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Biomedical subjects

H Jackson

Publications and source records attributed to H Jackson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Flow cytometric apoptosis assays indicate different types of endonuclease activity in haematopoietic cells and suggest a cautionary approach to their quantitative use.

Two flow cytometric apoptosis assays, the terminal deoxynucleotidyl transferase (TdT) assay and in situ nick translation (ISNT) assay, were assessed for their ability to quantitate drug-induced apoptosis in CLL lymphocytes. In contrast to HL60 cells, biotinylated dUTP could not be effectively incorporated into apoptotic CLL lymphocytes using exogenous TdT. This suggested that CLL lymphocytes possess a different type of endonuclease that cleaves DNA, leaving blunt or 3' recessed DNA breaks, which are poor substrates for TdT. This possibility was tested using lambda exonuclease, which can convert a blunt or 3' recessed DNA break into a 3' overhang. Apoptotic CLL lymphocytes pre-treated with lambda exonuclease demonstrated increased nucleotide incorporation with TdT. Single-strand DNA breaks are also present in apoptotic CLL lymphocytes, as labelled nucleotides could be incorporated using the in situ nick translation assay. This study suggests that the efficiency of tailing reactions may be limited by the nature of the endonuclease activity in certain cell types and that validation with other parameters is an essential prerequisite to their quantitative use.

Apoptosis↗
PubMed1998

Spontaneous T cell responses to melanoma differentiation antigens from melanoma patients and healthy subjects.

The spontaneous cytotoxic T cell responses to melanoma differentiation antigens and influenza matrix peptide were compared in 20 HLA-A2+ melanoma patients and 17 healthy A2+ individuals. Cytotoxic T lymphocyte (CTL) responses were determined by mixed lymphocyte peptide culture (MLPC) involving two stimulations of unfractionated peripheral blood lymphocytes (PBLs) with peptide in vitro. CTL responses to Melan-A 9-mer (amino acids 27-35, AAGIGILTV) peptide were detected in 4 out of 16 normal individuals, but in none of the melanoma patients. CTL specific for influenza matrix peptide were frequently found in both normal individuals and melanoma patients, suggesting that generalized immuno-suppression was not responsible for this difference. No significant responses were observed in either normal individuals or melanoma patients to Melan-A 10-mer (26-35, EAAGIGILTV), two gp1OO epitopes (280-288, YLEPGPVTA; 457466, LLDGTATLRL) and two tyrosinase epitopes (1-9, MLLAVLYCL; 368-376, YMDGMSQV). Melan-A (27-35)-specific CTL cells generated by normal individuals and melanoma patients recognized both synthetic peptide-pulsed T2 cells and two HLA-A2+, Melan-A+ melanoma cell lines (ME272, LAR1) in an antigen-specific, MHC class I restricted manner. T cells generated against Melan-A 9-mer were also able to recognize Melan-A 10-mer-pulsed target cells. Spontaneous CTL responses to Melan-A 9-mer from three known responder normal individuals were further evaluated over a prolonged time course (6-11 months). All 3 subjects demonstrated specific Melan-A 9-mer responses throughout the study period, although lytic activity fluctuated over time for a given individual. We found the MLPC assay to be reliable and easy to perform for monitoring T cell responses, although it may still not be sufficiently sensitive to detect low numbers of precursor T cells.

Adjuvants, Immunologic↗
PubMed1998

Antigen specificity and tumour targeting efficiency of a human carcinoembryonic antigen-specific scFv and affinity-matured derivatives.

We have examined the biological properties of CEA6, a human carcinoembryonic antigen (CEA)-specific single-chain Fv (scFv) isolated by phage display, and five related clones derived by affinity maturation and selected for improved off-rate (Koff). All clones bind strongly and specifically to CEA-positive human tumours by immunocytochemistry and show negligible cross-reactivity with normal colon. Flow cytometry of scFv on human liver cells indicates a shift in fine epitope specificity resulting from mutagenesis. All monomeric scFv have been radioiodinated, retaining effectively full binding activity. A single intravenous injection into nude mice bearing human colon tumour xenografts confirms tumour targeting in all cases. As reported in other studies, the kidney is the main route of elimination of scFv at early time points. Tumour binding of the parental antibody CEA6 consistently gives the highest tumour-blood ratios at 24 h (mean 16:1). Clone TO6D11, which has a sevenfold reduced Koff relative to CEA6, showed no difference in tumour uptake at 24 h but persisted at the tumour site for longer than CEA6. This study demonstrates a possible correlation between binding affinity and tumour residence time when examined in this model.

Animals↗
PubMed1998

The cost of home-based care for HIV/AIDS patients in Zimbabwe.

