Comparative study of psychiatric morbidity among workers at a paint factory in Nigeria

A fetal lamb model was developed to investigate the capacity of fetal articular cartilage for repair after the creation of a superficial defect. Superficial defects, 100 micrometers deep, were made in the articular cartilage of the trochlear groove in the distal aspect of the femur in eighteen fetal lambs that were halfway through the 145-day gestational period; the contralateral limb was used as a sham control. The wounds were allowed to heal in utero for three, seven, fourteen, twenty-one, or twenty-eight days. Seven days after the injury, the defects were filled with a hypocellular matrix, which stained lightly with safranin O. At twenty-eight days, the staining of the matrix was similar to that of the sham controls and the chondrocyte density and the architectural arrangement of the cell layers had been restored. An inflammatory response was not elicited, and no fibrous scar tissue was observed.     

Mechanism of maxi-K channel activation by dehydrosoyasaponin-I

Dehydrosoyasaponin-I (DHS-I) is a potent activator of high-conductance, calcium-activated potassium (maxi-K) channels. Interaction of DHS-I with maxi-K channels from bovine aortic smooth muscle was studied after incorporating single channels into planar lipid bilayers. Nanomolar amounts of intracellular DHS-I caused the appearance of discrete episodes of high channel open probability interrupted by periods of apparently normal activity. Statistical analysis of these periods revealed two clearly separable gating modes that likely reflect binding and unbinding of DHS-I. Kinetic analysis of durations of DHS-I-modified modes suggested DHS-I activates maxi-K channels through a high-order reaction. Average durations of DHS-I-modified modes increased with DHS-I concentration, and distributions of these mode durations contained two or more exponential components. In addition, dose-dependent increases in channel open probability from low initial values were high order with average Hill slopes of 2.4-2.9 under different conditions, suggesting at least three to four DHS-I molecules bind to maximally activate the channel. Changes in membrane potential over a 60-mV range appeared to have little effect on DHS-I binding. DHS-I modified calcium- and voltage-dependent channel gating. 100 nM DHS-I caused a threefold decrease in concentration of calcium required to half maximally open channels. DHS-I shifted the midpoint voltage for channel opening to more hyperpolarized potentials with a maximum shift of -105 mV. 100 nM DHS-I had a larger effect on voltage-dependent compared with calcium-dependent channel gating, suggesting DHS-I may differentiate these gating mechanisms. A model specifying four identical, noninteracting binding sites, where DHS-I binds to open conformations with 10-20-fold higher affinity than to closed conformations, explained changes in voltage-dependent gating and DHS-I-induced modes. This model of channel activation by DHS-I may provide a framework for understanding protein structures underlying maxi-K channel gating, and may provide a basis for understanding ligand activation of other ion channels.     

Infections caused by multiresistant enterococci in Norway

During the last decade antimicrobial resistant pathogens have become a major medical problem. Internationally, multiresistant enterococci have increased nosocomial morbidity and mortality. Such strains are often resistant to ampicillin, aminoglycosides, and glycopeptides such as vancomycin. The spread of these strains has been shown to correlate to the use of antibiotics and the practice of suboptimal infection control within health care facilities. The current situation in Norwegian hospitals is presented, including the only six cases with infections and the three carriers of vancomycin resistant enterococci found to date. Surveillance in the hospitals shows that such strains are uncommon in non-infected patients. To maintain this favourable situation it is necessary to continue to practice effective methods of infection control and to employ sound antibiotic policies.     

Folding intermediates are involved in genetic diseases?

Recent experimental data show that some human genetic diseases are due to mutations in proteins which influence their trafficking and lead to retaining of proteins in the endoplasmic reticulum or their unproper processing. In this paper a hypothesis is proposed that these mutations are connected with an incomplete protein folding, blocking it at the stage of the kinetic molten globule or even earlier. If so, the specific drugs against these diseases may be ligands and other factors which facilitate the correct protein folding.     

Psychosocial concerns of Nigerian women with breast and cervical cancer

Many studies have demonstrated that the management of pain after surgery was unsatisfactory. New pain management techniques have been developed in recent years (patient-controlled analgesia, epidural analgesia). To extend the number of patients who may benefit from these recent techniques and/or to obtain the best efficacy from existing methods of pain relief, re-organisation should take place on surgical wards. For example, protocols describing pain management strategies should be written. Surveys and audits should be carried out regularly to check their efficacy. Moreover, patients should be fully informed of the range of treatments available and their adverse effects. Finally, all staff involved in providing acute pain relief should undergo training.     

Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots

Epidemiological evidence has suggested that some pediatric leukemias may be initiated in utero and, for some pairs of identical twins with concordant leukemia, this possibility has been strongly endorsed by molecular studies of clonality. Direct evidence for a prenatal origin can only be derived by prospective or retrospective detection of leukemia-specific molecular abnormalities in fetal or newborn samples. We report a PCR-based method that has been developed to scrutinize neonatal blood spots (Guthrie cards) for the presence of numerically infrequent leukemic cells at birth in individuals who subsequently developed leukemia. We demonstrate that unique or clonotypic MLL-AF4 genomic fusion sequences are present and detectable in neonatal blood spots from individuals who were diagnosed with acute lymphoblastic leukemia at ages 5 months to 2 years and, therefore, have arisen during fetal hematopoiesis in utero. This result provides unequivocal evidence for a prenatal initiation of acute leukemia in young patients. The method should be applicable to other fusion genes in children with common subtypes of leukemia and will be of value in attempts to unravel the natural history and etiology of this major subtype of pediatric cancer.