Cu2(+)-mediated oxidation of dialyzed plasma: effects on low and high density lipoproteins and cholesteryl ester transfer protein.

We previously reported that the expression of an epitope of apolipoprotein B (apoB), mapped to the C-terminus and defined by antibody Bsol7, increased during Cu2(+)-mediated oxidation of isolated low density lipoprotein (LDL). We describe now the properties of Bsol7 as a marker of LDL oxidation in whole plasma in relation to other effects of oxidative treatment of plasma, such as the distribution of apoA-I and cholesteryl ester transfer protein (CETP). In dialyzed plasma, no LDL oxidation was detected at Cu2+ concentrations (5 microM) sufficient for extensive oxidation of isolated LDL. At a higher Cu2+ concentration (50 microM), an increased expression of the Bsol7 epitope was observed; at 250 microM Cu2+, other evidence of LDL oxidation was found. The pattern of LDL response to Cu2+ observed in dialyzed plasma could be reproduced by adding 3% bovine serum albumin to isolated LDL. We demonstrate that the effect of albumin most likely results from its ability to bind copper ions. Incubation of plasma with increasing concentrations of Cu2+ resulted first in the disappearance of alpha 2-migrating HDL, the usual carrier of CEPT; free CETP and high molecular weight apoA-I-containing particles were also generated during oxidation. Addition of oxidized, but not native, LDL to plasma resulted in a transfer to LDL of some of the CETP initially associated with apoA-I. In conclusion, the increased immunoreactivity of the Bsol7 epitope was the most sensitive parameter of LDL oxidation, but other parameters, such as the presence of alpha 2-HDL and CETP-lipoprotein associations were even more sensitive evidence of lipoprotein oxidation.

Distribution and concentration of cholesteryl ester transfer protein in plasma of normolipemic subjects.

A MAb (TP-2) directed against human cholesteryl ester transfer protein (CETP) has been applied to the development of a competitive solid-phase RIA. Experiments with immobilized CETP have shown that upon incubation with plasma or HDL in the presence of Tween (0.05%) apo A-I (but not apo A-II) binds to CETP while TP-2 binding to CETP is concomitantly decreased. With high detergent concentration (0.5% Triton), the interference is eliminated and a specific RIA in which all plasma CETP fractions have the same affinity can be obtained. Plasma levels of CETP, apo A-I, lipids, and lipoproteins were measured in 50 normolipemic, healthy subjects of both sexes. CETP levels varied nearly fourfold with a mean value of 1.7 micrograms/ml. CETP was positively correlated only with apo A-I (r = 0.38) and HDL-triglyceride (r = 0.39). In 29 other normolipemic subjects, where several apolipoproteins were also measured, significant correlations of CETP with apo A-I (0.41), apo E (0.43), and HDL-cholesterol (0.41) were observed, but there was no significant relationship between CETP and either apo A-II, B, or D. In other experiments CETP was shown to be present mostly in HDL3 and VHDL, to display exclusively an alpha 2-electrophoretic migration, and to occur within discrete particles ranging in size from 129 to 154 kD. In conclusion, the association of CETP with apo A-I-containing lipoproteins probably explains the correlation between CETP and apo A-I levels. The relationship between CETP and apo E suggests either a common metabolism or a specific cooperative role in cholesterol ester transport for these proteins.

An immunochemical marker of low density lipoprotein oxidation.

Using monoclonal antibodies against apolipoprotein B (apoB) we studied changes in apoB immunoreactivity during copper ion-mediated oxidation of human low density lipoprotein (LDL). The radioimmunoassay experiments demonstrated the decrease of immunoreactivity of three different epitopes of apoB located in different parts of the protein; at the same time the immunoreactivity of another epitope, previously mapped to the C-terminal 20 amino acids of apoB increased markedly during the first 6 h of LDL oxidation and diminished gradually upon prolonged incubation with copper ions. The fate of LDL during oxidation was also monitored using electrophoretic techniques combined with immunodetection. These experiments showed a rapid fragmentation and disappearance of immunoreactive apoB. They also indicated that the diminishing LDL immunoreactivity detectable during oxidation is associated with apoB fragments still attached to the lipid core. The changes in apoB immunoreactivity during Cu2+ treatment of LDL are similar to those observed upon LDL aging. Therefore, it appears that the enhancement of immunoreactivity of the C-terminus of apoB is a general phenomenon associated with various kinds of oxidative modifications of LDL.

