Nonlymphoid reservoirs of HIV replication in children with chronic-progressive disease.

Autopsy tissues from 2 cohorts of age-matched HIV-infected children with similar plasma viral load (>10(5) HIV RNA copies/ml), but with distinct AIDS-associated disease manifestations, were examined for sites of persistent HIV replication. One group consisted of 3 children with severe lymphoid atrophy and peripheral blood CD4+ T cell counts of < 10/mm . Another group was composed of 6 children with extensive hyperplasia of mucosal-associated lymphoid tissues and blood CD4+ T cell counts >500/mm3.

Comparisons of the amplitude size and the reproducibility of three different electrodes to record the corneal flash electroretinogram in rodents.

To compare corneal electrodes commonly used in rodent eyes for repeat and left versus right eye accuracy and variability to record the flash electroretinogram (ERG). Animals studied were eight C57BL/6 mice and eight rats of the Wistar strain. Scotopic ERGs were recorded from eyes of dark-adapted anesthetized rodents to compare a custom-made gold-wire contact lens electrode (CLE), a cotton-wick silver-silver chloride electrode (SCLE), and a coiled stainless steel wire electrode (SSE).

A Pro250Arg substitution in mouse Fgfr1 causes increased expression of Cbfa1 and premature fusion of calvarial sutures.

Pfeiffer syndrome is a classic form of craniosynostosis that is caused by a proline-->arginine substitution at amino acid 252 (Pro252Arg) in fibroblast growth factor receptor 1 (FGFR1). Here we show that mice carrying a Pro250Arg mutation in Fgfr1, which is orthologous to the Pfeiffer syndrome mutation in humans, exhibit anterio-posteriorly shortened, laterally widened and vertically heightened neurocraniums. Analysis of the posterior and anterior frontal, sagittal and coronal sutures of early post-natal mutant mice revealed premature fusion.

Roles of BRCA1 and its interacting proteins.

Germline mutations of BRCA1 predispose women to breast and ovarian cancers. BRCA1 contains several functional domains that interact directly or indirectly with a variety of molecules, including tumor suppressors (p53, RB, BRCA2 and ATM), oncogenes (c-Myc, casein kinase II and E2F), DNA damage repair proteins (RAD50 and RAD51), cell-cycle regulators (cyclins and cyclin-dependent kinases), transcriptional activators and repressors (RNA polymerase II, RHA, histone deacetylase complex and CtIP) and others. Mounting evidence indicates that these physical associations are not artifacts; rather, BRCA1 is likely to serve as an important central component in multiple biological pathways that regulate cell-cycle progression, centrosome duplication, DNA damage repair, cell growth and apoptosis, and transcriptional activation and repression.

Sensitivity to fungal allergens is a risk factor for life-threatening asthma.

Background: Previous studies have suggested that sensitivity to Alternaria and Cladosporium may be risk factors for life-threatening asthma. We have investigated this by studying the relationship between skin tests for fungal spores and admission to an intensive care unit (ICU) for asthma.

Methods: Skin prick tests for fungal spores (Alternaria tenuis, Cladosporium cladosporoides, Helminthosporium maydis, and Epicoccum nigrum), cat dander, house-dust mite (Dermatophagoides pteronyssinus), and a seven-grass mix were performed in three groups of patients: patients admitted to an ICU with an attack of asthma; those who had received emergency treatment for asthma but had not been admitted to an ICU, and those who had never required emergency treatment for their asthma.

HIV-specific cytotoxic T lymphocytes traffic to lymph nodes and localize at sites of HIV replication and cell death.

We have tracked the in vivo migration and have identified in vivo correlates of cytotoxic T-lymphocyte (CTL) activity in HIV-seropositive subjects infused with autologous gene-marked CD8(+) HIV-specific CTL. The number of circulating gene-marked CTL ranged from 1.6 to 3.

Characteristics of the myopic patient population applying for refractive surgery.

Purpose: Assessment of the characteristics of the myopic patient population applying for refractive surgery in order to determine the potential market for myopic refractive surgery.

Methods: Records of consecutive patients who responded to an advertisement for refractive surgery to correct myopia were evaluated retrospectively with regards to patient demographics and the amount and distribution of the refractive error. Data were compared to that available from population-based statistics for distribution of myopia in the general population.

Is intraoperative topography predictive of postoperative topographical changes following refractive surgery?

Purpose: To evaluate the usefulness of measuring corneal topography intraoperatively by Intraoperative PAR Corneal Topography System (IOPAR CTS) to predict the postoperative topographical changes in patients undergoing refractive surgery.

Methods: Topographical measurements of 9 eyes of 9 patients were taken by IOPAR CTS: 6 immediately after Intrastromal Corneal Ring Segments (ICRS) placement surgery and 3 immediately after Photorefractive Keratectomy (PRK) surgery. The topographical images taken by IOPAR CTS were analyzed to determine the quality of the image produced and the correlation of the keratometric data from the central 3 mm of cornea with measurements taken from an autokeratometer (Auto-Km) and the EyeSys Corneal Analysis System (CAS) for the same eyes taken three months following the procedure.

