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PubMed1988

Value of a bipolar modified inferior lead in detection of inferior myocardial ischaemia.

Only bipolar leads are normally available for ambulatory monitoring. Bipolar precordial leads are reliable for detecting left coronary artery insufficiency, but may not detect changes caused by right coronary artery insufficiency. The magnitude and polarity of ST segment changes in a bipolar modified inferior lead and in CM5 were compared with those in standard electrocardiographic leads in 10 consecutive patients with acute myocardial infarction (eight inferior and two anteroseptal). The polarity of the ST segment in the modified orthogonal y lead was the same as that in aVF in all eight patients with inferior myocardial infarction and in six the size of the ST segment shift was identical in the two leads as well. In two patients the ST segment shift was larger in the modified orthogonal y lead than in aVF. In one of the two patients with anteroseptal myocardial infarction the polarity of the ST segment shift was the same in the modified orthogonal y lead and aVF. In the other patient it was slightly different. The CM5 lead did not reliably detect inferior myocardial ischaemia. A modified orthogonal y lead is suitable for the detection of inferior myocardial ischaemia.

Ambulatory Care↗
PubMed2000

Are the modified "simple questions" a valid and reliable measure of health related quality of life after stroke? United Kingdom Collaborators in the International Stroke Trial.

OBJECTIVES: Two "simple questions" were developed as a minimalist measurement tool to assess outcome in large trials and epidemiological studies after stroke. A previous study of their validity had disclosed ambiguities in their wording. In this study, the clarity, validity, and reliability of a modified version of these simple questions were examined. The relation between patients' responses to these questions and two widely used generic measures of health related quality of life were also studied. METHODS: A hospital based stroke register cohort of 152 patients, who were all visited at home by a study nurse, was used to study validity. A cohort of 1753 patients derived from the International Stroke Trial was used to study the relation with measures of quality of life. The sensitivity, specificity, and accuracy with which responses to each question predicted the patients' outcome measured using standard instruments was assessed. The distribution of scores for the EuroQol and SF-36 was examined for patients classified as dependent, independent, and fully recovered by the combined use of the modified simple questions. RESULTS: The modified "dependency" question had excellent sensitivity (>85%), specificity (>79%), and accuracy (>82%) for identifying dependency after stroke. The "problems" question had good sensitivity (65-88%) and moderate specificity (36-72%) for the detection of problems in a broad range of domains. The combined use of the modified dependency and problems questions provided a valid, simple, and reliable overall indicator of health related quality of life after stroke. CONCLUSIONS: The modified simple questions have excellent face validity and good measurement properties for the assessment of outcome after stroke. They are particularly well suited for large epidemiological studies and randomised trials.

Humans↗
PubMed1975

Effect of modifiers on the hydrolysis of basic and neutral peptides by carboxypeptidase B1.

The initial rates of hydrolysis of Bz-Gly-Lys and Bz-Gly-Phe by carboxypeptidase B (CPB) are increased in the presence of the modifiers beta-phenylpropionic acid, cyclohexanol, Bz-Gly, and Bz-Gly-Gly. The hydrolysis of the tripeptide Bz-Gly-Gly-Phe is also activated by Bz-Gly and Bz-Gly-Gly, but none of these modifiers activate the hydrolysis of Bz-Gly-Gly-Lys, Z-Leu-Ala-Phe, or Bz-Gly-phenyllactic acid by CPB. All modifiers except cyclohexanol display inhibitory modes of binding when present in high concentration. Examination of Lineweaver-Burk plots in the presence of fixed concentrations of Bz-Gly has shown that activation of the hydrolysis of neutral and basic peptides by CPB, as reflected in the values of the extrapolated parameters, Km(app) and kcat, occurs by different mechanisms. For Bz-Gly-Gly-Phe, activation occurs because the enzyme-modifier complex has a higher affinity than the free enzyme for the substrate, whereas activation of the hydrolysis of Bz-Gly-Lys derives from an increase in the rate of breakdown of the enzyme-substrate complex to give products. Cyclohexanol differs from Bz-Gly and Bz-Gly-Gly in that it displays no inhibitory mode of binding with any of the substrates examined, activates only the hydrolysis of dipeptides by CPB, and has a greater effect on the hydrolysis of the basic dipeptide than on the neurtal dipeptide. Moreover, when Bz-Gly-Lys is the substrate, cyclohexanol activates its hydrolysis by CPB by increasing both the enzyme-substrate binding affinity and the rate of the catalytic step, an effect different from that observed when Bz-Gly is the modifier. The anomalous kinetic behavior of CPB is remarkably similar to that of carboxypeptidase A, and is a good indication that both enzymes have very similar structures in and around their respective active sites. A binding site for activator molecules down the cleft of the active site is proposed for CPB to explain the observed kinetic behavior.

