In recent immunological studies, it has been suggested that trichloroethylene (TCE) participates in the onset of pneumatosis cystoides intestinalis (PCI) through a certain mechanism; however, the mechanism by which it develops remains unknown. Based on findings that secondary PCI is often linked with autoimmune disease, the possibility that some genetic or immunological mechanisms are involved in the development of PCI has been proposed. Pneumatosis cystoides intestinalis is not a type of disease where a dose-response relationship with TCE exposure can be recognized and it is difficult to reproduce its physiopathology through TCE exposure in ordinary experimental animals. In the present study, immunological changes caused by TCE exposure were investigated by employing MRL-lpr/lpr mice that are genetically labile to autoimmune diseases. To observe changes in B cell functions, serum antibody titres were measured; and for the T cell function, T cell subsets were examined. The animals were exposed to TCE at dosages of 0, 500, 1000 and 2000 ppm through inhalation 4 h a day, 6 days a week, for 8 weeks. It was found that only IgG production capacity was suppressed and there were no changes in T cell subsets with TCE concentrations up to 1000 ppm. At a concentration of 2000 ppm, changes were noted in both T and B cell functions. Typical organs that are responsible for immunological functions were examined for their morphological changes under a light microscope: the spleen and liver exhibited dose-response changes at a concentration of 500 ppm or greater. The development of immunoblastoid cells at a concentration of 1000 ppm indicated a possibility that a change has occurred in the immunological system. These findings show that exposure to TCE at high concentrations affects the immune system, but the study failed to induce PCI in the experimental animals. Further studies on TCE exposure at lower concentrations for longer periods are needed.

Anesthetics, Inhalation↗

PubMedDate not supplied

Cyclin D1 overexpression in invasive breast cancers: correlation with cyclin-dependent kinase 4 and oestrogen receptor overexpression, and lack of correlation with mitotic activity.

BACKGROUND: Cyclin D1 (CCND1) and its catalytic partner cyclin-dependent kinase 4 (cdk4) are known to play important roles in the G1/S check point of the cell cycle, and CCND1 overexpression has been reported to correlate with progression and prognosis of breast cancers. Oestrogen receptor (ER) levels determine the proliferative response to oestrogen by regulating binding. It has been postulated that CCNDI and cdk4 exert effects on mammary carcinogenesis in co-operation with ER. PATIENTS AND METHODS: CCND1 and cdk4 overexpression in 117 breast cancer cases with long-term follow-up were investigated by means of immunohistochemistry and differential polymerase chain reaction (PCR), using formalin-fixed and paraffin-embedded samples, and compared with ER status and mitotic indices. Additional Western blotting and reverse transcription (RT)/PCR/Southern blot hybridization were performed for 4 breast cancer cell lines and 15 fresh-frozen breast cancer samples to confirm CCND1 and cdk4 data. RESULTS: Immunohistochemically 27 cases were CCND1-positive (23.0%), and CCND1 amplification was evident in 21 (21/86; 24.4%). The two methods in combination demonstrated 37 cases (31.6%) to be positive for CCND1 overexpression. Western blotting revealed 60% of samples of fresh tissue to overexpress CCND1, corresponding well with the results of RT-PCR. There was thus a strong discrepancy between results for paraffin block and fresh samples, probably because of the short life of CCND1. In the case of cdk4, the respective percentages for positive cases were 54.7% and 73%. CCND1 and cdk4 overexpression (P < 0.0001), and CCND1 and ER positivity (P = 0.0128) correlated. In addition, samples overexpressing CCND1, cdk4 and ER tended to have slightly lower proliferative activity than samples where these were absent. However, no association with clinicopathological parameters was evident. cdk4 overexpression had no linkage with ER status or clinicopathological status. Neither CCND1 nor cdk4 expression affected prognosis. CONCLUSION: CCND1 overexpression does not correlate with cancer progression or prognosis or with mitotic activity. The results may suggest that an excess accumulation of CCND1 in breast cancer cells tends to suppress entry into the S phase of the cell cycle.

Blotting, Western↗

PubMedDate not supplied

Apoptosis and proliferative activity of non-Hodgkin's lymphomas: comparison with expression of bcl-2, p53 and c-myc proteins.

In order to clarify the role of spontaneous apoptosis of non-Hodgkin's lymphomas in the growth regulation system, apoptotic indices (AI) assessed by DNA nick end-labeling and proliferative activity, estimated in terms of KI-67 labeling indices (KI) and mitotic indices (MI), were compared. In addition, expression of bcl-2, p53 and c-myc was also examined in relation to these indicators. For this study, 103 lymphoma cases were used, comprising 72 of B cell and 31 of T cell origin (42 nodal and 62 extranodal). AI, KI and MI were significantly increased in line with bcl-2 negativity and p53 positivity, and there was no relation to the T, B cell classification or expression of c-myc. These indicators positively correlated overall. Positive correlation was stricter in groups believed to represent a good prognostic predictive factor, such as B cell origin, bcl-2(+), p53(-) and c-myc(-). Significant cross-correlation was noted only between bcl-2 versus T, B cell classification. However, no inverse correlation between bcl-2 and p53 was evident. These results suggest, in non-Hodgkin's lymphomas, that apoptosis plays an important role together with proliferative activity in counter-balancing tumor volume, and is strictly linked to bcl-2 expression, less so to p53 expression, but independent of T, B cell classification and c-myc expression. Apoptotic indices may be a predictive indicator for prognosis similar to proliferative activity.

Apoptosis↗

PubMedDate not supplied

[Clinical evaluation of basic fetoprotein in bladder cancer].

PURPOSE: The early diagnosis of bladder cancer allows for effective local treatment and optimizes the success of surgical therapy. Basic fetoprotein (BFP), measured using a rapid latex immuno-agglutination method, was introduced for the detection of transitional cell carcinoma. The objective of this study was to determine whether there was a correlation between urine BFP level and the grade or stage of bladder cancer, and whether the level could serve as a biochemical marker of bladder cancer. MATERIALS AND METHODS: Single voided specimens were obtained from 66 patients with confirmed or suspicious bladder cancer on cystoscopy, urine cytology or BFP. Each sample was divided into 3 aliquots of which 1 was for urine analysis, 1 was tested for BFP according to latex immunoagglutination method and 1 was sent for cytological examination. All patients subsequently underwent bladder biopsy. RESULTS: There were 54 (82%) patients with biopsy confirmed bladder cancer and 12 (18%) with benign conditions of the bladder. Overall sensitivity with BFP and urine cytology was 38.9% and 48.1% respectively. Specificity was 58.3% and 75.0%, and positive predictive value was 80.8% and 89.7%, respectively. The positive rate of BFP and cytology was higher in invasive cancer (75% and 100%, respectively) than in superficial cancer (36% and 28%). There was no correlation between BFP level and tumor grade, while cytology had a strong association. Linear regression analysis showed the significant correlation between BFP level and tumor size (r = 0.695, p < 0.0001). The detection rate of bladder cancer was higher by the combination of BFP and cytology than by using alone. CONCLUSIONS: BFP in conjunction with urine cytology can increase the detection rate of bladder cancer. But BFP alone cannot be used as a screening test for bladder cancer.

Adult↗