[Compression of the median and radial nerves of the proximal forearm].
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Chronic Disease↗
Biomedical subjects
M Oestreicher
Publications and source records attributed to M Oestreicher.
Clonal X-inactivation analysis of human tumours using the human androgen receptor gene (HUMARA) polymorphism: a non-radioactive and semiquantitative strategy applicable to fresh and archival tissue.
Assessment of clonality of cellular proliferations is important in experimental and clinical cancer research. X-chromosome inactivation studies are widely used to assess clonality, but most assays require relatively large amounts of high molecular weight DNA. Two PCR-based strategies, the phosphoglycerate kinase (PGK) and the human androgen receptor (HUMARA) clonality assays allow studies of small tissue samples. The HUMARA assay was adapted to non-radioactive analysis taking advantage of an automated sequencer providing high resolution of alleles and immediate quantitation. This assay was validated by comparison with X-inactivation patterns obtained by Southern analysis with the probes M27 beta and PGK. Fifteen gastrointestinal carcinomas, 25 benign goiter nodules and normal peripheral leukocytes of 27 individuals (12 who were under 15 years and 15 over 80 years) were analysed. Furthermore, DNA extracted from formalin-fixed paraffin-embedded tissue (FPT) was analysed with the two PCR-based methods and compared with X-inactivation patterns determined by Southern analysis of high molecular weight (HMW) DNA. This modified HUMARA assay is reliable in most patients; as with other clonality assays, constitutive skewing in normal tissue precludes clonal analysis in some individuals. Extremely skewed X-inactivation patterns were found in normal peripheral leukocytes of 7 out of 15 old females (over 80 years) and in 1 of 12 of the young females tested (under 15 years). Comparison of results obtained with HMW and FPT DNA yielded consistent results for the HUMARA assay whereas the PGK PCR assay was much less reliable. The HUMARA assay thus permits studies of selected areas of tissue sections without significant stromal components, allowing correlation of histological and genotype findings in fresh and archival specimens.
Adolescent↗
Frequent clonal loss of heterozygosity but scarcity of microsatellite instability at chromosomal breakpoint cluster regions in adult leukemias.
Microsatellites are important highly polymorphic genetic markers dispersed in the human genome. Using a panel of 22 (CA)n repeat microsatellite markers mapped to recurrent breakpoint cluster regions specifically involved in leukemia, we investigated 114 adult leukemias (25 acute lymphocytic leukemia [ALL], 32 acute myeloid leukemia [AML], 36 chronic lymphocytic leukemia [CLL], and 21 chronic myeloid leukemia [CML] in chronic phase) for somatic mutations at these loci. In each patient, DNA from fresh leukemia samples was analyzed alongside normal constitutive DNA from buccal epithelium. We detected loss of heterozygosity (LOH) in 81 of 114 patients (ALL 16/25, AML 25/32, CLL 30/36, CML 10/21). Deletions were most often seen in ALL at 11q23 and 19p13; in AML at 8q22 and 11q23; in CLL at 13q14.3, 11q13, and 11q23; and in CML at 3q26. Only six deletions were reported in 74 karyotypes analyzed, whereas in these same cases, 91 LOH events were detected by microsatellites. Of 26 leukemias with a normal karyotype, 16 nevertheless showed at least one LOH by microsatellite analysis. Replication errors were found in 10 of 114 patients (8.8%). Thus, microsatellite instability is rare in leukemia in contrast to many solid tumors. Our findings suggest that in adult leukemia, LOH may be an important genetic event in addition to typical chromosomal translocations. LOH may point to the existence of tumor suppressor genes involved in leukemogenesis to a degree that has hitherto been underestimated.
Adult↗
Somatic mutations detected by mini- and microsatellite DNA markers reveal clonal intratumor heterogeneity in gastrointestinal cancers.
