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1.  Arthritis and Benznidazole: More Closely Related than We Thought 
Chagas disease is a parasitic infection that leads to a significant public health problem in countries where the disease is endemic and where it is nonendemic. Benznidazole is the most commonly used drug for the etiological treatment of Chagas disease. Patients treated with benznidazole suffer frequent adverse drug reactions. Although arthralgia is common, arthritis has been reported as a very rare side effect. The objective of this study was to describe arthritis in a cohort of Trypanosoma cruzi-infected patients treated with benznidazole.
PMCID: PMC4291430  PMID: 25385100
2.  Medipix in space on-board the ISS 
Journal of Radiation Research  2014;55(Suppl 1):i62-i63.
On 16 October 2012, five active radiation detectors (referred to by NASA as Radiation Environment Monitors, or REMs) employing the Timepix version of the technology developed by the CERN-based Medipix2 Collaboration were deployed on-board the International Space Station (ISS) using simple USB interfaces to the existing ISS laptops for power, control and readout [ 1– 3]. These devices successfully demonstrated the capabilities of this technology by providing reliable dose and dose-equivalent information based on a track-by-track analysis. Figure 1 shows a sample comparison of the output from all five devices with respect to the on-board tissue equivalent proportional counter (TEPC) for both absorbed dose (top) and dose-equivalent (bottom) as defined in NCRP 142. The lower graph in each set is the TEPC. Several issues were identified and solutions to adjust for them have been included in the analysis. These include items such as the need to identify nuclear interactions in the silicon sensor layer, and to separate penetrating from stopping tracks. The wide effective range in fluence and particle type of this technology was also verified through the highest rates seen during the South Atlantic Anomaly passes and the heavy ions nominally seen in the Galactic Cosmic Rays. Corrections for detector response saturation effects were also successfully implemented as verified by reference to ground-based accelerator data taken at the Heavy-Ion Medical Accelerator Center (HIMAC) facility at the National Institute for Radiological Sciences in Japan, and at the NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory in New York. Flight hardware has been produced that will be flown on the first launch of the new Orion spacecraft, and flight hardware development is ongoing to accommodate the next generation of this technology as a baseline for radiation monitoring and dosimetry on future operational manned missions. Fig 1.Five ISS REM units compared with ISS IVTEPC in absorbed dose (a) and dose-equivalent (b).
PMCID: PMC3941488
3.  Temozolomide resistance in glioblastoma cells occurs partly through epidermal growth factor receptor-mediated induction of connexin 43 
Cell Death & Disease  2014;5(3):e1145-.
Glioblastoma Multiforme (GBM) is an aggressive adult primary brain tumor with poor prognosis. GBM patients develop resistance to the frontline chemotherapy, temozolomide (TMZ). As the connexins (Cx) have been shown to have a complex role in GBM, we investigated the role of Cx43 in TMZ resistance. Cx43 was increased in the TMZ-resistant low passage and cell lines. This correlated with the data in The Cancer Genome Atlas. Cx43 knockdown, reporter gene assays, chromatin immunoprecipitation assay, real-time PCR and western blots verified a role for Cx43 in TMZ resistance. This occurred by TMZ-resistant GBM cells being able to activate epidermal growth factor receptor (EGFR). In turn, EGFR activated the JNK-ERK1/2-AP-1 axis to induce Cx43. The increased Cx43 was functional as indicated by gap junctional intercellular communication among the resistant GBM cells. Cell therapy could be a potential method to deliver drugs, such as anti-EGF to tumor cells. Similar strategies could be used to reverse the expression of Cx43 to sensitize GBM cells to TMZ. The studies showed the potential for targeting EGF in immune therapy. These agents can be used in conjunction with stem cell therapy to treat GBM.
PMCID: PMC3973225  PMID: 24675463
connexin 43; glioblastoma; resistance; temozolomide EGF receptor; stem cell; immune therapy
4.  Vertical transmission of Citrobacter freundii 
PMCID: PMC1721695  PMID: 15102740
5.  Prophage-Like Elements in Bifidobacteria: Insights from Genomics, Transcription, Integration, Distribution, and Phylogenetic Analysis 
Applied and Environmental Microbiology  2005;71(12):8692-8705.
