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Biomedical subjects

J Vink

Publications and source records attributed to J Vink.

At least 19 recordsLinked to original sources
PubMed2001

Multiple primary melanomas.

BACKGROUND: Patients with clinically diagnosed dysplastic nevi or a family history of melanoma with or without histologically diagnosed dysplastic nevi seem to be at higher risk for the development of multiple melanomas. OBJECTIVE: Our purpose was to determine which factors increased the risk for the development of subsequent melanomas. METHODS: This was a retrospective study in 56 patients with 157 melanomas. RESULTS: Early age at onset (58.9%), clinically diagnosed dysplastic nevi (82.0%), a histologically diagnosed dysplastic nevus (64%), family history of clinically diagnosed dysplastic nevi (70.8%) or melanoma (64.7%) and a histologically diagnosed dysplastic nevus in combination with a family history of melanoma (48%) were found in a high percentage of patients. The mean age at diagnosis was 38.2 years. The mean interval between the first and second melanoma was 34.3 months. Of the second melanomas, 76.8% developed in a different anatomic region from the first melanomas. The mean tumor thickness (Breslow) decreased from 1.11 mm for the first melanomas to 0.90 mm for the second melanomas. CONCLUSION: The results suggest that genetic factors might be involved in a certain subset of patients in whom melanomas develop early and successively.

Adolescent↗
PubMed1998

Effect of topical tretinoin under occlusion on atypical naevi.

Atypical naevi are potential precursors of melanoma and markers of increased melanoma risk. To examine the possibility of chemoprevention of melanoma by retinoids, we studied the effect of topical tretinoin 0.1% (all-transretinoic acid; vitamin A acid) and tretinoin 0.1% with hydrocortisone on atypical naevi. Thirty patients with atypical naevi were enrolled in a prospective randomized double blind study. For each patient three comparable naevi were selected and randomized to receive tretinoin 0.1% (T), tretinoin 0.1% with hydrocortisone 1% (C) or a placebo cream (P) once a week under Actiderm occlusion for 4 months. Baseline views of the naevi, taken with a videomicroscope (magnification 20 x), were assessed for morphological changes compared with views taken 2 months after the beginning of treatment, 1 week after completion of treatment and 6 months later. After completion of the study all naevi in the T and C groups and six naevi in the P group were removed and evaluated histologically for the presence of atypia. The number of naevi that had changed in colour or size was significantly higher in the T and C groups compared with the placebo group. A size reduction took place in 42.9% (T) and 40.0% (C) of the naevi and the colour changed in 75.0% (T) and 66.7% (C). The effect of treatment, in general subtle, did not differ significantly between groups T and C, but naevi treated with C became significantly less irritated. Histologically, 75.0% of the naevi treated with T and 69.6% of the naevi treated with C were atypical. Therefore, no major change was seen in the clinical aspect of atypical naevi after treatment with tretinoin 0.1% or tretinoin with hydrocortisone 1%, and most of the treated naevi still met the histological criteria for atypia after the treatment period. The current management of follow-up of atypical naevi and excision when change to melanoma is suspected is therefore still recommended. Nevertheless, some response was seen, which may justify a further exploration of tretinoin and hydrocortisone 1% therapy for a longer treatment period in combination with research to clarify its mechanism.

Adult↗
PubMed1997

Characterization of interleukin-1 alpha-induced melanoma cell motility: inhibition by type I and type II receptor-blocking monoclonal antibodies.

