Search PubMed⌕ Search

Biomedical subjects

F T Bosman

Publications and source records attributed to F T Bosman.

At least 181 records · Page 10Linked to original sources

Recurrence of nephrocalcinosis after renal transplantation in an adult patient with primary hyperoxaluria type I.

The medical history of a 42-year-old patient with primary hyperoxaluria type I is presented. Primary hyperoxaluria was suspected after renal transplantation, when oxalate deposits were found in a biopsy of the kidney graft. Diagnosis of type I hyperoxaluria was confirmed by the finding that significantly increased amounts of glycolic acid and oxalic acid were excreted. Treatment of the patient with 500 mg pyridoxine daily resulted in a decrease of the excretion of oxalate to normal values.

Adult↗

Amplification of the nephrotoxic effect of cyclosporine by preexistent chronic histological lesions in the kidney.

In contrast to its importance in improving renal graft survival, nephrotoxicity is the most serious side effect of cyclosporine. Dosage reductions of CsA mitigate its nephrotoxic effect. However, CsA nephrotoxicity is still a problem in clinical transplantation. In this study the relationships among preexistent chronic histological lesions, donor age, and renal function after transplantation in 100 CsA treated renal allograft patients are described. Multivariate data analysis revealed a significant statistical effect of the presence of preexistent chronic histological lesions on nonimmediate function (-.42, less than 0.0001) that was relatively twice as large as the effects of cold ischemia time (-.21, less than 0.05). Also in predicting creatinine clearance at 1 and 3 months, preexisting chronic histological lesions had the most important effect (-.39, less than 0.0001; -.57, less than 0.0001, respectively), whereas the presence or absence of rejection episodes was less predictive (.24, less than 0.001; .20, less than 0.01, respectively). Preexistent chronic histological lesions had also significant effects in predicting conversion to azathioprine and prednisolone, because of CsA nephrotoxicity (-.42; less than 0.0001). The degree of CsA nephrotoxicity therefore varies according to the presence of preexistent chronic histological lesions. Because of the increase of these lesions with age, one has to be aware of an exaggerated CsA toxicity, especially in the older donor age group and in older patients treated with CsA for various reasons.

Age Factors↗

Type IV collagen immunoreactivity in colorectal cancer. Prognostic value of basement membrane deposition.

Using antibodies to type IV collagen, basement membrane (BM) deposition at the tumor-stromal border was studied in 163 cases of colorectal carcinomas. Immunoreactivity was scored semiquantitatively as moderate/extensive versus limited BM deposition and correlated with Dukes' stages and survival data. Cases with limited BM deposition showed an overall significant shorter survival and were overrepresented in Dukes' Stages C/D. Stratification of the cases, for limited versus moderate/extensive BM deposition and Dukes' Stages A/B and C/D, showed that in Dukes' Stages C/D, cases with moderate/extensive BM deposition reached a plateau phase in the survival curve after 2 years. Cases with limited BM deposition showed a continuous downward course on the survival curve. The results suggest that immunostaining of BM in cases in Dukes' C differentiates tumors with relatively high invasive and metastatic capacity from tumors with low invasive and metastatic capacity.

Basement Membrane↗

A multivariate analysis of pathologic prognostic indicators in large bowel cancer.

A multivariate analysis of the pathologic data of 350 patients with primary colorectal cancer was performed. In addition to conventional parameters such as shape and size of the primary tumor, central node involvement, angioinvasive growth, grade, and stage, new variables such as the immunoreactivity patterns of carcinoembryonic antigen (CEA), CA 19-9, mucin, serotonin, secretory component (SC), and the DNA index were tested for their potential prognostic value. Every variable except CA 19-9, serotonin, and DNA showed significant prognostic information in univariate analysis. However, in the multivariate analysis stage was the predictive factor with the highest hazard ratio, but absence of central node involvement, tumors with diameters between 3.5 cm and 6 cm, exophytic tumor growth, well-differentiated tumors, tumors with CEA immunoreactivity, absence for staining with serotonin, and diploid tumors also were included in the relative risk model. Thus, the aforementioned variables appear to play a role in the establishment of a prognostic index.

