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Biomedical subjects

A M Jackson

Publications and source records attributed to A M Jackson.

At least 55 records · Page 3Linked to original sources
PubMed1993

Partial control of hepatitis delta virus superinfection by immunisation of woodchucks (Marmota monax) with hepatitis delta antigen expressed by a recombinant vaccinia or baculovirus.

We have successfully limited the level of hepatitis delta viraemia occurring after superinfection of hepadna-virus infected woodchucks by prior immunisation with the short form of the hepatitis delta virus antigen expressed by a recombinant baculovirus or vaccinia virus. This phenomenon occurred in the absence of detectable circulating antibody to hepatitis delta virus antigen and in the absence of evidence of priming of the humoral immune response and may reflect the induction of a cytotoxic T-cell response. The latter would control viraemia by rapid lysis of delta antigen expressing hepatocytes. It is suggested that the T-cell epitopes involved may be located on the carboxyl end of the delta protein (amino acids 77-195).

Animals↗
PubMed1993

The immunomodulatory effects of urine from patients with superficial bladder cancer receiving intravesical evans BCG therapy.

Bladder cancer cells were stimulated with urine obtained from patients with superficial bladder cancer who had received treatment using intravesical bacillus Calmette-Guérin (BCG). The urine from the first 12 h following each of six BCG instillations was collected and examined for its biological effect. We evaluated effects that had previously been attributed to cytokines detected in the urine of such patients. The modulation of MHC class II antigen and intercellular adhesion molecule-1 (ICAM-1) expression were studied. Using neutralizing polyclonal antibodies to interferon gamma and tumour factor alpha the relative contribution of these molecules to the effects investigated were determined. When cells were stimulated for up to 48 h with first-instillation urine, little effect was seen in any of the parameters investigated. Urine from the sixth instillation, however, proved to be a potent immunomodulatory agent, inducing MHC class II molecule and ICAM-1 expression. Urine from instillations two to five mediated increasing immunomodulatory effects. When sixth-instillation urine samples were treated with neutralizing antibodies to interferon gamma prior to their addition to the bladder cancer cells, a marked and significant decrease in their potency was observed. Only in urine from one patient did any immunomodulatory capability remain after antibody treatment. Neutralizing antibodies to tumour necrosis factor alpha, however, failed to reduce the ability of any patient's urine to induce ICAM-1 expression. When both antibodies were used simultaneously no further decrease in potency was observed. These studies demonstrate for the first time the potential immunomodulatory and cytotoxic effects of urine produced by patients receiving intravesical BCG. Furthermore, in all samples tested, the major immunomodulatory component was shown to be interferon gamma. Although tumour necrosis factor alpha is produced as a result of BCG therapy, this cytokine did not appear to contribute to the parameters investigated, namely the induction of HLA class II antigens, and cell-surface ICAM-1.

BCG Vaccine↗
PubMed1993

The effect of recombinant cytokines on bladder cancer cells in vitro.

We have studied the Major Histocompatibility Class II-modulating and antiproliferative actions of recombinant interferon-gamma, tumor necrosis factor-alpha, interleukin-1 alpha, interleukin-2 and granulocyte macrophage-colony stimulating factor on bladder cancer cells in vitro. Indirect immunofluorescent staining employing monoclonal antibody probes in conjunction with flow cytometric analysis and tritiated thymidine incorporation assays were used. Interferon-gamma was a strong inducer and enhancer of class II antigens. Tumor necrosis factor-alpha could not induce the expression of class II antigens on tumor cells, which were initially class II-negative, but enhanced the expression on cells which already demonstrated low levels of the antigen. Interleukin-1, interleukin-2 and granulocyte macrophage-colony stimulating factor did not affect the major histocompatibility class II expression. Interferon-gamma and tumor necrosis factor-alpha both demonstrated powerful anti-proliferative effects on the bladder cancer cells, particularly those derived from low grade tumors (G1 and G2). Interleukin-1 alpha had no effect on tumor cell proliferation. In contrast interleukin-2 and granulocyte macrophage-colony stimulating factor had significant stimulatory effects on the proliferation of the low grade tumor cells (G1).

