Pigment changes in human skin after cryotherapy

We have investigated the changes in pigmentation and melanocyte distribution in human skin after a standardized freeze injury. All lesions developed hypopigmentation with a peripheral rim of hyperpigmentation. Abnormalities in pigmentation persisted for at least 6 months. Hyperpigmentation was predominantly an epidermal phenomenon. After brief freezes, hypopigmentation persisted despite the presence of functional melanocytes. After prolonged freezes, the consistent finding was an absence of melanosomes in keratinocytes, although melanocytes were present. We conclude that prolonged changes in skin color are frequent after brief freezes and that hypopigmentation is not synonymous with an absence of melanocytes. This suggests that hypopigmentation after the cryosurgical treatment of malignant melanocytic tumors may not equate with cure.     

The uptake of liposome-entraped 125I-labelled poly(vinylpyrrolidone) by rat jejunum in vitro

The uptake of free and liposome-entrapped ¹²⁵I-labelled poly(vinylpyrrolidone) was measured in an intestinal sac preparation from adult rats. An an equal concentration of ¹²⁵I-labelled poly(vinylpyrrolidone), the rate of uptake of the liposome-entrapped material was four times that of the free macromolecule.     

Regional survey of femoral neck fractures.

In the South-west Thames Region 2619 patients (2105 women and 514 men) were discharged with a diagnosis of femoral neck fracture in 1974. The equivalent of a 250-bedded hospital was occupied throughout the year. The incidence, average length of stay, and mortality rate rose with increasing age and there were differences in these indices in the five health areas. These results confirm the enormous burden placed on the hospital service by patients with fracture of the femoral neck but suggest that differences in practice in the five areas may contribute to the size of the problem.     

Methanol Production by a Broad Phylogenetic Array of Marine Phytoplankton

Methanol is a major volatile organic compound on Earth and serves as an important carbon and energy substrate for abundant methylotrophic microbes. Previous geochemical surveys coupled with predictive models suggest that the marine contributions are exceedingly large, rivaling terrestrial sources. Although well studied in terrestrial ecosystems, methanol sources are poorly understood in the marine environment and warrant further investigation. To this end, we adapted a Purge and Trap Gas Chromatography/Mass Spectrometry (P&T-GC/MS) method which allowed reliable measurements of methanol in seawater and marine phytoplankton cultures with a method detection limit of 120 nanomolar. All phytoplankton tested (cyanobacteria: Synechococcus spp. 8102 and 8103, Trichodesmium erythraeum, and Prochlorococcus marinus), and Eukarya (heterokont diatom: Phaeodactylum tricornutum, coccolithophore: Emiliania huxleyi, cryptophyte: Rhodomonas salina, and non-diatom heterokont: Nannochloropsis oculata) produced methanol, ranging from 0.8–13.7 micromolar in culture and methanol per total cellular carbon were measured in the ranges of 0.09–0.3%. Phytoplankton culture time-course measurements displayed a punctuated production pattern with maxima near early stationary phase. Stabile isotope labeled bicarbonate incorporation experiments confirmed that methanol was produced from phytoplankton biomass. Overall, our findings suggest that phytoplankton are a major source of methanol in the upper water column of the world’s oceans.     

Promoting Smoke-Free Homes: A Novel Behavioral Intervention Using Real-Time Audio-Visual Feedback on Airborne Particle Levels

Interventions are needed to protect the health of children who live with smokers. We pilot-tested a real-time intervention for promoting behavior change in homes that reduces second hand tobacco smoke (SHS) levels. The intervention uses a monitor and feedback system to provide immediate auditory and visual signals triggered at defined thresholds of fine particle concentration. Dynamic graphs of real-time particle levels are also shown on a computer screen. We experimentally evaluated the system, field-tested it in homes with smokers, and conducted focus groups to obtain general opinions. Laboratory tests of the monitor demonstrated SHS sensitivity, stability, precision equivalent to at least 1 µg/m³, and low noise. A linear relationship (R² = 0.98) was observed between the monitor and average SHS mass concentrations up to 150 µg/m³. Focus groups and interviews with intervention participants showed in-home use to be acceptable and feasible. The intervention was evaluated in 3 homes with combined baseline and intervention periods lasting 9 to 15 full days. Two families modified their behavior by opening windows or doors, smoking outdoors, or smoking less. We observed evidence of lower SHS levels in these homes. The remaining household voiced reluctance to changing their smoking activity and did not exhibit lower SHS levels in main smoking areas or clear behavior change; however, family members expressed receptivity to smoking outdoors. This study established the feasibility of the real-time intervention, laying the groundwork for controlled trials with larger sample sizes. Visual and auditory cues may prompt family members to take immediate action to reduce SHS levels. Dynamic graphs of SHS levels may help families make decisions about specific mitigation approaches.     

