Presence of lysine at aa 335 of the hemagglutinin-neuraminidase protein of mumps virus vaccine strain Urabe AM9 is not a requirement for neurovirulence

The recent global resurgence of mumps has drawn attention to the continued need for robust mumps immunization programs. Unfortunately, some vaccines derived from inadequately attenuated vaccine strains of mumps virus have caused meningitis in vaccinees, leading to withdrawal of certain vaccine strains from the market, public resistance to vaccination, or in some cases, cessation of national mumps vaccination programs. The most widely implicated mumps vaccine in cases of postvaccination meningitis is derived from the Urabe AM9 strain, which remains in use in some countries. The Urabe AM9 vaccine virus has been shown to exhibit a considerable degree of nucleotide and amino acid heterogeneity. Some studies have specifically implicated variants containing a lysine residue at amino acid position 335 in the hemagglutinin-neuraminidase (HN) protein with neurotoxicity, whereas a glutamic acid residue at this position was associated with attenuation. To test this hypothesis we generated two modified Urabe AM9 cDNA clones coding either for a lysine or a glutamic acid at position 335 in the HN gene. The two viruses were rescued by reverse genetics and characterized in vitro and in vivo. Both viruses exhibited similar growth kinetics in neuronal and non-neuronal cell lines and were of similar neurotoxicity when tested in rats, suggesting that amino acid 335 is not a crucial determinant of Urabe AM9 growth or neurovirulence.     

Comparison of the effects of three different combinations of general anesthetics on the electroretinogram of dogs

The objective of this study is to compare the effects of three different anesthetic combinations on the electroretinogram in the same animals under similar laboratory conditions. Thiopental–isoflurane (TI), medetomidine–ketamine (MK), and xylazine–ketamine (XK) were used on each of 12 healthy miniature schnauzer dogs (MS) with a period of at least 3 weeks in between subsequent anesthesia protocols, using the Dog Standard Protocol. The scotopic ERGs consisted of scotopic low stimulus strength (S) responses designated S1, S2, S3, S4, and S5, at 1, 5, 10, 15, and 20 min after dark adaptation, respectively, and scotopic standard stimulus strength (S-ST) responses. The photopic ERGs consisted of a photopic single flash (P) response and 31 Hz flicker (P-FL) responses. For S-ST (2.5 cd s/m²), the amplitude of the a-wave using TI was significantly lower than that using MK (adjusted P = 0.05) and XK (adjusted P = 0.03), and the implicit time of the a-wave was significantly shorter than that using MK (adjusted P = 0.04). For P (2.5 cd s/m²), the amplitude of the b-wave using XK was significantly higher than that using MK (adjusted P = 0.01). The implicit times of the b-wave using TI was significantly longer and shorter than that of MK for S1, S2 and P-FL and for S4 and S-ST, respectively, and than that of XK for S2 and P-FL and for S5 and S-ST, respectively. The results of the present study showed that TI affected both the amplitude and the implicit time of the a-wave for S-ST and the implicit time of the b-wave relatively more so than was the case when using XK or MK. Therefore, it appears that either XK or MK could be advantageous to use rather than TI for clinical studies.     

Primary Hemiarthroplasty for Proximal Humeral Fractures in the Elderly: Long-Term Functional Outcome and Social Implications

Abstract Background: Primary shoulder hemiarthroplasty is an established treatment modality for complex fractures of the proximal humerus. Long-term functional outcome is often disappointing. However, little is known about social implications particularly in the elderly. Methods: A single-institution case series of consecutive geriatric patients (age > 70 years) treated with shoulder hemiarthroplasty for complex fractures of the proximal humerus between 1994 and 1997 was analysed. Postoperative morbidity, long-term function, radiological outcome and social implications were evaluated. Results: Seventy-seven patients fulfilled the study criteria. Median age at the time of operation was 80 years (range 70–93 years). Systemic and local postoperative complications were observed in 8% including 2 patients (3%) with revision surgery. Postoperative mortality was 1%. Forty-eight patients (62%) were available for follow-up (median 49 months, range 25–80 months), 22 (29%) died from causes unrelated to hemiarthroplasty before follow-up and 7 patients (9%) did not attend follow-up examination. Median Constant-Murley score was 41 points (range 17–77 points). Long-term results concerning pain were satisfying. The Oxford shoulder score ranged from 14 to 40 (median 30). Forty-one patients (85%) still lived in their original environment and managed their daily life independently despite poor shoulder function. Four patients (8%) lived in a retirement home and 3 (6%) in a nursery home. Eighty percent of our patients were still able to use public transportation, do the daily shopping and wash their whole body by themselves. Conclusion: Most patients managed their daily life independently despite poor shoulder function.     

<Emphasis Type="Italic">Bcl11b</Emphasis>mutations identified in murine lymphomas increase the proliferation rate of hematopoietic progenitor cells

Background  

The telomeric region of mouse chromosome 12 has previously shown frequent allelic loss in murine lymphoma. The Bcl11b gene has been identified and suggested as a candidate tumor suppressor gene within this region. In this study, we aimed to elucidate whether Bcl11b is mutated in lymphomas with allelic loss, and whether the mutations we detected conferred any effect on cell proliferation and apoptosis.     

Genetic Analyses of the Mouse Deafness Mutations Varitint-Waddler (Va) and Jerker (Espnje)

Genetic studies on spontaneous mouse mutants with hearing defects have provided important insights into the function of genes expressed in inner ear hair cells. Here we report on our genetic analyses of the deaf mutants varitint-waddler (Va) and jerker (Espnje). A high-resolution genetic map localizes VaJ to a 0.14 ± 0.08 cM region between D3Mit85 and D3Mit259 on distal chromosome 3. By comparative mapping, the human ortholog resides at 1p22.3 between markers D1S3449 and D1S2252. To study the effect of different genetic backgrounds on the hearing phenotype, Espnje and VaJ were crossed to various inbred strains. Auditory-evoked brainstem response tests on F2 progeny demonstrate that expression, inheritance, and penetrance of the hearing phenotype are solely controlled by the mutant allele. To test for a genetic interaction between Espnje and Cdh23v, auditory function was analyzed in double heterozygotes; no significant increases of thresholds of sound pressure levels were observed. The results establish the framework for cloning the Va gene and provide valuable insights into the genetics of deafness mutations in the mouse.     

Biology and Biomechanics in Osteosynthesis of Proximal Humerus Fractures

Abstract Surgical treatment of proximal humeral fractures still remains a challenge. This is primarily due to the fact that sufficient implant fixation in humeral head fractures is often not achieved due to substantial bone tissue loss with increasing age. In the last few years the locking plates and locking nails have been introduced into clinical practice with varying results. The biomechanical studies have focused on locking plate osteosynthesis as well. The following paper focuses on bone quality, biomechanical studies and biology of proper osteosynthesis and reviews the most recent literature.