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Biomedical subjects

C Mulder

Publications and source records attributed to C Mulder.

At least 37 records · Page 2Linked to original sources

Dose-response effects of fish-oil supplementation in healthy volunteers.

We performed a randomized, controlled study on the dose-response effects of daily supplementation of 1.5, 3, and 6 g of the marine fatty acids eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) as their ethyl esters for 12 wk in 45 healthy normotriglyceridemic male volunteers. Significant dose-related increases of the n-3 fatty acids 20:5, 22:5, and 22:6 in plasma phospholipids (p less than 0.0001) were found, corresponding roughly to decreases of the n-6 fatty acids 18:2 and 20:4 (p less than 0.001). Serum triglycerides and HDL3-cholesterol concentrations showed a dose-dependent reduction (p less than 0.05) and HDL2 cholesterol increased (p less than 0.05). Results for 3 and 6 g n-3 fatty acids were similar. No dose-dependent effects were observed in the VLDL-, LDL-, and total HDL-cholesterol subfractions; blood pressure; bleeding time; erythrocyte deformability; or capacity of polymorphonuclear leukocytes to kill Staphylococcus aureus. This study indicates that 3 g n-3 ethyl ester fatty acids appears to be the appropriate supplementation dose in humans, at least regarding lipid-profile changes and the ability to incorporate such fatty acids in the plasma phospholipids.

Adult

Linoleic-acid-enriched diet: long-term effects on serum lipoprotein and apolipoprotein concentrations and insulin sensitivity in noninsulin-dependent diabetic patients.

Long-term (30 wk) effects on serum lipoproteins and insulin sensitivity of two diets, one with a low polyunsaturated to saturated fat ratio (P:S 0.3) and one with a P:S of 1.0, were compared in 14 patients with noninsulin-dependent diabetes mellitus (NIDDM) in a crossover study. Total and LDL-cholesterol levels declined by 7.6% (p less than 0.01) and 9.8% (p less than 0.01), respectively, during the high P:S diet. VLDL-, HDL2-, and HDL3-cholesterol; triacylglycerol; and apolipoprotein A1, A2, and B levels were not affected by the change in P:S. Despite a modest increase of insulin-mediated glucose disposal at physiologic insulinemia during the high P:S diet, no influence was seen on glycemic control, and on blood glucose, plasma insulin, and C peptide responses to mixed meals. In conclusion, a linoleic-enriched diet in patients with NIDD causes a less atherogenic lipoprotein profile but does not influence glycemic control and carbohydrate tolerance.

Adult

Characterization of HIV-1 neutralization escape mutants.

Infection by molecularly cloned HIV-1, in the presence of a high-titre neutralizing monoclonal antibody (MAb), resulted in the selection of plaques in MT4 cells releasing HIV resistant to neutralization by the same MAb. The epitope recognized by the MAb was mapped to the V3 neutralization epitope at amino acids 305-321. The HIV-1 variants showed a reduced binding capacity for the selecting MAb as determined by immunofluorescence. Polymerase chain reaction (PCR) amplification of complementary DNA derived from viral RNA, cloning and sequencing identified a base pair (bp) change C----G at position 6663 in variant 110.5/1, predicting a change at amino acid 308 Arg----Gly. No other changes in the epitope were observed by sequencing three other variants. Differential hybridization of PCR amplified viral RNA and DNA, with oligonucleotides specific for the observed bp change or the 'wild type' sequence, indicated that the variants 110.5/1 and 110.5/7 were genotypically mixed for 308Gly/Arg. Subsequent screening of biologically 'recloned' variants 110.5/1 and 110.5/7 identified two subclones homozygous for the 308Gly change. The Arg----Gly change appears to affect the binding of the antibody to the epitope, since the linear peptide substituting 308Gly for 'wild type' 308Arg was 100 times less potent in blocking the neutralization of parental HIV. Amino-acid residue 308 thus appears to be crucial for antibody binding to the epitope. In addition, mutations distant from the monoclonal antibody binding site may also affect neutralization by antibodies recognizing the V3 loop.

Amino Acid Sequence

Evaluation of human and simian immunodeficiency virus plaque and neutralization assays.

