No abstract

Several laboratories, including our own have reported the synthesis and activity of certain low relative molecular mass inhibitors of mammalian serine proteases, especially human leukocyte elastase (HLE, EC 3.4.21.37), an enzyme whose degradative activity on lung elastin has been implicated as a major causative factor in the induction of pulmonary emphysema, and which is present in the azurophil granules of human polymorphonuclear leukocytes (PMN). Normally, these granules fuse with phagosomes containing engulfed foreign material (such as bacteria), and HLE, in combination with other lysosomal enzymes, catabolizes the particles. Under certain pathological conditions, however, PMN become attached to host protein (elastin fibres, basement membrane, connective tissue, immune complexes), and in response to this adherence, the granules may fuse with the PMN outer membrane and release their contents, including HLE, directly onto the tissue. Besides emphysema, HLE may also contribute to the pathogenesis of disease states such as adult respiratory distress syndrome, and its potential involvement in rheumatoid arthritis makes HLE inhibitors of considerable interest. It is known that cephalosporin antibiotics (for example, cephalothin (compound I, Table 2)) are acylating inhibitors of bacterial serine proteases which help synthesize the cell wall by performing a transpeptidation reaction on a peptidyl substrate bearing a D-Ala-D-Ala terminus. We now report that neutral cephalosporins (that is, compounds not bearing a free carboxyl at position C-4) can be modified to become potent time-dependent inhibitors of HLE.

The purpose of the present study was to examine the efficacy of the multisensory teaching approach to improve reading skills at the firstgrade level. The control group was taught by the Houghton-Mifflin Basal Reading Program while the treatment group was taught by the Language Basics: Elementary, which incorporates the OrtonGillingham-based Alphabetic Phonics Method. The results showed that the treatment group made statistically significant gains in phonological awareness, decoding, and reading comprehension while the control group made gains only on reading comprehension.

Several national reports have suggested the usefulness of systematic, explicit, synthetic phonics instruction based on English word structure along with wide reading of quality literature for supporting development in early reading instruction. Other studies have indicated, however, that many in-service teachers are not knowledgeable in the basic concepts of the English language. They may be well versed in children's literature but not know how to address the basic building blocks of language and reading. The authors hypothesized that one of the reasons for this situation is that many instructors responsible for training future elementary teachers are not familiar with the concepts of the linguistic features of English language. This hypothesis was tested by administering a survey of language concepts to 78 instructors. The results showed that even though teacher educators were familiar with syllabic knowledge, they performed poorly on concepts relating to morphemes and phonemes. In a second study, 40 instructors were interviewed about best practices in teaching components and subskills of reading. Eighty percent of instructors defined phonological awareness as letter-sound correspondence. They also did not mention synthetic phonics as a desirable method to use for beginning reading instruction, particularly for students at risk for reading difficulties. In conclusion, providing professional development experiences related to language concepts to instructors could provide them the necessary knowledge of language concepts related to early literacy instruction, which they could then integrate into their preservice reading courses.

Resident mouse peritoneal macrophages have three phospholipase activities: a phospholipase A2 active at pH 4.5, a Ca2+-dependent phospholipase A2 active at pH 8.5 and a phosphatidylinositol-specific phospholipase C activity. When macrophages are exposed to zymosan in culture, the cellular activity of pH-4.5 phospholipase A2 is diminished in a manner dependent on zymosan concentration and time of exposure, whereas the cellular activities of pH-8.5 phospholipase A2 and phospholipase C remain unchanged. The depletion of pH-4.5 phospholipase A2 activity from the cell is paralleled by a quantitative recovery of this activity in the culture medium in a manner similar to the cellular depletion and extracellular recovery of two lysosomal enzymes. This release is specifically elicited by an inflammatory substance such as zymosan, since macrophages incubated with 6 micrometer latex spheres retain pH-4.5 phospholipase A2 activity and lysosomal enzyme activities intracellularly.