Aged↗

Xenografting of normal colonic mucosa in athymic mice.

Colonic mucosa was implanted subcutaneously into nude mice in order to investigate the potential use of xenografts as an in vivo model system for the study of colonic epithelial proliferation and differentiation. The xenografts were followed for 5 weeks. Proliferation was studied by bromodeoxyuridine (BrdU) incorporation followed by visualization of the DNA-synthesizing cells with an anti BrdU monoclonal antibody. Differentiated cells were visualized by histochemical staining of goblet- and enterochromaffin cells and of columnar cells by immunoperoxidase staining for carcinoembryonic antigen (CEA), secretory component, and serotonin. In different strains of mice different observations were made. Less immunocompetent strains (Balb c nu/nu, NMRI nu/nu) developed abscesses at the site of the xenograft as well as wasting disease. These phenomena almost never occurred in CD-1 nu/nu mice. The success rate was highest in CD-1 nu/nu mice. After about 1 week, only crypt base cells remained vital and started to repopulate crypts with epithelial cells showing normal colonic differentiation features such as CEA, secretory component, and serotonin immunoreactivity and mainly sulphomucin production. After longer periods of time, crypts started to form cyst-like structures due to accumulation of secretion products and dead cells. DNA-synthesizing cells were seen in the basal areas of recognizable crypts and in the cyst-like structures in a random distribution. These results indicate that normal colon mucosa xenografted into nude mice maintains its proliferative and differentiating capacity for at least 5 weeks.

Animals↗

Progesterone receptor quantification with radiolabeled promegestone (R 5020) in frozen sections of endometrium and breast cancer tissue.

A technique for the determination of the progesterone receptor content at sections was developed. Series of coverglass-mounted unfixed frozen sections were incubated with [3H]R5020 only, to determine total binding, or with excess unlabeled R5020, to determine non-specific binding. Ligand binding in the tissue sections was measured by liquid scintillation counting after repeated washing of the coverslips. Elution of ligand binding proteins into the incubation buffer was quantitated with the dextran-coated charcoal method. Specific ligand binding was related to the total tissue protein content which was determined on parallel, unmounted sections. Scatchard analysis showed specific saturable and high affinity (Kd = 0.01-2 nM) section-bound and soluble binding sites in cryostat sections of calf uterus, human endometrium and breast cancer samples. Ligand specificity was studied by competition of [3H]R5020 with a 100-fold excess of various steroid receptor ligands. The competition was excellent for R5020 and progesterone, negligible for estrogens and slight for androgens and corticosteroids. These binding characteristics provide evidence that with this assay progesterone receptors are determined. Exchange experiments showed that with this method total, free as well as occupied, progesterone receptors can be measured. A highly significant linear correlation, and agreement in PR status classification between assay on cytosol and sections was obtained for a series of 21 breast cancer samples. Finally, progesterone receptor analysis using cryostat sections results in the recovery of 2-3 times more PR from the same amount of tissue as compared to the use of cytosol. These results indicate that progesterone receptors can be reliably assayed with Scatchard analysis using cryostat sections, which requires less tissue than the cytosol assay. This method, which is simple and easy to perform could be of practical importance, particularly when only small tissue samples (which also have to be analyzed morphologically or histochemically) are available and when quantitative radiochemical progesterone receptor data are required for direct comparison with (immuno-) histochemical information.

Animals↗

The prognostic value of morphometrical features and cellular DNA content in cis-platin treated late ovarian cancer patients.

