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1.  Clinical-guide risk prediction of hepatocellular carcinoma development in chronic hepatitis C patients after interferon-based therapy 
British Journal of Cancer  2013;109(9):2481-2488.
Interferon (IFN)-based therapies could eradicate hepatitis C (HCV) and reduce the risk of hepatocellular carcinoma (HCC). However, HCC could still happen after sustained virological response (SVR). We aimed to develop a simple scoring system to predict the risk of HCC development among HCV patients after antiviral therapies.
From 1999 to 2009, 1879 patients with biopsy-proven HCV infection treated with IFN-based therapies were analyzed.
Multivariable analysis showed old age (adjusted HR (aHR)=1.73, 95% CI=1.13–2.65 for aged 60–69 and aHR=2.20, 95% CI=1.43–3.37 for aged ⩾70), Male gender (aHR=1.74, 95% CI=1.26–2.41), platelet count <150 × 109/l (HR=1.91, 95% CI=1.27–2.86), α-fetoprotein ⩾20 ng ml−1 (HR=2.23, 95% CI=1.58–3.14), high fibrotic stage (HR=3.32, 95% CI=2.10–5.22), HCV genotype 1b (HR=1.53, 95% CI=1.10–2.14), and non SVR (HR=2.40, 95% CI=1.70–3.38) were independent risk factors for HCC. Regression coefficients were used to build up a risk score and the accuracy was evaluated by using the area under the receiver operating characteristic curve (AUC). Three groups as low-, intermediate-, and high-risk are classified based on the risk scores. One hundred sixty patients (12.78%) in the derivation and 82 patients (13.08%) in the validation cohort developed HCC with AUC of 79.4%, sensitivity of 84.38%, and specificity of 60.66%. In the validation cohort, the 5-year HCC incidence was 1.81%, 12.92%, and 29.95% in low-, intermediate-, and high-risk groups, with hazard ratios 4.49 in intermediate- and 16.14 in high-risk group respectively. The risk reduction of HCC is greatest in patients with SVR, with a 5-year and 10-year risk reduction of 28.91% and 27.99% respectively.
The risk scoring system is accurate in predicting HCC development for HCV patients after antiviral therapies.
PMCID: PMC3817320  PMID: 24084770
risk score; hepatitis C virus; interferon; hepatocellular carcinoma
2.  A Case of Oropharyngeal Bullous Pemphigoid Presenting with Haemoptysis 
Case Reports in Otolaryngology  2015;2015:631098.
Objective. Bullous pemphigoid is well known for its cutaneous features; however in rare cases it may present with mucosal involvement. We report a case of bullous pemphigoid presenting with haemoptysis, initially presenting to the Ear, Nose and Throat Department for investigation. Methods. An 87-year-old lady was admitted with haemoptysis. She also complained of a spreading, pruritic, bullous rash, which first began three weeks previously. Initial investigations, which included nasendoscopy, revealed a normal nasal mucosa and a normal postnasal space. A large deroofed blister was observed on the soft palate. The presenting symptoms and signs raised the suspicion of an immunobullous disease including bullous pemphigoid. Conclusion. Bullous pemphigoid (BP) is a subepidermal immunobullous disease that typically manifests in elderly patient populations. Although rare, BP can present in a mucocutaneous fashion akin to its more aggressive variant, mucous membrane pemphigoid (MMP). Differentiation of the two is based on clinical grounds, with the prevailing feature for the latter being the predominance of mucosal involvement, which may be extensive. The mainstay of treatment for bullous pemphigoid is steroid therapy, which may be administered both topically and systemically. A deeper understanding into the pathophysiology of the various immunobullous diseases may assist in our understanding of how the various disease entities manifest themselves.
PMCID: PMC4302357  PMID: 25632365
3.  Pilot- and bench-scale testing of faecal indicator bacteria survival in marine beach sand near point sources 
Journal of applied microbiology  2009;107(1):72-84.
Factors affecting faecal indicator bacteria (FIB) and pathogen survival/persistence in sand remain largely unstudied. This work elucidates how biological and physical factors affect die-off in beach sand following sewage spills.