From a study on the cost and quality of community home-based care (CHBC) for HIV/AIDS patients in Zimbabwe, programme and household costs were estimated. Interviews, using a structured questionnaire, were held with 60 patients and caregivers sampled from six types of established CHBC schemes. Detailed cost information was collected from four home care programmes, two urban and two rural. The cost of a home visit in the two urban programmes studied was estimated to be Z$129 (US$16) in one, and Z$183 (US$23) in the other. In one of the two rural schemes, the cost of a home visit was Z$313 (US$38), in the other this was Z$343 (US$42). A large proportion of these costs were not of direct benefit to the patients, as approximately 56-75% of the total cost per home visit was spent getting to the patient. The costs of a home visit in a rural home-based care programme corresponded to the costs of 2.7 inpatient days in a district hospital. The family cost of caring for a bedridden AIDS patient over a three-month period was estimated to be between Z$556-841. Caregivers spent as much as 2.5-3.5 hours a day on routine patient care. The programme costs are high, and schemes do not generally assess effectiveness, nor cost-effectiveness. The high cost of home visits leads to less frequent visits, leaving a larger part of both the burden and the cost of care to the families and the patients.

Cost of Illness↗
PubMed1998

Cognitively-oriented psychotherapy for early psychosis (COPE). Preliminary results.

BACKGROUND: The present study describes the results of the pilot testing of a therapy we have developed for people with first-episode psychosis. Cognitively-oriented psychotherapy for early psychosis (COPE) is aimed at facilitating the adjustment of the person, and at preventing or alleviating secondary morbidity in the wake of the first psychotic episode. METHOD: Eighty people formed three groups: those who were offered and accepted COPE (COPE subjects); those who refused COPE (refusal subjects); and those who were offered neither COPE nor any other continuing treatment from our service (control subjects). The individuals were assessed prior to, and at the end of, COPE treatment (a 12-month period) on the Integration/Sealing Over, Explanatory Model, Scale for the Assessment of Negative Symptoms, Brief Psychiatric Rating Scale, Quality of Life, SCL-90-R, and Beck Depression Inventory measures. RESULTS: People who received COPE obtained significantly superior scores (P < 0.05) to the control group on four of the seven measures but only significantly out-performed the refusal group on one of the seven measures (P < 0.05). The COPE group performed significantly worse on the BDI than the refusal group (P < 0.05). Effect sizes are also provided for each measure. CONCLUSIONS: There seems to be a place for psychological therapy in this group of people but our results need to be replicated in a more definitive randomised controlled trial and such a study is now in progress.

Adult↗
PubMed1997

Use of pulsed irrigation evacuation in the management of the neuropathic bowel.

Management of the neuropathic bowel is one of the major issues in the treatment of patients with severe spinal cord injury (SCI). Pulsed irrigation evacuation (PIE) has been evaluated in several small studies for the clearing of fecal impactions in patients with a neuropathic bowel. We evaluated our experience with 398 PIE procedures performed on inpatients and outpatients at our facility. It has proven to be both safe and effective in a wide variety of patients with this disorder, and is a useful addition to traditional methods in the management of the neuropathic bowel.

Adult↗
PubMed1997

Covert poisoning with difenacoum: clinical and toxicological observations.

1. The coumarin anticoagulant difenacoum was detected by high performance liquid chromatography (HPLC) with multi-wavelength UV detection in plasma from a 41 years old man who presented with a severe deficiency of vitamin K-dependent clotting factors of unknown aetiology. A longitudinal toxicological study of the consequent coagulopathy is described. 2. Plasma concentrations of difenacoum declined from 0.97 to 0.11 mgl-1 in 47 days with a terminal half life of 11.7 days. Rifampacin (300 mg bd) had no apparent effect on the terminal half life of the drug. Subsequently plasma concentrations of difenacoum and descarboxyprothrombin (DCP) unexpectedly increased. 3. Seven months after exposure clotting times were prolonged. The patient continued to have episodes of epistaxis, haematoma, purpurae and bruising and he required frequent treatment with Fresh Frozen Plasma in additional to oral phylloquinone (200 mg day-1). 4. Intermittent and unexpected increases in plasma concentrations of difenacoum and descarboxypro-thrombin suggested that covert, repeated ingestion of the anticoagulant was the most likely cause of the poisoning. The measurement of low concentrations of plasma phylloquinone except following supervised ingestion of the vitamin indicated that as an outpatient, the subject was not compliant with treatment despite his protestations to the contrary. He continued to deny this even when confronted by laboratory findings and at no time did he ever admit to self-poisoning.

4-Hydroxycoumarins↗
PubMed1997

Causes of blindness in northwest Cambodia.

A hospital-based study in the northwest of Cambodia identified 453 blind adults and 30 blind children seen consecutively at the provincial ophthalmic department between January and September 1994. Blindness was defined as a visual acuity of less than 3/60 in the better eye. Cataract was the cause of blindness in 266 (59%) adults, of which 15 cases (3.3%) were surgical complications. Sixty-three cases (14%) were due to glaucoma and 53 (11.5%) patients had corneal scars, of which 12 (2.5%) were due to trachoma. Bilateral trauma, usually due to landmine injuries, accounted for 17 patients (4%). Of the 30 blind children, corneal scarring accounted for 12 cases (40%), congenital causes for 14 (47%) and optic atrophy secondary to meningitis for 4 (13%). There is at present an inadequate ophthalmological service for the vast majority of people living outside the capital Phnom Penh. These hospital-based data suggest that there is a need to train general doctors to surgically manage patients with visual loss from cataract and glaucoma, which together account for 70% of all cases of blindness, and highlight the need for a large population-based survey.

