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Biomedical subjects

W Jacobs

Publications and source records attributed to W Jacobs.

At least 19 recordsLinked to original sources
PubMed1999

Schistosomal granuloma modulation. I. Schistosoma mansoni worm antigens CAA and CCA prime egg-antigen-induced hepatic granuloma formation.

Adult Schistosoma mansoni worms can positively modulate soluble egg antigen (SEA)-induced granulomas formed around SEA-coupled beads implanted in the liver. In this study, our aim was to further unravel the immunopathological characteristics of S.mansoni-worm-derived antigens in vivo. (a) Adult worm antigen (AWA)-coupled Sepharose beads, implanted into the liver, induced granulomas, containing numerous eosinophilic granulocytes and elicited marked periparticular fibrosis (composed of interstitial matrix proteins and basement membrane components). (b) Quantitative morphological analysis demonstrated that in naive mice, AWA-induced hepatic granuloma formation peaked in volume 16 days after injection of the beads. An accelerated response against AWA-coupled particles (peak volume at 8 days) was observed in mice carrying a single-sex, male S. mansoni infection. (c) When the granuloma volume induced by SEA-coupled beads in unisexually S. mansoni infected mice was compared to granulomas induced by beads laden with both SEA and AWA in unsensitized mice, no significant differences in granuloma volume were seen, indicating the existence of in vivo egg/worm antigen cross-sensitization. (d) Naive mice, sensitized with the worm antigens circulating anodic antigen (CAA) or circulating cathodic antigen (CCA), mounted a strongly accelerated response towards SEA-coupled beads implanted in the liver. We infer that, in vivo, worm antigens cross-sensitize with egg antigens and have both granulomogenic and fibrogenic characteristics. The S. mansoni soluble worm antigens CCA and CAA prime hepatic egg-antigen-induced granuloma formation possibly through the presence of immunogenic carbohydrates. These mechanisms lead to an accelerated response against SEA.

Animals↗
PubMed1999

Schistosomal granuloma modulation. II. Specific immunogenic carbohydrates can modulate schistosome-egg-antigen-induced hepatic granuloma formation.

To further investigate the factors involved in the modulation of the schistosomal granuloma, mice were primed with immunogenic carbohydrates which were common to soluble egg antigen (SEA) and adult worm antigen. Mice sensitized with LewisX trisaccharide or lacto-N-fucopentaose-III (LNFP-III) displayed an increased cellular response towards SEA-coupled beads implanted in the liver by mesenteric injection, resulting in the formation of larger periparticular granulomas. When animals were sensitized with bovine serum albumin or a structurally related carbohydrate, an accelerated response was not seen. Since LNFP-III is built up of LewisX molecules, and LewisX carbohydrates are common to SEA and worm antigens such as the gut-secreted antigens CCA and CAA (two antigens that could prime egg-antigen-induced granuloma formation), this may explain why adult, live Schistosoma mansoni worms positively modulate egg-antigen-induced hepatic granuloma formation in the murine host. These observations provide new insights into the role of carbohydrates in parasite-host immunity and may yield important implications for choosing worm-derived antigens for the development of anti-schistosome vaccines.

Animals↗
PubMed1998

[Control of the identity of blood samples for the surveillance of research on swine vesicular disease and Aujeszky's disease].

A surveillance programme for swine vesicular disease (SVD) and Aujeszky disease was set up in 1993 in the Netherlands. Blood samples are taken from pigs by local veterinarians to enable testing for the presence of antibodies against these viruses. A programme to guarantee the identity of pigs tested for these diseases has been in operation since late 1995. In this programme, pigs are identified on the basis of the DNA profiles of blood and hair samples. The hair samples are collected by the department of Animal Health Control. Analysis proves whether blood and hair samples are from the same animal. A total of 655 animals have been tested from 94 farms. In 38.6% of these farms differences were found between blood and hair samples.

Animal Identification Systems↗
PubMed1998

Syndecan-1 expression in malignant mesothelioma: correlation with cell differentiation, WT1 expression, and clinical outcome.

