Localization by immunoelectron microscopy of Schistosoma mansoni antigens in the glomerulus of the hamster (Mesocricetus auratus) kidney

Gene therapy has the potential to provide cancer treatments based on novel mechanisms of action with potentially low toxicities. This therapy may provide more effective control of loco-regional recurrence in diseases such as non-small cell lung cancer (NSCLC), as well as systemic control of micrometastases. Despite current limitations, retroviral and adenoviral vectors can in certain circumstances provide an effective means of delivering therapeutic genes to tumour cells. Although multiple genes are involved in the process of carcinogenesis, mutations of the p53 gene are the most frequent abnormality identified in human tumours. Pre-clinical studies both in vitro and in vivo have shown that restoration of p53 function can induce apoptosis in cancer cells. Phase I clinical trials now show that p53 gene replacement therapy is feasible and safe using both retroviral and adenoviral vectors, and that it induces tumour regression in patients with advanced NSCLC and recurrent head and neck cancer. Other pre-clinical studies indicate that gene therapy may have useful synergy with cytotoxic and radiation therapy. This paper describes the different gene therapy strategies under investigation and the pre-clinical data that provides a rationale for the gene replacement approach, reviews clinical trial data and presents novel ideas for improving current vectors and gene delivery to tumours.     

Serum growth hormone-binding protein (GHBP) in domestic animals as measured by ELISA

This research was conducted to develop and characterize a competitive ELISA for bovine serum growth hormone-binding protein (GHBP) using recombinant bovine GHBP and a polyclonal rabbit antiserum. In addition to bovine, however, the assay was found to measure some activity in equine, chicken, porcine, ovine, and human sera. The reference standard curve had an effective range of 3 to 200 ng/mL. Recovery of increasing amounts of GHBP added to ovine serum was 103% but seemed to overestimate the amount of GHBP at low concentrations (intercept = 2.5 ng/mL). Recovery from bovine and porcine serum was near ideal but seems to be overestimated at concentrations higher than 50 ng/microL. Within and between assay coefficients of variation were 12.1 and 18.9%, respectively, for a sheep serum pool. Neither exogenous GH (20 ng/mL) nor prolactin (100 ng/mL) interfered with the measurement of GHBP in serum. The GHBP activity measured in increasing doses of serum from ovine, porcine, and bovine inhibited the assay in a parallel manner. This observation suggests that the GHBP antiserum contains antibodies that are directed toward epitopes of GHBP, which are common among these species. Serum GHBP concentrations were similar among samples from a line of miniature Brahman and normal stature Brahman and Angus cattle. In mature ewes, there were no differences in serum GHBP among three different breed types. An increase (P < .0001) in serum GHBP was observed in pigs between 1 and 6 mo of age but no sex effect was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Protective effect against Rhodococcus equi infection in mice of IgG purified from horses vaccinated with virulence associated protein (VapA)-enriched antigens

G proteins couple receptors to effectors and thus regulate multiple biological processes. Here we report on the phenotypes of G alpha i2-deficient and G alpha o-deficient mice. G alpha i2-deficient mice display a blunted inhibitory regulation of adenylyl cyclase, alterations in T cell maturation and function, a growth retardation and also develop a lethal diffuse colitis with clinical and histopathological features closely resembling ulcerative colitis in humans, including the development of adenocarcinoma of the colon. G alpha o-deficient mice are also viable, but significantly smaller than wild-type controls.     

The role of class I and class II HLA antigens in primary open angle glaucoma (POAG)

Several clinical and epidemiological studies have shown the role of genetic factors in the pathogenesis of primary open angle glaucoma (POAG). In this study, 30 patients affected by this disease were tissue-typed for HLA Class I and Class II antigens. The results pointed up an increased incidence of some antigens and, particularly, a statistically significant association with DQ1 and DR11 alleles.     

