Biomedical subjects

J Roth

Publications and source records attributed to J Roth.

At least 289 records · Page 16Linked to original sources

PubMed1993

Adaptation of a non-radioactive in situ hybridization method to electron microscopy: detection of tenascin mRNAs in mouse cerebellum with digoxigenin-labelled probes and gold-labelled antibodies.

In this study we describe a method for the detection of mRNAs at the ultrastructural level using a non-radioactive in situ hybridization method based on digoxigenin-labelled cRNA probes and gold-labelled digoxigenin-specific antibodies. We applied this protocol to an analysis of the expression of the extracellular matrix protein tenascin in the developing cerebellar cortex of the mouse. To gain an impression of the sensitivity attainable with digoxigenin-labelled probes, we first established at the light microscopic level that the hybridization signal obtained with the non-radioactive probe is as sensitive as that obtained with a 35S-labelled probe. The non-radioactive hybridization protocol was then combined with electron microscopic post-embedding and immunogold detection techniques. Tenascin-specific, digoxigenin-labelled cRNA probes were hybridized to ultrathin sections of Lowicryl K4M-embedded tissue and the probe/target mRNA hybrids were detected using gold-labelled antibodies to digoxigenin. In agreement with the observations from in situ hybridization at the light microscopic level, specific labelling was observed in Golgi epithelial cells in the region of the Purkinje cell layer and cells in the internal granular layer, which could be identified as astrocytes by ultrastructural criteria. Labelling was detectable in association with free ribosomes and ribosomes of the rough endoplasmic reticulum. In addition, focal hybridization signals were occasionally found in the nucleus. No signal was observed in Golgi epithelial cells or astrocytes using sense or in any other cerebellar cell type using either sense or anti-sense probes. The described in situ hybridization technique uses ultrastructural criteria to associate the presence of a given mRNA species with a particular cell type. Additionally, it provides information about the target mRNA's subcellular distribution, thus offering the possibility to study intracellular transport of particular mRNAs.

Acrylic Resins↗

PubMed1993

Monoclonal antibodies that recognize the trisaccharide epitope Gal alpha 1-3Gal beta 1-4GlcNAc present on Ehrlich tumor cell membrane glycoproteins.

Monoclonal antibodies were prepared against the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc, a sequence which occurs on the surface of Ehrlich ascites tumor cells as well as in thyroglobulin, laminin and a variety of other proteins. This was accomplished by immunizing BALB/c mice with the fraction of Ehrlich cell membrane glycoproteins obtained by affinity chromatography on a Griffonia simplicifolia I (GS I) column which selectively binds alpha-D-galactosyl-terminated structures. Detection of Gal alpha 1-3Gal beta 1-4GlcNAc-specific antibodies was accomplished by employing glycoproteins containing the trisaccharide sequence; fusion with spleen cells from an immunized mouse was accomplished in the presence of polyethylene glycol (PEG1500). An enzyme-linked immunosorbent assay (ELISA) system was used to identify two clones (2.10G and 6.8E), which recognized the desired trisaccharide conjugate. These clones also recognized a thyroglobulin fraction isolated by GS I affinity chromatography and murine laminin, both of which possess the Gal alpha 1-3Gal beta 1-4GlcNAc sequence. Inhibition of antibody-trisaccharide reactivity, examined employing an ELISA assay, revealed that two trisaccharides, Gal alpha 1-3Gal beta 1-4GlcNAc/Glc, were the best inhibitory haptens; Gal beta 1-4GlcNAc (LacNAc), Gal alpha 1-3Gal and Gal beta 1-4Glc (lactose) were poor inhibitors. Indirect immunofluorescence staining of unfixed Ehrlich cells using the monoclonal antibody at 4 degrees C revealed fluorescence over the entire cell surface. Indirect immunogold labeling of semithin and ultrathin sections of aldehyde fixed and Lowicryl K4M-embedded Ehrlich cells resulted in specific labeling of the cell surface and internal structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Congenital mesoblastic nephroma: an immunohistochemical and lectin study.

