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J M Lawson

Publications and source records attributed to J M Lawson.

At least 19 recordsLinked to original sources
PubMed2001

A purpose-built iodine-125 irradiation plaque for low dose rate low energy irradiation of cell lines in vitro.

The phenomenon of hyper-radiosensitivity (HRS) to very low acute single doses of radiation has been demonstrated in several cell lines in vitro and in vivo, and has been studied in theory and in practice. The theory suggests a similar hypersensitivity when cells are continuously exposed to radiation at very low dose rates. These low dose rates are used when radioactive seed (iodine-125 or palladium-103) implants of the prostate are used as an alternative to surgery or external beam radiotherapy. To investigate the radiobiology of hypersensitivity of this type on various cell lines in vitro, an iodine-125 seed irradiator has been designed and built for safe use in the Gray Laboratory. In practice, the calculated dose rate has been used for consistency. Discrepancies between calculated and measured dose rates are discussed.

Brachytherapy↗
PubMed2001

Growth-inhibitory effects of CD40 ligand (CD154) and its endogenous expression in human breast cancer.

CD40 binding produces multifaceted growth signals in normal and malignant B cells, whereas its physiological role is less well characterized in epithelial cancers. We examined the growth outcome of CD40 ligation in human breast cancer cells, using CD40+ (T47D and BT-20) and CD40-negative (MCF-7, ZR-75-1) cell lines as defined by flow cytometric analysis, immunohistochemistry, and reverse transcription-PCR. Treatment with the soluble recombinant CD40 ligand (CD40L) molecules gp39 or CD40L-trimer significantly reduced [3H]thymidine uptake in BT-20 and T47D cells by up to 40%, but did not affect the growth of CD40-negative MCF-7 or ZR-75-1 cells. Similarly, significant growth inhibition was observed after co-incubation with CD40L-transfected murine L cells (55.0 +/- 8.9%, P < 0.001) that express membrane CD40L constitutively, or with paraformaldehyde-fixed, CD3+ CD40L+ PBLs from three different HLA-mismatched donors (39.7 +/- 3.7%, P < 0.01). Untransfected L cells and non-CD40L-expressing lymphocytes did not produce significant growth inhibition. The in vivo antitumorigenic effects of CD40L were examined using a s.c. severe combined immunodeficient-hu xenograft model. Pretreatment with two different soluble recombinant CD40L constructs (CD40L and gp39) produced similar xenograft growth-inhibitory effects [67 +/- 24% (n = 4), and 65 +/- 14% (n = 8) inhibition, respectively], which were reversed by co-treatment with the CD40L-neutralizing antibody LL48. In vitro analysis indicated that CD40L-induced growth inhibition was accompanied by apoptotic events including cell shrinkage, rounding, and detachment from the adherent T47D culture monolayer. Thirty-one and 27% of gp39-treated T47D and BT-20 cells underwent apoptosis, respectively, as compared with 56 and 65% from the same cell lines after treatment with the Fas agonistic antibody CH-11. An up-regulation of the proapoptotic protein Bax in T47D and BT-20 cells was observed, which indicated that this Bcl-2 family member may contribute to this growth-inhibitory effect. To explore the clinical relevance of CD40L-CD40 interaction, retrospective immunohistochemical analysis was carried to characterize in situ CD40- and CD40L-expression in breast cancer patient biopsies. All of the infiltrating ductal (5 of 5 cases tested) and lobular (4 of 4 cases) breast carcinomas, carcinomas in situ (6 of 6 cases), and mucinous carcinoma tested (1 case) expressed CD40. Varying proportions of tumor cells also expressed CD40L in the majority of infiltrating ductal (3 of 5 cases) and lobular (3 of 4 cases) carcinomas, and carcinomas in situ (4 of 6 cases), as determined by immunohistochemistry and validated by RT-PCR detection of the CD40L message in only CD40L positive-staining cases. Tumor infiltrating mononuclear cells from infiltrating carcinomas and carcinomas in situ expressed CD40 (10 of 10 cases), but less commonly CD40L (1 case of infiltrating lobular carcinoma, 2 cases of carcinoma in situ). Our findings indicate that the CD40 signaling pathway is active in human breast carcinoma cells. However, tumor-infiltrating lymphocytes from primary tumor tissues may be limited in their capacity to directly modulate tumor growth through the CD40L-CD40 loop.

Animals↗
PubMed2000

Cellular immune profile of patients with advanced cancer before and after taxane treatment.

