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Biomedical subjects

M A van Dijk

Publications and source records attributed to M A van Dijk.

32 records · Page 2Linked to original sources

Phylogenetic relationships of the hoatzin, an enigmatic South American bird.

The hoatzin (Opisthocomus hoazin) lives in the humid lowlands of northern and central South America, often in riparian habitats. It is a slender bird approximately 65 cm in length, brownish with lighter streaks and buffy tips to the long tail feathers. The small head has a ragged, bristly crest of reddish-brown feathers, and the bare skin of the face is bright blue. It resembles a chachalaca (Ortalis, Cracidae) in size and shape, but its plumage and markings are similar to those of the smaller guira cuckoo (Guira guira). The hoatzin (pronounced Watson) has been a taxonomic puzzle since it was described in 1776. It usually has been viewed as related to the gallinaceous birds, but alliances to other groups have been suggested, including the cuckoos. We present DNA sequence evidence from the 12S and 16S rRNA mitochondrial genes, and from the nuclear gene that codes for the eye lens protein, alpha A-crystallin. The results indicate that the hoatzin is most closely related to the typical cuckoos and that the divergence occurred at or near the base of the cuculiform phylogenetic tree.

Animals↗

Hemolytic uremic syndrome after high dose chemotherapy with autologous stem cell support.

BACKGROUND: Chemotherapy intensification may lead to new forms of toxicity such as hemolytic uremic syndrome. METHODS: Three patients are described who developed this complication 4 to 6 months after high dose chemotherapy followed by autologous stem cell support. The literature on this subject is reviewed. RESULTS: One patient was conditioned with BEAC (carmustine, etoposide, cytosine arabinoside, and cyclophosphamide) and received autologous bone marrow. The other two underwent triple peripheral stem cell transplantation after conditioning with CTC (carboplatin, cyclophosphamide, and thiotepa). Symptoms were hypertension, microangiopathic hemolytic anemia, thrombocytopenia, and renal insufficiency. One patient had a retinal vein thrombosis. One patient died of a cardiac arrest shortly after the diagnosis was made. The remaining two achieved a partial remission: one with fresh frozen plasma without plasmapheresis and fresh frozen plasma, but improved on high dose intravenous immunoglobulin and vincristine. CONCLUSIONS: Hemolytic uremic syndrome is a serious complication of the more intensive chemotherapy made possible by stem cell support. Because of the rapidly growing indications for this approach, an increase in this type of vascular complication is expected.

Adult↗

The hexapeptide LFPWMR in Hoxb-8 is required for cooperative DNA binding with Pbx1 and Pbx2 proteins.

The Hox gene products are DNA-binding proteins, containing a homeodomain, which function as a class of master control proteins establishing the body plan in organisms as diverse as Drosophila and vertebrates. Hox proteins have recently been shown to bind cooperatively to DNA with another class of homeodomain proteins that include extradenticle, Pbx1, and Pbx2. Hox gene products contain a highly conserved hexapeptide connected by a linker of variable length to the homeodomain. We show that the hexapeptide and the linker region are required for cooperativity with Pbx1 and Pbx2 proteins. Many of the conserved residues present in the Hoxb-8 hexapeptide are required to modulate the DNA binding of the Pbx proteins. Position of the hexapeptide relative to the homeodomain is important. Although deletions of two and four residues of the linker peptide still show cooperative DNA binding, removal of all six linker residues strongly reduces cooperativity. In addition, an insertion of 10 residues within the linker peptide significantly lowers cooperative DNA binding. These results show that the hexapeptide and the position of the hexapeptide relative to the homeodomain are important determinants to allow cooperative DNA binding involving Hox and Pbx gene products.

Amino Acid Sequence↗

Localization of Pbx1 transcripts in developing rat embryos.

Recently, a new family of homeodomain proteins has emerged, that includes extradenticle, ceh-20, Pbx1, Pbx2 and Pbx3. The Pbx family has been shown to modulate the biological activities of the Hox proteins. We demonstrate here by in situ hybridization that Pbx1 transcripts are present in many embryonic tissues. Highest levels of Pbx1 expression in the developing embryo, from 12 to 20 days post coitum, are found in neuronal tissues, including brain, spinal cord and ganglia. In addition, Pbx1 transcripts are also detectable in the gut, lung, olfactory epithelium and kidney. The expression pattern of Pbx1 overlaps with that of many of the Hox gene products and is consistent with them acting in parallel to regulate common target genes.

Animals↗

Hox gene products modulate the DNA binding activity of Pbx1 and Pbx2.

A new family of homeodomain proteins has recently been identified that includes extradenticle, ceh-20 and three mammalian proteins Pbx1, Pbx2 and Pbx3. We show here that two members of this family, Pbx1 and Pbx2 bind cooperatively to DNA with both Hoxb-7 and Hoxb-8. Engrailed-2 modulates the DNA binding activity of the Pbx proteins to a different target site. E2A-Pbx1, a chimeric Pbx1 gene product involved in pre-B acute lymphoblastoid leukemia, has retained its ability to interact with the Hox proteins. These data show that vertebrate Hox and Pbx gene products have the ability to bind cooperatively to DNA.

Animals↗

Intracranial aneurysms in polycystic kidney disease linked to chromosome 4.

Autosomal dominant polycystic kidney disease is genetically heterogenous, with at least two chromosomal loci accounting for the disease. When the mutation is located on chromosome 16 (PKD1), extra-renal manifestations such as the rupture of intracranial aneurysms are well known. In the case of localization on chromosome 4 (PKD2), in which the renal disease runs a milder course, not much is known about the incidence of extrarenal manifestations. A PKD2 family is reported in which two members had subarachnoidal bleeding due to intracranial aneurysms; there was strong clinical evidence of subarachnoidal bleeding in a third family member. This indicates that the familial clustering of intracranial aneurysms may also occur in PKD2 families. Because of the considerable mortality and morbidity of intracranial aneurysms, screening with magnetic resonance angiography in PKD2 patients with a positive family history of intracranial aneurysms is recommended.