We investigated clonal intratumor heterogeneity by comparing different areas of each tumor in 20 gastrointestinal cancers from female patients (1 esophageal cancer, 5 stomach cancers, and 14 colorectal cancers). In all 19 cases informative for X-inactivation analysis with the M27 beta and/or the phosphoglycerate kinase probes, the tumors were clonal. Separate areas from a given tumor showed identical X-inactivation patterns, providing evidence for its single-cell origin. Of 20 cancers, 11 showed p53 gene mutations (base pair insertions, point mutations, and one case of a base pair deletion) in exons 5-8. A particular p53 gene mutation was identical in all tumor areas investigated per case. The minisatellite probes detected loss of heterozygosity or new mutant alleles at 1p33, 1q21, 5q35, 17p13, or 18q21. In seven cases mutations at particular loci were restricted to one or two areas per tumor, while in another seven cases they were common to all tumor areas. Loss of heterozygosity or new alleles detected at the microsatellite loci D2S123, D3S1611, D5S107, D17S261, or D18S34 [(CA)n repeats] were common to all tumor areas in 7 of 19 cases. In another seven cases, however, microsatellite mutations at these loci were restricted to one to three areas per tumor. Tracing clonal intratumor heterogeneity would permit one to study the hierarchy of mutational events in cancers where no premalignant lesions can be harvested. Most important, our study indicates that clonal intratumor heterogeneity might lead to sampling errors in the molecular diagnosis of cancer biopsy specimens when using mini- or microsatellite markers.
Alleles↗
Clonality and X-inactivation patterns in hematopoietic cell populations detected by the highly informative M27 beta DNA probe.
About 80% to 90% of females are informative for X-inactivation/methylation analysis with the probe M27 beta, which would therefore seem attractive in assessing clonality in hematologic cell populations. Eighteen acute lymphoid or myeloid leukemias, three chronic lymphocytic leukemias, and three chronic myelogenous leukemias as well as 12 malignant non-Hodgkin's lymphomas mostly showed extremely skewed clonal X inactivation (median allelic cleavage ratio [ACR] of unmethylated/inactive M27 beta alleles was 50, range 1 to 100) or hypermethylation of both alleles. Two lymphomas showed random M27 beta X inactivation but clonal antigen-receptor gene rearrangements. In normal peripheral blood leukocytes from 105 healthy females aged 2 to 96 years, the median ACR was 2 (range 1 to 100). Thus, it was significantly lower than in the leukemias (P = .0001, Mann-Whitney test), but extremely skewed patterns (ACR > 10.8, ie, > 80th percentile) were seen not only in the leukemias but also in 21/105 samples (20%) of normal leukocytes, and significantly more frequent in a population of elderly women (aged 75 to 96 years) compared with healthy children (aged 2 to 8 years) and younger women (aged 20 to 58 years) (P = .00125; chi 2 test). We conclude that in a population of cells derived from the hematopoietic system where clonality is uncertain, skewed M27 beta patterns are not reliable indicators for the presence of a clonal neoplastic disorder. The basis for severe X-inactivation skewing is unclear at present, but this finding raises interesting questions regarding the composition of the hematopoietic stem cell pool.
Acute Disease↗
Polyclonal and monoclonal thyroid nodules coexist within human multinodular goiters.
Although somatic mutations have been identified in a subset of thyroid nodules, the pathogenesis of nodules in multinodular goiters remains unclear. Clonal analysis indicates whether a nodule arises from the polyclonal proliferation of a group of cells or forms a clone from a genetically altered cell. Individual thyroid nodules have been shown to be of polyclonal or monoclonal origin. In this study we examined the clonality of several different nodules in patients with multinodular goiters. Clonality was established using the X-chromosomal probe M27 beta, which detects a multiallelic polymorphism at the locus DXS255 in 90% of females. Twenty-five nodules from 9 multinodular goiters were analyzed; 9 nodules were polyclonal, and 16 were monoclonal. Three goiters contained only polyclonal nodules, whereas 3 contained only monoclonal nodules. Polyclonal and monoclonal nodules coexisted in 3 goiters. In 2 goiters, the monoclonal nodules were shown to derive from different progenitor cells. We conclude that polyclonal and monoclonal nodules may coexist in multinodular goiters and that monoclonal nodules can originate from different cells. The coexistence of polyclonal and monoclonal nodules suggests that different pathogenic mechanisms occur simultaneously or that monoclonal nodules emerge secondarily from a polyclonal population due to a growth advantage from a genetically altered cell.
Adult↗
The degree of inhibition of thyroid follicular cell proliferation by iodide is a highly individual characteristic of each cell and differs profoundly in vitro and in vivo.
