PubMed Health⌕ Search

Biomedical subjects

D McIntosh

Publications and source records attributed to D McIntosh.

At least 37 records · Page 2Linked to original sources
PubMed1990

The intracellular movement and cycling of ricin.

The binding, internalization and recycling of the plant toxin ricin, was studied using electron microscopy and biochemical techniques. For the electron microscope study, ricin was visualized using a gold-labeled second antibody, in the cells of the EJ human bladder carcinoma line growing in monolayer culture. The labeled antibody/toxin complex was found to enter the cell in coated pits and to accumulate in endosomes and to a lesser extent in vesicles associated with the Golgi system. The complex recycled to the cell surface partly in uncoated vesicles, but largely in multivesicular bodies which appeared to exocytose their contents to the extracellular space. Twenty hours after the initial contact with ricin as much as 50% of the cellular label was found on the cell surface mainly associated with shed vesicles. When cells were treated with unlabeled ricin holotoxin and then after 20 h stained post-fixation, ricin molecules, partly associated with vesicles, were present on the cell surface. Biochemical studies showed that ricin was internalized by cells and then released in an intact form to the extracellular space. It was found that less than 10% of the released material had been degraded during its passage through the cells, which is in accord with the low level of label found in the lysosomal system during the morphological study.

Antitoxins↗
PubMed1989

Whole-abdomen radiation therapy in ovarian carcinoma: its role as a salvage therapeutic modality.

A significant proportion of patients with epithelial ovarian carcinoma eventually fail after initial responses to chemotherapy. Further treatment with chemotherapy consisting of either the same combination or second-line regimens has been ineffective in producing durable responses. Thus, between June 1983 and June 1987, thirty patients with epithelial ovarian carcinoma who failed one or more chemotherapeutic regimens were treated with whole-abdominopelvic-cavity radiation therapy. Prior to the radiation the amount of residual disease after debulking was noted to be microscopic in 16 patients and macroscopic in 14 patients. Radiation was delivered with an open-field technique that extended from the domes of the diaphragm to the obturator foramina. Doses of 2500 cGy were planned to the whole abdomen, with a boost of another 2500 cGy to the pelvic and or paraaortic nodes when indicated. Higher doses were delivered to the areas of gross disease in the pelvis. Only 2 patients were unable to complete the planned therapy. Another 26% of the patients required interruption of the therapy secondary to hematologic toxicity but eventually completed the treatment. With an overall median follow-up of 14 months, 56% of the patients remain alive. Two-year actuarial survival and recurrence-free survival rates are 47 and 32%, respectively. The survival and recurrence-free survival rates for the group with microscopic residual disease--61 and 33%, respectively--are better than those for the patients with macroscopic residual disease--36 and 18%. The abdominopelvic cavity was the first site of failure in all but one of the 17 patients who have failed. In spite of the higher doses, pelvic failure alone or as a component occurred in 54% of the patients. Small bowel obstruction necessitating surgical intervention as a complication of therapy was seen in 13% of the patients.

Abdomen↗
PubMed1989

A new cell line (8701-BC) from primary ductal infiltrating carcinoma of human breast.

A cell line, designated 8701-BC, was established in culture from tissue fragments of primary ductal infiltrating carcinoma of human breast. The cell cultures after the sixth passage were devoid of contaminating fibroblasts as judged by the positive staining of all cells with the specific epithelial cell markers carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and cytokeratin 8. The epithelial nature of these cells was confirmed by ultrastructural analyses which demonstrated the retention of specific structural properties characteristic of the original tumour. The cells possessed an abnormal karyotype with 55-60 chromosomes per cell with numerous rearrangements. They do not express HLA antigens and the c-myc gene was not amplified. The 8701-BC cells have a doubling time of approx. 29h and have been maintained in culture for more than 100 passages. These properties suggest the establishment of a human neoplastic cell line which, with its ability to produce homotrimer collagen in vitro, will provide a useful model system for the study of tumour cell:stromal matrix interactions.

