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The presence of chloride-formate anion exchange in vascular smooth muscle cells (VSMCs) and cardiac myocytes was investigated. Imposing an outward chloride gradient in sarcolemmal microsomes isolated from canine aorta stimulated [14C]formate uptake compared with the absence of a chloride gradient (24.3 +/- 2.33 versus 9.8 +/- 1.41 pmol/mg protein for 30 seconds, P < .03) and induced transient uphill [14C]formate uptake. The chloride-formate exchange was significantly inhibited in the presence of 1 mmol/L 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) or furosemide (57% and 61%, respectively). Incubation of rat cultured VSMCs in a medium containing [14C]formate resulted in uptake of formate that was significantly DIDS and furosemide sensitive (79.34 +/- 2.47, 43.03 +/- 2.37, and 44.65 +/- 1.68 pmol/mg protein for 4 minutes in control, DIDS, and furosemide groups, respectively). Preincubation of the VSMCs in chloride-free medium significantly reduced the DIDS-sensitive (36.31 versus 16.85 pmol/mg protein for 4 minutes, P < .001) and furosemide-sensitive (34.72 versus 8.78 pmol/mg protein for 4 minutes, P < .001) [14C]formate uptake. These results are compatible with the presence of chloride-formate exchange in VSMCs. Influx of [14C]formate into sarcolemmal vesicles isolated from canine heart was significantly higher in the presence of an outward chloride gradient than in its absence (18.1 +/- 2.3 versus 9.6 +/- 1.7 pmol/mg protein for 30 seconds, P < .03). The chloride-formate exchange was significantly inhibited in the presence of 1 mmol/L DIDS or furosemide (41% and 52%, respectively). We conclude that the distribution of chloride-formate exchange may be more universal than previously suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

Late blight is caused by the oomycete Phytophthora infestans (Mont.) de Bary and is one of the most devastating diseases of potato and tomato. Late blight occurs in all major potato- and tomato-growing regions of Canada. Its incidence in North America increased during 2009 and 2010 (2). Foliar disease symptoms appeared earlier than usual (June rather than July) and coincided with the identification of several new P. infestans genotypes in the United States, each with unique characteristics. Prior to 2007, isolates collected from potato and tomato crops were mainly US8 or US11 genotypes (1). However, P. infestans populations in the United States have recently experienced a major genetic evolution, producing isolates with unique genotypes and epidemiological characteristics in Florida and throughout the northeastern states (2). Recent discoveries of tomato transplants with late blight for sale at Canadian retail outlets prompted an examination of the genotypes inadvertently being distributed and causing disease in commercial production areas in Canada. Analysis of isolates of P. infestans from across Canada in 2010 identified the US23 genotype for the first time from each of the four western provinces (Manitoba, Saskatchewan, Alberta, and British Columbia) but not from eastern Canada. Allozyme banding patterns at the glucose phosphate isomerase (Gpi) locus indicated a 100/100 profile consistent with US6 and US23 genotypes (4). Mating type assays confirmed the isolates to be A1 and in vivo metalaxyl sensitivity was observed. Restriction fragment length polymorphic analysis of 50 isolates from western Canada with the multilocus RG57 sequence and EcoRI produced the DNA pattern 1, 2, 5, 6, 10, 13, 14, 17, 20, 21, 24, 24a, 25 that was indicative of US23 (3). The recently described P. infestans genotype US23 appears to be more aggressive on tomato, and although isolates were recovered from both tomato and potato, disease symptoms were often more severe on tomato. Results indicate that movement and evolution of new P. infestans genotypes have contributed to the increased incidence of late blight and that movement of the pathogen on retail plantlets nationally and internationally may provide an additional early season source of inoculum. A major concern is that the introduced new A1 populations in western Canada have established a dichotomy with the endogenous A2 populations in eastern Canada, increasing the potential for sexual recombination producing oospores and additional genotypes should these populations merge. References: (1) Q. Chen et al. Am. J. Potato Res. 80:9, 2003. (2) K. Deahl. (Abstr.) Phytopathology 100(suppl.):S161, 2010. (3) S. B. Goodwin et al. Curr. Genet. 22:107, 1992. (4) S. B. Goodwin et al. Phytopathology 88:939, 2004.

Two 2.5-cm2 full-thickness skin wounds were created surgically over the lateral aspect of the cannon bone of each limb of 6 horses (n = 48 wounds). Dressings evaluated were a nonadherent gauze pad (group 1); a synthetic semiocclusive dressing, (group 2); equine amnion (group 3); and a synthetic fully occlusive dressing (group 4). Wounds were assessed subjectively at each dressing change, and total wound area, area of granulation tissue, and area of epithelium in each wound were determined by computerized digital analysis of photographs of the wounds. Complete healing time (wound covered by epithelium) also was determined for each wound. Statistical comparisons were made, using Kruskal-Wallis analysis and a Mann-Whitney U test. Median time to complete healing was: group 1, 53 days; group 2, 71 days; group 3, 63 days; and group 4, 113 days. Time to complete healing was significantly longer for wounds of group-4 horses than all other groups, and wounds of group-1 horses healed faster than did those of group-2 horses (P0.05). Wounds in group-4 horses required significantly (Por = 0.05) more excisions of granulation tissue (median, 11.5 times) than did those in group-1 (median, 3.5), group-2 (median, 5.5) or group-3 (median, 2.5) horses. Epithelial tissue was detected later in wounds of group-4 horses (median, 27 days) than in wounds of horses in groups 1, 2 or 3 (median, 17 days); however, this difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

The following case is presented to illustrate the roentgenographic and clinical findings of a condition of interest to the orthopaedic surgeon. The initial history, physical findings, and roentgenographic examinations are found on this page. The final clinical and roentgenographic differential diagnoses are presented on the following pages.