Antigens, Neoplasm↗
PubMed1992

Expression of interferon-gamma receptors on bladder cancer cells: does it correlate with biological response?

Previously we have shown a differential biological response of three human bladder cancer cell lines (RT4, RT112 and MGH-U1) to gamma interferon (IFN-gamma). The present study examines the relationship between the biological response and the expression of the interferon-gamma receptor on the tumour cell surface. Using a competitive radioligand binding assay and Scatchard analysis, we measured the number and affinity of the IFN-gamma receptors on each of the above cell lines. Individual cells from each line expressed large numbers (29,100-41,800) of high-affinity receptors (kd = 2.4-3.9 x 10(10) M). There was no statistically significant difference in either of these parameters between the three lines. We therefore conclude that the biological response of these bladder lines to IFN-gamma does not relate to the number or affinity of its receptor on the plasma membrane of these tumour cells.

Carcinoma, Transitional Cell↗
PubMed1992

Expression of adhesion molecules by bladder cancer cells: modulation by interferon-gamma and tumour necrosis factor-alpha.

The constitutive expression by eight human bladder cancer cell lines of the cell adhesion molecules intercellular adhesion molecule-1 and intercellular adhesion molecule-2 was studied using monoclonal antibody probes in conjunction with flow-cytometry. Tumour lines of low grade (G1) did not constitutively express intercellular adhesion molecule-1, rather they were found to express intercellular adhesion molecule-2. The G2 cells expressed no intercellular adhesion molecule-2, however, a low percentage did express intercellular adhesion molecule-1. High grade cells (G3) only expressed intercellular adhesion molecule-1 on their cell surface but at higher levels than the G2 cell line. Exposure of the bladder cancer cell lines to interferon-gamma induced and augmented the expression of intercellular adhesion molecule-1 by all except one of the cell lines (UMUC3). Intercellular adhesion molecule-2 expression remained unaltered. The modulation of intercellular adhesion molecule-1 expression was dependent on the concentration of interferon-gamma and the duration of stimulus. De novo intercellular adhesion molecule-1 expression, induced by interferon-gamma, was rapid (< 4 hours) with only a short period of stimulation being required (< 10 seconds). The rapid increase in expression of intercellular adhesion molecule-1 required de novo protein synthesis and was not the result of release of intercellular adhesion molecule-1 from an intracellular pool. Interferon-gamma and tumour necrosis factor-alpha were found to act synergistically in the induction and augmentation of intercellular adhesion molecule-1 expression. Optimal induction occurred with 10 Uml-1 of both molecules. These results suggest a correlation between constitutive adhesion molecule expression and the histopathological grade of the tumour. The implications of these findings for Bacillus Calmette Guerin and interferon-gamma immunotherapy of bladder cancer is discussed.

Carcinoma, Transitional Cell↗
PubMed1992

An investigation of factors influencing the in vitro induction of LAK activity against a variety of human bladder cancer cell lines.

We investigated the sensitivity of transitional cell carcinoma cells, derived from the human bladder, to lymphokine activated killer cells. Recombinant interleukin-2 activated peripheral blood mononuclear cells were studied for their ability to mediate the cytolysis of a panel of four established human bladder transitional cell carcinoma cell lines. Lymphokine activated killer activity was assessed using a standard four hour chromium release assay. All four bladder cancer cell lines proved to be susceptible to lymphokine activated killer mediated cytolysis. This was found to be dependent upon the dose of cytokine and upon the duration of the activation period. The four cell lines were differentially susceptible to lysis (specific cytotoxicity at effector to target ratio of 40:1; RT112 = 22.9%, RT4 = 49.2%, MGH-U1 = 49.1%, EJ18 = 62.3%). The varying susceptibility of lymphokine activated killer mediated cytotoxicity was found to be independent of the histological grade of the parent tumour or the donor of effector cells. Both interferon-alpha and tumour necrosis factor-alpha also elicited lymphokine activated killer cell activity, although the maximum specific cytotoxicity achieved was considerably lower than that obtained with interleukin-2 alone. Interleukin-2, at optimal concentration, and tumour necrosis factor-alpha were found to behave synergistically in the generation of lymphokine activated killer effectors. However, concentrations of tumour necrosis factor-alpha higher than 100 Uml.-1 resulted in a decrease in specific cytotoxicity. These findings suggest a possible use of adoptive immunotherapy in human bladder cancer and indicate the optimum conditions for the generation of such effector cells.