Methods and Results
Solar disinfection with mechanical mixing was pilot-tested as a disinfection procedure after a large sewage spill in Los Angeles. Effects of solar exposure, mechanical mixing, predation and/or competition, season, and moisture were tested at bench scale. First-order decay constants for Escherichia coli ranged between −0·23 and −·102 per day, and for enterococci between −0·5 and −1·0 per day. Desiccation was a dominant factor for E. coli but not enterococci inactivation. Effects of season were investigated through a comparison of experimental results from winter, spring, and fall.
Moisture was the dominant factor controlling E. coli inactivation kinetics. Initial microbial community and sand temperature were also important factors. Mechanical mixing, common in beach grooming, did not consistently reduce bacterial levels.
Significance and Impact of the Study
Inactivation rates are mainly dependent on moisture and high sand temperature. Chlorination was an effective disinfection treatment in sand microcosms inoculated with raw influent.
PMCID: PMC3938294  PMID: 19302327
degradation; detection; disinfection; indicators; soil; water quality
4.  Acute appendicitis: relationships between CT-determined severities and serum white blood cell counts and C-reactive protein levels 
The British Journal of Radiology  2011;84(1008):1115-1120.
The aim of this study was to evaluate the relationships between the severity of appendicitis as depicted on CT and blood inflammatory markers of serum white blood cell (WBC) count and C-reactive protein (CRP).
CT images in 128 patients (109 surgically proven and 19 with clinically excluded appendicitis) were retrospectively reviewed. Two radiologists by consensus evaluated and scored (using a 0, 1 or 2 point scale) severities based on CT-determined appendiceal diameters, appendiceal wall changes, caecal changes, periappendiceal inflammatory stranding and phlegmon or abscess formation. We investigated whether CT findings were significantly related to elevated WBC counts or CRP levels and performed the correlations of WBC counts and CRP levels with CT severity scores. Patients were also subjectively classified using four grades from normal (Grade I) to perforated appendicitis (Grade IV) on the basis of CT findings to evaluate differences in WBC counts and CRP levels between grades.
Only appendiceal wall changes and the phlegmon or abscess formation were related to elevated WBC counts and CRP levels, respectively (p<0.05). CT severity scores were found to be more strongly correlated with CRP levels (r = 0.669) than with WBC counts (r = 0.222). On the basis of CT grades, the WBC counts in Grade I were significantly lower than in other grades (p<0.001), whereas CRP levels in Grade IV were significantly higher than in other grades (p<0.001).
CRP levels were found to correlate with CT-determined acute appendicitis severity and could be a useful predictor for perforated appendicitis, whereas WBC counts might be useful to detect early acute appendicitis.
PMCID: PMC3473821  PMID: 21123307
5.  The fraction of ischaemic heart disease and stroke attributable to smoking in the WHO Western Pacific and South‐East Asian regions 
Tobacco Control  2006;15(3):181-188.
Tobacco will soon be the biggest cause of death worldwide, with the greatest burden being borne by low and middle‐income countries where 8/10 smokers now live.
This study aimed to quantify the direct burden of smoking for cardiovascular diseases (CVD) by calculating the population attributable fractions (PAF) for fatal ischaemic heart disease (IHD) and stroke (haemorrhagic and ischaemic) for all 38 countries in the World Health Organization Western Pacific and South East Asian regions.
Design and subjects
Sex‐specific prevalence of smoking was obtained from existing data. Estimates of the hazard ratio (HR) for IHD and stroke with smoking as an independent risk factor were obtained from the ∼600 000 adult subjects in the Asia Pacific Cohort Studies Collaboration (APCSC). HR estimates and prevalence were then used to calculate sex‐specific PAF for IHD and stroke by country.
The prevalence of smoking in the 33 countries, for which relevant data could be obtained, ranged from 28–82% in males and from 1–65% in females. The fraction of IHD attributable to smoking ranged from 13–33% in males and from <1–28% in females. The percentage of haemorrhagic stroke attributable to smoking ranged from 4–12% in males and from <1–9% in females. Corresponding figures for ischaemic stroke were 11–27% in males and <1–22% in females.
Up to 30% of some cardiovascular fatalities can be attributed to smoking. This is likely an underestimate of the current burden of smoking on CVD, given that the smoking epidemic has developed further since many of the studies were conducted.
