice.
Genetic polymorphism in the H-2:Qa:Tla region of chromosome 17 is associated with constitutive variation of bodily odor phenotypes which permit individual olfactory recognition among mice. To determine whether known genes in the H-2:Qa:Tla complex are concerned in the constitution of odor phenotypes, mice were tested for their ability to sense a difference between the B6/By (H-2b) and congeneic B6.C-H-2bm1 strains, which differ genetically by mutation of the H-2K gene. As in previous studies of the sensory discrimination of H-2:Qa:Tla phenotypes, mice were trained by reward in a Y maze to distinguish the odors of urine samples, and the successful distinctions of B6/By from B6.C-H-2bm1 were confirmed by transfer of training, without reward, to coded samples of urine from genetically equivalent urine donor mice which the trained mice had not previously encountered. Cosegregation of odor phenotype with H-2b and H-2bm1 was demonstrated by transfer of training to typed H-2b and H-2bm1 homozygous segregants of F2 generations of appropriate crosses. Although it is not excluded that the differences in odor phenotype which distinguish H-2b and H-2bm1 mice are directly related to the structure of the H-2b and H-2bm1 products, it is equally possible that H-2-related odor phenotypes arise from effects of H-2 genetic variation on metabolic pathways either directly, or indirectly through developmental polymorphism.
Animals↗
Two Ly-2 T helper cell subsets distinguished by Qa-1 phenotype. The priming environment determines whether one or both subsets will be generated.
The Qa-1 cell surface phenotype reportedly distinguishes two Ly-1 T cell subsets conjointly required for T helper effector activity. Ly-1 cells, obtained from several different priming regimens, were negatively selected with anti-Qa-1 plus complement and compared with unselected Ly-1 cells for helper cell activity. Priming isolated T cells on antigen-pulsed macrophages in the absence of B cells favors the generation of the Ly-1:Qa1- subset, which is capable of efficient helper activity in the absence of the Ly-1:Qa-1+ subset. Priming T cells in an environment containing B cells generates both Ly-1:Qa-1- helper effector cells and Ly-1:Qa-1+ cells which contribute to the helper effect. Whether Ly-1:Qa-1+ cells are capable of independent helper activity cannot be determined, and, as such, Ly-1:Qa-1+ cells are more appropriately termed "help associated" rather than "helper effector." Our results assign a membrane phenotype, Qa-1, which distinguishes an Ly-1 help-associated B cell requiring subset in our system and may prove to be a general marker in a number of systems of Ly-1 inducer cell subsets which functionally require or recognize B cells or their products.
Animals↗
Chemosensory recognition of phenotypes determined by the Tla and H-2K regions of chromosome 17 of the mouse.
It is known that mice can distinguish the H-2 haplotypes of other mice by scent and that urine is a potent source of the characteristic odors governed by H-2. It now is shown that genetic disparity confined to the Qa:Tla region of chromosome 17, adjacent to H-2, is accompanied by distinctive urinary scents that can be distinguished by trained mice in a Y maze. This was confirmed by the transfer of training procedure in which mice trained to distinguish the urine of B6 mice from the urine of recombinant congeneic B6-Tlaa mice successfully distinguished the urines of Tlaa and Tlab homozygous F2 segregants of the cross B6 X B6-Tlaa in the absence of reward, including blind trials with coded urine samples. It also is shown that genetic disparity confined to the K end of H-2 is accompanied by distinctive urinary scents recognized in the Y maze. Thus, mice trained to distinguish the urines of B10 from B10.A congeneic mice successfully distinguished various combinations of B10, B10.A, and B10.A (2R, 3R, 5R, and 18R) recombinant congeneic mice representing genetic differences limited to the K end of H-2. It is suggested that the individual scents of mice comprise several odorous components, at least some of which may be incidental to quantitative or qualitative metabolic variations arising from polymorphism of genes such as H-2.
Animals↗