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The discharge of saline groundwater results in the formation of sodic soil scalds in irrigated, dryland and urban environments of southeastern Australia. Sodic soils are dispersive, and this leads to soil erosion and a loss in agricultural productive capacity. These sodic soils commonly show polygonal cracking and pressure ridges indicating the presence of swelling clays. Infrared spectroscopy of scald surfaces and XRD (X-ray diffraction) analyses of the clay fractions of the sodic soils show the presence of amorphous clays, smectite, illite or mixed smectite/illite layer clays. Non-salinised soils adjacent to the salt scalds are commonly predominantly kaolinitic. SEM images and normative EDS mineral analyses of the clay fractions of these soils show that crystalline particles, predominantly of kaolinite, are progressively replaced by poorly crystalline smectite, illite and amorphous material. Normative mineral analyses determined from the bulk soil composition, based on a derived composition of submicron...

A case control study was performed to identify risk factors for colic caused by simple colonic obstruction and distension (SCOD) in the horse. Case horses were recruited from 2 veterinary school clinics. Control horses were population based and matched by time of year. A number of risk factors were considered in the following areas: general carer and premises information; exercise information; husbandry information (housing- and pasture-related); feeding information; breeding information; behavioural information; travel information; preventive medicine information and previous medical information. All variables with a P value of

Summary The aim of this study was to estimate the incidence of colic in horses in Thoroughbred training premises in 1997 in the British Isles. The seasonal pattern and outcome of colic episodes were also investigated, together with any association between premises level variables and colic. Data were collected by a postal questionnaire. The results showed a colic incidence density of 7.19/100 horse years (s.e. 0.42) and a cumulative incidence of colic of 5.80% (s.e. 0.30). Premises were grouped according to whether they had more Flat than National Hunt horses (Flat premises) or more National Hunt than Flat horses (NH premises). A similar rate of colic episodes was found in each group. However, significantly higher cumulative incidences of one episode of colic were found in the Flat premises and of multiple episodes in the NH premises, respectively. The outcome of each episode of colic showed spontaneous recovery in 28.7%, medical recovery in 63.1%, surgical recovery in 2.0% and death in 6.2% of cases. This indicated an overall mortality rate from colic of 0.45 deaths/100 horse years. The seasonal pattern of episodes of colic showed a spring and autumn peak, with significant differences in the seasonal pattern between the Flat and NH premises. Relative risk analysis and logistic regression modelling with random effects showed significant associations between the number of episodes of colic and the number of horses on the premises (allowing for the number of horses on each premises, the larger premises had a decreased risk of colic). After adjusting for the number of horses, 3 other variables were associated with colic; Flat premises (with an increased risk), the owner being the sole person looking after the horses (a decreased risk) and the premises being a combined training and breeding establishment (a decreased risk).

RT-PCR methods have been applied to the detection and sequencing of the glycoprotein gene of putative spring viraemia of carp viruses (SVCV) and pike fry rhabdoviruses (PFRV), includ- ing isolates from tench, grass carp, roach, bream and false harlequin, sheatfish and orfe. Phylogenetic analysis of a 550 nucleotide (nt) region of the glycoprotein gene identified 4 groups, I to IV. Signifi- cantly, the majority of viruses previously identified as PFRV formed a distinct cluster (Genogroup IV) which shared

A novel approach for using field spectrometry for determining both the mineralogy and the lithology of drill core pulps (powders) is developed and evaluated. The methodology is developed using material from a single drillhole through a mineralized sequence of rocks from central New South Wales. Mineral library spectra are used in linear unmixing routines to determine the mineral abundances in drill core pulps that represent between 1 m and 3 m of core. Comparison with X-Ray Diffraction (XRD) analyses shows that for most major constituents, spectrometry provides an estimate of quantitative mineralogy that is as reliable as that provided by XRD. Confusion between the absorption features of calcite and those of chlorite causes the calcite contents determined by spectrometry to be unreliable. Convex geometry is used to recognize the spectra of those samples that are extreme and are representative of unique lithologies. Linear unmixing is used to determine the abundance of these lithologies in each drillhole sample and these abundances are used to interpret the geology of the drillhole. The interpreted geology agrees well with conventional drillhole logs of the visible geology and photographs of the split core. The methods developed provide a quick and cost-effective way of determining the lithology and alteration mineralogy of drill core pulps.

