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Biomedical subjects

A Houghton

Publications and source records attributed to A Houghton.

At least 19 recordsLinked to original sources
PubMed1992

Retroviral gene transfer induced constitutive expression of interleukin-2 or interferon-gamma in irradiated human melanoma cells.

Cytokines are important modulators of host antitumor responses. Two of these cytokines, interleukin-2 (IL-2) and interferon gamma (IFN-gamma), are produced after antigen-induced activation of helper lymphocytes. The cytokines are released into the immediate vicinity where they either interact with the appropriate receptors on effector cell populations or are rapidly degraded. To mimic this physiologic release of cytokines at the effector-target site, we used retroviral vectors to transduce melanoma cells with the IL-2 or IFN-gamma cDNA. Five melanoma cell lines were transduced with IL-2- or IFN-gamma-containing vectors and secreted IL-2 at 1 to 40 U/mL/10(6) cells/24 h or IFN-gamma 1 to 8 U/mL/10(6) cells/24 h, respectively. After gamma irradiation, these cells continued to secrete cytokines for about 3 to 4 weeks. Secretion of IFN-gamma induced upregulation of major histocompatibility complex class I molecules in a subset of melanoma cell lines. IL-2 production by human melanoma xenografts induced tumor rejection in BALB/c nu/nu mice, showing the in vivo effect of this cytokine. This study shows that (1) human melanoma cells can be stably transduced with cytokine-containing retroviral vectors; (2) cytokines are secreted constitutively by the transduced tumor cells and have the expected biologic effects in vitro and in vivo; and (3) after gamma irradiation, cytokines continue to be secreted for several weeks. These data suggest that irradiated cytokine-secreting allogenic or autologous tumor cells can be used in vaccination protocols for cancer patients.

3T3 Cells↗
PubMed1992

Aluminium beverage cans as a dietary source of aluminium.

OBJECTIVE: To examine the possibility that aluminium beverage cans contribute to the dietary level of aluminium. METHOD: The aluminium content of a variety of beverages from aluminium cans and glass containers was measured. RESULTS: The contents of 106 aluminium cans and bottles representing 52 different beverages all had a higher aluminium content than Newcastle tap water at 1.4 mumol/L, ranging as high as 385 mumol/L. Non-cola soft drinks averaged 33.4 mumol/L from cans and 5.6 mumol/L from bottles. Cola drinks averaged 24.4 mumol/L from cans and 8.9 mumol/L from bottles, whereas beer in cans or bottles averaged about 6 mumol/L. CONCLUSIONS: In general, the aluminium content of beverages from aluminium cans was higher than that from glass containers, and it rose with decreasing pH. Within a given category there was a wide variation in aluminium content. If the speculative link between aluminium intake and Alzheimer's disease is established then beverages from aluminium cans, particularly soft drinks, may be a risk factor.

Aluminum↗
PubMed1992

Promoting social interaction of children with disabilities in integrated preschools: a failure to generalize.

In this study, the Classwide Social Skills Program (CSSP) was introduced for all children in four integrated preschool classes, and generalization of effects was measured across settings and over time for 14 children with disabilities between the ages of 3 and 5 years. Results indicated that the CSSP increased the positive play of children with disabilities to levels comparable to classmates without disabilities. Levels of teacher reinforcement toward the children with disabilities increased as well. These increases in teacher and child behaviors, however, did not generalize to 3- or 6-month follow-up periods nor to another play session in the day. Implications for promoting social interaction in integrated preschool settings are discussed.

Behavior Therapy↗
PubMed1992

Selective medical examination at school entry: should we do it, and if so how?

A prospective study was conducted on 82 consecutive 5+ examinations performed by four school doctors over a period of two months. The aim was to assess the impact of applying selection criteria for examination. Information gathered included immunization status, history of previous developmental assessments and previous detection of problems, and the result of the examination for each child. Forty-three per cent of children were up to date with their immunizations, 66 per cent had had a six-week check and 38 per cent and 17 per cent had been assessed at 15 months and 2 1/2 years respectively. Forty-eight problems were detected in 37 children (45 per cent), of which 27 had not been previously detected. Of these, 19 were detected by the school nurse before the examination as a result of hearing (nine) and vision (10) testing and measurement of height and weight (one). Of the remaining problems, four were presented by the parent, one by the teacher and two were detected by the school doctor. If a policy of selective examination had been in place in which children were called for examination only if they had never been assessed before, or where there were no records of a previous assessment, or if their immunizations were incomplete, or they had previous problems, or the school nurse or teacher or parent had expressed concern, all but four children would have been examined. It was concluded that this particular method of selection would be unproductive and that a system whereby the school nurse was responsible for screening and selection for examination would be preferable.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1991

Generation of pigmented stripes in albino mice by retroviral marking of neural crest melanoblasts.