Pharmacological concentrations of iodide (> 1 x 10(-6) mol/l) are known to inhibit thyroid follicular cell growth in vitro. However, the inhibitory effect varies widely, depending on experimental conditions, and usually does not exceed 50%. We demonstrate that iodide (10(-4) mol/l) inhibits the growth of FRTL-5 cells in different passages by 11-67%. When five subclones of FRTL-5 cells were compared to the wild type, iodide-induced growth inhibition varied between 25% and 46%. The individual degree of inhibition of each clone was reproducible in two subsequent passages, suggesting that it is a stable constitutive trait. When FRTL-5 cells were grown first in three-dimensional clusters and then transplanted onto nude mice with high endogenous thyrotropin secretion, iodide at a serum concentration of less than 5.7 x 10(-7) mol/l nearly completely blocked cell replication in the transplants but not in the mice's own thyroid. Five cell lines, prepared from autonomously growing hyperthyroid feline multinodular goiters, were nearly completely resistant to the growth-inhibitory effect of iodide. These observations suggest that the sensitivity towards the growth-inhibiting effect of iodide is a highly variable, stable trait of each thyrocyte, even in cloned cell populations. Some FRTL-5 cells and, even more so, cells prepared from autonomously growing nodular feline goiters are resistant constitutively to the growth-inhibiting effect of iodide.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Effect of various cytologic preparation techniques on form, texture and densitometric nuclear parameters of normal and dysplastic bladder urothelial cells].
An important prerequisite for densitometric and morphometric measurements on cytological specimens is the standardized cell preparation. Optimal results can only be achieved when the analyses are carried out on a regular monolayer of cell nuclei. Comparing the conventional cytological smear with a new centrifugation technique we demonstrate statistically significant differences of the two methods in texture, size and parameters describing the DNA content of normal and dysplastic urothelial cells.
Cell Nucleus↗
[The effect of food intake on the gastric emptying of gastric juice-resistant tablets and capsules].
To test the effect of food intake on gastric emptying of gastric juice-resistant drugs, emptying time of a 11 x 6 mm tablet and a 20 x 7 mm capsule was measured by means of a metal detector in 10 healthy persons (5 men and 5 women; mean age 25 [18-30] years) after fasting and after eating three main and three in-between meals. After fasting the tablets left the stomach after 78 +/- 18 min, the capsules after 60 +/- 16 min, while meal intake delayed emptying by a factor of 10 to 12 +/- 1.3 hours and 10 +/- 1.8 hours, respectively. The slightly shorter emptying time of capsules was statistically not significant. The results indicate that gastric juice-resistant tablets taken during day-time may, if several meals are eaten, accumulate in the stomach and then be emptied together at night. It is recommended that such drugs be taken in the fasting state in the morning and between meals, while avoiding in-between meals.
Adolescent↗
[Morphology and function of macrophages in AIDS in broncho-alveolar lavages (BAL)].
HIV infects susceptible T-cell and mononuclear phagocyte targets. Unlike the dramatic changes that occur with T-cells during HIV disease, changes in monocyte and macrophage phenotype and function are qualitatively minimal. The aim of the study was to quantitatively analyze the morphology of macrophages in broncho-alveolar lavages in patients without AIDS, with AIDS, with AIDS complicated by Pneumocystis carinii and in carcinoma patients. In patients with AIDS, the nuclei of macrophages demonstrate a higher integrated optical density (2P less than 0.10), are bigger in size (2P less than 0.05) and have less notches (2P less than 0.02).
Acquired Immunodeficiency Syndrome↗
Some fundamental aspects of morphometry in clinical pathology, demonstrated on a simple, multipurpose analysis system.