Breast Neoplasms↗
PubMed1988

Effects of a structured behavior modification treatment program on locus of control in behaviorally disturbed children.

The effect of a 10-day behavior modification treatment program on locus of control was investigated. The subjects were children (N = 130; 6 to 12 years old) with severe behavioral disorders who were predominantly from low socioeconomic backgrounds, from broken homes, and socially deprived. Pre- and post-testing was done with the Nowicki-Strickland Preschool and Primary Internal-External Control Scale (Nowicki & Duke, 1974) and the Nowicki-Strickland Locus of Control Scale for Children (Nowicki & Strickland, 1973). Children between the ages of 10 and 12 responded to therapy with a significant increase in internality, but younger children did not.

Age Factors↗
PubMed1987

Temporary inhibition of Moloney-murine sarcoma virus (M-MSV) induced-tumours by adoptive transfer of ricin-treated T-lymphocytes.

The potential use of tumour-specific T-lymphocytes loaded with ricin in cell targeting experiments was investigated. Moloney-murine sarcoma virus (M-MSV)-specific T-lymphocytes, obtained in mass mixed leucocyte-tumour cell culture (MLTC) and a M-MSV-specific cytotoxic T-lymphocyte (CTL) clone, were incubated with 125I-labelled ricin in order to evaluate toxin uptake and release. The internalized ricin (4.5 X 10(-17) mol and 6.5 X 10(-17) mol per 10(2) MLTC and CTL clone cells, respectively) was released rapidly during the first 30 min following treatment, and at a constant but slower rate over the next few hours. The cytotoxic activity of ricin-treated cells evaluated against antigen-related target cells, in a short term incubation 51Cr release assay, was unaffected during the first 30 min after treatment but decreased with time over the next few hours. However, the growth of antigen related as well as of unrelated tumour cells was strongly inhibited by the addition of ricin-treated cells to the culture system, thus indicating that released ricin is toxic for untreated target cells. The in vivo localization pattern of ricin-treated radiolabelled MLTC cells was found to be comparable with that of untreated cells 1 h after i.v. injection into syngeneic sublethally irradiated mice. After 6 h, however, more radiolabel was recovered from the liver of mice receiving ricin-treated MLTC cells. Ricin-treated M-MSV-specific T-lymphocytes were injected i.v. into tumour bearing sublethally irradiated mice. A temporary tumour growth inhibition (up to 6 days) was achieved following transfer of low doses of ricin-treated MLTC or CTL clone cells (1 X 10(6) and 0.5 X 10(6), respectively). In contrast, in M-MSV injected control mice, receiving only free toxin (from 5 to 20 ng) or untreated tumour-specific effector cell tumours grew progressively. The therapeutic effect was apparently specific since the injection of ricin-treated alloreactive T-lymphocytes did not influence tumour growth. These results suggest that M-MSV-specific T-lymphocytes loaded with ricin can deliver toxin to the target tumour mass and have a transient therapeutic effect.

Animals↗
PubMed1987

Tissue staining properties of lectins from the seeds of the jack fruit (Artocarpus integrifolia) and the winged bean (Psophocarpus tetragonolobus).

N-acetyl-D-galactosamine binding lectins from winged bean (Psophocarpus tetragonolobus) and jack fruit (Artocarpus integrifolia) were isolated, purified and conjugated with horse radish peroxidase and their tissue staining properties studied. Despite having an apparently common inhibiting sugar, the lectins showed differences in their staining properties. The lectin from the winged bean stained none of the mouse and human tissues tried even after neuraminidase treatment whereas the jack fruit lectin stained most of the untreated cells. The staining was found to be improved by the prior treatment of the cells with neuraminidase and inhibited completely by the inhibiting sugar. The differences in the staining properties of the lectins are discussed.

Animals↗
PubMed1986

Comparison between fenoterol/ipratropium bromide combinations and salbutamol administered as nebulizer solution assessing dose-response and duration of action.

