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Biomedical subjects

M Timmermans

Publications and source records attributed to M Timmermans.

15 recordsLinked to original sources

Development of leaf shape.

Variation among vascular plants in the initiation and patterning of leaves results in a diverse array of leaf shape, including the strap-like leaf of many grasses and the broad lamina of most eudicots. Recent findings highlight the importance of interactions between the shoot apical meristem (SAM) and developing leaf primordia in axis specification and the establishment of leaf shape. Global regulators of epigenetic states have been implicated in these interactions and may play a role in distinguishing founder cells and stem cells within the SAM.

Genes, Plant↗

The urokinase-type plasminogen activator system in resected non-small-cell lung cancer. Rotterdam Oncology Thoracic Study Group.

BACKGROUND: Urokinase-type plasminogen activator (uPA), its receptor (uPAR) and plasminogen activator inhibitors (PAI-1 and PAI-2), all play important roles in tumour invasion and metastasis. The tumour levels of the components of the urokinase-type plasminogen activator system (uPA-system) may help to identify individuals with a poor prognosis in postoperative non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: The levels of uPA, uPAR PAI-1 and PAI-2 were measured by enzyme-linked immunosorbent assay (ELISA) in triton-extracts, prepared from 88 NSCLC tissues (stage I-IIIa) and 74 normal lung tissues from the same patients. RESULTS: The expression levels of uPA, uPAR, PAI-1 and PAI-2 were significantly higher in tumour tissues as compared to their normal equivalents (all, P < 0.0001). Significant relations were found between gender and uPA (P = 0.04) or uPAR (P < 0.001), and between PAI-2 and pathological stage (P = 0.03). For none of the studied factors of the uPA-system a significant relation with survival was found, neither in all patients, nor in the subgroups of patients with squamous-cell lung carcinoma or adenocarcinoma. CONCLUSIONS: The expression levels of the components of the uPA-system were higher in NSCLC tissue as compared to normal lung tissue, but there were no significant relationships between their levels and survival.

Carcinoma, Non-Small-Cell Lung↗

Identification and cloning of a glucan- and lipopolysaccharide-binding protein from Eisenia foetida earthworm involved in the activation of prophenoloxidase cascade.

Coelomic fluid of Eisenia foetida earthworms contains a 42-kDa protein named coelomic cytolytic factor 1 (CCF-1) that was described previously to be involved in cytolytic, opsonizing, and hemolytic properties of the coelomic fluid. Cloning and sequencing of CCF-1 reveal significant homology with the putative catalytic region of beta-1,3- and beta-1,3-1,4-glucanases. CCF-1 also displays homology with coagulation factor G from Limulus polyphemus and with Gram-negative bacteria-binding protein of Bombyx mori silkworm, two proteins involved in invertebrate defense mechanisms. We show that CCF-1 efficiently binds both beta-1,3-glucan and lipopolysaccharide. Moreover, CCF-1 participates in the activation of prophenoloxidase cascade via recognition of yeast and Gram-negative bacteria cell wall components. These results suggest that the 42-kDa CCF-1 protein of E. foetida coelomic fluid likely plays a role in the protection of earthworms against microbes.

Acute-Phase Proteins↗

Spontaneous rupture of the pancreaticoduodenal artery: three cases.

We report 3 cases of spontaneous rupture of pancreaticoduodenal arteries (PDA). In the first case, an aneurysm of the PDA was demonstrated with stenosis of the celiac trunk; in the second case occlusion of the hepatic artery was shown. In both cases, arterial pancreatic arcades were enlarged and blood flow was retrograde from the superior mesenteric artery. Local high intravascular pressure due to retrograde blood flow through the arterial pancreatic arcades was thought to be the cause of aneurysm development and arterial rupture which necessitated surgical intervention. The third patient presented with a mycotic aneurysm that could be treated by intra-arterial embolization. The characteristics of this rare affliction are discussed, as is the treatment which first entails percutaneous embolization.

Aged↗

Expression of estrogen, progesterone and epidermal growth factor receptors in primary and metastatic breast cancer.

