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Biomedical subjects

J W Mulder

Publications and source records attributed to J W Mulder.

At least 91 records · Page 5Linked to original sources
PubMed1997

HIV-1 RNA levels in the cerebrospinal fluid may increase owing to damage to the blood-brain barrier.

Human immunodeficiency virus type 1 (HIV-1) RNA can be detected in the cerebrospinal fluid (CSF) of 75-90% of all HIV-infected patients. However, it is not yet known which factors influence the amount of HIV-1 in the CSF, either qualitatively or quantitatively. We have analysed HIV-1 RNA in CSF samples from 24 HIV-infected patients using zidovudine who underwent lumbar puncture in order to establish a diagnosis for a neurological disorder. Several factors were examined for possible correlation with the amount of HIV-1 RNA in the CSF: age, gender, the medical indication for lumbar puncture, the most recent CD4 cell count in blood, zidovudine dose, duration of treatment with zidovudine, the zidovudine concentration in plasma and CSF, and the total protein concentration in plasma and CSF. The only statistically significant factor was the total protein level in the CSF, which showed a positive relation with the amount of HIV-1 RNA in the CSF. This study indicates that increased levels of HIV-1 RNA in the CSF of neurologically symptomatic patients are the result of damage to the blood-brain barrier.

AIDS Dementia Complex↗
PubMed1996

Potential false-positive results with antigen enhancement for immunohistochemistry of the p53 gene product in colorectal neoplasms.

Immunohistochemistry (IHC) for intranuclear p53 gene product is a simple, routine alternative to molecular genetic analysis of the p53 gene. Several methods for antigen enhancement are currently in use for IHC. This study evaluates the effect of extreme antigen enhancement for p53, using a monoclonal antibody (DO7) and a polyclonal antibody (CM1). The cases studied were five colorectal carcinomas, two specimens of normal colorectal mucosa, and four colorectal carcinomas with genetic alterations which are expected to preclude p53 gene product expression, namely mutation to a STOP codon in the p53 gene detected by denaturing gradient gel electrophoresis with subsequent sequencing and allelic loss of 17p in the region where p53 is located, detected by restriction fragment length polymorphism analysis. The findings suggest that extreme antigen enhancement may cause false-positive results with a distinct nuclear staining pattern when MAb DO7 is used as a primary antibody. It is concluded that all antigen enhancement methods should be thoroughly tested to evaluate their validity and that there may be a limit to the extent to which antigen enhancement can be applied in IHC for p53 protein.

Antibodies, Monoclonal↗
PubMed1996

Clinical and pathological associations with p53 tumour-suppressor gene mutations and expression of p21WAF1/Cip1 in colorectal carcinoma.

Inactivation of the p53 tumour-suppressor gene is common in a wide variety of human neoplasms. In the majority of cases, single point mutations in the protein-encoding sequence of p53 lead to positive immunohistochemistry (IHC) for the p53 protein, and are accompanied by loss of the wild-type allele. Recently, the WAF1/Cip1 gene was identified as one of the genes induced by wild-type p53, and increased expression of p21WAF1/Cip1 has been found to reflect the status of the p53 tumour-suppressor pathway. We investigated the inactivation of p53 in a relatively small, but well-characterised, group of 46 colorectal carcinomas that were previously studied for allelic alterations, ras oncogene mutations and DNA aneuploidy. Alterations in p53 were identified by IHC, loss of 17p and DNA sequence analysis of exons 5-8, whereas p21WAF1/Cip1 protein expression was determined by IHC. p53 mutations were identified in 19 of the 46 tumours (41%), whereas positive IHC for p53 was found in 21 of the 46 tumours (46%). Positive IHC for p21WAF1/Cip1 was detected in 16 of 42 cases (38%). We found no relationship between p21WAF1/Cip1 staining and p53 protein expression or p53 mutational status. Inactivating mutations in the p53 gene correlated with LOH at 17p but not with LOH at 5q or 18q, Dukes' stage, tumour grade or DNA ploidy. There was a higher survival rate independent of Dukes' stage in the group with no alterations in p53 compared with those with evidence of dysfunction of p53, but the difference was not statistically significant. We conclude that inactivation of p53 and altered expression of p21WAF1/Cip1 are common in colorectal carcinoma but do not correlate with each other or with the clinical or pathological parameters investigated.