Thrombospondin (TSP) binds to its cellular receptor, CD36 (glycoprotein IV or IIIb), and participates in many adhesive cell interactions. We have shown that the CD36-TSP interaction occurs in a stepwise, conformation-dependent process. CD36 sequence 139-155 binds TSP and induces a second CD36-binding site, which binds CD36 sequence 93-110 with high affinity. To characterize this high affinity CD36-binding site on TSP, an anti-TSP monoclonal antibody (mAb), 7A-1e, was identified that showed augmentation of TSP binding in the presence of CD36 peptide P139-155. Purified mAb 7A-1e IgG specifically blocked both P139-155-augmented CD36 binding and P139-155-dependent CD36 peptide P93-110 binding to TSP, indicating that the binding sites on TSP for mAb 7A-1e and P93-110 are closely related. mAb 7A-1e IgG inhibited collagen-induced platelet aggregation in platelet-rich plasma. SVTCG is a cell adhesive motif in TSP. Both mAb 7A-1e and P93-110 specifically bound to a TSP peptide containing SVTCG, and the binding of mAb 7A-1e or P93-110 to TSP was inhibited by soluble SCTCG peptide. The SVTCG cell adhesive domain in TSP is the conformation-dependent, high affinity binding site for CD36 sequence 93-110.

The psychological functioning of 20 adult liver transplant candidates was evaluated. Using standardized assessment instruments, we found few personality disturbances and normal levels of anger. However, clinically significant levels of depression and anxiety were reported for 28% and 37% of the sample, respectively. Moreover, patients whose coping strategies were characterized by avoiding the exigencies of their illness reported more depression, more anxiety, and increased psychopathology. Disease severity was also positively correlated with anxiety and avoidant coping strategies. Implications of these findings for the pre-transplant psychological evaluation are discussed.

Eighty-four patients with primary disorders of muscle were referred for assessment of respiratory insufficiency between 1978 and 1991. The eventual diagnoses were: 'limb girdle syndromes' (18 patients), adult onset acid maltase deficiency (14), dystrophia myotonica (13), inflammatory disorders (10), congenital myopathies (nine), rigid spine syndromes (five), dystrophies (Duchenne (six), facioscapulohumeral (four), Becker (one)) and miscellaneous (four). Presentations were often insidious, with progressive nocturnal hypoventilation culminating in respiratory failure or arrest, recurrent respiratory tract infections, or obstructive sleep apnoea. Respiratory symptoms developed relatively early in patients with acid maltase deficiency and inflammatory disorders but parallelled the development of limb weakness in limb girdle, myotonic and congenital syndromes. Sixty-six patients received respiratory support for a median of 5 years (1-34 years) using various techniques of negative and positive pressure ventilation. Fourteen patients received short-term support for an episode of respiratory failure before being weaned, 51 required nocturnal domiciliary ventilation and one was dependent on continuous domiciliary support. Tracheostomy was performed in 32 patients and used for domiciliary nocturnal ventilation in 25. Twenty-eight patients have subsequently died.

Left ventricular myocardial blood flow and metabolic parameters were studied in dogs with severe heart failure induced by rapid ventricular pacing. The impact of early administration of enalapril was also evaluated. Seventeen dogs were randomly assigned in a blinded fashion to receive enalapril at a dose of 10 mg orally per day or a matching placebo commencing 1 week after initiation of pacing. Six dogs underwent sham operations and served as a control for the myocardial blood flow and metabolic studies. In general, there was no significant difference in myocardial blood flow among the control dogs, the placebo-treated, and the enalapril-treated, paced dogs. However, tissue adenosine triphosphate was markedly reduced in both the enalapril-treated, paced dogs (2.43 +/- 0.55 mumol/gm wet weight, mean +/- SD) and the placebo-treated, paced dogs (2.79 +/- 0.39 mumol/gm) compared with the level in control dogs (4.77 +/- 0.88 mumol/gm, both p0.01). Tissue glycogen and lactate levels were similar in the three groups. The time to development of severe heart failure tended to be longer in the enalapril-treated dogs (33 +/- 12 days) than in the placebo-treated dogs (24 +/- 10 days, p = 0.07). In pacing-induced heart failure, therefore, an imbalance between energy supply and demand may contribute to the left ventricular dysfunction, myocardial ischemia does not play a major role, and early treatment with enalapril may prolong the time to development of severe heart failure.

Adherence of erythrocytes to vascular endothelium likely contributes to the pathophysiology of episodic microvascular occlusion in patients with sickle cell disease (Wick, et al., 1987). In addition, coagulation activation has been reported in sickle patients during complications such as pain episodes (Francis and Johnson, 1991). Since platelets contain adhesion proteins (e.g. von Willebrand factor, thrombospondin and fibrinogen), we investigated whether factors released from activated platelets from sickle patients promote adherence of sickle erythrocytes to human microvascular endothelial cells (MEC) under flow conditions.

Resonant electronic (A←X) absorption transitions in high-enthalpy gas flows carry with them information on density and thermodynamic state. By spectral examination of the absorption (or re-emission as fluorescence) of a suitable source the information can be extracted. In this paper the utility of the approach for diagnostics of hypersonic flow properties is examined. Some important aspects of the method requiring special attention are discussed, including high-resolution characterization of the resonant lamp source, treatment of Doppler shifts, collisional broadening, nonequilibrium vibrational state population, and modeling of the spectrometer response function. Finally, some approaches for application to hypersonic propulsion are discussed.

