Search PubMed⌕ Search

Biomedical subjects

C Mulder

Publications and source records attributed to C Mulder.

At least 37 records · Page 2Linked to original sources

Computerised psychoeducation for patients with eating disorders.

OBJECTIVE: To assess a new computer-based method of health education for patients with bulimia and anorexia nervosa. METHOD: Fifty-four patients with DSM-III-R diagnosed eating disorders were allocated randomly to one of two groups, one receiving a computer-presented health education package called DIET, the other experiencing a placebo computer-based program. Each group contained 14 anorexia nervosa patients, four anorexic patients with bulimia and nine bulimic patients. Groups were equivalent in terms of the severity of their eating disorder as measured on the Eating Disorders inventory and their estimated premorbid intelligence according to the National Adult Reading Test. Both groups were assessed before and after intervention on a questionnaire measuring knowledge of eating disorders and a questionnaire measuring attitudes to eating-disordered behaviour. RESULTS: The DIET group members were significantly improved when compared to the placebo group in terms of both their knowledge and attitudes towards their disorder. The patients rated the DIET program as being both easy to use and helpful. CONCLUSION: The DIET program has been found to be a resource-efficient means of health education for patients with eating disorders. Further research is required to assess whether the program has therapeutic effects in terms of behavioural improvement.

Adolescent↗

Detection of occult liver metastases by measurement of biliary carcinoembryonic antigen concentrations.

OBJECTIVE: To assess whether biliary CEA concentrations can be used as early markers of occult liver metastases in patients with colorectal cancer. DESIGN: Consecutive open study. SETTING: University hospital, The Netherlands. SUBJECTS: 76 patients with a primary colorectal carcinoma (group 1) and 19 patients who had recently undergone a curative resection of a locally advanced carcinoma (group 2). INTERVENTIONS: Bile sampling by transhepatic puncture of the gallbladder. MAIN OUTCOME MEASURE: Recurrence of tumour. RESULTS: Twenty-one of the 76 patients (28%) with primary colorectal carcinoma had liver metastases; all had a raised biliary CEA concentration. Of the remaining 55 patients 39 (71%) also had raised CEA concentrations. At a median follow-up of 30 months, only seven patients had developed liver metastases, indicating a high number of false-positive results. In Group 2 7/19 patients (37%) had a CEA concentration above the cut-off point. Six of them developed recurrent tumour; 2 patients had liver metastases and 4 others had extrahepatic recurrences. None of the 12 patients with biliary CEA concentrations within the reference range has developed recurrent tumour. CONCLUSION: Biliary CEA concentrations do not predict the presence of occult liver metastases if bile samples are taken during resection of the primary tumour. If samples are taken some time afterwards, a raised CEA concentration seems to predict recurrence at an early stage, either in or outside the liver.

Adult↗

Inhibition of herpes simplex virus type 1 helicase-primase by (dichloroanilino)purines and -pyrimidines.

Herpes simplex virus type 1 (HSV1) encodes a heterotrimeric helicase-primase comprised of the products of three of the seven DNA replication-specific genes. Several dihalo-substituted derivatives of N2-phenylguanines and 2-anilinoadenines weakly inhibited the intrinsic DNA-dependent NTPase activity of the HSV1 helicase-primase, and these compounds inhibited the DNA-unwinding activity of the enzyme. The primase activity of the enzyme was strongly inhibited by 3,4- and 3,5-dichloroanilino derivatives of adenine and 2-aminopyrimidines. These compounds and nucleoside analogs of 2-(3,5-dichloroanilino)purines inhibited viral DNA synthesis in HSV1-infected HeLa cells in culture but also inhibited cellular DNA synthesis, likely as a result of inhibition of cellular primase and/or DNA polymerases.

Aniline Compounds↗

Regulation of the BZLF1 promoter of Epstein-Barr virus by second messengers in anti-immunoglobulin-treated B cells.

Initiation of the Epstein-Barr virus (EBV) lytic cycle is dependent on the transcription of the BZLF1 gene. The BZLF1 gene promoter (Zp) was activated by crosslinking of cell surface immunoglobulin (Ig) with anti-Ig antibody in B cells, even in the absence of other viral genes. We identified several anti-Ig response elements within Zp, which were originally defined as 12-O-tetradecanoylphorbol-13-acetate (TPA) response elements (ZI repeats and ZII, an AP-1-like domain). Since anti-Ig crosslinking leads to activation of protein kinase C (PKC) and an increase in intracellular calcium level, Zp was tested for the response to these cellular factors. Treatment with calcium ionophore A23187 increased Zp activity. When the calcium ionophore was used in conjunction with TPA, a PKC activator, the Zp induction was synergistically enhanced. 1-(5-Isoquinolinyl sulfonyl)-2-methylpiperazine, an inhibitor of PKC, inhibited the anti-Ig inducibility of Zp. Calmodulin antagonists, compound R24571 and trifluoperazine, blocked the Zp activation with anti-Ig. These findings suggest that Zp responds directly to changes in the activity of both PKC and calcium/calmodulin-dependent protein kinase. Requirement of tyrosine kinase activation for the anti-Ig-mediated Zp activation was also demonstrated through the use of the tyrosine kinase inhibitor herbimycin. These cellular gene regulatory molecules induced with anti-Ig may cooperatively play an important part in achieving efficient EBV activation as seen with anti-Ig treatment in B cells.

Antibodies↗

Cerebrospinal fluid ferritin levels of patients with Parkinson's disease, Alzheimer's disease, and multiple system atrophy.

