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Biomedical subjects

T Vogt

Publications and source records attributed to T Vogt.

At least 109 records · Page 6Linked to original sources

Prognostic significance of DNA cytometry in comparison with histologic measurements in malignant melanomas.

In the present study we evaluated the prognostic impact of both DNA cytometry and quantitative histology in patients with malignant melanoma (MM). In contrast to previous investigations on sections, rapid image analysis (IA) of imprint specimens was performed to measure DNA cytometric features; 34 cases of stage I MM with low (< 1.5 mm, n = 20) and higher tumor thickness (TTH) (> 1.5 mm, n = 14) were analyzed. We found significant correlations between cytometric features and TTH, which is accepted as the most important prognostic criterion in MM. Higher TTH was closely correlated with the rate of markedly aneuploid nuclei, which is indicated by the 5c exceeding rate (5cER; r, 0.89; p < 0.001). The gain of chromatin in thicker tumors was accompanied by higher mean nuclear area (MAREA; r, 0.60; p < 0.001) and mean DNA content (MDNA; r, 0.58; p < 0.001). Additional evidence for prognostic significance of cytometry was obtained by preliminary survival analysis of 16 cases (four patients died within 2 1/2 years and 12 patients survived for at least 4 1/2 years). Applying multivariate stepwise discriminant analysis, a combination of TTH, level of invasion (LEV), 2c deviation index (2cDI), and modified standard deviation of the DNA values (SDNAM) proved to be most effective. One hundred percent of the cases were correctly classified as survivors or nonsurvivors. TTH and the 5cER were found to be the best univariate criteria for prognosis. In the U test according to Mann and Whitney, a significant discrimination of survivors and nonsurvivors was possible using either TTH or the 5cER, respectively (p < 0.02). Thus, we would like to conclude that IA of imprint specimens can be recommended as a rapid and simple additional method for grading.

Algorithms↗

Flavonol 3-O-glycosyltransferases associated with petunia pollen produce gametophyte-specific flavonol diglycosides.

Wild-type petunia pollen accumulates high levels of flavonol 3-O-glycosides. Pollen from conditionally male-fertile petunia has no flavonols and is unable to germinate. Pollen function is restored both in vivo and in vitro by providing flavonol aglycones, but not flavonol glycosides, to the pollen. In the present study, incubation of an in vitro suspension of conditionally male-fertile pollen with kaempferol or quercetin resulted in the accumulation of kaempferol and quercetin 3-O-glycosides in the pollen. We identified two glycosyltransferase activities associated with the intact pollen grain that catalyze the formation of a gametophyte-specific class of flavonol glycosides. Feeding studies showed that product formation was highly specific for flavonols with an unsubstituted 3-hydroxyl group and was not dependent on an external source of UDP-hexose. Ultraviolet spectral analysis, fast atom bombardment mass spectrometry, 1H-nuclear magnetic resonance, and 13C-nuclear magnetic resonance identified the products as kaempferol and quercetin 3-O-(2"- O-beta-D-glucopyranosyl)-beta-D-galactopyranoside, identical with the flavonol 3-O-glycosides present in wild-type pollen. The sugars are linked in a 1-->2 configuration that results in a pollen-specific class of compounds. To retain both glycosyltransferase activities in a cell-free extract, it was necessary to add triton X-100, suggesting that one or both of the proteins may be associated with a pollen membrane. A model for flavonol glycoside biosynthesis and uptake into the pollen is discussed in terms of the germination requirement for flavonols.

Carbohydrate Conformation↗

Interphase cytogenetic analysis of prostatic carcinomas by use of nonisotopic in situ hybridization.

To gain a better understanding of chromosomal aberrations in direct correlation with histology, we studied tumor material from 35 patients (36 regions) with primary prostate carcinoma by nonisotopic in situ hybridization. Nine biotinylated DNA probes were used on serial paraffin sections (centromer-specific probes for X, Y, 1, 7, 8, 10, 17, and 18, and a telomer-specific probe for 1p; ONCOR). Of the 324 hybridized sections, 94% were suitable for evaluation. In 34 of the 35 cases (35 of 36 regions) 1-8 chromosomal aberrations were detected. Chromosome X showed supernumerary centromer copies in 44% of cases. The probes for chromosomes 1, 1p, 10, and 18 demonstrated deletions in 25, 23, 40 and 58% of cases, respectively. Gains as well as deletions were present for Y, 7, 8, and 17 in 31, 25, 36, and 58% of cases, respectively. In 27% of cases discordant copy numbers of the centromer- and the telomer-specific probes for chromosome 1 were observed. No aberration which might be specific for prostate cancer could be established. The rate of aneusomy increased significantly with histological grade. Intratumoral heterogeneity of chromosomal aberrations was revealed in one case. Due to the higher sensitivity of nonisotopic in situ hybridization, aneusomic cases outnumbered cases with cytometrically determined DNA aneuploidy. In view of published results of metaphase preparations, the high frequency of aneusomy and some of the chromosomal aberrations detected by nonisotopic in situ hybridization were unexpected.

