Reversed Holocene temperature-moisture relationship in the Horn of Africa.

Anthropogenic climate change is predicted to severely impact the global hydrological cycle1, particularly in tropical regions where agriculture-based economies depend on monsoon rainfall2. In the Horn of Africa, more frequent drought conditions in recent decades3,4 contrast with climate models projecting precipitation to increase with rising temperature5. Here we use organic geochemical climate-proxy data from the sediment record of Lake Chala (Kenya and Tanzania) to probe the stability of the link between hydroclimate and temperature over approximately the past 75,000 years, hence encompassing a sufficiently wide range of temperatures to test the 'dry gets drier, wet gets wetter' paradigm6 of anthropogenic climate change in the time domain. We show that the positive relationship between effective moisture and temperature in easternmost Africa during the cooler last glacial period shifted to negative around the onset of the Holocene 11,700 years ago, when the atmospheric carbon dioxide concentration exceeded 250 parts per million and mean annual temperature approached modern-day values. Thus, at that time, the budget between monsoonal precipitation and continental evaporation7 crossed a tipping point such that the positive influence of temperature on evaporation became greater than its positive influence on precipitation. Our results imply that under continued anthropogenic warming, the Horn of Africa will probably experience further drying, and they highlight the need for improved simulation of both dynamic and thermodynamic processes in the tropical hydrological cycle.

Identification of superoxide dismutase as a potential urinary marker of carbon tetrachloride-induced hepatic toxicity.

The aim of this study was the identification of a novel protein marker of hepatotoxicity in rat urine. Rats were dosed by gavage with carbon tetrachloride (CCl(4)) to induce acute liver injury. Surface enhanced laser desorption/ionisation (SELDI) ProteinChip technology revealed the appearance of a 15.7 kDa protein in the CCl(4)-treated rat urine. One-dimensional sodium dodecyl sulphate polyacrylamide electrophoresis (SDS-PAGE) identified an 18.4 kDa protein in the CCl(4)-treated rat urine. The appearance of either protein was coincident over a time course during which they first appeared at 12h post-dosing, peaked at 36h and had disappeared again within 3 days post-dosing. The protein was identified by in-gel digestion and nano-electrospray (nano-ES)-tandem mass spectrometry as Cu/Zn superoxide dismutase (SOD-1). SOD activity was found to be increased by 61.4-fold in CCl(4)-treated rat urine. Western blots of tissue homogenates from the rats revealed a time-dependent loss of SOD-1 from the livers of CCl(4)-treated rats matching the time course of SOD-1 appearance in urine. SOD-1 is not specifically located in liver; however, its appearance in urine in response to acute CCl(4)-induced hepatotoxicity is a novel finding; this coupled with loss from the liver following injury suggests urinary SOD-1 may be a potential marker of hepatotoxicity.

Mass spectrometry-based proteomics in the life sciences.

Over the last 20 years, mass spectrometry-based proteomics has become an indispensable tool in the cellular and molecular life sciences. This has been enabled by the 'soft ionisation' techniques of electrospray and matrix-assisted laser desorption-ionisation, which allow the gentle ionisation and vaporisation of large, thermally labile biomolecules. Innovative instrumentation designs and biochemical strategies have brought success in the large-scale identification and quantification of proteins, as well as the characterisation of their complexes and post-translational modifications. This review describes the instrumentation used for proteomics research. It presents an overview of the current applications of mass spectrometry-based proteomics to the cellular and molecular life sciences, and discusses challenges that exist for research in the future.

Identification of cytochrome P450 enzymes in human colorectal metastases and the surrounding liver: a proteomic approach.

We describe the direct identification of multiple cytochrome P450 (CYP) enzymes in healthy and cancerous tissue. CYPs in human liver colorectal metastases were compared with those in the surrounding liver using a mass spectrometry-based proteomic approach. Nano-scale reversed phase liquid chromatography combined with electrospray ionisation tandem mass spectrometry has been used to identify CYPs with no pre-selection of the proteins anticipated. Fourteen distinct CYP enzymes from the subfamilies 1A, 2A, 2B, 2C, 2D, 2E, 3A, 4A, 4F, 8B and 27A were positively identified; 13 in the liver samples and 12 in the tumour tissue. It was found that three of the colorectal metastases expressed essentially the same drug-metabolising pattern of CYPs as the surrounding liver, whilst three tumour samples from different individuals showed no CYP expression. This was likely in at least one case to be due to low sample mass. The CYP expression profile in an individual tumour is likely to be an important determinant in predicting the outcome of cancer chemotherapy.

A proteomic approach to the identification of cytochrome P450 isoforms in male and female rat liver by nanoscale liquid chromatography-electrospray ionization-tandem mass spectrometry.

Nanoscale reversed-phase liquid chromatography (LC) combined with electrospray ionization-tandem mass spectrometry (ESI-MS/MS) has been used as a method for the direct identification of multiple cytochrome P450 (P450) isoforms found in male and female rat liver. In this targeted proteomic approach, rat liver microsomes were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by in-gel tryptic digestion of the proteins present in the 48- to 62-kDa bands. The resultant peptides were extracted and analyzed by LC-ESI-MS/MS. P450 identifications were made by searching the MS/MS data against a rat protein database containing 21,576 entries including 47 P450s using Sequest software (Thermo Electron, Hemel Hempstead, UK). Twenty-four P450 isoforms from the subfamilies 1A, 2A, 2B, 2C, 2D, 2E, 3A, 4A, 4F, CYP17, and CYP19 were positively identified in rat liver.

Microtox testing of pentachlorophenol in soil extracts and quantification by capillary electrochromatography (CEC)--a rapid screening approach for contaminated land.

