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Biomedical subjects

W Riesen

Publications and source records attributed to W Riesen.

17 recordsLinked to original sources

[The effect of lipid level lowering diets on bile lipids and plasma lipoproteins in normal persons].

The effects of two fat-modified diets, one rich in polyunsaturated and the other in oleic acids, were studied in 10 healthy young males with regard to bile lipid composition, plasma lipids and lipoproteins. The two experimental diets were given for 2 weeks each and findings compared with those from the subject's normal diet. The fat-modified diets had marked but comparable effects on plasma total cholesterol (decreases by 23% and 16% respectively), on LDL-cholesterol (decreases by 27% and 17% respectively) and on HDL-cholesterol (decreases by 26% and 27% respectively). HDL apolipoproteins A-I and A-II were unaffected. Therefore, the apo A-I/HDL-cholesterol and apo A-II/HDL-cholesterol ratios significantly increased. The "lithogenic index" as a measure for the relationship of cholesterol to bile acids and phospholipids, and thus for the solubility of cholesterol in gallbladder bile, was not affected by the lipid lowering diets, which therefore should not increase the risk of cholelithiasis.

Adult

[Antibody treatment of digoxin intoxication in a patient with renal failure (author's transl)].

A 72-year-old man with coronary heart disease and renal failure required hospitalization because of digoxin intoxication with severe arrhythmias and generalised heart failure. The intoxication was successfully treated and sinus rhythm rapidly restored after administration of heterologous digoxin-specific F(ab')2 antibody fragments. There were no side-effects and the heart failure improved after treatment.

Aged

[The effect of diuretic therapy on serum lipoproteins: an undesirable effect?].

The effect of diuretics on serum lipids and lipoproteins was evaluated in 23 patients with essential hypertension treated with chlorthalidone for six weeks. Compared to placebo conditions, diuretic therapy significantly increased serum beta (+8%, p less than 0.05) or low-density-lipoprotein (LP) cholesterol (+17%, p less than 0.025). Since alpha-LP or high-density-LP cholesterol was unchanged or tended to decrease slightly, there was also an increase in the beta/alpha-LP (+26%, p less than 0.025) or low/high-density-LP cholesterol (21%, p less than 0.025) ratio. Serum cholesterol (+4%), triglycerides (+3%), phospholipids and the Apo-LP A-I, A-II and B were not changed significantly. Blood pressure and plasma potassium were decreased (p less than 0.01), blood volume and serum insulin were not changed significantly, and serum glucose was increased mildly. Plasma renin, aldosterone and norepinephrine levels rose significantly (p less than 0.05), while circulating epinephrine was unaltered. Alterations in LP were not related to variations in blood pressure, blood volume, plasma electrolytes or serum glucose or insulin; and they did not correlate with chlorthalidone-induced increases in plasma renin, aldosterone or norepinephrine. Treatment with certain diuretics may have an adverse influence on lipoprotein metabolism.

Adolescent

Treatment of a case of lanatoside C intoxication with digoxin-specific F(ab')2 antibody fragments.

In animal experiments arrhythmias induced by cardiac glycosides which prove fatal if untreated can be terminated by administration of glycoside-specific antibodies. Immunotherapy with digoxin-specific antibody fragments had hitherto only been employed on one occasion, namely in a person who had taken a massive overdose of digoxin with suicidal intent and who had failed to respond to symptomatic treatment. The present paper describes the use of F(ab')2 fragments of digoxin-specific antibodies in a female patient with lanatoside C intoxication to treat the associated life-threatening cardiac arrhythmia. The arrhythmia was rapidly terminated and normal sinus rhythm was restored. Treatment with the heterologous antibodies did not cause any side-effects.

Antibodies

Fluorometric determinations of the relative immunoglobulin content of plasma cells of patients with monoclonal gammopathy.

The relative cytoplasmic immunoglobulin content of fixed plasma cells taken from the bone marrow of five patients with myeloma and five patients with benign monoclonal gammopathy was determined with a microscope fluorometer. In eight of the ten piasma cell populations studied, the distribution of the fluorescence intensities was close to normal. In three of these eight populations a significant difference in the variances of the heavy and light chain fluorescence intensities was found. Variances of heavy and light chain fluorescence intensities were smaller in patients with an immunoglobulin A-type gammopathy than in those with an immunoglobulin G-type gammopathy. No difference was found if normalized relative frequency distribution patterns of heavy or light chain fluorescence intensities of patients with myeloma were compared with those of patients with benign monoclonal gammopathies.

