Investigation of TSH dependency, circulating thyroid autoantibody, and morphological features of recurrent nontoxic goitre

Pathogenetical factors possibly responsible for recurrence of nontoxic goitre in a nonendemic area are evaluated. A group of 22 female patients admitted for surgical treatment of recurrent nontoxic goitre was compared with a control group of 86 female nontoxic goitrous patients not operated upon before. Preoperative serum baseline thyrotrophin levels in the recurrent goitre group were low normal and did not differ significantly from those in the control group. Circulating thyroid microsomal autoantibodies, thyroglobulin antibody titers, and the densities of lymphocytic aggregation in goitrous tissue did not differ significantly in the two groups. Thus, none of the parameters studied were likely explanations of regrowth of goitre.     

Large genomic rearrangements in MECP2

In 1999, mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2) were first reported in patients with Rett syndrome (RTT). The MECP2 gene is located at Xq28 and consists of 4 exons. About 80-90 % of the classic RTT patients harbor mutations in the coding region of MECP2, while the molecular cause is unknown in the remaining 10-20%. Several groups have searched for large rearrangements within the MECP2 and the results indicate that a fraction of MECP2-negative RTT cases has large deletions of the MECP2. In this study we have used the Multiplex Ligation-dependent Probe Amplification (MLPA) technique to screen 45 RTT patients, who have previously been tested negative for mutations in the coding region of MECP2. The MECP2-MLPA is a semi-quantitative multiplex PCR approach. It determines the relative number of copies of each MECP2 exon. With this approach we detected seven RTT patients with genomic deletions and further characterized the deletions using real time quantitative PCR (qPCR) and long-range PCR. The seven patients were given a severity score and their X chromosome inactivation profiles were determined in order to identify a possible genotype-phenotype correlation. The results from this study indicate that large deletions in MECP2 cause classic RTT.     

Local muscle blood flow and sustained contractions of human arm and back muscles

The endurance during sustained contraction of elbow, flexors, elbow extensors, and back extensors was tested in 3 human subjects. The force level used was varied between ca. 15 and ca. 75% of maximal isometric strength (IS). The clearance of¹³³Xe from contracting muscles was registered during and after the endurance test. In this way it was possible to determine whether muscle blood flow (MBF) was increased or had stopped during the contraction. Experiments with artificial ischaemia of the upper arm together with MBF measurements showed that MBF was of no importance for continuing sustained contractions above a certain force level, which was 50, 25, and 40% of IS for elbow flexors, elbow extensors and back extensors, respectively. However, the level where longer lasting (>15 min) sustained contraction is possible is directly related to MBF. These levels were 22, 15, and 20% IS for elbow flexors, elbow extensors, and back extensors, respectively.     

Frequency of deletion of short arm satellites in acrocentric chromosomes

The frequency of deletion of short arm satellites has been examined in various populations. Four out of 2509 males in psychiatric institutions and prisons had Dps- or Gps- (1·6 per 1000), and five out of 6187 persons in the general population had Dps- or Gps- (0·8 per 1000). The difference is not significant.

The segregation rate of the chromosome with lack of short arm satellite material did not deviate from unity in the few families where such calculations were possible. There was no increase in abortions or non-disjunction in the families with an acrocentric chromosome lacking short arm satellite material.

The study indicates that the frequency of Dps- and Gps- in the population is between 0·5 and 1·0 per 1000 and that the lack of short arm satellite material is without any deleterious effect on phenotype.

     

Infection studies with canine distemper virus in harbour seals

Summary Infection studies in harbour seal (Phoca vitulina) were conducted with the Snyder-Hill strain of canine distemper virus (CDV) that is virulent for dog and mink. The inoculated seals showed clinical symptoms which were to some degree similar to those observed in CDV infections of sensitive species of carnivores. Viral replication in lymphoid cells was followed by an extended period of immunosuppression. The results did not provide conclusive evidence for viral replication in surface epithelia of seals, and accordingly no spread of the infection to contact seals and mink was demonstrated. The pathogenicity of the infection did not increase upon a second viral passage in seal. The serological data showed that CDV-infected seals mounted an early virus specific antibody response. Overall, the results indicated that the harbour seal was not especially sensitive to CDV infection. The differences in the in vivo biological properties of CDV and PDV add to the distinction between these viruses at the genomic and antigenic levels.     

H-reflexes are smaller in dancers from The Royal Danish Ballet than in well-trained athletes

Summary The size of the maximalH-reflex (H _max) was measured at rest and expressed as a percentage of the maximalM-response (M _max) in 17 untrained subjects, 27 moderately trained subjects, 19 well-trained subjects and 7 dancers from the Royal Danish Ballet. TheH _max/M _max was significantly larger in the moderately and well-trained subjects than in the untrained subjects but smaller in the ballet dancers. It is therefore suggested that both the amount and the type of habitual activity may influence the excitability of spinal reflexes.     

HIV-1 infection of in vitro cultured human monocytes: early events and influence of anti HIV-1 antibodies

Summary To characterize the role of the humoral immune response on HIV-1 infection of monocytes and macrophages (Ms) we examined the susceptibility of in vitro cultured monocyte/Ms to various HIV-1 isolates and the influence of heterologous and particularly autologous anti HIV-1 sera on this infection. Depending on the period of in vitro cultivation and the virus isolate used different patterns of susceptibility were detected. One week old monocyte/Ms were highly susceptible to HIV-1 infection, in contrast to monocyte/Ms cultured 4 weeks. The infection by virus isolated immediately after seroconversion lead to persistent infection with high level of antigen production in contrast to infection by homologous virus isolated later. MAb against the V3-IIIB loop and sCD4 inhibited the infection of monocyte/Ms in a dose dependent manner, indicating that infection requires binding to CD4 and that post binding events may be common to the infection of lymphocytes. Anti HIV-1 sera showed neutralizing activity against heterologous and even autologous escape virus. This finding, together with the observation that monocytes and Ms are infected in vivo, suggests that protection against HIV-1 infection of monocytes and Ms in vivo may not be obtainable by the humoral immune response alone.     

An HLA study in 74 Danish haemochromatosis patients and in 21 of their families

HLA-A and -B alleles in 74 Danish patients and 21 homozygous relatives with idiopathic haemochromatosis (IH) were compared with those in a sample of 1719 chromosomes from healthy Danish control subjects. The following alleles occurred with higher frequencies in IH compared to controls: A3: 53.6% vs. 15.1% (Pc less than 0.001); B7: 33.1% vs. 15.6% (Pc less than 0.001); B14: 6.9% vs. 3.0% (Pc greater than 0.05); B38: 5% vs. 0.9% (Pc greater than 0.05); B47: 4.0% vs. 0.4% (Pc greater than 0.05). Pedigree analyses disclosed 19 different haplotypes in IH subjects, compared to 286 haplotypes in controls. The following haplotypes occurred with higher frequency in IH compared to controls: A3,B5: 10.3% vs. 0.3% (Pc less than 0.001); A3,B7: 25.6% vs. 6.6% (Pc = 0.001); A3,B14: 3.4% vs. 0.6% (Pc greater than 0.05); A3,B47: 6.9% vs. 0.2% (Pc greater than 0.05). The major IH marker HLA-A3 was found in 56% of the haplotypes. The patterns of HLA-alleles associated with IH in Denmark show similarities to those in Central Europe, Australia, USA and Canada, being A3,B7 dominated and those in Central Sweden, England and Ireland, being A3,B14 dominated.