The aim of this study was (1) to investigate the value of morphometry, (2) to fix a set of parameters suitable for analyzing diagnostic problems, and (3) to create a general strategy for data storage and for user-friendly data management. The intrinsic value of morphometry lies in the fact that in contrast to other morphologic methods, it permits the presentation of findings in the form of numbers. The following set of morphometric parameters, in the broad sense of the term morphometry, is standard in our laboratory: planimetric parameters (shape descriptors), parameters of the gray value histogram (descriptors of the general gray value distribution), texture parameters (descriptors of the correlation between various image segments), invariant moments (descriptors of the size and localization of textural image segments) and densitometric parameters. The introduction of morphometric procedures into the daily routine is facilitated if data registration and evaluation are performed separately. Original data generated by direct measurement are primary or raw data, which are stored as such. In a separate, second step these raw data are used to compare more or less complex morphometric parameters, which are called "secondary data". A system designed for separate data registration and evaluation can easily be adapted to new methodologic developments. For instance, primary data on objects (gray values, coordinates of the contour) measured one time in the past can be reused at any other time for computing new features from these data. This procedure is comparable to the possibilities in immunohistochemical staining: new immunohistochemical stains can be applied to newly prepared sections of old tissue blocks.
Computer Communication Networks↗
[Prerequisites for the application of statical morphometry in diagnostics].
The aims of the present paper were: 1. to test a set of parameters suitable for quantifying morphological features; 2. to create a generally valuable strategy for data storage and for a user friendly data management; 3. to examine the parameter set and the conception for an optimal data management by the quantification of cytological specimens of pleural effusions. The significance of a distinction between "primary parameters" (data directly captured during the measurement) and "secondary data" (data calculated from the primary data) is explained. In the first step of classification of the cytological specimens 81.8% of the patients with reactive alterations of mesothelial cells (n = 11) and 100% of the patients with tumours (mesotheliomas and metastasis of adenocarcinomas) (n = 19) were correctly classified with the aid of a little "expert system". In the second step (discrimination between mesotheliomas (n = 6) and metastasis of adenocarcinomas (n = 13] all patients were correctly classified.
Cytodiagnosis↗
[Prevention of infection at the operative site: irrigation with iodine derivatives, or NaCl. A prospective and randomized study in general surgery].
A prospective randomized study was undertaken among 540 patients submitted to a surgical operation. The operative site and the wall before skin closure have been washed either with saline or with Betadine-R solution. Bacteriological samples were taken before irrigation. The contamination rate reached 60% in visceral surgery, 30% in bone surgery. Postoperative wound sepsis nearly reached 6%. There was no difference between the NaCl and Betadine groups.
Humans↗
Growth regulation of cancer metastases by their host organ.
We analyzed mechanisms responsible for organ-specific metastasis by using two melanoma sublines derived from the same mouse tumor, of which one colonizes the lungs (F10) and the other colonizes the liver (L8) after intravenous injection. Both lines were obtained by selective growth in lung or liver after injection of tumor cells into a tail vein or portal vein. Contrary to common concepts, the cells of the liver-colonizing melanoma line do not accumulate preferentially in the liver after intravenous administration in vivo. However, the selective survival and proliferation of these melanoma cells in the target organ (liver) may be explained by the unexpected observation that they can be specifically stimulated to proliferate in the presence of hepatocytes, whereas the cells of the lung-colonizing line cannot. Growth promotion under coculture conditions in vitro was monitored both by thymidine incorporation into DNA and by increase in cell numbers. The proliferative stimulus is not mediated by an easily diffusible factor but rather depends upon direct contact between liver cells and those tumor cells that metastasize to that particular organ.
Animals↗
Radioreceptor assay for alpha-MSH using mouse B16 melanoma cells+.
A radioreceptor assay for alpha-MSH is described which is based on cultured mouse B16 melanoma cells and bioactive monoiodinated [Nle4]-alpha-MSH tracer. The assay was used (1) to study the binding characteristics of alpha-MSH to B16 cells, (2) to determine the relative binding activity of MSH peptides, and (3) to measure MSH in tissue extracts. The association of alpha-MSH to B16 cells reached a stable plateau after 3 h at 15 degrees C. At 25 degrees or 37 degrees C, the binding was transient and at 0-1 degree C, the association was very slow. The hormone-receptor complex was relatively stable between 0 degrees and 15 degrees C whereas a 50% dissociation was reached after 90 min at 25 degrees C and after 35 min at 37 degrees C. The mean KD for alpha-MSH of four saturation experiments was 1.3 nM and the number of receptors 9570 per cell. 1,10-Phenanthroline had a stabilizing effect in the binding assay when used at a 0.3 mM concentration. From the MSH peptides tested in the binding assay, some showed similar potencies in three bioassays (tyrosinase, melanin and Anolis skin), whereas others displayed considerably lower bioassay values than expected from the binding data. This shows that binding and bioactivity can be dissociated in some of the MSH peptides. The biological activity of MSH from the neurointermediate lobe of the rat pituitary as measured by its binding to B16 cells corresponds fairly well with RIA results; in the anterior lobe, alpha-MSH values are overestimated because of the large amount of ACTH present.