At the time (1542) when Jean Rotz presented Henry VIII with a variation compass, and an accompanying treatise1 on its making and use, the question of magnetic variation was an acute one. It formed part of a wider controversy concerning the general validity of the sea-chart which had been raised among seamen. As to this, Dr. Pedro Nuñez, writing a treatise in 1537 addressed to his friend and pupil the Infante Dom Luys of Portugal, said that there were skilled pilots who derided the chart and declared it to be ‘a mais falsa causa do mundo’—the falsest thing in the world. Hastening to its defence, Nuñez dealt at length with the navigating errors introduced by ignoring the convergence of the meridians, and showed besides that a rhumb, or line of constant bearing, was a spiral curve on the globe. He dealt only incidentally with the variation of the compass needle and how to measure it, and this may explain why Rotz made this second source of error his main theme. The parallel N.–S. lines and E.–W. lines of the compass roses making a rectangular net on the chart are completely misleading, he says, for only the ‘diametral line’ (agonic line, line of no variation) actually runs through the poles of the world, the others lie at angles one with the other according to the magnetic variation.

The long-term sequelae of the tuberculous infection of the hip may be local or distant, biological or immunological. We describe a 73-year-old woman with a secondary ankle arthrosis as a late biomechanical sequel to arthrodesis of the ipsilateral tuberculous hip. To the authors’ best knowledge, a similar case report has not been published previously in the medical literature.

To compare British Pakistani parents' and their relatives' attitudes to prenatal testing (PND) and termination of pregnancy (TOP) for a range of conditions.A total of 222 British Pakistani participants: 117 parents of children with a child with a genetic condition (52 fathers and 65 mothers) and 103 of their relatives (51 males and 52 females) completed a structured questionnaire about their attitudes toward PND and TOP for 30 different conditions.Parents were more accepting of PND (P0.001) and TOP (P0.001) than their relatives for most of the conditions. Male relatives were consistently least interested in PND and TOP, except for conditions at the serious end of the continuum, where over 90% would opt for PND for quadriplegia and anencephaly, and over 60% would opt for TOP for these conditions.The lower level of interest in PND and TOP in relatives, particularly men, may be due to lack of information disseminated by parents about their child's recessive inheritance and its implications for relatives, resulting in poor understanding of genetic risk. These findings highlight the need for the provision of proactive genetic counselling to raise awareness of genetic risk and facilitate informed reproductive decision-making in at-risk relatives.

The case notes of all children admitted during the preceding five years for observation with painful hips (509 patients) were analysed to determine significant diagnostic factors and thus to design and admission policy. Most orthopaedic disorders (62 patients) were apparent on the initial radiographs, with the important exception of osteomyelitis/septic arthritis (21 patients). The remaining 426 patients were diagnosed by exclusion as having an irritable hip. The latter two groups were similar with respect to age, sex, and duration and nature of symptoms. A number of clinical features and laboratory investigations recorded within 12 hours of admission, however, were shown to have significant discriminative value. These were severe spasm, tenderness, pyrexia > or = 38 degrees C, and an erythrocyte sedimentation rate of > or = 20 mm/hour (the white cell count was not significant). Combination of any two of these produced a specificity and sensitivity for sepsis of 91% and 95% respectively (95% confidence interval 0.64 to 0.97). A protocol designed from this data analysis is now being tested and is expected to result in a significant reduction in admission rates.

