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Biomedical subjects

D H Solomon

Publications and source records attributed to D H Solomon.

At least 109 records · Page 6Linked to original sources
PubMed1986

Use of carotid endarterectomy in five California Veterans Administration medical centers.

Although carotid endarterectomy is a controversial and frequently performed surgical procedure, little is known about the clinical appropriateness of its use in actual practice. Are the majority of procedures performed for highly accepted clinical reasons? We studied the clinical appropriateness of 107 procedures performed on 95 patients in 1981 in five Veterans Administration teaching medical centers. Standards for judging appropriate use were based on the recommendations of a multidisciplinary panel of nine physicians. Fifty-five percent of the procedures studied were judged clearly appropriate, 32% equivocal, and 13% clearly inappropriate. The rate of serious operative complications was 5.6%. These results suggest that carotid endarterectomy is overutilized within at least some segments of the Veterans Administration population.

Age Factors↗
PubMed1986

Variations in the use of medical and surgical services by the Medicare population.

We measured geographic differences in the use of medical and surgical services during 1981 by Medicare beneficiaries (age greater than or equal to 65) in 13 large areas of the United States. The average number of Medicare beneficiaries per site was 340,000. We found large and significant differences in the use of services provided by all medical and surgical specialties. Of 123 procedures studied, 67 showed at least threefold differences between sites with the highest and lowest rates of use. Use rates were not consistently high in one site, but rates for procedures used to diagnose and treat a specific disease varied together, as did alternative treatments for the same condition. These results cannot be explained by the actions of a small number of physicians. We do not know whether physicians in high-use areas performed too many procedures, whether physicians in low-use areas performed too few, or whether neither or both of these explanations are accurate. However, we do know that the differences are too large to ignore and that unless they are understood at a clinical level, uninformed policy decisions that have adverse effects on the health of the elderly may be made.

Aged↗
PubMed1986

Serum thyroid hormone binding inhibitor in nonthyroidal illnesses.

We have employed the recently developed competitive ligand binding assay (CLBA) to study thyroid hormone binding inhibitor (THBI) in ether extracts of sera of 25 patients admitted to the Medical Intensive Care Unit with a variety of nonthyroidal illnesses (NTI). THBI was detected in 60% (15/25) of patients using one sample/patient and in 88% (15/17) using multiple (two to six) samples from different days. Mortality rate and mean serum concentrations of total T4, total T3, and albumin were similar in THBI-positive and THBI-negative patients. There was a tendency for a higher frequency of low serum total T4 in THBI-positive (10/15) than in THBI-negative (3/10) patients but the difference was not statistically significant (P less than 0.1 by Chi square). However, the mean dialyzable fraction of T4 (DFT4 0.11 +/- 0.02%, n = 9 v 0.054 +/- 0.004%, n = 10) and DFT3 (0.54 +/- 0.05% v 0.40 +/- 0.032%) were both significantly (P less than 0.05) higher in THBI-positive patients than THBI-negative patients. There was a significant correlation between THBI and DFT4 (r = 0.55, P less than 0.02) or DFT3 (r = 0.54, P less than 0.02). Prior extraction of serum with ether reduced DFT4 in NTI patients with high baseline DFT4 but not in normal subjects or NTI patients with mildly abnormal baseline DFT4. Addition to a normal serum (0.1 mL) of evaporated ether extract of a pooled NTI serum (0.10- to 3.0-mL equivalent) increased DFT4 progressively from 0.025% to 0.14%. Similar extract of a pooled serum of normal subjects had little or no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

The inner ring (5-) monodeiodination of thyroxine (T4) in cerebral cortex during fetal, neonatal, and adult life.