Aged↗

[Encephalopathy following poisoning with an anticholinergic agent].

A 55-year-old chemical laboratory technician developed mydriasis and ocular hypertension, which lasted for 6 weeks, after synthesizing several kilograms of a scopolamine-related test agent with anticholinergic action and then decanting a powdery intermediary substance, the dust of which he may have inhaled. Six weeks later he suddenly had symptoms of an acute intoxication while synthesizing a scopolamine-related substance. The anticholinergic delirium regressed completely within one day requiring no treatment. But subsequently he developed symptoms of a toxic encephalopathy. This only partially regressed over the following 3 years. Its probable cause is thought to have been either the manifestation of an already existing organic cerebral psychiatric syndrome or an as yet unknown effect of the test substance.

Acute Disease↗

Comparison of DNA ploidy in prostatic intraepithelial neoplasia and invasive carcinoma of the prostate: an image cytometric study.

Prostatic intraepithelial neoplasia (PIN) is regarded as the most important premalignant lesion of prostatic epithelium. The aim of this investigation was to find clues to formal pathogenesis of prostatic cancer. For this purpose DNA ploidy (determined by means of image cytometry [ICM] using 4-microns-thick Feulgen-stained paraffin sections) of PIN and invasive carcinoma was compared. Prostatic tissue of 72 patients (mean age, 67.5 years; 82 areas with carcinoma and 71 areas with PIN) was examined. In 44 cases PIN and carcinoma were coexistent in the same prostates, the PIN grade being high in 77% of these cases (P < .05). In higher-grade PIN and higher-grade carcinoma the c-values, 2.5c-exceeding-rate, and aneuploidy rate increased (P < .01). Carcinomas associated with diploid PIN (either low or high grade) showed diploidy and aneuploidy in an equal number of cases, whereas 70% of aneuploid PIN cases (all high grade) were associated with aneuploid invasive carcinomas (P < .01). Conversely, in 71% of the cases with aneuploid carcinoma the coexistent PIN (either low or high grade) was diploid. Our findings show that aneuploidy can be acquired at a preinvasive stage of carcinogenesis in the prostate and suggest that aneuploid high-grade PIN might be regarded as a precursor of some but not all aneuploid prostatic carcinomas. Image cytometry analysis seems to be a promising method for further subclassification of high-grade PIN lesions into groups with putatively lower or higher risk. However, further investigation is necessary to confirm the clinical importance of these results.

Adult↗

The ABCD rule of dermatoscopy. High prospective value in the diagnosis of doubtful melanocytic skin lesions.

BACKGROUND: The difficulties in accurately assessing pigmented skin lesions are ever present in practice. The recently described ABCD rule of dermatoscopy (skin surface microscopy at x10 magnification), based on the criteria asymmetry (A), border (B), color (C), and differential structure (D), improved diagnostic accuracy when applied retrospectively to clinical slides. OBJECTIVE: A study was designed to evaluate the prospective value of the ABCD rule of dermatoscopy in melanocytic lesions. METHODS: In 172 melanocytic pigmented skin lesions, the criteria of the ABCD rule of dermatoscopy were analyzed with a semiquantitative scoring system before excision. RESULTS: According to the retrospectively determined threshold, tumors with a score higher than 5.45 (64/69 melanomas [92.8%]) were classified as malignant, whereas lesions with a lower score were considered as benign (93/103 melanocytic nevi [90.3%]). Negative predictive value for melanoma (True-Negative divided by [True-Negative+False-Negative]) was 95.8%, whereas positive predictive value (True-Positive divided by [True-Positive+False-Positive]) was 85.3%. Diagnostic accuracy for melanoma (True-Positive divided by [True-Positive+False-Positive+False-Negative]) was 80.0%, compared with 64.4% by the naked eye. Melanoma showed a mean final dermatoscopy score of 6.79 (SD, +/- 0.92), significantly differing from melanocytic nevi (mean score, 4.27 +/- 0.99; p < 0.01, U test). CONCLUSION: The ABCD rule can be easily learned and rapidly calculated, and has proven to be reliable. It should be routinely applied to all equivocal pigmented skin lesions to reach a more objective and reproducible diagnosis and to obtain this assessment preoperatively.