So far, there is only fragmentary and unconfirmed information on bacteriophages infecting the genus Bifidobacterium. In this report we analyzed three prophage-like elements that are present in the genomes of Bifidobacterium breve UCC 2003, Bifidobacterium longum NCC 2705, and Bifidobacterium longum DJO10A, designated Bbr-1, Bl-1, and Blj-1, respectively. These prophagelike elements exhibit homology with genes of double-stranded DNA bacteriophages spanning a broad phylogenetic range of host bacteria and are surprisingly closely related to bacteriophages infecting low-G+C bacteria. All three prophage-like elements are integrated in a tRNAMet gene, which appears to be reconstructed following phage integration. Analysis of the distribution of this integration site in many bifidobacterial species revealed that the attB sites are well conserved. The Blj-1 prophage is 36.9 kb long and was induced when a B. longum DJO10A culture was exposed to mitomycin C or hydrogen peroxide. The Bbr-1 prophage-like element appears to consist of a noninducible 28.5-kb chimeric DNA fragment composed of a composite mobile element inserted into prophage-like sequences, which do not appear to be widely distributed among B. breve strains. Northern blot analysis of the Bbr-1 prophage-like element showed that large parts of its genome are transcriptionally silent. Interestingly, a gene predicted to encode an extracellular beta-glucosidase carried within the Bbr-1 prophage-like element was shown to be transcribed.
PMCID: PMC1317369  PMID: 16332864
7.  Association between obesity and asthma in 4-11 year old children in the UK 
Thorax  2001;56(2):133-137.
BACKGROUND—There is evidence of a positive association between asthma and obesity in adults and in children. We investigated, in a large sample of English and Scottish primary school children, whether there is a consistent association between fatness and asthma symptoms in Britain.
METHODS—A cross sectional analysis was made of 18 218 children aged 4-11 years who participated in the 1993 or 1994 surveys of the National Study of Health and Growth (NSHG). Children belonged either to English or Scottish representative samples, or an English inner city sample. Asthma attacks in the previous year, occasional wheeze, or persistent wheeze were the symptoms used in the analysis. Body mass index (BMI) and the sum of triceps and subscapular skinfolds converted to standard deviation scores (SDS) were used to assess levels of fatness.
RESULTS—A total of 14 908 children (81.8%) were included in the analysis. In the multiple logistic analysis BMI and asthma (asthma attacks or wheeze) were associated in the representative sample (OR for the comparison of the 10th and 90th centiles of BMI 1.28,95% CI 1.11 to 1.48), but sum of skinfolds was unrelated to asthma symptoms in most analyses. The association between asthma and BMI was stronger in girls than in boys in the inner city sample, but less convincingly in the representative sample.
CONCLUSIONS—Levels of obesity are associated with asthma symptoms regardless of ethnicity. The association is more consistent for BMI than for sum of skinfolds, partly because obese children are more advanced in their maturation than other children. There is some evidence that, as in adults, the association is stronger in girls than in boys, but only in the multiethnic inner city sample.

PMCID: PMC1745999  PMID: 11209102
8.  Age and Helicobacter pylori decrease gastric mucosal surface hydrophobicity independently 
Gut  1998;43(4):465-469.
Background—Gastric mucosal surface hydrophobicity (GMSH) is an essential component of the mucosal defence system that is decreased by Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs). Gastric ulcers occur predominantly in elderly subjects, and may thus reflect diminished mucosal resistance. 
Aims—To investigate whether aging decreases GMSH. 
Patients—One hundred and twenty patients without peptic ulcer disease were divided into three age groups: I (41 years or below); II (41-64 years); and III (65 years or above). 
Methods—Biopsy specimens were taken from the antrum, corpus, and cardia for histology (Sydney system), urease testing for H pylori, and for contact angle measurement of GMSH with a goniometer. The presence of specific H pylori antibodies was checked by immunoblotting. 