At present automated genotyping in diagnosis involves the detection, digitrzation, and analysis of labeled DNA using computer software. This chapter describes the use of the Applied Biosystems (Foster City, CA) 373 DNA Sequencer and Genescan 672 software for sizing fluorescently labeled PCR products in a diagnostic molecular genetics laboratory. The Applied Biosystems Genotyper software is not covered since this is not used at present in this laboratory. An outline of the steps involved in automated genotyping, from polymerase chain reaction (PCR) to archiving data, is shown in Fig. 1. Fig. 1. Overview of the procedure. Labeled PCR products are produced by either incorporation of fluorescent dNTPs or labeled primers. A polyacrylamide gel is cast, scanned, and prerun, and the Genescan collection and analysis files are set up. The PCR products are mixed with a size standard, denatured, and loaded onto the prerun gel. After electrophoresrs the collected data is transferred to another Macintosh for analysis. A results file is generated and the PCR products are scored and checked. The results file is then archived.

By convention, most indwelling urethral catheters are removed in the morning. The authors carried out a randomized prospective study of 101 patients with postoperative urethral catheters and compared midnight removal with the more usual practice of morning removal. Patients were randomized into two groups: group A (n=46) had their catheters removed at 6:00 am and group B (n=49) had their catheters removed at midnight. Six patients were excluded from the study (1 patient on distigmine and 5 with preexisting urinary tract infections). The groups were comparable in age, use of night sedation, operative procedures and incidence of postoperative urinary tract infections. Patients in group B passed urine a median of 1 hour 40 minutes earlier, with a median volume 175 ml greater than group A (P=0.012 and

The Fc epsilon RI couples the mast cell-surface binding of IgE and Ag to a complex series of intracellular events culminating in cell activation and degranulation. The alpha-chain of Fc epsilon RI constitutes the Ig-binding subunit of this heterotetrameric receptor, and is itself a member of the Ig gene superfamily. We have isolated a human genomic DNA clone containing the entire Fc epsilon RI alpha gene, and completely sequenced a region from 1257 bp 5' of the transcription start site, to 513 bp 3' of the last exon of the gene. As with the previously characterized rat and mouse genes, human Fc epsilon RI alpha consists of five exons and four introns, and spans 5889 bp of genomic DNA. The splice donor and acceptor sites deduced by comparison with the cDNA sequence corresponded exactly to the locations found in analogous rodent genes. By mapping the 5' end of Fc epsilon RI alpha transcripts we found three major transcription initiation sites 24, 27, and 29 bp upstream of the ATG translation initiation codon. As well, several longer minor transcripts were seen, with a maximum of 60 nt of 5'-untranslated sequence. About 650 bp of DNA upstream of the ATG translation initiation codon were compared among human, rat, and mouse Fc epsilon RI alpha sequences in search of common motifs that might mediate conserved regulatory interactions with DNA binding proteins. A 172-bp region of the human Fc epsilon RI alpha 5'-flanking sequence was highly conserved in both rodent species. Further studies will be required to determine whether these or other sequences are involved in Fc epsilon RI alpha gene regulation.

Clinical laboratory diagnostic capabilities are needed to guide health and medical care of astronauts during long-duration space missions. Clinical laboratory diagnostics, as defined for medical care on Earth, offers a model for space capabilities. Interpretation of laboratory results for health and medical care of humans in space requires knowledge of specific physiological adaptations that occur, primarily because of the absence of gravity, and how these adaptations affect reference values. Limited data from American and Russian missions have indicated shifts of intra- and extracellular fluids and electrolytes, changes in hormone concentrations related to fluid shifts and stresses of the missions, reductions in bone and muscle mass, and a blunting of the cellular immune response. These changes could increase susceptibility to space-related illness or injury during a mission and after return to Earth. We review physiological adaptations and the risk of medical problems that occur during space missions. We describe the need for laboratory diagnostics as a part of health and medical care in space, and how this capability might be delivered.

The effects of spaceflight on immune cell function were determined in rats flown on COSMOS 2044. Control groups included vivarium, synchronous, and antiorthostatically suspended rats. The ability of natural killer cells to lyse two different target cell lines was determined. Spleen and bone marrow cells obtained from flight rats showed significantly inhibited cytotoxicity for YAC-1 target cells compared with cells from synchronous control rats. This could have been due to exposure of the rats to microgravity. Antiorthostatic suspension did not affect the level of cytotoxicity from spleen cells of suspended rats for YAC-1 cells. On the other hand, cells from rats flown in space showed no significant differences from vivarium and synchronous control rats in cytotoxicity for K-562 target cells. Binding of natural killer cells to K-562 target cells was unaffected by spaceflight. Antiorthostatic suspension resulted in higher levels of cytotoxicity from spleen cells for 51Cr-labeled K-562 cells. The results indicate differential effects of spaceflight on function of natural killer cells. This shows that spaceflight has selective effects on the immune response.