The linkage with apolipoprotein (a) in lipoprotein (a) modifies the immunochemical and functional properties of apolipoprotein B.

Lipoprotein (a) [Lp(a)] was isolated from several donors and its apolipoprotein (a) [apo(a)] dissociated by a reductive treatment, generating the apo(a)-free form of Lp(a) [Lp(a--)] that contains apolipoprotein B (apo B) as its sole protein. Using anti-apo B monoclonal antibodies, the properties of apo B in Lp(a), Lp(a--), and autologous low-density lipoprotein (LDL) were compared. Marked differences in apo B immunoreactivity were found between these lipoproteins, due to the presence of apo(a) in Lp(a). Apo(a) enhanced the expression of two epitopes in the amino-terminal part of apo B while it diminished the immunoreactivity of three other epitopes in the LDL receptor binding domain. Accordingly, the binding of the lipoproteins to the LDL receptor was also decreased in the presence of apo(a). In a different experimental system, the incubation of antibodies that react with 27 distinct epitopes distributed along the whole length of apo B sequence with plastic-bound Lp(a) and Lp(a--) failed to reveal any epitope of apo B that is sterically hindered by the presence of apo(a). Our results demonstrate that the presence of apo(a) modified the organization and function of apo B in Lp(a) particles. The data presented indicate that most likely the modification is not due to a steric hindrance but that some more profound conformational changes are involved. We suggest that the formation of the disulfide bridge between apo B and apo(a) in Lp(a) alters the system of disulfide bonds present in apo B and thereby modifies apo B structure.

5-substituted arabinofuranosyluracil nucleosides: synthesis and antiviral properties.

A number of 5-alkyl (ethyl, propyl, isopropyl, butyl) analogues of araU, their alpha-anomers and N3-isomers have been synthesized by a number of different procedures, based on the catalytic condensation of the appropriate 5-alkyl-2,4-bis-(trimethylsilyloxy)-pyrimidine with 2,3,5-tri-O-benzyl-alpha-D-arabinofuranosyl chloride. The resulting protected nucleosides were deblocked by a new procedure based on the use of BF3 X Et2O in C2H5SH. The chloromercuri derivative of araU, on reaction with allyl chloride in the presence of Li2PdCl4, gave the 5-allyl derivative, which was catalytically reduced to the corresponding 5-propyl analogue. The antiviral activities of these compounds have been evaluated. 5-Allyl-araU showed moderate specific activity (MIC 20 micrograms/ml) against herpes simplex type 1 virus in PRK cell cultures. Structure-activity relationships are discussed for the 5-alkyl deoxy- and arabino- uracil nucleoside series.

Studies on the utilization of octane by algae.

The objective of this study was to investigate the influence of various octane concentrations on a mixed culture of Scenedesmus obliquus, Chlorella vulgaris and Oscillatoria sp. and the ability of these algae to utilize octane as the sole source of organic carbon in the medium. The same investigations were carried out for a mixed culture consisting of algae and the strain Acinetobacter calcoaceticus, and for A. calcoaceticus alone. The results obtained show that all of the strains under study, both algal and bacterial, can grow even at high octane concentrations and that they are able to utilize octane.

Pyrimidine arabinofuranosyl nucleosides with 5-substituted long, branched and unsaturated chains: synthesis and antiherpes properties.