Animals↗
PubMed1990

Enhanced binding of phospholipase-A2-modified low density lipoprotein by human adipocytes.

Recognition of low density lipoprotein (LDL) by human adipocytes is not dependent on the classical LDL (apoprotein B-E) receptor. To assess whether LDL phospholipids have a role in adipocyte-LDL interactions, binding studies were carried out with human LDL modified with cobra venom phospholipase A2 (PLA2) and freshly isolated adipocytes and purified adipocyte plasma membranes prepared from surgical biopsies. LDL incubated with PLA2 showed increased monoacylphospholipid content, decreased diacylphospholipid content, and increased anodic migration on agarose gel electrophoresis. LDL cholesterol, triglyceride, and protein content remained unchanged. Typically, modification of 16 and 47% of LDL phospholipids enhanced specific binding of 125I-labelled LDL to plasma membranes progressively from 3.1 micrograms LDL bound/mg membrane protein (control) to 5.8 and 28.2 micrograms LDL bound/mg membrane protein, respectively. Nonspecific binding was not altered significantly. Excess unlabelled native LDL and high density lipoprotein (HDL3) effectively inhibited binding of PLA2-modified LDL. Freshly isolated adipocytes also showed enhanced binding and uptake of PLA2-modified LDL (0.1 vs. 0.9 micrograms LDL/10(6) cells x 2 h), control vs. modified). The results demonstrate that alterations of LDL phospholipids significantly enhance LDL binding and suggest a regulatory role for phospholipids in lipoprotein-cell interaction. Furthermore, the results support the view that human adipose tissue may be involved in the metabolism of modified lipoproteins, in vivo.

Adipose Tissue↗
PubMed1998

A modified Bessel filter for amplitude demodulation of respiratory electromyograms.

We studied a device that is commonly used for amplitude demodulation of respiratory muscle electromyograms (EMG). This device contains a rectifier and a low-pass filter called a modified third-order Paynter filter. We characterized this filter and found that it has good transient characteristics that suit its task as an EMG demodulator, but it has poor high-frequency attenuation that passes interfering, higher frequency components to the output waveform. Therefore, we designed and constructed a new filter with transient characteristics that are comparable to those of the modified Paynter filter but with superior high-frequency attenuation. This new filter is a modified seventh-order Bessel filter. We also identified a simple technique to convert an existing modified Paynter filter back to an original Paynter filter. The original Paynter filter has a wider pass band than the modified Paynter filter but superior stop-band attenuation.

Electrocardiography↗
PubMed2005

Health considerations regarding horizontal transfer of microbial transgenes present in genetically modified crops.

The potential effects of horizontal gene transfer on human health are an important item in the safety assessment of genetically modified organisms. Horizontal gene transfer from genetically modified crops to gut microflora most likely occurs with transgenes of microbial origin. The characteristics of microbial transgenes other than antibiotic-resistance genes in market-approved genetically modified crops are reviewed. These characteristics include the microbial source, natural function, function in genetically modified crops, natural prevalence, geographical distribution, similarity to other microbial genes, known horizontal transfer activity, selective conditions and environments for horizontally transferred genes, and potential contribution to pathogenicity and virulence in humans and animals. The assessment of this set of data for each of the microbial genes reviewed does not give rise to health concerns. We recommend including the above-mentioned items into the premarket safety assessment of genetically modified crops carrying transgenes other than those reviewed in the present study.

Journal Article↗
PubMed1999

Modified standard pancreaticoduodenectomy for the treatment of pancreatic head cancer.