Impaired ability to excrete a water load occurs in a substantial number of patients with advanced cirrhosis and in animals with experimental cirrhosis. The nonosmotic stimulation of arginine vasopressin release from the pituitary has been implicated as an important factor in the abnormal water excretion in patients and animals with cirrhosis. In this study, arginine vasopressin hypothalamic gene expression was studied in cirrhotic rats. Cirrhosis was induced by a combination of phenobarbital treatment in drinking water and weekly intragastric administration of carbon tetrachloride for 13 to 15 wk. Severe cirrhosis was confirmed by morphological analysis and the presence of ascites. Plasma arginine vasopressin was also significantly higher in rats with cirrhosis (control = 1.77 +/- 0.16 and cirrhotic rats = 4.14 +/- 0.62 pg/ml, n = 9, p0.002). Hypothalamic arginine vasopressin messenger RNA was also significantly higher in cirrhotic rats (control = 762.1 +/- 132.3 and cirrhotic rats = 1,834.2 +/- 271.9 pg/hypothalamus, n = 9, p0.005). Pituitary arginine vasopressin content was significantly lowered in cirrhotic rats (control = 3.69 +/- 0.98 and cirrhotic rats = 1.57 +/- 0.09 micrograms/pituitary, n = 9, p0.05). No difference was seen in hypothalamic arginine vasopressin content between the two groups (control = 4.64 +/- 0.34 and cirrhotic rats = 4.23 +/- 0.33 ng/hypothalamus, n = 9, NS). Oxytocin messenger RNA in the hypothalamus was also not significantly different between the two groups (control = 8.61 +/- 0.68 and cirrhotic rats = 9.33 +/- 0.65 unit of density, n = 9, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Context. In the past years, evidence for the existence of outward-moving (Doppler blue-shifted) plasma and slow-mode magnetoacoustic propagating waves in various magnetic field structures (loops in particular) in the solar corona has been found in ultraviolet images and spectra. Yet their origin and possible connection to and importance for the mass and energy supply to the corona and solar wind is still unclear. There has been increasing interest in this problem thanks to the high-resolution observations available from the extreme ultraviolet (EUV) imagers on the Solar TErrestrial RElationships Observatory (STEREO) and the EUV spectrometer on the Hinode mission. Aims. Flows and waves exist in the corona, and their signatures appear in EUV imaging observations but are extremely difficult to analyse quantitatively because of their weak intensity. Hence, such information is currently available mostly from spectroscopic observations that are restricted in their spatial and temporal coverage. To understand the nature and origin of these fluctuations, imaging observations are essential. Here, we present measurements of the speed of intensity fluctuations observed along apparently open field lines with the Extreme UltraViolet Imagers (EUVI) onboard the STEREO mission. One aim of our paper is to demonstrate that we can make reliable kinematic measurements from these EUV images, thereby complementing and extending the spectroscopic measurements and opening up the full corona for such an analysis. Another aim is to examine the assumptions that lead to flow versus wave interpretation for these fluctuations. Methods. We have developed a novel image-processing method by fusing well established techniques for the kinematic analysis of coronal mass ejections (CME) with standard wavelet analysis. The power of our method lies with its ability to recover weak intensity fluctuations along individual magnetic structures at any orientation, anywhere within the full solar disk, and using standard synoptic observing sequences (cadence

Sleep Paralysis is the persistence of REM atonia into the wakefulness. It is found in normal subjects, but is frequently seen in narcolepsy, in conjunction with hypnogogic hallucinations and cataplexy. We investigated whether sleep paralysis may be associated with sleep disorders other than narcolepsy. A retrospective review of all patients seen at St Thomas9 Sleep Disorders Centre over a 9-year period was undertaken looking for sleep paralysis as a presenting symptom. In total, 15 patients were identified who presented with sleep paralysis without other features of narcolepsy. Three had a family history of isolated sleep paralysis, five had isolated sleep paralysis without family history, and seven were found to have episodes of desaturation or apnoea in REM sleep on polysomnography. Treatment with oral appliances, CPAP or ENT surgery resulted in resolution in sleep paralysis symptoms in three patients, and in one patient weight loss alone caused improvement. None were subsequently diagnosed with narcolepsy. Sleep paralysis can be isolated or in associated with narcolepsy, but it can be the presenting symptom of OSA. In this situation appropriate treatment of OSA may lead to resolution of the sleep paralysis. Isolated sleep paralysis does not appear to be a presentation of narcolepsy.

The ovarian renin-angiotensin system (RAS) has been studied extensively in the virgin cycling rat, but little information is available about this system in pregnant and postpartum rats. We show that renin and angiotensin I-converting enzyme (ACE)--the key enzymes involved in angiotensin II (Ang II) formation--and Ang II receptors, are present in pregnant and postpartum rat ovaries. From gestation Days 2-4 to 10-12, active ovarian renin ranged from 1.12 +/- 0.13 to 1.27 +/- 0.19 ng Ang I/h/mg and comprised between 68 and 86% of total (active+inactive) ovarian renin activity. Between Days 10-12 and Days 14-16 of pregnancy, ovarian active renin activity increased slightly, but inactive renin disappeared, suggesting its activation; the remaining active renin then decreased 62% by Days 18-20 (p0.05). On postpartum Day 2, both active and total ovarian renin activity exceeded that of Days 2-20 of pregnancy (p0.05); levels of both then declined sharply by postpartum Day 3 (p0.05). In pregnant rats, levels of ovarian Ang II receptors, identified by the specific binding of [125I]-[Sar1,Ile8]Ang II to ovarian membranes, were high between Days 2-4 and 10-12 of pregnancy, ranging from 12.8 +/- 1.7 to 15.7 +/- 3.4 fmol/mg, but steadily declined by 82% between gestation Days 10-12 and 18-20 (p0.05). Postpartum Ang II receptor levels on Days 2, 3, and 4 showed a gradual increase from low levels comparable to Days 18-20 of pregnancy. Ovarian ACE activity did not change throughout pregnancy or during the postpartum period.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasmodium falciparum-infected erythrocytes (parasitized red blood cells [PRBCs]) can adhere to uninfected erythrocytes (RBCs) to form rosettes, and adhere to the endothelial cell (EC) surface antigen CD36. These adherence phenomena have previously been considered quite different. We show that anti-CD36 monoclonal antibodies (MoAbs) reverse rosetting of PRBCs from both a culture-adapted line (Malayan Camp [MC] strain) and a natural isolate, GAM425. Three MoAbs that block adherence of PRBCs to ECs or C32 melanoma cells also reversed rosetting by greater than 50% at levels of less than 1 microgram/mL (OKM5, OKM8, and 8A6). Two other MoAbs that react with purified CD36 (1D3 and 1B1), but do not react with the surface of C32 cells, failed to reverse rosetting. When rosettes were disrupted and the RBCs and PRBCs were pretreated separately with antibodies before mixing to allow rosette reformation, only pretreatment of RBCs had an effect. MoAb 8A6 pretreatment of RBCs blocked rosette reformation, while MoAb 1B1 pretreatment did not. Rosetting was also reversed by purified human platelet CD36. In conjunction with evidence that CD36 is expressed on normal human erythrocytes (van Schravendijk et al, Blood 80:2105, 1992), we conclude that this CD36 is able to act as a host receptor for rosetting in the MC strain and some natural isolates of P falciparum.