In 73 CAP-1 treated stage III and IV ovarian cancers, the prognostic significance of morphometric features and cellular DNA content has been evaluated in comparison with histologic type, grade of differentiation and a number of clinical characteristics. Borderline tumours were excluded from the study. Median follow-up was 44 months, median survival time 36 months. Single features associated with prognosis were (in order of decreasing significance according to single variate analysis): FIGO stage (P = 0.0002), bulky disease (P = 0.004), standard deviation and mean of nuclear area (P = 0.0006 and P = 0.01), cellular DNA content (P = 0.01), mitotic activity index (P = 0.08) and volume percentage epithelium (P = 0.13, not quite significant). Tumours with a mean nuclear area greater than 70 micron2 (which occurred in 35% of the cases) were nearly all aneuploid. Multivariate analysis showed that the statistically most significant prognostic combination of features consisted of mean nuclear area, presence or absence of bulky disease and FIGO stage (in order of decreasing importance) (Mantel-Cox = 23.07, P less than 0.00001). A low value for the multivariate function of this combination of features was associated with a poor prognosis within 24 months, a high value with a favourable outcome. Another favourable combination of features appeared to be diploid cellular DNA content and a low mitotic activity index (11 patients, one died). However, even with the prognostically most favourable combination of these features, several patients died. Of all combinations of features investigated, only two were associated with an excellent prognosis (low mitotic activity index and low volume percentage epithelium). Cancers of 7 patients (10%) displayed such features, and none of them died during the follow-up period (minimally 20 and maximally 54 months). It is concluded that morphometric and flow cytometric analysis can provide significant and objective information to predict the prognosis of cis-platin-treated advanced ovarian cancer patients.

Adult↗

Quantitative assessment of long-term changes in insulin secretion after canine duct-obliterated pancreas transplantation.

In this study, we have quantitatively assessed the changes in insulin-secreting capacity after duct-obliterated segmental pancreatic autotransplantation in dogs. To this end, we have used a technique for the sampling of the complete and undiluted pancreatic venous blood with simultaneous flow measurement, by which means the actual insulin-secreting capacity was determined in a direct fashion. Histologic changes were analyzed in addition in order to address the underlying mechanisms of the changes in insulin-secreting capacity. Intraoperative glucose-stimulated insulin secretion of the left pancreatic lobe was measured before (group I, n = 8), at 6 weeks (group II, n = 5), and at 18-24 months (group III, n = 7) after duct-obliterated segmental pancreatic autotransplantation. At all 3 intervals, histologic analysis was performed. Since the experiments in groups I-III were performed under general anesthesia, a 4th group of dogs (group IV, n = 6) was studied in addition in order to determine the effect of general anesthesia on glucose metabolism. K-values appeared to be reduced to 1/5 and peripheral insulin response (AUC) to about 1/3 of the values obtained from fasting conscious dogs. Although all animals in groups I-III had normal fasting glucose levels and normal K-values at each test interval, a 75% reduction of insulin secretion after duct-obliterated transplantation was observed. Insulin secretion not only showed marked quantitative changes but significant qualitative alterations in glucose-stimulated insulin response were found. Disturbance of functional islet architecture appears to be the main causative factor in the decrease in insulin secretion. If applicable to man, our results indicate that especially the duct-obliterated graft, with its borderline endocrine capacity, is prone to loss of sufficient graft function by the damage induced by eventual rejection crises.

Animals↗

Quantification of oestrogen receptors in breast cancer: radiochemical assay on cytosols and cryostat sections compared with semiquantitative immunocytochemical analysis.

A radiochemical oestrogen receptor assay on cytosol was correlated with a radiochemical and an immunohistochemical oestrogen receptor assay using cryostat sections from 50 breast cancer specimens. Oestrogen receptors were reliably quantitated in 6 micron cryostat sections with Scatchard analysis using radiolabelled oestradiol, and a good quantitative and qualitative relation with cytosol oestrogen receptor assay was found. Parallel sections were used for routine histological tissue verification and for direct comparison with immunohistochemistry for oestrogen receptor. Specific immunoperoxidase staining with a rat monoclonal antibody was scored by semiquantitative evaluation of the staining intensity of cancer cell nuclei. Oestrogen receptor scoring was highly reproducible when performed by the same observer. The semiquantitative immunohistochemical oestrogen receptor score correlated significantly better with the radiochemical assay on sections than with cytosol assay. Oestrogen receptor in breast cancer can be reliably assayed by semiquantitative evaluation of cryostat sections immunostained for oestrogen receptor, but only if the procedure is adequately standardised. The results underline the importance of cellular heterogeneity as a cause of variation in oestrogen receptor assay evaluation in breast cancer.