Syndecan-1 binds basic fibroblast growth factor (bFGF), modulates neovascularization, plays a role in epithelial differentiation and is up-regulated by WT1. Malignant mesothelioma of the pleura is one of the most aggressive tumours known and expresses high levels of angiogenic growth factors. This study has analysed syndecan-1 expression in mesothelioma tumours and cell lines by immunohistochemistry and immunoblotting, using anti-syndecan-1 antibody directed against the core protein, and has examined its relation to morphology, bFGF, WT1, and intra-tumoural microvascular density (IMD). Shedding of syndecan-1 in the conditioned medium of mesothelioma cell lines was detected in variable amounts. These studies indicate that (1) there is no correlation of syndecan-1 with either bFGF expression or IMD in mesotheliomas in vivo; (2) syndecan-1 is strongly expressed in the epithelial type of mesothelioma and in the epithelial component of biphasic mesotheliomas and the expression is reduced or lost in sarcomatoid differentiation; together with the finding that (3) syndecan-1 correlates with WT1 immuno-expression, this suggests that syndecan-1 might relate to the differentiation state of mesothelial/mesothelioma cells; and (4) syndecan-1-positive tumours are associated with a longer survival (p = 0.02) than mesotheliomas with no or little syndecan-1 expression, on univariate analysis. These findings therefore indicate that syndecan-1 can be an important prognostic indicator in mesotheliomas and its loss may be important in the epithelial-mesenchymal transformation of mesothelioma cells.

Adenocarcinoma↗
PubMed1998

Adhesion molecules in intestinal Schistosoma mansoni infection.

Adhesion molecules constitute essential elements in inflammation, mediating various cellular interactions. We investigated the expression of adhesion molecules mediating cell-cell [intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1)] and cell-matrix interactions [very late antigen-4 (VLA-4), VLA-6, and syndecan-1] in intestinal granulomas of mice infected with the parasite Schistosoma mansoni. Up-regulation of ICAM-1, LFA-1, and VLA-4 was seen in ileal and colonic granulomas, at both the acute (8 weeks postinfection) and the chronic stage (13-16 weeks postinfection). Up-regulation of VLA-6 was absent in all intestinal granulomas. Syndecan-1 immunoreactive (antigen-driven) B-lymphocytes were seen in the proximity of egg-antigen-laden macrophages in the inner part of ileal and colonic granulomas, although B-cells are considered to be absent in ileal granulomas. Estimation of intestinal granuloma volumes demonstrated the lack of down-modulation observed in ileal granulomas. From our results we infer that adhesion molecules constitute important elements in schistosomal intestinal granuloma formation. Organ-related differences between hepatic and intestinal granulomas exist (e.g., granuloma volume), but these differences are not morphologically reflected in a differential expression of the adhesion molecules ICAM-1, LFA-1, and VLA-4. Syndecan-1 immunoreactive B-lymphocytes also appear to be involved in ileal granuloma formation.

Animals↗
PubMed1998

Transforming growth factor-beta, basement membrane components and heparan sulphate proteoglycans in experimental hepatic schistosomiasis mansoni.

In an attempt to elucidate further the immunopathological pathways that underlie fibrogenesis induced by Schistosoma mansoni, we have studied the distribution of basement membrane compounds, heparan sulphate proteoglycans (HSPG) and the fibrogenic cytokine transforming growth factor (TGF)-beta in two models of experimental schistosomiasis mansoni (experimental murine infection and synchronous granulomas induced by injection of egg-antigen-coupled beads into the caecal vein). Deposition of the basement membrane proteins type IV collagen, laminin and entactin in schistosomal granulomas was seen 3 days after the implantation of egg-antigen-coupled beads in the liver and persisted over time (32 days). Up-regulation of the membrane-bound HSPG syndecan-1 was observed in the schistosomal granuloma. These syndecan-1-immunoreactive cells represented a distinct subpopulation of granuloma cells; they were different from both mature, unstimulated B-cells (CD40-positive) and endothelial cells (CD105-positive). Deposition of the matrix HSPG perlecan within the granuloma was most prominent 8-16 days after injection. TGF-beta expression was observed in acute (8 weeks) and chronically (13 weeks) infected mice, mainly at the periphery of the schistosomal granuloma and on Kupffer cells in the liver parenchyma. From these observations, we infer that schistosomal fibrosis is composed of various groups of matrix components and that TGF-beta, which is secreted by granuloma cells, is one of the fibrogenic mediators in schistosomal fibrogenesis.

