Characterizations of Pneumocystis carinii and rat lung lipids: glyceryl ethers and fatty alcohols

Pneumocystis carinii carinii and rat lung phospholipids contained 3-6% 1-alkyl-2-acyl glycerols composed of the glyceryl ether species, 1-O-octadecyl glycerol (batyl alcohol), 1-O-octadec-9-enyl glycerol (selachyl alcohol), 1-O-hexadecyl glycerol (chimyl alcohol), and 1-O-hexadec-9-enyl glycerol. Of the major phospholipid classes, phosphatidylinositol (PI) and phosphatidylserine contained the highest percentage of alkyl acyl glycerols. Methylprednisolone treatment caused an increase in alkyl acyl PI of rat lung lipids from 12% to 45%. As the PI concentration in lung phospholipids increases in rats treated with methylprednisolone, the increase in alkyl acyl PI was substantial; the proportions of alkyl acyl phosphatidylethanolamine and alkyl acyl lyso phosphatidylcholine (PC) also increased. Pneumocystis phospholipids contained higher proportions of alkyl acyl PC than the phospholipids of the lungs from normal and immunosuppressed uninfected rats. The glyceryl ether compositions of P. carinii carinii PC and lyso PC were similar, which suggests that lyso PC in the organism is derived by phospholipase A2 action on PC. This was not the case for PC and lyso PC of the lung controls. Analysis of the free fatty alcohols, precursors of glyceryl ethers identified only saturated species in P. carinii carinii and rat lung controls. Thus, the introduction of a double bond in the alcohol moiety of glyceryl ethers occurs after formation of the ether linkage between fatty alcohol and the glyceryl backbone.     

Morphology of P and M retinal ganglion cells of the bush baby

P/midget ganglion cells mediate red-green color opponency in anthropoids. It has been proposed that these cells evolved as a specialization to subserve color vision in primates. If that is correct, they must have evolved about the same time as the long-wavelength ('red') and medium-wavelength ('green') pigment genes diverged, thirty million years ago. Strepsirhines are another group of primates that diverged from the ancestor of the anthropoids at least 55 million years ago. If P/midget ganglion cells evolved to subserve color vision, they should be absent in strepsirhines. We tested this hypothesis in a nocturnal strepsirhine, the greater bush baby Otolemur. The retinal ganglion cells were labeled with the lipophilic tracer Dil and the results show that bush babies have P/midget and M/parasol cells similar to those found in the peripheral retinas of anthropoids. A number of studies have shown that the P and M pathways of bush babies share many similarities with those of anthropoids, and our results show that the same is true for their retinal ganglion cells. These results support the hypothesis that the P system evolved prior to the emergence of red-green color opponency.     

Imputation for exposure histories with gaps, under an excess relative risk model

An Onchocerca volvulus expression library was differentially screened to identify a molecular marker distinguishing sowda (lichenified onchodermatitis) from other onchocerciasis forms. One clone, PG3, was recognized by pooled sera from patients with sowda, but not by pooled sera from patients with generalized onchocerciasis; it was not recognized by sera from patients with lymphatic filariasis or other helminth infections. The DNA of PG3 hybridized strongly with O. volvulus Eco RI-digested DNA, but not with DNA from Brugia spp., Trichinella spp., and humans. A weak reaction was observed with DNA from O. gibsoni and Acanthocheilonema viteae. The PG3 DNA sequence showed a high homology with both human and nematode collagens. Confirmation of the collagen-like nature of the sowda-specific PG3 product was obtained by amino terminal sequencing of the PG3 expression product, as well as by demonstrating its susceptibility to collagenase digestion. The characteristic recognition of the O. volvulus collagen specified by clone PG3 was confirmed by measuring antibody levels to the expressed product in individual sowda and generalized onchocerciasis sera, respectively. Identification of a nematode collagen antigen mainly recognized in sowda patients raises the possibility that this extreme form of dermatitis might arise through cross-reactivity between anti-O. volvulus collagen antibodies and human collagen. However, a relationship between the PG3 recognition by antibodies and the sowda pathogenesis could not be demonstrated.     