The pigment cells of the skin are derived from melanoblasts which originate in the neural crest. The dorsoventral migration of melanoblasts has been visualized in pigment stripes seen in aggregation chimeras, and the width of these bands has suggested that the entire pigmentation of the coat is derived from a small number of founder cells. We have generated mosaic mice by marking single melanoblasts in utero to gain information on the clonal history of pigment-forming cells. A retroviral vector carrying the human tyrosinase gene was constructed and microinjected into neurulating albino mouse embryos. Albino mice are devoid of pigmentation due to deficiency of tyrosinase. Thus, transduction of the wild-type gene into the otherwise normal melanoblasts should rescue the mutant phenotype, giving rise to patches of pigmentation, which correspond to the area colonized by the mitotic progeny of a marked clone. Mosaic animals derived from the injected embryos indeed showed pigmented bands with a width strikingly similar to the 'standard' stripes seen in aggregation chimeras. These results are consistent with the notion that the unit width bands seen in aggregation chimeras represent the clonal progeny of a single melanoblast and verify Mintz's (1967) conclusion that a few founder melanoblasts give rise to coat pigmentation. The pigment cells of the eye are of dual origin: the melanocytes in choroid and outer layer of the iris are derived from the neural crest and those in the pigment layer of the retina from the neuroepithelium of the optic cup. Marked clones in both lineages were observed in the eyes of many mosaic animals.

Animals↗
PubMed1990

Urinary uric acid:creatinine ratio, serum erythropoietin, and blood 2,3-diphosphoglycerate in patients with obstructive sleep apnea.

A noninvasive, inexpensive method of excluding significant sleep-associated hypoxemia would be desirable for patients being investigated and treated for obstructive sleep apnea (OSA). Sixty-eight such patients provided specimens before and after sleep studies for estimation of urinary uric acid:creatinine ratio (UA:Cr), serum erythropoietin (EPO), and blood 2,3-diphosphoglycerate (2,3-DPG). Mean (SD) morning 2,3-DPG was higher in 26 patients with overnight hypoxemia than in 42 normoxemic patients (2.54 [0.46] versus 2.24 [0.44] mmol/L; p = 0.01). Neither overnight change nor absolute values of serum EPO or urinary UA:Cr were significantly different between hypoxemic and normoxemic groups. There was a diurnal variation in serum EPO in normoxemic patients (P.M. EPO = 14.8 [7.1] mU/ml; A.M. EPO = 10.7 [7.1] mU/ml; p less than 0.05) but not in hypoxemic patients. Eighteen hypoxemic patients were restudied after using nasal continuous positive airway pressure (nCPAP) for at least 4 wk. Seven normoxemic patients not using nCPAP were restudied after a similar time. There were no significant differences between pretreatment and posttreatment nights in absolute values or percentage overnight change of blood 2,3-DPG or serum EPO in either group. In the hypoxemic (nCPAP) group, overnight change in urinary UA:Cr was lower on the second night (p = 0.04); there was no significant change in the control group. We conclude that although urinary UA:Cr, serum EPO, and 2,3-DPG may be physiologically related to hypoxemia, none of these measures can be used to predict accurately the presence of moderate nocturnal hypoxemia in patients with OSA or in monitoring the effect of their therapy.

2,3-Diphosphoglycerate↗
PubMed1990

Recurrent phaeochromocytoma.

The recurrence of symptoms and hypertension in a patient who has previously undergone an operation for phaeochromocytoma should alert the physician to the need to investigate for recurrent tumour. Failure to perform complete excision of the adrenal gland containing the tumour may lead to disseminated recurrence.

Adrenal Gland Neoplasms↗
PubMed1989

Rehabilitation after lower limb amputation: a comparative study of above-knee, through-knee and Gritti-Stokes amputations.