Breast Neoplasms↗

Monoclonal antibodies in immunocytochemistry.

In this review the application of monoclonal antibodies for immunocytochemical purposes is discussed. An important basic principle is that from a methodological point of view that there are no essential differences between monoclonal and polyclonal antibody based immunocytochemistry. Specificity of the primary antibody is the most important prerequisite for reliable immunocytochemistry. Enzyme immunoassay, immunoblotting, antigen spot testing and tissue testing are the recommended procedures for specificity analysis. Studies of the most frequently used linking systems have shown that they are all suitable for use in conjunction with monoclonal antibodies. This also applies to the most important labels. It is concluded that monoclonal antibody based immunocytochemistry is one of the most valuable tools available in cell biology and pathology.

Antibodies, Monoclonal↗

Influence of implantation site on growth, antigen expression and metastatic potential of human colonic cancer HT29 and 5583 xenografts in nude mice.

In order to study the interaction between tumors and host environmental factors, we xenografted cells from the human colonic carcinoma cell lines HT29 and 5583-S in the subcutis, cecum, spleen and liver of nude mice and compared growth characteristics, metastatic potential and some phenotypic features of the xenografts in these sites. No remarkable differences were observed between the tumors at different inoculation sites in regard of their expression of carcinoembryonic antigen and secretory component or type of mucin produced. Also the proportion of DNA synthesizing cells as determined by bromodeoxyuridine incorporation appeared to be comparable in the studied implantation sites. Local invasive growth characteristics and metastatic potential, however, showed marked differences. Subcutaneous and cecal xenografts frequently showed tumor cell invasion into the surrounding tissue, vasoinvasive growth and discontinuous basement membrane deposition, whereas splenic and hepatic implants demonstrated more encapsulation, no invasion of blood vessels and more continuous basement membrane deposition. Subcutaneous xenografts produced no metastasis. With HT29 cells liver and lymph node metastases occurred frequently from the splenic as well as the cecal xenografts. 5583 cells regularly produced liver metastases from the splenic xenografts, whereas no metastasis from cecal xenografts were observed. We conclude that although the patterns of invasive growth and the metastatic potential differ for various implantation sites, antigen expression and cell kinetic features of tumor implants are hardly influenced by the site of inoculation.

Animals↗

Retrospective analysis of the prognostic significance of DNA content and proliferative activity in large bowel carcinoma.

In the present study we have evaluated the prognostic significance of ploidy levels and proliferative activity in 279 cases of large bowel carcinomas which were included in a surgical prospective randomized trial. Ploidy levels and proliferative activity were determined on nuclei isolated from paraffin-embedded tissues of 279 colorectal carcinoma patients, with a mean follow-up of 51.9 months. Product limit survival analysis demonstrated a borderline significant association (P = 0.0689 by generalized Breslow; P = 0.0336 by generalized Savage) between ploidy and survival, with a 75th quantile survival of 49.8 months for patients with diploid tumors and 35.9 months for patients with aneuploid tumors. After stratification for staging, Dukes' C cases showed a statistically significant association between tumor ploidy and survival (P = 0.0224 by generalized Breslow, P = 0.0110 by generalized Savage). Product limit survival analysis for proliferative activity and survival showed a similar outcome with the strongest association in Dukes's C stage of disease (75th quantile survival of 38.9 months for low proliferative and 18.0 months for high proliferative tumors).

Aneuploidy↗