Biomedical subjects
Publications and source records attributed to O Bartsch.
A case of bilateral microphthalmos with orbital cysts is presented with clinical, echographic, CT and genetical findings. An incomplete trisomy 22 is shown as the likewise cause of the malformation. No further symptoms known to be part of the cat-eye-syndrome could be detected.
The acrocallosal syndrome (ACS) is a rare malformation syndrome characterized by a distinct pattern of craniofacial, brain and limb anomalies. It was first described by Schinzel in 1979 and followed by 25 other cases reported in the literature. Neurodevelopmental aspects include hypotonia of prenatal onset, seizures and moderate to severe mental retardation. The condition is probably of autosomal recessive inheritance but is closely resembles the Greig cephalopolysyndactyly syndrome (GCPS), an autosomal dominantly inherited disorder mapped to the short arm of chromosome seven. We reviewed the literature for aspects of associated cystic malformations in addition to agenesis of the corpus callosum and report on another patient with ACS. Prognosis is dependent on the degree of hypotonia and early onset of epilepsy rather than the degree of craniofacial and limb malformations.
In 1983, a chromosome analysis was carried out in a newborn preterm infant with minor anomalies (preauricular skin tag, maldescensus testis). All analysed metaphases showed a small extra chromosome, which was symmetric, dicentric and bi-satellited. In spite of in depth analysis, its origin remained obscure. Recent re-evaluation using fluorescence in situ hybridization (FISH) led to the diagnosis of a dicentric chromosome 22. The FISH technique is an important new tool in chromosome diagnostics. The phenotype of this infant only vaguely resembles the cat eye syndrome. The syndrome should be diagnosed clinically and not only based on the results of chromosome analysis.
The effects of three non-myelotoxic cancer drugs on the growth of neuroblastoma cells were investigated in vitro and in vivo: dihydroxyphenylalanine (L-dopa, a drug with selective toxicity for melanoma cells), DL-buthionine sulphoximine (BSO, a drug with radiosensitizing effects), and tamoxifen (a drug used in the treatment of human mammary carcinoma). In vivo these substances significantly reduced the weight of neuroblastoma tumour transplants in the mice (nude/nude) (P less than 0.05). A dose/effect relationship could be established. In vitro, the D50 was determined, using fibroblasts as controls. The growth of neuroblastoma tumours was inhibited by different mechanisms: L-dopa and its metabolite dopamine reduced the activity of tyrosinase, BSO reduced glutathione levels, and L-dopa and tamoxifen raised cAMP concentrations.
A method for chromosome-specific staining and its use in clinical cytogenetics is described. This fluorescence in situ hybridization protocol for repetitive DNA probes results in yellow-green fluorescent signals on orange-red stained chromosomes. Special characteristics are its simplicity, the use of digoxigenin-11-dUTP for labeling, and the combination of high stringency criteria for hybridization and low stringency for washing. The method is particularly advantageous in cases with structurally abnormal extra chromosomes (ESACs), marker chromosomes of gonosomal origin, and chromosomal mosaicism. It may also facilitate the screening of cases for fragile X. The chromosome-specific staining can be done within 1 working-day.
In vitro, we were able to induce a differentiation of human (SK-N-MC, IMR-32, Leo-2) and murine neuroblastoma cells (NA-2, C-1300, NIE-115) with dibutyryl cyclic 3'5'-adenosine monophosphate (dbcAMP), hypothalamic factor (HF), and somatostatin. As morphological criteria of cellular differentiation we used the decrease in cell proliferation and the formation of neurites. Functional parameters were the increase of A cholinesterase activity, cAMP level, and protein content, and the decrease of cGMP level. After application of dbcAMP and HF, the effects were stronger than after somatostatin. We believe that the action of HF and somatostatin is caused by an increase in cAMP levels. In the in vivo experiments, human and murine neuroblastoma cells (NA-2, C-1300, and Leo-2) were transplanted into nude/nude mice. After HF treatment of 14 mice with NA-2 tumors, 4 of the mice were tumor-free, and mean tumor weight was reduced to one-third of the controls. Of the animals with C-1300 and Leo-2 tumors, half became tumor-free, and mean tumor weight was reduced to one-fourth. The results indicate that the induction of cellular differentiation by factors and hormones may in future become a method of therapy for human neuroblastoma.
We report on two sibs with partial dup (7q), a retarded 9-month-old boy and an aborted fetus of 17 weeks' gestational age. Besides minor anomalies, the boy had frontal bossing, macrocephaly with hydrocephaly, a high forehead, and a large fontanelle. GTG banded chromosomes showed a 14p+ abnormality. Because his mother carries a balanced, de novo translocation with a breakpoint in band 7q33, the boy has a duplication of the distal portion of band 7q33 and the segment 7q34----qter. Our findings suggest that the phenotype in terminal duplications of 7q may, in some patients, be recognized clinically.
