Search PubMed⌕ Search

Biomedical subjects

H Jackson

Publications and source records attributed to H Jackson.

At least 73 records · Page 4Linked to original sources

Does topical flurbiprofen affect the pupillary response to acetylcholine?

Pre-operative topical non-steroidal anti-inflammatory drugs (NSAIDs) are known to be effective in maintaining pupillary dilation during cataract surgery. However, previous studies have suggested that pre-treatment with these agents interferes with the miosis produced by intraoperative acetylcholine injection. This study was designed to determine whether the pupillary response to acetylcholine injection is reduced following pre-operative topical flurbiprofen 0.03%. Pupil diameters were measured with a millimetre rule, and the measurements verified using computerised image analysis of digitised video images. Eyes treated with flurbiprofen were compared with controls. There was no significant difference in pupillary diameter before corneal incision, but following aspiration of soft lens matter and insertion of intraocular lens the pupil was significantly larger in the flurbiprofen group (p = 0.002). At 1.0, 2.5 and 5.0 minutes following injection of acetylcholine no significant difference in the degree of miosis was detected. This study confirms that topical flurbiprofen maintains dilation during cataract surgery, and does not find any evidence to suggest that intra-operative response to acetylcholine is reduced.

Acetylcholine↗

Spermatogenic and mutagenic damage after paternal exposure to systemic indium-114m.

The cytotoxic and mutagenic consequences of systemic administration of 114mIn have been examined. Adult male rats were dosed intraperitoneally with 14.8 or 3.7 MBq/kg 114mIn. Approximately 0.25% of the injected radioactivity was localized within the testis by 24 h and was retained with an effective half-life of 49.5 days. Breeding studies were started 3 days after injection, males being housed with two females for seven consecutive mating trials of 19 days, separated by 2 days. Indium-114m caused a reduction in litter size and an increase in the incidence of pre- and postimplantation losses and dominant lethal mutations. These effects became evident from 24 days but were most marked between 87-126 days after treatment and persisted up to 147 days. When animals were mated 200 days after treatment, no significant changes were observed. In a parallel study, administration of 14.8 MBq/kg 114mIn resulted in decreased testis and epididymal weight and sperm reserves. Maximal reduction occurred between 87-108 days after injection followed by recovery toward control values, but neither organ had reached normal levels at 200 days. A single dose of 3.7 MBq/kg, however, had no effect on reproductive organ weight or sperm content. Male F1 progeny from the 14.8 MBq/kg group of the second mating period (commencing at 24 days) displayed decreased testis weights and sperm content and provoked a higher incidence of dominant lethal mutations. This effect was not observed in male progeny from any other time or the alternative dose level.

Animals↗

Classes of primitive murine megakaryocytic progenitor cells.

We describe high proliferative potential colony-forming cells-megakaryocyte (HPP-CFU-Mk) from mouse bone marrow preparations using known cytokine combinations. These primitive precursors, which generate at least 80 megakaryocytes per colony, were detected from bone marrow populations enriched for primitive cells, either following treatment with 5-fluorouracil (5-FU) or after enrichment from normal bone marrow using immunological procedures. HPP-CFU-Mk were most reproducibly grown in the presence of interleukin-1 (IL-1) plus IL-3 plus IL-6, and mostly grew as a single large aggregate, rarely forming multiple foci. Cell separation studies showed that the HPP-CFU-Mk have membrane properties that characterized these cells as being intermediate between high proliferative myeloid primitive progenitors (high proliferative colony-forming cells [HPP-CFC]) and committed megakaryocyte progenitors (CFU-Mk). The data show that HPP-CFU-Mk can be designated as primitive cells on the basis of their being spared in vivo after 5-FU treatment, their proliferative potential to produce megakaryocytes, and their cofractionation with a proportion of primitive myeloid progenitor cells.

Animals↗

Exogenous Nocardia asteroides endophthalmitis following cataract surgery.

