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Biomedical subjects

B Waxler

Publications and source records attributed to B Waxler.

11 recordsLinked to original sources
PubMed1994

Anesthetic agents modify tissue proteinase inhibitor content and tumor behavior.

Anesthetic agents may modify the tissue content of low molecular weight proteinase inhibitors (mol wt less than 50,000) and affect the colonization and proliferation of B16-F10 melanoma cells in lungs. Lungs of female mice exposed to halothane in oxygen had significantly greater low molecular weight proteinase inhibitor activity than those from unexposed female mice. The amount of activity in male mice similarly exposed did not differ from unexposed controls. Lungs of exposed female mice also had greater activity as compared with males similarly exposed. No differences occurred in identical experiments with ketamine. High-performance liquid chromatography revealed that the inhibitor in all groups of both sexes shared a major peak with a molecular weight similar to that of the trypsin inhibitor aprotinin. Female mice bearing B16-F10 melanoma cells and exposed to halothane in oxygen had significantly more small lung tumor nodules than tumor-bearing female mice injected with ketamine. However, the total number of nodules did not differ between the two groups. These observations support the hypothesis that stimulation of proteinase inhibitory activity by halothane in oxygen may be responsible for an inhibition of tumor cell proliferation, resulting in smaller tumor nodules and no effect on the incidence of colonization.

Animals↗
PubMed1990

Osteoblast low-molecular-weight proteinase inhibitor. I. Isolation and characterization of activity from osteoblastic cells and bone.

Isolated mouse calvarial cells having phenotypic characteristics of osteoblasts, mouse parietal bone segments, mouse serum, and control mouse lung fibroblasts were extracted in NaCl and ultrafiltered to recover final concentrates having nominal molecular weights between 50,000 and 1000 daltons. Final concentrates of osteoblasts and bone but not of serum or control fibroblasts were positive for the inhibition of trypsin degradation of fibrin. Osteoblast final concentrates inhibited trypsin hydrolysis of the synthetic substrate p-tosyl-L-arginine methyl ester. Osteoblast and bone final concentrates comigrated with Trasylol but were electrophoretically distinct from alpha 1-antiproteinase. Final concentrates of osteoblast and bone extracts did not inhibit tadpole collagenase using the [3H]glycine-labeled diffuse chick collagen fibril assay. High-performance liquid chromatography (HPLC) of osteoblast final concentrates after purification using immobilized trypsin affinity chromatography revealed the presence of a major peak that was positive for the inhibition of trypsin. Molecular weight determination by HPLC indicated that the inhibitor(s) range in nominal molecular weight from 4300 to 5100 daltons. The presence of low-molecular-weight serine proteinase inhibitory activity in bone suggests its participation in the regulation of bone resorption through the regulation of enzyme activation of collagenase, and possibly its role in defense against bone matrix enzymatic degradation during tumor cell invasion.

Animals↗
PubMed1985

Multicellular tumor spheroid interactions with bone cells and bone.

In vitro coculture techniques were used to study HSDM1C1 murine fibrosarcoma multicellular tumor spheroid (HSDM1C1-MTS) interactions with mouse calvarial bone cells having osteoblastic characteristics and mouse bone explants. HSDM1C1-MTS attached to confluent bone cell monolayers and their attachment rate was quantified. HSDM1C1-MTS interaction with bone cells was further demonstrated by the release of 3H-deoxyuridine from prelabeled bone cells during coculture with multicellular tumor spheroids. HSDM1C1-MTS-induced cytotoxicity was mimicked by the addition of 10(-5) M prostaglandin E2 (PGE2) to 3H-deoxyuridine-labeled bone cells. The effects of low (10(-9) M) and high (10(-5) M) concentrations of PGE2 on bone cell proliferation were also studied. Higher concentrations of PGE2 inhibited bone cell proliferation. HSDM1C1-MTS resorbed living explants in the presence of indomethacin, suggesting that other tumor cell products may also participate in bone resorption. HSDM1C1-MTS caused direct bone resorption as measured by the significantly elevated release of 45Ca from prelabeled, devitalized calvaria. However, the growth of a confluent bone cell layer on devitalized, 45Ca-prelabeled calvaria resulted in a significant reduction in the amount of 45Ca released subsequent to the seeding of HSDM1C1-MTS onto the explants. Bone cells at the bone surface may act as a barrier against invasion and tumor cell-mediated bone resorption. Violation of this cellular barrier is achieved, in part, by tumor cell products.

