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Biomedical subjects

R Albert

Publications and source records attributed to R Albert.

7 recordsLinked to original sources

Three-dimensional image processing for morphometric analysis of epithelium sections.

The reproducible classification of poorly differentiated abnormal epithelium specimens is still a diagnostic problem. The computer-aided method described here improves the differentiation between benign and malignant epithelium specimens. Hematoxylin and eosin-stained sections of normal squamous epithelium, dysplasia, carcinoma in situ, and carcinoma were scanned in a TV microscope system and analyzed by means of image processing methods on a DEC 5000/200 workstation. From the 15-20 microns thick histological sections, 3-5 focus positions in steps of 1-4 microns were scanned. The segmentation of the cell nuclei was performed automatically by color analysis and geometric operations. For each nucleus the best focus level was selected and at this level the center of the cell was calculated. Graph theoretical methods were applied to analyze the morphometry of the epithelium specimens. The minimal spanning tree was computed in the three-dimensional (3D) space of the sections with the selected centers of the nuclei as vertices. The best feature found for discrimination of the specimens is the average length of all edges in a tree. In the two-dimensional (2D) analysis we had to accept an error probability of about 20% in differentiation of dysplasia and carcinoma. In contrast to this we differentiated normal squamous epithelium, dysplasia, and carcinoma with a correct classification rate of 100% in the 3D analysis.

Carcinoma

Intestinal absorption of the octapeptide SMS 201-995 visualized by fluorescence derivatization.

The absorption of an intact oligopeptide was investigated in rat and dog small intestine using the metabolically stable somatostatin analogue SMS 201-995. The synthetic octapeptide was coupled to 4-nitrobenzo-2-oxa-1,3-diazol to have a fluorescent label for the direct visualization. The 4-nitrobenzo-2-oxa-1,3-diazol-labeled peptide was active in displacing the corresponding hormone 125I-Tyr3-SMS 201-995 (Sandostatin; Sandoz Pharmaceuticals, Basel, Switzerland) from its high-affinity binding site in rat cortex membranes with an IC50 = 4.6 x 10(-10) mol/L. The release of growth hormone from cultured anterior pituitary cells was inhibited by the fluorescent somatostatin analogue with the same potency as by somatostatin 14 (IC50 = 6 x 10(-10) mol/L). Incubation with mucosal scrapings followed by high-performance thin-layer chromatography analysis showed that the peptide was stable against proteolysis. 4-Nitrobenzo-2-oxa-1,3-diazol SMS 201-995 was well absorbed from enterocytes of rat small intestine. The absorption was highest into jejunal cells and it could be inhibited by an excess of unlabeled peptide. A significantly lower absorption was detected in crypts compared with villus tips. No fluorescence could be seen in intestinal mucin and goblet cells. After oral administration, the 4-nitrobenzo-2-oxa-1,3-diazol-labeled peptide rapidly appeared in the blood of rats and dogs, reaching a bioavailability of 4.3% and maintaining pharmacological activity. This suggests that enterocytes are able to absorb intact oligopeptides being stabilized against proteolytic degradation through a transcellular mechanism.

Animals

[111In-DTPA-D-Phe1]-octreotide, a potential radiopharmaceutical for imaging of somatostatin receptor-positive tumors: synthesis, radiolabeling and in vitro validation.

Somatostatin receptor-positive human tumors can be detected using radioiodinated analogues of somatostatin, both in vitro and in vivo. [123I-Tyr3]-octreotide has been successfully used in the visualization of somatostatin receptor-positive tumors by gamma camera scintigraphy, but this radiopharmaceutical has some major drawbacks, which can be overcome with other radionuclides such as 111In. As starting material for a potentially convenient radiopharmaceutical, a diethylenetriaminopentaacetic acid (DTPA) conjugated derivative of octreotide (SMS 201-995) was prepared. This peptide, [DTPA-D-Phe1]-octreotide (SDZ 215-811) binds more than 95% of added 111In in an easy, single-step labeling procedure without necessity of further purification. The specific somatostatin-like biologic effect of these analogues was proven by the inhibition of growth hormone secretion by cultured rat pituitary cells in a dose-dependent fashion by octreotide, [DTPA-D-Phe1]-octreotide and non-radioactive [115In-DTPA-D-Phe1]-octreotide. The binding of [111In-DTPA-D-Phe1]-octreotide to rat brain cortex membranes proved to be displaced similarly by natural somatostatin as well as by octreotide, suggesting specific binding of [111In-DTPA-D-Phe1]-octreotide to somatostatin receptors. The binding of the indium-labeled compound showed a somewhat lower affinity when compared with the iodinated [Tyr3]-octreotide, but indium-labeled [DTPA-D-Phe1]-octreotide still binds with nanomolar affinity. In conjunction with in vivo studies, these results suggest that [111In-DTPA-D-Phe1]-octreotide is a promising radiopharmaceutical for scintigraphic imaging of somatostatin receptor-positive tumors.