The effect of danaparoid sodium (danaparoid) on endotoxin-induced experimental disseminated intravascular coagulation (DIC) in rats

Microencapsulated genetically engineered cells have the potential to treat a wide range of diseases. For example, in experimental animals, implanted microencapsulated cells have been used to secrete growth hormone to treat dwarfism, neurotrophic factors for amyotrophic lateral sclerosis, beta-endorphin to decrease pain, factor XI for hemophilia B, and nerve growth factors to protect axotomized neurons. For some applications, microencapsulated cells can even be given orally. They can be engineered to remove unwanted molecules from the body as they travel through the intestine, and are finally excreted in the stool without being retained in the body. This application has enormous potential for the removal of urea in kidney failure, ammonia in liver failure and amino acids such as phenylalanine in phenylketonuria and other inborn errors of metabolism.     

The prospects for using the genetically engineered surface antigen of the hepatitis B virus (HBsAg) expressed by recombinant poxvirus strains as the basis for vaccines against hepatitis B

The use of a recombinant poxvirus (RPV) strain, expressing HBsAg in the process of reproduction in different bioreactor systems under stationary and bioreactor conditions of cultivation, made it possible to obtain highly purified HBsAg. The identity and purity of HBsAg was confirmed by the analysis of its amino acid composition, SDS electrophoresis in polyacrylamide gel, electron microscopy and high-performance liquid chromatography. Good prospects of the use of RPV-expressed gene engineering HBsAg as the basis vaccines against hepatitis B was demonstrated in 10 experimental batches of vaccine. All batches of the preparation had pronounced immunogenicity and were safe and nontoxic in animal experiments. The ID50 of experimental batches did not exceed 211 ng/ml, which, according to the data of comparative experiments, was lower than, or equal to, corresponding values of analogous foreign commercial preparations, based on plasma or yeast HBsAg.     

The comparative value of the human basophil degranulation test and classical serology (immunofluorescence, haemagglutination, electrosyneresis, Vogel and Minning's Test) in the diagnosis of bilharzioses due to Schistosoma mansoni and Schistosoma haematobium

The Human Basophil Degranulation Test (HBDT), using Benveniste's technique, was compared to four serological techniques in a group of 42 cases of intestinal and urinary bilharziosis: indirect immunofluorescence, passive haemagglutination, electrosyneresis, and Vogel and Minning's test. The HBDT proved to be 88% more sensitive than each of the other techniques. It showed excellent specificity in a group of 32 negative controls, allergic subjects or patients with other helminth infestations. This study establishes the HBDT as one of the best immunological diagnostic tests of bilharziosis. However, the HBDT is not quantitative and only indicates reaginic sensitivity. It should be used together with tests of humoral immunity.     

Progress in oesophagoscopy. The role of the conventional oesophagoscope as against the supple fibroscope (author's transl)

In the history of endoscopy, laryngologists have played an important role in knowledge of the oesophagus. For those familiar with gastroscopy, the supple fibroscope represents a diagnostic instrument which may be used for observation of the oesophagus with the exception of natural or pathological areas of stenosis. It offers considerable possibilities in the photographic documentation of lesions. It is relatively easy to perform though not completely harmless. The rigid oesophagoscope remains an effective method of investigation of the whole oesophagus, including the oesophageal opening. It remains the best method for the performance of endoscopic surgery and in particular the extraction of foreign bodies. It is not dangerous in the hands of a competent and trained operator. Rather than opposing each other, the two instruments may be seen to be complementary.     

Perception and discrimination as a function of stimulus orientation: The "oblique effect" in man and animals.

A review of both behavioral and neurophysiological studies of orientation preferences indicates that performance for a large variety of perceptual tasks is superior for stimuli aligned in horizontal or vertical orientations, as compared to stimuli in oblique orientations. This phenomenon appears in the human adult and child and throughout the animal kingdom. Neurophysiological mechanisms for orientation analysis have been found in the higher visual pathways of many animals, and the suggestive evidence is compelling that these mechanisms underlie the orientation preferences reported behaviorally. Additional methods for determining the cause of these effects are suggested. (11 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of anti-inflammatory substances on free muscle transplants in the experimental animal (author's transl)