Inner ring (-5) monodeiodination of T4 was studied by incubating T4 (approximately 0.26 mumol/L) with rat cerebral cortical homogenate (approximately 4 mg protein) in the presence of dithiothreitol (up to 400 mmol/L) and quantifying the amount of the product, rT3, by a specific radioimmunoassay. The production of rT3 was dependent on duration of incubation (up to 2 hours), amount of tissue protein (up to 8 mg), temperature (optimal at 37 degrees C) and pH (optimal, 7.0) of the incubation mixture and the concentration of DTT (maximally stimulated at 400 mmol/L). The apparent Km and Vmax of the T4-inner ring monodeiodinating activity were 36 nmol/L and 1.75 pmol/mg protein/h, respectively. The activity was inhibited by T3 and 3,5-T2, but not by 3'5'-T2, PTU, methimazole, sodium salicylate, or 8-anilino-I-naphthalene sulfonic acid. Ipodate weakly inhibited T4-to-rT3 monodeiodination. Hyperthyroidism induced by T4 (100 micrograms/d IP X 3 days), T3 (80 micrograms/d IP X 3 days) or DIMIT (45 micrograms/d IP X 3 days) significantly stimulated T4-to-rT3 conversion; DIMIT was the most potent agent. Hypothyroidism inhibited T4-to-rT3 converting activity in cerebral cortex. Fasting for three days had no appreciable effect on T4-to-rT3 conversion in cerebral cortex. Cerebral cortical T4 5-deiodinase activity in the pregnant rat at term was about 50% of that in the adult nonpregnant rat, whereas that in the fetus was about three-fold higher than that in the nonpregnant adult.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1986

Hyperthyroidism in the elderly.

It is not uncommon for thyrotoxicosis to appear in an atypical manner in older patients. The classical symptoms are often absent. The disease is frequently characterized by cardiac, gastrointestinal, neuromuscular, and neuropsychiatric symptoms. As hyperthyroidism is readily amenable to effective treatment that can improve the quality of life, the clinical suspicion of this disease is always indicated and exclusion of this diagnosis should always be pursued. Recognizing the admittedly great difficulty in making, or even suspecting, the diagnosis of hyperthyroidism in the elderly, our rule is to test for hyperthyroidism in essentially all geriatric patients presenting chronic systemic symptoms or signs. On the other hand, we do not recommend community-wide screening of persons over 60 for hyperthyroidism. Community-wide screening falls far below the break-even point in cost-benefit analysis. The most sensible detector of hyperthyroidism now widely available is the serum free T3 index (FT3I), but it may be falsely normal because of the effect of systemic illness on extrathyroidal T4-to-T3 conversion. The advent of ultrasensitive methods for TSH may change these statements considerably. It may become the single screening procedure for both hyper- and hypothyroidism.

Aged↗
PubMed1986

The role of thyroxine (T4)-binding serum proteins in oleic acid-induced increase in free T4 in nonthyroidal illnesses.

We studied the effects of various concentrations of oleic acid (0.1-3.3 mM), such as are often found in the serum of patients with nonthyroidal illness, on the dialyzable (free) fraction of T4 (DFT4) in three types of serum samples: pooled normal serum (PNS), pooled pregnancy serum (PPS), and pooled serum of hospitalized patients (PSHP). The samples were extracted with diethyl ether to remove endogenous fatty acids before being tested in the DFT4 assay. Oleic acid caused only a moderate increase in DFT4 in PNS; a significant (greater than 2 SD above control) increase (15%) was found with 2.0 mM oleic acid, and the maximal dose of oleic acid (3.3 mM) caused a 33% increase in DFT4. However, the DFT4-increasing effect of oleic acid was enhanced (increase in DFT4 of 33% caused by 0.9-1.2 mM oleic acid) when the serum tested had low (0.5 times normal) albumin and prealbumin concentrations with either normal (50% PPS) or half-normal TBG (50% PNS). The effect of oleic acid in 100% PSHP was significantly (P less than 0.005) greater than that in 100% PNS, and it was close to that in 50% PNS (increase in DFT4 with 3.3 mM oleic acid, 118% in PSHP vs. 98% in 50% PNS). Normalization of serum albumin in PSHP by adding exogenous albumin markedly reduced the DFT4-increasing effect of oleic acid; the maximal increase in DFT4 of 64% with 3.3 mM oleic acid in albumin-normalized PSHP was equalled with 1.3 mM oleic acid in unmodified PSHP. The data suggest that the serum concentrations of albumin and other T4-binding proteins are important in modulating the DFT4-increasing effect of oleic acid and that oleic acid may contribute to the reduced serum binding of T4 in nonthyroidal illness.

Dialysis↗
PubMed1986

Physician ratings of appropriate indications for six medical and surgical procedures.