Bence Jones Protein

The prevention and reversal of digoxin intoxication with specific antibodies.

The formation of digoxin-specific antibodies was induced in sheep by immunization with a digoxin-albumin conjugate. The efficacy of the antibodies was investigated in anesthetized cats. When the digoxin-specific antibodies were administered prophylactically as a gammaglobulin, IgG or F (ab')2 preparation, the dose of digoxin needed to induce ventricular dysrhythmia was significantly greater (p less than 0.001) for the pretreated animals than for the controls. To investigate therapeutic efficacy, the animals were digitalized with digoxin over a period of three days and were given digoxin injections on the fourth day to provoke ventricular tachycardia. Of the control animals, three died before two hours had elapsed and the arrhythmia persisted in the two remaining animals. By contrast, a stable sinus rhythm was restored in all animals which were treated with F (ab')2 fragment of the digoxin-specific antibodies after onset of ventricular tachycardia. The doses of digoxin required to trigger renewed ventricular dysrhythmia in these animals were greater than those required at the start of the experiment. The potential clinical use of digoxin-specific antibodies is discussed in the light of these results and reports in the literature.

Animals

Inhibition of human anti-Gd cold agglutinins by sialyllactose.

Two examples of IgM kappa-monotopic cold agglutinins occurring in patients with non-Hodgkin lymphomas, reacted with erythrocyte autoantigens, which were protease-resistant but were inactivated by neuraminidase. The cold agglutinins were inhibited by the trisaccharide sialyllactose [NeuNAc(alpha,2 leads to 3) Gal (beta, 1 leads to 4)Glc], which is not related to oligosaccharides known to inhibit anti-I/-i cold agglutinins, Anti-Pr cold agglutinins are not inhibited by sialyllactose, although N-acetylneuraminic acid (NeuNAc) is an essential component not only of Gd but also of Pr determinants. Gd determinants are not bound to erythrocyte membrane glycoproteins, but are apparently bound to membrane glycolipids (gangliosides).

Agglutinins

Serological identification of the new cold agglutinin specificity anti-Gd.

The specificity anti-Gd of human cold autoagglutinins is characterized using untreated and enzyme-treated human red blood cells. Gd determinants of human RBC are resistant to proteases, but are inactivated by neuraminidase (RDE). In contrast, I/i determinants are not inactivated by proteases or RDE, while Pr1-3 determinants are inactivated by proteases and RDE, and Pra determinants are resistant to RDE, but are inactivated by proteases.

Agglutinins

Restriction of immunoglobulin heterogeneity, autoimmunity and serum protein levels in aged people.

Ninety-one sera of persons above 80 years of age were screened for autoantibody activity against lipoproteins (anti-LDL 7, anti-HDL 6 positive), for rheumatoid factor activity (Latex 14, Waaler-Rose 7 positive) and for antinuclear factors (11 positive). Among the sera with autoantibody activity 29 percent showed deviations of the normal kappa/lambda ratio of immunoglobulins, as opposed to 22 percent of the sera without detected autoantibody activity. In 3 percent of the sera an M component was detected. Determination of the alpha1-acid glycoprotein, alpha1-antitrypsin, haptoglobin, haemopexin, complement component C3c and C4, IgG, IgA and IgM levels showed significant increases in alpha-, and beta-globulins as well as in IgG and IgA in sera of the aged persons as compared to a normal population between 20 and 60 years old. No significant difference was noted between the gamma-globulin concentration in sera of aged persons with or without autoantibody activity. The evaluation of the relationship between serum protein levels and alterations of the kappa/lambda ratio indicated that the alpha- and the beta-globulins were significantly raised in sera with altered kappa/lambda ratios, whereas, with the exception of M component containing sera the gamma-globulin levels seemed not significantly affected by changes in this ratio.

Aged

[Thrombocytopenia in Waldenstrom's disease with specific antithrombocytic properties of the IgM paraprotein].

