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K James

Publications and source records attributed to K James.

At least 73 records · Page 4Linked to original sources
PubMed1998

Prognosis of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer by immunological urinary measurements: statistically weighted syndrome analysis.

PURPOSE: The goal of this research was to discover new biological indicators in urine which could be used for short-term prognosis of local Bacillus Calmette-Guerin (BCG) therapy outcome in patients with superficial bladder cancer. PATIENTS AND METHODS: We measured and statistically evaluated soluble immunological molecules in urine from bladder cancer patients (n = 34) receiving BCG intravesically. Urine was collected following each of 6 weekly treatments, processed and assayed. The data base included measurements of interleukin-1 (IL-2, IL-4, IL-6, IL-10, IL-12, soluble intercellular adhesion molecule-1 (sICAM-1), tumour necrosis factor-alpha (TNF alpha), soluble CD14 (sCD14), interferon-gamma (IFN gamma), GM-CSF, volume of urine and its pH. The clinical response was evaluated by urine histology and random quadrant biopsy 3 months after the start of therapy. Patients were divided into 2 groups, with good and poor therapeutic effect. The initial complete response rate was 62% (21/34). The data base was analyzed using traditional multivariate statistical methods and a pattern recognition method which deals with combinatorial-statistical analysis (statistically weighted syndromes (SWS) method) of the gradated features. The SWS method is capable of identifying robust patterns in small "fuzzy" sets with high dimensional objects and some missing values. RESULTS: Only one parameter gave significant differences at p < 0.05, GM-CSF at instillation 6. Repeated measurement analysis of variance, backward stepwise multiple logistic regression and linear discriminant analysis failed to show any significance. However, significant differences in the structure of correlation between features in the groups with and without therapeutic effect were observed and four highly informative variables (the masses of sICAM-1, TNF alpha, sCD14 and pH) relating to 5th-6th installations were selected by SWS. These features provided accurate individual prediction of therapeutic outcome for all our patients. Cross-validation analysis and computer simulation showed the statistically significant stability of the prediction. CONCLUSION: We have selected a set of urinary variables that could be considered as a perspective combination of indicators (syndromes) of outcome of pre-operation BCG therapy of patients with superficial bladder cancer. A larger patient database will provide testing and evaluation of the biological and clinical significance of selected features. The computational syndrome-disease approach should be applicable for the solution of decision-making problems for management of cancer.

Adjuvants, Immunologic↗
PubMed1997

Organ culture of human lymphoid tissue. II. Marked differences in cytokine production and proliferation between slice and suspension cultures of human spleen.

Recently, we have established a method for the culture of human spleen slices in vitro. The procedure allows thin slices (200-350 microns) of human spleen to be cultured for up to 7 days. Using this method, we have previously established that unstimulated spleen slices spontaneously synthesize and secrete considerably higher levels of immunoglobulin than suspension cultures of the same tissue run in parallel. In this study, we report that there are also marked differences in the cytokine secretion profile between slices and suspensions and in their proliferative response. In brief, control and PHA-stimulated spleen slices secrete high levels of IL-1 beta, IL-6, IL-8 and IL-11 while the levels found in suspension supernatants are appreciably lower. By way of contrast, high levels of IL-2, IL-4, IL-10 and TNF alpha are found in suspension culture supernatants following PHA stimulation while the response in slice cultures is extremely low. These differences are also reflected in the results obtained at the cellular (intracellular cytokine) level. Additional studies reveal that spontaneous immunoglobulin production observed in spleen slices can be inhibited by the addition of specific antibodies to IL-1 beta, IL-6 and TNF alpha and that the bulk of the IL-6 and IL-1 beta detected in culture supernatants represents de novo synthesis. Finally, the background and mitogen-stimulated proliferative response of tissue slices is meagre compared with that observed in spleen suspensions suggesting that proliferation in the former is held under strict control. Collectively, we believe that the tissue slice procedure described provides us with a system for studying integrated events in lymphoid tissues in vitro and evaluating immunomodulatory substances of potential clinical importance.

Adolescent↗
PubMed1997

Phase I studies of fluorouracil, doxorubicin and vinorelbine without (FAN) and with (SUPERFAN) folinic acid in patients with advanced breast cancer.

