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D Van Velzen

Publications and source records attributed to D Van Velzen.

At least 19 recordsLinked to original sources
PubMed2000

Unbiased and efficient estimation of the total number of terminal bronchiolar duct endings in lung: a modified physical disector.

A novel modification of the physical disector is described which was used to estimate the total number of terminal bronchiolar duct endings (TBDEs) in human infant lung. TBDEs are closed three-dimensional space curves of complex shape that are inherently difficult to count from histological sections. However, careful consideration of the microanatomy of the terminal duct endings provides us with the opportunity to define a very simple and unbiased counting rule. To apply the rule in practice we also need to determine a suitable disector height. Owing to the complex shape of the TBDE we had no prior knowledge of what disector height would be suitable for counting the TBDE structures. Exhaustive serial sectioning of complete TBDE structures was carried out and showed that any disector height under 90 microm would give unbiased counts. A further empirical study was then undertaken to determine the most efficient disector height. This was found to be 50 micro. The total number of TBDEs in the upper lobe of the right lung of six human infants aged between 13 and 25 weeks was also estimated. The estimates of numerical density obtained with our modification of the physical disector were multiplied by estimates of lung lobe volume obtained using Cavalieri's Principle. The total number of TBDEs in the lobes ranged from 15 323 to 57 768, with a mean of 40 306. The average coefficient of error of the number estimates was 19%, which was deemed precise enough given the biological coefficient of variation between TBDE number of 36%.

Bias↗
PubMed2000

Audiometric analysis of a Belgian family linked to the DFNA10 locus.

OBJECTIVE: To report the otologic and audiometric characteristics of a nonsyndromic postlingual sensorineural hearing impairment in a Belgian family linked to DFNA10. STUDY DESIGN: Retrospective study of the otologic and audiometric data of 17 genetically affected persons. SETTING: Tertiary referral center. PATIENTS: All members of a Belgian kindred who carried the haplotype linked to the inherited hearing impairment of DFNA10. INTERVENTIONS: Diagnostic otologic and audiometric analysis. MAIN OUTCOME MEASURES: Pure-tone audiometry. RESULTS: To find the frequencies that were most affected by the genetic defect, the excess hearing loss of the 17 patients was calculated per frequency in comparison with the respective p50 and p95 thresholds of the normal population. CONCLUSIONS: The genetically affected persons of a Belgian family shared a progressive symmetric sensorineural hearing loss that started in the first to fourth decade. Thirty-five percent of the affected family members had tinnitus, and only one patient had very mild vestibular complaints. At onset, hearing losses were mainly situated at the midfrequencies. With increasing age, all frequencies became affected. The hearing loss was initially mild, with a spontaneous evolution to a moderate or severe hearing impairment. The progression of the hearing loss for the pure-tone average (between 0.5 and 4 kHz) was 1.08 dB/year for this family, compared with 0.50 dB/year and 0.35 dB/year at the 95th and 50th percentiles of the normal population, respectively.

Adult↗
PubMed1999

Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families.

We have previously found linkage to chromosome 1p34 in five large families with autosomal dominant non-syndromic hearing impairment (DFNA2). In all five families, the connexin31 gene ( GJB3 ), located at 1p34 and responsible for non-syndromic autosomal dominant hearing loss in two small Chinese families, has been excluded as the responsible gene. Recently, a fourth member of the KCNQ branch of the K+channel family, KCNQ4, has been cloned. KCNQ4 was mapped to chromosome 1p34 and a single mutation was found in three patients from a small French family with non-syndromic autosomal dominant hearing loss. In this study, we have analysed the KCNQ4 gene for mutations in our five DFNA2 families. Missense mutations altering conserved amino acids were found in three families and an inactivating deletion was present in a fourth family. No KCNQ4 mutation could be found in a single DFNA2 family of Indonesian origin. These results indicate that at least two and possibly three genes responsible for hearing impairment are located close together on chromosome 1p34 and suggest that KCNQ4 mutations may be a relatively frequent cause of autosomal dominant hearing loss.

Amino Acid Sequence↗
PubMed1997

Linkage analysis of progressive hearing loss in five extended families maps the DFNA2 gene to a 1.25-Mb region on chromosome 1p.

Thus far, 13 genes for autosomal dominant hearing loss have been localized to specific chromosomal regions, but none of the genes has been cloned. Only a single family has been linked to each of these loci, with the exception of DFNA2. DFNA2 was originally mapped in two extended families originating from Indonesia and the United States. In this study we report linkage to DFNA2 in three additional large families with autosomal dominant hearing loss from Belgium and The Netherlands. These five DFNA2 families show a similar progressive sensorineural hearing loss, starting in the high frequencies and also affecting the middle and low frequencies later in life. Combining the information from all linked families, the candidate region that is most likely to contain the DFNA2 gene was reduced to a 1.25-Mb region between markers D1S432 and MYCL1. Different haplotypes segregating with the hearing loss were found in all five families, suggesting that different mutations are present in the same gene. These results indicate that DFNA2 is most likely an important gene for autosomal dominant hearing loss.