The serum of a patient suffering from thrombocytopenia associated with Waldenström's macroglobulinemia was found to contain an IgM paraprotein with unusual characteristics. Following isolation of this IgM paraprotein, dilutions up to 0.01 mg/ml caused immunofluorescence of thrombocytes from man, sheep, rabbit, and horse. In control studies with isolated IgM paraprotein from another non-thrombocytopenic patient with Waldenström's disease, positive immunofluorescence could be elicited only when a 1000-fold greater concentration of the paraprotein was used. The IgM paraprotein from our thrombocytopenic patient and that from the control patient showed comparable differences in immunofluorescence of thrombocytes and megacaryocytes when bone marrow smears were used for incubation. Further studies following papain cleavage of the IgM paraprotein with antithrombocytic activity showed that the combining activity was located in the Fab fragment. This observation characterizes the IgM paraprotein from our patient as an antibody directed to a substance in human and animal thrombocytes. Paraproteins with antibody-like activity for thrombocytes have not been identified previously; the present observation suggests that this mechanism should be considered a possible cause of thrombocytopenia associated with macroglobulinemia.

Blood Platelets

An IgM Waldenström with specificity against phosphorylcholine.

Anti-phosphorylcholine specificity has recently been shown to occur with relatively high incidence among IgA myeloma proteins secreted by oil-induced plasma cell tumors in the BALB/c strain of mice. A similar screening of human myeloma sera indicates that in man activity for phosphorylcholine is very rare. Among 904 human sera containing IgG, IgA, and IgM M-components only one reacted with phosphorylcholine-containing antigens. This serum was obtained from a patient with macroglobulinemia Waldenström. The active homogeneous protein could be isolated by affinity chromatography using a Sepharose-phosphorylcholine immunoadsorbent. It was an IgM immunoglobulin; the light chains were of the kappa type. The association constant for the reaction with phosphorylcholine was homogeneous and equalled 6.4 times 10-4 l. mol-1 at 25 degrees and 8.1 times 10-4 l. mol-1 at 2 degrees, indicating that the binding reaction is exothermic. The valences of the pentamer IgM, the 7S IgM subunit produced by reduction with cysteine, and the Fab fragment obtained by cleavage with papain were 10, 2, and 1, respectively. By all criteria available for antibody-like binding such as high specificity, restriction of the binding sites to the Fab part of the molecule and correct stoichiometry this IgM exhibits the fundamental characteristics associated with conventionally induced antibodies.

Aged

Autoantibodies with antilipoprotein specificity and hypolipoproteinemia in patients with cancer.

Sera from 151 patients with a variety of cancers were screened for antibody-like activity against lipoproteins. Eighteen % of the sera exhibited activity against autologous and homologous high-density lipoproteins and 3% exhibited activity autologous and homologous low-density lipoprotiens. Antibody-like binding was proven by its restriction to the Fab fragment of IgG. The reactive part of the lipoprotein molecule was shown to be the appoprotein. Quantiation of the serum lipoproteins indicated that thehigh-density lipoprotien concentration in the sera of cancer patients was significantly lower (psmaller than 0.01) when antibody was present. These observation suggest that autoimmune mechanisms may be responsible for the decreased high-density lipoprotein serum levels in some patients with cancer.

Antigen-Antibody Reactions

The relationship between hypervariable regions, antigen-binding specificity and the three-dimensional structure of antibodies.

The amino acid sequences of the V domains (VL + VH regions) of 3 antibodies raised to type III pneumococcal polysaccharide in individual outbred rabbits are reported. With the exception of the second hypervariable section of the L chains, these antibodies have very different sequences in the hypervariable segments of the V domains. Within the third hypervariable region of the H chain, each antibody has a different length. On the sole basis of the amino acid sequences of these three anti-pneumococcal antibodies, the results do not support the concept of a simple correlation between primary structure in the hypervariable sections (known to determine the shape of the combining site) and antigen-binding specificity. In view of the large number of amino acid interchanges in the hypervariable positions and because of the size difference between the rabbit H chains, it is likely that each anti-SIII H chain studied here represents the product of a different structural germ line gene. In contrast to such a complex immune response to a relatively simple polysaccharide antigen, an extensive structural uniformity has been observed in the heavy chains of mouse myeloma proteins with phosphorylcholine activity and a mu chain from a human Waldenström IgM endowed with the same activity. The finding of a very similar heavy chain variable region in two different species which are separated by about 75 million years in evolution favours the concept of stable transmission of variable region genes throughout evolution.

Amino Acid Sequence