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- Li, M., et al.
(författare)
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Non-human Primate Models to Investigate Mechanisms of Infection-Associated Fetal and Pediatric Injury, Teratogenesis and Stillbirth
- 2021
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Ingår i: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 12
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Forskningsöversikt (refereegranskat)abstract
- A wide array of pathogens has the potential to injure the fetus and induce teratogenesis, the process by which mutations in fetal somatic cells lead to congenital malformations. Rubella virus was the first infectious disease to be linked to congenital malformations due to an infection in pregnancy, which can include congenital cataracts, microcephaly, hearing impairment and congenital heart disease. Currently, human cytomegalovirus (HCMV) is the leading infectious cause of congenital malformations globally, affecting 1 in every 200 infants. However, our knowledge of teratogenic viruses and pathogens is far from complete. New emerging infectious diseases may induce teratogenesis, similar to Zika virus (ZIKV) that caused a global pandemic in 2016-2017; thousands of neonates were born with congenital microcephaly due to ZIKV exposure in utero, which also included a spectrum of injuries to the brain, eyes and spinal cord. In addition to congenital anomalies, permanent injury to fetal and neonatal organs, preterm birth, stillbirth and spontaneous abortion are known consequences of a broader group of infectious diseases including group B streptococcus (GBS), Listeria monocytogenes, Influenza A virus (IAV), and Human Immunodeficiency Virus (HIV). Animal models are crucial for determining the mechanism of how these various infectious diseases induce teratogenesis or organ injury, as well as testing novel therapeutics for fetal or neonatal protection. Other mammalian models differ in many respects from human pregnancy including placentation, labor physiology, reproductive tract anatomy, timeline of fetal development and reproductive toxicology. In contrast, non-human primates (NHP) most closely resemble human pregnancy and exhibit key similarities that make them ideal for research to discover the mechanisms of injury and for testing vaccines and therapeutics to prevent teratogenesis, fetal and neonatal injury and adverse pregnancy outcomes (e.g., stillbirth or spontaneous abortion). In this review, we emphasize key contributions of the NHP model pre-clinical research for ZIKV, HCMV, HIV, IAV, L. monocytogenes, Ureaplasma species, and GBS. This work represents the foundation for development and testing of preventative and therapeutic strategies to inhibit infectious injury of human fetuses and neonates.
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| 2. |
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| 3. |
- Raval, Aparna, et al.
(författare)
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Downregulation of death-associated protein kinase 1 (DAPK1) in chronic lymphocytic leukemia
- 2007
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 129:5, s. 879-890
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Tidskriftsartikel (refereegranskat)abstract
- The heritability of B cell chronic lymphocytic leukemia (CLL) is relatively high; however, no predisposing mutation has been convincingly identified. We show that loss or reduced expression of death-associated protein kinase 1 (DAPK1) underlies cases of heritable predisposition to CLL and the majority of sporadic CLL. Epigenetic silencing of DAPK1 by promoter methylation occurs in almost all sporadic CLL cases. Furthermore, we defined a disease haplotype, which segregates with the CLL phenotype in a large family. DAPK1 expression of the CLL allele is downregulated by 75% in germline cells due to increased HOXB7 binding. In the blood cells from affected family members, promoter methylation results in additional loss of DAPK1 expression. Thus, reduced expression of DAPK1 can result from germline predisposition, as well as epigenetic or somatic events causing or contributing to the CLL phenotype.
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| 4. |
- Kartus, Jüri, 1955, et al.
(författare)
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Long-term clinical and ultrasound evaluation after arthroscopic acromioplasty in patients with partial rotator cuff tears
- 2006
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Ingår i: Arthroscopy. - 1526-3231. ; 22:1, s. 44-9
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Clinical and ultrasound evaluation of patients who had undergone debridement of a partial rotator cuff tear in conjunction with an arthroscopic acromioplasty. TYPE OF STUDY: Retrospective follow-up study. METHODS: Thirty-three consecutive patients were included in the study; 26 of the 33 (79%) patients underwent ultrasound evaluation of both shoulders and were examined by independent observers after a follow-up period of 101 months (range, 60 to 128 months; minimum, 5 years). RESULTS: The median time between onset of symptoms and surgery was 24 months (range, 6 to 360 months). At follow-up, the Constant score was 65 points (range, 15-98). The Constant score on the contralateral side was 84 points (range, 15-96; P < .0001). The strength in abduction was 4.7 kg (range, 1.2 to 11.1 kg) on the operated side and 5.1 kg (range, 1.8 to 10.4 kg) on the contralateral side (not significant). Twelve of the 26 patients reported discomfort or pain in the contralateral shoulder and during the follow-up period, and 3 of 26 had undergone an arthroscopic acromioplasty of the contralateral shoulder. Two of 26 patients underwent further surgery of the index shoulder during the follow-up period. The visual analogue score for pain for the index shoulder was 20 mm (range, 0 to 85). The ultrasound evaluation revealed that 9 of 26 patients had a full-thickness rotator cuff tear in the index shoulder and, of these, 3 of 9 were bilateral. CONCLUSIONS: It appears that an arthroscopic acromioplasty and rotator cuff debridement in patients with partial tears does not protect the rotator cuff from undergoing further degeneration. LEVEL OF EVIDENCE: Level IV.
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| 5. |
- Kartus, Jüri, 1955, et al.
(författare)
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Repair of type-2 SLAP lesions using Corkscrew anchors. A preliminary report of the clinical results
- 2004
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Ingår i: Knee Surg Sports Traumatol Arthrosc. - 0942-2056. ; 12:3, s. 229-34
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to perform a clinical assessment of patients who had undergone arthroscopic repair of a type-2 SLAP lesion using one double-looped Corkscrew anchor. Fifteen consecutive patients who agreed to fill in a pre- and post-operative questionnaire were included in the study. The aetiology was traumatic in 10/15 patients and non-traumatic in 5/15. At the index operation four patients underwent a concomitant acromioplasty, while four patients underwent supplementary anterior labrum fixation using suture anchors. Thirteen/15 (87%) of the patients were physically re-examined by independent observers after a follow-up period of 25 months (11-32). The questionnaire involved a patient-administered assessment of ten common activities of daily living. At follow-up, the Rowe score was 84 points (51-98) and the Constant score was 83 points (35-100). The external rotation in abduction was 85 degrees (60-110) on the operated side and 90 degrees (80-110) on the non-operated side ( p<0.05). The isometric strength in abduction was 8.3 kg (0.8-14.4) on the operated side and 8.9 kg (2.7-15.5) on the non-operated side ( p=0.006). Significant improvements ( p<0.05) compared with the pre-operative assessments were found in 2/10 activities of daily living. Another 4/10 activities seemed to improve but did not reach statistical significance ( p<0.08). Eleven of 15 patients returned to their pre-injury activity level. In conclusion, the majority of patients returned to their pre-injury activity level and the subjective patient-administered evaluations appeared to improve after arthroscopic repair of type-2 SLAP lesions using one double-looped Corkscrew anchor. We feel encouraged to continue using this technique.
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