A study of 169 unilateral amputees under three Disablement Services Centres was performed. The study comprised 88 above-knee, 54 through-knee and 27 Gritti-Stokes amputations. Satisfactory rehabilitation occurred in 33 per cent of above-knee, 62 per cent of through-knee and 44 per cent of Gritti-Stokes patients (56 per cent overall). The better rehabilitation of through-knee versus above-knee amputees (P less than 0.02) was also found in a group of patients matched for comparable age and duration of amputation as well as in a group of age-matched vascular amputees. Through-knee amputees relied significantly less on wheelchairs than above-knee (P = 0.016) and Gritti-Stokes (P = 0.05) amputees. The prosthesis used for the through-knee and Gritti-Stokes amputations was considered unsightly in 50 per cent of cases (versus 31 per cent for the above-knee prosthesis). The superior rehabilitation with through-knee amputations should prompt us to improve both our technique for this amputation and the prostheses currently available. A through-knee amputation should be performed in preference to an above-knee amputation in the case where either is surgically possible, and a below-knee amputation not feasible.

Adult↗
PubMed1988

Monoclonal antibodies in the treatment of hematopoietic malignancies.

The development of practical methods for producing specific, highly purified monoclonal antibodies (MoAbs) targeted to specific tumor-cell antigens has opened new vistas in therapy for both hematologic malignancies and solid tumors. Numerous phase I trials with first-generation MoAbs have revealed both the broad therapeutic promise of MoAbs in anticancer therapy and the obstacles that must be overcome before they can be utilized fully in the clinical setting. MoAbs can be used to activate or manipulate the patient's immune system to destroy malignant cells. They also can be used as carriers for antitumor agents such as chemotherapeutic compounds, radiation, and toxins. Because many MoAbs are prepared from mouse cells, a common problem has been the development of resistance to the heterologous mouse protein. Strategies to circumvent this resistance include the use of human MoAbs, the production of chimeric mouse-human MoAbs, and the induction of tolerance to the mouse MoAbs. The possibility of combination therapy using MoAbs in conjunction with chemotherapy, lymphokines, or other biological response modifiers also is being explored.

Antibodies, Monoclonal↗
PubMed1985

Autoimmune response of patients with paraneoplastic cerebellar degeneration to a Purkinje cell cytoplasmic protein antigen.

Sera from 6 of 12 patients with paraneoplastic cerebellar degeneration (PCD) contained anti-Purkinje cell antibodies, as determined by indirect immunofluorescence on frozen sections of normal human cerebellum. Samples of cerebrospinal fluid from 2 of the patients with serum antibodies were tested, and both specimens contained anti-Purkinje cell antibody. The anti-Purkinje cell antibodies were polyclonal, fixed complement, and were present in all patients at serum dilutions of 1:1,000 or greater. Antibody activity could not be suppressed by preabsorption of sera with human or animal brain and tissue powders or with fresh crude human cerebellar extracts. No anti-Purkinje cell antibodies were detected in control sera from 167 neurologically normal cancer patients, 32 normal volunteers, 10 patients with other causes of cerebellar degeneration, or 8 patients with other paraneoplastic neurological diseases. Preliminary evidence suggests that the Purkinje antigen is a protein that is often concentrated in the periphery of the cytoplasm in disc-shaped structures. Patients with antibodies often developed signs of PCD near the time of detection of the tumor and had relentless progression of neurological disease. Patients without antibodies frequently had cancer for months to years before PCD developed, and often had spontaneous stabilization of neurological disease with time. Four patients without and 3 patients with antibodies underwent plasmapheresis without response.

Aged↗
PubMed1979

Solar cycles and malignant melanoma.

There has been a sixfold increase in the incidence of malignant melanoma in the State of Connecticut during the past forty years. Superimposed on a steady incidence rise are cycles of markedly increased incidence rates which follow periods of maximum sunspot activity. We propose that the effect of sunspot cycles on human melanoma occurrence is mediated by modulation of stratospheric ozone and thus indirectly affects UV flux at the earth's surface. This hypothesis would predict a time lag in melanoma incidence cycles, relative to sunspot activity, with increasing distance from polar caps. This appears to be the case. The increase in melanoma incidence related to a given reduction in ozone depletion in this hypothesis, is in great excess of existing models relating anthropogenic ozone depletion and skin cancer.

Connecticut↗
PubMed1979

A throat spray.

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Aerosol Propellants↗
PubMed1978

Increased incidence of malignant melanoma after peaks of sunspot activity.

The age-adjusted incidence-rate for malignant melanoma in the State of Connecticut has risen from 1.1 per 100 000 individuals in 1935 to 6.2 per 100 000 individuals in 1975. Superimposed on a steady rise in incidence are 3-5 year periods in which the rate of increase in incidence rises. These periods have a cycle of 8-11 years and follow times of maximum sunspot activity.

Age Factors↗