Alleles↗
PubMed1996

Stereological estimation of the absolute number of glomeruli in the kidneys of lambs.

An association between the arrest of renal development and intra-uterine growth retardation (IUGR) has been demonstrated in human beings and it has been suggested that the same defect may occur in the kidneys of lambs affected by IUGR. Using design-based stereological methods, the physical disector and Cavalieri's principle, smaller absolute numbers of glomeruli were found in all six IUGR lambs studied with a low birthweight and in two of six control lambs studied with a normal birthweight than in other lambs with a normal birthweight. There was no difference in absolute numbers of glomeruli between twin births and singletons. The absolute numbers of glomeruli in three stillborn lambs were distributed among results obtained from the normal and IUGR lambs in accordance with their individual bodyweights. IUGR had a profound detrimental effect on the renal development of the lambs.

Abortion, Veterinary↗
PubMed1996

T-cell predominant balanitis in a traumatic tetraplegic patient: a case report.

T-cell predominant balanitis is described in a 38 year old uncircumcised tetraplegic man whose presenting feature was non-progressive red lesions over the inner prepuce and the glans penis without signs of infection, phimosis, or meatal stenosis. There was no regional lymphadenopathy. He was not exposed to any of the high risk factors for human immunodeficiency virus infection. As the lesion did not respond to topical antibacterial, antifungal, and corticosteroid medications applied in that order, circumcision was performed. Following circumcision, the remaining lesion over the glans penis regressed completely over a period of 1 month. Histopathology of the excised prepuce revealed that both areas of normal nonkeratinizing squamous epithelium as well as areas with hyperplasia. No atypia was noted and Bowenoid changes were not seen. Immunohistochemical studies on the inflammatory infiltrate in the excised prepucial lesion using tissue proliferation markers (PCNA and MIB-1) revealed active proliferation of the band-like infiltrate shown by immunophenotyping (anti-human T cell, CD45RO, clone UCHL1 and L26, pan-B marker) to consist predominantly of T-cells, further supporting the hypothesis of a local immune-mediated inflammatory process as the final pathogenic mechanism of the penile lesion.

Adult↗
PubMed1996

Growth characteristics of the human nasal septum.

Using a specially designed algorithm for the measurement of the surface area of shapes with highly irregular contours, growth curves were developed for post-natal septal growth in humans using post-mortem specimens of a study population of 30 cases, distributed over the age range from birth to 62 years. From the results a rapid growth phase for the total septum is evident immediately after birth, lasting until the second year of life. Then, a gradual deceleration of growth is recognized with a plateau eventually being reached at the age of 36 years. Mathematical analysis of the growth curve shows that the curve for the total septum is the sum of two separate mathematical equations, representing the cartilaginous and bony contribution, respectively. It is demonstrated that the cartilaginous septum reaches adult dimensions (lateral surface area) at the age of two years. Subsequent growth of the septum is due to expansion of the perpendicular plate, i.e. the bony parts of the septum.

Adolescent↗
PubMed1994

The extracellular matrix components, tenascin and fibronectin, in Hirschsprung's disease: an immunohistochemical study.

Previous in vitro studies have suggested that successful neural crest cell migration in the developing gut could be influenced by the composition of the extracellular matrix components, tenascin and fibronectin. The authors aimed to gain insight into the pathogenesis of Hirschsprung's disease (HD) by studying the distribution of tenascin and fibronectin in bowel specimens of patients with HD. Immunohistochemical examination was performed in specimens from 10 HD patients (8 aganglionic, 5 transitional, and 10 normoganglionic zones) and 18 age- and site-matched controls undergoing other types of gastrointestinal surgery. The distribution of tenascin was restricted to the basement membranes of the smooth muscle and vasculature, and in the basement membranes surrounding neuronal ganglia in all the controls and in 10 proximal normoganglionic HD specimens. More intense tenascin immunofluorescence was observed in the smooth muscle basement membranes of the muscularis externa of eight aganglionic and five transitional zones of HD. Wide-spread distribution of fibronectin was found in all the basement membranes as well as in the lamina propria and submucosa of all control and 10 normoganglionic HD sections. However, more intense immunofluorescence with fibronectin was observed in all the layers of eight aganglionic and five transitional zones of HD specimens. The present findings show that the mesenchymal and basement membrane extracellular matrix constitution is abnormal in the affected bowel of HD. Although a causal relationship has not been demonstrated, corroborative evidence from earlier animal experiments in other studies suggests that the extracellular matrix abnormalities may contribute to the pathogenesis of HD.