Prions and lymphoid organs: Solved and remaining mysteries

Prion colonization of secondary lymphoid organs (SLOs) is a critical step preceding neuroinvasion in prion pathogenesis. Follicular dendritic cells (FDCs), which depend on both tumor necrosis factor receptor 1 (TNFR1) and lymphotoxin β receptor (LTβR) signaling for maintenance, are thought to be the primary sites of prion accumulation in SLOs. However, prion titers in RML-infected TNFR1^−/− lymph nodes and rates of neuroinvasion in TNFR1^−/− mice remain high despite the absence of mature FDCs. Recently, we discovered that TNFR1-independent prion accumulation in lymph nodes relies on LTβR signaling. Loss of LTβR signaling in TNFR1^−/− lymph nodes coincided with the de-differentiation of high endothelial venules (HEVs)—the primary sites of lymphocyte entry into lymph nodes. These findings suggest that HEVs are the sites through which prions initially invade lymph nodes from the bloodstream. Identification of HEVs as entry portals for prions clarifies a number of previous observations concerning peripheral prion pathogenesis. However, a number of questions still remain: What is the mechanism by which prions are taken up by HEVs? Which cells are responsible for delivering prions to lymph nodes? Are HEVs the main entry site for prions into lymph nodes or do alternative routes also exist? These questions and others are considered in this article.     

Proof of safety vs proof of hazard

This paper refines and extends the work of Bross (1985, Biometrics 41, 785-793). One method to determine whether an environment is safe or hazardous is to frame the problem in the context of hypothesis testing. Any "proof" of safety or hazard will depend on the size of both the Type I and Type II errors associated with the test. Many past environmental monitoring programs, however, have ignored the power of the design, regardless of whether the objective was proof of safety or hazard.     

An epitope on C4 β light (L) chains detected by human anti-Rg; its relationship with β chain polymorphism and MHC associations

Two out of ten Rg-specific antisera tested contain a third antibody specific for the β chain of C4. Analysis of the β chains of 66 unrelated individuals by sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that the epitope detected is located exclusively on the light (L) β chain. A strong, but incomplete, association between the β chain epitope and the expression of the Rg: 2 determinant on the α chain of the same protein was also observed. While H (heavy) and L β chains were not associated with a particular C4 isotype, previously unrecorded associations of β chain polymorphism with theDR locus have been established.     

Cloning and expression of the toxin B gene ofClostridium difficile

Results from our cloning studies on toxin A indicated that the gene for toxin B resided approximately 1 kb upstream of the toxin A gene. Clone pCD19, which contains the 5-end of the toxin A gene and a small open reading frame, was found to contain 1.2 kb of DNA which, when subcloned, expressed a nontoxic peptide that reacted with toxin B antibodies. The rest of the toxin B gene was located on the 6.8 kb cloned fragment of plasmid pCD19L. The two fragments overlapped 0.8 kb. Lysates containing protein expressed by the 6.8 fragment were cytotoxic and lethal, and were neutralized by toxin B antibody. The two fragments were ligated to give the complete toxin B gene. The protein expressed by the complete gene was cytotoxic and lethal, and showed complete immunological identity with toxin B. Further analysis of the expressed protein and the toxin B gene confirmed our earlier findings showing that toxin B has a molecular weight of 240,000 or greater.     

Antigenic determinants expressed by human C4 allotypes; a study of 325 families provides evidence for the structural antigenic model

The antigenic determinants of human C4 have been defined by human IgG antisera, Rodgers (Rg) and Chido (Ch), in hemagglutination-inhibition assays (HAI). Eight (2 Rg and 6 Ch) are of high frequency, > 90% , and 1, WH, is of low frequency, 15 %. The phenotypic combinations are complex; generally, C4A expresses Rg, and C4B has Ch, but reverse antigenicities have been established both by HAI and by sequence data of selected C4 allotypes. A study of 325 families provides data on the antigenic expression of each C4 allotype and demonstrates strong associations. A structural model for the antigenic determinants of C4 proteins has been proposed and is completely supported by the family material. Of the 16 possible antigenic combinations for C4 proteins, only 3 are undetected. A new Ch combination has been recorded in two French families. The reported sequence variation within the C4d region can account for the antigenic determinants but leaves the location of electrophoretic variation in C4 still unclear.