Animals↗
alpha-MSH receptor autoradiography on mouse and human melanoma tissue sections and biopsies.
MSH receptors and their binding characteristics of [125I]-labelled derivatives of alpha-MSH have been studied extensively on various mouse and human melanoma cell lines in culture. The aim of this study was to determine the binding characteristics of alpha-MSH radioligands to MSH receptors occurring in experimental mouse and human melanoma tumours as well as in human melanoma biopsies. For this reason, solid tumours were grown on experimental animals by inoculation of murine B16-F1 and human D10 and HBL melanoma cells. After excision and cryosectioning of the tumours, frozen tissue sections were incubated with [(125I)Tyr2]-alpha-MSH or [(125I)Tyr2,Nle4,D-Phe7]-alpha-MSH and specific alpha-MSH binding sites were visualized by subsequent autoradiography. The presence of increasing concentrations of unlabelled alpha-MSH during incubation with tracer led to a dose-dependent displacement of the radioligand. Quantitative analysis of the autoradiograms produced dissociation constants which were comparable with those obtained with cell binding assays: KD = 1.87 and 1.31 nmol/l for B16 tumours and cells, respectively; 0.32 and 0.33 nmol/l for D10, and 2.24 and 1.36 nmol/l for HBL tumours and cells, respectively. This indicates similar binding properties of alpha-MSH radioligands to both cultured melanoma cells and tissue sections of melanoma tumours from experimental animals. Similar binding characteristics were also observed with human melanoma tissue sections originating from biopsies of melanoma patients.
Animals↗
[Prospective study of administering a single-dose prophylactic antibiotic in primarily indicated abdominal cesarean section].
A prospective study was carried out with the participation of 60 pregnant women to elucidate the question if a unilateral antibiotic-prophylaxis is also indicated for a primary caesarean section. With the help of a random-list two collectives were formed with 30 pregnant women each. After delivery of the child one collective was given 4 g Mezlocillin (Baypen) i.v., the other collective did not receive an antibiotic. We analyzed the postoperative period of storage, postoperative fever, postoperative quality of healing, endometritis, urinary tract infection and the necessity of a postoperative antibiotic therapy. In addition we investigated swabs of the ear of the newborn, swabs from the cervix of the mother and blood culture of umbilical vein. Significantly less postoperative disorder of healing could be observed in the prophylaxis collective. All other investigated parameters did not show any significant differences in both collectives. Also there were no significant differences of infections in both collectives, therefore there is no indication for an antibiotic prophylaxis at a primary caesarean section.
Cesarean Section↗
[Daily variations in pregnancy hormones].
In a prospective study estriol, estradiol, progesterone, human placental lactogen (HPL) prolactin and SP1 (a placental glycoprotein specific for pregnancy), were performed in the second half of uncomplicated pregnancies in order to answer the question if there exist a circadian rhythm of these hormones in serum. All serum concentrations were measured by radioimmunoassay at 8.00, 10.00, 16.00, 20.00, 24.00 and 4.00 o'clock. 58 pregnant women with uncomplicated pregnancies show no circadian rhythm of serum levels from estriol, progesterone, HPL and SP1, while serum levels of estradiol and prolactin have a significant circadian rhythm. The estradiol serum levels are significant higher at 8.00 and 12.00 o'clock, significant less at 24.00 and 4.00 o'clock. The prolactin serum levels are significant less at 16.00 and 20.00, at 4.00 and 8.00 significant higher. In 20 pregnancies complicated by preeclampsia and 12 pregnancies complicated by intrauterine growth retardation serum levels of all hormones were measured at 8.00, 10.00, 16.00, 20.00, 24.00 and 4.00 o'clock. The serum concentrations in complicated pregnancies show no difference to the serum levels in uncomplicated pregnancies.
Estrogens↗