We convened three panels of physicians to rate the appropriateness of a large number of indications for performing a total of six medical and surgical procedures. The panels followed a modified Delphi process. Panelists separately assigned initial ratings, then met in Santa Monica, California where they received reports showing their initial ratings and the distribution of the other panelists ratings. They discussed the indications and revised the indications lists, then individually assigned final ratings. There was generally better agreement on the final ratings than on the initial ratings. Based on reasonable criteria for agreement and disagreement, and excluding one outlying procedure, the panelists agreed on ratings for 42 to 56 per cent of the indications, and disagreed on 11 to 29 per cent.

Angiography↗
PubMed1986

Triphenylethylenes: a new class of protein kinase C inhibitors.

The Ca2+- and phospholipid-dependent phosphotransferase activity of protein kinase C was inhibited by the triphenylethylene compounds clomiphene [drug concentration causing 50% inhibition (IC50) = 25 microM], 4-hydroxytamoxifen (IC50 = 25 microM), and N-desmethyltamoxifen (IC50 = 8 microM). The Ca2+- and phospholipid-independent phosphorylation of protamine sulfate, which is catalyzed by protein kinase C, was not inhibited by the triphenylethylenes, suggesting that they do not interact directly with the active site of protein kinase C. The inhibitory potency of each triphenylethylene was reduced when the phospholipid concentration was increased, providing evidence that these drugs inhibited protein kinase C by interacting with phospholipids. The potencies of the effects of the triphenylethylenes on protein kinase C in the lipid environment of intact cells were evaluated by determining their efficacies in the inhibition of [3H]phorbol 12,13-dibutyrate (PDBu) binding to mouse embryo C3H/10T1/2 cells. Micromolar concentrations of each drug inhibited [3H]PDBu binding in these cells. N-Desmethyltamoxifen, 4-hydroxytamoxifen, and tamoxifen inhibited protein kinase C with the same order of potency as that which has been reported for their inhibition of MCF-7 cell growth by Reddel et al. (1983). N-Desmethyltamoxifen and 4-hydroxytamoxifen were also more potent than tamoxifen in the inhibition of the growth of mouse embryo fibroblast C3H/10T1/2 cells. These correlations suggest that the mechanism of growth inhibition by tamoxifen and its metabolites includes interactions with protein kinase C.

Animals↗
PubMed1986

Use of a styrene-maleic anhydride copolymer as an adjuvant with testosterone-serum albumin immunogens and its application to increasing ovulation rate in the ewe.

A synthetic poly(styrene-maleic anhydride) copolymer of average molecular weight 470,000 potentiated a testosterone-binding antibody response during immunization of sheep with immunogenic testosterone-3-carboxymethyloxime-serum albumin conjugates. The copolymer had weaker immunostimulatory activity than Freund's complete adjuvant (FCA). The minimum effective dose of the copolymer was about 30 mg at which secondary but not primary immune responses could be detected by radioimmunoassay. There was a generally weak anamnestic response in immune sheep as secondary and teritary responses tended to decline promptly from peak values; tertiary antibody titres usually did not exceed secondaries. The use of the copolymer as a solution or emulsion had no apparent effect on its immunoadjuvant activity when administered intramuscularly but the soluble form was inactive when given intraperitoneally. The testosterone-binding antibody that was produced using either the copolymer or FCA had considerable sensitivity to deactivation by mercaptoethanol. The ovulation rate of a group of 20 Merino ewes following immunization with testosterone-serum albumin using the copolymer adjuvant was significantly higher than an equal group of untreated control ewes.

Animals↗
PubMed1985

N-alpha-Tosyl-L-lysine chloromethyl ketone and N-alpha-tosyl-L-phenylalanine chloromethyl ketone inhibit protein kinase C.

TLCK (N-alpha-tosyl-L-lysine chloromethyl ketone) inhibits protein kinase C whether or not the enzyme is under the regulation of Ca2+ and phospholipid. TLCK (IC50 = 1 mM) is a much more potent inhibitor of protein kinase C than TPCK (N-alpha-tosyl-L-phenylalanine chloromethyl ketone) (IC50 = 8 mM), suggesting that the lysyl moiety of TLCK may be specifically recognized by the active site of protein kinase C. These results extend the evidence that the active site of protein kinase C recognizes basic amino acids, and suggest that the active sites of protein kinase C and the cAMP-dependent protein kinase, which is also inhibited by TLCK and TPCK, are structurally related.

Amino Acid Chloromethyl Ketones↗
PubMed1985

Skin is an active site for the inner ring monodeiodination of thyroxine to 3,3',5'-triiodothyronine.

