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Biomedical subjects

J Koudstaal

Publications and source records attributed to J Koudstaal.

At least 37 records · Page 2Linked to original sources

Androgen receptor content in human endometrium.

Human endometrium changes morphologically and biochemically during the various phases of the menstrual cycle, influenced by not only estrogens and progesterone, but probably also by androgens. The purpose of this study was to investigate the androgen receptor (AR) content in human endometrium and myometrium and its significance. AR immunocytochemistry was performed on 30 paraffin-embedded uterine sections of pre-menopausal women who were scheduled for hysterectomy because of benign gynaecologic abnormalities. AR receptor content was seen in all cell types of the human endometrium and myometrium and was cyclic dependent. AR immunostaining of stromal and smooth muscle cells was more profound than AR staining of glandular cells. There was more AR expression in the proliferative phases than in the secretory phases: in the late secretory phase there was no immunostaining in any of the cell types. AR expression is primarily under androgenic control. Inside the cell testosterone may be 5 alpha-reduced to dihydrotestosterone (DHT). Due to local competition between testosterone and the excess of progesterone in the secretory phase for the same iso-enzyme 5 alpha-reductase, the level of DHT will be diminished in the late secretory phase. If AR synthesis in endometrium would be DHT dependent, the virtual disappearance of DHT would explain the lack of AR expression in the late secretory phase. Whether the cyclic pattern of AR expression is merely an epiphenomenon to progesterone production, or whether androgens play a causal role in the cyclic modulation of endometrium is subject to further research.

Cell Nucleus↗

Comprehensive study of several general and type-specific primer pairs for detection of human papillomavirus DNA by PCR in paraffin-embedded cervical carcinomas.

We have compared the efficacies of three general primer pairs for the detection of human papillomavirus (HPV) DNA in formaldehyde-fixed paraffin-embedded carcinomas. The use of these primer pairs leads to underestimates of the HPV prevalence (GP5/6, 61.1%; CPI/IIG, 57.4%; MY09/11, 46.9%; combined, 72.8%). The efficacy of each primer pair seemed to be inversely correlated to the length of the amplimer produced. By using newly developed type-specific primer pairs (amplimer length, approximately 100 bp), an increase in HPV DNA detection (87.6%) was found.

Base Sequence↗

Number and proliferation of neuroendocrine cells in normal human airway epithelium.

Pulmonary neuroendocrine cells (PNECs) are ubiquitous in human adult airway epithelium, and are implicated in pulmonary disease as PNEC hyperplasia has been described in a great number of different pulmonary lesions. The purpose of this study was to determine the baseline quantity and proliferative fraction of adult PNECs in the conducting airway epithelium of normal lungs. Autopsy was performed within 6 h of death on 250 subjects. In 9 of 250 cases without pulmonary disease, seven sequential samples were taken from trachea down to respiratory bronchioles, fixed in formalin, and embedded in paraffin. After microwave pretreatment in citrate buffer, sequential immunohistochemical staining was carried out, using MIB-1 (antibody directed against recombinant parts of the Ki-67 antigen) as marker for the proliferation fraction and chromogranin-A (CgA) for the identification of PNECs. Quantification of all epithelial cells of the conducting airways, MIB-1, and CgA immunoreactive cells, and length of basement membrane was interactively performed using image analysis. The results show that microwave treatment significantly enhances the sensitivity of CgA without loss of specificity. In total, 326,500 epithelial cells and 105 cm of basement membrane (BM) length were counted (3,101 cells/cm BM). The proliferation fraction of all epithelial cells was 0.76 +/- 0.53% (mean +/- SD). No mitosis was seen. The mean quantity of PNECs was 0.41 +/- 0.17% of all epithelial cells (12.5 cells/cm BM). Many dendritic PNEC processes parallel to the basement membrane could be appreciated between adjacent epithelial cells. No difference in the number of PNECs was found between large and small conducting airways. PNECs were not observed in the alveoli. Only 13 PNECs were immunoreactive for MIB-1; the proliferative fraction of PNECs was 1 to 2%. In histologically normal adult human conducting airway epithelium, the average overall proliferation fraction is 0.76%. The proliferation fraction of PNECs is equal to the overall proliferative fraction. The fraction of PNECs is 0.41%, using anti-CgA antiserum after microwave pretreatment of slides, 12 times more than previously reported. Many dendritic neuroendocrine cell processes were seen between non-neuroendocrine epithelial cells adjacent to the basement membrane. The widely held belief that neuroendocrine cells are of little importance in the adult lung is contradicted by the relative high density of PNECs and its cytoplasmic processers.

