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Objective: Thymidylate synthase (TS) is the rate-limiting enzyme in the synthesis of pyrimidine nucleotides and as such a critical target for fluoropyrimidines, which are widely used in the treatment of colorectal cancer (CRC). The purpose of this study was to investigate TS expression in the primary tumours (PTs) and their metastases (M) in advanced CRC., Material and Methods: TS expression was determined immunohistochemically in paraffin-embedded biopsies of PT-M pairs in 39 CRC patients, as related to the clinical data., Results: There was no difference in the mean TS index of PTs compared with that of M, 1.25 and 1.14, respectively (p=0.12). TS expression of PTs was above the mean more often than that of M (61.5% and 41.0%, respectively, p=0.035). High TS expression in PTs was significantly related to high expression in M (the Fisher exact test, p=0.001). Using the absolute index values, TS expression in PT and M was significantly correlated (Pearson R=0.501, p=0.001). In 29/39 (74.3%) pairs, PT and M had concordant expression levels (Cohen's kappa 0.508, 95% CI 0.260-0.756, p=0.001; intraclass correlation coefficient (ICC) = 0.679, 95% CI 0.358-0.836, p=0.0001). No significant association was found between TS expression and any of the clinicopathological variables, disease outcome (DFS, DSS) or its response to treatment in univariate or multivariate analysis., Conclusions: Albeit usually higher, TS expression in PT was closely correlated with TS expression in M. This suggests that measurement of TS in primary CRC accurately predicts TS expression in subsequent metastases, which may help in selecting those patients most likely to respond to 5-FU-based regimens.

Kidney biopsy reports given during 2003 were collected from the authors' pathology database. A total of 111 biopsies were performed. Five tumor samples were not studied with electron microscopy (EM). Of the remaining 106 biopsies, 85 were studied with EM. EM was not performed in 10/24 transplant biopsies, or in 11/82 cases of suspected primary kidney disease. The role of EM was evaluated by grouping the samples in 3 categories: (1) EM was essential for diagnosis, (2) EM contributed to the interpretation and cleared uncertainties, and (3) EM had no influence on the diagnostic process. In transplant biopsies EM influenced the final diagnosis in 86% of cases (category 2). In biopsies performed for primary kidney disease EM was essential for diagnosis in 18.3% clearly contributed in 53.5%, and had no influence on the final diagnosis in 28.2% of cases. The study suggests that the importance of EM has not decreased during the last few years. Because only about 25% of the EM reports did not have any influence on the diagnostic process, it is recommended that kidney biopsy protocols should include EM in all biopsy cases, or at least tissue should be reserved for EM studies of all cases. Because of the influence of EM on the diagnostic process the need for EM in pathology training should be emphasized.

A retrospective study was performed on 59 pancreatic cancer patients diagnosed during 1970-1988. The mean follow-up time of all individual patients was 6.9 months (range, 0-37 months). Histologic grade, clinical stage (UICC), and volume-corrected mitotic index (M/V index) were correlated to the survival of patients. Histologic grade (p = 0.167) and clinical stage (p = 0.066) were not related to overall survival with statistical significance. The M/V index was significantly associated with overall survival (p = 0.004). M/V index (p = 0.004), clinical stage (p = 0.029), and histologic grade (p = 0.126) predicted survival at 1 year after diagnosis. M/V index divided grade-II tumors into two prognostically different groups (p = 0.050). Seven of 59 patients who survived more than 12 months had an M/V index less than 2, and patients who survived less than 6 months had significantly higher M/V index values (chi-square = 528.3, p less than 0.001). The metastasizing potential of pancreatic cancer and lymph node involvement was also associated with the M/V index. Histologic grade and M/V index were positively correlated (chi-square = 38.6, p less than 0.001, r = 0.702). On the basis of our results, it seems that the M/V index is better than histologic grade or clinical stage in predicting survival of pancreatic cancer patients. This result suggests the potential use of the M/V index in selecting patients for different modes of therapy.

A retrospective study was performed on 83 bladder cancer patients diagnosed at the Department of Surgery, Kuopio University Central Hospital, during the years 1965-1987. The follow-up time was 22 years, and the mean follow-up time of individual patients was 13 years (range 9.4-22 years). Histological grade (WHO), volume corrected mitotic index (M/V index) and clinical stage (UICC) were correlated to the survival of patients. Histological grade, M/V index and clinical stage were associated with crude survival (all causes of death included) with little predictive power. The recurrence of the disease could be predicted by the M/V index, but not by histological grade or clinical stage. When bladder cancer deaths only were included, histological grade (chi 2 = 26.6, p less than 0.001), M/V index (chi 2 = 6.6, p = 0.042) and clinical stage (chi 2 = 31.7, p less than 0.001) were clearly associated with prognosis. Also the metastasizing potential of bladder carcinomas could be predicted by the M/V index and by the histological grade at the time of primary diagnosis. Histological grade and M/V index were positively correlated (chi 2 = 16.7, p = 0.002, r = 0.47). In multivariate analysis clinical stage, histological grade and M/V index predicted prognosis in the order of importance.