The effect of repeated subcutaneous injections of hydrocortisone and phenylbutazone on connective tissue formation was investigated in free rat muscle transplants. The follow-up investigation took place 4 weeks after transplantation of the long extensor muscles of the digits to the vastus lateralis group of the rectus femoris muscle. Connective tissue measurements were performed on the basis of hydroxyproline determinations. It was observed that in the untreated transplant there is twice as much connective tissue (expressed as a percentage) as in the same muscle remaining in situ. Hydrocortisone did not reduce the amount of connective tissue in the transplant. Phenylbutazone reduced the amount of connective tissue by 27%. At the same time the total weight of the transplants treated with hydrocortisone and phynylbutazone was reduced by 15% and 33% respectively. Attention is drawn to the myotoxic properties of hydrocortisone and phenylbutazone. Hence, in spite of the inhibited connective tissue formation there is no improvement in muscle fibre regeneration and their use cannot be recommended.     

The effect of the preliminary intake of mineral waters in acute alcoholic intoxication (an experimental study)

Complaints from patients often indicate their difficulty in coping with the health care system. Nurses need to acknowledge these complaints and help the patient resolve the problem. They need to see complaints as part of a continuous dialogue with their patients and their families. In addition, nurses need to use these complaints to assess the needs of the patient and to evaluate the care and delivery of services. This article presents nine steps the nurse can take when a patient or family member has a complaint.     

The effect of nafamostat mesilate (FUT-175) and gabexate mesilate (FOY) on multiorgan oxidant-antioxidant balance in acute experimental pancreatitis

This study was undertaken to determine whether synthetic proteinase inhibitors--nafamostat mesilate (FUT-175) and gabexate mesilate (FOY) have any influence on multiorgan oxidant-antioxidant balance in acute haemorrhagic pancreatitis induced in Wistar rats using a retrograde intraductal injection of 5% Na-taurocholate. Rats were treated with FUT-175 25 x 10(-3) g.kg-1.h-1) or FOY (2.5 x 10(-3) g.kg-1.h-1) and sacrificed at 3 h. Malondialdehyde and sulfhydryl groups concentration, as an index of oxidative stress, we measured in pancreatic, lung and liver tissue. In rats with acute pancreatitis treated with these proteinase inhibitors, oxidative stress expressed by malondialdehyde elevation and sulfhydryl groups depletion, was markedly diminished. It was observed in the pancreas and lung, and to a lesser extent in the liver. These effects of FUT-175 or FOY treatment, at least in part, may account for recently postulated favorable systemic effects of such a medication.     

The effect of prostatilen on the hemostatic indices in chronic prostatitis (a clinical and experimental study)

Continuous monitoring of dynamic changes of transcranial regional cerebral oxygenation (rSO2) was performed in 7 healthy volunteers (mean age 40.9 +/- 12.6 years; range 25-62 years) during normo- and hyperbaric oxygenation (HBO at 2.5 and at 1.95 ATA) using an INVOS 3100 cerebral oximeter. A significant change between HBO and control phase could be found in rSO2, alterations (p < 0.05; ANOVA, Tukey test). The results suggest that the calculation of rSO2 may be a useful method to monitor changes of oxygen saturation under hyperbaric conditions. However, the absolute quantification of rSO2 is useless at the moment and needs further investigation.     

Hepatitis B virus (HBV) and the inflammatory/immune response. I. The natural environment of the antigen presentation and immunologic chaos induced by the virus

In this paper, the authors update on the immunopathology of hepatitis B virus (HBV) infection, with special reference to the roles of inflammatory and natural immune responses (macrophages and NK cells) in the viral clearance. The role of specific immune responses being related to the influence of the environment of the antigen presentation (macrophages, NK cells, and their related cytokines IL-12 and IFN-gamma) on Th cells within the liver. The viral scape leading to chronic hepatitis B is thought to be due (a) to the suppressive actions of the virus on NK cells and IFN-gamma production (b) to the downregulation of IL-12/IL-15 production provoked by the inflammatory response (factor C3 of the complement system) on IL-12-producing macrophages: immunologic chaos.     