Eight cases of congenital mesoblastic nephroma (CMN) were examined. Three CMNs were of the classical (typical) variant, two were cellular (atypical), and three showed a mixed pattern. A panel of nephron segment-specific tubular epithelial markers (the lectins Tetragonolobus purpureas, Phaseolus vulgaris erythroagglutinin, and Arachis hypogaea and antibodies to epithelial membrane antigen, cytokeratin, and Tamm-Horsfall protein) were used to differentiate epithelial structures within the tumor. Antibodies against vimentin, desmin, and muscle-specific actin were used as mesenchymal markers. A monoclonal antibody to the long (embryonic) form of polysialic acid (PSA) on the neural cell adhesion molecule was used as a putative renal oncodevelopmental marker. An antibody to proliferating cell nuclear antigen also was applied, which revealed increased proliferative rate in cellular CMNs. In addition to clearly entrapped native renal tubules, CMNs contain tubular structures with immature, dysplastic epithelium and occasional epithelial cell clusters embedded deep within the tumor. These immature tubules and clusters express distal nephron, including collecting duct markers and, occasionally, vimentin and PSA. We propose that these primitive tubules and epithelial structures may originate from the ureteric bud. An epithelial differentiation of the tumor cells also is possible. In one pure cellular CMN and two mixed CMNs the cellular component showed diffuse staining for PSA. The PSA (neural cell adhesion molecule) expression of the cellular component suggests that CMN may originate from the uninduced nephrogenic mesenchyme.

Child↗

PubMed1993

Effect of bovine immunodeficiency-like virus infection on immune function in experimentally infected cattle.

Bovine immunodeficiency-like virus (BIV) is a bovine lentivirus that has antigenic and genetic homology with the human immunodeficiency virus. Little work has been reported on the effect of BIV infection on bovine immune function. This study was designed to evaluate lymphocyte blastogenesis, mononuclear cell subset numbers, neutrophil function, hematology, and clinical signs in three groups of cattle. These groups were evaluated at 0-2 months post inoculation (PI, Group 1), 4-5 months PI (Group 2), or 19-27 months PI (Group 3). BIV infected animals were inoculated with the R-29 isolate of BIV in tissue culture cells, peripheral blood mononuclear cells from a R-29 infected calf, or a molecular clone of the R-29 isolate. Most inoculated animals seroconverted to BIV by Western immunoblot. BIV was reisolated from most of the animals inoculated. BIV infection was associated with an increase in the lymphocyte blastogenic response to the mitogen phytohemagglutinin in Groups 2 and 3. Neutrophil antibody dependent cell mediated cytotoxicity and neutrophil iodination were decreased (P < 0.05) in BIV infected cattle (Groups 2 and 3 and Group 3, respectively). All animals were clinically normal during the evaluation periods. Notable differences were not observed in the other assessments performed. Work with additional BIV isolates and over longer time frames is warranted.

Analysis of Variance↗

PubMed1993

Expression of intercellular adhesion molecule-1 by murine macrophages is up-regulated during differentiation and inflammatory activation.

Intercellular adhesion molecule-1 (ICAM-1, CD54) is a cell-surface glycoprotein which has been shown to play an important role for cell/cell interaction. Little is known about its occurrence in the murine monocyte/macrophage (M phi) lineage; hence, we analyzed ICAM-1 expression in cells and cell lines representing different stages of M phi maturation and studied its regulation during inflammatory activation. Flow cytometric analysis of bone marrow-derived M phi cultured in the presence of M-CSF, of thioglycollate-elicited peritoneal M phi and of M1 myeloblasts differentiated by lipopolysaccharide (LPS) treatment revealed that ICAM-1 is increasingly expressed during monocytic maturation. Accordingly, the myelomonocytic cell lines RMB.TG, WEHI.TG, J774A and P388D, which can be ordered in a linear differentiation sequence, showed increasing levels of ICAM-1 expression. Furthermore, ICAM-1 expression by bone marrow-derived M phi could be up-regulated by tumor necrosis factor-alpha, interferon-gamma and LPS. In two models of murine experimental inflammation, i.e. induction phase of contact hypersensitivity and cutaneous leishmaniasis, which are both dependent on M phi/T cell interaction, M phi expressing ICAM-1 were found to be highly abundant. In addition, it was demonstrated that co-culture of Leishmania maior parasites with bone marrow M phi led to up-regulation of ICAM-1 on these cells. In conclusion, our data clearly demonstrate that ICAM-1 is increasingly being expressed during maturation of murine M phi. Cytokines and inflammatory stimuli modulate M phi ICAM-1 expression as well thus referring to its considerable role during inflammation, e.g. providing accessory or costimulatory signals for T cell activation.

