Computerized axial tomography in the diagnosis of head and neck tumours

The development of computerised axial tomography is briefly described and the application of this investigative procedure to the diagnosis of tumours in the maxillo-facial region is illustrated by two cases.     

A G-->A transition creates a branch point sequence and activation of a cryptic exon, resulting in the hereditary disorder neurofibromatosis 2

We describe a G-->A transition within intron 5 of the NF2 gene. This mutation creates a consensus splice branch point sequence. To our knowledge this is the first report of a mutation that creates a functional branch point sequence in a human hereditary disorder. The new branch point sequence is located 18 bp upstream of a consensus splice acceptor site. A consensus splice donor site is found 106 bp 3' of the acceptor site. Asa consequence the G-->A transition results in an alternatively spliced mRNA containing an additional exon 5a of 106 bp derived from intron sequences. We cloned the mutant cDNA and show that due to an in-frame stop codon the cDNA codes for a truncated NF2 protein. The mutation was observed in three affected members of an NF2 family. In a tumour of one of the family members both alternatively spliced and wild-type mRNA were found, although the wild-type allele of the gene is absent due to an interstitial deletion on chromosome 22. We also show that immunoprecipitations reveal the presence of full-length wild-type NF2 protein in the tumour lysate. These data support the hypothesis that some degree of normal splicing of the mutant precursor RNA is taking place. It is therefore likely that this residual activity of the mutant allele explains the relatively mild phenotype in the family. These data also indicate that complete inactivation of the gene is not required for tumour formation.      

Serum trypsin inhibitory capacity and alpha 1-antitrypsin levels in liver cirrhosis and hepatoma.

alpha 1-Antitrypsin levels were measured in sera of 134 patients with cirrhosis and in 64 with cirrhosis and hepatoma. S-TIC was determined in 105 patients with cirrhosis and in 54 with cirrhosis and hepatoma. The mean alpha 1-at and S-TIC values in patients with cirrhosis were 369.59 +/- 14.072 mg% and 1,808 +/- 0.05 mg/ml respectively. In patients with cirrhosis and hepatoma the mean alpha 1-at level was 406.595 +/- 17.834 mg% and the S-TIC mean values was 2.064 +/- 0.82 mg/ml. Although these values are higher than those found in the healthy controls, the differences are not statistically significant.     

Genetic and electrophoretic studies in three Greek families inheriting the traits for both sickling and thalassemia

Summary Seven patients with hemoglobin S-thalassemia disease belonging to three Greek families are described. Interaction of the genes for hemoglobin S and for thalassemia was evident in all but one cases. Hemoglobin analyses consisting of a combination of paper electrophoresis and the alkali denaturation technic revealed the S+A+F pattern in three, the S+F+A pattern in one, the A+S+F in one, the S+A in one and the S+F pattern in another case.The importance of the hemoglobin pattern for the differential diagnosis of sickle cell-thalassemia disease from the sickle cell trait and the homozygous sickle cell anemia is discussed. From the genetical point of view the existence of modifying thalassemia genes is discussed.

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Zusammenfassung Es wird über 7 Patienten aus drei griechischen Familien mit Hämoglobin S-Thalassämie berichtet. Bei allen Fällen, bis auf einen, war eine Wechselwirkung der Erbanlagen für Hämoglobin-S und für Thalassämie augenscheinlich. Bei Hämoglobinuntersuchungen, welche mit der Papier-Elektrophorese und der Alkali-Denaturierung vorgenommen wurden, ließen sich S+A+F in drei, S+F+A in einem, A+S+F in einem, S+A in einem und S+F in einem anderen Falle erkennen.Außerdem wird auf die besondere Wichtigkeit des Hämoglobindildes für die Differentialdiagnose bei Sichelzellen-Thalassämie gegenüber Sichelzellen-Trägern und homozygoten Sichelzell-Anämien hingewiesen. Vom genetischen Gesichtspunkt ausgehend wird auch die Gegenwart modifizierter Thalassämiegene besprochen.

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Aided by the Department of Clinical Research, Lederle Laboratories, New York, U.S.A.     

Immunological Studies of Patients with Down's Syndrome

Abstract. Recurrent diarrhoea and weight loss in many adult patients with Down's syndrome (DS), initiated a search for malabsorption based on determination of serum IgG and IgA antibody levels to dietary antigens. The results were compared with measurements of autoantibodies and serum zinc levels. DS patients had increased IgG and IgA activities to gluten proteins, casein and ovalbumin compared with an age- and sex-matched group of other mentally retarded patients in the same institution. Intestinal biopsy was performed in six of the 38 patients; one had total and one partial villous atrophy. Serum zinc was significantly lower in DS patients (median 14.7 μmol/l, range 5.5–20 μmol/l) than in the controls (median 16.4 μmol/l, range 12.7–19.5 μmol/l). DS patients with increased IgA activity to gluten weighed less and had lower concentrations of zinc in serum than DS patients with normal IgA activity. Twenty-eight per cent of the DS patients had autoantibodies to the thyroid gland. Our results suggest intestinal malfunction in DS, perhaps related to a defect of immune regulation caused by reduced levels of zinc in serum.