T4 (0.26 microM) was incubated in 0.1 M phosphate buffer (pH 7.4) containing 10 mM EDTA with homogenates (3-5 mg protein) of various rat tissues and up to 400 mM dithiothreitol (DTT) for 1 h at 37 C; the rT3 generated was measured by RIA of ethanol extracts of the incubation mixture. Among the various tissues of the male rat, homogenates of skin and cerebral cortex were very active in the conversion of T4 to rT3; other tissues demonstrated little or no T4 5-monodeiodinating activity (MA). The tissue content of rT3 was also greatest in these two tissues. The MA in skin increased linearly with incubation period (up to 4 h) and with increasing concentration of protein (up to 5 mg), substrate (up to 10 microM) and DTT (up to 400 mM); its optimal pH was 7.4, and optimal temperature was 37 C. Its Km and maximum velocity approximated 0.29 microM and 9.6 pmol/h X mg protein, respectively, in the presence of 400 mM DTT. There was no appreciable difference in T4 to rT3 MA of skin from different parts of the body. The MA was most abundant in microsomes and least in cytosol. The MA was unaffected by propylthiouracil (up to 25 microM), methimazole (up to 100 microM), sodium salicylate (up to 80 microM), or 8-anilino-1-naphthalene sulfonic acid (up to 75 microM). Ipodate (up to 80 microM) weakly inhibited the MA. T3 and 3,5-diiodothyronine inhibited dermal T4 to rT3 MA in a dose-dependent manner; T3 was 3-12 times more potent than 3,5-diiodothyronine on a molar basis in different experiments. Treatment of euthyroid rats with 3,5-dimethyl-3'isopropylthyronine (45 micrograms/day, ip) for 3 or 5 days significantly increased dermal T4 to rT3 MA. Similar treatment of rats with T4 (100 micrograms/day, ip) or T3 (20 or 80 micrograms/day, ip) did not change with MA appreciably. Hypothyroidism markedly inhibited the MA, and fasting inhibited it modestly. Pregnancy was associated with marked reduction in the MA of skin in the mother [0.30 +/- 0.11 (+/- SE) vs. 7.2 +/- 2.2 ng/h X mg protein; P less than 0.02] and fetus (0.67 +/- 0.075; P less than 0.025).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Evidence for an inhibitor of extrathyroidal conversion of thyroxine to 3,5,3'-triiodothyronine in sera of patients with nonthyroidal illnesses.

To determine whether an inhibitor of extrathyroidal conversion (IEC) of T4 to T3 is present in sera of patients with nonthyroidal illness (NTI), we incubated rat liver homogenate (approximately 4 mg protein) with T4 (2.5 microM) and dithiothreitol (5 mM) in the presence of evaporated diethyl ether extracts of normal or NTI sera. The T3 produced was quantified by RIA. Extracts of NTI sera caused dose-dependent inhibition in the conversion of T4 to T3. T3 produced in the presence of 20 NTI sera (1.0 mleq aliquots) was 76 +/- 5.5% (mean +/- SE; range, 18-116) that of normal sera (100 +/- 4.1% n = 10; P less than 0.01); it was more than 2 SD below the normal mean in eight patients. Inhibition of T3 production by NTI sera was correlated highly significantly with the activity of a thyroid hormone-binding inhibitor (THBI) also present in ether extracts of these sera (r = 0.82; n = 20; P less than 0.001). Since THBI may be a lipid, we studied the effect of lipids on hepatic conversion of T4 to T3. Several fatty acids were potent inhibitors of the conversion in vitro. Doses (in micromoles) causing 50% inhibition in different experiments varied between 0.2-0.52 for arachidonic acid, 0.3-0.56 for linolenic acid, 0.38-0.40 for linoleic acid, and 0.8-0.9 for oleic acid. Other lipids had less or no inhibitory activity. The inhibition of hepatic T4 5'-monodeiodination by arachidonic acid was competitive in nature (Ki, approximately 0.11 mM). Pretreatment of rat liver with phospholipase A2 for 10-60 min led to a progressive reduction in the conversion of T4 to T3. Moreover, the evaporated ether extract of phospholipase A2-treated rat liver homogenate reduced T4 to T3 conversion by untreated rat liver homogenate. There was a significant correlation between serum concentrations of free fatty acids and IEC activity in NTI sera (r = 0.74; n = 10; P less than 0.02). The various data suggest that 1) many NTI sera contain a potent IEC; 2) some fatty acids are potent IECs; 3) like THBI, IEC may be a lipid moiety; and 4) activation of tissue phospholipases may contribute importantly to reduced extrathyroidal T3 production in NTI, presumably by releasing inhibitory fatty acids that act locally first and more generally after their release into the circulation.