Adenocarcinoma↗
PubMed1996

Virologic and immunologic benefits of initial combination therapy with zidovudine and zalcitabine or didanosine compared with zidovudine monotherapy. Wellcome Resistance Study Collaborative Group.

A randomized controlled study was done to determine whether initial combination therapy with zidovudine and zalcitabine or zidovudine and didanosine would delay the emergence of zidovudine-resistant virus. Human immunodeficiency virus (HIV)-1-infected patients with <300 CD4 cells/mm3 and <4 weeks of prior zidovudine therapy were randomized to zidovudine, zidovudine plus zalcitabine, or zidovudine plus didanosine. Combination therapy did not delay the emergence of zidovudine-resistant virus isolates. However, combination therapy resulted in a significant increase in CD4 cells through 72 weeks compared with zidovudine monotherapy and a greater and more sustained decline in serum HIV-1 RNA. Although this trial was not designed as a clinical end-point study, patients assigned to zidovudine plus didanosine combination therapy experienced a significant delay in time to first AIDS-defining event or death compared with those assigned to zidovudine monotherapy.

Adult↗
PubMed1996

Silicone breast implant bleed and rupture: clinical diagnosis and predictive value of mammography and ultrasound.

Silicone breast implants have been used since 1962. Reliable methods to detect rupture and silicone gel bleed are needed, even more so because of increasing concern about the possible hazards of silicone. In cases in which clinical examination is not conclusive, additional radiodiagnostic evaluation may be useful in diagnosing intracapsular and extracapsular rupture of mammary prostheses. In the series presented, combined ultrasound and mammography shows a sensitivity for prosthesis rupture of 64% and a specificity of 81%. Silicone gel bleed cannot be detected by means of clinical examination or by combined mammography and ultrasound.

Adult↗
PubMed1996

Neovaginoplasty in male transsexuals: review of surgical techniques and recommendations regarding eligibility.

The surgical aim of genital reassignment surgery in male-to-female transsexuals is to create a perineogenital complex as feminine in appearance and function as possible. In this paper, we present a review of the various methods to line the neovagina in male-to-female transsexuals. These methods may be classified in five categories involving, respectively, application of nongenital skin grafts, penile skin grafts, penile skin flaps, nongenital skin flaps, and pedicled intestinal transplants. Based on this review and our extensive personal experience, we come to certain recommendations regarding the eligibility of these methods.

Female↗
PubMed1995

Soluble tumor necrosis factor receptors as surrogate markers for the assessment of zidovudine treatment in asymptomatic HIV-1 infection.

In untreated, asymptomatic human immunodeficiency virus type 1 (HIV-1) infection, elevated serum concentrations of soluble receptors for tumor necrosis factor (sTNFR) types I and II are associated with progression to AIDS. To assess the utility of sTNFRs as markers for the assessment of antiretroviral treatment, sTNFRs were sequentially determined in 47 asymptomatic HIV-1-infected men, who participated in a double-blind, randomized, placebo-controlled study. Progression to AIDS or severe AIDS-related complex occurred in six zidovudine (ZDV)- and six placebo-treated subjects. During ZDV treatment (n = 28) both types of sTNFRs declined compared with baseline and placebo, whereas they increased during placebo treatment (n = 19). A sustained decline of sTNFRs occurred only in subjects who experienced no disease progression. During the first 3 months of ZDV treatment, the hazard ratio for disease progression when sTNFR type II rose above the baseline value plus 5% was significantly increased (hazard ratio: approximately 25; 95% confidence interval: approximately 1.5-400; p < 0.03). Simultaneously determined CD4+ counts and serum neopterin levels showed a similar pattern in progressors and nonprogressors. Thus, in contrast to CD4+ counts and neopterin levels, sTNFR concentrations, especially those of the type II STNFR, appear to be valuable surrogate markers for monitoring the efficacy of ZDV treatment in asymptomatic HIV-1 infection.