Since 1980 extended surgery has been used to treat pancreatic cancer in many institutions in Japan in the hope of achieving curative resection and a good outcome. The resection rate increased, but the final outcome was unsatisfactory, and the question of postoperative quality of life (QOL) following extended surgery has instead become the central issue. During the past 22 years (October 1976 to June 1998) 169 of the 188 patients with invasive pancreatic ductal carcinoma at Mie University Hospital were treated surgically. A standard operation was performed in the early period (October 1976 to April 1981, n = 34), an extended operation was performed in the middle period (May 1981 to March 1993, n = 100), and a modified standard operation was performed in the late period (April 1993 to June 1998, n = 35). 'Standard operation' means pancreaticoduodenectomy (PD) with D1 lymph node dissection (regional), and 'extended operation' means PD with D2-D3 lymph node dissection. Our 'modified standard operation' consists of PD with lymph node dissection limited to the anterior pancreaticoduodenal (APD), posterior pancreaticoduodenal (PPD), pyloric (PY), hepatoduodenal ligament (HDL), common hepatic artery (CH) and right half of the superior mesenteric (SM) nodes. Thus, the extent of lymph node dissection in the modified standard procedure lies between the level in the standard and extended procedure, but the PD is the same, with only slight modification in the reconstruction procedure. We consider the standard operation to be a less curative procedure and the extended operation to be a very stressful procedure and accordingly we have modified it (modified standard operation) in our recent cases out of consideration for patients' QOL. We found that postoperative QOL and survival were much better in the late period than in the early and middle periods.

Humans↗
PubMedDate not supplied

Modified Giemsa staining for rapid diagnosis of malaria infection.

OBJECTIVES: To develop and evaluate a rapid method for the diagnosis of malaria infection by microscopy of stained blood films. SUBJECTS AND METHODS: Blood specimens were collected from randomly selected confirmed malaria cases (n = 75) and suspected malaria cases (n = 175). The microscopy was done on each set of blood films stained by modified and the standard Giemsa staining methods. RESULTS: All the 75 previously diagnosed malaria cases were confirmed by the microscopy of blood films stained by both methods. Forty-nine (28%) of the 175 cases suspected for malaria infection showed malarial parasites on microscopy of blood films stained by both methods. However, due to homogeneous staining and clearer background of the blood films it was possible to determine the parasite species in 65% of the cases on microscopy of the thick films stained with the modified method compared to only 20% with the standard method. Further, the turnaround time for reporting the microscopy test result was 15-20 and 45-50 min with modified and standard staining methods, respectively. CONCLUSION: Our data showed that performance of the modified staining method in detecting malarial parasites was comparable to that of the standard staining method. Moreover, the modified staining method was rapid, easy to use, and reliable.

Animals↗
PubMed2005

Comparative study of tolerance between unmodified and high doses of chemically modified allergen vaccines of Dermatophagoides pteronyssinus.

BACKGROUND: The physiochemical modification of allergens to reduce allergenicity, while retaining immunogenicity, provides a chance for the administration of higher doses of immunotherapy, with a decreased risk of systemic reactions. OBJECTIVE: To evaluate the safety of doses of depigmented glutaraldehyde-polymerized vaccine of Dermatophagoides pteronyssinus increasing those used in normal clinical conditions in comparison with regular doses of a non-modified vaccine. MATERIALS AND METHODS: The study was double-blind, parallel and included two patient groups. Twenty-three patients were treated weekly during 9 visits for the build-up phase, followed by 2-weekly maintenance doses (a total of 11 injections per patient). Eleven patients (mean age 22 years) received immunotherapy with the standardized modified vaccine. The maximum dose used was the result of depigmenting and polymerizing 100 times the maximum dose used with the native extract. The maximum concentration used was 990 mug/ml of freeze-dried material. Twelve patients (mean age 24 years) received a standardized, unmodified allergenic extract. The maximum concentration used was 70 mug of freeze-dried material/ml, with a potency of 10 HEP(L)/ml. The tolerance was evaluated recording all the side reactions related to immunotherapy and graded following the recommendations of the European Academy of Allergology and Clinical Immunology. RESULTS: In both groups, all immediate local reactions were clinically not relevant. Patients treated with the native extract experienced 42 local immediate and 24 delayed reactions (1 of them had a diameter >10 cm), whereas patients treated with the modified extract experienced 30 local immediate and 21 delayed reactions (2 of them had a diameter >10 cm). Four systemic reactions in 2 patients, 1 immediate of grade 1 and 3 delayed of grade 2 were reported in the group treated with native extract and 1 delayed of grade 2 in the group treated with the modified preparation. CONCLUSIONS: The modified extract of D. pteronyssinus, used at concentrations which are 10 times higher than those regularly administered in clinical practice, demonstrated to be safe to treat D. pteronyssinus-sensitive patients. The majority of the local reactions (immediate and delayed) were clinically not relevant (diameter <5 cm). No systemic reactions of grade 3 or 4 were noted.