The study was performed to assess the efficacy of three ipratropium/fenoterol combinations and salbutamol when administered as nebulizer solution to patients with reversible airway obstruction. 11 patients, of whom 10 completed, aged 18 years or over, were chosen. For inclusion they were required to demonstrate a 15% improvement in absolute FEV1 within 10 min of administering an inhaled beta-adrenergic agonist. The study consisted of a randomised, double-blind, cross-over comparison between three combinations of ipratropium/fenoterol and salbutamol: ipratropium 0.5 mg/fenoterol 1.25 mg; iptratropium 0.5 mg/fenoterol 2.5 mg; ipratropium 0.5 mg/fenoterol 5.0 mg, and salbutamol 5.0 mg. In this relatively small number of patients there was no overall significant difference between the three doses of combination when PEFR, FEV1 and FVC were considered. However, the results for each of the three combinations were better than those for salbutamol and these reached the level of statistical significance (p less than 0.01) for the medium and high doses. PEFR measured between 3 and 8 h again demonstrated improved results for the three combinations compared with salbutamol reaching a level of statistical significance (p less than 0.01) for the high and medium doses.

Adolescent↗
PubMed1986

A comparison between fenoterol/ipratropium bromide combinations and salbutamol administered as nebulizer solutions assessing dose-response and duration of action.

A double-blind, randomized crossover trial was carried out in 10 patients with reversible airways obstruction to assess dose-response and duration of action of 0.5 mg ipratropium combined with 1.25 mg, 2.5 mg or 5.0 mg fenoterol compared with 5.0 mg salbutamol given alone. Each solution was nebulized from a volume of 4 ml and administered via a mouth-piece at approximately the same time on each of 4 test days. Measurements were made of FEV1, FVC and PEFR before and at intervals after nebulization. The results showed that each dose of the combination produced greater improvements in the lung function parameters than did salbutamol alone and the degree of response was proportional to the dose of the combination. No significant treatment differences were recorded in systolic or diastolic blood pressure between any of the treatments, but the combined preparations produced significantly higher pulse rates than did salbutamol.

Aerosols↗
PubMed1986

The ego and the self in the thought of Sigmund Freud.

An analysis of the development, nature, and inter-relations of the three main senses in which Freud used the term 'Das Ich' (the 'I'). They are: the ego--one's person as subject, who desires, thinks, feels, acts. The use of this concept is very flexible, ranging from a global sense which includes the whole psychic system, to the narrower idea of the conscious purposive agent, to the technical concept of the 'system ego': a psychic subsystem which plays the key role in organizing and directing the activity of the person as subject. the self--one's person as the object of one's narcissistic or aggressive cathectic investment: the person one believes, wishes, or hopes oneself to be, as distinct from the actual object, one's (or another's) actual person. The idea of such an object (nowadays called an 'intentional object') derives from Franz Brentano, Freud's teacher. the character--a stable syndrome of interrelated traits of behaviour or thought. Both the ego and the self have characters, which are formed in different ways, and which resemble each other only to a varying degree.

Ego↗
PubMed1982

A comparison of the in vitro and in vivo activities of conjugates of anti-mouse lymphocyte globulin and abrin.

Anti-mouse lymphocyte globulin and normal immunoglobulin have been conjugated to abrin using two procedures, one involving linkage through an amide bond and a piperazine ring and the other the introduction of two amide bonds flanking a disulphide bridge. The four conjugates produced were equipotent as inhibitors of protein synthesis in rabbit reticulocyte lysates. Each antibody-containing conjugate was a more effective inhibitor of protein synthesis in cultured cells than the equivalent normal immunoglobulin-containing conjugate. In addition the conjugates with disulphide linkage groups were ten times more potent than their counterparts. The disulphide conjugates were also twice as toxic to mice in an acute toxicity test but when used to suppress their immune responses to sheep red blood cells it was the non-disulphide-linked conjugates that were superior. In all instances antibody-containing conjugates were more powerful immunosuppressants than those containing normal IgG. The results are taken to indicate a relative lack of stability of the disulphide conjugates in the tissues.

Abrin↗