Interleukin-1 alpha (IL-1 alpha) induces cell motility in a variety of benign cell types and in some but not all malignant cell lines in vitro. This study characterizes the IL-1 alpha-induced motility of an aggressive human melanoma cell line that expresses both type I and type II IL-1 receptors. We tested the effect of monoclonal antibodies including function-blocking moAbs against the type I and type II IL-1 receptors on melanoma cell motility to determine which receptor is involved in signal transduction of IL-1 alpha-induced melanoma cell motility. IL-1 alpha significantly increases MM-RU melanoma cell migration in a dose-dependent manner using modified Boyden chamber assays at concentrations 10 to 100 times less than concentrations that significantly inhibit cell growth. Computer-assisted time-lapse image analysis reveals that the motility is inhibited in a dose-dependent manner by neutralizing antibodies against IL-1 alpha. Function-blocking monoclonal antibodies against either type I or type II IL-1 receptors show a significant inhibition of cytokine-induced enhanced cell migration. When both the anti-IL-1 receptor antibodies are added together, the motility-response is completely blocked to control levels. Taken together the data indicate that the IL-1 alpha-induced motility of MM-RU melanoma cells is mediated through both type I and type II IL-1 receptors. The significant inhibition of motility by neutralizing IL-1 alpha or blocking either one or both of the IL-1 receptors indicates an integration of IL-1-induced signals in the induction of melanoma cell migration.

Antibodies, Blocking↗
PubMed1994

Differential effects of interleukin 1-alpha (IL-1 alpha) or tumor necrosis factor-alpha (TNF-alpha) on motility of human melanoma cell lines on fibronectin.

Interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) induce a motogenic response in a number of benign and malignant cells. We examined the chemokinetic effects of these cytokines on the cell migration of four melanoma cell lines on fibronectin using modified Boyden chambers and video-time lapse analysis. Flow cytometry analysis of IL-1 receptors, TNF receptors, and shifts in beta 1 integrin expression were correlated with the effects of these cytokines on cell migration on fibronectin. The four melanoma cell lines exhibited heterogeneous expression of types I and II IL-1 receptors as well as p60 TNF receptors. Scant p80 TNF receptor expression was detected on only one cell line. Three of four melanoma cell lines demonstrated type I IL-1 receptors by Western blotting. IL-1 alpha and TNF-alpha induced heterogeneous modulation of beta 1 integrin expression in the four melanoma cell lines tested; downward shift of the alpha 2, alpha 3, alpha 4, and beta 1 integrin subunits was detected among three of the melanoma cell lines as were upward shifts of the alpha 4, alpha 5, and alpha 6 integrin subunits among three of the melanoma cell lines. IL-1 alpha and TNF-alpha induced enhanced migration on fibronectin in one of the melanoma cell lines and were related to an upward shift in the alpha 4 and alpha 5 integrin subunit expression. Taken together, the findings indicate that expression of a particular receptor for IL-1 or TNF does not necessarily signal a motogenic response in melanoma cells, but induces heterogeneous shifts in beta 1 integrin expression. However, upregulation in alpha 4 and alpha 5 integrin subunits appears to relate to enhanced migration on fibronectin.

Blotting, Western↗
PubMed1994

Role of beta 1 integrins in cell spreading and migration of human nevomelanocytes and dysplastic nevi cells on collagen type IV and laminin.

We characterized beta 1 integrin subunit expression on three different cultures of benign human nevomelanocytes (NMC) and on four different cell cultures of human dysplastic nevus (DN) cells by flow cytometry analysis and examined their role in mediating cell spreading and migration on collagen type IV (CN IV) and laminin (LN) coated substrates by using a quantitative video image analysis system. The seven human NMC and DNC cultures expressed heterogeneous levels of beta 1, alpha 2, alpha 3 and alpha 6 integrin subunits. Image analysis showed that a significant increase (P < 0.001) in cell spreading and migration of the DN cells was induced on increasing coating concentrations of CN IV and LN. However, the NMC did not show an increase in cell spreading or migration on these substrates when compared to the substrates coated with denatured BSA only. The CN IV-induced cell spreading of the DN cells was significantly inhibited by anti-beta 1 mAb (AIIB2), anti-alpha 2 mAb (P1E6), or anti-alpha 3 mAb (P1B5), but not by mAb against alpha 6 integrin subunit (GoH3). The DN cell spreading on LN was not significantly inhibited by these mAbs. In contrast, the migration of the DN on CN IV and LN was significantly inhibited by anti-beta 1 mAb, anti-alpha 2 mAb, anti-alpha 3 mAb and anti-alpha 6 mAb. These data suggest that the alpha 2 and alpha 3 subunit are important for cell spreading of the DN on CN IV, although they are less important in cell spreading on the extracellular matrix component LN.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1993

Relationship between apolipoprotein E and low density lipoprotein particle size.