Adolescent↗
PubMed1997

Inhibitive effect of a resin-modified glass ionomer cement on remote enamel artificial caries.

Glass ionomer cements (GICs) demonstrate the inhibition of caries lesions formed immediately adjacent to the restoration. This in vitro study was conducted to evaluate the distance at which a resin-modified GIC is able to exert its cariostatic effect on artificial enamel lesions ('remote effect'). Resin-modified GIC or bis-GMA resin was applied on the cervical third of the labial surface of 10 paired halves of bovine incisors. Specimens were separately immersed for 3 weeks in lactic acid gel which was changed every other day to reduce fluoride accumulation. Artificial lesions were examined by the cross-sectional microhardness (MHN) method. Volume percent mineral, mineral loss (delta Z value) and change in mineral content (delta M) were computed for each MHN profile, performed at distances of 0.2, 0.5, 1.0, 2.0, 4.0 and 7.0 mm from the edge of the materials. delta Z values of the resin-modified GIC group were significantly lower than those of the bis-GMA control group at all remote sites (t test, p < 0.05). The delta M caused by resin-modified GIC was more pronounced within 1.0 mm from the material which suggested that the demineralization inhibition can be divided into the near effect (< 1.0 mm). In this in vitro study, resin-modified GIC provided caries resistance in bovine enamel located at a considerable distance from the margin of the material.

Animals↗
PubMed2005

Effect of surface modified liposomes on the aggregation of platelets and tumor cells.

Metastasis is still the most serious reason for the high mortality of cancer patients. It is a complex process in which platelets play a crucial role. Several attempts have been performed to inhibit the metastatic process, some of these using modified liposomes. The aggregation behaviour of human platelets and HT29 colon carcinoma cells in the presence of liposomes with a modified surface has been investigated in the present study. Liposomes (PC/CH/DMPE) were unmodified, sterically stabilized by polyethylene glycol (PEG-DSPE), or equipped with the carbohydrate ligand sialyl Lewis(X) (conjugated to PEG-DMPE or DMPE as anchor) intended to specifically compete with ligands expressed by HT29 cells. We found in vitro that an addition of surface modified liposomes to human platelets in plasma caused an up to 2.9-fold increase in platelet aggregation. In addition, when HT29 tumor cells were mixed with platelets and surface modified liposomes, the number of tumor cells found in aggregates increased significantly from 8.3 % (only tumor cells) to 30.2 %. This result was supported by fluorescence micrographs demonstrating a strong association of platelets and liposomes around the tumor cells. In addition, a clear decrease in number and a change in the distribution of metastases after intravenous injection of HT29 cells in combination with liposomes was observed in vivo. While in control mice metastases in lung, liver and in intestine were prevailing, liposomal treatment resulted in a new localization of metastases in muscles. Taking together, the ability of surface modified liposomes to enhance aggregate formation of platelets and tumor cells has been demonstrated for the first time. The capability of these vesicles to interfere with the metastatic process might have implications for the use of such liposomes for therapeutic applications.

Blood Platelets↗
PubMed1995

Generation, characterization, and histochemical application of monoclonal antibodies selectively recognizing oxidatively modified apoB-containing serum lipoproteins.