The prognostic value of epidermal growth factor receptor (EGFR) expression and its biological role in estrogen receptor-positive (ER+) and ER-negative (ER-) primary breast cancer is controversial. In this study, distributions of ER, progesterone receptor and EGFR have been established using immunohistochemistry in both primary breast tumors and their matched axillary lymph node metastases of 26 patients or their matched distant metastases of 2 patients. In addition, 5 patients with bilateral breast cancer were studied. ER+ tumor cells were detected in 22 (69%) and EGFR+ tumor cells were detected in 11 (34%) primary breast carcinomas. Expression of ER and EGFR was inverse regarding the individual tumor cells in both primary tumors and metastases. Relationship of EGFR expression with poorly differentiated and large breast tumors was observed. Furthermore, primary tumors with a predominant lobular component were ER+ and, with one exception, EGFR-. Invasive ductal carcinomas were more frequently EGFR+. No apparent differences in receptor expression were observed between primary tumors and lymph node metastases or chronously or metachronously occurring bilateral breast cancers. Only one ER+ primary tumor showed a switch to EGFR expression in the involved lymph node. Our study shows that a shift in receptor phenotype between primary tumors and lymph node metastases is a rare event and, thus, additional analyses of involved lymph nodes will not likely serve as a better predictor for response to anti-estrogen therapy. We conclude that expression of EGFR is not a prerequisite for development of metastases.

Adult↗

Differential expression of estrogen, progesterone, and epidermal growth factor receptors in normal, benign, and malignant human breast tissues using dual staining immunohistochemistry.

Distribution of estrogen (ER), progesterone (PR) receptors, and epidermal growth factor (EGF) receptors was assayed by dual staining immunohistochemistry on 28 selected cytosolic ER-positive breast carcinomas and 22 nonmalignant breast tissues. ER-positive tumor cells were detected in 26 (93%) and EGF receptor positive tumor cells were detected in 7 (25%) carcinomas. In five tumors both ER and EGF receptors were detected but localized in distinct tumor cells. Only in one case of ductal carcinoma in situ co-expression was observed in a subset of tumor cells. In contrast, simultaneous expression of ER/PR and EGF receptors was observed in non-neoplastic ductal remnants in the majority of the carcinomas and the fibroadenomas. In addition, double-positive cells were occasionally detected in luminal epithelial cells of normal breast tissue and mastopathies. This study shows that ER/PR and EGF receptors in breast tumor cells are inversely related at the single cell level. However, demonstration of ER/PR and EGF receptors in individual normal luminal cells shows that expression is not mutually exclusive.

Breast↗

Induction of micronuclei and karyotype aberrations during in vivo mouse skin carcinogenesis.

The induction of chromosome and/or genome mutations during the first steps of skin carcinogenesis was followed in male NMRI mice, treated with a 'two-stage' [9,10-dimethyl-1,2-benzanthracene (DMBA) + phorbol-12-myristate-13-acetate (TPA)], or a 'three-stage' [DMBA+methyl methanesulphonate (MMS) + phorbol-12-retinoate-13-acetate (RPA)] protocol. The scoring of micronuclei (MN) in basal and suprabasal keratinocytes allows a relatively fast in vivo estimation of clastogenic and aneugenic effects of various compounds and treatments. Relevant stages were then further analysed by karyotyping the in vivo treated keratinocytes that were allowed to divide during short in vitro cultivation. DMBA used as initiator in both protocols was able to induce MN. The well-known clastogen MMS had an acute but transient effect on MN induction when used alone or as convertor in the three-stage protocol. Neither the propagator RPA, nor the 'full-promotor' TPA, which can carry out conversion as well as propagation, induced statistically significant numbers of MN when applied on mouse skin. Combined treatments, DMBA+MMS and MMS+RPA, showed higher MN frequencies than when MMS treatments were given alone. The full carcinogenic protocols showed significant frequencies of MN but the time points of appearance differed, indicating that the accumulation of aberrations could be more important than the order of appearance. Karyotypic analysis of those stages where the MN assay detected genome and/or chromosome aberrations revealed no specific loss of chromosomes that might be directly related to the carcinogenic process. When chromosome loss and aberrations were both taken into consideration together, chromosomes 7 and 11 and surely 9, 17 and 18 were more frequently involved than others.