The relationships between the particle size of low density lipoproteins (LDL) and various lipid parameters, including apolipoprotein (apo) E concentration and apo E phenotype, were analyzed in plasma samples obtained from 196 apparently healthy 35-year-old males. The LDL particle size was determined by gradient gel electrophoresis. Using stepwise multiple regression analysis it was found that LDL particle size correlated negatively to the plasma concentrations of triglyceride (r = -0.497, P < 0.001), apo E (r = -0.415, P < 0.001), apo B (r = 0.395, P < 0.001) and cholesterol (r = -0.235, P < 0.001) and correlated positively to the plasma concentrations of apo A-I (r = 0.297, P < 0.001) and apo A-II (r = 0.145, P < 0.05). However, the LDL particle size did not differ significantly among the different apo E phenotypes. Indeed, when entered as a variable in the multiple regression analysis, the apo E phenotype was not correlated to the LDL particle size. It is concluded that the LDL particle size is related to the plasma concentrations of triglyceride, apo E, apo B, apo A-I, apo A-II and cholesterol and is not affected by the apo E phenotype in healthy 35-year-old males.

Adult↗
PubMed1993

Role of alpha 3 beta 1 and alpha 2 beta 1 integrins in melanoma cell migration.

Recent findings indicate that variable expression of beta 1 integrins may play a role in differential melanoma cell motility. Primary melanoma (PM) and metastatic melanoma (MM) cultures, derived from the same patient, were tested for their beta 1, alpha 2, alpha 3 and alpha 6 integrin subunit expression and cell migration on type IV collagen (CN IV) or laminin (LN). The MM cell line expressed markedly increased levels of the beta 1, alpha 2 and alpha 3, but not alpha 6 subunit compared to the PM cell line. The MM cell migration rate was significantly higher than that of the PM cell line on LN- or CN IV-coated substrates. Furthermore, the cell migration rate of both lines was significantly higher (p < 0.001) on these substrates than on the control substrates. The MM and PM cell migration was significantly inhibited by function-blocking anti-beta 1 and anti-alpha 3 MAbs, but not by the anti-alpha 6 MAb tested. In contrast, the anti-alpha 2 MAb significantly inhibited MM but not PM cell migration. These data show that the alpha 3 subunit plays a significant role in melanoma cell motility on CN IV and LN and that the alpha 2 subunit has a significant contribution to the motility of the MM cell line.

Antibodies, Monoclonal↗
PubMed1993

Role of beta-1 integrins in organ specific adhesion of melanoma cells in vitro.

BACKGROUND: Recent data suggest that the extracellular matrix of organs and heterogeneous integrin expression of tumor cells may influence metastasis distribution. EXPERIMENTAL DESIGN: Three human melanoma cell lines were characterized for integrin expression, in vitro binding to cryostat sections of different organs, and ability to generate experimental metastases in triple immunodeficient mice. RESULTS: The three cell lines exhibited heterogeneous expression of integrins, binding to cryostat sections, and organ colonization. A primary melanoma cell line (PM-WK) did not give rise to experimental metastases, showed scant or mild attachment to only a few organ tissue sections, and showed absent or minimal expression of alpha-integrin subunits tested (VLA 1-6) and alpha v beta 3. In contrast, two lymph node derived lines exhibited distinct patterns of organ colonization: MM-RU colonized only the lungs and expressed predominantly alpha 2 beta 1 and alpha v beta 3 integrin, whereas MM-AN colonized lung and extrapulmonary sites including pancreas and subcutaneous brown fat and expressed predominantly alpha 2 beta 1 and alpha 6 beta 1 integrin. In vitro, MM-RU exhibited marked attachment to lung, brown fat, kidney, and adrenal with no binding to liver, pancreas, brain, or muscle tissue sections, whereas MM-AN had a similar binding profile but with additional attachment to liver and pancreas. Function blocking anti-beta 1 monoclonal antibody inhibited the attachment of MM-RU and MM-AN cells to these tissues (p < 0.001), whereas function blocking anti-alpha 5 and an unrelated monoclonal antibody (HLA class I) did not. Function blocking anti-alpha 2 monoclonal antibody inhibited MM-RU cell adhesion (p < 0.001) but not MM-AN adhesion. However, the function blocking monoclonal antibody alpha 6 beta 1 significantly inhibited the binding of MM-AN to these tissues. CONCLUSIONS: These data suggest that alpha 2 beta 1 and alpha 6 beta 1 mediate differential melanoma cell attachment to organ tissue sections in vitro and that differences in integrin expression of these melanoma cells may be involved in differential organ colonization in vivo.