We present a case of Nocardia asteroides endophthalmitis following cataract surgery. It is the second to be reported and the first in which vision has been preserved. Symptoms commenced 5 days after surgery and there followed a chronic relapsing anterior uveitis which lasted for 4 months. Nocardia asteroides was finally cultured from an aqueous aspirate and a combination of specific antimicrobial treatment and surgery resulted in a satisfactory visual outcome. Exogenous nocardial intraocular infection is rare and must be distinguished from fungal infection as the organism is resistant to antifungal agents.

Cataract Extraction↗

Press coverage of AIDS in Zimbabwe: a five-year review.

Five years of newspaper coverage of HIV and AIDS in Zimbabwe is examined. Both the number of items and the amount of space devoted to the topics has increased steadily over the 5 years. The nature and content of the items show a continuing bias towards issues more closely associated with western patterns of the epidemic, and comparative neglect of personal stories, local issues and items with a counselling focus. Language is also examined and found to reflect a victim and war imagery. The implications for health education in the country are considered and specific recommendations for more constructive media coverage are made.

Acquired Immunodeficiency Syndrome↗

No joking matter: formal and informal sources of information about AIDS in Zimbabwe.

One hundred and forty-two social work students in Harare, Zimbabwe, were questioned concerning their sources and memory of information concerning the human immunodeficiency virus (HIV) and AIDS. Newspapers were cited most frequently as the major source of information. Family and friends were not reported to be major sources of information. An analysis of the kinds of items most frequently recalled showed that articles concerning personal portrayals were the most powerful vehicles for AIDS information. Metaphors and similes for AIDS produced by the students mirrored those commonly reported elsewhere. Jokes were studied as indicators of informal opinions, and these showed negative views of American involvement in AIDS issues.

Acquired Immunodeficiency Syndrome↗

The role of interleukin 6 in megakaryocyte formation, megakaryocyte development and platelet production.

Megakaryocytopoiesis is the cellular amplification and differentiation of precursors into immature megakaryocytes, and the cytoplasmic maturation of these megakaryocytes, a process terminating in the release of platelets into the circulation. Interleukin 6 (IL-6) stimulates megakaryocytopoiesis in the bone marrow, increasing platelet numbers in the circulation. IL-6 alone is poorly active on the growth of stem cell populations, but acts in synergy with stem cell factor (c-kit ligand) to expand the committed myeloid progenitor compartments but not the megakaryocyte progenitors. IL-6 has a direct action on megakaryocyte progenitors but only in synergy with low doses of interleukin 3 (IL-3), increasing the number of immature megakaryocytes and enhancing the processes of development into mature megakaryocytes. IL-6 is about 10 times more active on megakaryocytes than on megakaryocyte progenitors in cell culture. It is active alone and will stimulate increases in cell size and DNA content. IL-6 does not appear to stimulate the process of platelet release. IL-6 is found in bone marrow, in both macrophage subsets and megakaryocytes, indicating that it may be an important physiological regulator of both paracrinal (microenvironmental) and autocrinal mechanisms controlling megakaryocyte development in bone marrow.

Animals↗

A comparative binding of platinum anti-tumour compounds to plasma proteins in the rat (in vivo) and mouse (in vitro).