The purpose of this study is to determine immune recovery and function after treatment with docetaxel or paclitaxel. Peripheral blood mononuclear cells were harvested before chemotherapy and at weekly times afterwards for cycle 1. Leukocyte subsets ICD45hiCD14lo polymorphonuclear neutrophils, CD45hiCD14hi monocytes, CD45hiCD14- lymphocytes, CD3+CD4/CD8+ T cells, CD3-CD19+ B cells, CD3-CD16/CD56+ natural killer (NK) cells], and circulating cytokine levels [tumor necrosis factor-alpha, gamma-interferon (gamma-IFN), and interleukins (IL-2, IL-10, IL-12)] were followed. In addition, T-cell mitogenic function, NK function, and lymphokine activated killer (LAK) function was assessed. Ten patients were entered in the trial. T-cell frequency, B-cell frequency, and CD4/CD8 ratio did not change. IL-10 serum levels significantly decreased in paclitaxel-treated patients (4.4+/-1.3 pg/ml at week 4 versus 7.8+/-2.1 pg/ml at baseline; p < 0.05). IL-2, IL-12, and gamma-IFN levels were not detectable. NK cytotoxic activity decreased in docetaxel-treated patients. LAK cell activity was not altered. Four patients achieved a partial or complete response. They demonstrated higher than normal CD4:CD8 T-cell ratios and an improved phytohemagglutinin stimulation index (SI = 2.5). In conclusion, our findings suggest that immune function was affected more significantly after docetaxel treatment. Investigational approaches, which enhance cellular immunity, may be of greater relevance after treatment with docetaxel. Additional studies monitoring NK function after chemotherapy are recommended.

Aged↗
PubMed2000

T cells and fibroblasts in affected extraocular muscles in early and late thyroid associated ophthalmopathy.

AIM: To determine whether there are differences in the lymphocytic cell infiltrate present in affected extraocular muscles (EOM) during early and late stages of thyroid associated ophthalmopathy (TAO). METHODS: 17 biopsies of affected EOMs were collected from two groups of TAO patients (n=14): the first of five patients with early, active TAO, and the second of nine patients with late, inactive TAO. The control group was of EOM biopsies taken from 14 non-TAO patients undergoing squint surgery. Immunohistochemical analysis was undertaken using the relevant monoclonal antibodies and an avidin-biotin system and the three groups compared. RESULTS: Both CD4+ and CD8+ T cells were found in the cellular infiltrate in early, active TAO specimens which were much less evident either in late, inactive stage disease or in control tissue. There was also a significant increase in both CD45RO+ and CD45RB+ cells and macrophages in early TAO compared with the others. Increased expression of HLA-DR antigen by interstitial cells including fibroblasts was detected in both early and late disease but the EOM fibres remained morphologically intact and did not express MHC class II antigens at any time. CONCLUSION: These results demonstrate that T cells are only significantly present in early disease but increased HLA-DR antigen expression on fibroblasts is observed at all stages. This suggests that T cells are much more involved in the early than the later stages of the disease process and that early activation of fibroblasts occurs. Early intervention with immunosuppressive therapy to downregulate cytokine production by T cells may significantly influence the sequelae caused by EOM fibrosis.

Adult↗
PubMed1999

Eradication of Helicobacter pylori normalizes elevated mucosal levels of epidermal growth factor and its receptor.

OBJECTIVE: Helicobacter pylori (H. pylori) infection has been linked to gastric cancer. The factors that promote carcinogenesis remain unknown. Epidermal growth factor (EGF) has been shown to be a potent epithelial mitogen and oncoprotein when sustained over expression occurs. Our aim was to compare gastric mucosal levels of EGF and its receptor (EGFR) among controls, H. pylori infected subjects, and subjects following H. pylori eradication using quantitative flow cytometric analysis. METHODS: Patients referred for evaluation of dyspepsia underwent EGD and six antral biopsies were performed (two each for rapid urease testing (RUT), histopathology, and flow cytometry). Controls were those found to be H. pylori negative while subjects had confirmed infection. The study patients were treated, then had repeat EGD with biopsies. RESULTS: There were 17 controls and 28 cases. Mean EGF and EGFR values were 2.69 and 2.46 for controls and 4.67 and 4.64 for subjects. Subjects' mean EGF was 73% higher (p = .035) and EGFR was 88% higher (p = 0.029) than controls. After treatment, the subjects' mean values declined 55% (p = 0.0001) for EGF and 40% (p = 0.002) for EGFR. Three subjects had persistent infection and showed no change in their EGF/EGFR levels. No difference was found among factor levels with respect to endoscopic findings. CONCLUSIONS: Both EGF and EGFR from gastric antral biopsies are increased nearly 2-fold in infection with H. pylori. Infection eradication reduces levels of both factors to those of controls. One major pathogenic mechanism for gastric mucosal hyperproliferation and possibly carcinogenesis related to H. pylori may be the over expression of EGF and increased receptor density of EGFR on gastric mucosal cells.

Adult↗
PubMed1998

Long-term results of botulinum toxin in consecutive and secondary exotropia: outcome in patients initially treated with botulinum toxin.

INTRODUCTION: Long-term ocular alignment can be difficult to achieve in patients with consecutive and secondary (sensory) exotropia, and botulinum neurotoxin A (BTXA) is a recognized alternative to surgery in this group. PATIENTS AND METHODS: We reviewed the results of 44 patients aged 15 to 77 years (mean 31 years) who underwent their first BTXA injections from 1989 to 1990. In 30% of cases the choice of toxin treatment was made by the patient. In the remainder BTXA was recommended by the clinician to assess the risk of postoperative diplopia. Thirty-three patients (75%) were consecutively exotropic and 68% of patients had had previous strabismus surgery. The mean preinjection deviation was 41 delta of exotropia (range 12 to 85 delta exotropia) and the minimum mean angle change after 1 injection was 27 delta (range 0 to 57 delta). The average number of injections was 3 (range 1 to 17). RESULTS: Of the patient group, 59% went on to strabismus surgery, 14% continued to attend for maintenance treatment, and 9% were discharged with a small, stable deviation. The remainder were either followed up elsewhere or failed to reattend. CONCLUSIONS: Botulinum toxin appears to be a satisfactory treatment for constant exotropia in patients at risk of postoperative diplopia who have undergone multiple operations but, because more than half the group went on to surgery, surgery as a first therapy may be preferable in uncomplicated cases.