Amino Acid Sequence

[Centroblast morphology: a morphometric evaluation by means of computer-aided image analysis].

In cytologic preparations, cell images from 30 cases of high grade malignant Non-Hodgkin's lymphoma (NHL) and 10 cases of tonsillitis have been analysed using a colour TV microscope system, high resolution scanning and image processing. Multivariate analysis of 30 cell features allowed satisfying recognition and discrimination of centrocytes, centrocyte-like centroblasts, ordinary centroblasts and multilobated centroblasts. In addition, according to their image analytical data, the ordinary centroblasts from NHL formed 5, and those from tonsillitis 4 well defined, homogeneous clusters. Even at simultaneous analysis, there was an essential overlap only between centroblast subtype 3 from NHL and subtype 9 from tonsillitis, but reliable discrimination of all the rest.

Computers

Performance characteristics of methods of analysis used for regulatory purposes. Part II. Pesticide formulations.

The precision parameters of the method-performance (collaborative) studies published in the AOAC Journal from 1915 through 1990 for pesticide formulations have been recalculated on a uniform basis by the International Union of Pure and Applied Chemistry 1987 protocol. About 93% of the 953 accepted assays, which are predominantly gravimetric (G), volumetric (V), and gas (GC) and liquid (LC) chromatographic methods, exhibit relative standard deviations among laboratories (RSDR) that are generally less than 2 times the values predicted from the Horwitz equation: RSDR (%) = 2 exp (1-0.5 log C), where C is the concentration expressed as a decimal fraction. UV, VIS, and IR spectrophotometric (S) methods are somewhat poorer, with about 80% of the reported RSDR values less than twice the predicted RSDR value. The precision parameters of pesticide formulations analyzed by the older methods (G, V, GC) are equivalent to those previously found for drug preparations in the same concentration range; the precision parameters of pesticide formulations analyzed by LC and S are somewhat poorer. Overall, however, the precision parameters of pesticide formulations are generally independent of analyte, method, and matrix, and are primarily a function of concentration. The method-acceptability decisions of the AOAC for pesticide formulations during the past 75 years can be approximated retrospectively by using a criterion for RSDR that is less than 2 times the RSDR calculated from the Horwitz equation.

Databases, Factual

Precision parameters of methods of analysis required for nutrition labeling. Part I. Major nutrients.

Major components of foods and feeds are fat, protein, and carbohydrates. Fat and protein are determined by direct measurements that are interpreted as the quantity of the constituent. Carbohydrates are usually calculated by difference. For this calculation, values for moisture/solids, ash, and "fiber" are also needed. The readily available collaborative studies for the determination of these major components are reviewed in an attempt to assign precision parameters to validated methods of analysis. When a number of studies for the same analyte, in the same food, by the same method are available, it is seen that the precision parameters among laboratories (standard deviations, SR; relative standard deviations, RSDR) and the ISO maximum tolerable difference functions (repeatability value, r; reproducibility value, R) are not characterized by any conventional distribution. The precision data are best summarized as a median or average parameter and the interval containing the centermost 90% of reported values. Typically, the precision of methods of analysis can be expressed as a function of concentration only, independent of analyte, matrix, and method. The average RSDR value from each collaborative data set can then be used as the numerator in a ratio containing, as the denominator, the value calculated from the Horwitz equation: RSDR = 2 exp (1 - 0.5 log C) where C is the concentration as a decimal fraction. A series of ratios consistently above 1, and especially above 2, probably indicates that a method is unacceptable with respect to precision. By this criterion, only the protein (Kjeldahl) determination is unqualifiedly acceptable with a 90% interval for RSDR of 1 to 3% at C values above about 0.01 (1 g/100 g). Fat, moisture/solids, and ash are acceptable down to limiting concentrations in the region of 1 to 5 g/100 g, if a test portion large enough to provide at least 50 mg of weighable residue or volatiles is specified. Measurements of individual carbohydrates and fiber-related analytes have unexpectedly poor precisions among laboratories. The variability, although high, may still be suitable for nutrition labeling. Reliability of analyses for the control of labeling of the primary nutrients must be achieved through quality assurance programs that require strict adherence to the directions of empirical methods and the use of suitable reference materials for absolute methods.

Databases, Bibliographic