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Biomedical subjects

S G Gordon

Publications and source records attributed to S G Gordon.

48 records · Page 3Linked to original sources

Comparison of procoagulant activities in extracts of normal and malignant human tissue.

Cancer procoagulant A (CPA) was originally described in extracts of tumor tissue, but whether this represented a quantitative and/or a qualitative difference from procoagulant activity in normal tissue extracts was not clear. Procoagulant activity was quantitated in extracts of 12 matched normal and malignant human tissue samples from the large intestine, breast, lung, and kidney. The specific activity of procoagulants in the tumor extracts was not greater than that in the extracts of normal tissue. Two enzymatic characteristics of CPA that distinguish it from tissue thromboplastin are its inhibition by diisopropylfluorophosphate (DFP) and its lack of dependence on factor VII. These specific tests were used to evaluate qualitative differences between procoagulants from normal and malignant intestinal tissues. In the paired normal and malignant tissue extracts, all tumor samples were inhibited by DFP and were active in factor VII-depleted bovine plasma (F7D-BP). In contrast, the extracts of normal tissue were insensitive to DFP and, except for one extract, were inactive in F7D-BP. Four of 9 other tumor extracts (44%) were positive for both of these tests for CPA, whereas the other 5 extracts were positive for only one of the two tests. The results suggest that extracts of normal and malignant tissues contained similar levels of procoagulant. However, malignant tissue contained a procoagulant enzymatically different from normal tissue thromboplastin. Furthermore, most of the malignant tissue extracts seemed to contain little or no thromboplastin.

Blood Coagulation Factors↗

Evidence for increased protease activity secreted from cultured fibroblasts from patients with pseudoxanthoma elasticum.

Abnormal polyanion metabolism in cultured fibroblasts from patients with pseudoxanthoma elasticum (PXE) was studied by incubating normal and PXE fibroblasts in culture medium containing 35SO4 for 96 hr and measuring differences in secreted 35SO4-labelled proteoglycans (35S-PG). PXE medium contained less high molecular weight (MW) 35S-PG and more low MW 35S-labelled molecules than normal medium. Addition of diisopropylfluorophosphate (DFP), a serine protease inhibitor, to the media after the 96 hr incubation resulted in no change in the MW distribution of 35SO4-labelled molecules in normal media. However, DFP treated PXE medium contained significantly more high MW 35S-PG than either untreated PXE medium or DFP treated normal medium. High MW 35S-PG was isolated from PXE fibroblast culture medium and incubated with serum free medium from either normal or PXE fibroblast cultures. There was significantly more degradation of this 35S-PG to low MW 35S-labelled molecules by PXE medium than by normal medium. 32P-DFP, which binds to the active site of serine proteases, was added to serum free medium from normal and PXE cultures. The specific radioactivity of PXE medium was 4 times greater than that of normal medium. These lines of evidence are consistent with the hypothesis that a biochemical defect in cultured PXE fibroblasts is the increased secretion of a serine protease that can degrade sulfated proteoglycans.

Fibroblasts↗

In vitro uptake of calcium by dermis of patients with pseudoxanthoma elasticum.

The calcification of dermal elastic fibers is a characteristic feature of affected skin from patients with pseudoxanthoma elasticum (PXE). Punch biopsies of normal skin and of affected and unaffected skin from patients with PXE were obtained to study dermal calcification in vitro. Before incubation, the calcium, magnesium, and phosphorus content of normal and PXE unaffected dermis were similar and that of PXE affected dermis was significantly higher. Dermal samples were incubated for 2 and 4 days at 37 degrees C. in a calcium phosphate buffer and the Ca and P content were measured. After 4 days of incubation, both PXE affected and unaffected dermis took up significantly more Ca and PO4 than normal dermis. Thus in vitro uptake study could clearly distinguish between normal and PXE dermis. PXE is a disease of variable expression and mild or subclinical forms are difficult to diagnose. Dermal biopsies from clinicallu normal relatives of patients with PXE were obtained and the in vitro uptake of Ca and PO4 was measured. The results show that several of these individuals had elevated uptakes of Ca and PO4 similar to the unaffected dermis of the PXE patient. The results suggest that this test may be used as a diagnostic aid in the detection of individuals with mild forms of PXE and may be a genetic marker for PXE.

Calcinosis↗

A micromethod for the quantitative analysis of calcium, magnesium, and phosphorus in human skin.

An inexpensive and simple micromethod is described for determining calcium, magnesium, and phosphorus in a 4 mm. punch biopsy of human skin. This small biopsy requires no sutures, and can be repeated frequently with minimal trauma to patients in long-term studies. Normal ranges of calcium (125 to 300 mg. per kilogram of dry defatted weight (DDW), phosphates (450 to 980 mg. per kilogram of DDW), and magnesium (75 to 112 mg. per kilogram of DDW) are similar to reported results on much larger biopsies. Skin calcium but not skin magnesium or phosphate was significantly higher in 40- to 76-year-old subjects when compared to the 20- to 39-year-old individuals. Comparison of an acid extraction method with the standard ashing procedure showed no significant differences in calcium and magnesium content, but the acid extractable phosphate was significantly lower than the total phosphorus found in the ash.

Adult↗

Studies of trans-3-methyl-2-hexenoic acid in normal and schizophrenic humans.

The report that sweat of certain schizophrenics contains the branched chain fatty acid, trans-3-methyl-2-hexenoic acid (TMHA), stimulated an investigation to evaluate the relationship between this fatty acid and schizophrenia. A sensitive and specific gas-liquid chromatography-mass spectroscopic procedure was developed for analyzing biological fluids for TMHA. Analysis of sweat samples from normal and schizophrenic subjects indicated that the sweat of both groups contains comparable quantities of this fatty acid. In addition, the fate of intravenously administered (14)C-labeled TMHA was shown to be similar in normal and schizophrenic subjects. It is concluded that there is no relationship between TMHA and schizophrenia.

Caproates↗

Acetyl CoA carboxylase: the purified transcarboxylase component.

Acetyl CoA carboxylase of Escherichia coli has been resolved into three functionally dissimilar proteins: (1) biotin-carboxyl carrier protein (BCCP); (2) a biotin carboxylase component that catalyzes the Mn-ATP-dependent carboxylation of BCCP to form CO(2) (-)-BCCP; and (3) a transcarboxylase component that catalyzes the transfer of the carboxyl group from CO(2) (-)-BCCP to acetyl CoA to form malonyl CoA.The transcarboxylase has been purified 1700-fold. Evidence that this protein catalyzes the transcarboxylase step includes the demonstration that it (a) catalyzes the carboxylation of BCCP, (b) catalyzes the BCCP-dependent exchange between [(14)C]acetyl CoA and malonyl CoA, (c) binds labeled acetyl CoA and malonyl CoA, and (d) catalyzes the decarboxylation of CO(2) (-)-BCCP. On the basis of this evidence, it is concluded that the transcarboxylase component contains sites for the acyl CoA group and for biotin, the covalently bound prosthetic group of BCCP.

Autoradiography↗