Animals↗
PubMed1984

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↗
PubMed1983

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↗
PubMed1983

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↗
PubMed1982

The resistance of epithelia to vascularization: proteinase and endothelial cell growth inhibitory activities in urinary bladder epithelium.

The avascularity of epithelia may be attributed to the presence of an extractable, low-molecular-weight factor. This factor contains potent inhibitors of proteolytic enzymes, as well as a growth inhibitory activity directed against endothelial cells in vitro. It is extracted from the epithelium of bovine urinary bladders by 1 M NaCl. The extract is ultrafiltered through an Amicon XM-50 membrane, then concentrated and dialyzed into a 0.9% NaCl solution, using a UM-2 membrane. This ultrafiltrate, called the UM-2 retentate (UM-2R), contains approximately 6 micrograms protein/g tissue. The UM-2R has a low content of uronic acid and is practically devoid of hydroxyproline. SDS-PAGE reveals that the UM-2R consists of six major proteins. The UM-2R contains a Trasylol-like proteinase inhibitor that expresses strong trypsin inhibitory activity. Comparisons between bladder and serum UM-2Rs and electrophoretic mobility assays indicate that this proteinase inhibitory activity is derived from the bladder epithelium and not from the serum. The UM-2R is cytotoxic to cultured endothelial cells. Cultures of other cell types (normal and neoplastic) are not affected. The bladder-derived proteinase and endothelial cell growth inhibitory activities may protect epithelia from vascular invasion.

Animals↗
PubMed1979

Electrophoresis of tissue glycosaminoglycans as an aid in the diagnosis of mesotheliomas.

The histologic distinction between mesotheliomas and adenocarcinomas on mesothelial surfaces is sometimes difficult. High concentrations of hyaluronic acid in pleural and peritoneal fluids of mesothelioma patients have been reported. This paper describes results of glycosaminoglycan electrophoresis of papain digests of 7 mesotheliomas and 27 other tumors. Either all or almost all demonstrable glycosaminoglycans in mesotherliomas was hyaluronic acid. Control tissues had variable electrophoretic patterns showing other glycosaminoglycans in addition to hyaluronic acid. In the clinical context of differentiating mesotheliomas and adenocarcinomas in tissue samples, this technique seems simple, economical, and relatively specific.

Adenocarcinoma↗
PubMed1979

Cell stroma interactions in aortic endothelial cell cultures.

The behavior of bovine aortic endothelial cell cultures indicates that they interact with the extracellular materials they produce. In nonconfluent cultures the basal part of the cell is oriented on the plastic of the culture dish with the apex facing the culture medium. At confluence, fibrillar and ruthenium red-stained material, partly proteoglycan in nature, appears beneath the cells. In older cultures, a second layer of endothelial cells grows beneath the original one next to the plastic. This layer is oriented differently, being inverted in that the apex of the cells points to the plastic and the base toward secreted extracellular materials. Because of this orientation, cells tend to peel off the dish. The morphologic sequences thus suggest that polarity of endothelial cells in culture depends on its environment, with a hierarchy of polarity. In the absence of matrix materials, orientation is determined by the plastic. When extracellular materials form, endothelial cells then orient on them. Thus, the cells appear to manufacture and secrete the molecules on which their topography depends. Smooth muscle cells from the same bovine aortas do not seem to have this polarity. Glycosaminoglycans synthesized by the two cell types also differ.

Animals↗