The Keio Journal of Medicine

ABSTRACT

Intersubjectivity, Affective Neuroscience, and the Neurobiology of
Autistic Spectrum Disorders
Kenneth J.Aitken

Knowledge of social development in infancy and the developmental psychopathologies depend on an understanding of the process through which relationships develops between the infant and his/her caregivers. We call this eintersubjectivity' - an intrinsically social phenomenon which depends on social abilities with which the infant is equipped at birth; on accrued behaviours; and on the availability of complimentary processes in his/her caregivers. These processes, their development, and their biological underpinnings are the subject of eaffective neuroscience'.
The application of descriptive methodology to developmental psychopathology builds on detailed analysis of early recordings. This has enabled a range of differences to be characterized in infants who have gone on to be diagnosed as autistic. Such studies have typically looked in only in high-risk groups, More recent studies using such methods identify infants who lack these early prognostic markers but who also go on to develop autism.
Genetic analysis is starting to provide answers to why particular individuals are affected and why certain individuals benefit from particular approaches. Many genetic conditions and gene markers are associated with ASDs at a greater than expected frequency. These were discussed and the relevance of understanding some of the differences in neurobiology for treatment and management were presented.
 



TLR5-mediated immune responses to enteric microbes
Andrew Gewirtz

Toll-like receptors (TLR) recognize a variety of highly conserved microbial products and thus mediate the innate ability of complex eukaryotes to recognize the presence of bacteria and viruses. TLRs have been widely studied in innate immune cells, particularly macrophages and dendritic cells, which respond well to many TLR ligands. In contrast, the epithelial cells that line the gastrointestinal tract are unresponsive to most TLR ligands but yet express TLR5 on their basolateral surface and are highly responsive to bacterial flagellin. Consequently, TLR5 serves as the primary means by which such epithelial cells detect flagellated bacteria with ligation of TLR5 by flagellin resulting in the potent induction of antibacterial/cytoprotective gene expression. While such TLR5-mediated gene expression promotes acute inflammation, it also protects the intestine against a variety of pathogens and chemical insults. Accordingly, mice lacking TLR5 are unable to control their commensal microbiota and exhibit spontaneous colitis and increased intestinal damage in response to flagellated pathogens. In contrast to other TLR ligands, flagellin is also a potent target of the adaptive immune system in part due to its ability to activate innate immunity. Thus innate and adaptive immune responses to flagellin appear to play an important role in host defense of the intestine.
 



Handmade Cloning in Cattle and Pigs
Gábor Vajta

Although genetic failures and epigenetic mechanisms have been identified as potential causes of low developmental rates, abortions, stillbirths, and developmental abnormalities, many of these problems can be avoided by refinement of the cloning technology. Additionally, the increasing number of healthy clones does not show any deviation from their naturally produced counterparts. An efficient, simple, inexpensive and reliable nuclear transfer method would considerably increase the possibilities of application. In cattle, the handmade cloning (HMC) technique was found as a competitive alternative of traditional nuclear transfer. However, application of this approach to pigs required a series of modification in the method because of the sensitivity of porcine oocytes and the different requirements for reprogramming and embryo culture. During the past three years, a series of modifications in the original technology has eventually resulted in a highly efficient porcine HMC method. Initial surgical embryo transfer experiments performed with compacted morulae and blastocyst resulted in approx. 50% pregnancy and farrowing rates. Up to 22% of the transferred HMC embryos developed to healthy offspring, and up to 10 piglets were born from one sow. Very recently, 6 offspring were also born from vitrified blastocysts. Ongoing embryo transfer experiments may prove the value of the technique for transgenic piglet production. Considering that the method requires only one stereomicroscope and an inexpensive fusion machine; and one scientist may produce 40 to 50 blastocyst (enough for transfer in one sow) in 3 to 4 hours, HMC seems to be a highly competitive alternative of traditional cloning.
 



Myoblasts transplantation into denervated rat muscles
Taro Koyama

The purpose of this investigation is to observe whether cultured myoblasts take in denervated muscle and differentiate myofiber without reinnervation. Cultured myoblasts survived in not only intact muscle but also denervated muscle without reinnervation at 1week after transplantation. The cells differentiated myofibers in both intact and denervated muscles at 2 weeks and 4 weeks after transplantation. The ratio of denervated muscle weight to intact muscle weight decreased from 1week to 4 weeks after myoblasts transplantation, but the decrease is not significant for first 2 weeks. These data suggest that transplanted myoblasts could survive and differentiate myofibers in denervated muscle and myoblasts transplantation before reinnervation may prevent denervated muscle atrophy and improve muscle regeneration after nerve repair.