Surgery in the elderly.

The elderly (those 75 years of age or older) are a heterogeneous group. They present with both elective and urgent surgical problems, and risk assessment, decision-making and perioperative care are typically more challenging than in younger patients. An appreciation for this heterogeneity and an understanding of how physiologic changes of aging affect surgical care are essential if the best outcomes are to be achieved.

Mutational analysis of a plant branchpoint and polypyrimidine tract required for constitutive splicing of a mini-exon.

The branchpoint sequence and associated polypyrimidine tract are firmly established splicing signals in vertebrates. In plants, however, these signals have not been characterized in detail. The potato invertase mini-exon 2 (9 nt) requires a branchpoint sequence positioned around 50 nt upstream of the 5' splice site of the neighboring intron and a U11 element found adjacent to the branchpoint in the upstream intron (Simpson et al.

The development of a protocol for the use of 5-HT3 antagonists in chemotherapy-induced nausea and vomiting.

The purpose of this study was to evaluate the effectiveness of three 5-HT3 antagonists in routine clinical practice. The ultimate aim was to develop an antiemetic protocol, selecting a single 5-HT3 antagonist. Each of the drugs was studied for a 4-month period and data was collected from patients on nausea, vomiting (both acute and delayed) and side-effects by means of a diary card.

A differential role for the mitogen-activated protein kinases in lipopolysaccharide signaling: the MEK/ERK pathway is not essential for nitric oxide and interleukin 1beta production.

Endotoxin (lipopolysaccharide, LPS) is a component of the outer membrane of Gram-negative bacteria and promotes the activation of macrophages and microglia. Although these cells are highly LPS-responsive, they serve unique tissue-specific functions and exhibit different LPS sensitivities. Accordingly, it was of interest to evaluate whether these biological differences reside in variations within LPS signaling pathways between these two cell types.

Kif1C, a kinesin-like motor protein, mediates mouse macrophage resistance to anthrax lethal factor.

Background: Inbred mouse strains exhibit striking differences in the susceptibility of their macrophages to the effects of anthrax lethal toxin (LeTx). Previous data has shown that this difference in susceptibility lies downstream of toxin entry into macrophages. A locus controlling this phenotype, called Ltxs1, has been mapped to chromosome 11, but the responsible gene has not been identified.

Cutting edge: the nucleotide receptor P2X7 contains multiple protein- and lipid-interaction motifs including a potential binding site for bacterial lipopolysaccharide.

The nucleotide receptor P2X7 has been shown to modulate LPS-induced macrophage production of numerous inflammatory mediators. Although the C-terminal portion of P2X7 is thought to be essential for multiple receptor functions, little is known regarding the structural motifs that lie within this region. We show here that the P2X7 C-terminal domain contains several apparent protein-protein and protein-lipid interaction motifs with potential importance to macrophage signaling and LPS action.

Expression of intron-containing GUS constructs is reduced due to activation of a cryptic 5' splice site.

An intron-containing beta-glucuronidase (GUS) gene has been used widely in promoter analyses and as a plant transformation marker. Maximal plant gene expression requires accurate and efficient removal of the intron from the expressed pre-mRNA transcripts by splicing. Detailed analysis of splicing of potato ST-LS1 and pea legumin introns from GUS constructs revealed the activation of a cryptic 5' splice site in the GUS coding sequence 4 nt upstream from the authentic intron 5' splice site.

Differential expression of potato U1A spliceosomal protein genes: a rapid method for expression profiling of multigene families.

The spliceosomal protein, UIA, is a component of the U1snRNP essential to pre-mRNA splicing. From the ubiquitous nature of the splicing machinery, expression of U1A genes is expected to be constitutive. However, many plant genes are organised in multigene families that exhibit variation in expression profiles.

Enteric neuroblasts require the phosphatidylinositol 3-kinase pathway for GDNF-stimulated proliferation.

The enteric nervous system (ENS) develops from neural crest cells that enter the gut, migrate, proliferate, and differentiate into neurons and glia. The growth factor glial-derived neurotrophic factor (GDNF) stimulates the proliferation and survival of enteric crest-derived cells. We investigated the intracellular signaling pathways activated by GDNF and their involvement in proliferation.

Genetic, physical, and transcript map of the Ltxs1 region of mouse chromosome 11.

Lethal factor (LF) is a toxin secreted by Bacillus anthracis that plays an important role in the pathogenesis of anthrax. Intoxication with LF results in a macrophage-specific cytolysis that is not well understood. Interestingly, inbred mouse strains exhibit dramatic differences in the susceptibility of their cultured macrophages to killing by LF, and a gene that influences this phenotype, called Ltxs1, has been mapped to mouse chromosome 11.

Estrogen modulation of prolactin gene expression requires an intact mitogen-activated protein kinase signal transduction pathway in cultured rat pituitary cells.

Expression of the PRL gene is regulated by many factors, including cAMP, estradiol (E2), phorbol esters, epidermal growth factor (EGF), and TRH. The promoter region of the rat PRL gene has been shown to contain DNA sequences that are thought to support the direct interaction of estrogen receptors (ERs) with DNA. It is by this direct ER/DNA interaction that estrogen is thought to modulate expression of PRL.

Prevention of HIV infection in street-recruited injection drug users. The Collaborative Injection Drug User Study (CIDUS).