Animals↗
PubMed1998

Morphometrical and immunopathological dissection of the hepatic Schistosoma haematobium granuloma in the murine host.

This paper presents the results of a study aimed at identifying the immunopathological and morphometrical characteristics of liver granulomas induced by the parasite Schistosoma haematobium. The OF1 mouse is a susceptible host for experimental infection with the Egyptian NAMRU-3 strain of S. haematobium. Formation of liver granulomas started after 13-14 weeks of infection. These hepatic granulomas reached a maximum volume after 20 weeks of infection (MGV: 1.82 +/- 0.15 x 10(7) micron 3) and regressed thereafter (1.55 +/- 0.16 x 10(7) micron 3 after 24 weeks). Strong cellular upregulation of the adhesion molecules ICAM-1, LFA-1, syndecan-1, VLA-4, but not VLA-6 is seen, both in acute and chronic granulomas. Finally, pathological differences exist between hepatic S. mansoni and S. haematobium granulomas particularly at the level of extracellular matrix deposition. S. haematobium induced peri-ovular deposition of mainly fibronectin and to a lesser extent type I and IV collagen.

Animals↗
PubMed1998

Temporomandibular disorders: clinical and laboratory analyses for risk assessment of criteria for surgical therapy, a pilot study.

Temporomandibular disorder (TMD) is a broad category involving dysfunction of the skeletomuscular structures of the head and neck, and the temporomandibular joint (TMJ). A total of 66 patients, 54 with TMD, participated in this study. Group 1 (G1) had 31 patients suffering from early to intermediate stage disease, and no prior surgeries. G1 patients had arthrotomy/meniscectomy performed on the diseased joint(s). Group 2 (G2) consisted of 23 patients with late stage disease. All G2 patients had previously had unsuccessful TMJ surgery and were treated with either a partial or total joint prosthesis. Group 3 (G3) consisted of 12 patients who were clinically and radiographically asymptomatic. Medical histories including inflammatory bowel disease, headaches, vertigo, tinnitus and anemia, as well as surgical tonsillectomies, appendectomies and cholecystectomies, were significantly greater in G1 and G2 when compared to G3. Serological testing included HLA subtype, positive (ANA) antinuclear antibody, erythrocyte sedimentation rate (ESR), anemia profile, hormonal levels of prolactin and estradiol, and rheumatoid factor (RF). HLA frequencies, as well as some serological analyses, were significantly different among the three groups. These findings suggest that surgical failure may be secondary to autoimmune dysfunction with a predisposition to multisystem disease. The utilization of genetic markers, serological testing, and thorough medical and surgical histories should allow the clinician to determine which patients are potentially better surgical risk candidates for treatment of TMD.

Adolescent↗
PubMed1998

[Mandibular distraction using a dynamic osteosynthesis system: MD-DOS. Concepts and surgical technic].

MD-DOS (mandibular distraction with a dynamic osteosynthesis system) is an intra-oral mandibular distractor that can be placed via the oral route, enabling application under local anesthesia. The aim of the article is to describe the technical-surgical aspects of the treatment concept, based on an initial experience of 35 cases. The device is characterised by a single horizontal posterior fixation screw-implant, a vertical hinge that copes with the lateral force vector in the condyles, a telescopic distraction module, and an anterior fixation unit that is fixed with monocortical screws. The main indication was mandibular lengthening in Angle Class II, deep bite cases. The third molars could be removed in the same session. Of importance was the horizontal placement of the posterior fixation unit (PFU), together with the distraction module, in order not to interfere with lateral jaw movements and with the lower sulcus. Equally important was the use of at least one 7.5 mm long osteosynthesis screw together with at least three 5.5 mm screws. Near complete mobilisation of the segments, firmly blocking the posterior fixation unit with the vertical hinge in a perpendicular position, and placing MD-DOS as close as possible to the dental arch, were also important parameters for success.

