The G----A mutation at position +22 3' to the Cap site of the beta-globin gene as a possible cause for a beta-thalassemia.

We describe the occurrence of a chromosome with a G----A mutation at position +22 relative to the Cap site that was found in five patients with beta-thalassemia. All patients had a common type of beta-thalassemia mutation on the second chromosome, namely the frameshift at codon 8 (-AA), the IVS-I-110 (G----A) and the IVS-II-1 (G----A) mutations. The beta genes of two patients, including the 5' and 3' untranslated regions, were completely sequenced and no other mutations, except a few polymorphic sites, were observed. Dot-blot analyses failed to demonstrate this G----A mutation at +22 in nearly 400 beta-thalassemia chromosomes and 180 normal chromosomes. Heterozygotes have the features of a high Hb A2-beta-thalassemia heterozygosity, although the hematological parameters might be less abnormal than observed in heterozygotes for the more common beta-thalassemia mutations. The possibility has been presented suggesting that this mutation might impair the binding of mRNA to ribosomes. Another mutation in this segment of DNA, i.e. a C----G mutation at position +20, is observed exclusively on a chromosome which also carries the C----G mutation at IVS-II-745. It is postulated that the +20 C----G mutation accentuates the beta-thalassemia condition caused by the IVS-II-745 mutation; the mechanism might be similar to that suggested for the G----A at +22 mutation.     

Chinese in west Malaysia: the geography of beta thalassaemia mutations

The overseas Chinese in West Malaysia are almost exclusively from the south-eastern provinces of China-Kwangtung, Fukien, and Kwangsi. To institute a comprehensive thalassaemia control programme for this region we have characterised the beta thalassaemia mutations in 16 Chinese patients from West Malaysia: 4 beta thalassaemia mutations were seen: a) an A----G substitution in the TATA box [-28 base pairs (bp)], an A----T substitution in codon 17 [17 A----T], c) a 4 base pairs - TCTT deletion in codon 41-42 [frameshift mutation (FSC 41-42)], and d) a C----T substitution at the second intervening sequence (IVS 11) position 654. Similar mutations have been described in patients from the south-eastern provinces of China. The delineation of the specific mutations present will enable effective prenatal diagnosis for beta thalassaemia of ethnic Chinese in West Malaysia to be instituted.     

The effect of age on treatment choice and survival in elderly breast cancer patients

To investigate the effect of age on treatment choice and survival in patients with breast cancer, data from the cancer registry of the Netherlands Cancer Institute (NKI, Amsterdam, The Netherlands) on 611 women have been analyzed. All patients 55 years and older admitted to the NKI for primary treatment of breast cancer between 1981 and 1986 were selected. For women 75 years and older, physicians were less likely to use treatment of adjuvant radiation therapy after a mastectomy and more often employed primary hormonal therapy only for local stage disease than for younger patients. Life-table analysis showed that disease-specific survival at 7 years for patients 65 through 74 years of age was significantly better (65%) than that of the youngest (55%) and the oldest age group (50%). In multivariate regression analysis (Cox), age older than 74 years was significantly and independently associated with a shorter disease-specific survival as compared with patients younger than 75 years. This difference in survival, however, does not seem to be the result of the difference in treatment between the age groups, but suggests an influence of age-related factors such as comorbid diseases and weak physical condition, which manifest themselves most strongly in the oldest age category and make the older woman more vulnerable to the course of malignant disease.     

Differences in erythrocyte sodium transport between human plasma and artificial medium: the role and character of sodium efflux and influx stimulating plasma factors.

The main objective of this study was to further characterize the plasma factor(s) which stimulate sodium efflux from erythrocytes, which we reported previously. Dialysis of plasma against an artificial medium using membranes with varying molecular mass cut-off points revealed relative molecular mass(es) of the factor(s) of 100-1000 Da. The factor(s) could be absorbed on Dowex at pH 1.5 and Amberlite at pH 11.0, indicating 'Zwitterionic' character. They are hydrophilic and resistant to acid hydrolysis. These characteristics and direct measurements of contents made amino acids likely candidates for the efflux stimulating properties of the factor(s). Indeed, plasma amino acids added to artificial medium could abolish the sodium efflux difference between plasma and the artificial medium. The efflux stimulating effect of amino acids appeared not to be the result of sodium influx stimulation. A coincident finding was that plasma also contains dialyzable sodium influx stimulating factor(s) which are not amino acids.     

Pre- and Postnatal Neuroimaging of Congenital Cerebellar Abnormalities

The human cerebellum has a protracted development that makes it vulnerable to a broad spectrum of developmental disorders including malformations and disruptions. Starting from 19 to 20 weeks of gestation, prenatal magnetic resonance imaging (MRI) can reliably study the developing cerebellum. Pre- and postnatal neuroimaging plays a key role in the diagnostic work-up of congenital cerebellar abnormalities. Diagnostic criteria for cerebellar malformations and disruptions are based mostly on neuroimaging findings. The diagnosis of a Dandy-Walker malformation is based on the presence of hypoplasia, elevation, and counterclockwise upward rotation of the cerebellar vermis and cystic dilatation of the fourth ventricle, which extends posteriorly filling out the posterior fossa. For the diagnosis of Joubert syndrome, the presence of the molar tooth sign (thickened, elongated, and horizontally orientated superior cerebellar peduncles and an abnormally deep interpeduncular fossa) is needed. The diagnostic criteria of rhombencephalosynapsis include a complete or partial absence of the cerebellar vermis and continuity of the cerebellar hemispheres across the midline. Unilateral cerebellar hypoplasia is defined by the complete aplasia or hypoplasia of one cerebellar hemisphere. Familiarity with these diagnostic criteria as well as the broad spectrum of additional neuroimaging findings is important for a correct pre- and postnatal diagnosis. A correct diagnosis is essential for management, prognosis, and counseling of the affected children and their family.