The French temperance movement and problem of rural alcoholism.
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Biomedical subjects
Publications and source records attributed to E A Arnold.
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We have found that in liquid cultures of spleen cells of adult Syrian hamsters of the F1D strain, the hematopoietic microenvironment is adequate to sustain proliferation of splenic stem cells for periods of greater than 4 mo, and permits granulocytic, monocytic, and megakaryocytic differentiation without secondary repopulation or addition of exogenous growth factors to the basic medium of RPMI 1640 plus 20% horse serum. Intimate topographical relations are established between spleen stromal cells and hematopoietic cell components of the culture is adherent "cell-producing" islets. Some of these islets are associated with multiple hematopoietic cell types such as myeloid, monocytic, and megakaryocytic cells. Other islets are associated with a single cell type such as megakaryocytes, which suggests a limited potential of some adherent stromal cells to direct the differentiation of precursor cells. Cultures of this type provide a simple and convenient model for investigation of the mechanisms controlling differentiation of hematopoietic stem cells, not only for granulocytic and monocytic cells, but for megakaryocytic cells as well.
Sucrose density gradient analysis of cytosol from normal and neoplastic rat prostatic tissues exhibited a peak of (3H) retinoic acid binding in the 2S region, corresponding to the cytoplasmic retinoic acid binding protein (cRABP). In the Fisher-Copenhagen F1 rat, cRABP was present in the lateral lobe, but could not be detected in the ventral nor in the dorsal prostatic lobes. Four sublines of the R-3327 rat prostatic tumor contained similar levels of this binding protein. The absence of cRABP in the normal tissue of origin of the R-3327 tumor, the rat dorsal prostate, and reappearance in the neoplastic tissues follows a pattern described in other human and animal tumors. The occurrence of cRABP in the well-differentiated as well as in the anaplastic R-3327 tumors in which markers which reflect a state of differentiation and hormonal regulation, such as androgen receptor, 5 alpha reductase, and secretory acid phosphatase are either markedly reduced or absent, points to cRABP as a marker of malignant transformation.
Estrogen and progesterone receptor levels were determined simultaneously in tumor samples obtained from 105 patients who subsequently received a trial of hormonal or chemotherapy for metastatic carcinoma of the breast. Twenty-three of 33 estrogen receptor positive patients in contrast with three of 22 estrogen receptor negative patients achieved an objective response to hormonal therapy. More significantly, it was found that 12 of 16 estrogen receptor positive patients compared with only six of 34 estrogen receptor negative patients responded to combination chemotherapy. Simultaneous measurement of progesterone receptor improved the selection of tumors responsive to chemotherapy, as only four of 30 patients who were estrogen receptor negative-progesterone receptor negative achieved a response. Furthermore, the cumulative survival time of 36 months after the first recurrence of carcinoma of the breast was significantly lower in estrogen receptor negative patients receiving chemotherapy. These data indicate that patients with estrogen receptor negative carcinoma of the breast are resistant to standard hormonal and chemotherapeutic measures for metastatic disease and carry a poor prognosis.
The relationship between structure and function in eukaryotic chromatin has been studied in rat liver cells. To elucidate the functional significance of "accessible" DNA, the transcription of this DNA (prepared by titration of liver chromatin with poly-D-lysine) has been examined by RNA-DNA hybridization. The maximum extent to which nuclear RNA will hybridize to the nonrepeated fraction of "accessible" DNA has been measured and compared to the extent that whole chromatin DNA will hybridize. The results show that "accessible" DNA has the same number of sequences complementary to nuclear RNA as does total DNA. In addition DNA-DNA reassociation experiments indicate that there is only a small difference between the total unique sequence populations of "accessible" and total DNA. These results indicate that nonrepeated "accessible" DNA is not preferentially transcribed in the cell as is predicted by some models of chromatin structure.
The structure of eukaryotic chromatin has been investigated by isolating and analyzing the "accessible" DNA fraction of rat liver chromatin. This DNA fraction has been isolated by titrating the chromatin with the protese-resistant D isomer of polylysine to bind the "accessible" DNA sites. After removal of chromosomal proteins by digestion with pronase, all DNA not protected from attack by bound polylysine was removed by digestion with DNase. Even after exhaustive treatment with pronase and DNase approximately 30% of the chromatin DNA remains resistant to nuclease attack. Analysis of the isolated DNA shows it to be mainly double-stranded with an average size of 200-250 base pairs. The DNA is slightly A-T rich and contains both repetitive and "single-copy" nuleotide sequences. The results suggest that there are extensive regions in chromatin where the DNA is not tightly complexed with protein. Furthermore, the DNA of these regions is similar in gross properties to the DNA of the total genome.
A previous survey of 48 subjects with XYY chromosome complement showed a wide scatter of values for plasma concentration of testosterone and luteinizing hormone (LH). To account for this scattering and in view of the impulsive behavior often attributed to XYY subjects, it was postulated that paroxysmal activity in the cerebral cortex produced paroxysmal stimulation at the level of the hypothalamus. To investigate this possibility, plasma concentrations of testosterone, dihydrotestosterone, follicle stimulating hormone (FSH), and LH were determined on seven consecutive days in four XYY subjects and five XY control men as well as bimonthly for four months in two XYY detainees and three XY control detainees. The variability of plasma androgen and gonadotropin levels in XYY subjects was similar to that of XY control men. The results thus do not support the above hypothesis as an explanation of the widely scattered plasma androgen values in XYY individuals. The "XYY syndrome" is probably heterogeneous and includes a number of patients with some degree of hypogonadism. Testicular biopsy, sperm count, and meiotic studies were carried out in eight XYY men. In one case the meiotic study showed two Y-chromatin bodies. Results of these various investigations support the diagnosis of maturation arrest of the germ cells with consequent oligospermia. Low fertility is therefore expected to be frequent among XYY subjects, although when fertilization does occur, it can result in normal XY or in XYY infants.
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Specific polyanions release DNA template restrictions for DNA synthesis in isolated rat liver nuclei. The degree to which DNA synthesis is enhanced can be correlated with a spectrum of changes in nuclear structure Each polyanion which is effective in the release of template restriction produces a characteristic alteration in nuclear ultrastructure. Polyanions which have no effect on DNA synthesis do not appear to cause any change in nuclear organization or ultrastructure. Parallel measurements of nuclear DNA release and nuclear volume changes also indicate that template-activating polyanions cause remarkable changes in the structural organization of the treated nuclei. These results indicate that DNA template activation involves direct interactions between polyanions and nuclear constituents and suggest the possibility that naturally occurring polyanions might have a role in the control of gene activity
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