Adult↗

extradenticle raises the DNA binding specificity of homeotic selector gene products.

Recently, a Drosophila gene has been identified, extradenticle, whose product modulates the morphological consequences of homeotic selector genes. We show here that extradenticle protein raises the DNA binding specificity of Ultrabithorax and abdominal-A but not that of Abdominal-B. We further show that extradenticle modulates the DNA binding activity of engrailed to a different target site. While a region N-terminal of the extradenticle homeodomain is required for Ultrabithorax and abdominal-A cooperativity, engrailed requires a domain C-terminal of the extradenticle homeobox. These studies show directly how the DNA binding specificity of selector gene products can be raised by extradenticle and provides a mechanism, cooperative DNA binding, that allows selector gene products to achieve some of their biological specificity.

Animals↗

The liver-specific promoter of the human insulin-like growth factor II gene is activated by CCAAT/enhancer binding protein (C/EBP).

The human gene coding for insulin-like growth factor II (IGF-II) contains four promoters (P1-P4), that are subjected to tissue-specific and development-dependent regulation. Expression of promoter P1 is detected only in adult liver tissue, whereas promoter P3 is the major IGF-II promoter in fetal liver and is further expressed in other fetal tissues and in adult non-hepatic tissues. C/EBP is a tissue- and development-specific transcription factor that is expressed predominantly in adult liver, adipose tissue and lung. The effect of C/EBP on the expression of constructs containing IGF-II promoter P1 or P3 linked to the luciferase gene was investigated in cotransfection assays using Hep3B cells. We found that promoter P1 can be activated by C/EBP, whereas this transcription factor has no effect on the expression of promoter P3. By gel retardation and DNasel footprinting it was demonstrated that C/EBP can bind to a region of P1 located between 82 and 109 basepairs upstream of the cap site. Furthermore, we showed that deletion of this C/EBP binding region strongly reduces the ability of C/EBP to stimulate transcription from P1. These results indicate that C/EBP is a major component in the specific activation of the human IGF-II promoter P1 in adult liver.

Base Sequence↗

Elements required for activation of the major promoter of the human insulin-like growth factor II gene.

The human insulin-like growth factor II (IGF-II) gene contains four promoters, P1-P4. In fetal liver promoter P3 is the major promoter, which consists of a proximal region that supports general transcription, and a cell-specific region located more upstream. In addition to the TATA box, the proximal region contains four binding sites for nuclear proteins, designated PE3-1 to PE3-4. To determine the influence of the proteins binding to these elements, the transcriptional activity of the proximal region of P3 was investigated. Promoter P3 was analyzed in Hep3B cells, which express high levels of IGF-II mRNA derived from this promoter, and in HeLa cells, that have an inactive IGF-II gene. By analysis of 5'-deletion constructs in an in vitro transcription system and in transient expression assays, and by competition with specific oligonucleotides it was shown that the factors binding to the elements PE3-4, PE3-2 and PE3-1 play an important role in the regulation of promoter P3.

Base Sequence↗

Initial characterization of the four promoters of the human insulin-like growth factor II gene.

The human insulin-like growth factor II (IGF-II) gene contains four promoters (P1-P4), which are expressed in a tissue-specific and development-dependent way. Analysis of IGF-II mRNAs in different tissues has revealed that promoters P3 and P4 are expressed in all fetal and in nonhepatic adult tissues. In adult liver, however, the promoters P2, P3 and P4 are completely shut off and another promoter, P1, is activated. To obtain more insight in the mechanisms involved in the regulation of IGF-II gene expression we have performed an initial characterization of the IGF-II promoters employing transient expression of IGF-II promoter constructs in Hep3B and HeLa cells. These studies have revealed that promoters P1, P3 and P4 are active in both cell lines tested, while no activity of promoter P2 could be detected. Employing gel retardation and DNaseI footprint analysis we have identified in the three IGF-II promoters a number of elements which are bound by nuclear proteins.

Aging↗

Histological analysis of ultrasonic images of the prostate: an accurate technique.

Ultrasonography of the prostate furnishes images which still cannot be fully interpreted morphologically. In a cadaver study, the ultrasound images of two groups (21 and 19) prostates, obtained in a water bath, were compared with histology slides taken at corresponding levels. In the first part of the study, using a 4 MHz probe, there was a correlation between hyperechoic lesions and stone formations in 9 out of 15 cases. A relation between hypoechoic lesions and the existence of a carcinoma could also be established in 4 out of 12 cases. In the second part of the study, using a 7 MHz probe, there was a correlation between hyperechoic lesions and stone formations in all cases. Hypoechoic lesions correlated with the presence of a carcinoma in 1 out of 8 cases. The technique used appears to be well suited for the comparative study of ultrasound images and histology. Application of the 7 MHz probe is preferable as, because of a better resolution, smaller lesions can be detected. The results of this study are not very encouraging for the use of transrectal ultrasound for the detection of small prostatic carcinomas.

Aged↗

Ultrasonic determination of prostatic volume: a cadaver study.

In a cadaver study we aimed to prove that the application of Hastak's technique of planimetric volumetry of the prostate, using transrectal ultrasonography, is an accurate method. We used Brüel and Kjaer equipment (type 1846 + 1850, 4 mHz) in measuring 25 prostates of cadavers (all older than 40 years). Ultrasonically and physically measured volumes were compared. Only small differences (+4 to -6 cm3) were due to measurement errors. We conclude that planimetric volumetry of the prostate by transrectal ultrasonography is accurate.

Adult↗