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R J Fallon

Publications and source records attributed to R J Fallon.

At least 19 recordsLinked to original sources
PubMed1992

The serpin-enzyme complex (SEC) receptor mediates the neutrophil chemotactic effect of alpha-1 antitrypsin-elastase complexes and amyloid-beta peptide.

The serpin-enzyme complex (SEC) receptor mediates catabolism of alpha 1-antitrypsin (alpha 1-AT)-elastase complexes and increases in synthesis of alpha 1-AT in cell culture. The SEC receptor recognizes a pentapeptide domain on alpha 1-AT-elastase complexes (alpha 1-AT 370-374), and the same domain in several other serpins, amyloid-beta peptide, substance P, and other tachykinins. Thus, it has also been implicated in the biological properties of these ligands, including the neurotoxic effect of amyloid-beta peptide. In this study, we examined the possibility that the SEC receptor mediates the previously described neutrophil chemotactic activity of alpha 1-AT-elastase complexes, and whether the other ligands for the SEC receptor have neutrophil chemotactic activity. The results show that 125I-peptide 105Y (based on alpha 1-AT 359-374) binds specifically and saturably to human neutrophils, and the characteristics of this binding are almost identical to that of monocytes and hepatoma-derived hepatocytes. Peptide 105Y and amyloid-beta peptide mediate chemotaxis for neutrophils with maximal stimulation at 1-10 nM. Mutant or deleted forms of peptide 105Y, which do not bind to the SEC receptor, have no effect. The neutrophil chemotactic effect of alpha 1-AT-elastase complexes is blocked by antiserum to peptide 105Y and by antiserum to the SEC receptor, but not by control antiserum. Preincubation of neutrophils with peptide 105Y or substance P completely blocks the chemotactic activity of amyloid-beta peptide, but not that of FMLP. These results, therefore, indicate that the SEC receptor can be modulated by homologous desensitization and raise the possibility that pharmacological manipulation of this receptor will modify the local tissue response to inflammation/injury and the neuropathologic reaction of Alzheimer's disease.

Alzheimer Disease↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

Scottish experience with the serologic diagnosis of Legionnaires' disease.

Four-hundred fifty-nine sera from 342 persons were examined at Ruchill Hospital, Glasgow, using an agar-grown heat-killed, ether-treated antigen derived from the Philadelphia 1 strain of the Legionnaires' disease bacterium. They were examined, in parallel, at the Center for Disease Control (CDC), Atlanta. Overall agreement (results agreeing +/- one twofold dilution) was reached with 90% of sera. Important differences were obtained with 10 (2.2%) sera. With three of these 10 sera the CDC alone obtained a significant titre (256) whereas with the other seven the Glasgow laboratory alone obtained a titre of 256. Altogether 28 persons (8.2%) with an agreed titre of 256 or higher were identified. However, some of these people had been ill 4 years before serum was obtained for examination. These persistent high titres make the serologic diagnosis of Legionnaires' disease difficult.

Antibodies, Bacterial↗