Nerve growth factor (NGF)-mediated protection of neural crest cells from antimitotic agent-induced apoptosis: the role of the low-affinity NGF receptor

Prevention by nerve growth factor (NGF) of apoptotic death in neural cells has been variously ascribed to binding of NGF to its low-affinity (p75) or high-affinity (trkA) receptor or to a cooperative interaction between the two. In a series of studies using, in turn, neuroblastoma cell lines that express only p75, mutant NGF species that bind selectively to either p75 or trkA, and a polyclonal antibody that binds to the NGF-binding domain of p75, we demonstrate that NGF binding to p75 is both necessary and sufficient for the abrogation of apoptosis in neuroblastoma cells treated with antimitotic agents.     

Tobacco-related instruction in undergraduate nursing education in Illinois

Tobacco use is responsible for more deaths in the United States than any other factor. Nurses are in a unique position to convey life-saving messages to clients regarding tobacco use. To gauge the type and extent of tobacco-related background knowledge acquired by nurses in the course of their education, the Nurses' Committee of the Illinois Division of the American Cancer Society (ACS) surveyed 70 nursing programs in the state of Illinois. The number of lecture hours spent on tobacco-related issues was greater in LPN programs than in either associate or baccalaureate degree programs, and instruction was scattered throughout the curriculum of each program. Most schools reported heavy reliance on adult medical-surgical textbooks to convey tobacco-related content. The most recent editions of the textbooks used by the schools were reviewed, and they also were found to adopt a scattered approach, with a disappointing lack of depth regarding the hazards of tobacco. It is recommended a single course be identified as responsible for relaying tobacco-related content and information supplied by general medical-surgical textbooks be supplemented by materials drawn from other sources.     

A phase I study of adenovirus-mediated wild-type p53 gene transfer in patients with advanced non-small cell lung cancer

Mutations of the tumor suppressor gene p53 are the most common genetic alterations observed in human cancer. Loss of wild-type p53 function impairs cell cycle arrest as well as repair mechanisms involved in response to DNA damage. Further, apoptotic pathways as induced by radio- or chemotherapy are also abrogated. Gene transfer of wild-type p53 was shown to reverse these deficiencies and to induce apoptosis in vitro and in preclinical in vivo tumor models. A phase I dose escalation study of a single intratumoral injection of a replication-defective adenoviral expression vector encoding wild-type p53 was carried out in patients with incurable non-small cell lung cancer. All patients enrolled had p53 protein overexpression as a marker of mutant p53 status in pretreatment tumor biopsies. Treatment was performed either by bronchoscopic intratumoral injection or by CT-guided percutaneous intratumoral injection of the vector solution. Fifteen patients were enrolled in two centers, and were treated at four different dose levels ranging from 10(7) to 10(10) PFU (7.5 x 10(9) to 7.5 x 10(12) particles). No clinically significant toxicity was observed. Successful transfer of wild-type p53 was achieved only with higher vector doses. Vector-specific wild-type p53 RNA sequences could be demonstrated in posttreatment biopsies of six patients. Transient local disease control by a single intratumoral injection of the vector solution was observed in four of those six successfully transduced patients. There was no evidence of clinical responses at untreated tumor sites. Wild-type p53 gene therapy by intratumoral injection of a replication-defective adenoviral expression vector is safe, feasible, and biologically effective in patients with advanced non-small cell lung cancer.     

Ti-gate metal induced PHEMT degradation in hydrogen

Through accelerated life test in hydrogen, we have found, for the first time, that in addition to Pt metal, Ti metal in a Ti/Pt/Au-gate PHEMT can also induce a significant hydrogen effect by reacting with a small amount of hydrogen gas in the ambient. The hydrogen sensitivity of a PHEMT device caused by Ti gate metal is significantly less than that due to Pt. Since Ti is not a hydrogen catalyst, the resulting hydrogen sensitivity indicates that a catalytic reaction between the gate metal and hydrogen gas is not required to have a detrimental hydrogen effect. The data also show that the degradation evident in the PHEMT devices due to the Ti-H₂ interaction is similar to that from the Pt-H₂ interaction. It is clear from this work that attempting to solve the hydrogen degradation problem by eliminating the Pt gate metal in a PHEMT is ineffective