Animals↗

PubMed1993

Endoscopic ultrasonography in the quantitative assessment of response to chemotherapy in patients with adenocarcinoma of the esophagus and esophagogastric junction.

We used endoscopic ultrasonography (EUS) to clinically stage eight patients with adenocarcinoma of the esophagus and to monitor their disease after subsequent courses of experimental preoperative chemotherapy. Stage of disease (TNM), tumor area, and tumor width were determined at each session. These results were then compared with barium esophagram and histopathology from resection specimens. EUS provided a consistent interpretation of the stage of disease and accurately predicted histopathologic findings. Measurement of tumor area and maximal width did not reliably correlate with the response to chemotherapy as assessed by barium esophagram. Although this technique seems promising, it cannot yet be recommended as a means of predicting response to chemotherapy.

Adenocarcinoma↗

PubMed1993

Nickel chloride and cobalt chloride, two common contact sensitizers, directly induce expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule (ELAM-1) by endothelial cells.

Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1, E-selectin) are endothelial surface molecules that play a role for leukocyte recruitment to sites of inflammation, e.g., during contact hypersensitivity. We studied the effects of sensitizing agents (2,4-dinitro-benzenesulfonic acid, metal salt haptens) and chemically related substances on endothelial adhesion molecule expression. Using flow cytometry and an enzyme-linked immunosorbent assay, NiCl2 and, to a lesser extent, CoCl2 were found to up-regulate ICAM-1, VCAM-1, and ELAM-1 expression on cultured human umbilical vein endothelium whereas the other substances tested showed no effects. Induction of adhesion molecules by NiCl2 required de novo mRNA and protein synthesis. Up-regulation could be blocked by kinase inhibitor H-7 but not staurosporine, suggesting involvement of phosphorylation events independent of protein kinase C activation. Concomitant application of NiCl2 and neutralizing antibodies to IL-1 did not block up-regulation by the hapten demonstrating that the latter did not act via an IL-1-dependent autocrine mechanism. Regarding ELAM-1 induction, pre-treatment for 24 h with NiCl2 produced hyporesponsiveness to IL-1 and TNF-alpha upon restimulation, suggesting that NiCl2 and these cytokines may partially share a common pathway of activation. In addition, analysis of cultured foreskin specimens revealed that NiCl2 may induce up-regulation of ELAM-1 on microvascular endothelium in vivo. Our data demonstrate that both Ni++ and Co++ to which simultaneous contact sensitivity is frequently observed have the ability to directly up-regulate endothelial adhesion molecules. This shared property may represent an adjuvant mechanism that promotes sensitization and elicitation events in contact hypersensitivity to these haptens.

Capillaries↗

PubMed1993

Initial experience with transvenous implantable cardioverter defibrillator lead systems: operative morbidity and mortality.