Iron is believed to play a role in the pathogenesis of both Parkinson's disease (PD) and Alzheimer's disease (AD). We measured ferritin, which is considered to be the iron storage protein, in CSF of patients with PD, AD, and multiple system atrophy (MSA) as well as control subjects. We found a significant increase in CSF ferritin in AD compared with both PD and age-matched controls. No significant differences were found between PD patients with dementia (PDD) and non-demented PD patients. For non-demented PD patients a positive correlation between CSF ferritin and age was found. Our results may indicate that iron has a role in the pathophysiology of AD.

Age Distribution↗

Methodology-dependent variations in reticulocyte counts using a manual and two different flow cytometric procedures.

This paper describes a comparison between the microscopic brilliant cresyl blue and the flow cytometric thiazol orange (FACScan) and auramine O (Sysmex) methods for enumeration of reticulocytes. The mean intra-assay coefficients of variation for the microscopic, FACScan and Sysmex methods were established to be 33.9 and 5% respectively. A rather poor correlation was observed between the microscopic count and both flow cytometric methods (FACScan r = 0.61; Sysmex r = 0.57). However, the correlation between the flow cytometric methods was satisfactory (r = 0.79). Reference ranges for the reticulocyte count, corresponding with the 2.5th and 97.5th percentile, were determined for the microscopic (8-30/1000), FACScan (11-27/1000) and Sysmex (8-18/1000) methods. Sysmex R-3000 methodology definitely revealed the lowest and narrowest reference range. In conclusion, because of higher reproducibility, flow cytometric analysis of reticulocytes is an attractive alternative procedure for the microscopic enumeration method.

Flow Cytometry↗

Microtiter enzyme-linked immunosorbent assay using recombinant derived antigens versus western blot in the confirmation of presence of antibodies against the human immunodeficiency virus type 1.

A microtiter enzyme-linked immunosorbent assay using recombinant derived antigens was compared with the Western blot (Dupont) in the confirmation of the presence of antibodies against the human immunodeficiency virus type 1 (HIV-1). Of 104 sera (104 individuals) that were negative by a screening ELISA, 91 were also negative by both confirmation assays. In three sera only the microtiter assay was found to be indeterminate, and in nine other sera only Western blot. The only microtiter assay positive serum was from a male patient at risk for infection with HIV. 279 sera from 83 patients were found positive by screening. Of these, 223 sera were positive in both confirmation assays, and no serum was negative. Only one serum was indeterminate by the microtiter ELISA in contrast to 55 sera, including follow-up samples from 25 patients, most of whom had AIDS, by Western blot (Dupont criteria). However, the number of Western blot indeterminate sera decreased substantially applying less stringent criteria for interpretation. In conclusion, the microtiter ELISA performed well as a confirmation test for the presence of antibodies against HIV-1. In addition, the results demonstrate that in the microtiter assay the envelope peptide kp41 is highly discriminative in detecting anti-HIV-1 negative and anti-HIV-1 positive sera.

AIDS Serodiagnosis↗

Use of serum tumor markers in the differential diagnosis between ovarian and colorectal adenocarcinomas.

In the search for a method to facilitate the preoperative discrimination of ovarian carcinomas from colorectal carcinomas serum levels of 6 tumor markers were measured in 47 patients presenting with ovarian cancer and compared to levels found in 24 female patients with advanced, untreated colorectal cancer. The markers studied were CA 125, CA 15.3, CA 19.9, CEA and two recently developed mucin markers, CA M29 and CA M26. Levels of CA 125, CA 15.3, CEA and CA M29 showed significant differences between both groups. In predicting ovarian cancer, sensitivity was highest for CA 125 at 94% (35 U/ml cutoff level). However, the specificity of CA 125 was at 71% low. Specificity increased significantly by using a combination of a CA 125-positive score (greater than 35 U/ml) and a simultaneous negative CEA score (less than or equal to 5 ng/ml) (specificity 100%, sensitivity 81%). A CA 125/CEA serum ratio greater than 25 resulted in the highest discriminative power with a specificity of 100% and a sensitivity of 91% resulting in an overall test accuracy of 94%. It is concluded that the serum tumor markers used, especially a combination of CA 125 and CEA, are helpful in the preoperative differential diagnosis between adenocarcinomas of ovarian and colorectal origin.

Adenocarcinoma↗

Early events in Epstein-Barr virus genome expression after activation: regulation by second messengers of B cell activation.

RNA transcription from the BamHI Z and BamHI R and HindIII G regions of the Epstein-Barr virus (EBV) genome was studied after treatment of Akata cells with anti-immunoglobulin G (IgG), with second messenger agonists or antagonists to determine how latent EBV activation is regulated by B cell second messengers. Northern gel analysis demonstrated that BZLF1, BZLF1 + BRLF1, and BMLF1 + BSLF2 transcripts were induced at 2 hr and increased in concentration at 4 hr after induction with anti-IgG; transcripts from BRRF1, BaRF1, BMLF1, and BMRF1 were initiated at 4 hr; a transcript from BRRF2 appeared at 6 hr. The patterns of transcription from these genes after repeated stimulations with calcium ionophore A23187 + dioctanoylglycerol paralleled those with anti-IgG except that times of initiation were delayed by about 2 hr. Nuclear run-off assay of BZLF1 gene showed rapid increases in their transcriptions from 30 to 60 min after anti-IgG treatment. The protein kinase C antagonist, staurosporine, completely blocked the appearance of these transcripts, while 8-bromo cAMP + theophylline suppressed the transcription by about 40%. The regulation of EBV activation in Akata cells with anti-IgG or with second messenger agonists or antagonists can be explained by regulation at the level of transcription of immediate-early genes of EBV.

Alkaloids↗

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↗