Isolation and characterization of a cDNA coding for a novel human 17.3K myelin basic protein (MBP) variant

Human fetal spinal cord poly A (+) mRNA was found to direct the synthesis of three major myelin basic protein (MBP) variants with molecular weights of 17K, 18.5K, and 21.5K when translated in reticulocyte lysates. In order to investigate the structural relationships between these MBP variants and their corresponding mouse variants, human fetal spinal cord and mouse brain cDNA libraries were constructed and screened for MBP cDNAs. A number of MBP cDNA clones were isolated and characterized. One of these, PP535 contained the entire coding region of the mouse 14K MBP; and another mouse cDNA clone, PP1.85, was almost full-length and coded for either the 21.5K MBP or the 18.5K MBP. A human clone (KK36), 1,173 nucleotides in length, contained the entire coding region of an MBP variant with a molecular weight of 17,342. The structure of this clone within its coding region is significantly different from the corresponding mouse 17K MBP cDNA. It is missing two sequences found in the mouse 17K MBP cDNA (exons 2 and 5); and it contains a sequence (exon 6) that is missing from the mouse 17K MBP cDNA. Thus, this human 17.3K cDNA codes for a "17K" human MBP variant that is quite different from the corresponding mouse variant and is identical to the human 18.5K MBP except for a deletion of a peptide consisting of 11 amino acids that includes the single tryptophan residue of the 18.5K MBP. An analysis of the structure of this 17.3K human MBP cDNA suggests that the major pathway for splicing the primary human MBP gene product may be different from that in the mouse.     

Distribution of the [3H]-label from low doses of radioactive ochratoxin a ingested by rats,and evidence for DNA single-strand breaks caused in liver and kidneys

The distribution of a single low dose of [³H]ochratoxin A (OTA) in different tissues of male Wistar rats, after administration by intubation, was investigated after 5 h, 24 h and 48 h. This dose corresponds to concentrations encountered in naturally contaminated feed (4 ppm). The distribution of [³H]-label varied with the time elapsed after administration; at 5 h the highest specific label was found in the stomach contents and in decreasing order in: intestinal contents, lung, liver, kidney, heart, fat, intestine, testes, and the lowest in muscles, spleen and brain. With exception of brain, fat, stomach and lung, all tissues showed maximum levels at 24 h, after which time the label decreased steadily, whereas in fat it increased.After a 12-week feeding experiment, with doses of 288.8 g/kg corresponding to an intake of 4 ppm in feed each 48 h, the DNA in liver and kidneys was investigated for damage. By the alkaline elution method combined with micro-spectrofluorimetric determinations of DNA, evidence for DNA single-strand breaks was obtained. These findings support reports on the carcinogenic action of OTA.     

Biomechanical comparison of semirigid junctional fixation techniques to prevent proximal junctional failure after thoracolumbar adult spinal deformity correction

BACKGROUND CONTEXTAdult spinal deformity patients treated operatively by long-segment instrumented spinal fusion are prone to develop proximal junctional kyphosis (PJK) and failure (PJF). A gradual transition in range of motion (ROM) at the proximal end of spinal instrumentation may reduce the incidence of PJK and PJF, however, previously evaluated techniques have not directly been compared.PURPOSETo determine the biomechanical characteristics of five different posterior spinal instrumentation techniques to achieve semirigid junctional fixation, or “topping-off,” between the rigid pedicle screw fixation (PSF) and the proximal uninstrumented spine.STUDY DESIGNBiomechanical cadaveric study.METHODSSeven fresh-frozen human cadaveric spine segments (T8–L3) were subjected to ex vivo pure moment loading in flexion-extension, lateral bending and axial rotation up to 5 Nm. The native condition, three-level PSF (T11–L2), PSF with supplemental transverse process hooks at T10 (TPH), and two sublaminar taping techniques (knotted and clamped) as one- (T10) or two-level (T9, T10) semirigid junctional fixation techniques were compared. The ROM and neutral zone (NZ) of the segments were normalized to the native condition. The linearity of the transition zones over three or four segments was determined through linear regression analysis.RESULTSAll techniques achieved a significantly reduced ROM at T10-T11 in flexion-extension and axial rotation relative to the PSF condition. Additionally, both two-level sublaminar taping techniques (CT2, KT2) had a significantly reduced ROM at T9-T10. One-level clamped sublaminar tape (CT1) had a significantly lower ROM and NZ compared with one-level knotted sublaminar tape (KT1) at T10-T11. Linear regression analysis showed the highest linear correlation between ROM and vertebral level for TPH and the lowest linear correlation for CT2.CONCLUSIONSAll studied semirigid junctional fixation techniques significantly reduced the ROM at the junctional levels and thus provide a more gradual transition than pedicle screws. TPH achieves the most linear transition over three vertebrae, whereas KT2 achieves that over four vertebrae. In contrast, CT2 effectively is a one-level semirigid junctional fixation technique with a shift in the upper rigid fixation level. Clamped sublaminar tape reduces the NZ greatly, whereas knotted sublaminar tape and TPH maintain a more physiologic NZ. Clinical validation is ultimately required to translate the biomechanics of various semirigid junctional fixation techniques into the clinical goal of reducing the incidence of proximal junctional kyphosis and failure.CLINICAL SIGNIFICANCEThe direct biomechanical comparison of multiple instrumentation techniques that aim to reduce the incidence of PJK after thoracolumbar spinal fusion surgery provides a basis upon which clinical studies could be designed. Furthermore, the data provided in this study can be used to further analyze the biomechanical effects of the studied techniques using finite element models to better predict their post-operative effectiveness.     