Experiments were carried out aboard COSMOS 2044 to determine the effects of spaceflight on immunologically important cell function and distribution. Control groups included vivarium, synchronous, and antiorthostatically suspended rats. In one experiment, rat bone marrow cells were examined in Moscow, for their response to recombinant murine granulocyte/monocyte colony-stimulating factor (GM-CSF). In another experiment, rat spleen and bone marrow cells were stained in Moscow with a variety of antibodies directed against cell surface antigenic markers. These cells were preserved and shipped to the United States for analysis on a flow cytometer. Bone marrow cells from flown and suspended rats showed a decreased response to granulocyte/monocyte colony-stimulating factor compared with bone marrow cells from control rats. Of the spleen cell subpopulations examined from flown rats, only those cells expressing markers for suppressor-cytotoxic T- and helper T-cells showed an increased percentage of stained cells. Bone marrow cells showed an increase in the percentage of cells expressing markers for helper T-cells in the myelogenous population and increased percentages of anti-asialo granulocyte/monocyte-1-bearing interleukin-2 receptor-bearing pan T- and helper T-cells in the lymphocytic population. Cell populations from rats suspended antiorthostatically did not follow the same pattern of distribution of leukocytes as cell populations for flown rats. The results from COSMOS 2044 are similar, but not identical, to earlier results from COSMOS 1887 and confirm that spaceflight can have profound effects on immune system components and activities.

A virus was isolated during disease outbreaks in bream Abramis brama, tench Tinca tinca, roach Rutilis rutilis and crucian carp Carassius carassius populations at 6 fishery sites in England in 1999. Mortalities at the sites were primarily among recently introduced fish and the predominant fish species affected was bream. The bream stocked at 5 of the 6 English fishery sites were found to have originated from the River Bann, Northern Ireland. Most fish presented few consistent external signs of disease but some exhibited clinical signs similar to those of spring viraemia of carp (SVC), with extensive skin haemorrhages, ulceration on the flanks and internal signs including ascites and petechial haemorrhages. The most prominent histopathological changes were hepatocellular necrosis, interstitial nephritis and splenitis. The virus induced a cytopathic effect in tissue cultures (Epithelioma papulosum cyprini [EPC] cells) at 20 degrees C and produced moderate signals in an enzyme immunoassay (EIA) for the detection of SVC virus. The virus showed a close serological relationship to pike fry rhabdovirus in both EIA and serum neutralisation assays and to a rhabdovirus isolated during a disease outbreak in a bream population in the River Bann in 1998. A high degree of sequence similarity (> or = 99.5% nucleotide identity) was observed between the English isolates and those from the River Bann. Experimental infection of juvenile bream, tench and carp with EPC cell-grown rhabdovirus by bath and intraperitoneal injection resulted in a 40% mortality of bream in the injection group only. The virus was re-isolated from pooled kidney, liver and spleen tissue samples from moribund bream. The field observations together with the experimental results indicate that this rhabdovirus is of low virulence but may have the potential to cause significant mortality in fishes under stress.

We report 22 patients (19 women and three men) of mean age 20.8 years who had painful snapping sensations in the groin. Most were able to reproduce the click by extending the affected hip from a flexed, abducted and externally rotated position and most were tender in the adductor triangle. Plain radiographs and an arthrogram were normal. A clinical diagnosis of subluxation of the iliopsoas tendon was made. Conservative management failed in 14 patients, two of whom had bilateral pain. All 14 had surgical release of the iliopsoas tendon through a medial approach. At follow-up (mean 17 months) the click had resolved in ten hips, was occasional but painless in five and unchanged in one. The syndrome of a painful 'snapping' psoas may result in disproportionately disabling symptoms. It may be diagnosed on clinical grounds and effectively treated, when severe, by release of the iliopsoas tendon.

