Search PubMed⌕ Search

Biomedical subjects

H M Jones

Publications and source records attributed to H M Jones.

At least 55 records · Page 3Linked to original sources
PubMed1990

Isoquinolinesulfonamide protein kinase inhibitors H7 and H8 enhance the effects of granulocyte-macrophage colony-stimulating factor (GM-CSE) on neutrophil function and inhibit GM-CSF receptor internalization.

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) increases neutrophil surface expression of the cellular adhesion molecule CD11b and primes the respiratory burst stimulated by the bacterial peptide f-met-leuphe (FMLP). We have examined the effects of the isoquinolinesulfonamide protein kinase inhibitors H7 and H8 on these functions of GM-CSF using whole blood assays. Concentrations of H7 and H8 that inhibited the 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulated upregulation of CD11b expression and activation of the respiratory burst, both augmented the effects of GM-CSF. H7 and H8 enhanced the GM-CSF-stimulated increase in CD11b expression to 215% +/- 10% (P less than .05) and 233% +/- 45% (P less than .05), respectively, of the value obtained with GM-CSF alone. The GM-CSF priming of the FMLP-stimulated oxidative burst was increased to 190% +/- 44% (P less than .01) by preincubation with H7 and to 172% +/- 25% (P less than .01) with H8. Preincubation with H8 did not affect overall binding of 125I-GM-CSF to neutrophils, but inhibited GM-CSF receptor internalization after ligand binding (P less than .05). These data indicate that the effects of GM-CSF are not mediated by protein kinase C and that a phosphorylation event down-modulates the neutrophil response to GM-CSF. It suggests that internalization of the receptor-ligand complex is not a rate-limiting step in signal transduction, and that regulation of the rate of internalization may be an important level of control of the activity of GM-CSF.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Development of antibodies to unprotected glycosylation sites on recombinant human GM-CSF.

In 4 out of 16 patients receiving recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) in phase I/II studies antibodies developed to the recombinant protein. The antibodies react with sites on the native protein backbone which are normally protected by O-linked glycosylation but which are exposed in rhGM-CSF produced in yeast and Escherichia coli. Antigenicity of recombinant human proteins due to non glycosylation may have relevance to the choice of host system for production of factors for clinical use.

Antibodies↗
PubMed1990

Oral premedication in children. A comparison of trimeprazine with a trimeprazine, droperidol and methadone mixture.

One hundred children who presented for minor general surgical procedures were randomly assigned to receive one of two oral premedications. Those in group A (n = 50) were given 3 mg/kg of trimeprazine and those in group B (n = 50) a mixture of trimeprazine 1.0 mg/kg, droperidol 0.15 mg/kg and methadone 0.08 mg/kg. Patients in group B were more likely to be asleep on arrival in the anaesthetic room (p less than 0.02) and were less likely to be distressed at induction of anaesthesia (p less than 0.02). Thiopentone requirements were less in group B (p less than 0.001). The incidence of side effects was similar in the two groups. It is concluded that the mixture produces more satisfactory sedation than trimeprazine.

Administration, Oral↗
PubMed1990

The effects of rhGM-CSF on the neutrophil respiratory burst when studied in whole blood.

A simple semiquantitative cytofluorometric method has been developed for measuring neutrophil respiratory burst activity in whole blood samples. This technique avoids the introduction of laboratory artefacts which modulate neutrophil function. In addition, flow cytometric analysis allows the response to be studied in individual cells. We show here that neutrophils examined freshly ex vivo, exhibit only weak respiratory burst activity in response to stimulation with the chemotactic peptide FMLP (10(-6) M). Prior incubation with rhGM-CSF results in an increase in the number of responding cells from 13.5 +/- 2.36% (mean +/- SEM) to 46.7 +/- 6.3% (P less than 0.0001) with an increase in total respiratory burst activity of 567% (P = 0.001). The majority of neutrophils in whole blood (67.1 +/- 8.1%) exhibit respiratory burst activity in response to stimulation with phorbol ester (1 micrograms/ml of TPA), and this response is also significantly primed by rhGM-CSF (P = 0.004). The enhancement of respiratory burst activity induced by rhGM-CSF is due to both recruitment of previously unresponsive neutrophils, and to intensification of the response of the responding cells. In vivo administration of rhGM-CSF also results in priming of the respiratory burst in response to FMLP, although the enhancement of activity is not as great as that obtained when pre-infusion blood samples are incubated with rhGM-CSF in vitro.