Adolescent↗
PubMed1997

The relative population sizes of megakaryocytic cells in mouse bone marrow as determined by mpl ligand responsiveness.

The relative population sizes of mpl ligand-responsive megakaryocytic cells were investigated, and all megakaryocytes grown in culture were assessed. Three groups were analyzed: 1) immature cells with the ability to form single mature megakaryocytes; 2) cells with the ability to divide once before forming megakaryocytes (doublets); and 3) progenitor cells with the ability to form colonies, i.e., to undergo both cytokinesis and maturation. Immature cells forming single megakaryocytes proved most sensitive to the mpl ligand. Committed megakaryocyte progenitors required approximately 30 times more mpl ligand to achieve maximum growth than did the immature megakaryocyte population. Similar numbers of committed megakaryocyte progenitors responded to interleukin (IL)-3 and to mpl ligand. The amplification potential of these progenitor cells responding to each growth factor was assessed by measuring the number of megakaryocytes per colony. In response to mpl ligand progenitor, cells generated smaller colonies, with most cell divisions completed at a signifcantly earlier time point compared with progenitor cells responding to IL-3. The growth of more primitive megakaryocyte progenitors was best achieved in combination with other growth factors, notably IL-3; mpl ligand alone was ineffective in this regard. A novel finding was the significant number of megakaryocytes that grew in culture as closely coupled pairs (doublets). Data reported indicate that doublet formation may be a result of detection and stimulation of immature megakaryocytes rather than the diminished mpl ligand responsiveness of a proportion of megakaryocyte progenitors. By combining the number of mpl ligand-responsive cells forming single megakaryocytes with those forming megakaryocyte doublets, it is estimated that the size of the immature megakaryocyte pool greatly exceeds previous calculations. Thus we conclude that the immature megakaryocyte population is significantly larger than previously estimated and that these cells are the most sensitive to mpl ligand. Accordingly, these cells are potentially crucial in bone marrow responsiveness to mpl ligand that results from acute thrombocytopenia, being capable not only of endomitosis and maturation but perhaps of cell division as well.

Animals↗
PubMed1996

Bilateral blindness due to trauma in Cambodia.

Ocular trauma is a major cause of monocular blindness in both the developed and developing world, but is not seen as a significant cause of bilateral blindness. Trauma is therefore generally thought of as a major cause of blind eyes without being a major cause of blind people. Because of the difficulties of surgical treatment of ocular trauma in many developing countries, long-term management is usually aimed at prevention, e.g. by improving safety standards in the workplace. The situation in countries such as Cambodia, which have high landmine densities, is different. Cambodia has an estimated 4-10 million landmines which cause significant morbidity and mortality. This hospital-based study of blindness in the north-west of Cambodia found that of 453 bilaterally blind individuals, 17 (4%) were blind as a result of trauma, and 14 of these were males 15-35 years old. Fourteen cases were due to bilateral penetrating injuries caused by landmine explosions, and usually occurred in association with other severe injury. The other main causes of blindness were cataract (59%), glaucoma (14%) and corneal scarring (12%). Penetrating ocular trauma is a significant cause of bilateral blindness in Cambodia, and predominantly affects young men. It is estimated that it would take 250 years to clear Cambodia of landmines at current activity levels.

Adolescent↗
PubMed1996

Retinopathy in haemoglobin C trait.

Retinopathy associated with sickle-C and sickle cell disease is well described. Sickle trait and haemoglobin C trait are generally considered benign conditions, with infrequent systemic manifestations. Rare cases of retinopathy in sickle trait, in the presence of contributory factors, exist and we recently reported three such patients. The occurrence of retinopathy in haemoglobin C trait is even less well documented. Haemoglobin C does not cause red blood cell sickling but is known to decrease erythrocyte plasticity and increase blood viscosity. We report three cases in which haemoglobin C trait was associated with significant peripheral vascular occlusion and seafan formation (confirmed by fluorescein angiography) similar to that seen in sickle retinopathy. Two patients had coexistent systemic disease (hypertension and diabetes mellitus). Vitreous haemorrhage was the presenting feature in two patients. It is evident that haemoglobin C trait may be associated with sight-threatening complications.

Adult↗
PubMed1996

Baculovirus-mediated high level expression of a human thiopurine methyl transferase.

We have expressed the human thiopurine methyltransferase cDNA in a baculovirus vector in Sf21 (Spodoptera frugiperda) cells. This system expresses the enzyme at levels such that the thiopurine methyltransferase enzyme may be readily visualised by Coomassie blue stained sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The expressed enzyme catalysed the methylation of 6-mercaptopurine with an apparent Km of 892 microM, similar to that observed in human liver cytosol ie. 657 microM however, the Vmax was 13,500 pmole/mg/min, which is approximately 400 times higher than the Vmax observed in human liver cytosol ie. 33 pmole/mg/min. The thiopurine methyltransferase inhibitors 6-thioxanthine, p-methoxybenzoic acid and 3,5-dimethoxy benzoic acid were found to be potent inhibitors of the expressed enzyme.

Animals↗