Anesthesia, Dental↗
PubMed1998

Tyramine-amplified immunohistochemical testing using "homemade" biotinylated tyramine is highly sensitive and cost-effective.

Immunohistochemical testing using biotinylated tyramine is a recently described technique that results in a strong amplification of the detection signal using antibodies at very high dilutions. In this report we compare the sensitivity and cost-effectiveness of the technique using "homemade" biotinylated tyramine with those of two commercially available kits. The technique using homemade tyramine was easy to follow and highly sensitive and resulted in a 2.5- to 5-fold reduction in costs compared with the commercial kits. Tyramine-amplified immunohistochemical testing using homemade biotinylated tyramine is a valuable and inexpensive tool for both the diagnostic and experimental histopathology laboratory.

Biotinylation↗
PubMed1997

Expression of intercellular adhesion molecule-1 and lymphocytefunction-associated antigen-1 in experimental Schistosoma mansoni infection and in synchronous periparticular hepatic granulomas in mice: immunohistochemistry, confocal laser scanning microscopy, and immunoelectron microscopy.

Adhesion molecules play an important role in inflammatory and immunological responses. We assessed the expression pattern of intercellular adhesion molecule-1 (ICAM-1) and lymphocytefunction-associated antigen-1 (LFA-1) in the livers of mice experimentally infected with Schistosoma mansoni and in synchronous hepatic granulomas induced by injection of soluble egg antigen (SEA)-coupled Sepharose beads in a mesenteric vein of mice. By immunohistochemistry, confocal laser scanning microscopy, and immunoelectron microscopy, ICAM-1 was localized on endothelial cells, sinusoidal-lining cells (Kupffer cells and sinusoidal endothelium), the hepatocyte cell membrane facing Disse's space, and inflammatory cells in the granuloma. LFA-1 was visualized on the inflammatory cells of the granuloma and on phagocytic sinusoidal-lining cells, most likely Kupffer cells. ICAM-1- and LFA-1-immunoreactive cells were present in the granuloma as early as at 3 days after injection of SEA-coupled beads and persisted with time. As granulomas became older, nonimmunoreactive granuloma cells appeared. We conclude that adhesion molecules play an important role in the genesis of the schistosomal granuloma.

Animals↗
PubMed1997

Inhibitory effects of CAI in glioblastoma growth and invasion.

While distant metastases are rare in patients with primary brain malignancies, local growth and invasion are common and life-threatening. Regional infiltration is responsible for the failure of local therapies, resulting in tumor recurrence, progression, and death. The process of invasion requires cellular adhesion, local proteolysis and migration. CAI, carboxyamide-triazole, is an anticancer agent developed as an inhibitor of selected signal transduction pathways. Studies on the effects of CAI on human glioblastoma growth and invasiveness are presented. CAI inhibited proliferation of 6 of 8 cell lines tested in a dose-dependent fashion in vitro (IC50 range 1.5-44 microM), with no effect on the U373 line. Inhibition of adhesion to tissue culture plastic was observed for the H4, T98G, and U373 lines pretreated with CAI; H4 and T98G were inhibited in adhesion to collagen type IV. Incubation with CAI decreased production of the 72 kDa and 92 kDa type IV collagenases in all cell lines, ranging from 16 to 93% inhibition. These observations show that the effects of CAI on cell line behavior can vary between lines that are similar in origin. Despite variability in the inhibitory effects for proliferation and adhesion, CAI is consistently able to inhibit the invasive phenotype of all glioma cell lines in vitro using the Matrigel barrier assay (IC50 range 13-28 microM). These observations suggest that CAI may have benefit in the treatment of gliomas and high grade astrocytomas.

Antineoplastic Agents↗
PubMed1997

Adult Schistosoma mansoni worms positively modulate soluble egg antigen-induced inflammatory hepatic granuloma formation in vivo. Stereological analysis and immunophenotyping of extracellular matrix proteins, adhesion molecules, and chemokines.