The serum concentration of the new marker CA 15-3 was determined by a kit method, which is based on the use of two different monoclonal antibodies 115D8 and DF3, in a coated tube immunoradiometric technique. The mean CA 15-3 values in breast cancer patients (n = 40) were significantly higher than in patients with benign breast disease (n = 52, p less than 0.001) and in control subjects (n = 32, p less than 0.001). When we used the cut-off level 35 kU/l for CA 15-3, 0/32 of control subjects, 1/52 (2%) of patients with benign breast disease, 8/40 (20%) of all breast cancer patients, 6/19 (32%) of breast cancer patients with axillary nodal involvement and 1/1 of breast cancer patients with distant metastases were above this level. Among the same patients the CEA serum test was positive at a cut-off level of 5 micrograms/l in 7/40 (18%) cancer cases, and in 6/19 (32%) of cancer patients with nodal involvement. When we used the cut-off level 35 kU/l for CA 15-3 and 5 micrograms/l for CEA 1/52 (2%) of patients with benign breast disease, 10/40 (25%) of all breast cancer patients, 7/19 (37%) patients with axillary nodal involvement and 1/1 of breast cancer patients with distant metastases were positive in one or both of the tests. The serum CA 15-3 and CEA values were higher in patients with tumour size above 2 cm in diameter than in patients with smaller tumours (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructure of human respiratory cilia was studied in ultrathin serial sections and in random fields of sections. The apex of the cilium had dense gray material under the plasma membrane, where the "central" pair of tubules (often slightly eccentrically placed) and the single peripheral tubules ended. Thereafter the cilium thickened gradually about 1 micron below the apex and after that remained reasonably constant. At about 0.5 micron below the apex was a transformation zone (0.1 micron long), where both double and single peripheral tubules were seen. Dynein arms were not seen in the transformation zone but occurred approximately 0.1 micron below it. In a cilium, one peripheral double tubule was absent in the transformation zone but was seen about 0.2 micron below. This resulted in an artificial 8 + 2 pattern in a few sections. In cross sections at levels with peripheral double tubules the mean of the minor axes of the cilia was 0.198 +/- 0.009 micron (+/- SD) calculated from the serial sections of one patient. In 20 patients the variation was greater and the mean was higher: 0.210 +/- 0.042 micron (+/- SD).

1. Inhalation exposure to xylene of technical grade (300 p.p.m. in air, 6 h a day, 5 days a week, up to 18 weeks) enhanced the overall mono-oxygenation reactions (7-ethoxycoumarin O-deethylase and 2,5-diphenyloxazole hydroxylase( as well as the UDP-glucuronyltransferase activity in rat liver microsomes. 2. The simultaneous ingestion of aqueous 15-20% ethanol as drinking fluid increased the cytochrome P-450 concn. and the mono-oxygenation activity even more than the xylene exposure alone. 3. Xylene-ethanol treatment resulted in additive or less than additive effects on the measured hepatic enzyme activities. 4. Renal ethoxycoumarin deethylase activity was enhanced both by ethanol ingestion and by xylene inhalation, and the response was additive after the combined exposure. 5. Liver histology revealed that even though the xylene exposure alone did not produce detectable liver damage, the xylene-ethanol treatment produced more severe liver damage than did ethanol ingestion alone.

To study the effect of various valvular heart diseases on the quantitative histology of myocardium, 38 human hearts with valvular lesions were examined (11 aortic stenoses, nine mitral stenoses, nine mitral incompetence and nine combined aortic and mitral valve lesions). The control group consisted of ten hearts without any valvular lesions. With morphometrical methods the volume fractions of myocardial components (myocardial fibres, interstitial space and diffuse connective tissue), the numerical density of arterioles and the mean fibre diameter were estimated. Myocardial fibrosis was more severe in hearts with valvular lesions than in the controls (5.4% vs 3.3%, P less than 0.01), but did not correlate with the anatomical severity of the valvular lesions. The most severe myocardial fibrosis was found in hearts with mitral incompetence (6.7%). Fibre hypertrophy was most severe in hearts with aortic stenosis and in hearts with mitral incompetence (22 microns and 23 microns, respectively). In hearts with severe valvular lesions the mean fibre diameter was 23 microns and in hearts with mild to moderate lesions 19 microns (P less than 0.01). Good correlation was observed between the mean fibre diameter and the weight of the left ventricle (r = 0.81, P less than 0.01). The volume fractions of connective tissue and interstitial space were significantly higher and the volume fraction of myocardial fibres was correspondingly lower in the subendocardium than in the subepicardium in hearts with either pressure overload (aortic stenosis) or volume overload (mitral incompetence). In conclusion, myocardial fibrosis occurs in patients with various valvular lesions, but the severity of the fibrosis does not correlate with the anatomical severity of valvular lesions.(ABSTRACT TRUNCATED AT 250 WORDS)