CD36 (glycoprotein IV or IIIB) is an integral plasma membrane protein of wide cellular distribution and functions as a receptor site for thrombospondin (TSP), an adhesive protein important in cell-cell and cell-matrix interactions. OKM5, a monoclonal anti-CD36 antibody, has been reported to block CD36 cell adhesive functions suggesting that the OKM5 epitope on CD36 is functionally important. A panel of 10 synthetic CD36 peptides was made. One peptide, P139-155, specifically inhibited the immunoadsorption of CD36 by OKM5, and P139-155 was directly immunoadsorbed by OKM5, indicating that CD36 sequence 139-155 represents part of the OKM5 epitope. TSP bound to immobilized P139-155 in a dose-dependent and saturable manner. Surprisingly, P139-155 significantly augmented, instead of inhibited, binding of CD36 to TSP. This peptide did not induce platelet aggregation but augmented ADP- and collagen-induced aggregation in platelet-rich plasma. Another CD36 peptide, P93-110, which had no effect on OKM5 immunoadsorption, blocked binding of CD36 to immobilized TSP and partially inhibited collagen-induced platelet aggregation. P93-110 by itself did not bind to TSP; however, in the presence of P139-155, there was a marked enhancement of P93-110 binding to TSP, with a stoichiometry consistent with the trimeric nature of TSP. The data suggest that CD36-TSP interaction is a two-step process; the sequence 139-155 region of CD36 binds first to TSP, triggering a change in TSP to reveal a second site, which binds the 93-110 region of CD36 with high affinity. CD36 peptides can be used as stimulators or inhibitors in cellular adhesive events involving TSP-CD36 interaction. Conformational changes leading to the exposure or activation of high affinity binding sites may occur in both the receptor and the ligand upon cell-cell and cell-matrix adhesion.

Adherence of Plasmodium falciparum-infected RBCs (PRBC) to endothelial cells causes PRBC sequestration in cerebral microvessels and is considered to be a major contributor to the pathogenesis of cerebral malaria. Both CD36 and thrombospondin (TSP) are glycoproteins that mediate PRBC adherence to endothelial cells in vitro. Because they are both expressed on the surface of endothelial cells, they probably contribute to PRBC sequestration and vascular occlusion in vivo. By applying affinity labeling of receptor binding sites with purified ligands, we showed for the first time that both CD36 and TSP can bind independently to the PRBC surface and that the PRBC receptor(s) for CD36 and TSP are localized specifically to the electron-dense knob protrusions of the PRBC surface. These findings may help in efforts to develop a malaria vaccine to prevent cerebral malaria.

The thresholds used to define a positive result for bronchial provocation challenges (BPC) are arbitrary. Requiring smaller decrements in expired flow to define a positive study would capture more cases of reactive airways (increased sensitivity) but would include some "normal" responses (decreased specificity). To examine the relationship between threshold definition and the ability to correctly classify subjects as either normal or as having airways hyperresponsiveness (AHR), four different BPC tests were administered on different days to 20 patients with a clinical diagnosis of exercise-induced bronchospasm (EIB) and 20 control subjects. The four BPC tests were indoor exercise on a cycle ergometer, methacholine inhalation challenge (MIC), eucapnic voluntary hyperventilation (EVH) with dry gas, and EVH with cold gas. Our results indicate that the thresholds which best separate the two groups are different for each of the four BPC techniques. For methacholine inhalation (MIC), a fall in FEV1 (d%FEV1) of 15 percent or greater at 188 cumulative breath units was 100 percent specific for AHR but had a sensitivity of only 55 percent. Eucapnic voluntary hyperventilation (EVH) with room temperature dry gas was 100 percent specific at a d%FEV1 of 11 percent, but, at that threshold, sensitivity was only 50 percent. EVH with cold air was 100 percent specific at a d%FEV1 of 12 percent but sensitivity was only 35 percent. The bicycle ergometer challenge was far too insensitive to be of value in evaluating AHR. Based on their respective receiver operating characteristic curves, the best separation of the two subject groups occurred at a d%FEV1 of 5 percent and 12 percent for the two EVH techniques and MIC, respectively. An individual's response to one test was highly correlated with the response to either of the other two (r = 0.66, p less than 0.001 for dry vs cold gas EVH; r = 0.56, p less than 0.001 for dry gas EVH vs methacholine; and r = 0.69, p less than 0.001 for cold gas EVH vs methacholine). Thus, MIC and EVH techniques are equally useful in defining AHR and each has its optimal threshold for a positive test result.