9,10-Dimethyl-1,2-benzanthracene↗

Immunohistochemical study of the BCAR1/p130Cas protein in non-malignant and malignant human breast tissue.

BCAR1/p130Cas is a docking protein involved in intracellular signaling pathways and in vitro resistance of estrogen-dependent breast cancer cells to antiestrogens. The BCAR1/p130Cas protein level in primary breast cancer cytosols was found to correlate with rapid recurrence of disease. A high BCAR1/p130Cas level was also associated with a higher likelihood of resistance to first-line tamoxifen treatment in patients with advanced breast cancer. Using antibodies raised against the rat p130Cas protein, we determined by immunohistochemical methods the BCAR1/p130Cas localization in primary breast carcinomas, in tumors of stromal origin, and in non-neoplastic breast tissues. The BCAR1/p130Cas protein was detected in the cytoplasm of non-malignant and neoplastic epithelial cells and in the vascular compartment of all tissue sections analyzed. Immunohistochemistry demonstrated variable intensity of BCAR1/p130Cas staining and variation in the proportion of BCAR1/p130Cas-positive epithelial tumor cells for the different breast carcinomas. Double immunohistochemical staining for BCAR1/p130Cas and estrogen receptor confirmed coexpression in non-malignant luminal epithelial cells and malignant breast tumor cells. The stromal cells in non-malignant tissues and tumor tissues as well as breast tumors of mesodermal origin did not stain for BCAR1/p130Cas. This immunohistochemical study demonstrates a variable expression of BCAR1/p130Cas in malignant and non-malignant breast epithelial cells, which may be of benefit for diagnostic purposes.

Adult↗

[Gastric metastases of ovarian adenocarcinoma. Apropos of a case].

A case report and review of literature. Four types of neoplastic dissemination exist in presence of ovarian adenocarcinomas. Commonly, these tumors metastasize along intraperitoneal ways or lymphatic channels. Less frequently, the tumors are invading surrounding organs by direct extension. Rarely, there is a hematogenous dissemination. The observation of a gastric metastasis is reported; we consider it as a hematogenous one. Reviewing the literature, we find few similar cases. Gastric metastases originate more frequently from malignant melanomas, adenocarcinomas of the breast and bronchogenic tumors.

Cystadenocarcinoma↗

[Repeated perforations of the small intestine in muscular agenesis in a newborn infant. Apropos of a case. Review of literature].

A rare case of intestinal muscular layers agenesis is described. Ten other cases were founded in the literature and are briefly reported. Association of ischemia and congenital abnormality of the muscular layers is probably the cause of the perforation. Prognosis is very bad: all the children with clinical symptoms (occlusion or perforation) died.

Humans↗

Are perforated gastroduodenal ulcers related to Helicobacter pylori infection?

The prevalence of Helicobacter pylori gastritis in 36 patients with a perforated ulcer undergoing endoscopy prior to or at least 2 months after perforation was 56%, intermediate between that of age and sex matched healthy blood donors (36%) who had measurement of circulating antibodies to Helicobacter pylori and of ulcer patients without perforation matched for age, sex and ulcer location (86%). In the 20 patients with Helicobacter pylori gastritis, 8 had a history of peptic ulcer and 7 of 9 patients with a follow-up of at least 12 months and no preventive treatment had a symptomatic relapse. The group of patients without infection included 6 young patients (< 40) who did not use non steroidal anti-inflammatory drugs and 10 older patients (> 60): 9 used non steroidal anti-inflammatory drugs and seven had a normal gastric mucosa on biopsy. One patient without Helicobacter pylori had a second perforation, the only relapse in this group. We conclude that patients with perforated ulcers are a heterogeneous group with a recurrent ulcer disease mainly in patients with Helicobacter pylori.

Adult↗