To investigate either the role oxidized LDL plays in atherosclerosis or structural changes on the surface of oxidized LDL, monoclonal antibodies (mAbs) are an important tool. After immunizing mice with Cu(2+)-oxidized LDL (oxLDL) and fusion of splenocytes, hybridoma supernatants were screened and cloned. Two mAbs, OB/04 and OB/09 (IgG and IgM), were further characterized. In solid-phase fluorescence immunoassays and Western blot analysis both mAbs reacted with oxLDL, LDL oxidized by a free radical-generating azo compound, or oxVLDL but not with native LDL, acetylated LDL, oxHDL3, azo-oxidized HDL3, or HDL3 modified with malondialdehyde (MDA). In competitive immunoassays with LDL modified by oxidized fatty acid-derived aldehydes, mAb OB/09 strongly reacted with MDA-LDL or MDA-VLDL and LDL modified with 4-hydroxyhexenal followed by 4-hydroxynonenal but not with 4-hydroxyoctenal or hepta-2,4-dienal. mAb OB/04 had a weak affinity for LDL after modification with these aldehydes except for MDA-LDL. LDL modified with arachidonic acid oxidation products (AAOPs) was also recognized by this mAb. However, albumin modified either by the aldehydes applied or by AAOPs did not react with either mAb. Thus, the data indicate that each of the mAbs recognizes a different epitope that is expressed only on apoB-containing lipoproteins upon oxidative modification. An immunostaining with mAb OB/04 was obtained in areas rich in macrophages and in connective tissue of a human atherosclerotic lesion.

Amidines↗
PubMed1995

Immunologic detection and measurement of hypochlorite-modified LDL with specific monoclonal antibodies.

Oxidation of LDL is thought to contribute to the early stages of atherogenesis. Because myeloperoxidase is present in atherosclerotic lesions and can produce the strong oxidant hypochlorous acid (HOCl), which converts LDL into its high-uptake atherogenic form in vitro, we raised polyclonal and monoclonal antibodies (MoAbs) against HOCl-modified LDL (HOCl-LDL). Characterization of the polyclonal anti-human HOCl-LDL Abs showed that they cross-reacted strongly with 4-hydroxynonenal-, malondialdehyde-, and Cu(2+)-oxidized LDL. Similarly, polyclonal and some monoclonal Abs against aldehyde- and Cu(2+)-modified LDL cross-reacted with HOCl-LDL. In contrast to the polyclonal Abs, two selected hybridoma cell line supernatants containing MoAbs raised against HOCl-LDL (MoAb-A and MoAb-B) did not cross-react with either native LDL or aldehyde- or Cu(2+)-modified LDL. MoAb-A (clone 1B10A11, subtype IgG1 kappa) recognized an epitope that appeared to be specific for HOCl-LDL and depended on the tertiary structure of the (lipo)protein, as judged by a lack of cross-reactivity with HOCl-modified human and bovine serum albumin and a loss of reactivity associated with lipoprotein denaturation. MoAb-B (clone 2D10G9, subtype IgG2b kappa), on the other hand, gave identical titration curves with HOCl-LDL and HOCl-modified albumins, suggesting that this antibody recognized epitopes that are commonly generated on proteins that have been oxidized with HOCl. Thus, MoAb-A and MoAb-B may be useful tools for the investigation of a possible role for HOCl-mediated damage to (lipo)proteins in atherosclerosis and other inflammatory diseases.

Aldehydes↗
PubMed1997

Modified LDL decreases the binding of prostaglandin E2, I2, and E1 onto monocytes in patients with peripheral vascular disease.