Results—Fifty two patients (43%) were infected, and 68 were uninfected with H pylori. GMSH at all biopsy sites was lower in H pylori infected subjects (p=0.0001), but also decreased with age independently of infection status (p=0.0001). The most notable decrease in GMSH occurred between age groups I and II in those with, and between age groups II and III in those without, H pylori infection. GMSH was greater in antral than in corpus mucosa in both infected (p=0.0001) and uninfected patients (p=0.0003). 
Conclusions—A physiological decrease in GMSH with aging may contribute to the risk of ulcer development in the elderly, and may act synergistically with H pylori and/or NSAIDs on gastric mucosal defence. 

Keywords: gastric mucosal defence; surface hydrophobicity; aging; Helicobacter pylori
PMCID: PMC1727283  PMID: 9824570
9.  Intestinal metaplasia at the gastro-oesophageal junction: Helicobacter pylori gastritis or gastro-oesophageal reflux disease? 
Gut  1998;43(1):17-21.
Background—Intestinal metaplasia, whether in the cardia or the distal oesophagus, has been uniformly defined as specialised columnar epithelium, suggesting a relation with Barrett's oesophagus. It is, however, not clear whether the risk factors associated with intestinal metaplasia are identical at both sites. 
Aims—To investigate biopsy specimens obtained below the squamocolumnar junction (SCJ) in relation to endoscopic aspect, gastric histology, and clinical presentation. 
Patients and methods—In 423 patients investigated the endoscopic aspect of the SCJ was classified as unremarkable (group I, n=315) or suggestive of Barrett's oesophagus (group II, n=108). Standardised biopsy specimens from the antrum, corpus, and directly below the SCJ were investigated. 
Results—Intestinal metaplasia was detected at the SCJ in 13.4% of group I patients, where it was significantly associated with gastric intestinal metaplasia (odds ratio (OR) 6.96; confidence interval (CI) 2.48 to 19.54) and H pylori (OR 7.85; CI 2.82 to 21.85), and in 34.3% of group II patients where it was significantly associated with reflux symptoms (OR 19.98; CI 6.12 to 65.19), erosive oesophagitis (OR 12.16; CI 3.86 to 38.24), and male sex (OR 6.25, CI 2.16 to 18.14), but not with H pylori or gastric intestinal metaplasia. 
Conclusion—This study suggests that the pathogenesis of intestinal metaplasia at the SCJ is not uniform: at an endoscopically unremarkable SCJ it is a sequela of H pylori gastritis, but coexisting with endoscopic features of Barrett's oesophagus it is associated with male sex and gastro-oesophageal reflux disease. 

Keywords: intestinal metaplasia; Barrett's oesophagus; gastric cardia; Helicobacter pylori gastritis; gastro-oesophageal reflux disease
PMCID: PMC1727162  PMID: 9771400
10.  Hepatitis B virus precore mutation and fulminant hepatitis in the United States. A polymerase chain reaction-based assay for the detection of specific mutation. 
Journal of Clinical Investigation  1994;93(2):550-555.
Hepatitis B virus (HBV) variants with precore mutation(s) resulting in the absence of HBeAg production have been associated with the occurrence of fulminant hepatitis in Japan, Israel, and southern Europe, where the prevalence of this HBV strain appears common. In areas such as United States, where HBV infection is not endemic, the role of this mutant virus in fulminant hepatitis is unknown. We developed an amplification refractory mutation detection system to detect specifically the presence of the G to A mutation at nucleotide position 1898, which is the most frequently observed mutation resulting in a precore stop codon. In addition, this method provided a quantitative measurement of the relative ratio of one strain to the other. Using this system, we tested HBV strains for the presence of the stop codon mutation in sera from 40 cases of fulminant hepatitis B occurring in the United States. Serum HBV DNAs from 28 patients were analyzed successfully. A mixture of wild-type and mutant strains in various ratios were observed in 15 patients, wild type exclusively in 11, and mutant exclusively in 2. Four of these patients had undergone liver transplantation for HBV-associated cirrhosis and developed fulminant HBV-associated hepatitis after transplantation. Pre- and posttransplant serum samples from one patient were analyzed: a mixture of wild-type and mutant HBV strains was detected in both samples. Our study demonstrated that both wild-type and mutant HBV strains are associated with fulminant hepatitis, and that in some patients in the United States, factors other than precore mutations contribute to the development of fulminant hepatitis.