Blood↗
PubMed1989

Assessing collateral circulation in the hand--four methods compared.

Four ways to assess the collateral circulation in the hand were compared. No correlation was shown between the Doppler ultrasound method and those that used either the pulse monitor or the Ohmeda Biox 3700 pulse oximeter. The study was unable to confirm suggested benefits of these methods in assessing adequacy of collateral flow in the hands of unconscious patients.

Collateral Circulation↗
PubMed1989

The role of calcium in gonadotropin-releasing hormone induction of follicle-stimulating hormone release by the pituitary gonadotrope.

Binding of gonadotropin-releasing hormone (GnRH) to the pituitary gonadotrope induces activation of a membrane associated calcium channel, resulting ultimately in luteinizing hormone release. The role of calcium mobilization in GnRH-induced follicle-stimulating hormone (FSH) release was explored using anterior pituitary glands from female rats in a perifusion tissue culture system. While perifusion with GnRH (10 ng/ml) induced a constant level of gonadotropin release, the calcium channel blocker verapamil (10(-4)M) depressed FSH release, as did dantrolene (10(-4)M), an antagonist of intracellular calcium mobilization. When the calcium ionophore A23187 (10(-5) M) was substituted for GnRH, FSH release was not only maintained but increased. Antagonism of the activity of calmodulin (CAM) with trifluoperazine (10(-4)M), however, did not depress FSH release. Cellular content of cAMP and cGMP increased in response to GnRH. When FSH secretion was ionophoretically induced by A23187, however, little cAMP was detected. These results support a role for calcium mobilization in the second messenger cascade underlying GnRH-induced FSH release. The role for calcium in the disparate release of FSH and LH were further discussed in the context of these data.

Animals↗
PubMed1988

Effect of cardiopulmonary bypass on circulating concentrations of leucocyte elastase and free radical activity.

Circulating concentrations of leucocyte elastase and free radical activity were measured in 11 adults undergoing cardiopulmonary bypass. In all patients the bypass procedure was associated with pronounced changes in plasma elastase concentrations, and peak enzyme concentrations correlated closely with the duration of bypass (r = 0.91, p less than 0.001). Serial measurement of octadeca-9, 11-dienoic acid, a non-peroxide marker of free radical activity, showed significant changes only in the plasma free fatty acid fraction, suggesting a direct relation to the action of heparin rather than to the bypass procedure as such. These studies support the hypothesis that neutrophil activation plays a central role in the organ dysfunction that may complicate cardiopulmonary bypass and suggest that elastase release rather than free radical generation may be the appropriate marker of the event.

Aged↗
PubMed1987

The response of cultured gonadotrophs to inhibin: the role of calcium mobilization.

The role of calcium mobilization and calmodulin activation in the induction of the selective suppression of follicle stimulating hormone (FSH) release by the gonadal protein inhibin was assessed employing a rat gonadotroph monolayer culture system. Inhibin, in porcine follicular fluid (60 microliters/ml), did inhibit FSH release in the face of GnRH stimulation. Antagonism of calcium mobilization with verapamil (10(-4) M) and dantrolene (10(-4) M) failed to restore the FSH response when administered with GnRH and inhibin. Trifluoperazine (10(-4) M), a calmodulin antagonist acted similarly. Cellular calmodulin content increased in response to gonadotropin-releasing hormone (GnRH), as did the concentration of cGMP, while both responses were prevented by the administration of inhibin. Trifluoperazine suppressed cGMP concentration to levels below baseline. These data suggest that while calmodulin and the cyclic nucleotides do not mediate the cellular response to inhibin, they may play a role in the control of gonadotropin synthesis. A link may exist between calmodulin, the concentration of which increased in response to GnRH and was suppressed by inhibin, and the elevation of cellular cGMP content induced by GnRH. Further investigation is warranted to assess a possible action of inhibin which is antagonistic to that of calcium in the transduction of GnRH stimulation into FSH release by the pituitary gonadotroph.