A number of CD4+ T cell lines were compared for their ability to act as target cells for human immunodeficiency virus (HIV) infection in syncytium- and plaque-forming assays. MT-4 and C8166 cells were the most sensitive indicator cells for HIV- and simian immunodeficiency virus (SIV)-induced cytopathic effects, and gave rise to macroscopic (MT-4) and microscopic (C8166) plaques. The MT-4 plaque assay was evaluated for the measurement of HIV- and SIV-neutralizing antibodies.

Animals

A rapid and sensitive immunosorbent assay for urinary albumin.

We describe a fast, simple and sensitive microtiter scale competitive ELISA for the determination of urinary albumin. All reagents are commercially available. In the standard procedure, a minimum concentration of 0.8 mg albumin/L can be measured, although, applying another dilution, 0.04 mg/L can be detected. Within-batch coefficient of variation was 6.9% and 5.6% (at 1:20 and 1:50 dilution, respectively); between-batch variation was 8.6% and 5.6% respectively. The influence of urine pH and other urine components is minimised in the assay diluting with a casein-containing buffer.

Albuminuria

Epstein-Barr virus-positive and -negative B-cell lines can be infected with human immunodeficiency virus types 1 and 2.

Human immunodeficiency virus type 1 (HIV-1) can infect CD4+ lymphocytes, monocytes-macrophages, and various other cell lines, including B-cell lines. To study the parameters of B-cell infections, we examined the susceptibility of 24 B-lymphoid cell lines to both HIV-1 and HIV-2 infections. These cell lines included a series of Epstein-Barr virus (EBV) genome-negative Burkitt's lymphoma cell lines and their EBV-converted counterparts. To infect these cells we used two HIV-1 isolates and one HIV-2 isolate. Infections were monitored with a cytoplasmic RNA dot-blot and a syncytium assay. HIV infection was also studied by a novel method based on electrophoresis of DNA liberated from cells that were lysed in situ in the well of an agarose gel. All human B-cell lines could be infected with HIV-1, regardless of the presence of EBV genomes; thus, EBV infection had no major effect on HIV susceptibility of B-cell lines. Integrated proviral HIV genomes could be detected by Southern blot analysis of DNA extracted from long-term, non-HIV-producing B-cell lines. This study suggests that B-lymphoid cells may serve as reservoirs for latent or persistent HIV infections in vivo, even in the absence of EBV infection.

B-Lymphocytes

Effects of protein intake variation and omega-3 polyunsaturated fatty acids on renal function in chronic renal disease.

Fifteen patients with chronic renal disease of various origin were investigated after 4 weeks protein restriction, after 4 weeks high protein intake and finally, after 8 weeks dietary supplementation with omega-3 polyunsaturated fatty acids (PUFA's), while adhering to a high protein intake. The highest values for effective renal plasma flow and glomerular filtration rate were observed after 8 weeks dietary supplementation with omega-3 PUFA's without a relationship with baseline values. Calculated renal resistance fell after omega-3 PUFA supplementation. Whether long term dietary supplementation with omega-3 PUFA's will influence the progression of chronic renal insufficiency in man needs further study.

Adult

Virus-associated hemophagocytic syndrome: identification of an immunoproliferative precursor lesion.

Virus-associated hemophagocytic syndrome (VAHS) is a nonneoplastic, generalized histiocytic proliferation with marked hemophagocytosis associated with a systemic viral infection. Histologic studies of lymph nodes usually show lymphoid depletion and histiocytic proliferation. In this report we describe the case of a patient with Epstein-Barr virus-associated VAHS in which initial lymph node biopsy samples showed an immunoproliferative lesion that preceded the usual generalized histiocytic proliferation. This finding suggests that some cases of VAHS may have an immunoproliferative precursor lesion.

Adult

In vitro immortalization of marmoset cells with three subgroups of herpesvirus saimiri.

Sequences within the rightmost 7 kilobases of the unique L DNA of herpesvirus saimiri are required for oncogenicity of the virus. The same DNA region has been found to be highly variable among different strains of herpesvirus saimiri. On the basis of this variability, herpesvirus saimiri strains were classified into groups A, B, and non-A, non-B. Herpesvirus saimiri strains representing the three groups were used successfully for in vitro immortalization of phytohemagglutinin-activated, interleukin 2 (IL-2)-expanded peripheral blood lymphocytes of common marmosets (Callithrix jacchus). Peripheral blood leukocytes could be immortalized from only a subset of common marmosets (5 of 13). All of the immortalized cell lines contained covalently closed circular viral DNA molecules and initially showed a low level of virus production. Cells immortalized by group A and group non-A, non-B strains did not require IL-2 in the medium. However, the only group B immortalized cell line, 473-SMHI, did not grow well in the absence of IL-2. The different characteristics of cell lines immortalized by herpesvirus saimiri strains belonging to different groups may help to elucidate some functions coded by the highly variable DNA region which is involved in the oncogenic process.