PMCID: PMC2564655  PMID: 16728748
attributable fraction; ischaemic heart disease; stroke; smoking; Western‐Pacific; South‐East Asia
6.  Faecal indicator bacteria enumeration in beach sand: a comparison study of extraction methods in medium to coarse sands 
Journal of applied microbiology  2009;107(5):1740-1750.
The absence of standardized methods for quantifying faecal indicator bacteria (FIB) in sand hinders comparison of results across studies. The purpose of the study was to compare methods for extraction of faecal bacteria from sands and recommend a standardized extraction technique.
Methods and Results
Twenty-two methods of extracting enterococci and Escherichia coli from sand were evaluated, including multiple permutations of hand shaking, mechanical shaking, blending, sonication, number of rinses, settling time, eluant-to-sand ratio, eluant composition, prefiltration and type of decantation. Tests were performed on sands from California, Florida and Lake Michigan. Most extraction parameters did not significantly affect bacterial enumeration. anova revealed significant effects of eluant composition and blending; with both sodium metaphosphate buffer and blending producing reduced counts.
The simplest extraction method that produced the highest FIB recoveries consisted of 2 min of hand shaking in phosphate-buffered saline or deionized water, a 30-s settling time, one-rinse step and a 10 : 1 eluant volume to sand weight ratio. This result was consistent across the sand compositions tested in this study but could vary for other sand types.
Significance and Impact of the Study
Method standardization will improve the understanding of how sands affect surface water quality.
PMCID: PMC2810257  PMID: 19659700
E. coli; enterococci; faecal bacteria; sand
7.  VHL Type 2B gene mutation moderates HIF dosage in vitro and in vivo 
Oncogene  2009;28(14):1694-1705.
Von Hippel-Lindau (VHL) disease is caused by germline mutations in the VHL tumor suppressor gene, with Type 2B missense VHL mutations predisposing to renal cell carcinoma, hemangioblastoma, and pheochromocytoma. Type 2B mutant pVHL is predicted to be defective in hypoxia inducible factor (HIF)-α regulation. Murine embryonic stem (ES) cells in which the endogenous wild-type Vhl gene was replaced with the representative Type 2B VHL hotspot mutation R167Q (Vhl2B/2B) displayed preserved physiologic regulation of both HIF factors with slightly more normoxic dysregulation of HIF-2α. Differentiated Vhl2B/2B-derived teratomas over-expressed the joint HIF targets Vegf and EglN3 but not the HIF-1α-specific target Pfk1 and displayed a growth advantage over Vhl-/--derived teratomas, suggestive of a tight connection between perturbations in the degree and ratio of HIF-1α and HIF-2α stabilization and cell growth. Vhl2B/2B mice displayed mid-gestational embryonic lethality, while adult Vhl2B/+ mice exhibited susceptibility to carcinogen-promoted renal neoplasia compared with wild-type littermates at twelve months. Our experiments support a model in which the representative Type 2B R167Q mutant pVhl produces a unique profile of HIF dysregulation, thereby promoting tissue-specific effects on cell growth, development, and tumor predisposition.
PMCID: PMC2667565  PMID: 19252526
von Hippel-Lindau; hypoxia inducible factors; renal cell carcinoma
9.  Inhibition of endosomal sequestration of basic anticancer drugs: influence on cytotoxicity and tissue penetration 
British Journal of Cancer  2006;94(6):863-869.
The basic drugs doxorubicin and mitoxantrone are known to be concentrated in acidic endosomes of cells. Here, we address the hypotheses that raising endosomal pH with the modifying agents chloroquine, omeprazole or bafilomycin A might decrease sequestration of anticancer drugs in endosomes, thereby increasing their cytotoxicity and availability for tissue penetration. Chloroquine, omeprazole and bafilomycin A showed concentration-dependent effects to raise endosomal pH, and to inhibit sequestration of doxorubicin in endosomes. Chloroquine and omeprazole but not bafilomycin A decreased the net uptake of doxorubicin into cells, but there was no significant effect on uptake of mitoxantrone. Omeprazole and bafilomycin A increased the cytotoxicity of the anticancer drugs for cultured cells, as measured in a clonogenic assay, whereas chloroquine had minimal effects on cytotoxicity despite reduced uptake of doxorubicin. Omeprazole but not chloroquine or bafilomycin A increased the penetration of anticancer drugs through multicellular layers of tumour tissue. We conclude that modifiers of endosomal pH might increase therapeutic effectiveness of basic drugs by increasing their toxicity and/or tissue penetration in solid tumours.
