Differences in spirometry interpretation algorithms: influence on decision making among primary-care physicians.

Background: Spirometry is recommended for the diagnosis of asthma and chronic obstructive pulmonary disease (COPD) in international guidelines and may be useful for distinguishing asthma from COPD. Numerous spirometry interpretation algorithms (SIAs) are described in the literature, but no studies highlight how different SIAs may influence the interpretation of the same spirometric data.

Aims: We examined how two different SIAs may influence decision making among primary-care physicians.

Chronic cough. Three most common causes.

Objective: To describe an approach to diagnosis and treatment of patients with chronic cough. QUALIITY OF EVIDENCE: MEDLINE was search for reports of studies comducted between 1970 and 2000 on chronic cough and its epidemiology, natural history, diagnois, and theraphy. Articles were further selected based on clinical relevance and design.

Inhibition of major histocompatibility complex class I antigen presentation in pig and primate cells by herpes simplex virus type 1 and 2 ICP47.

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) express an immediate-early protein, ICP47, that effectively inhibits the human transporter associated with antigen presentation (TAP), blocking major histocompatibility complex (MHC) class I antigen presentation to CD8+ T cells. Previous work indicated that the mouse TAP is relatively resistant to inhibition by the HSV-1 and HSV-2 ICP47 proteins (ICP47-1 and ICP47-2) and that mouse cells infected with HSV-1 are lysed by anti-HSV CD8+ cytotoxic T lymphocytes (CTL). Therefore, mice are apparently not suitable animals in which to study the in vivo effects of ICP47.

Herpes simplex virus type 2 ICP47 inhibits human TAP but not mouse TAP.

Herpes simplex virus serotype 1 (HSV-1) expresses an immediate-early protein, ICP47, that effectively blocks the major histocompatibility complex class I antigen presentation pathway. HSV-1 ICP47 (ICP47-1) binds with high affinity to the human transporter associated with antigen presentation (TAP) and blocks the binding of antigenic peptides. HSV type 2 (HSV-2) ICP47 (ICP47-2) has only 42% amino acid sequence identity with ICP47-1.

Stable binding of the herpes simplex virus ICP47 protein to the peptide binding site of TAP.

The herpes simplex virus (HSV) ICP47 protein inhibits the MHC class I antigen presentation pathway by inhibiting the transporter associated with antigen presentation (TAP) which translocates peptides across the endoplasmic reticulum membrane. At present, ICP47 is the only inhibitor of TAP. Here, we show that ICP47 produced in bacteria can block human, but not mouse, TAP, and that heat denaturation of ICP47 has no effect on its ability to block TAP.

Herpes simplex virus turns off the TAP to evade host immunity.

Many viruses have evolved mechanisms to avoid detection by the host immune system. Herpes simplex virus (HSV) expresses an immediate early protein, ICP47, which blocks presentation of viral peptides to MHC class I-restricted cells. The properties of the newly synthesized class I molecules in HSV-infected cells resemble those of cell lines deficient in the transporter associated with antigen processing (TAP) in that class I molecules are retained in the endoplasmic reticulum, and the heavy chain and beta 2-microglobulin subunits dissociate in detergent extracts but the complex can be stabilized by peptides.