Recent data suggest that various eicosanoids including prostaglandins play an important regulatory role in the development of atherosclerotic lesions. Peripheral blood monocytes have been implemented in early atherogenesis because they express receptors specific for modified LDL. In this study we investigated the binding of tritium prostaglandins E2 (3H-PGE2), E1 (3H-PGE1) and I2 (3H-PGI2) onto intact peripheral monocytes isolated from 20 patients (32-71 years) with manifested ischemic peripheral vascular disease stage II according to Fontaine and compared the results with those obtained in 16 healthy volunteers (21-68 years). In control subjects, Scatchard analyses of the binding data indicated a single class of high-affinity binding sites for 3H-PGE2 (maximal binding capacity [Bmax] = 11,400 +/- 3200 sites/cell; dissociation constant [Kd] = 1.3 +/- 0.5 nmol/L) and two classes of binding sites for 3H-PGE1 (Bmax1 = 11,200 +/- 4900 sites/cell, Kd1 = 1.5 +/- 0.5 nmol/L; Bmax2 = 47,800 +/- 6100 sites/cell, Kd2 = 12.8 +/- 5.9 nmol/L) as well as for 3H-PGI2 (Bmax1 = 10,100 +/- 3700 sites/cell, Kd1 = 1.7 +/- 0.7 nmol/L; Bmax2 = 81,200 +/- 5200 sites/cell, Kd2 = 14.2 +/- 6.5 nmol/L). In the patients, an absence of the higher-affinity binding class and significantly (P < .01) fewer lower-affinity binding sites were found for each ligand (PGE2: Bmax = 6600 +/- 3600 sites/cell, Kd = 12.1 +/- 3.2 nmol/L; PGI2: Bmax = 6400 +/- 3100 sites/cell, Kd = 22.1 +/- 8.3; PGE1: Bmax = 5300 +/- 1700 sites/ cell, Kd = 20.5 +/- 7.0 nmol/L). After incubation of monocytes with modified LDL (oxidized LDL or acetylated LDL), the binding of prostaglandins was significantly (P < .01 to P < .001) decreased, whereas native VLDL, LDL, and HDL did not interfere with prostaglandin binding. Prostaglandin-induced adenosine 3'-5' cyclic monophosphate (cAMP) formation by monocytes was significantly (P < .01) lower in patients (the concentrations causing 50% elevation of basal cAMP formation [ED50] were 3.8 +/- 2.4 nmol/L for PGE2, 6.3 +/- 3.5 nmol/L for PGE1, and 5.6 +/- 4.1 nmol/L for PGI2) than in the control subjects (ED50 was 1.6 +/- 1.2 nmol/L for PGE2, 4.8 +/- 2.5 nmol/L for PGE1, and 3.1 +/- 1.4 nmol/L for PGI2). After preincubation with modified LDL, the PG-induced cAMP production by monocytes was remarkably decreased in both patients and control subjects (P < .05). Our results suggest a direct effect of modified LDL on PGE2, PGE1, and PGI2 binding onto monocytes by reducing the number of cell surface-expressed receptors available. Modified LDL also reduces the sensitivity of monocytes to prostaglandins, which results in decreased cAMP production. The complex interactions between prostaglandins and lipoproteins may play an important role during atherogenesis.

Adult↗
PubMed2001

Ldl modified by hypochlorous acid is a potent inhibitor of lecithin-cholesterol acyltransferase activity.

Modification of low density lipoprotein (LDL) by myeloperoxidase-generated HOCl has been implicated in human atherosclerosis. Incubation of LDL with HOCl generates several reactive intermediates, primarily N-chloramines, which may react with other biomolecules. In this study, we investigated the effects of HOCl-modified LDL on the activity of lecithin-cholesterol acyltransferase (LCAT), an enzyme essential for high density lipoprotein maturation and the antiatherogenic reverse cholesterol transport pathway. We exposed human LDL (0.5 mg protein/mL) to physiological concentrations of HOCl (25 to 200 micromol/L) and characterized the resulting LDL modifications to apolipoprotein B and lipids; the modified LDL was subsequently incubated with apolipoprotein B-depleted plasma (density >1.063 g/mL fraction), which contains functional LCAT. Increasing concentrations of HOCl caused various modifications to LDL, primarily, loss of lysine residues and increases in N-chloramines and electrophoretic mobility, whereas lipid hydroperoxides were only minor products. LCAT activity was extremely sensitive to HOCl-modified LDL and was reduced by 23% and 93% by LDL preincubated with 25 and 100 micromol/L HOCl, respectively. Addition of 200 micromol/L ascorbate or N-acetyl derivatives of cysteine or methionine completely prevented LCAT inactivation by LDL preincubated with </=200 micromol/L HOCl. Protecting the free thiol groups of LCAT with 5,5'-dithio-bis-(2-nitrobenzoic acid) before exposure to HOCl-modified LDL, which inhibits lipid hydroperoxide-mediated inactivation of LCAT, failed to prevent the loss of enzyme activity. Our data indicate that N-chloramines from HOCl-modified LDL mediate the loss of plasma LCAT activity and provide a novel mechanism by which myeloperoxidase-generated HOCl may promote atherogenesis.

Chloramines↗
PubMedDate not supplied

In vivo catabolism of biologically modified LDL.