PMCID: PMC2361369  PMID: 16495919
basic anticancer drugs; tissue penetration; chloroquine; omeprazole; endosomal pH
10.  Giant retroperitoneal hemangiopericytoma. 
Postgraduate Medical Journal  1995;71(841):692-695.
Hemangiopericytomas are rare vascular tumours that are derived from pericytes. Retroperitoneal hemangiopericytomas are usually bulky but clinically silent when diagnosed because of their slow rate of growth. A 49-year-old man, who presented with only vague symptoms of abdominal fullness for several months, was found on computed tomography to have a huge well-defined mass with areas of low attenuation and well-enhanced septa. The tumour was successfully resected and was confirmed to be a malignant retroperitoneal hemangiopericytoma. It measured 30 cm in the greatest dimension. We are prompted to present this case as it is believed to be the largest tumour reported to date.
PMCID: PMC2398329  PMID: 7494778
11.  Case of difficult intubation overcome by the laryngeal mask airway. 
A case of difficult intubation is described in which the problem was overcome by use of the laryngeal mask airway (LMA). The patient had difficulty in mouth opening due to severe burn scar contracture around the mouth and limited access prevented tracheal intubation. The use of LMA is shown to have obviated the need for tracheal intubation in the case of a patient whose injuries would have made this technique difficult.
PMCID: PMC3053760  PMID: 8198766
12.  Interaction of Nutrition and Infection: Macrophage Activity in Vitamin B12-Deficient Rats Infected with Trypanosoma Lewisi 
Macrophage activity was studied in rats infected with Trypanosoma lewisi in three protocol groups: one group was fed complete diet, a second group was given a vitamin B12-deficient diet, and a third group was fed a pair-fed control (calorically restricted) diet. Throughout the observational period, in animals fed complete and pairfed diets, marked increases in acid phosphatase levels in peritoneal macrophages were directly related to the degree of parasitemia. Acid phosphatase levels in rats deprived of vitamin B12 were approximately one third that of animals with an adequate supply of the vitamin. Irrespective of the diets, the infection with T lewisi also elicited increased macrophage phagocytosis of polystyrene latex particles and macrophage spreading. Both of these activities occurred at a much slower rate in the vitamin B12-deficient animals.
PMCID: PMC2625497  PMID: 3295263
13.  Interaction of Nutrition and Infection: Effect of Vitamin B12 Deficiency on Resistance to Trypanosoma Lewisi 
A metabolic imbalance technique was employed to study vitamin B12 deficiency in rats infected with Trypanosoma lewisi. Throughout the observational period, animals on the deficient diet had lowered serum vitamin B12 levels compared with complete and pair-fed animals. The decline in the level of the vitamin, ten days after the initiation of the experiment, continued progressively until the termination of the study. Body weight gains and food consumption in rats on complete, vitamin B12-deficient, or pair-fed diets and inoculated with T lewisi showed significant increase over inoculated controls. The rates of body weight and food consumption in vitamin B12-deficient animals were significantly less than that of the adequately fed animals.
The indices of lowered resistance to infection in the vitamin B12-deficient rats were manifoid. Deficient rats suffered earlier and higher parasitemia followed by persistent infection. The delay in the synthesis of the reproductive inhibiting antibody (ablastin) resulted in prolonged variability in the length of the trypomastigotes. Severe depression in the primary and secondary antibody responses (IgG and IgM) to in vivo immunization of sheep erythrocytes was also observed in the deficient animals. In comparison, the level of IgG antibody decreased approximately one fifth the control values.
PMCID: PMC2561845  PMID: 3889354
14.  Trypanosoma Lewisi: In Vitro Oxygen Uptake by Parasites Grown in Albino and Black Rats 
Oxygen consumption of Trypanosoma lewisi grown in albino and black rats was measured by the direct method of Warburg. Respiration rates in buffered Ringer's solution, with and without glucose and in normal serum from the respective hosts, were determined for T lewisi grown in albino and black rats. Significantly higher respiratory rates were obtained for trypanosomes grown in albino hosts: 31 percent higher in buffered Ringer's solution with glucose and 26 percent higher in homologous serum.