Adult↗
PubMed1985

Relationship between serum free fatty acids and thyroid hormone binding inhibitor in nonthyroid illnesses.

We measured the serum concentration and relative distribution of various free fatty acids (FFA) by gas/liquid chromatography in normal subjects and nonthyroid illness (NTI) patients with or without detectable serum thyroid-hormone binding inhibitor (THBI). The mean serum concentration of total FFA was 0.72 +/- 0.08 (SE) mM in eight normal subjects; it was similar (0.63 +/- 0.12) in eight THBI-negative NTI patients, but was significantly higher (3.1 +/- 1.0; P less than 0.05) in eight THBI-positive NTI patients (THBI index, 3.9 +/- 0.3 vs. 1.0 +/- 0.05 in normal subjects). Relative distribution of FFA in THBI-negative patients did not differ significantly from that in normal subjects. In THBI-positive patients, however, serum concentrations of palmitic, palmitoleic, stearic, and oleic acids were significantly above normal. Among fatty acids with appreciable THBI activity, oleic acid was most abundant in THBI-positive patients; its concentration of 1.3 +/- 0.32 mM in patients was about 6-fold higher than the corresponding normal value (0.21 +/- 0.02; P less than 0.005). The serum concentration of THBI correlated significantly with levels of both total FFA (r = 0.69; P less than 0.005) and oleic acid (r = 0.80; P less than 0.001). Addition of 0.33 mM oleic acid to THBI-negative NTI serum or 0.66 mM oleic acid to normal serum increased THBI activity to a level greater than 2 SD above the normal mean, i.e. 1.6. The various data suggest that 1) circulating FFA contribute importantly to THBI activity in sera of NTI patients; 2) oleic acid contributes more to THBI activity of NTI sera than do other FFA.

Adult↗
PubMed1985

Long term treatment of Graves' hyperthyroidism with sodium ipodate.

To investigate the long term usefulness of sodium ipodate (Oragrafin) in the management of Graves' hyperthyroidism, we studied the effects of ipodate (500 mg, orally, daily for 23-31 weeks) on serum T3, T4, rT3, and some clinical parameters in five newly diagnosed Graves' hyperthyroid patients. Mean pretreatment serum T3, T4, and rT3 concentrations were 780 ng/dl, 25.4 micrograms/dl, and 118 ng/dl, respectively. One day after the first dose of ipodate, serum T3 decreased by 62% (P less than 0.01), and it was within the normal range thereafter throughout treatment. The serum T4 concentration decreased by 20% (P = 0.09) at 24 h and by 43% (P less than 0.05) at 14 days. Subsequently, serum T4 was 41-65% lower than before treatment throughout the study; rT3 increased 24 h after the first dose of ipodate (118% above baseline; P = 0.1), remained elevated (97-109%) for 10 weeks, and then gradually decreased to the pretreatment level. A marked gain in body weight [5.1 +/- 1.1 (+/- SEM) kg] occurred in all patients. After discontinuation of ipodate, mean thyroid radioiodine (RAI) uptake values increased serially in four patients and were similar to pretreatment values: pretreatment, 74 +/- 6% (+/- SEM); after 7 days, 66 +/- 8%; after 14 days, 71 +/- 7%; after 28 days, 69 +/- 7%. The fifth patients's RAI uptake was 12-16% (vs. a pretreatment value of 48%) from 7-28 days after the end of a 31-week course of ipodate. He remained euthyroid without further treatment for the subsequent 4 months. We conclude that 1) ipodate (500 mg daily) reduces serum T4 and T3 levels as fast and as much as does the 1-g daily dose studied previously; 2) long term use (for 23-31 weeks) of ipodate for the treatment of Graves' hyperthyroidism is clinically feasible; no adverse effects occurred during or after ipodate treatment; and 3) RAI uptake returns to pretreatment levels as early as 7 days after the discontinuation of ipodate. Hence, use of ipodate does not prevent use of 131I therapy for those patients for whom it is otherwise desirable.