PMCID: PMC293877  PMID: 8113393
11.  Heterogeneity of familial porphyria cutanea tarda. 
Journal of Medical Genetics  1988;25(10):669-676.
The concentration of immunoreactive uroporphyrinogen decarboxylase has been measured in erythrocytes from 17 patients with porphyria cutanea tarda (PCT) from 10 families, from 74 of their relatives, and from 47 control subjects. The 10 families were divided into two groups according to their erythrocyte enzyme concentrations. Group A contained four families in which at least two subjects had overt PCT. All members of these families, including seven patients with overt PCT, had normal erythrocyte uroporphyrinogen decarboxylase concentrations and activities. Apart from their family history, patients in group A were clinically and biochemically indistinguishable from cases of type I (sporadic) PCT. Group B contained six families with the only previously described form of familial PCT (type II PCT) in which decreased erythrocyte uroporphyrinogen decarboxylase segregates as an autosomal dominant trait. These findings show that familial PCT is heterogeneous and suggest that inheritance contributes to the pathogenesis of at least some cases of type I PCT.
PMCID: PMC1051560  PMID: 3225822
12.  Detection of subunits of pertussis toxin in Tn5-induced Bordetella mutants deficient in toxin biological activity. 
Infection and Immunity  1987;55(5):1309-1313.
Monoclonal antibodies with specificity for pertussis toxin subunits S1, S2, and S4 were used in Western blots to show that the subunits were not secreted into culture medium from Tn5 insertion mutants. The mutants are deficient in toxin biological activities due to an insertion in the S3 subunit structural gene. The Western blots demonstrated that each of the respective subunits was exported in a wild-type strain. Anti-S1 and anti-S2 monoclonal antibodies were capable of detecting subunits in solubilized whole-cell material from a wild-type strain and from the Tn5 mutants lacking only in biologically active toxin (Tox-). Another Tn5 insertion mutant, lacking all known B. pertussis virulence factors (Vir-), did not produce any of the subunits either in whole cellular extracts or in culture supernatants. The data demonstrate that Tn5 Tox- insertion mutants, though defective in toxin activity, synthesize some toxin subunits. The presence of the S3 subunit is most likely a necessity for transport of the toxin from cells. Alternatively, a nonstructural gene coding for a protein involved in transport of the toxin across the membrane may be affected by the Tn5 mutation.
PMCID: PMC260506  PMID: 2883124
13.  Anaphylaxis or so-called encephalopathy in mice sensitized to an antigen with the aid of pertussigen (pertussis toxin). 
Infection and Immunity  1987;55(4):1004-1008.
Sensitization of mice with 1 mg of bovine serum albumin (BSA) or chicken egg albumin (EA) given intraperitoneally and 300 to 400 ng of pertussigen (pertussis toxin [Ptx]) given intravenously (i.v.) induced a high degree of anaphylactic sensitivity when the mice were challenged i.v. with 1 mg of antigen 14 days later. Regardless of H-2 haplotype, all of the strains tested (CFW, BALB/cJ, DBA/2J, and C3H.SW/SnJ) were susceptible to anaphylaxis. Sensitization of mice by a multiple-dose procedure that has been reported to induce fatal encephalopathy in mice (L. Steinman, A. Weiss, N. Adelman, M. Lim, R. Zuniga, J. Oehlert, E. Hewlett, and S. Falkow, Proc. Natl. Acad. Sci. USA 82, 8733-8736, 1982) (1 mg of BSA on day -1, 100 to 400 ng of Ptx on day zero 1 mg of BSA on day +1, 100 to 400 ng of Ptx on day +2, and 1 mg of BSA on day +6) induced shock in BALB/cJ, DBA/2J, and C3H.SW/SnJ mice, but not in CFW mice. When EA was used instead of BSA, CFW, BALB/cJ, and C3H.SW/SnJ mice did not develop fatal shock, whereas DBA/2J mice did. When dose 3 of antigen (BSA or EA) was postponed to day +21, all mouse strains sensitized by the multiple-dose procedure were found to be susceptible to shock. The fatal shock induced by this procedure, as well as that induced by giving a single sensitizing dose of antigen and Ptx, could be prevented by one to three 1-ml doses of saline given i.v. at the time signs of severe shock appeared. Although only one dose of saline was often sufficient to save the mice, two or three doses were usually needed. Microscopic changes were not found in midsagittal sections of the brains of mice sensitized by either procedure. This was true of mice that died from shock or were saved from shock by injections of saline. From these results, we concluded that the proposed model for encephalopathy induced in mice by Ptx and BSA demonstrates only the well-known anaphylactogenic effect of Ptx or pertussis vaccine. Since there are many other more sensitive methods to detect Ptx, induction of anaphylaxis is not of much value for detection or quantitation of Ptx in pertussis vaccine.