Incubation of human low density lipoprotein (LDL) at 37 degrees C in the presence of human umbilical vein endothelial cells (EC) caused a time-dependent shift in the charge and density of LDL. The physical changes of the human LDL occurred parallel with an increase in its clearance from the serum and uptake in the liver when injected into rats. The serum decay of the EC-modified LDL (44 hours incubation) was 20 times faster than for control LDL. EC-modified LDL, cleared from the blood, was quantitatively recovered in the liver. Isolation of the different liver cell types (parenchymal, Kupffer, and endothelial cells) after in vivo injection of 125I-EC-modified LDL showed that approximately 30 times more radioactivity was associated with the endothelial cells than with the parenchymal cells (per milligram of cell protein). In vitro experiments indicated that EC-modified-LDL was processed by the rat liver endothelial cells via a high affinity, saturable pathway related to the pathway by which these cells processed acetyl-LDL. We concluded that, if EC-modified LDL is generated in vivo, the liver, and in particular the endothelial cells, forms the major protection system against the occurrence of atherogenic particles in the blood.

Animals↗
PubMed1976

Enzymatic properties of native and N-ethylmaleimide-modified cardiac myosin from normal and thyrotoxic rabbits.

Cardiac myosin from thyrotoxic animals (myosin-T) exhibits elevated Ca2+ -ATPase activity which is resistant to further stimulation by sulfhydryl modification. In the present study, we have compared the enzymatic properties of myosin-T with those of myosin from euthyroid rabbits (myosin-N) and the derivatives of myosin-T and myosin-N formed by blocking the most rapidly reacting class of thiols (SH1) with N-ethylmaleimide (NEM). Vmax for Ca2+ -ATPase of myosin-T was about 250% greater than myosin-N and was nearly the same as NEM-modified myosin-N. Values for the apparent Km of myosin-T and NEM-modified myosin-N were 200% greater than the value for unmodified myosin-N. Vmax and Km for K+ (EDTA)-ATPase activity of NEM-modified myosin-T and myosin-N were identical. The Ca2+ saturation, pH, and salt-dependency curves for the ATPase activity of myosin-T were parallel to the curves for myosin-N and differed from those for the NEM-modified myosins. Myosin-T exhibited an increased rate of hydrolysis of ATP, CTP, and UTP in both low (0.05m) and high (0.5m) KCl medium. NEM-modified myosin-N showed increased hydrolysis of ATP and CTP in low KCl medium and increased hydrolysis of ATP, CTP, and UTP in high KCl medium. These results support the hypothesis that the enzymatic behavior of myosin-T may be caused by an alteration in the active site near the SH, thiols. The unique enzymatic properties of myosin-T did not seem to be the result of a major change in structure. The electrophoretic pattern of light chains from myosin-T and myosin-N was the same in polyacrylamide gels containing either 8 M urea at pH 8.6 or sodium dodecyl sulfate. Also, myosin-T had a normal amino acid composition and lacked 3-methyl-histidine and hot acid-stable phosphate.

Adenosine Triphosphatases↗
PubMed1992

Three types of naturally occurring modified lipoproteins induce intracellular lipid accumulation due to lipoprotein aggregation.

Low density lipoprotein (LDL) from patients with coronary atherosclerosis and diabetes mellitus as well as in vitro desialylated LDL, glycosylated LDL, and lipoprotein (a) caused a twofold to fourfold rise in cholesteryl ester in cultured human blood monocytes and intimal smooth muscle cells isolated from normal aorta. Native LDL from healthy subjects failed to induce intracellular lipid accumulation. We have demonstrated by laser correlative photometry and gel filtration chromatography that in vivo and in vitro modified lipoproteins form aggregates under cell culture conditions. The degree of modified lipoprotein aggregation directly correlated with the ability of these lipoproteins to elevate the cholesteryl ester content of cultured cells. Modified lipoprotein aggregates isolated by gel filtration induced a threefold to fivefold elevation in cellular cholesteryl ester content. Aggregates of 125I-modified LDL were taken up and degraded fivefold to sevenfold more effectively as compared with nonaggregated lipoproteins. The uptake and degradation of 125I-labeled aggregates were strongly inhibited by unlabeled aggregates, latex beads, and cytochalasin B but not by native or acetylated LDL. These data indicate that uptake of lipoprotein aggregates occurred by phagocytosis. Obtained results suggest that modified lipoprotein aggregation may be the key condition for lipid accumulation.

Cells, Cultured↗