Respiratory mechanics during mechanical ventilation: a model study on the effects of leak around a tracheal tube

Recently published studies indicate a potential clinical application of PET in head and neck tumors. In the preoperative staging phase, PET enables confirmation of regional lymph node extension and guides nodal neck dissection or systemic treatment. In this phase, a high negative predictive value, near 100%, could make it possible to avoid many negative neck dissections. This is a reliable technique for confirming or excluding the presence of recurrent/residual tumor and for obtaining an early evaluation of chemotherapeutic and radiotherapeutic response. PET imaging in many cases makes it possible to locate and guide histological study of tumors with an unknown primary. PET imaging for these indications is a perfect complementary method for clinical exploration and better than other imaging techniques.     

Combination oral contraceptives and cardiovascular disease

The abundance of rapid eye movement (REM) sleep in the neonatal mammal and its subsequent decline in the course of development, as well as the dramatic and widespread enhancement of CNS activity during REM sleep, led us to propose that this state plays a functional role in the normative physiological and structural maturation of the brain [54]. When, after 1 week of monocular deprivation (MD), a second week of MD was coupled with behavioral deprivation of REM sleep, the structural alteration in the visual system provoked by MD alone (interlaminar relay cell-size disparity in the lateral geniculate nucleus (LGN) was amplified. With the addition of REM deprivation during MD, the LGN cells connected to the surgically patched eye, which are smaller than normal after MD, became even smaller, whereas the LGN cells receiving input from the seeing eye, which display compensatory hypertrophy after MD, grew even larger. We believe that the interlaminar disparity effect widened because during REM deprivation, the already vision-compromised LGN cells associated with the patched eye also lose the ascending brainstem activation reaching them during the REM state. Loss of the two main sources of 'afference' by these LGN cells permits their seeing-eye LGN counterparts to gain even greater advantage in the competition for synaptic connections in cortex, which is reflected in the relative soma sizes of the LGN relay cells. It is likely that the relatively abundant REM state in early maturation provides symmetric stimulation to all LGN relay cells, irrespective of eye of innervation. The symmetric activation propagated from brainstem to LGN acts to 'buffer' abnormal, asymmetric visual input and, thereby diminishes the extreme, asymmetric structural alteration that results from MD in the absence of REM sleep. We conclude that REM sleep-generated CNS discharge in development has the effect of 'protecting' the CNS against excessive plasticity changes. This is consistent with the possibility that REM sleep plays a role in the genetically programmed processes that direct normative brain development.     

Different immunological mechanisms contribute to cartilage destruction in antigen-induced arthritis

Antigen-induced arthritis in guinea pigs was used as a model to investigate the pathogenic mechanisms responsible for cartilage destruction in chronic joint inflammation. The activation of macrophages, their effects on cartilage metabolism, and the development of autoimmunity to cartilage constituents were studied during the progression of arthritis. The results show that in arthritic animals the macrophages are systemically activated, with a peak in the early phase of inflammation. Interleukin 1, produced by the activated cells, suppresses the proteoglycan synthesis in cartilage explants and cultured chondrocytes and increases the proliferation of the cells in vitro. During the progression of arthritis humoral and cell-mediated immune responses to collagen type II and cartilage proteoglycans occur correlating with the severity of arthritis. It is concluded that different immunological mechanisms may be involved in cartilage destruction during antigen-induced arthritis. Mediator-induced metabolic reactions dominate in the early phase, whereas autoimmunity to cartilage might play an essential role in later phases of arthritis.     

Selective interference with class I major histocompatibility complex presentation of the major immediate-early protein following infection with human cytomegalovirus

Responses of cytotoxic T-cells (Tc) to human cytomegalovirus (CMV) represent the predominant mechanism by which hosts resist CMV infection. The CMV major immediate-early protein (IE) is present throughout the virus replicative cycle. Studies were performed to determine whether Tc specific for IE effectively lyse CMV-infected targets and are thus capable of providing protective immunity against infection. After in vitro stimulation of peripheral blood mononuclear cells with CMV-infected autologous fibroblasts, Tc specific for IE were not readily detectable in CMV-reactive polyclonal Tc lines. However, after stimulation of peripheral blood mononuclear cells with cells selectively expressing IE, weak but detectable IE-specific Tc responses were observed. The frequency of IE-specific Tc clones derived from cultures stimulated with IE-expressing cells was 50 to 100 times lower than the frequency of Tc clones specific for other CMV proteins isolated from cultures stimulated with CMV-infected cells. All of the IE-specific Tc clones, which efficiently lysed targets selectively expressing IE, demonstrated minimal lysis of CMV-infected fibroblasts, despite abundant IE expression in these target cells. In contrast to these results with IE, other viral proteins were efficiently presented during all phases of CMV infection. These data suggest that CMV has evolved a unique mechanism for selectively limiting the presentation of the potentially immunogenic IE protein, which may preclude IE-specific Tc from providing protective immunity to CMV infection.     

The kinetics of ACTH expression in rat leukocyte subpopulations

The peripherin gene has three potential ATG translation initiation sites at positions 38, 56, and 290. The second ATG has been proposed to be the initiation codon used for translation of the protein, but there is no experimental evidence for this conjecture. We have isolated a full-length peripherin cDNA (designated as p61-11) from a rat brain cDNA library. Upon sequencing, we found that this cDNA contains a point mutation at the second potential translation initiation codon, which changes this ATG to ACG. When expressed in SW13 cl.2 vim- cells, a cell line without any detectable cytoplasmic intermediate filaments, the protein product of p61-11 cannot form a filamentous network and the major product is 45 kDa in size, which is most likely initiated from the third ATG. The protein product from the first ATG (57 kDa in size) of p61-11 is also detected albeit in smaller amounts. We introduced a frame-shift mutation upstream of the third ATG in p61-11 to create p61-11FS and showed that the third ATG is able to initiate translation efficiently even in the presence of the first ATG, and the 45 kDa protein leads to a diffuse nonfilamentous staining pattern in vim- cells confirming that the first ATG may not be the preferred translation initiation codon, since it cannot suppress a downstream ATG. We increased the translation efficiency from the first ATG of p61-11 by mutating the three nucleotides preceding this first ATG and thereby placing it in a better Kozak consensus sequence for translation initiation. The resulting 57 kDa protein is able to form a filamentous network in vim- cells. We corrected the mutation in the original p61-11 by polymerase chain reaction and generated two peripherin constructs: perM1M2 (which contains all three translation initiation codons) and per delta 1M2 (the first ATG is deleted, but the other two are present). When transfected, their protein products, about 57 kDa in size, form filamentous networks in the absence of other cytoplasmic intermediate filaments. Since there is no 45 kDa protein detected for these latter two constructs, it is reasonable to conclude that in the presence of the second ATG, little or no translation is initiated from the third ATG. Taken together, these results strongly suggest that the second ATG is the preferred translation initiation codon for the peripherin gene.