Generation of leukemia inhibitory factor and basic fibroblast growth factor-dependent induced pluripotent stem cells from canine adult somatic cells

For more than thirty years, the dog has been used as a model for human diseases. Despite efforts made to develop canine embryonic stem cells, success has been elusive. Here, we report the generation of canine induced pluripotent stem cells (ciPSCs) from canine adult fibroblasts, which we accomplished by introducing human OCT4, SOX2, c-MYC, and KLF4. The ciPSCs expressed critical pluripotency markers and showed evidence of silencing the viral vectors and normal karyotypes. Microsatellite analysis indicated that the ciPSCs showed the same profile as the donor fibroblasts but differed from cells taken from other dogs. Under culture conditions favoring differentiation, the ciPSCs could form cell derivatives from the ectoderm, mesoderm, and endoderm. Further, the ciPSCs required leukemia inhibitory factor and basic fibroblast growth factor to survive, proliferate, and maintain pluripotency. Our results demonstrate an efficient method for deriving canine pluripotent stem cells, providing a powerful platform for the development of new models for regenerative medicine, as well as for the study of the onset, progression, and treatment of human and canine genetic diseases.     

Factor versus cluster models of schizotypal traits. II: relation to neuropsychological impairment.

Heterogeneity in cognitive performance in schizophrenia and schizotypy may be accounted for, by differences in predominant symptom presentation. However, studies have not demonstrated consistent relations between specific cognitive impairments and specific trait dimensions in either population. Studies of group differences, particularly those using groups defined by cluster analyses are rare, but suggest that the negative trait dimension is more associated with executive function deficits, positive trait dimension with memory and attentional difficulties, and the disorganized trait dimension with attention problems. The present study examined the relation of schizotypal trait dimensions and executive function deficits in schizotypal individuals using two methods. Correlations between schizotypal factor scores and cognitive measures demonstrated that high negative symptoms were associated with poor performance on the WCST, while high scores on other trait dimensions were related to a better WCST performance. High scores in all trait dimensions were related to the na?ve rater's observations of unusual social behavior. A cluster analysis revealed three groups of schizotypals (predominantly negative presentation, predominantly positive symptom presentation, and high on all dimensions). The cluster with predominantly negative symptoms performed worse, than all other schizotypal groups and unselected controls, on the WCST and a higher percentage of them were rated as clinically impaired on the neuropsychological battery. However, schizotypals who were high on all trait dimensions were rated as having the most unusual social behavior by the na?ve raters. Overall, results support the hypothesis of a relation between executive function deficits and negative symptoms in schizotypal individuals.     

Adhesion of bacteria to the human small-intestinal mucosa. A scanning electron microscopic study

During the period 1 January 1980 to 30 June 1986, a total of 543 small-intestinal biopsy specimens from adults with gastrointestinal symptoms were available for routine analysis with correlated scanning electron microscopy and light microscopy. Adhesion of microorganisms was found in 77 biopsy specimens. Microorganisms in 64 specimens were classified as bacteria, in 10 as microfungi and in 4 as protozoa, including 1 specimen with both bacteria and microfungi. The structural types of bacteria found were morphologically cocciform, 8; short rod-shaped, 14; and long rod-shaped, 43. One specimen demonstrated adhesion of two structural types of bacteria. Bacteria were found in specimens from all age groups in roughly equal frequency. There was no difference in villus structure when comparing specimens from the groups with and without adhering bacteria, whereas ultrastructural alteration--that is, thinning of glycocalyx layer--was significantly more frequent in the group with bacteria. Moreover, within the group of specimens with bacteria the presence of long rod-shaped bacteria was associated with both damage of villus structure and deviation of cell surface ultrastructure. An increased amount of neutrophil granulocytes as an indicator of acute inflammation was found in 6 of 51 specimens with bacterial adhesion but in none of a matched reference material. In contrast, the amount of plasma cells and lymphocytes in the lamina propria and the amount of intraepithelial lymphocytes did not differ.     

Effect of Interferential Current Stimulation in Management of Osteo-arthritic Knee Pain

The primary purpose of this study was to assess the effect of interferential current stimulation on osteo-arthritic knee pain in the black Nigerian population.Thirty patients with a history of not less than three months' knee pain with radiographic confirmation of osteo-arthritis took part in the study. Patients were allocated alternately into an interferential current stimulation group and a placebo group.All the patients participated in a baseline exercise therapy programme with dietary advice. They received a total of eight 20-minute treatment sessions in four weeks. The treatment group received interferential current stimulation at a frequency of 100 Hz and pulse length of one-thirtieth of a second for the first 15 minutes of their treatment session. The stimulus was then reduced to 80 Hz for the next five minutes while other parameters remained unchanged. For the placebo group the electrodes of the stimulator were positioned appropriately but the stimulator was not tuned.The analysis of variance demonstrated a significant result (P < 0.01). Post hoc analysis revealed differences between initial and final pain values in the interferential current stimulation group. Similar results were observed in the placebo group, but the pain rating in the interferential current stimulation group was found to be significantly better than that for the placebo group.It was concluded that interferential current stimulation is more effective than a placebo in relieving osteo-arthritic knee pain in black Nigerian patients with symptomatic hypermobility.     

Impact of age and amyloidosis on thiol conjugation of transthyretin in hereditary transthyretin amyloidosis.

Variant forms and post-translational modifications of transthyretin (TTR) can be identified by electrospray ionisation mass spectrometry (ESI-MS). The aim of the present study was to investigate thiol conjugation of transthyretin and it's relation to age and symptomatic amyloid disease in different populations of variant TTR carriers. Plasma samples from 70 individuals from Denmark, Argentina, Sweden and Japan, with 2 different TTR mutations were analysed. The percentage cysteine (Cys) conjugated wild and variant TTR were calculated from the corresponding peaks of the spectra, and multiple regression analysis was employed to disclose relationships between age, symptomatic amyloid disease and origin. Age, origin and presence of symptomatic disease, were found to be independent factors related to transthyretin conjugation. A higher percentage of conjugated to unconjugated TTR was disclosed in symptomatic, but not in asymptomatic carriers. In summary: Thiol conjugation of TTR is dependent on age and presence of symptomatic amyloid disease. Furthermore, it varies between different populations. Variant TTR is more susceptible to thiol conjugation than the wild type. Post-translational factors may be related to amyloid formation and/or toxicity.