The effects of metoclopramide (MCP) and bromocriptine (BC) on the growth of neuroblastoma (NB) cells and their influence on the plasma membrane binding of several neurotransmitters were studied. In the first part of this study, in vitro experiments were done with three human and two murine NB cell lines. Dibutyryl cyclic 3',5'-adenosine monophosphate is known to differentiate NB cells in vitro and served as a reference substance during the experiments. MCP significantly reduced the replication rate in NB cells and increased cellular differentiation by morphological as well as by functional criteria. BC, in contrast, stimulated cell replication. Similar to dibutyryl cyclic 3',5'-adenosine monophosphate, MCP increased the binding capacity of the plasma membrane for the beta-adrenergic hormones dopamine and noradrenaline. In the second part, the effects of BC and MCP upon NB tumor growth were investigated in vivo in the mouse. Significant changes in tumor growth were induced; BC promoted and MCP inhibited the NB tumor growth in a dose-dependent relationship. The findings are discussed, along with the observed accompanying changes in serum copper and in the peripheral blood count.
For the treatment of tall stature in girls, oestrogens are usually given in high doses. In this study, growth data of 35 constitutionally tall girls treated with only 0.1 mg/day ethinyl oestradiol (EE) are reported (Group 1). The data were compared with those of 23 untreated girls with comparable bone ages and growth potential (Group 2), and with those of 5 girls treated with 0.3 mg/day EE (Group 3). All groups were followed until cessation of growth. In group 1, the median bone age at the onset of treatment was 12.50 years (Greulich-Pyle, range 10.50-13.75), and the median height prediction was calculated to be 184.4 cm (Bayley-Pinneau, range 179.5-191.5). Following oestrogen treatment of 21 months duration (range 10-37) the median adult height was reduced by 4.3 cm (range 0.0-9.0), or 3.9 cm if corrected for the error of prediction in the control group. The effect was greater in those girls with bone ages below 12.5 years at the onset of treatment (6.7 cm/corrected value 7.4 cm) than in the older girls (4.2 cm/3.6 cm). In Group 2 (controls) the median final adult height was over-estimated by 0.4 cm (range-4.9 to 4.9), but was under-estimated by 0.7 cm in those girls with bone ages below 12.5 years. In girls of comparable bone age similar reductions were obtained whether 0.3 mg/day EE (Group 3) or 0.1 mg/day was given (4.4 vs. 4.2 cm). A comparison of these results with published data indicates that higher EE doses (0.3-0.5 mg/day) have only little, if any, greater effect on the growth of girls than the dosage of 0.1 mg/day EE used in this study.
Rubinstein-Taybi syndrome (RTS) is a dominant Mendelian disorder characterised by mental retardation, a typical facies, broad thumbs and short stature. Previous reports indicated that 4-25% of RTS patients have a submicroscopic 16p13.3 deletion of the CBP gene. Using FISH and cosmid probes RT100, RT191 and RT203 we studied 45 RTS patients from Germany, the Czech Republic, Austria and Turkey and found four deletions (8.9%, pooled data including other studies: 11%). All deletions were interstitial; three spanned the CBP gene (RT100-RT203) and one was smaller (RT100 only). Previous studies reported no phenotype-genotype correlation between RTS patients with or without a deletion. Our findings suggest a more severe phenotype. The mean age at presentation was 0.96 years in patients with a deletion as against 11.12 years in those without. Patients A and B with a deletion died in infancy which is rare in RTS and was not observed among the other patients. Patients A and D had accessory spleens, Patient A with hypoplastic left heart, abnormal pulmonary lobulation and renal agenesis. This is the second report of hypoplastic left heart and the first report of polysplenia with RTS. The signs suggest a developmental field defect (disturbance of laterality) either as a newly recognised pattern of RTS, or alternatively a novel contiguous gene syndrome.
Determination of tumor cell maturity and induction of cell differentiation are significant issues in oncology. We studied here in vitro the effects of cyclic AMP and cyclic GMP on human cervix carcinoma cells (HeLa cells), using normal human cervix cells as controls. Relative plasma membrane fluidity (which corresponds with the adhesive power of the cell, membrane permeability, and the ability to maintain the ionic milieu), cell cycle characteristics, and protein kinase C activity (a regulator of the cell cycle) were determined. In the untreated HeLa cells, membrane fluidity and protein kinase C activity were increased versus the controls. Administration of dbcAMP decreased the membrane fluidity and the protein kinase C activity, prolonged the G0/G1 phase of the cell cycle and shortened the S + G2 + M phase; with dbcGMP, the opposite changes were recorded (all findings, p < 0.05). Findings from HeLa cells treated with dbcAMP approached those from the normal controls. Each of the parameter studied reflected the differentiation of the HeLa cells during dbcAMP treatment. They may be of potential use for the determination of tumor cell maturity in clinical oncology.