Introduction of non-thoracotomy lead systems (Medtronic, Inc.) for the implantable cardioverter defibrillator (ICD) has expanded the indications for use of this mode of therapy. Patients previously considered "too ill" to undergo a thoracotomy as well as patients who are at a high risk for developing sudden death but without previous cardiac arrest, are now considered candidates. The initial experience with the non-thoracotomy lead system at our institution was analyzed for morbidity and mortality. Thirty-four patients underwent attempted intravascular lead implantation, with 30 having initial successful implantation (88.2%). There were 23 males; average ejection fraction (EF) was 38.6%. Three patients developed pulmonary edema and low output immediately after the procedure. Three patients developed electromechanical dissociation during defibrillation threshold testing. A prolonged testing time for the non-thoracotomy lead system was noted when compared to the thoracotomy system (57.39 vs 32.30 min; P < 0.0000). There were more intraoperative morbidities with the non-thoracotomy leads than with the thoracotomy system. There were no perioperative deaths. The potential consequences of prolonged anesthesia time and extensive defibrillation threshold testing should be considered when choosing the route of ICD implant, the type of anesthesia, and the intraoperative testing protocol for each patient.

Defibrillators, Implantable↗

PubMed1993

Long-term stability of defibrillation thresholds with intrapericardial defibrillator patches.

From March 1982 to May 1, 1992, 105 consecutive patients underwent initial implant of cardioverter defibrillators (ICD) at our institution. Twenty-nine patients (23 male and 6 female, average ejection fraction 32.24%) with ICD systems implanted via thoracotomy and either intra- or extrapericardial patches, had one or more revisions including 56 generator changes or staged implant procedures, three patch revisions, one patch lead fracture without revision, and one sensing lead revision. The time between pulse generator revisions averaged 19.5 months. Initial defibrillation threshold mean was 12.8 joules (n = 25); at first revision, 14.46 joules (n = 29), (P = NS); by fifth revision, 15.0 joules (n = 2), (P = NS). One patch was noted to be crinkled at 70 months; one patch had migrated by 39 months, and two patch leads had fractured at the costal margin by 69 and 90 months. One patient with marginal defibrillation thresholds had an additional patch placed at revision to an upgraded ICD unit. Once acceptable defibrillation threshold (DFT) is obtained, the long-term intrapericardial DFT remains stable unless a specific problem occurs. As a small, nonstatistically significant increase in DFT may occur, caution must be exercised in patients with marginal DFTs.

Amiodarone↗

PubMed1993

Role of hypothalamic interleukin-6 and tumor necrosis factor-alpha in LPS fever in rat.

The purpose of this study was to determine, using push-pull perfusion, the levels of interleukin (IL)-1-like, IL-6-like, and tumor necrosis factor-alpha (TNF)-like activity in the anterior hypothalamus during lipopolysaccharide (LPS)-induced fever in rats. Additionally, slow anterior hypothalamic infusions of human recombinant IL-6 (hrIL-6) or TNF (hrTNF) for several hours were performed to determine possible febrile effects of these two cytokines. Artificial cerebrospinal fluid (aCSF) was infused as a control. Samples of cerebrospinal fluid were collected 60 min before and 60, 180, 300, and 420 min after the intraperitoneal injection of LPS. A control group was injected intraperitoneally with saline. The core temperature (measured by biotelemetry) of LPS-injected rats was significantly higher (P < 0.05) than the temperature of the rats injected with saline at 180, 300, and 420 min after the injection. The average postinjection IL-6 levels were significantly higher (P < 0.05) in the LPS-injected group. TNF was significantly higher (P < 0.05) than the baseline only at 180 min. There were no changes in levels of IL-1-like activity. Infusion of hrIL-6 at a level similar to the peak IL-6 level measured during LPS-induced fever resulted in a slowly developing and long-lasting increase in core temperature. Infusion of hrTNF at a level corresponding to the peak TNF level measured during LPS-induced fever did not induce a significant increase in core temperature. These results support the hypothesis that elevated hypothalamic concentrations of IL-6 are involved in the induction of fever elicited by peripheral (intraperitoneal) injection of LPS.

Animals↗

PubMed1993

Kinetics of systemic and intrahypothalamic IL-6 and tumor necrosis factor during endotoxin fever in guinea pigs.