We examined 67 different mutations in 16 different amplicons in a comparison of mutation detection by fluorescent single strand conformation polymorphism (F-SSCP) and by denaturing HPLC (DHPLC). F-SSCP was used to analyze fluorescent amplicons with internal size standards and automated fragment analysis (GeneScan, PE Applied Biosystems, Foster City, CA). In DHPLC, unlabelled amplicons were analyzed by reverse phase HPLC with fragment detection by absorbance at 260nm. Both methods had high sensitivity (95-100%) and specificity (100%). Overall, F-SSCP with external temperature control was the more sensitive method, but DHPLC was particularly useful for the rapid analysis of novel fragments.

Specificity of the oral glucose tolerance test (OGTT) for the diagnosis of small intestinal malabsorption in the horse was assessed by comparing the results of OGTT with the results of a histopathological examination of the small intestine in 42 adult horses affected by chronic weight loss. The horses were assigned to three groups on the basis of the results of the test. Five horses were considered to have a normal OGTT absorption result (Group 1); all the horses had a histologically normal small intestine. Twenty-five horses had a partial malabsorption result (Group 2) seven of which had normal small intestinal morphology, whereas the remaining 18 had a variety of pathological lesions including lymphosarcoma, villous atrophy, granulomatous enteritis and eosinophilic gastroenteritis. Twelve of the 42 horses had a total malabsorption result (Group 3), and all had a severe infiltrative lesion in the small intestinal wall (either lymphosarcoma or granulomatous enteritis).

Cleavage-based methods of mutation detection offer a simple and intuitive means to detect and in most cases locate mutations within DNA fragment sizes ranging from 500 to 1500 bases. Their main advantages as a presequencing screening technology when scanning for unknown mutations is the potential to increase throughput by multiplexing. Combined with lower reagent costs per sample, mutation scanning methods offer significant advantages over currently available sequencing techniques and are likely to be of increasing importance as genomic sequence data becomes more readily available. Although enzymatic methods offer the advantages of simpler and less hazardous protocols, at present the most robust cleavage methods are based around chemical methods.

The nuclear transcription factor-kappaB (NF-kappaB) and free radicals are known to be involved in apoptosis. We studied the effects of a series of di-aryl-substituted pyrazole NF-kappaB inhibitors including tepoxalin on tumor necrosis factor alpha (TNFalpha)-induced apoptosis in murine fibrosarcoma WEHI 164 cells. We found that potent inhibitors of NF-kappaB were also effective in attenuating apoptosis. WEHI 164 cells that had been dually treated with tepoxalin and the antioxidant pyrrolidine dithiocarbamate (PDTC) were significantly protected from TNFalpha-induced killing. To study the role of free radicals in mediating TNFalpha-induced apoptosis, stable WEHI 164 cells overexpressing Bcl-2, an antioxidant protein, were generated. These cells were protected from TNFalpha-induced apoptosis and neither tepoxalin nor PDTC provided further significant protection. These results suggest that Bcl-2, PDTC, and tepoxalin may attenuate apoptosis in this system by affecting the same signaling pathway or converging pathways. Because tepoxalin suppresses the release of free radicals, PDTC scavenges free radicals and Bcl-2 is an antioxidant protein, free radicals are among the key mediators of this TNF-induced killing event. Tepoxalin and antioxidants may be useful in developing new therapeutics for treating neurodegenerative diseases, autoimmune deficiency syndrome, and ischemia-reperfusion injuries.

Since the early work of Mann and Spoerry, probiotics in the form of fermented milk products have been reputed to have cholesterol-lowering properties in humans. However, studies conducted since the early 1970s have produced equivocal findings, with interpretation of the outcomes complicated by use of excessive quantities of product, inadequate sample sizes, failure to control nutrient intake and energy expenditure and variations in baseline blood lipids. More recent studies are of better quality, but fail to provide convincing evidence that 'live' fermented milk products have cholesterol-lowering efficacy in man. Future studies using probiotics should ensure adequate sample sizes sufficient to detect relatively small changes in blood cholesterol and should be conducted over longer periods of time. The recent introduction of the concept of prebiotics has directed attention towards the possibility that alterations in gut microflora induced by the fermentation of non-digestible components of the diet may also have the potential to influence systemic lipid metabolism. This possibility has been strengthened by the observation that in animals, dietary oligofructosaccharides cause suppression of hepatic triglyceride and VLDL synthesis, resulting in marked reductions in triglyceride, and to a lesser extent cholesterol, levels. Evidence for similar effects in humans is sparse and more studies are needed, particularly with respect to effects on postprandial triglyceride concentrations.