AIDS-Related Complex↗
PubMed1995

Study on didanosine concentrations in cerebrospinal fluid. Implications for the treatment and prevention of AIDS dementia complex.

It has been hypothesized that didanosine has a low efficacy in the prevention and treatment of patients with the dementia complex of acquired immunodeficiency syndrome (AIDS) because "... the drug has not been detected in the cerebrospinal fluid". We investigated didanosine concentrations in cerebrospinal fluid (CSF) and plasma of four patients with AIDS who were using didanosine chronically. Didanosine levels, 4 h after the last drug administration, averaged 0.16 (+/- 0.03) mumol/l in CSF and 0.70 (+/- 0.27) mumol/l in plasma. When compared with historical data from patients using zidovudine, didanosine concentrations in CSF appeared to be approximately half (on a molar base) those of zidovudine concentrations in the CSF. Whether this difference in CSF levels is the explanation for the presumed lower efficacy of didanosine in the prevention and treatment of AIDS dementia complex remains to be proven. However, it is clear from this study, in contrast with earlier suggestions, that didanosine is able to pass the blood-CSF barrier in human immunodeficiency virus-infected individuals.

AIDS Dementia Complex↗
PubMed1995

Difference in expression of CD44 splice variants between proximal and distal adenocarcinoma of the large bowel.

To help determine whether adenocarcinomas of the proximal and distal large bowel reflect distinct entities, the expression of two splice variants of the metastasis-associated cell adhesion molecule CD44, carrying exons v5 and v6 respectively, was investigated retrospectively in fresh frozen samples of 23 proximal and 41 distal carcinomas by immunohistochemical staining with specific anti-CD44v5 monoclonal antibody VFF8 and anti-CD44v6 monoclonal antibodies VFF4 and VFF7. Tumours were staged as: Dukes A, 0; Dukes B, 27; Dukes C, 31; and Dukes 'D', six. Compared with distal tumours, proximal lesions expressed significantly more CD44v5 (96 versus 87 per cent, P = 0.02) and CD44v6 (83 versus 61 per cent, P = 0.01). CD44v5 and CD44v6 are considered markers for tumour progression and aggressive behaviour. Their high expression in proximal carcinomas seems to contrast with the general belief that these tumours show less aggressive behaviour than left-sided lesions. Further study of the biological significance of the expression of CD44 splice variants is therefore needed.

Adenocarcinoma↗
PubMed1995

Splice variants of the cell surface glycoprotein CD44 associated with metastatic tumour cells are expressed in normal tissues of humans and cynomolgus monkeys.

Certain isoforms of the CD44 glycoprotein family play an essential role in the metastatic spread of tumour cells. Protein expression of such CD44 isoforms has also been observed in a variety of human malignancies. In this study, we compared the expression of exon v5- and v6-containing CD44 isoforms in normal human and cynomolgus monkey (Macacca fasciculata) tissues. Cloning and sequencing of cynomolgus CD44 exons v5 and v6 revealed a homology of 97% and 95%, respectively, between man and monkey. Two monoclonal antibodies (MAbs) directed against an epitope encoded by human exon v5 (VFF8) and an epitope encoded by exon v6 (VFF18) were used to determine expression of CD44 isoforms in man and monkey. Immunohistochemical screening of a representative profile of normal human and cynomolgus tissues revealed that expression of exon v5- and v6-containing CD44 isoforms was almost identical in the two species. Exon v6 staining was observed only in a subset of epithelial tissues, whereas v5 staining was additionally detected on certain non-epithelial tissues. These data suggest that cynomolgus monkey could serve as a system to test the usefulness of antivariant CD44 MAbs with regard to antibody-based tumour therapy.

