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Biomedical subjects

R J Fallon

Publications and source records attributed to R J Fallon.

At least 109 records · Page 6Linked to original sources

Fluorimetric measurements and chromatin condensation patterns of nuclei from 3T3 cells throughout G1.

Using two cytological methods based on nuclear morphology, quinacrine dihydrochloride (QDH) staining and premature chromosome condensation (PCC), it has been possible to identify cell cycle positions within G1 of growing and arrested 3T3 cells. The fluorescent intensity of QDH-stained interphase cells appears to decrease as the cells pass from mitosis to S phase. Likewise, the length and thickness of prematurely condensed chromatids can be related to the cells; position within the G1 period. Data are presented that deal with three interrelated topics: 1) We determined by fluorometric measurements of nuclei from 3T3 cells that the visual observation of the decrease in QDH fluorescence during G1 reflects an actual decrease in total fluorescence and not a dispersion of the fluorescent chromatin in a larger nuclear area. 2) We correlated the results obtained by QDH staining with those of PCC on the same cell samples blocked in G1 by different conditions. Serum-starved and contact-inhibited cell nuclei had the highest intensity, hydroxyurea-treated ones had the lowest intensity, while that of isoleucine-deprived cells was in between. The same relative order of G1 positions was obtained based on PCC morphology. Thus, both methods monitor the state of chromatin condensation and can be used to identify cell cycle position within G1. 3) We showed with both methods that the states of chromatin resulting from the various G1 blocking conditions differ from each other.

Animals↗

Relation of cell cycle position and chromatin decondensation to ectopic hormone synthesis in HeLa cells.

Ectopic synthesis of human chorionic gonadotropin (hCG) in HeLa cells, mediated by sodium butyrate, is shown to be associated with cell cycle position in late G1 or early S phase where decondensation of chromatin is maximal. Inhibitors or conditions of culture that block HeLa cells in earlier stages of G1 do not increase hormone production. The time course of butyrate-mediated hCG synthesis shows a direct correlation with the degree of chromatin decondensation in synchronized HeLa cells. Using synchronized cultures, both late G1 and butyrate-treated G2 cells were observed to synthesize large amounts of hormone. However, the chromatin of butyrate-treated G2 HeLa cells resembles late G1 chromatin in its maximal decondensation. These findings suggest that ectopic hormone production in neoplastic cells may be related to decondensation of chromatin irrespective of the position of cells in the cell cycle.

Butyrates↗

Tuberculous meningitis.

To evaluate modern treatment and identify important factors influencing the outcome of tuberculous meningitis, clinical and laboratory findings in 52 patients aged from 9 months to 68 years have been reviewed. Patients were classified by clinical criterions at admission and at the start of treatment. Delay in commencing treatment was associated with deterioration and consequently poorer prognosis, but some severely ill patients made a good recovery. Forty-four survivors (85%) recovered, and only two patients (4%) had severe residual disability; eight (15%) of the patients died. Treatment should commence as soon as possible on clinical grounds without necessarily waiting for demonstration of Mycobacterium tuberculosis, as the organism can often be demonstrated in CSF withdrawn after the start of drug therapy.

Adolescent↗

Induction of human choriogonadotropin and follitropin in HeLa cell cultures by hyperosmolality.

The growth of cervical carcinoma cell (HeLa) cultures in a hyperosmolar environment stimulates increased production of the onco-developmental peptides human choriogonadotropin (hCG) and follitropin (FSH). This effect was observed in two sublines examined in this study, HeLa65 and HeLa71. hCG and FSH were measured by radioimmunoassay using antiserum against the beta-subunit of the hormone dimer, thus insuring immunochemical specificity, The amounts of hCG and FSH produced by HeLa65 and HeLa71 cells cultured in hyperosmolar medium were 2- to 50-fold higher than corresponding hormone levels in basal cultures. Synthesis of gonadotropins depended on concentration and duration of exposure to hyperosmolar medium. Levels of culture medium osmolality effective in inducing hormone production also inhibit the incorporation of 14C-thymidine into acid-insoluble macromolecules. Hyperosmolality thus stimulates the ectopic production of gonadotropic hormones while retarding cellular growth and nucleic acid synthesis.

Cell Division↗

Cell cycle analysis of sodium butyrate and hydroxyurea, inducers of ectopic hormone production in HeLa cells.

Sodium butyrate and hydroxyurea, effective inhibitors of DNA synthesis in HeLa cells, cause these cells to produce increased levels of the ectopic glycopeptide hormones human chorionic gonadotropin (hCG), follicle stimulating hormone (FSH), and free alpha chains for these hormones. The objective of this study was an assessment of the role of modulation of cell cycle events in the action of these two chemical agents. A variety of experimental approaches was employed to obtain a clear view of the drugs' effects on cells located initially in all phases of the cell cycle. Cells in early G1, G2, or M phase at time of addition of either inhibitor were not arrested at early time points, but by 48 hours became collected at a location characteristic for each drug, near the G1-S phase boundary. Flow microfluorometry (FMF) and thymidine labeling index revealed that butyrate-treated cells arrested late in G1 phase very close to S phase, while hydroxyurea-blocked cells continued to early S phase. Both inhibitors prevented cells originally in S phase from reaching mitosis. S cells exposed to hydroxyurea were killed by 48 hours, but those growing in 5 mM butyrate progressed to the end of S or G2 phase where they became irreversibly arrested although not removed from the monolayer. Analysis of the cell cycle location and viability of each subpopulation resulting from 48 hour exposure to butyrate or hydroxyurea is important for the study of the function of each cellular subset. Treatment of HeLa cells with lower concentrations of butyrate (1 mM) resulted in slowed yet exponential growth. Fraction labeled mitosis (FLM) analysis shows that this is a result of prolongation of the G1 phase.

Butyrates↗

Secretory proteins in the perfused human placenta.

A relatively simple perfusion technique of human placenta has been applied to the study of secretory proteins. Preferential secretion into the maternal circulation of human chorionic gonadotropin (HCG), human chorionic somatomammotropin (HCS), follicle-stimulating hormone (FSH), and placental alkaline phosphatase has been demonstrated, contrasting with the bidirectional secretion of progesterone. Evidence is presented for the net synthesis of HCS during perfusion. The technique offers advantages in the study of synthesis and secretion of placental materials.

Alkaline Phosphatase↗