Synchronized liver granulomas were induced by injecting Sepharose beads to which SEA soluble egg antigen (SEA) or the concanavalin A binding fraction of SEA had been coupled into a mesenteric vein in naive, single-sex (35 days) and bisexually (28 days) Schistosoma mansoni-infected and Plasmodium berghei-immunized mice. Stereological analysis revealed that peak granuloma formation was already reached 8 days after injection in single-sex infected mice compared with 16 days in naive animals. No difference in granuloma formation between naive and P. berghei-immunized animals and between unisexually and bisexually S. mansoni-infected mice was observed. This suggests that the positive immunomodulatory effect on the granulomogenesis is worm specific and not likely to be due to arousal of the immune system by unrelated factors, nor is it influenced by the gender or degree of maturation of female worms. At all stages in time, the concanavalin A binding-fraction-induced granulomas reached only 65 to 70% of the volume of SEA-induced granulomas. Immunophenotyping of extracellular matrix proteins around deposited heads revealed that fibronectin was the dominant extracellular matrix protein and that also type I and IV collagen and laminin were deposited. Temporal analysis of the expression of the adhesion molecules ICAM-1, LFA-1, VLA-4, and VLA-6 was performed. Morphological evidence is presented for the role of adhesion molecules in the initiation and maintenance of hepatic granuloma formation. The chemokine monocyte chemoattractant protein-1 was expressed in the granuloma and in hepatic artery branches. From these data, it is concluded that adult S. mansoni worms positively modulate schistosomal hepatic granuloma formation in vivo. Adhesion molecules and chemokines play important roles in schistosomal granuloma formation.

Animals↗
PubMed1996

Identification and molecular characterization of a m5 muscarinic receptor in A2058 human melanoma cells. Coupling to inhibition of adenylyl cyclase and stimulation of phospholipase A2.

We report the identification and biochemical characterization of an endogenous m5 muscarinic acetylcholine receptor (mAChR) in the A2058 human melanoma cell line. This is the first demonstration of a m5AChR outside the central nervous system. The unusual effector coupling of this endogenous m5AChR is presented. The coding region amplified by polymerase chain reaction was identical to the known m5AChR sequence. Binding studies indicated a Kd of 99 +/- 6 pM and a Bmax of 45 +/- 4 fmol/mg membrane protein. This m5AChR coupled to stimulation of arachidonic acid release and to a 50% inhibition of forskolin-stimulated cAMP accumulation. The inhibition of cAMP production was insensitive to pertussis toxin treatment, but was dependent upon extracellular calcium. In contrast to the odd mAChR pattern, no cAMP was produced in response to carbachol (CC) stimulation. Moreover, no release of inositol phosphates could be measured after CC treatment despite the presence of at least 2 phospholipase C isoforms in A2058 cells. CC-stimulated arachidonic acid release (EC50 = 17.8 +/- 0.1 microM) was dependent upon external Ca2+, with marked reduction after coincubation with EGTA, Co2+, or high doses of verapamil (IC50 = 166 microM) or diltiazem (IC50 = 243 microM). Brief exposure to phorbol 12-myristate 13-acetate augmented CC-stimulated arachidonic acid release, whereas prolonged phorbol 12-myristate 13-acetate treatment resulted in down-regulation of release. Activation of the m5AChR resulted in Ca2+ influx that was attenuated by muscarinic antagonism and removal of extracellular Ca2+. A2058 cells exposed to CC had no alteration of cell shape or growth potential in monolayer culture, however, a statistically significant reduction in density-independent growth was observed over the range of CC concentrations from 0.1 to 100 microM. This endogenous m5AChR has a novel signal transduction coupling profile and receptor activation reduces clonogenic potential.

Adenylyl Cyclase Inhibitors↗
PubMed1996

Antiobesity effect of diazoxide in obese Zucker rats.