Central nervous system (CNS) involvement in SLE. The diagnostic role of antibodies to neuronal antigens

Dysplasia in inflammatory bowel disease (IBD) is categorized as either flat or associated with a raised lesion or mass (dysplasia-associated lesion or mass [DALM]). One specific subtype of a dysplasia-associated lesion or mass consists of isolated discrete nodules or polyps that are difficult to distinguish from sporadic adenomas. Because the clinical management of these two lesions is different, we performed this study to (1) evaluate the clinical presentation, pathologic features, and natural history of polypoid dysplastic lesions and sporadic adenomas in patients with IBD and (2) determine whether there are clinical, endoscopic, or pathologic findings useful in differentiating between these two lesions. The morphologic features of 89 benign polypoid epithelial neoplasms from 59 patients with IBD (51 with ulcerative colitis, 8 with Crohn's colitis) were evaluated and correlated with the clinical, endoscopic, and follow-up data. In a separate analysis, patients were categorized arbitrarily as having (1) a probable sporadic adenoma if the polypoid epithelial neoplasm was not located within areas of histologically proven colitis, (2) a probable IBD-associated polypoid dysplasia if the lesion developed within an area of colitis, and associated flat dysplasia or an adenocarcinoma was detected during follow-up evaluation or (3) an indeterminate polyp, which was seen in the remainder of the cases. The clinical, endoscopic, and histologic data were compared among these three patient and polyp subgroups. There were 35 males and 24 females (median age, 57 years; range, 27-85 years). Median duration of disease was 10 years. Forty-nine percent of the patients had pancolitis; 66% had histologically active disease at the time of presentation. Nearly 70% of patients had only one polyp; the majority occurred in either the left colon or the rectum (66%). Most polyps were described as a sessile nodule, whereas only 7 (7.8%) were pedunculated. Polyps ranged from 2 mm to 50 mm (median, 5 mm); most had a tubular architecture (84.3%) and contained low-grade dysplasia (64%). In addition, most polyps had mildly increased lamina propria and intraepithelial neutrophilic and mononuclear inflammation. At follow-up evaluation (40 patients; median follow-up time, 13 months; range, 1-78 months), a further neoplastic lesion developed in 20%; low-grade flat dysplasia was seen in 5 (12.5%), and adenocarcinoma developed in 3 (7.5%). However, dysplasia or adenocarcinoma did not develop in the patients who had polyps located outside of areas of histologically proven colitis. In addition, at least one more benign polypoid epithelial neoplasm developed in 15 of 40 patients (37.5%). Patients with probable IBD-associated polypoid dysplasia had a statistically significant (p < 0.05), longer disease duration than patients with probable sporadic adenoma. A statistically significant, higher proportion of polyps with tubullovillous or villous architecture, an admixture of normal and dysplastic epithelium at the surface of the polyps, and increased lamina propria mononuclear inflammation was noted in probable IBD-associated polypoid dysplastic lesions compared with those considered to be sporadic adenomas. Several clinical and pathologic features may be useful to help categorize a polypoid dysplastic lesion as a sporadic adenoma or an IBD-related neoplasm in a patient with IBD. This distinction is important because the natural history of these two lesions (as shown by the results of this study) and their subsequent management are quite different.     

Immunoregulation in fish. I: Intramolecular-induced suppression of antibody responses to haptenated protein antigens studied in Atlantic salmon (Salmo salar L)

A protein that inhibits hemocyte aggregation has been isolated from hemolymph of Manduca sexta larvae and named hemocyte aggregation inhibitor protein (HAIP). HAIP has a M(r) = 50,000, pI = 8.5, and contains 7% carbohydrate. It is present at 230 +/- 20 micrograms/ml in hemolymph of day 3 fifth instar larvae. Antibodies to HAIP do not cross-react with M. sexta hemolin, which is similar in size and charge and also inhibits hemocyte aggregation. HAIP and hemolin have some similarity in amino acid composition and NH2-terminal sequence, but are different in overall secondary structure, as determined by CD spectroscopy. The concentration of HAIP in hemolymph is not affected by injection of larvae with bacteria. A protein of approximately 50,000 daltons that reacts with antibody to M. sexta HAIP is present in hemolymph of Bombyx mori, Heliothis zea, and Galleria mellonella. Although the function of HAIP in vivo is not yet clear, it may have a role in modulating adhesion of hemocytes during defensive responses.