Dermatology↗

DNA ploidy in carcinoma of the gallbladder. Prognostic significance and comparison of flow and image cytometry on archival tumor material.

The aim of this investigation was to determine whether the cytometrically assessed DNA ploidy is a parameter of prognostic significance in gallbladder carcinomas. For this purpose the DNA content of tumor cells from archival tumor material from 80 patients with cholecystic cancer was analysed retrospectively by using comparatively different cytometrical methods, namely flow cytometry (FCM) and image cytometry, using tissue sections (ICM-S) and nuclear suspensions (ICM-N). Conventional tumor classifications (according to pTNM and Nevin) were able to predict the further clinical course. DNA ploidy showed a statistically significant correlation only to histological grade (P < 0.001), but not to tumor stage and survival. Only a trend towards a poorer outcome for patients harboring non-diploid tumors became evident especially when no residual tumor was present postoperatively (R 0-stage; P = 0.08). The different cytometrical methods discussed in detail, showed a highly significant concordance in the determination of DNA index values (DI) and in the classification of the tumors as either diploid or non-diploid. In conclusion, our results indicate that cytometrical determination of DNA ploidy provides no further prognostic informations in gallbladder carcinomas as compared to conventional tumor staging.

Aged↗

Differentiation between malignant melanomas and benign melanocytic nevi by computerized DNA cytometry of imprint specimens.

Recently image analysis (IA) and DNA-cytophotometry (CP) have proved to be useful for the differentiation between benign and malignant melanocytic lesions on paraffin sections. Since, on sections, these procedures are very time-consuming, we tested in the present study whether IA of imprint specimens, which can be evaluated in less than 30 minutes, might also be sufficient. In 39 malignant melanomas (MM), 18 melanocytic nevi (MN), and 6 dysplastic nevi (DN), 12 different morphometric and DNA cytometric features were determined in 100 randomly selected nuclei. In univariate analysis, 5 features were found to be significantly different between the benign and malignant groups (p < 0.0001): mean value (MAREA) and standard deviation (SAREA) of nuclear area and the 80th, 90th, and 95th percentiles of DNA distribution. Using SAREA, the best univariate feature, 82.5% of the cases could be correctly separated. In multivariate analysis with a combination of three features--standard deviation of nuclear area (SAREA), mean DNA value (MDNA), and 95th percentile of DNA distribution (PERC95)--a correct diagnosis was achieved in 89.5% of the cases. Results obtained in the cases of DN indicated an increased proliferation, but did not allow the separation of DN from MM and MN. Since our technique allows a rapid analysis without loss of tissue, which might be important for histological analysis, and the classification rates are equal or still higher than reported in studies on sections, imprints of melanocytic lesions seem to be most appropriate for the calculation of DNA cytometric features as helpful diagnostic criteria in equivocal melanocytic lesions.

Adult↗

Mental health status as a predictor of morbidity and mortality: a 15-year follow-up of members of a health maintenance organization.

OBJECTIVES: This study sought to relate preexisting depression, worries, affect balance, and mental health symptoms to subsequent risk of morbidity and mortality. METHODS: A random sample of members of a health maintenance organization were interviewed at home in a 1970/71 survey. Baseline psychological measures from that survey were then related to 15-year mortality and first incidence of cancer, heart disease, hypertension, stroke, functional gastrointestinal disease, and hyperimmune diseases. RESULTS: Baseline depression and the Langner Mental Health Index predicted incidence of functional gastrointestinal and hyperimmune diseases. The relationship of the Langner index to hyperimmune diseases was particularly strong; mortality, cancer, heart disease, hypertension, and stroke incidence were not related to that index. Except for affect balance, which was worst in the elderly, indications of psychological dysfunction were strongest in the young. CONCLUSIONS: Psychological indices detected increased risk for functional gastrointestinal and hyperimmune diseases but were not related to mortality risk. Further research is needed to disaggregate relationships of the specific conditions that were included in the hyperimmune group. Functional gastrointestinal disease might be preventable with early attention to depressed persons and to those scoring high on the Langner index.

Adolescent↗

Purification and characterization of sinapine synthase from seeds of Brassica napus.