In this study, in which the development of the parasitemia was observed for 27 days, T lewisi populations were higher in albino rats than in black rats.
PMCID: PMC2561802  PMID: 6392572
15.  hTID-1 defines a novel regulator of c-Met Receptor signaling in renal cell carcinomas 
Oncogene  2011;30(19):2252-2263.
The c-Met receptor tyrosine kinase (MetR) is frequently overexpressed and constitutively phosphorylated in a number of human malignancies. Activation of the receptor by its ligand, hepatocyte growth factor (HGF), leads to increased cell proliferation, motility, survival and disruption of adherens junctions. In this study, we show that hTid-1, a DNAJ/Hsp40 chaperone, represents a novel modulator of the MetR signaling pathway. hTid-1 is a co-chaperone of the Hsp70 family of proteins, and has been shown to regulate a number of cellular signaling proteins including several involved in tumorigenic and apoptotic pathways. In this study we demonstrate that hTid-1 binds to unphosphorylated MetR and becomes dissociated from the receptor upon HGF stimulation. Overexpression of the short form of hTid-1 (hTid-1S) in 786-0 renal clear cell carcinomas (RCCs) enhances MetR kinase activity leading to an increase in HGF-mediated cell migration with no discernible effect on cell proliferation. By contrast, knockdown of hTid-1 markedly impairs both the onset and amplitude of MetR phosphorylation in response to HGF without altering receptor protein levels. hTid-1-depleted cells display defective migratory properties, coincident with inhibition of ERK/MAP kinase and STAT3 pathways. Taken together, our findings denote hTid-1S as an essential regulatory component of MetR signaling. We propose that the binding of hTid-1S to MetR may stabilize the receptor in a ligand-competent state and this stabilizing function may influence conformational changes that take place during the catalytic cycle that promote kinase activation. Given the prevalence of HGF/MetR pathway activation in human cancers, targeted inhibition of hTid-1 may be a useful therapeutic in the management of MetR-dependent malignancies.
PMCID: PMC3095899  PMID: 21242965
hTid-1; molecular chaperones; c-Met receptor tyrosine kinase; renal cell carcinoma; cell migration
16.  Trends in overweight and obesity over 22 years in a large adult population: the HUNT Study, Norway 
Clinical Obesity  2013;3(1-2):12-20.
Some reports indicate that the obesity epidemic may be slowing down or halting. We followed body mass index (BMI) and waist circumference (WC) in a large adult population in Norway (n = 90 000) from 1984–1986 (HUNT1) through 1995–1997 (HUNT2) to 2006–2008 (HUNT3) to study whether this is occurring in Norway. Height and weight were measured with standardized and identical methods in all three surveys; WC was also measured in HUNT2 and HUNT3. In the three surveys, mean BMI increased from 25.3 to 26.5 and 27.5 kg m−2 in men and from 25.1 to 26.2 and 26.9 kg m−2 in women. Increase in prevalence of obesity (BMI ≥ 30 kg m−2) was greater in men (from 7.7 to 14.4 and 22.1%) compared with women (from 13.3 to 18.3 and 23.1%). In contrast, women had a greater increase in abdominal obesity (WC ≥ 102 cm for men and WC ≥ 88 cm for women). There was a continuous shift in the distribution curve of BMI and WC to the right, demonstrating that the increase in body weight was occurring in all weight groups, but the increase of obesity was greatest in the youngest age groups. Our data showed no signs of a halt in the increase of obesity in this representative Norwegian population.
PMCID: PMC3734732  PMID: 23935708
Gender differences; Norway; obesity; overweight
17.  Hepatic cells' mitotic and peritoneal macrophage phagocytic activities during Trypanosoma musculi infection in zinc-deficient mice. 