We report the six-year results of a prospective, controlled demographic trial of developmental dysplasia of the hip (DDH) treated in the Pavlik harness using ultrasound supervision. Our aim was to assess the value of ultrasound and its role in monitoring reduction in the harness, in terms of progression or failure of reduction at an early state. From 1988 to 1994, a total of 221 patients with 370 ultrasonographically abnormal hips was treated in the Pavlik harness. This represents a treatment rate for the Southampton district of 5.1 per 1000 live births. Sixteen hips in 12 patients were not reduced in the harness and required surgical treatment; 95.7% were successfully reduced. One case of mild avascular necrosis (0.3%) was identified in those treated by harness alone. Of the 221 patients 87.8% remain under radiological review, with 3.2% of affected hips showing continued, mild acetabular dysplasia. We conclude that ultrasound monitoring has led to an acceptably low level of intervention, a high reduction rate and minimal iatrogenic complications. The trial is continuing.

The results of immunological analyses before, during and after spaceflight, have established the fact that spaceflight can result in a blunting of the immune mechanisms of human crew members and animal test species. There is some evidence that the immune function changes in short-term flights resemble those occurring after acute stress, while the changes during long-term flights resemble those caused by chronic stress. In addition, this blunting of the immune function occurs concomitant with a relative increase in potentially infectious microorganisms in the space cabin environment. This combination of events results in an increased probability of inflight infectious events. The realization of this probability has been shown to be partially negated by the judicious use of a preflight health stabilization program and other operational countermeasures. The continuation of these countermeasures, as well as microbial and immunological monitoring, are recommended for continued spaceflight safety.

The folate-sensitive fragile site FRAXE is located in proximal Xq28 of the human X chromosome and lies approximately 600 kb distal to the fragile X syndrome (FRAXA) fragile site at Xq27.3. The cytogenetic expression of FRAXE is thought to be associated with mental handicap, but this is usually mild compared to that of the more common fragile X syndrome that is associated with the expression of the FRAXA fragile site. The exact incidence of FRAXE mental retardation is uncertain. We describe here the results of a U.K. survey designed to assess the frequency of FRAXE in a population of individuals referred for fragile X syndrome testing and found to be negative for expansion events at the FRAXA locus. No FRAXE expansion events were found in 362 cytogenetically negative males studied, and one expansion event was identified in a sample of 534 males for whom cytogenetic analyses were either unrecorded or not performed. Further FRAXE expansion events were detected in two related females known to be cytogenetically positive for a fragile site in Xq27.3-28. To gain insight into the FRAXE phenotype, the clinical details of the identified FRAXE male plus three other FRAXE individuals identified through previous referrals for fragile X syndrome testing are presented. For the population studied, we conclude that FRAXE mental retardation is a relatively rare but significant form of mental retardation for which genetic diagnosis would be appropriate.

Between 1989 and 1992 we admitted 426 children with an irritable hip, 363 (85.2%) once and 63 (14.8%) on 143 occasions. We assessed the records retrospectively to determine whether the groups differed and in particular whether recurrence was followed by pathological sequelae. We identified no feature which distinguished between them at either presentation. The use of bone isotope scans was greatly increased in recurrent cases, without clinical benefit. No relationship between recurrence and subsequent abnormality was identified, with 22 (42%) of the recurrences taking place in the opposite hip. The only difference was a higher incidence of 'psychosocial factors' recorded in the notes of children who presented on more than two occasions. The incidence of recurrent irritable hip is larger than previously indicated and in the presence of normal radiographs and low-grade clinical signs, more detailed investigation on subsequent admission is unlikely to be helpful.