Basement Membrane↗
PubMed1994

Strictures of the colon in cystic fibrosis.

We describe the radiological and histopathological findings in five children with cystic fibrosis who presented recently to our hospital. Each child underwent surgery after failing to respond to medical management for suspected distal intestinal obstruction syndrome. Four patients had preoperative ultrasound and contrast enema examinations. Wall thickening and dilatation of the ascending colon was seen on ultrasound and contrast enema revealed a stricture of the ascending colon in all four. At surgery these findings were confirmed. All five patients had histopathological changes of post-ischaemic ulceration repair. One child had symptoms of intestinal obstruction 5 months after right hemicolectomy. Radiological investigation revealed a stricture in the descending colon which was resected. The histopathological changes were the same as before. Colonic strictures should be considered in cystic fibrosis patients who do not respond to medical management of distal intestinal obstruction syndrome.

Adolescent↗
PubMed1994

Analysis of relative proliferation rates of Wilms' tumor components using proliferating cell nuclear antigen and MIB-1 (Ki-67 equivalent antigen) immunostaining and assessment of mitotic index.

BACKGROUND: Flow-cytometric analysis of proliferation index (PI) has potential use in predicting prognosis in malignancy. Its relevance to heterogeneous tumors has not been conclusively studied. In nephroblastoma, where the epithelial components are considered more differentiated than others, potentially different PIs may exist within a single lesion based on the inverse relation between differentiation and proliferation. Proliferating cell nuclear antigen (PCNA) and MIB-1 (Ki-67 equivalent antigen) demonstration in histologic sections by immunoperoxidase methods may allow for determination of PI in relation to tissue type. EXPERIMENTAL DESIGN: A consecutive unselected series of 8 pediatric nephroblastoma patients was used to study the relation between PI and histologic differentiation as established by flow-cytometric analysis of nuclear suspensions prepared from formalin-fixed and paraffin-embedded tissue and by PCNA/MIB1 staining of parallel histologic sections. PI by PCNA/MIB1 was established using 5-microns paraffin sections, immunoperoxidase, and quantification procedures detailed in the literature. The mitotic index (MI) of tissue components was separately assessed using 5-microns hematoxylin and eosin-stained sections and counting procedures detailed in the literature. RESULTS: The 8 lesions showed a PI of 4 to 20% as determined by flow cytometry. Using PCNA staining, the epithelium showed a mean PI of 55.5% (range 40 to 80%), that was significantly higher (p < 0.001, Wilcoxon's two-tailed rank sum test) than blastema (mean PI: 34.1%, range 17.5 to 76.5%) and stroma (mean PI of 14.9%, range 5 to 24%, p < 0.001, Wilcoxon's two-tailed rank sum test). Although, probably due to tissue antigen preservation, acceptable MIB-1 staining was not achieved in all lesions (5 of 8), the results, although generally with lower labeling indices, confirmed the PCNA findings. The relative MI of epithelial components was higher than that of stroma and blastema in keeping with the immunocytochemical findings. In 6 of 8 cases, the PI by flow-cytometric analysis was lower than the lowest value for the PI (labeling index) of an individual tissue type found by PCNA or MIB staining. CONCLUSIONS: The differences found between PI of the different tissue components in nephroblastoma are difficult to understand if the epithelial components (with the highest PI values) are considered as differentiation products from the other components of the lesion. The relation between PIs as determined by PCNA/MIB-1 analysis/mitotic index, for the three components and the PI as established by flow cytometry is not simply explained by the relative volume of the tissue components.

Cell Division↗
PubMed1993

The full mutation in the FMR-1 gene of male fragile X patients is absent in their sperm.

Fragile X syndrome is characterized at the molecular level by amplification of a (CGG)n repeat and hypermethylation of a CpG island preceeding the open reading frame of the fragile X gene (FMR-1) located in Xq27.3. Anticipation in this syndrome is associated with progressive amplification of the (CGG)n repeat from a premutation to a full mutation through consecutive generations. Remarkably, expansion of the premutation to the full mutation is strictly maternal. To clarify this parental influence we studied FMR-1 in sperm of four male fragile X patients. This showed that only the premutation was present in their sperm, although they had a full mutation in peripheral lymphocytes. This might suggest that expansion of the premutation to the full mutation in FMR-1 does not occur in meiosis but in a postzygotic stage.

DNA Mutational Analysis↗
PubMed1993

Scalp cyst with heterotopic brain tissue.

A multilocular scalp lesion was noticed at birth in a female infant. There was no underlying skull defect. Histological examination revealed neural tissue staining with S-100 and GFAP, but not with a neurofilament stain, which is in keeping with a glial cell origin. Heterotopic brain tissue is a rare developmental abnormality, which usually has no effect on neurological development. It should be considered in the differential diagnosis of scalp lesions in neonates.