Carcinoma, Transitional Cell↗
PubMed1992

The inhibitory effects of interferon gamma on the growth of bladder cancer cells.

The inhibitory effect of interferon-gamma on the growth of three human bladder cancer cell lines, RT4, RT112 and MGH-U1, representing tumour grades 1, 2 and 3 respectively, was studied. The effects of 10, 100 and 1000 Uml.-1 of interferon-gamma on cell numbers and thymidine incorporation were measured at 24 hour intervals up to a maximum of seven days. Morphological appearances were also studied. Each line was susceptible to the growth inhibitory effects of interferon-gamma and this was both dose and time dependent. The effects of interferon-gamma, on the RT4 and RT112 cells were apparent from 24 hours, and were both cytostatic and cytotoxic in nature, whereas the effects on MGH-U1 cells were seen from 48 hours onwards and were only cytostatic. Cytological changes occurred in all three cell lines, being most pronounced in RT112. The growth of bladder cancer cells was inhibited by interferon-gamma, and in this study high grade tumour cells were least sensitive.

Carcinoma, Transitional Cell↗
PubMed1992

Muscular strength in idiopathic haemihypertrophy.

Nine patients (age 8.9, range 6.5 to 9.5 years) with idiopathic haemihypertrophy were followed at six month intervals for two years. The isometric voluntary contraction strength of the elbow flexors and knee extensors was measured bilaterally, and expressed per unit of muscle and bone cross sectional area of the upper arm (elbow flexors) and of the mid thigh (knee extensors). In absolute terms, the hypertrophic side was always stronger, and the increase in strength was strongly correlated with the increase in limb size bilaterally (P less than 0.01). The hypertrophic limb always exerted greater isometric strength, but if strength was standardized for an anthropometric estimate of upper arm and mid thigh cross sectional area, the normal and hypertrophic side were not significantly different. The limb length discrepancy, when expressed in percentage, remained constant at approximately 3%.

Analysis of Variance↗
PubMed1992

Role of adhesion molecules in lymphokine-activated killer cell killing of bladder cancer cells: further evidence for a third ligand for leucocyte function-associated antigen-1.

The lysis of eight human bladder cancer cell lines by lymphokine-activated killer cells (LAK) was found to be partially dependent upon the expression by the target cell of either intercellular adhesion molecule-1 (ICAM-1) or intercellular adhesion molecule-2 (ICAM-2). Using adhesion blockade studies these molecules were found to contribute towards sensitivity to lysis. Tumour lines of low grade (G1) did not constitutively express ICAM-1, but were found to express ICAM-2. High grade cells (G2, G3), however, only constitutively expressed ICAM-1 on their cell surface. Interferon-gamma (IFN-gamma) induced and augmented the expression of ICAM-1 by all except one of the cell lines (UMUC3) in a dose- and time-dependent manner. This was accompanied by an increased susceptibility to lymphokine-activated killer mediated cytolysis. Anti-ICAM-1 antibodies partially inhibited the increase in cell lysis due to IFN-gamma. However, this inhibition was not complete. When effector cells were treated with antibodies to leucocyte function-associated antigen-1 (LFA-1) the inhibition of lysis was greater and ranged from 72 to 96% with a mean of 87% inhibition. These results suggest that the increased sensitivity of IFN-gamma-treated bladder cancer cell lines to LAK cells is partially attributable to the induction of ICAM-1. However, blocking of ICAM-1 with antibodies could only partially inhibit the increased LFA-1-dependent lysis. This supports recent evidence for the existence of an additional ligand for LFA-1, other than ICAM-1 and ICAM-2.