Plasma protein binding of 195mPt-labelled cisplatin, carboplatin and iproplatin has been studied in vivo in rat and in vitro in mouse, using both electrophoresis and trichloroacetic acid precipitation. After intravenous injection plasma clearance rates were biphasic for all 3 compounds, (t1/2 alpha, 13-17 min) but cisplatin was retained thereafter longer than the others. By 5 min, gel electrophoresis showed protein labelling with all 3 drugs but none involved low mol.wt. proteins (< 16 kDa). At 2 h a notable proportion of the protein bound platinum was associated with the latter components. There was a general resemblance between the distribution patterns of cisplatin and carboplatin whereas iproplatin showed a persistent retention of the label with time to higher mol. wt. proteins. From in vitro incubation with mouse plasma, rates of interaction respectively were cisplatin t1/2 alpha, 35 min, beta 8 h, carboplatin t1/2, 44 h and iproplatin t1/2, 104 h. By electrophoresis the protein bound fraction pattern (1 h) was again similar for cisplatin and carboplatin with virtually no binding to low mol. wt. proteins. After 24 h these were now involved to a high degree (40%). Iproplatin showed relatively marked binding to proteins of higher mol. wt. but no transfer with time to the low mol. wt. protein zone. A possible explanation is the need for in vivo metabolism for this compound as manifest in the rat. It is suggested that the significance of interaction with low mol. wt. proteins merits further investigation in relation to the antitumour and toxicological actions of these drugs.

Animals↗

A highly potent and selective N-methyl-D-aspartate receptor antagonist from the venom of the Agelenopsis aperta spider.

Agatoxin-489, extracted from the venom of the Agelenopsis aperta spider, was studied on acutely isolated perfused hippocampal neurons of rat using the concentration clamp technique. Agatoxin-489 proved to be a selective N-methyl-D-aspartate antagonist; responses to applications of N-methyl-D-aspartate or L-aspartate were blocked by concentrations of agatoxin-489 ranging between 0.1 nM and 1 microM, while responses to kainate were not affected by agatoxin-489 at concentrations up to 10 microM. The actions of agatoxin-489 against responses to N-methyl-D-aspartate or L-aspartate were use- and voltage-dependent, being less pronounced with an increase in the holding potential from -100 to -30 mV. The action of agatoxin-489 could be completely or partially reversed only after washout in the presence of an N-methyl-D-aspartate agonist. The washout was more effective at positive membrane potentials ranging from 0 to +20 mV. These results imply that the spider toxin agatoxin-489, like dizocilpine, is a potent and selective N-methyl-D-aspartate antagonist which preferentially interacts with activated N-methyl-D-aspartate receptors and/or open N-methyl-D-aspartate-activated ionic channels.

Agatoxins↗

Symptomatic response to antipsychotics differs between recent onset and recurrent chronic schizophrenic patients.

The symptomatic response to standard antipsychotic treatment was assessed over the first 4 weeks of hospitalisation in 39 patients with DSM-III schizophrenia, active phase, using the Brief Psychiatric Rating Scale (BPRS). While highly significant improvement was noted overall, 36% of patients either did not improve or worsened. Furthermore there was no diminution in the withdrawal-retardation factor of the BPRS. Patients experiencing their first admission to hospital, all with recent-onset illness, were then compared with patients who presented with a recurrence and had illness of at least 3 years duration. Despite similarities in overall response, withdrawal-retardation scores did not diminish in recent-onset patients, in contrast to multiple admissions who demonstrated significant improvement. These findings suggest greater responsiveness of negative symptoms to treatment in patients with longstanding illness, and possibly a poorer prognosis in first admission patients with deficit manifestations.

Acute Disease↗

Cell-targeted 114Inm and drug (BCNU) combination therapy in a rat acute lymphoblastic leukaemia.

A proportion of syngeneic female rats inoculated intramuscularly with a lethal T-cell lymphoblastic (Roser) leukaemia are cured by a single intraperitoneal injection of bischloroethylnitrosourea (BCNU) (Carmustine) (10 mg kg-1) given towards the end of the preleukaemic phase (day 7). Additional therapy on day 4, using intravenous leukaemia cells lethally labelled with the radionuclide 114Inm, enhanced the overall cure rate by 30%. The spleen is a major site of indium concentration from the targeting cells so that the continuous local radiation field appears to result in a substantial reduction of the body load of leukaemia cells in the enlarged spleen particularly, thus enhancing the curative potential of the drug. The results demonstrate in principle that in patients in remission a single dose of targeted radiotherapy in the spleen combined sequentially with an appropriate drug might provide considerable aid in eliminating a residual population of leukaemia cells.