Alternative Splicing↗
PubMed1995

Evaluation of p53 protein expression as a marker for long-term prognosis in colorectal carcinoma.

Mutation of the p53 gene is reported to be of prognostic importance in colorectal carcinomas. Immunohistochemical staining of the accumulated p53 gene product may be a simple alternative for p53 mutation analysis. Previous studies addressing the prognostic importance of p53 expression, however, yielded contradictory results. Therefore, we evaluated the importance of p53 expression as a marker for long-term prognosis in a well-characterised study population of 109 colorectal carcinomas. After antigen retrieval with target unmasking fluid (TUF), immunostaining of p53 was performed with both monoclonal antibody DO7 and polyclonal antibody CM1. Objective quantification of the p53 signal was assessed by a computerised image analyser. p53 expression was higher in non-mucinous tumours than in mucinous tumours (p53 labelling index = 30% and 17% respectively, P = 0.05), and in metastatic tumours compared with non-metastatic tumours (p53 labelling index = 37% and 22% respectively, P = 0.05). Other histopathological features were not related to p53 expression. In multivariate analysis, Dukes' stage (P = 0.02) and histological grade (P = 0.05) stood out as independent markers for prognosis. p53 expression was not an independent marker for prognosis. At present, p53 expression is not a useful marker for long-term prognosis. Further insight into the relationship between p53 mutations and p53 expression is needed to elucidate more precisely the clinical relevance of p53 alterations.

Adult↗
PubMed1995

Expression of mutant p53 protein and CD44 variant proteins in colorectal tumorigenesis.

Colorectal tumorigenesis evolves through a series of molecular genetic changes, providing putative markers for tumour progression. This study investigated the relation between expression of the tumour suppressor gene p53 and splice variants v5 and v6 of the cell adhesion molecule CD44 by immunohistochemistry on tissue samples of early adenomas (n = 12), late adneomas (n = 12), Dukes's A and B carcinomas (n = 21), and Dukes's C and D carcinomas (n = 22) and compared these results with expression of these proteins in normal colonic mucosa (n = 17). A statistically significant trend of increasing expression was seen for both p53 (p < 0.005) and CD44 variant exon v6 (p < 0.0005) in subsequent stages of this tumour progression model. High expression of CD44 v5 was seen in most colorectal neoplasms (83%-96%), independent of stage. A statistically significant correlation was present between p53 expression and expression of variant v6 of CD44 (p < 0.01). Both p53 expression and CD44 v6 expression in adenomas increased with the degree of dysplasia (p < 0.05). The results of this study show that mutant p53 protein and variant v6 of the CD44 glycoprotein are markers of tumour progression in colorectal cancer.

Adenoma↗
PubMed1995

[Complete rehabilitation of the secondary cleft lip and palate patient].

This article presents the results of total reconstruction of the 'end stage of cleft lip and palate deformity' in fourteen patients. The deformity consisted of varying degrees of 1. midface retrusion and/or mandibular protrusion; 2 malocclusion; 3. nasal deformity; 4. lip deformity; 5. palate or alveolar fistulas and 6. nasal speech. These deformities resulted in aesthetic and functional problems. By a comprehensive approach in one session--total reconstruction--functional and aesthetic improvement was achieved in all patients.

Adult↗
PubMed1994

Colorectal cancer prognosis and expression of exon-v6-containing CD44 proteins.

CD44 variants containing v6 confer metastatic potential to rat carcinoma cell-lines. In man, CD44v6 is increasingly expressed during colorectal tumour progression. In 68 colorectal carcinoma patients, survival analysis showed that CD44v6 expression in the tumours was associated with tumour-related death. In patients who had an apparently radical resection of their primary tumour, CD44v6 expression had prognostic value independent of Dukes' stage. CD44v6 expression may reflect propensity for metastasis after apparently curative surgery, making adjuvant therapy an option in these patients.

Carrier Proteins↗