Animals↗
PubMed1987

Systematic studies invalidate the neonatally androgenized rat as a model for polycystic ovary disease.

As an adult, the neonatally androgenized (AZ) rat is anovulatory and exhibits follicular cysts. Thus, the AZ rat has been used as a model for polycystic ovary disease (PCO). However, its correlation with the human disease is not clear; so we have studied the AZ rat to determine its suitability as a PCO model. In Experiment I, reproductive hormones were measured at specific intervals between postnatal Days 15 and 90 in saline-treated and AZ rats. In Experiment II, AZ rats were treated with exogenous follicle-stimulating hormone (FSH) or subjected to unilateral ovariectomy (ULO) as analogies to therapies that have been used to treat human PCO. The results demonstrate that the luteinizing hormone (LH), FSH, testosterone (T), and estradiol (E2) concentrations of the AZ rat were not different from control values. Additionally, FSH therapy did not increase the E2 concentrations or the ovarian weight of the AZ rat. Furthermore, control and AZ rats exhibited similar post-ULO rises in FSH, but compensatory ovarian hypertrophy was not evident in the AZ rat. We conclude that 1) the hormonal and morphological patterns observed in the AZ rat do not correlate with those of PCO and 2) the androgenized rat does not provide an adequate model to study PCO.

Adrenal Glands↗
PubMed1987

Androgenic modulation of periovulatory follicle-stimulating hormone release in the rat.

We examined the relationship between the proestrous testosterone (T) surge and periovulatory follicle-stimulating hormone (FSH) release because previous evidence suggested that T may directly stimulate the selective release of FSH on estrus in the rat. In Experiment I, rats received flutamide (F) at either 1200 h on proestrus (F X 1) or 1800 h on Diestrus II and 1200 h on proestrus (F X 2). Additional animals received T-antiserum (T-A/S) at 1800 h on Diestrus II or vehicle (Control) at both times. In Experiment II, ovariectomized (OVX) rats (n = 11) were implanted with estradiol (E2)-filled capsules on Day 5 post-OVX; then, progesterone (P) capsules were implanted for 48 h beginning on Day 7 and again on Day 11. Six of these rats also received T capsules for 6 h on Days 7 and 11. All OVX rats were cannulated on Day 11 and bled every 4 h until they were killed on Day 12. In the first experiment, neither acute androgen receptor blockade with F X 1 nor T-A/S treatment altered the pattern of periovulatory FSH release, suggesting that the proestrous T surge does not directly stimulate estrous FSH release. However, longer blockade with F X 2 suppressed both the proestrous and estrous phases of FSH release, implying that an androgenic stimulus moderates periovulatory FSH release. In Experiment II, E2 and P capsules stimulated gonadotropin surges but not a selective, estrous-like release of FSH. Additional T therapy did not induce estrous-like FSH release again suggesting that surge-like elevations of T do not specifically result in selective FSH release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Tracheal versus intravenous atropine. A comparison of the effects on heart rate.

Atropine 600 micrograms was given either intravenously or intratracheally and the change in heart rate noted in a double-blind, randomised study of 40 anaesthetised patients. There was no significant difference between the two groups in the maximum increase in heart rate, 20.3 beats/minute in the tracheal compared to 21.4 beats/minute in the intravenous group. However, the maximum increase occurred significantly earlier in the tracheal group, 45.5 seconds after administration compared to 95.5 seconds in the intravenous group (p less than 0.01, 95% confidence interval 36.8-63.2 seconds). This study supports the clinical observation that tracheal and intravenous atropine are equally effective and suggests that the trachea should be the route of choice when a rapid response is required.