Animals↗
PubMed1992

CD44H regulates tumor cell migration on hyaluronate-coated substrate.

CD44 is a broadly distributed cell surface glycoprotein expressed in different isoforms in various tissues and cell lines. One of two recently characterized human isoforms, CD44H, is a cell surface receptor for hyaluronate, suggesting a role in the regulation of cell-cell and cell-substrate interactions as well as of cell migration. While CD44H has been shown to mediate cell adhesion, direct demonstration that CD44H expression promotes cell motility has been lacking. In this work we show that a human melanoma cell line, stably transfected with CD44H, displays enhanced motility on hyaluronate-coated surfaces while transfectants expressing an isoform that does not bind hyaluronate, CD44E, fail to do so. Migration of CD44H-expressing transfectants is observed to be blocked by a soluble CD44-immunoglobulin fusion protein as well as by anti-CD44 antibody, and to depend on the presence of the cytoplasmic domain of CD44. However, cells expressing CD44H cytoplasmic deletion mutants retain significant binding capacity to hyaluronate-coated substrate. Taken together, our results provide direct evidence that CD44H plays a major role in regulating cell migration on hyaluronate-coated substrate.

Base Sequence↗
PubMed1992

Actin organization and cell migration of melanoma cells relate to differential expression of integrins and actin-associated proteins.

We have recently described marked differences in cell migration rates and organization of actin in human melanoma cell lines isolated from various stages of tumor progression. Metastatic lines derived from lymph node metastases organized actin into stress fiber arrays and had high mean migration rates in vitro when compared to lines from other stages. Melanoma cells also reveal marked differences in localization of alpha-actinin and beta 1 integrins at stress fiber termination sites (focal contacts). Disruption of this organization is induced by antibodies against beta 1 integrins, alpha-actinin, recently postulated as having a role in linkage of actin to beta 1 integrins, is differentially expressed in melanoma cells by Northern blot analysis and a relatively high alpha-actinin to actin ratio is associated with stress fiber formation and increased cell migration. Furthermore, actin-binding protein, which cross-links actin filaments, is also significantly increased in lines exhibiting high migration rates. Control of migration and actin organization may be mediated by extracellular matrices and/or modulation of actin-associated proteins including alpha-actinin and actin binding protein. These findings provide evidence that an interaction of transmembrane adhesion molecules and elements of the cytoskeleton in melanoma cells may be responsible for differences in migration rates and capacity for metastasis.

Actinin↗
PubMed1991

Dysplastic nevi. Occurrence in first- and second-degree relatives of patients with 'sporadic' dysplastic nevus syndrome.