Adult↗

Progestin receptors in meningiomas. Comparison of cytosolic assays with immunocytochemical identification in cryostat and paraffin sections.

The results are reported of ligand binding and enzyme immunoassays in tumour cytosols, and of immunoperoxidase assays in cryostat and paraffin sections measuring oestrogen (ER) and progestin receptors (PR) in 22 meningiomas and three non-meningioma tumours (two neurinomas and one haemangiopericytoma). With regard to the meningioma tissues, cytochemical immunoperoxidase PR-staining was present in all cryostat sections and in all but one of the paraffin sections. There was a good degree of qualitative accordance between all assay methods; they revealed the picture of "typical" meningioma: high PR and low ER. In this series, immunoperoxidase staining for the detection of PR-receptors, both in cryostat and paraffin sections, rendered encouraging results, thus offering a method for the detection of progestin receptors, which can compete with cytosolic methods.

Adult↗

Efforts to improve interobserver agreement in histopathological grading.

The present study aimed to assess the interobserver variation in histopathological grading of 88 slides by four experienced pathologists who, before the start of the study, reached consensus about the method of grading through a joint session behind a discussion microscope. The results were compared with two previous studies, the first assessing the observer variation under normal conditions, the second doing the same after theoretical agreement about which morphological characteristics were relevant for grading. In the present study the pathologists first made a provisional diagnosis on low power view, followed by a final diagnosis on high power view, scoring various morphological characteristics as in the second study. The unweighted and weighted group kappa values for the final diagnosis were 0.41 and 0.71 respectively in the present study (after the consensus meeting), compared to 0.33 and 0.70 respectively in the second study (after only theoretical consensus), and 0.28 and 0.55 in the first study (without consensus). We conclude that a consensus meeting appears to be useful to improve the interobserver agreement.

Female↗

Intranodal and extranodal tumour growth in early metastasised non-small cell lung cancer: problems in histological diagnosis.

AIM: To question the observer reliability or agreement of reports on the intranodal and extranodal tumour growth patterns in early metastasised non-small cell lung cancer (NSCLC). METHODS: In a pilot study original histological sections of mediastinal lymph node metastases from NSCLC obtained by lymph node dissection (n = 82) or by mediastinoscopy (n = 62) were examined and classified independently by three pathologists as extranodal, intranodal, or indefinite. After clear criteria for these growth patterns had been defined sections were re-examined and recategorised one year later. Interobserver agreement was examined for both investigations. RESULTS: In the dissected lymph nodes the kappa value improved significantly from 0.52 (moderate agreement) at the first investigation to 0.72 (good agreement) at the second. In the mediastinoscopic lymph node biopsy specimens an increase in kappa value from 0.50 at the first to 0.67 at the second examination was found, although this improvement was not significant. In mediastinoscopic biopsy specimens a very high proportion of tissue samples showed indefinite tumour extension. CONCLUSION: Good reproducibility of intranodal and extranodal growth patterns in the histological examination of mediastinal lymph node metastases can be achieved, provided that pathologists use strictly defined criteria. In mediastinoscopic biopsy specimens it is often impossible to differentiate between intranodal and extranodal tumour growth.

Adenocarcinoma↗

Failed meniscus transplantation. A report of three cases.

Treatment of patients with an established disabling compartment arthrosis after total meniscectomy is an important clinical problem. Meniscal transplantation may be an alternative method of treatment. Between 1989 and 1992, 25 cryopreserved nontissue antigen matched meniscal transplantations were performed. In three patients with a medial meniscus, the transplantation failed because of partial loosening of the meniscus. The donor meniscus was removed in one case after 12 months and in the other two cases after 20 and 24 months. In two cases, there was a varus malalignment of the knee. In the third case, the knee was unstable because of an insufficient anterior and posterior cruciate ligament. The retrieved menisci were stained with enzyme and immunohistochemical reactions. Focal areas of degeneration were noted, with vital cells around the microvascular supply and at the synovial side. The growth potential of vital parts of the grafts, as shown by proliferation markers, seemed to be virtually nil. The success of meniscal transplantation seems to depend on factors responsible for vascularization. Malalignment and instability of the joint, causing abnormal pressure on the graft, may be responsible for vascular damage leading to degeneration and loosening of the graft.

Adult↗

Retinoic acid and cisdiaminodichloroplatinum in the treatment of murine teratocarcinomas in vivo in a nullipotent model.