Antigens, CD↗
PubMed1991

Successful antibiotic therapy of clostridial septic arthritis in a patient with bilateral total hip prostheses.

We report a case of clostridial bacteraemia with infection of a prosthetic hip joint. The patient was successfully treated with IV benzyl penicillin and fucidin followed by oral amoxycillin and probenecid, without surgical intervention. She had no recurrence of her infection in the 19 months before her death. This is believed to be the first reported case of clostridial infection affecting a prosthetic joint.

Aged↗
PubMed1991

The effects of recombinant human interferon-gamma on a panel of human bladder cancer cell lines.

We have examined the Major Histocompatibility Complex class II antigen inducing capabilities of recombinant human interferon-gamma, on a panel of human transitional cell carcinoma lines which have been raised from original tumours of varying histological grades: RT4 (grade 1), RT112 (grade 2) and MGH-U1 (grade 3). Cells were examined for class II antigens using an indirect immunofluorescent staining method and analysed on a fluorescence activated cell sorter. Twenty percent of RT4 cells constitutively expressed class II antigen. Both RT112 and MGH-U1 were repeatedly found to be negative for this antigen prior to treatment with interferon-gamma. Following treatment with interferon-gamma all three lines showed an increase in class II antigen expression, which was consistently dependent on both the length of incubation and concentration of interferon-gamma. A differential susceptibility was found amongst the three cell lines which may relate to the histological grade of the parent tumor.

Carcinoma, Transitional Cell↗
PubMed1991

Milk-induced, opioid-mediated antinociception in rats at the time of cesarean delivery.

Four experiments were conducted in rats within 2 hr of cesarean delivery to assess antinociception at birth and its possible opioid bases. Morphine antinociception was established in a dose-dependent fashion (0.0625-5.0 mg/kg bw). Analgesia was naloxone (1.0 mg/kg) reversible. In succeeding experiments, antinociception equivalent to that produced by 0.0625-0.125 mg/kg morphine injections was induced by a single 20-microliters bolus of milk (commercial half-and-half) that was delivered over 1-2 s to the middle of the tongue. This, too, was naloxone reversible. Milk-induced antinociception was maintained for at least 4 min. Finally, baseline latencies were progressively reduced during the first 2 hr after delivery to levels (8-10 s) that are typically obtained in older (10-day-old) rats. This decline was not opioid mediated because it was not affected by naloxone. Thus, at birth, delivering milk to the mouth in physiological volumes can exert opioid-mediated antinociceptive effects in rats born by cesarean delivery that had never suckled or experienced any other form of maternal contact.

Animals↗
PubMed1991

Microtia and short stature: a new syndrome.

Bilateral microtia, absent patellae, short stature, poor weight gain, and characteristic facial features are described in two female sibs. Other skeletal anomalies included complete habitual dislocation of the elbow, slender ribs and long bones, abnormal modelling of the glenoid fossae with hooked clavicles, and clinodactyly. Bone age was significantly delayed and there was flattening of the epiphyses. This unusual combination of features has many similarities to the syndrome described by Hurst et al.

Abnormalities, Multiple↗
PubMed1990

Donor site morbidity following osteocutaneous free fibula transfer.

Nine patients who had undergone free fibula transfer were reviewed to determine the incidence of donor site complications. Problems identified included distal oedema, cold intolerance, sensory loss and weakness. However, the functional deficit was not great and most patients were not troubled by their symptoms. More serious potential complications from raising this flap are considered.

Adult↗