In this study a cross-sectional survey was undertaken among 156 living family members of 31 probands originally classified as having sporadic (histologically verified) dysplastic nevus syndrome (DNS). Seven (13.2%) of 53 parents had clinically recognizable DNS. Twenty-six (36.1%) of the 72 sibs showed dysplastic nevi. The diagnosis of DNS in family members was based on mainly clinical examination; in eight family members--those with only mild manifestation of DNS--a nevus was removed for histologic confirmation. After correction for pedigree size, we found that 60% of patients with "type A sporadic" DNS actually had one or more relatives with a DNS phenotype. Only 25% (8/30) of the probands were ultimately true sporadic cases without a DNS-affected first- or second-degree relative. In 15% (5/31) of the probands no conclusions concerning the type of DNS could be made because the pedigree size did not allow such a conclusion. We also found a higher prevalence of dysplastic nevi among the younger generation as compared with the older generation in our probands with DNS and their families as well as in a general population study of 400 individuals. This generation-dependent difference in expression of the DNS phenotype suggests that besides a genetic factor, other factors may play a role in the development of the characteristic phenotype.

Adolescent↗
PubMed1990

Ocular melanoma in families with dysplastic nevus syndrome.

Five families with the dysplastic nevus syndrome, in each of which one member had ocular melanoma, are reported. These five families were examined within a 3-year period in one medical center. To date only five other families with such a combination have been reported. We suggest a causal relation between ocular melanoma and the familial dysplastic nevus syndrome.

Adolescent↗
PubMed1987

Optimization of the reversed-phase high-performance liquid chromatographic separation of synthetic estrogenic and progestogenic steroids using the multi-criteria decision making method.

The optimization of the reversed-phase high-performance liquid chromatographic separation of a mixture of ethynylestradiol, desogestrel and three related compounds is described. A procedure is used that allows the prediction of the capacity factors of each individual synthetic steroid, depending on the mobile phase composition. Therefore, complete chromatograms can be predicted and evaluated with the multi-criteria decision making method.

Chromatography, High Pressure Liquid↗
PubMed1987

Mianserin pharmacokinetics and behavior in hyperkinetic children.

The present study was conducted to derive pediatric mianserin pharmacokinetic parameters, which were compared to those from healthy young adults, and to obtain preliminary information regarding the utility of mianserin for the management of hyperkinesis in children. The sample consisted of six prepubescent children with hyperkinetic behavior disorders who had not responded, or had developed tolerance to, stimulant medication. Mianserin pharmacokinetics were derived from plasma samples obtained over a 36- to 50-hour period following a single oral dose which ranged from 0.28 to 0.72 mg/kg. Children evidenced a significantly faster elimination half-life and a significantly smaller apparent kinetic volume of distribution than did adults, whereas maximum plasma concentration, time to maximum concentration, and apparent oral plasma clearance were similar. Ratings of behavioral deviance were obtained from teachers and parents during placebo and mianserin titration to a maximum dose of 40 mg/day. Although half the children showed some decrease in hyperactivity ratings, the small sample size and high variability of response preclude conclusions regarding the efficacy of mianserin for childhood hyperkinesis. Possible side effects in our sample included akathisia, excitability, insomnia, and migraine-like headache, as well as cardiovascular effects of tachycardia and two instances of minor electrocardiographic change. Our pharmacokinetic findings will be of import should mianserin prove useful for such childhood disorders as depression and/or enuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Attention Deficit Disorder with Hyperactivity↗
PubMed1983

Determination of the anti-ischaemic drug bepridil in human plasma using gas chromatography with nitrogen-sensitive detection.

An assay has been developed to determine the anti-ischaemic drug bepridil (as its free base) in human plasma. The assay procedure comprises n-hexane extraction from basic plasma and gas chromatography using nitrogen-selective detection. An analogue of bepridil is used as internal standard. The accuracy and precision of the assay is determined by repeated analyses of drug-free plasma samples spiked with 5, 10, 20, 100, 400 and 1000 ng of bepridil per ml of plasma. The accuracy, defined as the relative difference between the mean bepridil concentration found and the true value, was 8% or better. The precision (relative standard deviation) was 13% at the 5 ng/ml level and 5% at the 1000 ng/ml level. The assay is suitable to monitor routinely bepridil plasma levels during clinical studies.

Bepridil↗