Adolescent↗
PubMed1997

Botulinum toxin in fourth nerve palsies.

BACKGROUND: Botulinum toxin A (BTXA) has not been used routinely in the management of fourth nerve (IV N) palsy. However, it is known that the results of surgery can be unpredictable with a risk of over- or under-correction. METHODS: The results were reviewed of 20 patients, aged 19-70 years, with unilateral and bilateral IV N palsies who received BTXA injections to the inferior oblique or inferior rectus muscles. The aetiology was congenital in 12 (60%), traumatic in six (30%), due to myasthenia in one (5%), and unclear in one (5%). Fifty per cent of patients had had previous strabismus surgery to a maximum of four procedures. The mean pre-injection vertical deviation was 11 prism dioptres. All but two patients had a single injection. Average follow-up was 19 months. RESULTS: Ten patients (group I) received BTXA as a primary therapy. Following inferior oblique injection, six patients received little benefit and went on to surgery (83%) or continued with prisms (17%). Five patients from group I who had inferior rectus toxin were discharged symptom-free. Group 2 (10 patients) received BTXA for residual deviations postoperatively; in this group all except one patient with no fusion achieved long-term benefit following inferior rectus BTXA. In those who had inferior oblique injections, BTXA was useful in one patient (25%). Inferior rectus injection produced a greater chance of temporary reversal of the deviation. CONCLUSIONS: BTXA is of greatest benefit in patients with residual deviations particularly when the inferior rectus is injected, but is of limited value as a primary therapy in chronic IV N palsy.

Adult↗
PubMed1996

Efficacy of ciprofloxacin in the eradication of Helicobacter pylori.

In small preliminary trials, ciprofloxacin has failed to eradicate Helicobacter pylori. Since fluoroquinolones have a marked reduction in bactericidal activity at acidic pH, we altered the gastric pH using omeprazole and investigated the efficacy of ciprofloxacin in eradicating H pylori. Forty-four consecutive patients infected with H pylori were prospectively studied in a randomized, double-blind, controlled trial comparing ciprofloxacin with a placebo for 2 weeks. Both treatment groups received bismuth and omeprazole. In 36 patients, follow-up endoscopy was done 4 weeks after the cessation of all study drugs. The H pylori infection cleared in 13 of 17 patients (76%) in the ciprofloxacin group versus 5 of 19 (26%) in the placebo group. Concurrent administration of omeprazole with ciprofloxacin resulted in increased bactericidal activity against H pylori. Ciprofloxacin when combined with omeprazole and bismuth is efficacious for eradication of H pylori.

Adult↗
PubMed1995

Endoscopic therapy for pancreatic pseudocysts.

The management of pancreatic pseudocysts is complex. It demands an understanding of the natural history of the disease and an appreciation of the strengths and weaknesses of the treatment options available. Endoscopic therapy represents a valuable alternative to surgery in the subset of patients with appropriate anatomy. Success and relapse rates for endoscopic treatment of pancreatic pseudocysts are comparable to alternative methods, but require careful patient selection and operator expertise. Complication rates vary widely in published studies. It is hoped that technical innovation will reduce the risks. For example, the use of an aspiration needle to localize the pseudocyst and endoscopic ultrasound to define local vascular anatomy are significant advances. Strictly limiting the size of the opening created in cyst-gastrostomy and cyst-duodenostomy should reduce the risk of hemorrhage. Although technically difficult, transpapillary drainage is an option worth considering in patients with fluid collections associated with pancreatic ductal disruption. No single technique offers the desired combination of 100% success and no complications. Surgery, percutaneous drainage, and therapeutic endoscopy offer a variety of treatment options that can be tailored to the needs of individual patients with pancreatic pseudocyst.

Biopsy, Needle↗
PubMed1994

A 39 year old man with chronic hepatitis.

The diagnosis of primary sclerosing cholangitis in association with autoimmune hepatitis was made in this case after the discovery of inflammatory bowel disease prompted a cholangiogram. Immunosuppressive therapy with cyclosporine prior to ERCP resulted in a significant decrease in serum aminotransferase. Liver histology and autoimmune serologies favored a diagnosis of AIH, while cholangiographic findings suggested PSC. A review of similar cases describing the simultaneous occurrence of AIH and PSC is presented. The shared autoimmune characteristics of the two diseases, such as serum autoantibodies, peripheral lymphocyte subsets and HLA haplotypes, raises the question of whether similar mechanisms of immune dysfunction can result in both processes. The existence of a PSC-AIH overlap syndrome may help provide the linkage between the two diseases.

Adult↗