The time course of activity of interleukin-6 (IL-6) and tumor necrosis factor (TNF) was measured in blood plasma and hypothalamic push-pull perfusates during the febrile response to intramuscular injection of bacterial endotoxin (Escherichia coli, 20 micrograms/kg) in 24 guinea pigs. Injection of endotoxin caused a dramatic increase of IL-6 activity in plasma. The logarithmic values of plasma IL-6 activities showed a linear correlation to the febrile change in body temperature (r = 0.898) during the whole time course of fever. IL-6 activity in hypothalamic perfusates increased 12-fold in the first hour after pyrogen application and declined slowly despite the further increase in body temperature. Hypothalamic IL-6 activity did not correlate with the febrile increase in body temperature (r = -0.048). TNF activity in plasma, not detectable before pyrogen application, had its peak in the first hour after endotoxin injection and rapidly declined to 15-20% of the peak activity within the next 2 h and to an undetectable value 5 h after injection. In the hypothalamus TNF was not detectable before endotoxin injection, but it could be monitored in most animals after pyrogen application without a clear correlation to the fever response. These results taken together indicate that endotoxin fever represents a physiological situation in which production and release of cytokines in the peripheral immune system and in the hypothalamus are regulated and stimulated in independent patterns.

Animals↗

PubMed1993

Neurobiological concepts of fever generation and suppression.

Fever is induced by interactions of bacterial pyrogens with cells from the immune system, which subsequently release a cascade of cytokines. After intramuscular injection of lipopolysaccharide (LPS) from E. coli, increased amounts of tumor necrosis factor (TNF) and interleukin-6 (IL-6) can be measured in blood plasma and in perfusates of the anterior hypothalamus, where body temperature is regulated. These substances are therefore candidates to be involved in the modification of thermoregulatory structures leading to the febrile rise in body temperature. This increase of body temperature is limited and sometimes even prevented by the actions of endogenous antipyretic neuropeptides like arginine vasopressin (AVP), adrenocorticotropin (ACTH) and melanocyte-stimulating hormones (MSHs) liberated within the brain or systemically during fever. For AVP, most experimental evidence confirms antipyretic pathways from the hypothalamic paraventricular nucleus to the septal area of the limbic system, which are activated during fever and by several stressful stimuli. Fever and endogenous antipyresis are interconnected and result from interactions between the immune system and the central nervous system.

Animals↗

PubMed1993

Ontogeny, circadian rhythm pattern, and hormonal modulation of 5 alpha-dihydrotestosterone receptors in the rat pineal.

Some physiological parameters of pineal 5 alpha-dihydrotestosterone receptor in the rat such as ontogeny, circadian rhythm pattern, and its modulation by various neuropeptides and neurotransmitters which have profound influences on the pineal hormone melatonin were examined. Pineal 5 alpha-dihydrotestosterone receptors measured at different ages of the animal revealed that on day 10 both cytosolic receptor (CR) and nuclear receptor (NR) levels were high. With growth and development both groups of receptors declined and during puberty started again to rise. During adulthood both receptors were high; however, NR rose further with full maturation. Both groups of receptors showed circadian rhythmicity. While the CR was significantly higher at 6.00 h than at any time point through 24 h, the NR peaked at 18.00 h when the difference between both groups was maximum. Castration caused significant increment of NR. Treatment of castrated animals with a low dose of testosterone propionate (0.25 mg) significantly stimulated both receptor groups, while treatment with a high dose (2.5 mg) failed to do so. Treatment with various substances such as antiandrogen, opioids, neuropeptides, and neurotransmitters significantly modulated the pineal androgen receptor population: cyproterone acetate and monosodium glutamate suppressed CR; growth hormone releasing hormone increased NR; growth hormone release inhibiting hormone had no significant effects on either group of receptors; exogenous melatonin and norepinephrine increased NR; beta-endorphin increased only NR, but methionine enkephalin stimulated both, and epithalamine had no significant effects on either group of receptors, but thymosin alpha 1 increased NR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

The contact allergens nickel chloride and cobalt chloride directly induce expression of endothelial adhesion molecules.