Hyperinsulinism and insulin resistance are characteristic findings in obese subjects. Obesity in both humans and experimental animals is associated with a reduced number of insulin receptors and a decreased insulin-mediated glucose disposal, whereas sensitivity to insulin's antilipolytic action is unaltered. To evaluate the antiobesity effect of diazoxide (DZ), an inhibitor of glucose-stimulated insulin release, 7-week-old Zucker obese and lean rats were studied. Obese and lean rats were grouped into DZ-treated (150 mg/kg/d) and control (C) groups. DZ-treated obese rats consumed similar amounts of calories per kilogram body weight (BW) compared with C obese animals, but gained less weight (P<.01). Postabsorptive plasma free fatty acids (FFA), cholesterol, and triglycerides were significantly higher in obese versus lean animals (P<.01). DZ treatment reduced plasma triglyceride levels in obese animals (P<.001), but had no significant effect on FFA or cholesterol concentrations. Plasma glucose concentrations in the postabsorptive state and during glucose tolerance tests (GTTs) were significantly lower in DZ obese versus C obese rats (P<.01) despite a decrease in plasma insulin concentrations in DZ-treated animals (P<.01). In contrast, DZ lean rats developed glucose intolerance (P<.05). Sensitivity and responsiveness to the antilipolytic effect of insulin in isolated adipocytes were significantly decreased in DZ obese as compared with C obese rats (P<.01). Moreover, adipocyte specific insulin receptor binding was increased in both DZ lean and DZ obese animals (P<.01). This was accompanied by increased basal and insulin-stimulated glucose transport in both genotypes (P<.01). In conclusion, DZ increased insulin receptor binding and glucose transport while decreasing hyperinsulinemia and insulin sensitivity to the antilipolytic action of insulin. This combined effect resulted in improved glucose tolerance and a decrease in weight gain in obese rats, implying that pharmacologic modification of the disturbed insulin metabolism of obesity may be therapeutically beneficial.

Adipocytes↗
PubMed1996

Stereological evaluation of malignant mesothelioma versus benign pleural hyperplasia.

The differential diagnosis between malignant mesothelioma and benign pleural hyperplasia constitutes a well-known problem. In the present study we examined unbiased stereological techniques to assess the mean nuclear volume (MNV) using the point-sampled intercepts (PSI) in 37 cases of malignant mesothelioma and in 28 cases of benign pleural hyperplasia. Neither the use of different fixatives nor the histological type of malignant mesothelioma produced any significant difference on the measured nuclear volume. The differences observed between the MNV data obtained from benign pleural hyperplasia and those from any of the three types of malignant mesothelioma were found to be highly significant. All lesions with an MNV larger than 250 microns3 were found in our study to correspond to the malignant mesothelioma type, while an MNV that was smaller than 200 microns3 could only be detected in benign specimens. These observations lead us to propose the MNV measurement using PSI as an additional tool to enhance the differential diagnosis of malignant mesothelioma versus benign pleural hyperplasia.

Cell Nucleus↗
PubMed1996

Outpatient reduction mammaplasty: a review of 338 consecutive cases.

Reduction mammaplasty is usually accomplished under general anesthesia, often with an overnight stay. With cost-containment pressures, the ability to perform this surgery in an outpatient setting would have obvious benefits. We present a series of 338 patients who have undergone bilateral reduction mammaplasty over a 3-year period. Two hundred eighty-six cases (84.6%) were performed on an outpatient basis and 52 (15.4%) were inpatients. Patient age ranged from 13 to 82 years. Significant differences were found between the two groups regarding average age (34.3 and 42.4 years, respectively) and average total resection weights (1,486.1 gm and 1,895.6 gm, respectively). The maximum total resection weight was 6,000 gm in the outpatient group and 7,140 gm in the inpatient group. Surgical techniques included inferior pedicle (N = 273), central mound (N = 54), and free nipple graft (N = 11). There were no substantial differences in the incidence of minor complications, including wound separation, seromas, hypertrophic scars, infection, and hypopigmentation. Autologous transfusion was utilized in 18 patients early in the series. Of the 175 patients (52%) who returned a follow-up questionnaire, all considered their outpatient experience a positive one. In addition, 33% of the inpatients who responded (N = 8/24) felt their hospital stay was unnecessary. Outpatient surgery resulted in a savings of $1,500 to $2,500 when compared to an overnight stay. Reduction mammaplasty can be performed safely in an outpatient setting and is not necessarily limited by age or extent of resection.

Adolescent↗