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Biomedical subjects

F H Wezeman

Publications and source records attributed to F H Wezeman.

33 records · Page 2Linked to original sources

Low molecular weight proteinase inhibitors. III. Quantification and isolation of activity from benign and malignant human breast tissue samples.

Both normal and malignant breast tissue contain proteinase inhibitors. Extracellular proteins produced by tumors have been demonstrated to be qualitatively similar to their counterparts in normal tissue, but they are often present in significantly less quantity than in normal tissue. In our investigation, normal breast tissue extracts were shown to contain significantly greater inhibitory activity directed against the degradation of casein by trypsin in the isolated fraction of the extracts compared with extracts from malignant tissues. The molecular weight of this isolated fraction is approximately 17,000 daltons. Our observations suggest that malignancy is accompanied by a reduction in the net inhibitory activity of this proteinase inhibitor.

Breast↗

Low molecular weight proteinase inhibitors. I. Extraction and identification of activity from normal and malignant human breast tissues.

Extracts of both normal human breast tissues and infiltrating ductal carcinoma tissues were ultrafiltered and concentrated to recover proteins having nominal molecular weights between 1000 and 50,000 daltons. Proteinase inhibitory activity of the final concentrates of tumours and normal breast controls were found to be distinct from the majority of proteinase inhibitory activity in human serum as judged by cellulose acetate electrophoresis. All final concentrates contained proteinase inhibitory activity with electrophoretic mobilities similar to that of Trasylol. Molecular sieve chromatography on high performance liquid chromatographs of the final concentrate of a tumour extract containing the greatest proteinase inhibitory activity indicated that the activity was present within 2 peaks having apparent molecular weights of 22,000 and 7000 daltons.

Adult↗

Low molecular weight proteinase inhibitors. II. Extraction and identification of activity from infiltrating ductal carcinoma during lactation.

Extracts of both infiltrating ductal carcinoma and non-tumorous tissue were obtained from the same mastectomy specimen of a lactating female patient. The extracts were ultrafiltered and concentrated to recover proteins having nominal molecular weights between 1000 and 50,000 daltons. Although the final concentrates of both samples contained proteinase-inhibitory activities with electrophoretic mobilities similar to that of Trasylol, only the extract from the tumour had significant trypsin-inhibitory activity as expressed by the inhibition of the hydrolysis of TAME (p-tosyl-L-arginine methyl ester). Molecular sieve chromatography by high performance liquid chromatography of the final concentrate of the tumour indicated that the activity was present in three peaks having apparent molecular weights of less than 17,000.

Adult↗

Ultrastructural immunohistochemical localization of anti-invasion factor (AIF) in bovine cartilage matrix.

Rabbit antibodies prepared against bovine cartilage anti-invasion factor (AIF) were tested for their affinity toward antigenic sites in glutaraldehyde-fixed bovine hyaline cartilage matrix. Ultrastructural localization of the antigen-antibody complex was accomplished by the unlabeled antibody peroxidase-antiperoxidase staining technique. Unextracted and salt-extracted (1 M NaCl or 3 M GuHCl) cartilage slices were incubated with anti-AIF antibodies at a working dilution of 1:20,000. Staining occurred in unextracted matrix distributed throughout the tissue, but with regional variation in the lacunar matrix. Significantly less stain was noted in extracted tissues. The results suggest that at least certain protein components in AIF are morphologically associated with matrix complexes in aldehyde-fixed tissue.

Angiogenesis Inhibitors↗

Morphology of osteoclasts in resorbing fetal rat bone explants: effects of PTH and AIF in vitro.

Osteoclastic bone resorption was studied using 45Ca-labeled fetal rat bones cultured in the presence of parathyroid hormone (PTH) and an anti-invasion factor (AIF) derived from bovine hyaline cartilage which is enriched in a collagenase inhibitor. The specific morphological expressions of osteoclasts cultured in PTH and AIF were observed in both light and electron microscopy and analyzed cytometrically. Stimulation of bone resorption with PTH revealed significant increases in the numbers and activity of osteoclasts, whereas bones cultured in the presence of AIF showed significant decreases in numbers of osteoclasts and altered cell features including the loss of osteoclast contact with bone surfaces. These structural modifications were evaluated with 45Ca release data derived from matched-pair explants of fetal rat bones, revealing the existence of a relationship between resorptive states of the cultured bones and morphological expressions of osteoclastic activity.

Animals↗

Ultrastructural localization of histones in epiphyseal chondrocytes.

Epiphyseal growth plate chondrocyte nuclei of growing rats were studied for histone content using the ammoniacal silver technique. This stain, which is specific for the demonstration of the arginine-rich fractions of histones, revealed that growth plate nuclei vary in their histone content. Nuclei of cells of the proliferating zone revealed a significantly greater amount of postformalin ammoniacal silver deposit consistent with the presence of arginine-rich histones.

Animals↗

25-hydroxyvitamin D: autoradiographic evidence of sites of action in epiphyseal cartilage and bone.

Tritiated 25-hydroxyvitamin D3 was administered to growing rats to morphologically documents its sites of action. Highly selective incorporation occurred in epiphyseal hypertrophic cells, epiphyseal matrix, osteoid, osteoblasts, and osteocytes of metaphyseal bone spicules. The labeled metabolite appeared in chondrocytic lacunar matrix coincident with hypertrophic cell death as evidenced by histological examination. The tritiated 25-hydroxyvitamin D3 became localized only in areas of active mineralization.

Animals↗

Calcitonin effects in primate pregnancy.

The acute effects of calcitonin (CT), a hypocalcemic hormone to act by inhibiting bone resorption, were studied in rhesus monkeys in late pregnancy. Salmon CT was injected intravenously into either mother or fetus and the concentration of total calcium and inorganic phosphorus in maternal plasma, fetal plasma, and amniotic fluid measured. Maternal CT administration produced a gradual fall in maternal plasma calcium levels and, to a lesser extent, in maternal plasma phosphorus levels. Both depth and duration of maternal hypocalcemia were related to dose. In addition, the dbree of hypocalcemic response was greater in pregnant than in nonpregnant animals at equivalent dosage levels. Hypocalcemia induced in the mother by CT injection was not reflected in fetal hypocalcemia. Fetal CT administration produced a triphasic response in fetal plasma calcium, consisting of a prompt initial drop followed by a return to or above the baselineand then a more gradual decline. Bth the initial and the secondary hypocalcemic responses in the fetus were dose-related in terms of depth and duration. These observations suggest that CT MAY BE AN IMPORTANT HORMONE IN BOTH MATERNAL AND FETAL PHYSIOLOGY.

Amniotic Fluid↗