Activation of vascular endothelium is a key event in the initial phase of an inflammatory reaction e.g. to contact allergens. In the present study the effect of two common contact sensitizers, NiCl2 and CoCl2, on endothelial expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1, E-selectin) was studied. NiCl2 and CoCl2 were found to upregulate these adhesion molecules on human umbilical vein endothelial cells (HUVEC) in a dose- and time-dependent manner as could be demonstrated by flow cytometry and enzyme-linked immunosorbent assay. During organ culture of foreskin samples treatment with NiCl2 led to upregulation of ELAM-1 and ICAM-1 but not VCAM-1 on microvascular endothelium. Induction of adhesion molecules by NiCl2 was found to depend on de novo mRNA and protein synthesis and could be blocked by the protein kinase inhibitor H-7 in a dose-dependent manner but not by HA-1004 and staurosporine. An autocrine IL-1-dependent mechanism mediating NiCl2 effects could be excluded. Our data demonstrate that allergens as NiCl2 and CoCl2 are capable of directly activating endothelium which is an important step in evolving inflammatory reactions and may thus be of relevance for the pathogenesis of contact hypersensitivity.

Allergens↗

PubMed1993

Formation of autophagosomes during degradation of excess peroxisomes induced by di-(2-ethylhexyl)phthalate treatment. II. Immunocytochemical analysis of early and late autophagosomes.

We have investigated the autophagocytic process of excess peroxisomes and mitochondria induced by di-(2-ethylhexyl)phthalate (DEHP) treatment using immunocytochemical techniques. Rat liver peroxisomes were induced by 2 weeks treatment with DEHP. The animals were then injected with leupeptin (2 mg/100 g body weight), and their livers were fixed by perfusion at various intervals. The liver tissues were embedded in LR White or Epon. Semithin sections of the Epon-embedded tissue were stained for cathepsin D, B, and H, and lysosomal glycoprotein (LGP107) by the immunoenzyme technique after removal of epoxy resin. Thin sections of LR White-embedded tissue were stained for the same antigens by the immunogold technique. Some liver specimens were processed to ultracryotomy, and frozen-thawed thin sections were immunostained for carboxylesterase E1 and alpha-glucosidase II, endoplasmic reticulum (ER) markers. Twenty minutes after leupeptin injection, many peroxisomes and mitochondria were surrounded by a double-layered membrane (isolation membrane) continuous with the ER. These membranes were positive for carboxylesterase E1 and alpha-glucosidase, but not for LGP107 as well as cathepsins. Forty to 60 minutes after leupeptin injection many autophagic vacuoles showing various developing stages appeared and accumulated. The early autophagic vacuoles were surrounded by a double-layered membrane, whereas the late autophagic vacuoles had a single limiting membrane. The former was negative for cathepsins as well as LGP107, but positive for carboxylesterase E1 and alpha-glucosidase II. The results suggest strongly that the isolation membrane is derived from the ER membrane and converted later into the lysosomal membrane and support our previous morphological observations.

Animals↗

PubMed1993

[Risk of development of colorectal carcinoma in patients with ulcerative colitis].

In patients with ulcerative colitis of prolonged duration and major extent there is according to the majority of investigations an increased risk of development of colorectal carcinoma; the magnitude of the risk which is of major importance for clinical practice, however, differs according to different authors. The present study comprises 189 patients with ulcerative colitis, 103 men and 86 women, perspectively followed up for a period of 12.5 years (8.0-24.5). In 60 patients the distal form was present, in 68 left-sided colitis and in 61 pancolitis. The patients were monitored systematically--clinically colonoscopically and endoscopically. The intervals between these check-ups were gradually shorter when the disease persisted for 10 or 12 years, i.e. the patients were checked once to twice a year. The endoscopic findings were focused in particular on evidence of dysplasia. The follow-up system was modified with regard to individual conditions. In the course of the follow-up colorectal carcinoma was detected in 9 patients (4.8%) with a persistence of the disease for 9-25 years (in one patient after 9 years, in 5 after 10-20 years and in 3 after longer periods). In three instances the left-sided form was involved, in 6 pancolitis. Dysplastic changes were mostly medium grade and were found at least once in all patients. The preoperative diagnosis of carcinoma was established for certain in three patients, there was major suspicion in four patients. In two patients the carcinoma was detected only on operation (in active forms of the disease). All carcinomas were resectable, 4 times DUKES A, 4 times B, once C. As to the remaining 180 patients, 32 were operated on account of colitis; in 28 at least once dysplasia was proved, with a rising trend as the disease had a prolonged duration. These results confirm the increased risk of carcinoma in ulcerative colitis with a long duration and with a major extent and justify systematic colonoscopic and endobioptic follow-up of these patients.