Over a period of 3 summers, 21 colostrum-fed Holstein bull calves, 1 to 3 days old, were assigned to 7 replicates, each consisting of 3 calves. Within each replicate of 3 calves, 2 were selected at random, to be given 100,000 to 146,000 sporulated coccidia oocysts (principally Eimeria bovis) orally 60 hours after arrival at the college research farm. On the thirteenth day after coccidia inoculation, 1 of the 2 calves that had been given coccidia and the third calf that had not been inoculated, were given coronavirus by intranasal and oral routes. Calves were observed daily, and consistency of feces was scored visually. Nasal swab specimens for indirect immunofluorescent antibody testing for coronavirus and fecal samples for oocyst determination were obtained approximately every third day. Of 7 calves that were given only coronavirus, 3 developed diarrhea of short duration. Of 7 calves that were given only coccidia oocysts, 6 developed diarrhea. All 7 calves inoculated initially with coccidia and subsequently with coronavirus developed diarrhea. For 5 of 7 replicates, calves that were given coccidia and coronavirus developed diarrhea first. When overall severity, measured by fecal score and by blood in the feces, was compared, calves inoculated with coccidia followed by coronavirus were more severely affected (P less than 0.05) than were calves that were given only coronavirus. Calves that were given only coccidia oocysts appeared more severely affected than calves that were given only coronavirus, but differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells of cloned lines of human squamous lung carcinomas elaborate large glycoproteins that are associated with their tumorigenic potential. Two groups of clones (called Le(a)-X-positive and Le(a)-X-negative) were studied that either do or do not express the Le(a)-X oligosaccharide associated with large glycoproteins and mucins secreted by these clones. Le(a)-X-positive cells elaborate a mucin gel complex associated with their apical surfaces, which appears as a mosaic of extracellular plates. Clones of this type are tumorigenic in nude rodents when injected s.c. or when introduced into the lungs via intrabronchial aerosol. By contrast, the Le(a)-X-negative clones do not form extracellular plates and are not tumorigenic in the lungs or subcutaneously. We demonstrate that the extracellular plates of Le(a)-X-positive cells exclude antibodies from interacting with the underlying squamous lung carcinoma cells and may therefore exert an immunoprotective effect. In support of this possibility it was found that: (a) There is a substantial inflammatory cell infiltrate associated with regressing nodules of Le(a)-X-negative cells in nude rodent lung and subcutaneous nodules, while there is no observable infiltration associated with progressing Le(a)-X-positive tumors. (b) In the brain (an immunoprivileged site) tumors develop and progress when either Le(a)-X-negative or -positive cells are introduced.

A major factor in the pathogenesis of human cerebral malaria is blockage of cerebral microvessels by the sequestration of parasitized human red blood cells (PRBC). In vitro studies indicate that sequestration of PRBC in the microvessels is mediated by the attachment of knobs on PRBC to receptors on the endothelial cell surface such as CD36, thrombospondin (TSP), and intercellular adhesion molecule-1 (ICAM-1). However, it is difficult to test this theory in vivo because fresh human brain tissues from cerebral malarial autopsy cases are not easy to obtain. Although several animal models for human cerebral malaria have been proposed, none have shown pathologic findings that are similar to those seen in humans. In order to develop an animal model for human cerebral malaria, we studied brains of rhesus monkeys infected with the primate malaria parasite, Plasmodium coatneyi. Our study demonstrated PRBC sequestration and cytoadherence of knobs on PRBC to endothelial cells in the cerebral microvessels of these monkeys. Cerebral microvessels with sequestered PRBC were shown by immunohistochemical analysis to possess CD36, TSP, and ICAM-1. These proteins were not evident in the cerebral microvessels of uninfected control monkeys. Thus, our study indicates, for the first time, that rhesus monkeys infected with P. coatneyi can be used as a primate model to study human cerebral malaria. By using this animal model, we may be able to evaluate strategies for the development of vaccines to prevent human cerebral malaria.

Using standard laboratory procedures it was found that different pulp types showed very different recycling effects. Mechanical pulp fibres became flatter and more flexible giving a denser, stronger sheet. Beaten chemical pulp fibres “hornified”, resulting in a bulkier, weaker sheet. Unbeaten chemical pulp fibres were initially curly; recycling removed the curl. A mechanical/chemical pulp blend revealed that these effects occur at different rates. In no case was there evidence of fibre strength loss, or of fibre embrittlement. In these laboratory experiments, fines loss during sheetmaking affected the magnitude of the sheet properties, but not the trends.

In vivo isolated lung perfusion is a novel technique for targeting anticancer therapy to the lung while avoiding systemic toxicity as normal lung toxicity from the antitumour therapy becomes the limiting factor. This study was performed to investigate the effects of hyperthermia on lung function in an intact animal model in which both acute and subacute toxicity could be monitored. Dogs underwent in vivo isolated lung perfusion. A control group was perfused to a lung temperature of 37 degrees C (group 1) and two other groups were treated in an identical manner except that the perfusion temperature was 43 degrees-44.8 degrees C in group 2 and greater than 45 degrees C in group 3. An assessment of lung injury was performed pre-perfusion, immediately post-perfusion and 2 weeks post-perfusion by measurement of extravascular lung water (Qev), serotonin uptake and wet weight to dry weight ratio. Our findings showed that the lung was tolerant to hyperthermia up to about 44 degrees C for 1 h. Analysis of 4 animals who survived perfusion above 3/44.0 degrees C showed a highly significant decrease in serotonin uptake between pre- and post-perfusion values (82.4 +/- 1.2 vs 40.4 +/- 3.9, P less than 0.02); at 2 weeks serotonin uptake had returned to normal in all 3 dogs. Fulminating pulmonary oedema developed at temperatures over 45 degrees C. Serotonin uptake may be a sensitive predictor of thermal lung injury.

We describe a rapid MR imaging technique, applying functional analysis to images obtained during the tissue transit of injected contrast material into the cerebral circulation, which has potential for assessment of the altered hemodynamics in cerebral ischemia. This technique utilized turbo-FLASH imaging maximizing the T1 relaxivity properties of gadopentetate dimeglumine with positive contrast enhancement.