The effects of zinc deficiency on hepatic cell mitotic and peritoneal macrophage phagocytic activities were examined in mice infected with Trypanosoma musculi or immunized with parasitic products. On a full-complement or pair-fed diet, infected and homogenate-inoculated mice showed mitotic activity gains of 7.9% to 80.3% and 6.5% to 99.0%, respectively. Infected and homogenate-inoculated mice on a zinc-deficient diet showed 21.8% to 95.7% and 17.2% to 65.2%, respectively, more dividing liver cells compared with controls. In comparison to controls, macrophages isolated from infected and homogenate-immunized mice on full-complement or pair-fed diets had phagocytized 13.4% to 31.4% more latex particles from day 50 to 80. In the zinc-deficient group, macrophages isolated from infected mice had significant numbers of phagocytized latex particles (1.8% to 38.5%) from day 20 to day 80 compared with controls. The homogenate-immunized mice also had increased numbers (18.6 to 30.8%) of phagocytized latex particles.
PMCID: PMC2608211  PMID: 9145631
18.  Growth of trypanosomes in vivo, host body weight gains, and food consumption in zinc-deficient mice. 
This study examined the effect of zinc deficiency on food consumption and the growth of mice infected with Trypanosoma musculi or immunized with parasite products. In addition, the effects of zinc deficiency on the growth and development of parasites in vivo was studied. Infected mice consumed more food than noninfected mice, and the level of food consumption in the zinc-deficient mice was much less and showed general decline during the observation period. Also, infected mice on both full-complement and zinc-deficient diets gained more body weight than control mice. Throughout the observational period, trypanosomes from zinc-deficient mice showed considerably higher variability in size as determined by coefficient of variation. In both dietary groups, the average length of trypanosomes was not significantly different.
PMCID: PMC2608193  PMID: 9002416
19.  Isolation and analysis of nephritic-producing immune complexes in Plasmodium berghei-infected mice. 
A nephritic condition was developed by infecting Swiss Webster albino mice with the malarial parasite Plasmodium berghei NK 65. These animals were tested for urinary protein and the presence of circulating immune complexes using reagent strips and a polyethylene glycol (PEG) precipitation assay. The circulating immune complexes were isolated from the sera using both affinity chromatography and PEG precipitation and from the kidney by acid elution. The isolated complexes were dissociated into their individual components and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The components of the complexes were transferred to nitrocellulose sheets and probed for the presence of malarial antigens using a rabbit anti-P berghei antisera. The overall humoral response to the malarial parasite was evaluated using a radial immunodiffusion assay. The present study confirmed that the malarial-infected animals not only developed the nephritic condition (as evident by the high levels of proteinuria) but also, as indicated by the PEG assay, have the presence of high levels of circulating immune complexes in their serum. The apparent absence in the SDS gels of any abnormal protein bands followed by the inability of the Western blot to reveal any malarial antigens provides some of the strongest evidence to date that these malarial proteins are not directly involved in the circulating immune complexes believed to be responsible for producing this nephritic condition.
PMCID: PMC2607896  PMID: 9583966
20.  Changes in immunoglobulin levels in zinc-deficient mice infected with Trypanosoma musculi. 
A metabolic imbalance technique was used to study the effects of zinc deficiency on immunoglobulin levels in mice infected with Trypanosoma musculi or immunized with parasite products. Zinc-deficient mice developed higher numbers of parasitemia earlier and exhibited prolonged infection. Irrespective of the diet, higher IgG1, IgG2b, and IgM levels, lower IgG2a and IgA levels, and uniform IgG3 levels were exhibited primarily by mice infected with T musculi and to a lesser extent by mice immunized with parasite products. Zinc-deficient mice showed smaller increases in IgG1 and IgM, but larger gains in IgG2b compared with mice on full-complement and pair-fed diets. However, IgG2a decreased significantly in zinc-deficient mice.
PMCID: PMC2607724  PMID: 7932840
21.  Activation of Escherichia coli heat-labile enterotoxins by native and recombinant adenosine diphosphate-ribosylation factors, 20-kD guanine nucleotide-binding proteins. 
Journal of Clinical Investigation  1991;87(5):1780-1786.