Induction of differentiation as a treatment modality for nonseminomatous germ cell tumors (NSGCTs) may promote the development of residual mature teratoma (RMT), which is usually associated with primary tumors that are capable of spontaneous somatic differentiation. Therefore, we studied the combination of a cytotoxic drug and a differentiation-inducing agent in vivo in three murine teratocarcinoma models with different levels of spontaneous somatic differentiation: E86-379 (moderate differentiation); NF-1 (poor differentiation); and MH-15 (no differentiation). We used retinoic acid (RA) as differentiation-inducing agent and cisdiaminodichloroplatinum (CDDP) as cytotoxic drug, plus a combination of both. In four separate experiments, the combination of RA and CDDP gave a significant further reduction of tumor size as compared with treatment with either RA or CDDP alone. Morphologically intact tumor after treatment with combined RA-CDDP contained a smaller proportion of undifferentiated tissue (embryonal carcinoma) than after CDDP alone. However, somatic differentiation was not induced in the tumor model lacking spontaneous somatic differentiation. Toxicity was reflected in loss of body weight and death of some animals and closely paralleled the degree of tumor reduction in all experiments.

Animals↗

Meningeal carcinomatosis as presenting symptom of a gallbladder carcinoma.

Meningeal carcinomatosis as presenting symptom is rare. We report a patient who presented with an isolated abducens nerve palsy and an unsteady gait. At autopsy the primary tumor proved to be a gallbladder carcinoma. Only one similar case has been reported. Several aspects are discussed, including the route by which the tumor cells could have reached the subarachnoid space.

Abducens Nerve↗

Fatal asthma attributed to patent foramen ovale.

A 37 year old woman was admitted to the hospital with acute severe asthma, shortly followed by respiratory failure and circulatory arrest. Despite intensive cardio-pulmonary resuscitation, during which extreme arterial hypoxaemia persisted, the patient died. Postmortem examination revealed a patent foramen ovale, with a diameter of 1 cm. A severe right-to-left shunt, initiated by acute pulmonary hypertension, was considered to be the cause of death. Because of the relatively high prevalence of patent foramen ovale in the normal population, we suggest this patency may enhance the risk of fatal outcome of acute severe asthma.

Adult↗

Heterogeneity of rat liver and spleen macrophages in gadolinium chloride-induced elimination and repopulation.

Blockade of phagocytosis and selective elimination of macrophages (m phi s) are generally accepted procedures for gaining knowledge about the function of m phi s in vivo. This study demonstrates that intravenous injection of gadolinium chloride (GdCl3) not only blocks phagocytosis by rat liver m phi s (Kupffer cells) but also selectively eliminates the large m phi s situated in the periportal zone of the liver acinus. Repopulation of m phi s starts at 4 days after injection. During repopulation, m phi s are less vulnerable to GdCl3. When repopulation is complete, the new m phi s show the same vulnerability as the original ones. Splenic m phi s are less vulnerable to GdCl3 because only some of the red pulp m phi s transiently disappear. The white pulp m phi s are not affected. Repopulation occurs sooner than in liver. These results indicate that administration of GdCl3 is a suitable approach to studying the in vivo function of large Kupffer cells.

Animals↗

Oestrogen and progesterone receptor immunocytochemistry in human hyperplastic and neoplastic endometrium.

Proliferative disorders of the endometrium may be associated with autocrine and paracrine actions between stromal and epithelial cells. To determine whether the stromal-epithelial relation with respect to oestrogen receptor (OR) and progesterone receptor (PR) is disturbed in (pre)malignant endometrium immunocytochemical OR and PR expression was quantitated by computerized image analysis. This was studied in the stromal and epithelial cells of endometrial specimens diagnosed as hyperplasia (n = 14), atypical hyperplasia (n = 16), and adenocarcinoma (n = 33). Paraffin sections were used for optimal preservation of histomorphology. A progressive loss of OR and PR content occurred with increasing malignant transformation. Stromal cells in atypical hyperplasia (P = 0.0007) and well-differentiated adenocarcinoma (P = 0.0008) exhibited a relative loss of PR content as compared with epithelial cells (P = 0.036 and P = 0.17, respectively). In atypical hyperplasia, the decrease in stromal PR content was not in parallel with persistent stromal OR immunostaining. Furthermore, stromal PR expression in atypical hyperplasia was significantly (P = 0.004) lower than in the surrounding hyperplasia, whereas the stromal OR staining as well as the epithelial OR and PR staining did not differ significantly. These observations may reflect a disturbance in hormonal interrelationships between endometrial cells in the development of endometrial neoplasia, indicating that stroma may modulate epithelial growth by paracrine mechanisms.

Adenocarcinoma↗