Achalasia is a cause of chronic aspiration pneumonia that may be complicated by pulmonary infection with Mycobacterium fortuitum. In any patient with achalasia, the presence of a pulmonary infiltrate that does not respond to routine antibiotic therapy should suggest the possibility of M fortuitum pulmonary infection, and sputum should be cultured for these organisms.

Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis, nephrotic syndrome, and pregnancy. Nonosmotic vasopressin release has been implicated in the water retention of these edematous disorders. The nonosmotic release of vasopressin is consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems in both experimental animals and in edematous patients. Moreover, the sympathetic nervous system has been shown to be involved in the nonosmotic release of vasopressin and activation of the renin-angiotensin system. These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial resistance. Neither total extracellular fluid volume nor blood volume is a determinant of renal sodium and water excretion. Rather, renal sodium and water retention is initiated by a decrease in effective arterial blood volume (EABV) due to either a fall in cardiac output or peripheral arterial vasodilation. The acute response to a decrease in EABV involves vasoconstriction mediated by angiotensin, sympathetic mediators, and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and aldosterone-mediated sodium retention. The resultant renal vasoconstriction limits the distal tubular delivery of sodium and water, thus maximizing the water-retaining effect of vasopressin and impairing the normal escape from the sodium-retaining effects of aldosterone. The elevated glomerular filtration rate and filtered sodium load in pregnancy allows increased distal sodium and water delivery in spite of a decrease in EABV, thus limiting edema formation during gestation.

We have used an isolated rat lung model to compare the quality of preservation of different flush techniques with each other and with topical cooling alone. Lung injury was assessed by recording lung weights after reperfusion after 4 and 6 hours of ischemia. The flush solutions studied were intracellular (Collins-Sacks), traditional extracellular, extracellular with low potassium plus dextran, and extracellular containing blood, mannitol, albumin, and prostacyclin (Wallwork's solution). Flushing with Wallwork's solution before both 4 and 6 hours of ischemia gave superior protection from lung edema after reperfusion over all the other methods.

The development of improved animal models for biological and preclinical studies of human lung cancer is important because lung cancer is the leading cause of cancer death in the United States. To determine whether the Rowett nude rat could serve as an orthotopic (organ-specific) model of this disease, nude rats (CR: NIH-RNU), with and without 500 rads of prior gamma-irradiation, were implanted intrabronchially with 10(7) cultured cells from 3 human lung cancer lines. Without irradiation, the NCI-H460 large-cell undifferentiated carcinoma had a 54% take-rate, whereas the NCI-H125 adenosquamous carcinoma and A549 adenocarcinoma had take-rates of 7 and 33%, respectively; irradiation increased the respective take-rates to 100, 83, and 90%. In irradiated rats, tumor age versus weight measurements showed progressive growth for all three tumors, with growth rates in the order: NCI-H460 greater than A549 greater than NCI-H125, requiring approximately 3, 5, and 9 weeks, respectively, for average tumor sizes to exceed 500 mg. The small-cell carcinoma cell line NCI-H345 was implanted only into irradiated rats and resulted in more slowly growing tumors. Histopathological study showed all model tumor types to have histological characteristics consistent with the clinical tumors from which the cell lines were derived. Each tumor type had a different growth pattern, with some of the the A549- and NCI-H125-derived tumors metastasizing to contralateral lung and/or regional lymph nodes. There was no evidence for immunological rejection in irradiated, tumor-bearing rats. Nonirradiated, implanted rats without gross tumor exhibited peribronchiolar mononuclear cell infiltration with or without fibrosis, suggesting prior immunological rejection. The successful orthotopic growth of these 4 human lung cancer cell lines in irradiated nude rats suggests that this model could be useful for biological and preclinical studies of human lung cancer, both in intact rats and via ex vivo perfusion of their tumor-bearing lungs.

Glycoprotein (GP) IIIb (also termed GPIV or CD36) is an integral platelet membrane protein, and has been identified as a binding site for thrombospondin, collagen, and malaria-infected erythrocytes. PAS-IV is an integral membrane protein found in lactating mammary epithelial cells and capillary endothelial cells. The N-terminal sequence of PAS-IV is nearly identical to that of GPIIIb and monospecific anti-PAS-IV antibody reacts with GPIIIb, indicating that PAS-IV is structurally related to GPIIIb. In this study, human platelet GPIIIb and bovine epithelial PAS-IV were compared in terms of structural, immunologic, and functional characteristics. The two-dimensional tryptic peptide map of both intact and deglycosylated PAS-IV was highly similar but not identical to that of GPIIIb. PAS-IV and GPIIIb reacted to an equal extent with monoclonal antibodies OKM5 and OKM8 by enzyme-linked immunosorbent assay. GPIIIb bound to surface immobilized thrombospondin (TSP) in a concentration-dependent and saturable manner, with approximately 60% reduction in binding in the presence of EDTA. PAS-IV bound to TSP with similar characteristics except that maximum binding was consistently approximately 50% of that of GPIIIb and binding was not inhibited by EDTA. GPIIIb supported adhesion of Plasmodium falciparum-infected erythrocytes (PRBC) in a dose-dependent manner while no significant adhesion of PRBC to PAS-IV was observed. Our data demonstrate that while epithelial PAS-IV and platelet GPIIIb are structurally and immunologically related, there are significant differences in their functional properties. Whether this result is due to different posttranslational glycosylation modifications or that PAS-IV and GPIIIb represent a family of related cell adhesive protein receptors remains to be determined.