Brain↗
PubMed1992

Quantitative and qualitative analysis of the extracellular matrix protein, laminin, in Hirschsprung's disease.

Previous immunohistochemical studies have shown an abnormal distribution of extracellular matrix (ECM) proteins, including laminin, in the smooth muscle layer of muscularis externa in Hirschsprung's disease (HD) bowel. These findings supported the hypothesis that an abnormal ECM microenvironment may be responsible for the failure of migration and/or development of the neural crest cells in the gut in HD. In order to determine the cause of the abnormality in laminin distribution, solid-phase enzyme-linked immunosorbent assays and immunoblots were used to quantitate the ECM protein laminin and characterize its subunits, respectively, in extracts of the dissected smooth muscle layer of the muscularis externa. In the aganglionic bowel, laminin (median concentration, 32.4 ng/mg of tissue) was found to be present in significantly greater quantity than in both the normoganglionic bowel of the same specimen (median, 17.2 ng/mg, P less than or equal to .05) and the normal bowel of age-matched controls (median, 9.7 ng/mg, P less than or equal to .05). Laminin concentration was also found to be significantly higher in normoganglionic HD bowel (median, 17.2 ng/mg) than in age-matched control specimens (median, 10.8 ng/mg, P less than or equal to .05). No difference was observed in the subunit composition of laminin in HD and control extracts analysed by immunoblot after polyacrylamide gel electrophoresis. This study demonstrates a quantitative abnormality of laminin in the bowel in HD, supporting the hypothesis that "abnormal microenvironment" may have a role in the pathogenesis of HD.

Blotting, Western↗
PubMed1992

The effect of intrauterine growth retardation on the development of renal nephrons.

OBJECTIVE: To investigate the effect of Type II (asymmetrical) intrauterine growth retardation (IUGR) on renal development. DESIGN: A prospective descriptive study. SETTING: Department of Fetal and Infant Pathology, Liverpool Children's Hospital. SUBJECTS: Six (severely) affected IUGR stillbirths of known gestational age with a control group of stillbirths with birthweight greater than 10th centile, and eight liveborn IUGR infants who died within a year of birth with a control group of appropriately grown infants who died within a year of birth (postnatal groups). TECHNIQUES: The kidneys from all the groups studied were analysed using unbiased, reproducible and objective design-based stereological techniques. MAIN OUTCOME MEASURES: Total renal nephron (glomerular) numbers and average volumes of total nephron and cortical and medullary nephron segments. RESULTS: Nephron number estimates lay below the control group's 5% prediction limit in five out of the six growth-retarded stillbirths, and were significantly (P less than 0.005, IUGR at 65% of the control mean) reduced in the postnatal group. Estimates of nephron (segment) volume did not differ between control and IUGR groups. CONCLUSIONS: Type II intrauterine growth retardation may exert a profound effect on renal development. The reduced nephron number at birth, together with the lack of any early postnatal compensation in either nephron number or nephron size, emphasizes the need for vigorous antenatal surveillance for IUGR and consideration of elective preterm delivery of affected fetuses. A systematic review of other organs, which develop in a similarly rapid fashion during the late intrauterine period, is indicated by this work. With one exception, all birthweights in the growth-retarded groups were below the third centile, thus the precise quantitative relation between progressive IUGR and renal function requires further assessment.

Birth Weight↗
PubMed1992

Abnormalities in the distribution of laminin and collagen type IV in Hirschsprung's disease.

In vitro neurite outgrowth and neuronal survival are promoted by laminin, and neuronal migration is promoted by collagen type IV. This led to the hypothesis that Hirschsprung's disease (HD) could be the result of an abnormal extracellular matrix microenvironment in the affected bowel during embryogenesis. Using indirect immunohistochemistry, we studied the distribution of laminin and collagen type IV in the bowel specimens of eight HD patients (four neonates and four infants) and 16 age- and site-matched controls from non-HD patients. In eight HD specimens, the tissue studied was from the aganglionic, transitional, and proximal normoganglionic zones. Uniform distribution of laminin and collagen type IV was observed in the basement membranes of all control specimens. The semiquantitative abnormality in the distribution of these proteins in HD occurred as follows: immunoreactivities were more intense in the inner circular layer, diminishing with a gradient in the outer muscularis externa in six of six aganglionic, four of five transitional, and three of eight normoganglionic sections. The qualitative abnormality of these proteins in HD was speckled immunofluorescence outside the basement membranes of the muscularis externa in all three zones of neonatal specimens only. These findings support the microenvironment hypothesis of the pathogenesis of HD.

Basement Membrane↗