Adult↗
PubMed1987

Regulation of Escherichia coli fumarate reductase (frdABCD) operon expression by respiratory electron acceptors and the fnr gene product.

The fumarate reductase enzyme complex, encoded by the frdABCD operon, allows Escherichia coli to utilize fumarate as a terminal electron acceptor for anaerobic oxidative phosphorylation. To analyze the expression of fumarate reductase, protein and operon fusions were constructed between the frdA and the lacZ genes and introduced onto the E. coli chromosome at the lambda attachment site. Expression of beta-galactosidase from either fusion was increased 10-fold during anaerobic versus aerobic cell growth, increased an additional 1.5-fold by the presence of fumarate, the substrate, and decreased 23-fold by nitrate, a preferred electron acceptor. The addition of trimethylamine-N-oxide as an electron acceptor did not significantly alter frdA'-'lacZ expression. Control of frd operon expression is therefore exerted at the transcriptional level in response to the availability of the electron acceptors oxygen, fumarate, and nitrate. Anaerobic induction of frdA'-'lacZ expression was impaired in an fnr mutant and was restored when the fnr+ gene was provided in trans, thus establishing that the fnr gene product, Fnr, is responsible for the anaerobic activation of frd operon expression. Nitrate repression of frdA'-'lacZ expression was observed under either aerobic or anaerobic cell growth conditions in both wild-type and fnr mutant strains, demonstrating that the mechanism for nitrate repression is independent of nitrate respiration and oxygen control imparted by Fnr. Studies performed with a fnr'-'lacZ protein fusion confirmed that the fnr gene is expressed both aerobically and anaerobically. A model is proposed for the regulation of frdABCD operon expression in response to the availability of the alternate terminal electron acceptors oxygen, nitrate, and fumarate.

Aerobiosis↗
PubMed1987

Autologous bone marrow transplantation for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia--a comparison.

Forty-two patients with acute leukaemia were treated with autologous bone marrow transplantation (ABMT) using a combination chemotherapy protocol for bone marrow ablation. The response to high-dose chemotherapy and ABMT and its associated morbidity and mortality have been compared in 24 patients with acute myeloid leukaemia (AML) and 18 patients with acute lymphoblastic leukaemia (ALL). In 16 patients with AML treated with ABMT during first complete remission (CR), ten patients (62.5%) remain in unmaintained remission; median follow up is 32 months. In eight patients with ALL treated in first CR, only one remains in remission 32 months post-ABMT, with three patients dying non-leukaemic deaths. Fourteen of 18 patients (AML and ALL) treated after first remission have died of recurrent leukaemia, two died non-leukaemic deaths and two remain well 31 and 55 months post-ABMT; both have ALL. The length of hospital stay and the amount of blood product support were similar in both groups. Haematological recovery post-ABMT was delayed in patients with AML compared to patients with ALL but this difference was not significant. Rapidly progressive lung infection was thought to be the cause of four early deaths (4/18) in patients with ALL but none in patients with AML. Severe gram-negative infections were significantly more common in patients with AML.

Adolescent↗
PubMed1986

A rise in the percentage of large unstained cells in the peripheral blood determined by the Hemalog D90 automated differential counter is a feature of impending myeloid engraftment following bone marrow transplantation.

The early phase of bone marrow regeneration has been monitored by automated differential counts on the peripheral blood using a Hemalog D90, following 107 transplant procedures. An elevated percentage of large unstained cells (LUCs) was detected in over 98% of cases and in 72% of cases the rise in percentage LUCs preceded the rise of the total leucocyte count into the detectable range on a Coulter counter (greater than 0.3 X 10(9)/1) by an average of 4 days. These LUCs are shown to be CD8 + T lymphocytes. The ability to detect the earliest signs of regeneration is particularly useful when regeneration is delayed and repeat marrow infusion is considered.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Survival of transfused adult cells in the fetus.

The survival of adult erythrocytes transfused into the circulation of a severely isoimmunised fetus was assessed. The survival time in the fetus was found to be considerably shorter than in adults.

Adult↗