The effects of volume loading on atrial pressures and dimensions, plasma levels of atrial natriuretic factor (ANF), and other neurohormonal variables were studied in 11 patients with normal hemodynamics with the patients in a supine -15 degree left decubitus posture by infusing 750 ml of normal saline solution over 30 minutes. Right and left atrial areas were measured by two-dimensional echocardiography. Plasma ANF level was sampled simultaneously from the pulmonary artery, aorta, and femoral artery and vein. At 30 minutes into the infusion, pulmonary capillary wedge pressure and right atrial pressure increased from 5.6 +/- 2.8 mm Hg (mean +/- SD) and 6.4 +/- 2.2 mm Hg to 10.2 +/- 3.2 and 9.5 +/- 2.2 mm Hg, respectively (both p less than 0.01). Left atrial area increased from 12.6 +/- 2.2 cm2 to 15.0 +/- 2.1 cm2 (p less than 0.05), whereas right atrial area did not change. Plasma ANF levels from all sampling sites increased significantly (e.g., 43 +/- 21 pg/ml to 71 +/- 62 pg/ml in the femoral artery, p less than 0.05). Plasma norepinephrine and renin levels were unchanged, whereas aldosterone level declined significantly. At 30 minutes after termination of the infusion, atrial pressures declined to baseline values in all patients. However, left atrial area remained significantly increased, and a trend for systemic arterial plasma ANF level to remain increased was seen. Plasma aldosterone level remained significantly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Mounier-Kuhn syndrome is a congenital abnormality of the trachea and main bronchi characterized by atrophy or absence of elastic fibers and thinning of muscle, which allows the trachea and main bronchi to become flaccid and markedly dilated on inspiration with narrowing or collapse on expiration or cough. The abnormal airway dynamics and pooling of secretions in broad outpouchings of redundant musculomembranous tissue between the cartilaginous rings predispose to the development of chronic pulmonary suppuration, bronchiectasis, emphysema, and pulmonary fibrosis. A broad spectrum of clinical abnormalities has been documented in Mounier-Kuhn syndrome, ranging from minimal disease with good preservation of pulmonary function to progressive disease leading to respiratory failure and death. In the appropriate clinical setting, Mounier-Kuhn syndrome is diagnosed in women from chest radiographs when the transverse and sagittal diameters of the trachea exceed 21 mm and 23 mm, respectively, and when the transverse diameters of the right and left main bronchi exceed 19.8 mm and 17.4 mm, respectively. In men it is diagnosed when the transverse and sagittal diameters of the trachea exceed 25 mm and 27 mm, respectively, and when the transverse diameters of the right and left main bronchi exceed 21.1 mm and 18.4 mm, respectively. The diagnosis can be confirmed easily by computed tomography.

The phospholipid and fatty acid compositions of the host infected erythrocyte plasma membrane (IEPM) have been determined for erythrocytes infected with the human malaria parasite Plasmodium falciparum. IEPM were prepared by selective lysis of the host erythrocyte (but not of the parasite membranes) with 0.1% saponin, followed by differential centrifugation. The purity of the IEPM was determined by measuring the membrane-specific enzyme markers acetylcholinesterase, glutamate dehydrogenase and lactate dehydrogenase, and by immunoelectron microscopy using monoclonal antibodies specific for human erythrocyte glycophorin A (4E7) and for a 195 kDa parasite membrane glycoprotein (Pf6 3B10.1). Both approaches demonstrated that the host erythrocyte plasma membrane preparation was free from contamination by parasite membranes. During intra-erythrocytic development of the parasite, the phospholipid composition of the erythrocyte membrane was strikingly altered. IEPM contained more phosphatidylcholine (38.7% versus 31.7%) and phosphatidylinositol (2.1% versus 0.8%) and less sphingomyelin (14.6% versus 28.0%) than normal uninfected erythrocytes. Similar alterations in phospholipid composition were determined for erythrocyte membranes of parasitized cells isolated by an alternative method utilizing polycationic polyacrylamide microbeads (Affigel 731). The total fatty acid compositions of the major phospholipids in IEPM were determined by g.l.c. The percentage of polyunsaturated fatty acids in normal erythrocyte phospholipids (39.4%) was much higher than in phospholipids from purified parasites (23.3%) or IEPM (24.0%). The unsaturation index of phospholipids in IEPM was considerably lower than in uninfected erythrocytes (107.5 versus 161.0) and was very similar to that in purified parasites (107.5 versus 98.5). Large increases in palmitic acid (C16:0) (from 21.88% to 31.21%) and in oleic acid (C18:1) (from 14.64% to 24.60%), and major decreases in arachidonic acid (C20:4) (from 17.36% to 7.85%) and in docosahexaenoic acid (C22:6) (from 4.34% to 1.8%) occurred as a result of infection. The fatty acid profiles of individual phospholipid classes from IEPM resembled in many instances the fatty acid profiles of parasite phospholipids rather than those of uninfected erythrocytes. Analysis of IEPM from P. falciparum-infected erythrocytes (trophozoite stage) revealed that, during intra-erythrocytic maturation of the parasite, the host erythrocyte phospholipid composition was markedly refashioned. These alterations were not dependent on the method used to isolate the IEPM, with similar results obtained using either a saponin-lysis method or binding to Affigel beads. Since mature erythrocytes have negligible lipid synthesis and metabolism, these alterations must occur as a result of parasite-directed metabolism of erythrocyte lipids and/or trafficking of lipids between the parasite and erythrocyte membranes.

A 36-year-old dental technician for 14 years developed paraesthesia and numbness in her legs. Neurophysiological studies revealed absent sensory nerve action potentials (SNAPs) from her lower limbs and normal upper limb SNAPs on presentation. Motor nerve studies were normal. Repeat studies 2 months after leaving her job showed some improvement in the lower limb SNAPs. It is suggested that her symptoms were caused by occupational exposure to methyl methacrylate monomer.