Escherichia coli heat-labile enterotoxins (LT) are responsible in part for "traveler's diarrhea" and related diarrheal illnesses. The family of LTs comprises two serogroups termed LT-I and LT-II; each serogroup includes two or more antigenic variants. The effects of LTs result from ADP ribosylation of Gs alpha, a stimulatory component of adenylyl cyclase; the mechanism of action is identical to that of cholera toxin (CT). The ADP-ribosyltransferase activity of CT is enhanced by 20-kD guanine nucleotide-binding proteins, known as ADP-ribosylation factors or ARFs. These proteins directly activate the CTA1 catalytic unit and stimulate its ADP ribosylation of Gs alpha, other proteins, and simple guanidino compounds (e.g., agmatine). Because of the similarities between CT and LTs, we investigated the effects of purified bovine brain ARF and a recombinant form of bovine ARF synthesized in Escherichia coli on LT activity. ARF enhanced the LT-I-, LT-IIa-, and LT-IIb-catalyzed ADP ribosylation of agmatine, as well as the auto-ADP ribosylation of the toxin catalytic unit. Stimulation of ADP-ribosylagmatine formation by LTs and CT in the presence of ARF was GTP dependent and enhanced by sodium dodecyl sulfate. With agmatine as substrate, LT-IIa and LT-IIb exhibited less than 1% the activity of CT and LT-Ih. CT and LTs catalyzed ADP-ribosyl-Gs alpha formation in a reaction dependent on ARF, GTP, and dimyristoyl phosphatidylcholine/cholate. With Gs alpha as substrate, the ADP-ribosyltransferase activities of the toxins were similar, although CT and LT-Ih appeared to be slightly more active than LT-IIa and LT-IIb. Thus, LT-IIa and LT-IIb appear to differ somewhat from CT and LT-Ih in substrate specificity. Responsiveness to stimulation by ARF, GTP, and phospholipid/detergent as well as the specificity of ADP-ribosyltransferase activity are functions of LTs from serogroups LT-I and LT-II that are shared with CT.
PMCID: PMC295291  PMID: 1902492
22.  Comparative histochemical studies of rats infected with a pathogenic and nonpathogenic trypanosome. 
Histochemical variations in tissues from rats inoculated with Trypanosoma lewisi and Trypanosoma rhodesiense were investigated. During peak parasitemia, the liver of rats inoculated with T lewisi showed increased glycogen distribution. However, glycogen depletion was noted in the liver and spleen of animals inoculated with living cells of T rhodesiense. Depletion was very apparent from day 4 to day 10. Throughout the period of observation, only a small amount of lipid infiltration occurred in tissues from animals inoculated with both organisms. Protein tests revealed a normal distribution of protein in tissues. Sections of the liver from rats inoculated with T lewisi showed strong alkaline phosphatase activity on days 7, 10, and 13. Alkaline phosphatase activity for T rhodesiense-infected animals was positive for days 4, 7, and 10. Strong positive reactions for acid phosphatase were observed on days 10 and 13 for some tissues (liver, spleen, and kidney) from rats inoculated with T lewisi. On days 4, 7, and 10, intense staining reactions also were observed for livers and spleens of animals inoculated with T rhodesiense. Regardless of tissues observed, histochemical variations were not observed in animals inoculated with the derivatives (ie, metabolic products and homogenates) of T lewisi and T rhodesiense.
PMCID: PMC2627071  PMID: 1875425
23.  Quantification of macular ischaemia in sickle cell retinopathy. 
Macular ischaemia has a central role in the pathophysiology and prognosis of retinal macular disease. We attempted to quantitate two of its major components as follows: vascular nonperfusion, by measuring the foveal avascular zone (FAZ), using fluorescein angiography; and functional damage, using automated perimetry of the central 30 degrees. Sickle cell disease was chosen for study because it was considered a prototype for a purely ischaemic retinopathy without an exudative component. We found that the FAZ measurement was reproducible and that the patients with maculopathy had statistically larger FAZs than the normal controls (p = 0.016, Wilcoxon rank sum test). In addition, scotomas measured by visual field perimetry were significantly larger in the sickle cell patients with maculopathy than in those without maculopathy. Our results showed that angiography and perimetry of the central 30 degrees were more sensitive tests for the detection of ischaemic macular disease than visual acuity and that macular ischaemia could be quantified by their use.
PMCID: PMC1041222  PMID: 3651368

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