Modulation of heteronymous reflexes from ankle dorsiflexors to hamstring muscles during human walking

In 16 human subjects, stimulation of the common peroneal nerve (CPN) was applied during walking and standing. The effect of the stimulation was evaluated from the rectified and averaged biceps femoris (BF) electromyographic (EMG) activity. In the swing phase of walking, the CPN stimulation evoked a suppression in the BF EMG in 12 of the subjects. In the early stance phase, the suppression was replaced by facilitation at a similar latency in 9 of the subjects. Of the other 3 subjects, in whom a suppression was observed during swing, a decrease in the suppression was observed in the stance phase in two of them. During a voluntary co-contraction of BF and tibialis anterior while standing, a suppression similar to that observed in the swing phase was observed. The thresholds of the suppression and facilitation were identical, suggesting that afferents of similar diameter were responsible. Cutaneous stimuli, which mimicked the sensation evoked by the CPN stimulation, but without activation of muscle afferents, did not produce similar effects in the BF EMG activity. It is suggested that the observed response and reflex reversal may reflect opening of an excitatory group I pathway in the early stance phase of walking with a concomitant shut-down of heteronymous group I inhibition.     

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.     

Central command and the cutaneous vascular response to isometric exercise in heated humans

Cutaneous vascular conductance (CVC) decreases during isometric handgrip exercise in heat stressed individuals, and we hypothesized that central command is involved in this response. Seven subjects performed 2 min of isometric handgrip exercise (35% of maximal voluntary contraction) followed by postexercise ischaemia in normothermia and during heat stress (increase in internal temperature ∼1°C). To augment the contribution of central command independent of force generation, on a separate day the protocol was repeated following partial neuromuscular blockade (PNB; i.v. cisatracurium). Forearm skin blood flow was measured by laser-Doppler flowmetry, and CVC was the ratio of skin blood flow to mean arterial pressure. The PNB attenuated force production despite encouragement to attain the same workload. During the heat stress trials, isometric exercise decreased CVC by ∼12% for both conditions, but did not change CVC in either of the normothermic trials. During isometric exercise in the heat, the increase in mean arterial pressure (MAP) was greater during the control trial relative to the PNB trial (31.0 ± 9.8 versus 18.6 ± 6.4 mmHg, P < 0.01), while the elevation of heart rate tended to be lower (19.4 ± 10.4 versus 27.4 ± 8.1 b.p.m., P = 0.15). During postexercise ischaemia, CVC and MAP returned to pre-exercise levels in the PNB trial but remained reduced in the control trial. These findings suggest that central command, as well as muscle metabo-sensitive afferent stimulation, contributes to forearm cutaneous vascular responses in heat stressed humans.     

Molecular epidemiology of hepatitis B virus infections in Denmark.

BACKGROUND: Denmark has a low incidence of acute hepatitis B (HBV) infections but the impact of an increasing number of immigrants with chronic HBV infection on HBV transmission is unknown. OBJECTIVES: To characterise individuals with chronic and acute HBV infection in a defined region and to examine the importance of different risk groups for the current HBV transmission. METHODS: During 2000-2001 all consecutive HBV infected individuals routinely diagnosed through the regional HBV serology laboratory in the County of Funen were classified according to ethnicity, presumed route of transmission and stage of infection based on clinical data mainly supplied by the requesting physician. HBV DNA was sequenced and subjected to phylogenetic analysis. RESULTS: Of 309 identified cases, 91 (29%) were classified as acute infection. HBV DNA sequencing was possible in 54 (59%) of these cases. Phylogenetic analysis showed that HBV isolated from injecting drug users (IDUs) was identical or closely related. Among acute cases acquired in Denmark 89% (74/83) were seen in IDUs (65) or in individuals presumably exposed to IDUs (nine) and phylogenetic analysis corroborated the assumption of IDU related transmission in every case with available sequence data. Among 83 ethnic Danes who acquired their HBV infection in Denmark, no new cases of transmission from immigrants were detected. CONCLUSION: Injecting drug use was the single most important factor for hepatitis B transmission in Denmark. The current Danish vaccination strategy is unable to protect IDUs from HBV infection and IDUs pose a greater risk of HBV transmission to the general population than immigrants.     

Deregulation of the G1/S-phase control in human testicular germ cell tumours

Deregulated cell cycle and defective genome-integrity checkpoints are among the hallmarks of cancer.Here we summarize our recent studies of key components of the GI/S machinery in normal human spermatogenesis, and their abnormalities in testicular germ cell tumours (TGCTs), with special emphasis on carcinoma in situ lesions (CIS). Our combined immunohistochemical and immunoblotting analyses of normal human adult and fetal testes, CIS, seminomas, embryonal carcinomas, and teratomas, revealed an 'unorthodox' spectrum of defects within the so-called RB pathway in TGCTs. The early aberrations included lack of expression of the retinoblastoma tumour suppressor (pRB) and the CDK inhibitor pl9ink4d, and overexpression of cyclin D2. Progression from CIS to invasive TGCTswas associated with loss of another two CDK inhibitors and tumour suppressors: pl6ink4a and pl8ink4c. We also found the lack of pRB and pl9ink4d in fetal gonocytes, the candidate target cell for all types of TGCTs. These findings, together with the status of the Chk2-p53 DNA-integrity checkpoint, are considered in relation to the origin, biology and pathogenesis of TGCTs, and potential implications of the GI/S defects for the curability of these tumours.