Whose Line Is It Anyway?: Dismantling the Foundations of Rape Culture

Archives of Sexual Behavior -     

Craniofacial Development: Neural Crest in Molecular Embryology

Craniofacial development, one of the most complex sequences of developmental events in embryology, features a uniquely transient, pluripotent stem cell-like population known as the neural crest (NC). Neural crest cells (NCCs) originate from the dorsal aspect of the neural tube and migrate along pre-determined routes into the developing branchial arches and frontonasal plate. The exceptional rates of proliferation and migration of NCCs enable their diverse contribution to a wide variety of craniofacial structures. Subsequent differentiation of these cells gives rise to cartilage, bones, and a number of mesenchymally-derived tissues. Deficiencies in any stage of differentiation can result in facial clefts and abnormalities associated with craniofacial syndromes. A small number of conserved signaling pathways are involved in controlling NC differentiation and craniofacial development. They are used in a reiterated fashion to help define precise temporospatial cell and tissue formation. Although many aspects of their cellular and molecular control have yet to be described, it is clear that together they form intricately integrated signaling networks required for spatial orientation and developmental stability and plasticity, which are hallmarks of craniofacial development. Mutations that affect the functions of these signaling pathways are often directly or indirectly identified in congenital syndromes. Clinical applications of NC-derived mesenchymal stem/progenitor cells, persistent into adulthood, hold great promise for tissue repair and regeneration. Realization of NCC potential for regenerative therapies motivates understanding of the intricacies of cell communication and differentiation that underlie the complexities of NC-derived tissues.     

World class health care

This article summarizes research findings on the roles of management approach and vision, delivery system design, human assets, advanced technology, and performance assessment in generating world class health care organizations.     

Extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy for urinary calculi: comparison of immediate and long-term effects

Extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy have become widely used technologies for removal of urinary calculi, despite a lack of adequate evaluative studies. The possibility of long-term adverse effects of these treatments has been raised, particularly an increase in stone recurrence and development of hypertension following extracorporeal shock wave lithotripsy. We conducted a retrospective study of 1,000 patients treated with extracorporeal shock wave lithotripsy or percutaneous nephrostolithotomy for upper tract stone disease to assess immediate effectiveness and complications, with prospective follow-up to assess stone recurrence and development of hypertension. The effectiveness of each treatment (defined in terms of patients rendered stone-free or having only fragments at discharge) was similar for most stone types. While stone recurrence rates in the first 2 years after treatment were similar in the two groups, cumulative recurrence at 3 years was higher following extracorporeal shock wave lithotripsy compared to percutaneous nephrostolithotomy (39% vs. 23%, p = 0.04). However, logistic regression and Kaplan-Meier analyses showed no significant difference in clinically evident recurrence for patients treated with extracorporeal shock wave lithotripsy. Cumulative incidence of clinically evident stone recurrence did not differ significantly between patients with fragments at discharge (20%) and patients rendered stone-free (15%) (p = 0.24). There was no difference in the development of new hypertension requiring medical treatment. Our findings indicate that extracorporeal shock wave lithotripsy is effective and associated with lower short-term morbidity than percutaneous nephrostolithotomy. Stone fragments left behind by lithotripsy do not appear to confer significant risk of early stone recurrence. Further study is necessary to define long-term risk of recurrence following extracorporeal shock wave lithotripsy.     

A New York kind of survey

Among the healthcare regulations enacted by New York State Health Commissioner Dr. David Axelrod is one requiring a comprehensive compulsory survey of each New York hospital by the state health department. A medical director offers his thoughts on the survey and describes its impact on his hospital.