PURPOSE: The Breast Cancer Site Group of the National Cancer Institute of Canada - Clinical Trials Group (NCIC-CTG) undertook two parallel phase I studies to determine the maximum tolerated dose (MTD) and recommended phase II dose of vinorelbine in combination with doxorubicin and fluorouracil (with or without folinic acid) in metastatic breast cancer. METHODS: Cohorts of five patients were to receive: (a) fluorouracil 500 mg/m2 and doxorubicin 50 mg/m2 on day 1 only and escalating doses of vinorelbine (15, 20, 25, 30 mg/m2) on days 1, 8 and 15 every 3 weeks (FAN regimen), or (b) fluorouracil 340 mg/m2 and folinic acid 200 mg/m2 on days 1, 2, 3, 4 and 5, doxorubicin 40 mg/m2 on day 1 only and escalating doses of vinorelbine (15, 20, 25, 30 mg/m2) on day 1 and again on day 5 every 4 weeks (SUPERFAN regimen). Eligibility included measurable or evaluable metastatic breast cancer and having received neither previous chemotherapy for metastatic disease nor anthracycline-containing adjuvant therapy. RESULTS: Of 26 and 12 patients enrolled in the FAN and SUPERFAN regimens, 26 and 12 were evaluable for toxicity and 21 and 9 for response, respectively. Median ages were 60.3 years (41-71 years) and 64.2 years (51-73 years). Both regimens required amendment after the first cohort with an original day- 15 vinorelbine dose omitted from the FAN regimen and more prolonged nadir granulocyte counts allowed. Myelosuppression was dose limiting. MTDs in the FAN and SUPERFAN regimens were vinorelbine 25 mg/m2 and 20 mg/m2. Other toxicities included mucositis, septicemia and febrile neutropenia. Peripheral neuropathy and constipation were mild. Of the 21 FAN patients evaluable for response, 3 (14%) had complete responses and 7 (33%) had partial responses, for an overall response rate of 48%; 9 (43%) had stable disease and 2 (9%) had progressive disease as their best response. Of the nine SUPERFAN patients evaluable for response, none had a complete response. There were two (22%) with partial responses, and six (67%) had stable disease and one (11%) had progressive disease as their best response. CONCLUSIONS: The SUPERFAN regimen was too toxic to pursue even at the lowest dose. The recommended phase II starting dose for the FAN regimen was vinorelbine 20 mg/m2. Although these were phase I studies response rates in evaluable patients were less than expected and toxicity did not allow the use of as much vinorelbine in the combinations as had been anticipated. The limited response data from our study would imply that combining vinorelbine with more toxic agents may not enhance response rates and may defeat the advantage of tolerability, especially in elderly patients.

Adult↗
PubMed1997

IL-6, DHEA and the ageing process.

The age-related increase in circulating IL-6 levels in humans which has been attributed to a decline in DHEA production by the adrenal gland is currently attracting attention because of its possible relevance to the aetiology and management of a number of age-related clinical disorders. The potential importance of these observations and suggestions has prompted us to perform more detailed studies on the relationship between IL-6 and DHEA. Using immunoassay techniques we have found in normal healthy individuals over the age of 40 an inverse relationship between plasma DHEA levels and the presence of detectable levels of IL-6 (more than 1 pg/ml). In vitro, studies also revealed that low dose (10(-6)-10(-8) M) of DHEA and DHEAS inhibited the production of IL-6 in unstimulated human spleen cell suspension cultures whilst enhancing its release by explant cultures of the same tissue. In contrast they had no effect on immunoglobulin production. These studies suggest that there is a real, but complex relationship between IL-6 production and DHEA levels which warrants further investigation.

Adult↗
PubMed1997

Worker social identity and health-related costs for organizations: a comparative study between ethnic groups.

Health implications of value conflicts at work and 3 coping resources (self-esteem, collective esteem, and social support at work) were examined for 38 African American and 64 European American workers. Comparisons indicated that the African American participants reported higher levels of value conflicts and collective esteem, but lower levels of social support. They also reported more health actions (i.e., absenteeism and doctor visits) likely to create organizational costs. Value conflicts and the 3 coping resources predicted health-related behavior. Collective esteem predicted health only for African American workers, though social support was a significant predictor only for European American workers. The study findings are integrated with existing literature on social identity at work, social support, and work influences on health.

Absenteeism↗
PubMed1997

Soluble urinary CD14 after intravesical bacille Calmette-Guérin immunotherapy for carcinoma in situ.