C8- and N7, C8-substituted guanine ribonucleosides comprise a class of molecules with potent immunostimulatory activity for a variety of humoral and cellular immune responses. Although it has been suggested that the immunostimulatory activity may be partially mediated by cytokine production, to date there has been no systematic evaluation of the spectrum of cytokines elicited by these nucleosides. In this study, we examine the cytokines produced by murine spleen cells in response to the di-substituted guanosine analog loxoribine (7-allyl-8-oxoguanosine). First, the levels of cytokine mRNA in spleens from vehicle- or loxoribine-treated mice were compared using PCR analysis with a panel of cytokine-specific primers. Enhancement of IL-1 alpha, TNF-alpha, TNF-beta, IL-6, IFN-alpha, and IFN-gamma mRNA was seen in the spleens of loxoribine-treated mice. IL-12 mRNA responses were more complex, with an increase in the p40 chain and a decrease in the p35 chain. In contrast, no increase was seen for mRNA levels of IL-2, IL-3, IL-4, IL-5, IL-7, or GM-CSF. ELISA assays on the supernatants of loxoribine-treated spleen cells demonstrated that IL-1 alpha, IL-6, TNF-alpha, and IFN-gamma were all produced in a dose-dependent fashion with TNF-alpha produced first, followed by IL-6 and IFN-gamma, and last by IL-1 alpha. IFN-alpha beta activity rose as quickly as TNF-alpha, leveling off at 8 to 12 hr, and was supplanted by a later-occurring surge of IFN-gamma production. IL-1 alpha, IL-6, TNF-alpha, and IFN-gamma were also detected in the sera of mice injected with loxoribine. When antibodies against the relevant cytokines were tested, only anti-IFN-alpha beta inhibited NK activity or lymphocyte proliferation and, in both cases, activity was partially restored by the addition of exogenous IFN-alpha beta. Taken together, these data indicate that loxoribine induces the production of a selective cohort of cytokines all of which have been shown to have immunostimulatory activity. However, only IFN-alpha beta appears to play a role in the enhancement of NK activity and lymphocyte proliferation.

Many potent nonsteroidal antiinflammatory drugs (NSAIDs) exert their effects by inhibiting the cyclooxygenase activity of prostaglandin H synthase-1 (PGHS1, thus disrupting prostaglandin biosynthesis. However, these drugs do not block the activation of NF-kappa B, an inducible transcription factor which regulates numerous inflammation-related genes. Here we demonstrate that PGHS1 peroxidase, a NSAID-insensitive activity of PGHS1, mediates NF-kappa B activation through an intracellular reactive oxygen signaling pathway. Overexpression of PGHS1 strongly potentiated NF-kappa B activation by phorbol esters and dramatically elevated the generation of intracellular reactive oxygen species (ROS) in response to low concentrations of t-butyl peroxide. Both functions were dependent on PGHS1 peroxidase activity and could be suppressed by the potent antioxidant pyrrolidine dithiocarbamate. In contrast, elimination of PGHS1 cyclooxygenase activity by NSAIDs or site-directed mutagenesis failed to block ROS production or NF-kappa B activation. Thus, PGHS1 peroxidase serves an intracellular signaling function leading to NF-kappa B activation, separable from its role in prostaglandin synthesis.

Clinical laboratory diagnostic capabilities are needed to guide health and medical care of astronauts during long-duration space missions. Clinical laboratory diagnostics, as defined for medical care on Earth, offers a model for space capabilities. Interpretation of laboratory results for health and medical care of humans in space requires knowledge of specific physiological adaptations that occur, primarily because of the absence of gravity, and how these adaptations affect reference values. Limited data from American and Russian missions have indicated shifts of intra- and extracellular fluids and electrolytes, changes in hormone concentrations related to fluid shifts and stresses of the missions, reductions in bone and muscle mass, and a blunting of the cellular immune response. These changes could increase susceptibility to space-related illness or injury during a mission and after return to Earth. We review physiological adaptations and the risk of medical problems that occur during space missions. We describe the need for laboratory diagnostics as a part of health and medical care in space, and how this capability might be delivered.