PMCID: PMC260453  PMID: 3557617
14.  Effect of pertussigen on inflammation caused by Freund adjuvant. 
Infection and Immunity  1984;44(3):637-641.
Pertussigen, one of the toxins from Bordetella pertussis, greatly increased the inflammatory response produced by complete Freund adjuvant in the footpads of mice. This effect was not produced by pertussigen when the emulsion was made with saline and incomplete Freund adjuvant, but if an antigen was included in incomplete Freund adjuvant, the strong potentiating effect was again demonstrated. As little as 100 ng of pertussigen given intravenously was effective, but 400 ng proved better, and this latter dose was used routinely. The most striking action occurred when pertussigen was injected on the same day or 3 days after complete Freund adjuvant, but an effect was demonstrated when given from 3 days before to 6 days after complete Freund adjuvant. The action of pertussigen was not apparent until about 6 to 8 days after complete Freund adjuvant. The footpad swelling reached its maximum by day 14 and remained undiminished until day 29. Forty days later, a significant effect was still present. Histologically, the cellular infiltrate in the feet of mice injected with complete Freund adjuvant was more intense in animal treated with pertussigen. Nude BALB/c mice receiving an emulsion of complete Freund adjuvant in the footpads did not respond with an increased inflammation after receiving pertussigen, suggesting the possible involvement of T cells in this phenomenon. The intense and prolonged inflammatory response produced in pertussigen-treated mice by Freund adjuvant containing antigenic substances may serve as a useful model to study chronic inflammation.
PMCID: PMC263653  PMID: 6539301
15.  Biological activities of crystalline pertussigen from Bordetella pertussis. 
Infection and Immunity  1981;33(3):820-826.
We studied various biological activities of crystalline pertussigen and found that in mice as little as 0.5 ng of pertussigen induced hypersensitivity to histamine, 8 to 40 ng induced leukocytosis, 2 ng increased production of insulin, 0.1 ng increased production of immunoglobulin E and immunoglobulin G1 antibodies to hen egg albumin, 9.5 ng increased susceptibility to anaphylactic shock, and 0.5 ng increased the vascular permeability of striated muscle. We also found that in Lewis rats 20 ng of pertussigen promoted the induction of hyperacute experimental allergic encephalomyelitis. Pertussigen given intraperitoneally was toxic to mice at a dose of 546 ng. Treatment of pertussigen with glutaraldehyde eliminated this toxicity. Mice immunized with 1,700 ng of detoxified pertussigen were protected against intracerebral challenge with 3 x 10(4) viable Bordetella pertussis cells. When as little as 0.5 ng of pertussigen was given intravenously to mice, the increased susceptibility of the animals to histamine could still be detected 84 days later. The biological properties of crystalline pertussigen indicate its similarity to leukocytosis-promoting factor, Islet-activating protein, late-appearing toxic factor, and mouse-protective antigen of B. pertussis.
PMCID: PMC350785  PMID: 6269999
16.  Mouse-protecting and histamine-sensitizing activities of pertussigen and fimbrial hemagglutinin from Bordetella pertussis. 
Infection and Immunity  1981;32(1):243-250.