To understand the molecular mechanisms that lead to sequestration of red blood cells infected with mature stages of Plasmodium falciparum and to examine the relevance of earlier studies on adherence properties of laboratory-derived P falciparum parasites to the natural parasite population, we analyzed Gambian and Tanzanian isolates for in vitro cytoadherence and antibody-mediated microagglutination. Eighteen cryopreserved isolates of ring-stage parasites were cultured for 20 to 30 hours in vitro, in the patients original erythrocytes, to the trophozoite and schizont stage. All parasites were positive in the microagglutination assay with at least one of four African hyperimmune sera. In a rosetting assay, only 2 of the 18 isolates were strongly positive (35% and 41% of parasitized erythrocytes with more than two uninfected cells bound). Thirteen isolates showed either intermediate (5% to 18%) or low (less than 5%) rosetting while three isolates did not form rosettes. Infected cell-binding of the different isolates to immobilized CD36 or thrombospondin, or C32 melanoma cells correlated with the percentage of mature parasites in the blood samples (r = .932 for CD36, r = .946 for thrombospondin, and r = .881 for C32 melanoma cells). There was a high correlation between binding to CD36 and thrombospondin (r = .982). The extent of infected cell rosetting with uninfected cells in these blood samples was not correlated with these other receptor properties. We also observed coexpression of rosetting and cytoadherence receptors on the same parasitized erythrocytes.

Endothelial cell CD36 (glycoprotein IV) has been purified from bovine heart tissue by detergent partitioning and immunoaffinity chromatography. Bovine CD36 differs from human CD36 in its apparent mass (85 versus 88 kDa), primary structure, and immunological cross-reactivity. Of the 18 N-terminal residues identified, 17 conformed to the human CD36 sequence. Mouse monoclonal antibodies E-1 and 8A6 defined bovine- and human-specific epitopes, respectively. Because human CD36 has been identified as a receptor for erythrocytes infected with the malaria parasite Plasmodium falciparum, we examined the ability of bovine CD36 to bind infected erythrocytes. Bovine CD36, unlike human CD36, did not bind infected erythrocytes, suggesting that human CD36-specific structural features are responsible for recognition of the infected erythrocyte ligand.

Physicians and other health care workers risk infection with human immunodeficiency virus (HIV), hepatitis B virus and other infectious agents. Most authorities have argued against routine testing of patients preoperatively for HIV infection because it would not prevent or reduce the risk of infection to health care workers. They agree with the policy of the Centers for Disease Control that advocates universal precautions for all patients. Surgeons have not been reassured by these arguments. They claim that their exposure to blood during operation exposes them to increased risk of infection. The risk of acquiring HIV from a single needle-stick injury is low. However, most surgeons are interested in their lifetime risk of infection. In this study, a mathematical model for predicting the risk of acquiring HIV in patients in a given hospital and the total number of needle-stick injuries are given. Using minimal likely HIV seroprevalence, this model predicts that at least 47 of the approximately 18,000 Fellows of the American College of Surgeons would become infected. New data showing early treatment can lead to increased longevity in infected patients with HIV, the fact that many health care workers do not follow universal precautions and other arguments are put forward to support a suggested routine--voluntary testing of all surgical patients for antibody to HIV.

A method allowing assessment of cardiac structure and function in the conscious dog using readily available instrumentation is desirable and should provide physiologic advantages when compared to anaesthesia. Accordingly, we studied 19 dogs (22 +/- 2.5 kg), using two-dimensional echocardiographic and Swan-Ganz and femoral artery catheterization; ten were conditioned to permit conscious studies and nine received anaesthesia. Dogs receiving anaesthesia were induced with intravenous thiopental (16 +/- 4 mg/kg), followed by a maintenance dose (7 +/- 1 mg/kg/h) plus morphine sulphate (213 +/- 5 micrograms/kg/h). Cardiac index, mean blood pressure, and systemic vascular resistance were similar between groups. However, anaesthesia as compared to conscious studies resulted in a marked tachycardia (147 +/- 30 bpm, vs 98 +/- 19 bpm, p less than 0.0005), significantly lower right atrial pressure (5 +/- 2 mmHg vs 8 +/- 2 mmHg, p less than 0.05), and a trend towards a lower pulmonary capillary wedge pressure (6 +/- 5 mmHg vs 9 +/- 3 mmHg). Simultaneous echocardiography showed left ventricular diastolic cross sectional area to be smaller in the anaesthesia group (8.5 +/- 1.7 cm2 vs 10.4 +/- 1.5 cm2, p less than 0.05); however, ejection fraction in the two groups was similar. Velocity of circumferential fiber shortening (Vcf), normalized for heart rate and preload, was significantly lower in the anaesthetised dogs (0.63 +/- 0.22 circ/sec vs 0.89 +/- 0.26 circ/sec, p less than 0.05); this decline in Vcf, in association with a lower systolic wall stress (85 +/- 29 10(3) dynes/cm2 vs 119 +/- 23 10(3) dynes/cm2, p less than 0.05) indicates that thiopental-morphine anaesthesia depresses contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

The charge-coupled device (CCD) can be used to detect photons at wavelengths from the near UV infrared down to the x-ray region. In this paper we review the development of CCDs with respect to quantum efficiency and imaging characteristics for XUV and x-ray wavelengths. In the XUV region—15-50 nm—the CCD must be used in back-illuminated mode because the gate structures grown on the front side are completely opaque at these wavelengths. This requires that the imaging area of the backside be thinned to approximately the depth of the depletion region (about 10 µm), as the penetration technologies have been developed for thinning the device. Physical conditions in the backside surface oxide play an important role in the ability of the device to collect signal photoelectrons in the depletion region. For example, trapped positive charge creates a potential barrier that can inhibit collection of the signal photoelectrons. Ion implementation has been successfully used to modify back surface potentials, permitting useful detective quantum efficiencies throughout the XUV and soft-x-ray regions.

In recent years, a variety of techniques have been developed to generate and detect ultrafast electromagnetic transients with bandwidths up to 1 THz1. The spectrum of these transients spans part of the microwave, submillimeter wave and far-infrared range of the electro-magnetic spectrum. The spectroscopic benefits include the enormous spectral bandwidth covered, the coherent detection that enables to extract both real and imaginary part of the dielectric response function, and a sensitivity that far exceeds the sensitivity of conventional far-infrared spectrometers in the same spectral range.