OBJECTIVE: To characterize the production of the monocyte activation marker, soluble CD14 (sCD14), after bacille Calmette-Guérin (BCG) immunotherapy for superficial bladder cancer. PATIENTS AND METHODS: Nineteen patients with carcinoma in situ were treated with a standard regimen of intravesical BCG. Urine samples were collected after each instillation and analysed; the levels of soluble CD14 were determined by an enzyme-linked immunosorbent assay, the molecular weight confirmed by Western blotting and the possible cell source investigated using immunohistochemistry. RESULTS: The mean levels of sCD14 were higher in patients with persistent carcinoma (designated as failures) than in those who had successful complete responses (responders) to BCG immunotherapy. The differences were statistically significant, with P = 0.034 at instillation 4 and P = 0.027 at instillation 5 for the total mass of sCD14, and P = 0.049 at instillation 4 for the concentration of sCD14. The predominant type of sCD14 in urine was the 48 kDa form, although in most patients there was a minor band of reactivity at 54 kDa. A panel of human bladder cancer cell lines did not react with the anti-CD14 monoclonal antibodies 3C10, 5C5 and BA8, and the antibodies also failed to react with malignant epithelial cells in frozen sections of untreated bladder tumour. Furthermore, sCD14 was not secreted by cultured bladder tumour cells. The source of urinary sCD14 is likely to be the resident and infiltrating macrophages in the bladder wall. Freshly isolated peripheral blood monocytes secreted sCD14 in response to BCG in a manner analogous to stimulation with bacterial lipopolysaccharide. CONCLUSION: A soluble form of CD14 is secreted into the urine of patients who receive intravesical BCG. The measurement of soluble urinary CD14 could be of prognostic significance for the response to immunotherapy.

BCG Vaccine↗
PubMed1997

[Cutaneous cancers in Togo].

A retrospective study was conducted during 20 years to determine the epidemiological features of skin cancer diagnosed in the pathology laboratory in Lome teaching hospital. During this period, 518 cases of theses affections were noted: 288 cases of carcinoma (56.6%); out of 288 carcinomas 254 were spinocellular carcinoma, which developed on 143 chronic phagedenic ulcer, the others cancer were: malignant melanoma 63 cases (12.3%), Kaposi's sarcoma 72 cases (13.9%), skin sarcoma 95 cases (18.3%). The results of this study shows that the spinocellular carcinoma were mostly the skin cancer in Black African, and confirm the particularity of malignant melanoma in Black subjects.

Adult↗
PubMed1997

The use of tissue slices in immunological investigations.

Our knowledge of cellular and molecular events taking place during various immune responses comes mainly from in vitro studies where isolated cells are exposed to defined stimuli. This reductionist approach has greatly advanced our understanding of the immune system. However, these studies do not truly reflect the complexity of the integrative events which take place in both primary and secondary lymphoid tissue in vivo. In order to address this problem we have developed a tissue culture procedure which involves the cultivating of precision cut human spleen slices at gas/liquid interface. We have shown, that cells in this culture system show marked differences in cytokine and immunoglobulin production in comparison with conventional single cell suspension cultures, obtained from the same spleen and run in parallel. In this review article we describe the basic technique, results which we have obtained in this system and discuss the possible basis of the observed differences.

Animals↗
PubMed1996

The effects of human seminal plasma and PGE2 on mitogen induced proliferation and cytokine production of human splenic lymphocytes and peripheral blood mononuclear cells.

The effects of human seminal plasma (HSP) and prostaglandin E2 (PGE2) on the proliferative responses of human splenic lymphocytes and peripheral blood mononuclear cells (PBMCs) to phytohaemagglutinin (PHA), anti-CD3 and anti-CD3 plus anti-CD28 mAb have been studied. Th1 and Th2 cytokines were also measured in the supernatants of selected cultures. Both HSP and PGE2 reproducibly inhibit the proliferative response to PHA and anti-CD3 mAb in a dose dependent manner. These effects were observed with both fresh and frozen human PBMCs and splenic lymphocytes. HSP and PGE2 however were less effective in inhibiting the co-stimulatory response induced by anti-CD3 plus anti-CD28 mAb. In addition, the HSP and PGE2 treatment used inhibited the production of the Th1 cytokines IL-2 and IFNg but had a differential modulatory effect on Th2 cytokine production, namely enhancing the production of IL-6 whilst simultaneously impairing the synthesis of IL-4 and IL-10.

Antibodies, Monoclonal↗