Adult↗
PubMed1985

Inhibition of protein kinase C by tamoxifen.

The antiestrogen drug tamoxifen inhibits rat brain protein kinase C in vitro, whether the enzyme is activated by Ca2+ and phospholipid (50% inhibitory dose, 100 microM), 12-O-tetradecanoylphorbol-13-acetate and phospholipid (50% inhibitory dose, 40 microM), or teleocidin and phospholipid. Tamoxifen does not inhibit the Ca2+- and phospholipid-independent phosphorylation of protamine sulfate by protein kinase C, indicating that the drug does not interact with the active site of the enzyme. The binding of [3H]phorbol dibutyrate to high-affinity membrane receptors of cultured mouse fibroblast cells is inhibited by tamoxifen (50% inhibitory dose, 5 microM). Our findings suggest that the growth-inhibitory and cytotoxic effects of tamoxifen, which have been observed at microM concentrations of the drug, may be in part due to its effects on protein kinase C.

Animals↗
PubMed1984

Thyromimetic effects of 3,5-dimethyl,3'-isopropyl thyronine (DIMIT) and 3,5-diethyl,3'-isopropyl thyronine (DIET) in various tissues of the rat.

We have examined the effects of treatment of the rat with 3,5-dimethyl-3'-isopropyl thyronine (DIMIT) and 3,5-diethyl-3'-isopropyl thyronine (DIET) on serum thyrotropin (TSH) concentration, heart weight, hepatic outer ring (5'-) monodeiodination of T4 to T3, cardiac outer ring monodeiodination of 3'-5'-diiodothyronine (3',5'-T2) to 3'-monoiodothyronine (3'-T1), and cerebral cortical monodeiodination of 3,5-T2 in the inner ring to 3-T1. Groups of four to seven rats were injected intraperitoneally either once a day or at eight-hour intervals for three days with saline or thyronines. Serum TSH was measured by radioimmunoassay. The various monodeiodinations were studied in homogenates of the tissues at optimal pH (7.35 for outer ring monodeiodinations and 8.0 for inner ring monodeiodination) and temperature (37 degrees C) in the presence of an excess of dithiothreitol. DIMIT was clearly active in all thyromimetic effects studied. It was about 10% as active as T4 in suppression of TSH. It stimulated hepatic monodeiodination of T4 to T3 in a similar manner to T4. DIMIT was also more comparable to T4 than to T3 in effect on heart weight and cardiac metabolism of 3',5'-T2 to 3'-T1. It was highly active, apparently more so than either T4 or T3, in cerebral cortical stimulation of metabolism of 3,5-T2 to 3-T1. In distinction to DIMIT, DIET had very little thyromimetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Inhibition of phagocytosis and chemiluminescence in human leukocytes by a lipid soluble factor in normal tissues.

Homogenates of normal rat tissues inhibited several functional parameters of normal human peripheral blood leukocytes, including luminol-dependent chemiluminescence induced by both soluble (phorbol myristate acetate) and particulate (Escherichia coli) stimuli; in vitro uptake of radiolabeled E. coli; and in vitro phagocytosis and killing of E. coli. The doses of rat tissue protein that caused a 50% inhibition of leukocyte chemiluminescence were ca. 6.2 micrograms for small intestine, 83 micrograms for kidney; 100 micrograms for heart; 132 micrograms for liver, 190 micrograms for skeletal muscle, and 307 micrograms for brain. The putative phagocytosis inhibitor (PI) in rat liver was more plentiful in particulate fractions than in the cytosol. The PI activity in the original or Miranol-solubilized rat liver homogenate was nondialyzable, and it was reduced substantially by heating at 90 degrees C for 30 min but not at 56 degrees C for 30 min. It was unaffected by aprotinin, a potent inhibitor of proteolytic activity. Treatment of tissues with trypsin did not reduce PI activity, whereas treatment with phospholipase A2 clearly increased it. The bulk (up to 88%) of PI in rat liver or small intestine could be extracted by lipid solvents, e.g., diethyl ether. Purified fatty acids were potent inhibitors of leukocyte chemiluminescence; other lipids had little or no inhibiting activity. The various data suggest that (i) normal tissues contain a potent PI and (ii) that the PI is a lipid moiety.

Blood Bactericidal Activity↗