Animals↗

The nature of an accessory cell in bone marrow stimulating murine megakaryocytopoiesis.

The nature of accessory cells in unstimulated mouse bone marrow that modulates in vitro megakaryocytopoiesis by releasing megakaryocyte potentiator (Mk-potentiator) activity was investigated. An active cell class was identified by the 7/4 and Ia cellular antigens. Bone marrow macrophages were obtained by their defined outgrowth in the presence of growth factors. Bone marrow macrophages grown in the presence of interleukin 3 (IL-3) were more active in producing Mk-potentiator than were macrophages grown in the presence of colony-stimulating factor 1 (CSF-1). The data indicate that the accessory cells producing Mk-potentiator are a select population of bone marrow macrophages that may be responsible for inducing megakaryocyte maturation under steady-state conditions.

Animals↗

Interleukin 3 directly stimulates both megakaryocyte progenitor cells and immature megakaryocytes.

A subset of stem cell antigen (sca-1)-positive mouse megakaryocyte progenitors was identified that correlates with other primitive precursors in bone marrow. The responsive bone marrow cells were obtained by depleting the marrow of cells bearing defined lineage markers (neutrophils, macrophages, and lymphoid cells) and enriched for primitive myeloid progenitor cells with high proliferative potential, selecting for cells expressing sca-1. The sca-1-positive megakaryocyte progenitors formed colonies in the presence of interleukin 3 (IL-3) alone. Immature megakaryocytes depleted of mature megakaryocytes and of cells expressing myeloid and lymphoid lineage markers were also responsive to IL-3. These data indicate that in the presence of high doses of IL-3, accessory cells are not obligatory for growth factor stimulation of megakaryocytopoiesis in vitro.

Animals↗

Arylamine toxins from funnel-web spider (Agelenopsis aperta) venom antagonize N-methyl-D-aspartate receptor function in mammalian brain.

The venom of the North American funnel-web spider Agelenopsis aperta contains a variety of arylamine toxins (the alpha-agatoxins) that paralyze insects by blocking glutamatergic neuromuscular transmission. We have tested six synthetic alpha-agatoxins for their ability to antagonize glutamate receptor function in mammalian brain. These compounds produce, at submicromolar concentrations, noncompetitive inhibition of N-methyl-D-aspartate (NMDA) receptor-mediated elevations in the concentration of cytosolic free calcium in cultured rat cerebellar granule neurons. In contrast, the alpha-agatoxins are relatively weak antagonists of elevations in the cytosolic free calcium concentration induced by non-NMDA receptor agonists. The alpha-agatoxins also produce reversible suppression of the NMDA receptor-mediated excitatory postsynaptic potential in rat hippocampal slices at concentrations that have little effect on the non-NMDA receptor-mediated population spike. We conclude that the alpha-agatoxins are selective and reversible noncompetitive antagonists at NMDA receptors in mammalian brain.

Animals↗

Arylamine spider toxins antagonize NMDA receptor-mediated synaptic transmission in rat hippocampal slices.

The effects of arylamine spider toxins on synaptic transmission in rat hippocampal slices were investigated. Two different responses were monitored: the AMPA receptor-mediated population spike recorded in control buffer (selectively antagonized by DNQX) and the NMDA receptor-mediated EPSP recorded in nominally magnesium-free buffer containing 20 microM DNQX (selectively antagonized by AP5, AP7, and dizocilpine (MK-801)). The synthetic arylamine spider toxins JSTX-3, argiotoxin-636, and argiotoxin-659 were 26 to 73 times more potent at antagonizing the NMDA receptor-mediated EPSP (IC50 values ranging from 12 to 24 microM) than the AMPA receptor-mediated population spike (IC50 values ranging from 612 to 878 microM). These results indicate that arylamine spider toxins are selective antagonists of NMDA receptors in the mammalian CNS.

Animals↗