Family-centered Care for Sick Newborns: A Thumbnail View

Family-centered care (FCC) for sick newborns is emerging as a paradigmatic shift in the practice of facility-based newborn care. It seeks to transforming a provider-centered model into a client-centered one and thus build a new therapeutic alliance. FCC is the cornerstone of continuum of care, imparting caregiving competencies to parents/caregivers both within institutions as well as after the discharge. This has potential gains for the newborn, family members, and facility-level staff. The initial model piloted in tertiary-care settings is now undergoing translation at five sites across the country; the outcomes are keenly awaited.     

Antiproliferative, cytotoxic and apoptogenic activity of Indian toad (Bufo melanostictus, Schneider) skin extract on U937 and K562 cells.

The antiproliferative, cytotoxic and apoptogenic activities of Bufo melanostictus (Indian common toad) skin extract (TSE) on U937 and K562 leukemic cell line has been investigated. TSE significantly (P<0.001) reduced the time-dependent cell proliferation and decreased MTT values in U937 and K562 cells. TSE (IC50 doses) suppressed the proliferating cell nuclear antigen expression in both the cells. It was demonstrated that, TSE (IC50 doses) primarily arrested the U937 and K562 cells at G1 phase of the cell cycle. Confocal microscopy showed the altered fragmented nuclei and apoptotic bodies formation in TSE (IC50 doses) treated U937 and K562 cells. Membrane blebbing, cell surface shrinkage and perforation were observed through scanning electron microscope. TSE-induced DNA fragmentation in U937 and K562 cells was reflected in single-cell gel electrophoresis. TSE significantly (P<0.001) increase the length-width ratio of DNA mass as compared to control in comet assay. The flow cytometric analysis of annexin-V binding to the cancer cells further supported the apoptotogenic activity of TSE. The effect of TSE on normal human peripheral blood mononuclear cells viability and cytotoxicity was studied in culture and found to be less cytotoxic than on the U937 and K562 cells. The findings from the present study suggested that TSE might possess potent antineoplastic agent having antiproliferative, cytotoxic and apoptogenic activity against U937 and K562 myeloid leukemic cells.     

Molecular cloning and sequencing of a cDNA for olfactory marker protein.

cDNA clones corresponding to mRNA for rat olfactory marker protein (OMP) were isolated from a cDNA library. The library was constructed from olfactory mucosa poly(A)+ RNA enriched for OMP mRNA and cloned into a pBR322-derived plasmid, pMG5. OMP cDNA clones were detected by using a 17-base oligonucleotide probe that contained all 16 possible sequences coding for a known partial amino acid sequence of rat OMP. The identity of these clones was confirmed by hybrid-selected translation and nucleotide sequencing. The sequence of one clone was determined and contained the complete OMP coding region of 486 nucleotides followed by 1630 nucleotides of the 3' untranslated region. The 3' untranslated region included the polyadenylylation signal 16 nucleotides upstream of the poly(A) tail. No other ATG-initiated open reading frame larger than 20 codons was present in register. RNA blot analysis of olfactory mucosa poly(A)+ RNA using this clone as a probe indicated that the level of OMP mRNA, but not its size, declined significantly within a few days following olfactory bulbectomy. OMP mRNA was not detected in 14 nonolfactory rat tissues. Surprisingly, a small amount of OMP mRNA was observed in olfactory bulb. The presence of OMP mRNA in olfactory bulb was confirmed by in vitro translation and immunoprecipitation. These results suggest either that a previously undescribed population of neurons in the olfactory bulb synthesize OMP or that OMP mRNA is transported to the bulb by axonal transport.     

Immune deviation: demonstration of split tolerance in vitro by inhibition of macrophage migration

Migration of cells, taken from animals immunized with ovalbumin in Freund's complete adjuvant which gave normal delayed hypersensitivity skin responses, was found to be significantly inhibited in the presence of antigen. Migration of peritoneal exudate cells from guinea-pigs in which immune deviation had been induced by immunization with antigen in Freund's incomplete adjuvant was not inhibited.     

Competitive binding to a charged leucine motif represses transformation by a papillomavirus E6 oncoprotein

E6 oncoproteins from HPV-16 and bovine papillomavirus type 1 (BPV-1) bind to similar leucine-rich peptides termed charged leucine motifs found on the cellular focal adhesion protein paxillin and the E3 ubiquitin ligase E6AP. BPV-1 E6 (BE6) mutants that do not bind to paxillin are defective at inducing cellular transformation. It is possible, however, that BE6 mutants that do not bind paxillin are defective for transformation for an unrelated reason than the ability to bind to charged leucine motifs. To address the role of BE6 interaction with charged leucine motifs, we fused a BE6-binding charged leucine motif to the amino terminus of BE6, thereby creating an autoinhibitory binding domain. We found that the fusion protein failed to bind to paxillin or transform murine C127 cells. Mutation of the amino terminal binding motif in the fusion protein restored both interaction with paxillin and transformation. This demonstrates that BE6 transformation requires binding to charged leucine motifs on particular cellular proteins and that transformation by papillomavirus oncoproteins can be repressed by competitive interactions with charged leucine motifs.     

Cystic duct and Heister's "valves"

The anatomy and physiology of the cystic duct have been relatively neglected by anatomists and the function of the spiral mucosal folds or "valves" of Heister, first described in 1732, remains obscure. The gross and microscopic anatomy of the cystic duct is reviewed together with results from laboratory investigations into the function of the cystic duct and its spirally arranged folds. The duct and spiral folds contain muscle fibers responsive to pharmacologic, hormonal, and neural stimuli. There is, however, no convincing evidence of a discrete muscular sphincter within the duct. Although the cystic duct is unlikely to play a major role in gallbladder filling and emptying, it appears to function as more than a passive conduit. Coordinated, graded muscular activity in the cystic duct in response to hormonal and neural stimuli may facilitate gallbladder emptying. The principal function of the internal spiral folds that are found in man and other animals may be to preserve patency of this narrow, tortuous tube rather than to regulate bile flow.     

Immunomodulation of autoimmune and inflammatory diseases with intravenous immunoglobulin

Abstract Intravenous immunoglobulin (IVIg) has been used in the treatment of primary and secondary antibody deficiencies for over two decades. Since the early 1980s, the therapeutic efficacy of IVIg has been established in idiopathic thrombocytopenic purpura, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, dermatomyositis and Kawasaki syndrome, and the prevention of graft versus host disease in recipients of allogeneic bone marrow transplants. Its use has also been reported in a large number of other autoimmune and systemic inflammatory conditions. In this review, we discuss the mechanisms by which IVIg exerts immunomodulatory effects in immune pathologies.