1-O-Sinapoylglucose:choline sinapoyltransferase ("sinapine synthase") has been purified from immature seeds of Brassica napus by sequential hydroxylapatite absorption, ion-exchange chromatography, and gel filtration. The purified enzyme has an apparent molecular weight of 65 kDa on gel filtration and a subunit structure on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of 28 kDa. Sinapine synthase has Km values in the high micromolar range for both substrates (1-O-sinapoylglucose and choline chloride) but these values are sensitive to the concentration of the second substrate. The enzyme displays a marked substrate specificity for 1-O-sinapoylglucose among other related glucose esters. No requirements for thiol protectants or divalent cations were found, but sinapine synthase activity is inhibited by Cu2+ and Hg2+ ions. Partial amino acid sequence data have been obtained from a tryptic digest of the 28-kDa polypeptide.

Acyltransferases↗

[Prostate cancers and potential precancerous conditions: DNA cytometric investigations and interphase cytogenetics].

The topic of this investigation was to compare precancerous lesions of the prostate (prostatic intraepithelial neoplasia -PIN- and atypical hyperplasia -AH-) and invasive carcinomas concerning DNA ploidy (image cytometry/ICM) and morphologically feasible chromosomal aberrations (interphase cytogenetics/NISH). The aim was to find clues to formal pathogenesis of prostatic cancer. Prostatic tissue of 76 patients (76 areas with carcinoma, 71 with PIN, and 12 with AH) was examined by means of ICM. In 44 cases of coincidental PIN and carcinoma, the gradings of PIN and carcinoma correlated. C-values, 2,5c-exceeding-rate, and aneuploidy rate turned out to increase in PIN and carcinoma with increasing grading (P < 0.01). In some of these cases NISH was carried out in serial sections by applying centromer-(X,Y,1,7,8,10,17,18) and telomer-(1p) specific DNA probes. The result of this approach was an increase in the number of chromosomal aberrations and chromosomes involved correlating with the grading. Our conclusion is that PIN 1 could be regarded as the precancerous lesion mainly to higher differentiated carcinomas, whereas PIN 2 and 3 should be considered a preneoplastic condition mainly of moderately and low differentiated carcinomas.

Chromosome Aberrations↗

Impaired neuromuscular transmission during partial inhibition of acetylcholinesterase: the role of stimulus-induced antidromic backfiring in the generation of the decrement-increment phenomenon.

Neuromuscular transmission was studied in the rat phrenic nerve-hemidiaphragm preparation with acetylcholinesterase (AChE) partially inactivated. Enzyme inhibition resulted in (1) increased single-twitch tension of the diaphragm; (2) compound muscle action potential (CMAP) containing repetitive discharges; (3) stimulus-induced antidromic backfiring (SIAB) seen in the phrenic nerve; and (4) repetitive nerve stimulation (RNS) eliciting a decrement-increment (D-I) phenomenon (i.e., amplitude reduction maximal with the second CMAP). Using a high-calcium and low-magnesium solution, SIAB and the decrement of the second CMAP during RNS were intensified, whereas closely spaced trains and (+)-tubocurarine (TC) abolished SIAB and simultaneously prevented the decrement of the second CMAP. Importantly, low concentrations of (+)-TC prevented SIAB in the phrenic nerve, while the repetitive discharges of the CMAP and the increase in twitch tension remained unaffected. This observation suggests that preterminal nicotinic receptors stimulated by released acetylcholine induce SIAB, whereas postsynaptic events are less important in the generation of SIAB. SIAB, a presynaptic event, appears to be responsible for the transient impairment of the neuromuscular transmission, i.e., the D-I phenomenon.

Acetylcholinesterase↗

An Arabidopsis mutant defective in the general phenylpropanoid pathway.

Mutants of Arabidopsis deficient in a major leaf phenylpropanoid ester, 2-O-sinapoyl-L-malate, were identified by thin-layer chromatographic screening of methanolic leaf extracts from several thousand mutagenized plants. Mutations at a locus designated SIN1 also eliminate accumulation of the sinapic acid esters characteristic of seed tissues. Because of increased transparency to UV light, the sin1 mutants exhibit a characteristic red fluorescence under UV light, whereas wild-type plants have a blue-green appearance due to the fluorescence of sinapoyl malate in the upper epidermis. As determined by in vivo radiotracer feeding experiments, precursor supplementation studies, and enzymatic assays, the defect in the sin1 mutants appears to block the conversion of ferulate to 5-hydroxyferulate in the general phenylpropanoid pathway. As a result, the lignin of the mutant lacks the sinapic acid-derived components typical of wild-type lignin.

Arabidopsis↗