Background: Injection drug users (IDUs) and their sex partners account for an increasing proportion of new AIDS and HIV cases in the United States, but public debate and policy regarding the effectiveness of various HIV prevention programs for them must cite data from other countries, from non-street-recruited IDUs already in treatment, or other programs, and from infection rates for pathogens other than HIV.

Methods: Participants were recruited from the street at six sites (Baltimore [Maryland], New York [two sites], Chicago [Illinois], San Jose [California], Los Angeles [California], and at a state women's correctional facility [Connecticut]), interviewed with a standard questionnaire, and located and reinterviewed at one or more follow-up visits (mean, 7.8 months later).

Requirements for mini-exon inclusion in potato invertase mRNAs provides evidence for exon-scanning interactions in plants.

Invertases are responsible for the breakdown of sucrose to fructose and glucose. In all but one plant invertase gene, the second exon is only 9 nt in length and encodes three amino acids of a five-amino-acid sequence that is highly conserved in all invertases of plant origin. Sequences responsible for normal splicing (inclusion) of exon 2 have been investigated in vivo using the potato invertase, invGF gene.

Incentives and accessibility: a pilot study to promote adherence to TB prophylaxis in a high-risk community.

Setting: A community-based directly observed preventive therapy (DOPT) program for treatment of latent tuberculosis infection among injection drug users (IDUs) in an inner-city neighborhood.

Objective: To test adherence to a 6-month course of DOPT using cash incentives and an easily accessible neighborhood location.

Design: Street-recruited IDUs (N = 205) were screened for Mycobacterium tuberculosis (TB) infection using the Mantoux test and two controls.

Splicing-independent processing of plant box C/D and box H/ACA small nucleolar RNAs.

Small nucleolar RNAs (snoRNAs) are involved in various aspects of ribosome biogenesis and rRNA maturation. Plants have a unique organisation of snoRNA genes where multiple, different genes are tightly clustered at a number of different loci. The maize gene clusters studied here include genes from both of the two major classes of snoRNAs (box C/D and box H/ACA) and are transcribed as a polycistronic pre-snoRNA transcript from an upstream promoter.

Steroid hormone regulation of vasopressinergic neurotransmission in the central nervous system.

Vasopressinergic neurotransmission is intimately linked to steroid hormone signaling. Both arginine vasopressin (VP) and the extrahypothalamic VP V1a receptors are regulated by steroid hormones. Here, we present work that has been done in our laboratory, investigating mechanisms underlying steroid hormone effects on the expression of both VP and its primary receptor in the brain, the VP V1a receptor.

Ltx1, a mouse locus that influences the susceptibility of macrophages to cytolysis caused by intoxication with Bacillus anthracis lethal factor, maps to chromosome 11.

The lethal factor (LF) toxin that is produced by Bacillus anthracis plays an important role in the pathogenesis of anthrax. LF has mononuclear phagocyte-specific intoxicating effects that are not well understood. We have identified genetic differences in inbred mouse strains that determine whether their cultured macrophages are susceptible to the cytolytic effect of LF intoxication.

Transcriptional effects of estrogen on neuronal neurotensin gene expression involve cAMP/protein kinase A-dependent signaling mechanisms.

Steroid hormones exert dramatic effects on neuronal expression of genes that encode neuropeptides. Expression of the neurotensin/neuromedin (NT/N) gene in preoptic area neurons is dramatically enhanced by estrogen in vivo, even though its promoter lacks palindromic estrogen response elements. We report here that estrogen promotes transcription of this gene by interactions with the cAMP cascade in a neuronal cell line, SK-N-SH, and in a mouse model.

HIV seroprevalence among street-recruited injection drug and crack cocaine users in 16 US municipalities.

Objectives: This study deter- mined human immunodeficiency virus (HIV) seroprevalence and factors associated with HIV infection among street-recruited injection drug users and crack cocaine smokers.

Methods: An analysis was performed on HIV serologies and risk behaviors of 6402 injection drug users and 3383 crack smokers in 16 US municipalities in 1992 and 1993.

Results: HIV seroprevalence was 12.

Processing of vertebrate box C/D small nucleolar RNAs in plant cells.

The recent isolation of a number of plant box C/D small nucleolar (sno)RNAs demonstrates the conservation in plants of sequence and structural elements of processed box C/D snoRNAs. Boxes C and D, and terminal inverted repeats are known to be essential for accumulation and processing in vertebrates and yeast. Processing of vertebrate box C/D snoRNAs was examined by expression of various mouse hsc70 intron 5-U14 constructs in tobacco protoplasts.

Case report: cerebellar hemi-hypoplasia.

Cerebellar hypoplasia is a prominent feature of fetal brain pathology. The lesion is rarely isolated or asymmetric. Various aetiological factors have been proposed.

Impact of law enforcement on syringe exchange programs: a look at Oakland and San Francisco.

Drug paraphernalia and prescription laws make syringe exchange programs (SEPs) illegal in most states in the U.S. Nonetheless, SEPs have been started in 25 states and the District of Columbia as of September 1995.

HIV risk profile of drug-using women who have sex with women in 19 United States cities.

The objective of this study was to analyze HIV-related risks of women injection drug users (IDU) and crack cocaine users (CCU) who have sex with women (WSW). IDU and CCU women (N = 3856) were recruited from street settings in 19 U.S.