Animals

The composition of plasma lipoproteins and erythrocyte membranes in cholesterol-fed pigs with partial ileal bypass.

The composition of plasma lipoproteins and erythrocyte membranes was studied in cholesterol-fed pigs with a partial ileal bypass. Cholesterol feeding caused marked increases in the plasma concentrations of cholesterol and phospholipids. In spite of continuation of cholesterol feeding, PIB reduced plasma concentrations of cholesterol and phospholipids towards basal values. PIB completely counteracted the dietary cholesterol induced alterations in the lipid composition of the apoprotein B containing plasma lipoproteins, but not in the HDL2 fraction. It is suggested that PIB specifically influences the metabolism of the atherogenic, apoprotein B containing lipoproteins. Dietary cholesterol caused significant increases in the ratios of cholesterol:phospholipids and phosphatidylcholine: sphingomyelin in erythrocytes. The high-cholesterol diet also increased the content of linoleic acid in erythrocyte phosphatidylcholine. PIB completely nullified the cholesterol-induced increase in the cholesterol:phospholipid ratio, but not the increase in the phosphatidylcholine:sphingomyelin ratio. The percentage of linoleic acid in erythrocyte phosphatidylcholine was unaffected by PIB. Neither cholesterol feeding nor PIB had an effect on the lipid fluidity of erythrocyte membranes, as measured by fluorescence polarization, using the probe diphenylhexatriene. Possible compensatory mechanisms operating to control homeostasis of lipid fluidity of erythrocyte membranes are discussed.

Animals

Pathogenesis of B cell lymphoma in a patient with AIDS.

Lymphoma occurs at increased frequency in patients with the acquired immunodeficiency syndrome (AIDS). We studied, using serologic and molecular techniques, one such lymphoma for (a) evidence of infection with human T lymphotropic virus, type III (HTLV-III), and Epstein-Barr virus (EBV), (b) monoclonal rearrangement of immunoglobulin and T cell receptor genes, and (c) rearrangement of the c-myc oncogene. Immunoglobulin and T cell receptor gene studies demonstrated that the tumor was of monoclonal B cell origin. Similar to cases of Burkitt's lymphoma unrelated to AIDS, there were DNA sequences in the lymphoma that hybridized to EBV-specific probes and demonstrated evidence of c-myc rearrangement. HTLV-III sequences were not detected in the malignant B cells. The pathogenesis of some B cell neoplasms in patients with the syndrome may involve transformation by EBV and deregulation of oncogene expression without direct infection of the malignant B cells by HTLV-III.

Acquired Immunodeficiency Syndrome

[Corneal opacity].

A case with bilateral corneal opacification in the form of a half-ring is described. Routine laboratory tests revealed no abnormalities, and serum lipoprotein composition was normal. The authors suspect that this was a case of primary lipoidal keratopathy.

Adult

Herpesvirus sylvilagus infects both B and T lymphocytes in vivo.

Herpesvirus sylvilagus infection of cottontail rabbits (Sylvilagus floridanus) was studied as a model of herpesvirus-induced lymphoproliferative disorders. Leukocytosis, splenomegaly, proliferation of T cells and virus production by lymphocytes characterized this infectious mononucleosis-like disease. Approximately two copies of circular herpesvirus sylvilagus genomes per cell were detected in spleen cells at 2 weeks postinfection, and circular genomes could still be observed after 4 months. Circular viral genomes were found in both B and T lymphocytes. Small amounts of linear viral DNA (0.1 to 0.3 copies per cell) were also detected in both B and T cells. These results indicated that the virus did not replicate in the majority of lymphocytes in vivo. Herpesvirus sylvilagus infection in cottontail rabbits could be useful as a model for studying the complex virus-host relationships of lymphotropic herpesviruses and perhaps as an animal model for Epstein-Barr virus infection in humans.

Animals