Several procedures have been applied to the preparation of 5-alkyl analogues of araU and araC via condensation of the appropriate 2,4-bis-O-(trimethylsilyl)-5-alkylpyrimidine with 2,3,5-tri-O-benzyl-alpha-D-arabinofuranosyl chloride. The resulting O'-benzylated nucleosides were deblocked with the aid of BF3 . Et2O in C2H5SH. The araC analogues were also prepared by conversions of the corresponding 5-alkyl-araU derivatives. The chloromercuri derivatives of araU and araC, were reacted with allyl chloride in the presence of Li2PdCl4. The resulting 5-allyl derivatives were catalytically reduced to the corresponding 5-propyl analogues. Catalysed condensation of 2,4-bis-O-(trimethylsilyl)-5-vinyluracil with 2,3,5-tri-O-benzyl-alpha-D-arabinosyl chloride, as well as with 1-O-acetyl-2,3,5-tri-O-benzoylarabinofuranose, was carried out under a variety of different conditions. Deblocking of the benzylated nucleosides with various reagents led invariably to addition to the vinyl substituent. In the case of benzoylated nucleosides, deblocking yielded largely the alpha-anomers. The antiherpes activities of the 5-alkyl compounds have been evaluated, as well as the susceptibility of the araC analogues to enzymatic deamination.

[Transient blindness as a complication of vertebral angiography]. / Przemijajaca slepota jako powikanie angiografii kregowej.

The authors report two cases of cortical blindness developing immediately after vertebral angiography. Visual disturbances were not associated with other symptoms art from nuchal rigidity in one patients. In both cases, cortical blindness regressed completely.

Circulating immune complexes in patients with neoplastic disorders.

A group of 100 patients with various neoplastic disorders and 25 healty subjects were studied by the 125I-Clq and 125I-mRF inhibition tests for the presence of circulating immune complexes in the sera. The presence of circulating immune complexes was detected in 32 and 23% of the 100 patients by the 125I-Clq inhibition test and 125I-mRF inhibition test, respectively. A discrepancy between the two radioimmunoassays in cancer sera may suggest a possibility of the occurrence of quantatively different types of circulating immune complexes in neoplastic disorders.

Monoclonal IgG1 immunoglobulinaemia with strictly pH dependent cryoprecipitability.

A monoclonal IgG1 lambda protein with peculiar cryoprecipitable characteristics was found in the serum of a patient with advanced multiple myeloma. The cryoprecipitate was observed only when the serum was exposed to the air. Further studies defined this phenomenon as being strictly pH-dependent. No antiglobulin activity (rheumatoid factor) was detected in the cryoglobulin. The isoelctric focussing of isolated cryoglobulin showed four distinct fractions around the pH 7.8 zone, which was comparable to the pH at which the cryoprecipitate began to form. Electrostatic bonds probably contribute to the mechanism involved in the formation of cryoprecipitate in this case.

Vasculitis and Sjögren's syndrome with IgA-IgG cryoglobulinemia terminating in immunoblastic sarcoma.

Generalized lymphadenopathy and other manifestations of Sjögren's syndrome developed in a 68 year old woman with a long history of systemic vasculitis and arthralgia. An unusual immunologic feature was hypogammaglobulinemia and immunoglobulin A (IgA) monoclonal immunoglobulinemia with mixed IgA-IgG cryoglobulin. At autopsy, the histopathologic findings were compatible with immunoblastic sarcoma. The monoclonal IgA protein, found in serum, pleural and pericardial fluids, showed rheumatoid factor activity. Immunocytes from the immunoblastic sarcoma were found to be the source of the monoclonal IgA protein.

[Primary malignant lymphoma of the central and peripheral nervous systems]. / Pierwotny chloniak zlosliwy osrodkowegó i obwodowego ukladu nerwowego.

The authors present a case of malignant lymphoma in a man aged 64 years. Neoplastic infiltrations mainly in the form of perivascular accumulations were limited to the central nervous system (both central and peripheral). In the histological examinations of internal organs including lymph nodes and spleen no neoplastic tissue was found.

[Use of azathioprine in the treatment of chronic form of Guillain-Barré syndrome]. / Zastosowanie azatiopryny w leczeniu przewleklej postaci zespolu Guillaina i Barrego.

After discussing the clinical problems of the chronic form of Guillain-Barré syndrome the authors describe 8 own cases, treated with azathioprine 100 mg daily. In 3 cases drug tolerance was poor and the treatment had to be stopped. Considerable improvement was achieved in 3 cases, slight in 1, and no improvement in one patient.