Haploid loss of the tumor suppressor Smad4/Dpc4 initiates gastric polyposis and cancer in mice.

The tumor suppressor SMAD4, also known as DPC4, deleted in pancreatic cancer, is a central mediator of TGF-beta signaling. It was previously shown that mice homozygous for a null mutation of Smad4 (Smad4-/-) died prior to gastrulation displaying impaired extraembryonic membrane formation and endoderm differentiation. Here we show that Smad4+/- mice began to develop polyposis in the fundus and antrum when they were over 6 - 12 months old, and in the duodenum and cecum in older animals at a lower frequency.

Lys650Met substitution in the tyrosine kinase domain of the fibroblast growth factor receptor gene causes thanatophoric dysplasia Type I. Mutations in brief no. 199. Online.

Thanatophoric dysplasia (TD) is one of the most common neonatal lethal skeletal dysplasias with micromelic shortening of the limbs, relative macrocephaly, flat vertebral bodies and a narrow thorax. TD has been divided into two types, type I (TD1) and II (TD2), based on clinical, radiological, histological, and molecular criteria. We identified a A to T heterozygous base subsitution at position 1949 predicted to cause a Lys650Met substitution in a term infant with TD1.

Occurrence of nosocomial bloodstream infections in six neonatal intensive care units.

Background: Nosocomial bloodstream infections (NBSIs) occur frequently in neonatal intensive care units (NICUs) and are associated with substantial morbidity and mortality. Little has been published regarding variation in NBSI among institutions.

Objective: To determine NBSI incidence among six NICUs and to explore how much variation is explained by patient characteristics and NICU practice patterns.

An exploration of the potential benefits of pet-facilitated therapy.

There is mounting evidence to suggest that those who keep pets are likely to benefit from various improvements in health. Despite founders of nursing such as Florence Nightingale advocating the importance of animals within the care environment, their integration into hospitals and other health care settings has been slow. The literature on animal-induced health benefits is reviewed and the conclusion is drawn that the potential benefits of pet therapy are considerable.

CNS myelin and sertoli cell tight junction strands are absent in Osp/claudin-11 null mice.

Oligodendrocyte-specific protein (OSP)/claudin-11 is a recently identified transmembrane protein found in CNS myelin and testis with unknown function. Herein we demonstrate that Osp null mice exhibit both neurological and reproductive deficits: CNS nerve conduction is slowed, hindlimb weakness is conspicuous, and males are sterile. Freeze fracture reveals that tight junction intramembranous strands are absent in CNS myelin and between Sertoli cells of mutant mice.

Estrogen replacement therapy, serum lipids, and polymorphism of the apolipoprotein E gene.

Background: Pharmacogenomics, the study of genetic loci that modulate drug responsiveness, may help to explain why estrogen replacement therapy (ERT) has differential effects on serum lipid and lipoprotein concentrations in postmenopausal women who inherit distinct alleles of the apolipoprotein E gene (APOE).

Methods: We compared total-cholesterol, triglyceride, and lipoprotein (LDL and HDL) concentrations in 66 postmenopausal women receiving ERT ([+]ERT) with 174 postmenopausal women not receiving ERT ([-]ERT), controlling for three APOE genotypes divided into three groups: E2 (epsilon2/epsilon3, n = 31), E3 (epsilon3/epsilon3, n = 160), and E4 (epsilon3/epsilon4 + epsilon4/epsilon4, n = 49).

Results: Mean total-cholesterol concentrations were lower in all three [+]ERT groups compared with their [-]ERT counterparts but were statistically significant only for women in group E4 (P = 0.

Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by FGFR3 mutations.

The platyspondylic lethal skeletal dysplasias (PLSDs) are a heterogeneous group of short-limb dwarfing conditions. The most common form of PLSD is thanatophoric dysplasia (TD), which has been divided into two types (TD1 and TD2). Three other types of PLSD, or TD variants (San Diego, Torrance, and Luton), have been distinguished from TD.

Pediatric AIDS-associated lymphocytic interstitial pneumonia and pulmonary arterio-occlusive disease: role of VCAM-1/VLA-4 adhesion pathway and human herpesviruses.

Because the mechanisms of lymphocyte accumulation in the lungs of children with AIDS-associated lymphocytic interstitial pneumonia (LIP) are unknown, we studied the relative contributions of known adhesion pathways in mediating lymphocyte adherence to endothelium and the potential role of human herpesviruses in the expansion of these lesions. LIP was characterized by lymphoid hyperplasia of the bronchus-associated lymphoid tissue (BALT) and infiltration of the pulmonary interstitium with CD8(+) T lymphocytes. In some individuals there was expansion of the alveolar septae with dense aggregates of B lymphocytes, many containing the Epstein-Barr viral (EBV) genome.

