Superiority of intravesical immunotherapy with Corynebacterium parvum and Allium sativum in control of murine bladder cancer

Intravesical immunotherapy with bacillus Calmette-Guerin (BCG), Corynebacterium parvum (CP), keyhole limpet hemocyanin (KLH), and an extract of Allium sativum (AS) was studied in mice transplanted intravesically with mouse bladder tumor cells (MBT-2). Female C3H/He mice were anesthetized with sodium pentobarbital. Two X 10(5) MBT-2 cells were delivered into the bladder transurethrally using a small catheter, immediately after the posterior wall of the bladder had been electrocauterized. Bladder tumor became palpable or demonstrable microscopically in two weeks. Immunotherapy with BCG (2 X 10(6) CFU), CP (250 micrograms), KLH (50 micrograms), or AS (25 mg) was administered directly into the bladder via urethral catheter on day 1, day 6, or days 1 and 6. On day 21 the bladders and spleens were excised and weighed, and the bladders were examined macroscopically and microscopically for evidence of tumor. The results of the study showed that two treatments given one and six days after tumor transplant yielded the lowest tumor incidence and that CP and AS appeared equally effective or even slightly more effective than BCG in this model. These results suggest that clinical evaluation of CP or AS may be worthwhile.     

Allium sativum (garlic) inhibits lipid synthesis by Candida albicans.

The effect of aqueous garlic extract on the macromolecular synthesis of Candida albicans was studied. Protein and nucleic acid syntheses were inhibited to the same extent as growth, but lipid synthesis was completely arrested. Blockage of lipid synthesis is likely an important component of the anticandidal activity of garlic.     

Rate-responsive pacing with a pacemaker that detects respiratory rate (Biorate): clinical advantages and complications

The respiratory-dependent pacemaker (RDP3 or MB-1, Biorate, Biotec International, S.p.A., Bologna, Italy) detects the respiratory rate by measuring thoracic impedance using a subcutaneous auxiliary lead. The sensed respiratory rate is used to determine the pacing rate response. This pacemaker had been implanted in 9 patients with a mean age of 58 (range 42-69) years. During symptom-limited treadmill exercise, rate-modulated pacing resulted in a significant increase in pacing rate (mean +/- SD, 124 +/- 10 vs. 71 +/- 3 beats/min p less than 0.001) and exercise capacity (343 +/- 147 vs. 463 +/- 120 s, p less than 0.05) compared to those achieved with constant rate ventricular pacing. Brief treadmill exercise tests showed appropriate rate response to increased walking speed and gradient. However, rate response was modified by arm swinging-induced motion artefact which affected the measured "impedance." Complications observed on follow-up included perforation of the auxiliary lead in 2 patients and symptomatic myopotential interference in 3 patients with the RDP3 pacemaker, all of whom required unit replacement. It is concluded that although the respiratory-dependent pacemaker can confer physiological benefit in patients with bradycardia, myopotential interference (largely overcome by the new version MB-1 with programmable sensitivity) and the auxiliary lead can be problematic in some patients.     

Pre-operative parenteral nutrition in patients with oesophageal cancer: a prospective, randomised clinical trial

A prospective randomised clinical trial was conducted to examine the efficacy of 2 weeks pre-operative parenteral nutrition (PPN) for the prevention of complications following surgery for oesophageal cancer. Forty patients were studied, the diet of twenty being supplemented by pre-operative parenteral nutrition. There were no significant differences in age, nutritional status, tumour staging and histology between the two groups of patients. The use of PPN resulted in a significant gain in body weight and nitrogen but failed to produce an overall reduction in post-operative morbidity and mortality rates. However patients receiving PPN exhibited two types of changes in serum albumin levels. Those with a fall in serum albumin levels associated with an increase in body weight (indicating an expansion of extracellular volume) had a significantly higher incidence of post-operative pulmonary complications than the group exhibiting a rise in serum albumin levels concomitant with increase in body weight. These data suggested that two weeks PPN might not be adequate in certain patients and a longer period of PPN is required. They also show no clinical benefit from the routine use of pre-operative parenteral nutrition in all patients, but do not exclude benefit in selected groups.     

Associations between total serum IgE levels and the 6 potentially functional variants within the genes IL4, IL13, and IL4RA in German children: the German Multicenter Atopy Study

BACKGROUND: Increased total serum IgE levels are a common characteristic of atopic disorders. Six potentially functional variants, including C-590T in the IL4 gene, C-1055T and Arg130Gln in the IL13 gene, and Ile50Val, Ser478Pro, and Gln551Arg in the IL4RA gene, have been evaluated for their involvement in the control of total serum IgE levels and related atopic disorders, but the results of these studies have been inconsistent. OBJECTIVE: We examined whether these 6 variants had genotypic effects on total serum IgE levels in 823 unrelated German children from a large infant cohort, the German Multicenter Atopy Study. METHODS: Marginal effect models were used for the analyses of the repeated IgE measurements. Weighted linear regression and family-based tests of association were performed to minimize the possibility of spurious effects caused by selection bias or confounding on the basis of ethnic background. RESULTS: There are significant associations between increased total serum IgE levels and 2 variants in the IL13 gene (P <.005 and.0002 for Arg130Gln and C-1055T, respectively). These genetic effects are unlikely to be due to solely linkage disequilibrium between 2 polymorphisms, population stratification, or nonrepresentative samples. In addition, exposure to maternal smoking appears to modify the above effects on total serum IgE levels. However, no statistical association was observed between this quantitative phenotype and the other 4 variants examined. CONCLUSION: These findings suggest that variants C-1055T and Arg130Gln of the IL13 gene might play an important role on total serum IgE production in this study population.     

Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children

1. Download : Download high-res image (177KB)
2. Download : Download full-size image

     

Effects ofβ 2-adrenergic agonists on isolated guinea pig lung mast cells

The mast cell protective effects of the newly developed long-acting ₂-adrenergic salmeterol and formoterol were compared with those of conventionally used ₂-adrenergic, non-specific -agonists, disodium cromoglycate (DSCG) and theophylline. With the exception of DSCG, all the test agents inhibited ovalbumin-induced histamine release from enzymically dispersed guinea pig lung mast cells in a dose-dependent fashion. At the maximum concentration tested, theophylline produced the highest level of protection, inhibiting up to 90% of ovalbumin-induced histamine release whereas DSCG produced only 10% inhibition. The maximum inhibition produced by all the ₂-adrenergic tested was around 45%. While salmeterol was equipotent with salbutamol, formoterol was at least a 100-fold more potent. Hence the present study confirmed the previously reported mast cell stabilizing actions of conventional ₂-adrenergic and extended the observation to the newly developed long-acting analogues.     

Presence and characterization of extraintestinal pathogenic Escherichia coli virulence genes in F165-positive E. coli strains isolated from diseased calves and pigs

The virulence genotype profile and presence of a pathogenicity island(s) (PAI) were studied in 18 strains of F165-positive Escherichia coli originally isolated from diseased calves or piglets. On the basis of their adhesion phenotypes and genotypes, these extraintestinal pathogenic strains were classified into three groups. The F165 fimbrial complex consists of at least two serologically and genetically distinct fimbriae: F165(1) and F165(2). F165(1) is encoded by the foo operon (pap-like), and F165(2) is encoded by fot (sfa related). Strains in group 1 were foo and fot positive, strains in group 2 were foo and afa positive, and strains in group 3 were foo positive only. The strains were tested for the presence of virulence genes found mainly in extraintestinal pathogenic E. coli (ExPEC) strains. Although all the strains were positive for the papA variant encoding F11 fimbriae incD, traT, and papC, the prevalence of virulence genes commonly found in PAIs associated with ExPEC strains was highly variable, with strains of group 2 harboring most of the virulence genes tested. papG allele III was detected in all strains in group 1 and in one strain in group 3. All other strains were negative for the known alleles encoding PapG adhesins. The association of virulence genes with tRNA genes was characterized in these strains by using pulsed-field gel electrophoresis and DNA hybridization. The insertion site of the foo operon was found at the pheU tRNA locus in 16 of the 18 strains and at the selC tRNA locus in the other 2 strains. Furthermore, 8 of the 18 strains harbored a high-pathogenicity island which was inserted in either the asnT or the asnV/U tRNA locus. These results suggest the presence of one or more PAIs in septicemic strains from animals and the association of the foo operon with at least one of these islands. F165-positive strains share certain virulence traits with ExPEC, and most of them are pathogenic in piglets, as tested in experimental infections.     

Pathological and molecular progression of astrocytomas in a GFAP:12 V-Ha-Ras mouse astrocytoma model

We previously characterized a genetically engineered mouse astrocytoma model with embryonic astrocyte-specific, activated ¹²V-Ha-RAS (GFAP-RAS) transgenesis. The GFAP-RAS line Ras-B8 appears normal at birth, but 50% of mice die by 4 months from low- and high-grade astrocytomas. We examined the development and progression of astrocytomas in the Ras-B8 genetically engineered mouse. At embryonic day 16.5 (E16.5), there were no pathological differences compared to control littermates, aside from transgene expression. Diffuse astroglial hyperplasia was the first distinguishing feature in the 1-week-old Ras-B8 mice; however, these astrocytes were not transformed in vitro or in vivo. From 3 to 8 weeks the incidence of low-grade astrocytomas progressively increased with 85% of 12-week-old mice harboring low- or high-grade astrocytomas, the latter characterized by increased proliferation, nuclear atypia, and angiogenesis. Tp53 mutations were detected in both astrocytoma grades, with high-grade astrocytomas expressing elevated levels of epidermal growth factor receptor and vascular endothelial growth factor, plus decreased levels of PTEN and p16, similar to human astrocytomas. We postulate that expression of ¹²V-Ha-RAS in astroglial precursors induces astroglial hyperplasia, but transformation and subsequent progression requires additional molecular alterations resulting from aberrant activated p21-RAS. Of interest, many of these acquired alterations occur in human astrocytomas, further validating GFAP-RAS as a useful model for studying astrocytoma development and progression.     

Detection of antibodies specific to an antigenic cell wall galactomannoprotein for serodiagnosis of Aspergillus fumigatus aspergillosis

Aspergilloma and invasive aspergillosis are important opportunistic infections caused by Aspergillus species, among which Aspergillus fumigatus is the most common species associated with human disease. We developed an enzyme-linked immunosorbent assay (ELISA)-based antibody assay with Afmp1p, a purified recombinant antigenic cell wall galactomannoprotein of A. fumigatus. Evaluation of the test with guinea pig sera against A. fumigatus and other pathogenic fungi indicated that this assay was specific for A. fumigatus. Clinical evaluation revealed that the assay was 100% sensitive for patients with aspergilloma and 33.3% sensitive for patients with invasive aspergillosis. No false-positive results were found for serum samples from 80 healthy blood donors, 6 patients with typhoid fever, 4 patients with melioidosis, 20 patients with penicilliosis marneffei, 5 patients with candidiasis, and 4 patients with cryptococcosis, indicating a high specificity of the test. Thus, this ELISA-based test for the detection of anti-Afmp1p antibody can be of significant value as a diagnostic for aspergillosis.