Adolescent↗

PubMed1993

Endocrine pancreatic tumors in MSV-SV40 large T transgenic mice.

Mice carrying a Moloney murine sarcoma virus-(MSV) simian virus 40 large T transgene develop heritable tumors including endocrine pancreatic tumors. We have established several independent transgenic mouse lines expressing this transgene. One of these lines, designated MSV125, is characterized by the development of congenital cataracts and either pancreatic or brain tumors. The development and histopathology of the pancreatic tumors were studied by light microscopy and immunocytochemistry for large T antigen, neuron-specific enolase, insulin, proinsulin, glucagon, somatostatin, pancreatic polypeptide, gastrin, and serotonin. The 23 tumors examined were similar to human endocrine pancreatic tumors with respect to their macroscopic and histological features. We classified 91% of the tumors as insulinomas based on the predominance of insulin immunoreactivity. In newborn and young transgenic animals, nesidioblastosis and islet cell proliferation, consisting mostly of insulin containing beta cells, was obvious and persisted into adulthood. In transgenic animals more than 2 months old, islet hyperplasia and dysplasia predominated from which single tumors developed. Hyperplastic and dysplastic islets were composed mostly of beta cells. Large T antigen was detectable not only in tumor cells, but also in cells of normal and hyperplastic islets and in islet anlagen of newborn transgenic mice, indicating expression of the transgene in the endocrine part of the pancreas. Large T antigen-immunoreactivity was restricted to the beta cells. Insulinomas of the MSV-simian virus 40 T antigen-derived MSV125 transgenic mouse line may represent a valuable model for the study of the development and biology of insulinoma.

Animals↗

PubMed1993

The Omnicarbon tilting-disc heart valve prosthesis. A clinical and Doppler echocardiographic follow-up.

From 1986 to 1990, 172 patients with a median age of 60.5 years (range 20 to 79 years) received 187 Omnicarbon valves (109 aortic valve replacements, 48 mitral valve replacements, and 15 double valve replacements). Patients were followed-up for a median observation period of 2.5 years (range 4 months to 5.2 years) by clinical and Doppler echocardiographic examination. Follow-up was complete in 98%. Operative mortality (death within 30 days) was 1.7%, and linearized late mortality was 2.6% per patient-year, corresponding to an actuarial survival rate for operative survivors of 89% after 4 years. The overall 4-year postoperative survival was 87% (93% for aortic valve replacement, 77% for mitral valve replacement). Compared with age- and sex-adjusted Swiss death rates, there was an excess mortality of 5% after 4 years. Percentages for freedom from valve-related complications at 4 years are as follows: thromboembolism, 98% (aortic valve replacement, 98%, and mitral valve replacement, 96%); anticoagulant-related hemorrhage, 95%; valve endocarditis, 96%; reoperation, 96%; and permanent valve-related impairment, 99%. The overall 4-year event-free survival was 76% (80% for aortic valve replacement and 69% for mitral valve replacement). New York Heart Association class improved in 88% of the patients by 1 to 3 grades, and only 3% remained in class III after operation. For the most commonly used aortic valve (23 mm), Doppler echocardiography revealed a peak pressure gradient of 29 +/- 10 mm Hg, a fractional shortening/peak pressure gradient ratio of 1.34 +/- 0.61, and a performance index of 0.35 +/- 0.08. In the most commonly used mitral valve (27 mm), the mean pressure gradient was 4.0 +/- 2.1 mm Hg. We conclude that excellent clinical and hemodynamic results can be obtained with the Omnicarbon prosthesis, in both the aortic and mitral positions.

Adult↗