We compared the protective activities of fimbrial hemagglutinin (FHA) and pertussigen and their respective antibodies in mice infected intracerebrally with Bordetella pertussis. We found that mice were protected by a 1.7-microgram/mouse dose of pertussigen which was free of detectable FHA and was detoxified by treatment with glutaraldehyde. A pertussigen preparation made from cells grown in shake cultures that did not contain demonstrable FHA protected mice at a dose of 1.4 microgram/mouse. FHA at a dose of 10 microgram/mouse protected mice from intracerebral infection, but it also sensitized mice to histamine at a dose of 2 micrograms/mouse, which indicated that it was contaminated with pertussigen. When FHA was obtained free of demonstrable pertussigen, it failed to sensitize mice to histamine at a dose of 30 micrograms/mouse and to protect mice from infection at a dose of 12 micrograms/mouse (largest doses tested). Passive protection tests with antisera known to contain antibodies to pertussigen protected mice from intracerebral infection, whereas sera lacking anti-pertussigen antibodies but containing high concentrations of anti-FHA antibodies did not protect mice. The most important antigen for the immunization of mice against intracerebral infection with B. pertussis appears to be pertussigen.
PMCID: PMC350613  PMID: 6260681
17.  Crystallization of pertussigen from Bordetella pertussis. 
Infection and Immunity  1981;31(1):495-499.
A method is described for crystallizing pertussigen from Bordetella pertussis. The crystalline material induced histamine hypersensitivity in mice at a dose of 0.5 ng of protein and leukocytosis at a dose of 100 ng and was toxic at a dose of 429 microgram. The histamine-sensitizing activity and the toxicity were as high as ever reported.
PMCID: PMC351809  PMID: 6260667
18.  Evidence for the synthesis and release of strongly immunosuppressive, noncytotoxic substances by Streptococcus intermedius. 
Journal of Clinical Investigation  1979;64(4):871-883.
Products secreted by Streptococcus intermedius were studied for their effects on the immune response. Three different preparations of crude extracellular products from S. intermedius (CEP-Si) were found to have powerful suppressor activity in vitro as shown by inhibition of human lymphocyte proliferation (uptake of [3H]thymidine) and protein synthesis in response to a wide variety of stimulants, including mitogens and antigens, and suppression of plaque formation by human cells in response to sheep erythrocytes. CEP-Si was noncytotoxic, because cells incubated with high concentrations of CEP-Si and subsequently washed were viable and recovered their ability to respond to mitogens, and because leukocyte migration was not inhibited by CEP-Si, nor was the release of leukocyte migration inhibitory factor from sensitized lymphocytes. The possibility of antigen or mitogen competition was excluded. The effects of CEP-Si in vitro were time dependent and did not require the presence of monocytes. Cells pretreated with CEP-Si and then washed suppressed plaque formation by fresh autologous cells in highly stimulated cultures. CEP-Si injected into C57BL/6 mice also strongly suppressed their immune response to sheep erythrocytes, and the in vivo suppression was correlated with the effects of CEP-Si in vitro.
PMCID: PMC372195  PMID: 383749
19.  Fimbrial hemagglutinin in stationary and shake cultures of Bordetella pertussis. 
Infection and Immunity  1979;25(2):764-767.
Bordetella pertussis produced hemagglutinin in stationary cultures; in cultures kept under constant shaking, hemagglutinin was found only during the first 48 h of incubation but not after 3 to 5 days. The type of medium had a pronounced effect on production of hemagglutinin. Strain differences in ability to produce hemagglutinin were also detected.
PMCID: PMC414509  PMID: 39897
20.  Purification and crystallization of fimbrial hemagglutinin from Bordetella pertussis. 
Infection and Immunity  1979;25(1):460-462.
A procedure to purify and crystallize fimbrial hemagglutinin from Bordetella pertussis is described. Redissolved crystals had the same specific activity as the original, purified solution of fimbrial hemagglutinin. About 97% of the weight of washed crystals was accounted for by amino acids.
PMCID: PMC414472  PMID: 39033
21.  Comparison of the histamine hypersensitivity and the Limulus amoebocyte lysate tests for endotoxin activity. 
Infection and Immunity  1978;22(1):292-294.