Lethal osteosclerotic skeletal dysplasia with intracellular inclusion bodies.

We report an apparently previously undescribed form of lethal osteosclerotic skeletal dysplasia in a 30-week male fetus with micromelic shortness of the limbs. Radiographic findings at necropsy included increased density in all bones, most marked in the skull, mandible, and pubis. The ribs were very short, abnormally modeled, and wide anteriorly.

In vivo migration and function of transferred HIV-1-specific cytotoxic T cells.

The persistence of HIV replication in infected individuals may reflect an inadequate host HIV-specific CD8+ cytotoxic T lymphocyte (CTL) response. The functional activity of HIV-specific CTLs and the ability of these effector cells to migrate in vivo to sites of infection was directly assessed by expanding autologous HIV-1 Gag-specific CD8+ CTL clones in vitro and adoptively transferring these CTLs to HIV-infected individuals. The transferred CTLs retained lytic function in vivo, accumulated adjacent to HIV-infected cells in lymph nodes and transiently reduced the levels of circulating productively infected CD4+ T cells.

Variation in incidence of indinavir-associated nephrolithiasis among HIV-positive patients.

Background: Nephrolithiasis may be an important consequence of indinavir therapy; however little has been published on the variation in incidence between different populations of patients or the possible mechanisms of calculus formation.

Objective: To examine variation in the incidence of indinavir-associated nephrolithiasis (IAN) in HIV-positive patients in relation to hemophilia and hepatitis C virus (HCV) infection.

Methods: Clinical data were abstracted retrospectively from the medical records of all adult patients treated with indinavir from September 1995 to September 1997.

Lethal osteosclerotic osteochondrodysplasia with platyspondyly, metaphyseal widening, and intracellular inclusions in sibs.

We report on a previously undescribed form of lethal osteosclerotic skeletal dysplasia in sibs from nonconsanguineous parents. Radiographic findings included increased density in the base of the skull, clavicles, vertebrae, ribs, and the metaphyseal regions of the long bones. There was midface hypoplasia, a large anterior fontanel, micrognathia, and hypoplastic, wafer-thin vertebrae.

Thanatophoric dysplasia type I with syndactyly.

We report on a case of thanatophoric dysplasia type 1 (TD1) due to a Tyr373Cys mutation in the fibroblast growth factor receptor 3 (FGFR3) gene with soft tissue syndactyly of the fingers and toes. Syndactyly has not been previously described in TD or other conditions with FGFR3 mutations, but occurs in several craniosynostosis syndromes due to mutations in FGFR2. We conclude that mutations in FGFR3 may also be associated with developmental abnormalities due to interference with programmed cell death.

Radiographic and morphologic findings in a previously undescribed type of mesomelic dysplasia resembling atelosteogenesis type II.

The mesomelic chondrodysplasias are a heterogeneous group of dwarfing disorders characterized by shortness of the middle segments of limbs. We report on a 25-week fetus with disproportionate shortness of limbs with an apparently distinct form of mesomelic dysplasia. Radiographic findings at necropsy included ulnar deviation of hands, talipes equinovarus, distal tapering of the humeri, and hypoplastic fibulae, radii, and ulnae.

Extra pelvic ossification centers in thanatophoric dysplasia and platyspondylic lethal skeletal dysplasia-San Diego type.

The platyspondylic lethal skeletal dysplasias (PLSD) are a group of heterogeneous disorders including thanatophoric dysplasia (TD) and the TD variants (San Diego, Torrance, and Luton types). TD is the most common form and has been divided into two subtypes (TD1 and TD2) based on clinical and radiologic criteria and analysis of mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. The variants are distinguished from TD by characteristic radiographic and chondro-osseous morphologic features.

Physiological and pathological secretion of cartilage oligomeric matrix protein by cells in culture.

Abnormalities in cartilage oligomeric matrix protein (COMP), a pentameric structural protein of the cartilage extracellular matrix, have been identified in pseudoachondroplasia and multiple epiphyseal dysplasia, two human autosomal dominant osteochondrodysplasias. However, the function of the protein remains unknown. With the goal of establishing a model to study the mechanisms by which COMP mutations cause disease, we have analyzed synthesis and secretion of COMP in cultured chondrocytes, tendon, and ligament cells.

The effects of nebulised isotonic saline and terbutaline on breathlessness in severe chronic obstructive pulmonary disease (COPD).

Background: There is anecdotal evidence that nebulised saline relieves breathlessness at rest in patients with severe chronic obstructive pulmonary disease (COPD). It is unclear whether nebulised beta agonists are any more effective than nebulised saline in relieving breathlessness at rest in these individuals.

Aim: To compare the effects of nebulised saline and nebulised terbutaline on breathlessness at rest in patients with severe COPD.