An approach to rapid soil testing which involved the use of simple solvent extraction methods was developed. The analytes of interest were priority pollutants of low water solubility which could not be readily removed from the soil using water. Direct toxicity testing of the soil samples by Microtox showed a high background toxicity which prevented realistic toxicity data from being obtained for the contaminants present. A range of different extraction solutions was used in an attempt to extract the contaminants while eliminating the matrix effects of the soil. It was necessary that the solvents selected for extraction of the soil samples were not of significant toxicity, as this could potentially mask the toxic effects of any compounds extracted from the soil. The extraction efficiencies of solvent systems were evaluated using pentachlorophenol (PCP) as a model compound of known toxicity in the Microtox assay. A rapid and cost-effective method was developed in order to determine the amount of PCP recovered from the soil by the extraction solvents employed. This method consisted of a solid phase extraction (SPE) step followed by quantification using capillary electrochromatography (CEC). Recoveries were greater when a higher proportion of organic solvent (methanol) was used in the extraction process, and lowest when water was used. An extraction based on water could provide information on the potential for leaching of contaminants from the soil into nearby water bodies in an environmental setting. An organic solvent extraction method could indicate how much toxicity soil-dependent organisms might be exposed to through ingestion. Extraction based on 50% (v/v) methanol in water was considered to be the most suitable overall extraction solution for soil screening, given that this permitted extraction of the water-insoluble compound PCP at a level which was clearly toxic in the Microtox assay while also retaining the capability to extract water-soluble contaminants.

Recurrent fracture of the humerus in a softball player.

Fracture of a normal humerus can occur during the act of throwing an object. We present the case of a young woman who sustained a spiral fracture of the distal humeral shaft with concomitant radial nerve palsy while throwing a softball and who, after clinical and radiographic evidence of bony healing, suffered a repeat humerus fracture, also while throwing a softball.

Endoscopic versus open carpal tunnel release: big deal or much ado about nothing?

Endoscopic release of the transverse carpal ligament is an increasingly popular method of treating carpal tunnel syndrome. Advocates of endoscopic carpal tunnel release claim decreased postoperative morbidity and earlier return to work as an advantage of this technique. Others caution that there is little if any short-term difference between endoscopic and open carpal tunnel release, no long-term difference, and an increased likelihood of significant nerve injury.

Evaluation of the painful wrist.

Evaluation of wrist pain begins with a review of findings from a thorough medical history, a detailed physical examination, and plain radiographs. If a diagnosis is not forthcoming, additional diagnostic studies may be obtained, including "special" radiographs, bone scans, arthrograms, arthroscopy, and computed tomography and magnetic resonance imaging scans. "Abnormal" findings on these additional studies must be correlated with findings from the medical history and physical examination.

The Allen test. A study of inter-observer reliability.

The Allen test was performed by four physician examiners on 200 hands of healthy volunteers. Positive results were found in 5.5% of hands. There was not a single case in which all four observers agreed. Considerable inter-observer disagreement is associated with the Allen test.

Squamous cell carcinoma of the perionychium.

Squamous cell carcinoma of the perionychium is a rare, slow-growing tumor which is frequently misdiagnosed. Confusion arises because many problems affecting the soft tissue at the fingertips are clinically similar. Physicians should be aware of the possibility of carcinoma when faced with a chronic inflammatory process unresponsive to treatment. Diagnosis is confirmed by biopsy. Treatment options include amputation of the distal digital segment and Mohs microscopically controlled excision.

Surgical treatment for osteoarthritis at the base of the thumb.

Osteoarthritis of the trapeziometacarpal joint can cause pain and disability. Surgical procedures for this problem include extra-articular ligamentous reconstruction, arthrodesis of the trapeziometacarpal joint, osteotomy of the thumb metacarpal, total joint arthroplasty, silicone interposition arthroplasty, and partial or complete resection of the trapezium. None of the operations results in a painless, stable thumb with good strength and motion in all cases. Disorders of the thumb metacarpophalangeal joint and the scaphotrapezio-trapezoid joints may accompany osteoarthritis of the trapeziometacarpal joint.

Relationship between visual acuity and observation distance.

The visual acuities of 17 young emmetropes and corrected ametropes were measured over the range of 7.5-0.19 m using a Bailey-Lovie chart. Accommodation stimulus-response measures were also taken over this range using retinoscopy to establish whether variations in visual acuity with observation distance could be attributed to accommodation behaviour. Tonic accommodation was recorded using the Canon R1 autorefractor and was compared with visual acuity and stimulus-response results. In general, visual acuity was found to be dependent on stimulus distance, being significantly reduced for most observers for the closest targets. There were three categories of observer performance for visual acuity as a function of observation distance; one group showing no change in visual acuity with distance, a second showing a flat function for distances 7.55-0.5 m, and then a decrease in visual acuity for shorter distances; and a third category that showed a maximum visual acuity in the 1.2-1.6 m region. This behaviour was unrelated to individual stimulus-response characteristics and there was no significant relationship between tonic accommodation and the distance where acuity was best for the third category observers.

Scaphoid fractures and scaphoid nonunion. Diagnosis and treatment.

Scaphoid nonunion can cause pain, loss of wrist motion, and loss of grip strength. Because initial roentgenograms are not always definitive, patients suspected of having a scaphoid fracture despite negative initial radiographs should undergo bone scan. Treatment of acute nondisplaced fracture of the scaphoid generally nonoperative, involving immobilization in a cast. Treatment of scaphoid nonunion is generally operative, and many procedures and their associated risks are reviewed. There is no consensus about the clinical implications of scaphoid malunion.