The histamine hypersensitivity test and the Limulus amoebocyte lysate test were compared for their effectiveness to quantitate endotoxin activity. The two tests compared favorably in all the trials, except with a sample of endotoxin from Brucella abortus that gave a positive Limulus amoebocyte lysate test at a concentration of 0.001 microgram, while failing to sensitize mice to histamine at a dose of 16 microgram per mouse. The Limulus amoebocyte lysate test was more sensitive than the histamine hypersensitivity test.
PMCID: PMC422150  PMID: 365749
22.  Vascular permeability changes in the central nervous system of rats with hyperacute experimental allergic encephalomyelitis induced with the aid of a substance from Bordetella pertussis. 
Infection and Immunity  1978;21(2):627-637.
Development of hyperacute experimental allergic encephalomyelitis in Lewis rats after intraperitoneal administration of a mixture of guinea pig spinal cord emulsion and pertussigen from Bordetella pertussis was accompanied by an increase in vascular permeability in the central nervous system. The increased permeability was most striking in the spinal cord and seemed to be associated with the ascending development of paralysis. Rats that had completely recovered from paralysis did not have any increased permeability in the central nervous system. Rats which developed paralysis after inoculation with either guinea pig spinal cord emulsion alone or with complete Freund adjuvant had only a small degree, if any, of increased permeability in the vascular system of the central nervous system.
PMCID: PMC422039  PMID: 211087
23.  New test for endotoxin potency based upon histamine sensitization in mice. 
Infection and Immunity  1977;18(2):352-355.
The results of a test of endotoxic potency based upon the development of histamine hypersensitivity in mice were compared with the results obtained by testing the same materials for pyrogenicity in rabbits and lethality for chicken embryos (CELD50). The results of the histamine hypersensitization test (HHT) correlated well with those of the other two tests. The sensitivity of the HHT was about the same as that of the CELD50 assay. The HHT may provide a relatively inexpensive, fast, and reliable assay method for endotoxin laboratories that do not have the facilities for the more elaborate assays.
PMCID: PMC421239  PMID: 200560
24.  Effect of Trichinella spiralis infection on passive cutaneous anaphylaxis in mice. 
Infection and Immunity  1977;15(1):84-90.
Infection of CFW mice with Trichinella spiralis induced a state of relative unresponsiveness to passive cutaneous anaphylaxis (PCA) induced with hen egg albumin and its corresponding antibodies. The unresponsiveness was to PCA produced either with immunoglobulin G1 (IgG1) or IgE type of antibodies, but was more pronounced with the latter. As few as 25 larvae given by stomach tube 20 days before induced this resistance, although 400 larvae induced a greater resistance. When 400 to 600 larvae were fed to mice, the refractoriness of these mice to PCA was noticed 15 days later. The sera of infected mice had the ability to inhibit mainly PCA induced by IgE. This inhibitory property of sera from infected mice was more pronounced 35 days after infection than 10 months later, when only weak inhibitory activity was detected. Purified rat IgE inhibited the PCA reactions induced in both mice and rats with mouse IgE-type antibody. At high concentrations, evidence of inhibition of the IgG1-induced PCA in mice was also obtained. We believe that the relative unresponsiveness of infected mice is due to an increase in production of IgE which competitively blocks the mast cell sites for other IgE molecules.
PMCID: PMC421332  PMID: 832910
25.  Increased histamine sensitivity in mice after administration of endotoxins. 
Infection and Immunity  1977;15(1):72-77.
CFW mice given submicrogram doses of endotoxins intravenously became highly susceptible to the lethal effects of 0.5 mg of histamine given intraperitoneally 1 to 2 h later. The histamine-sensitizing effects of the endotoxins were transitory and disappeared within 6 to 8 h. L-Epinephrine administered intravenously immediately after histamine challenge protected mice from death, but aterenol and isoproterenol were ineffective. The histamine-sensitizing effect in endotoxins was precipitated by anti-endotoxin sera with a concomitant eightfold loss in activity. However, dissociation of the immune complex in 0.25 M acetic acid fully restored histamine-sensitizing activity. The transitory nature of the hypersensitivity produced by endotoxin and the high heat resistance of the active material prove that it is different from the histamine-sensitizing effects of pertussigen.
PMCID: PMC421330  PMID: 188767

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