The current study tested the hypothesis that exposure to hypoxia enhances endothelin-1 (ET-1) gene expression and elevates circulating ET-1 levels in the rat. Rats were exposed to normobaric hypoxia (10% O2) or room air for 24 or 48 h. ET-1 in arterial blood was measured by radioimmunoassay. ET-1 gene transcript levels were measured by the slot blot technique on total RNA isolated from lung, right and left atria, right and left ventricles, kidney, spleen, liver, brain, main trunk of pulmonary artery, and thoracic aorta. Blots were probed with a 0.5 kb rat prepro ET-1 cDNA that does not cross-hybridize with mRNA for ET-2 or ET-3. Plasma ET-1 levels were increased significantly at 24 (10.03 +/- 2.33 pg/ml) and 48 h (14.02 +/- 3.44 pg/ml) of hypoxia compared with air controls (4.14 +/- 0.66 pg/ml). ET-1 mRNA levels were increased significantly (2-fold) in lung and right atrium after 48 h of hypoxia; no change was seen in organs perfused by the systemic vascular bed. These findings suggest that the hypoxia-induced increase in circulating ET-1 levels is mainly of pulmonary origin. A paracrine effect of ET-1 produced by lung endothelial cells could account for hypoxic pulmonary hypertension.

In some chorionic villus biopsy (CVB) cases the fetal/maternal origin of the tissue obtained is uncertain. An approach which only requires small amounts of CVB tissue to establish its origin is described. Since it is only the samples typed as female that could be either fetal or maternal, a paternal X chromosome contribution is sought by using highly polymorphic X-linked microsatellites.

Intraocular pressures, retinal vascular diameters, and visual acuities of nine men (ages 19-29), were repeatedly measured while the subjects were tilted 10 degrees head-down for 48 h and while they were seated before (baseline), and after the tilt. An immediate increase in intraocular pressure, measured by pneumatonometer (4.7 +/- 0.6 mm Hg, p less than 0.001) was recorded when subjects assumed the head-down position, and diurnal variations in intraocular pressures were observed for the 48 h. The initial and final head-down intraocular pressures were not significantly different (18.9 +/- 1.2 mm Hg vs. 17.9 +/- 1.4 mm Hg, respectively). However, when subjects resumed the sitting position, intraocular pressures fell below the initial sitting values (14.2 +/- 0.9 pre vs. 11.2 +/- 0.5 post, p less than 0.04). Computer image analysis of the retinal vasculature detected a 6% and 2% reduction in the caliber of arteries and veins, respectively, as compared with sitting baseline values. No changes in visual acuity were documented during the 48 h of head-down tilt. Our data suggest that the choroidal blood reservoir increases in volume over 48 h at continuous head-down position with a compensatory decrease in aqueous volume. These findings may explain intraocular pressure changes noted in astronauts during previous space missions and in studies associated with change in body position.

Experiments were carried out on cells from rats that had been flown on Soviet Biosputnik Cosmos 1887 to explore the effects of spaceflight on immune responses. Rat bone marrow cells were examined for their response to colony stimulating factor-M. Rat spleen and bone marrow cells were stained with antibodies directed against cell surface antigenic markers. The results of the studies indicate that bone marrow cells from flown rats showed a decreased response to colony stimulating factor. There was a higher percentage of spleen cells from flown rats staining positively for pan-T-cell, suppressor-T-cell and interleukin-2 receptor cell surface antigens. A small increase in the percentage of cells staining positively for helper-T-cell antigens was also noted. In addition, a higher percentage of cells that appeared to be part of the myelogenous population of bone marrow cells from flown rats stained positively for surface immunoglobulin.

Summary Two horses affected by chronic, intermittent colic were found, at post-mortem examination, to have localized annular thickening of a segment of the duodenum. Histological examination of the lesion in both cases revealed a tumour composed of bundles of oval or spindle-shaped cells that stained as muscle with van Gieson stain. The histological diagnosis was leiomyosarcoma. The tumour had caused partial bowel obstruction in both horses.