Secretion of γ-Interferon at the Cellular Level

Using a haemolytic plaque assay for gamma-interferon (IFN-gamma) secretion we found that in vitro Epstein-Barr virus (EBV) exposure of peripheral blood mononuclear cells from EBV immune individuals led to IFN-gamma secretion, which was apparent within 6 h after virus contact and peaked 12-24 h after induction. Live, ultraviolet-light-irradiated and heat-inactivated virions all caused IFN-gamma secretion. In contrast, blood mononuclear cells from EBV non-immune adults or neonates could not be activated to IFN-gamma production by EBV.     

Analysis of the Expression of I-Ak-like Antigens in Murine Fetal and Adult Tissues with the Monoclonal Antibody 10–2.16

The expression of I-Ak antigens in normal C3H/FeJ adult and 15-day embryonic mice has been investigated by indirect immunofluorescence staining of tissue cryostat sections with the anti I-Ak antigen monoclonal antibody 10-2.16. In adult mice I-Ak antigens were expressed in Langerhans-like cells in the skin, epithelium of the gastrointestinal tract, endometrium, thymic reticuloepithelial cells, and several capillary endothelia. On the other hand, these antigens were not detected in Kupffer cells, alveolar macrophages, brain or mammary gland. In 15-day-old embryos the expression of Ia-like antigens was restricted to thymic reticuloepithelial cells, isolated spleen cells, and capillaries of the gastrointestinal tract.     

Mutagenicity of bisphenol A (4,4'-isopropylidenediphenol) in vitro: effects of nitrosylation

Bisphenol A (4,4'-isopropylidenediphenol) is a common component of polycarbonate plastics and epoxy resins. Since bisphenol A-containing plastics and resins have found uses in food-contact items, its potential migration into foodstuffs and possible health consequences have been the focus of many recent studies. However, the potential mutagenic activation of bisphenol A by nitrosylation has received little attention. Incubation of bisphenol A with sodium nitrite under acidic conditions produced a yellow-brown product. When nitrosylated bisphenol A was tested in the Ames Salmonella/microsome assay at 100 ng to 1 mg/plate, dose-dependent increases in mutagenicity were found in both TA98 and TA100 Salmonella strains. These results indicated the presence of a direct-acting mutagenic activity causing both frameshift and base pair mutations, respectively. When compared to colony formation in untreated controls, the addition of rat liver S9 for metabolic activation had little influence on revertant colony formation. Unreacted bisphenol A dissolved in DMSO, acidic buffer, or inactivated nitrosylation solution showed negligible mutagenicity. When the nature of the mutagenic changes was examined using the Ames II trade mark Assay, a variety of base pair changes was found including T:A to A:T - S9, G:C to A:T +/- S9,C:G to A:T +/- S9 and C:G to G:C +/- S9. Bisphenol A also induced frameshift mutations at G:C sites. In addition, the presence of electrophiles was shown by the production of an intensely coloured orange-red product upon incubation of nitrosylated bisphenol A with the nucleophile 4-(4'-nitrobenzyl)pyridine. These findings suggest that migration of bisphenol A into nitrite containing foodstuffs, or its ingestion in the presence of nitrite, could lead to the formation of mutagenic compounds.     

CD8+ lymphocyte phenotype and cytokine production in long-term non-progressor and in progressor patients with HIV-1 infection

In most HIV-1-infected patients, clinical and immunological progression develops within a few years. Few infected people, termed long-term non-progressors (LTNP), remain healthy and immunologically stable for a long time. The factors governing the maintenance of this condition are not well known, but it is conceivable that CD8⁺ lymphocytes, cells that play a central role in controlling in vitro HIV replication, may have a part in vivo in this process. The aim of this study was to characterize the phenotypic profile and the cytokine production of CD8⁺ cells in a group of LTNP patients who had stable CD4⁺ cell counts (>500/mm³) for at least 7 years. Their CD8⁺ absolute numbers were similar to a control group composed of HIV-1⁺ patients who have a progressive decline of their CD4⁺ cell counts. However, our multiparameter immunofluorescence studies show that a clinical and immunologically stable condition is associated with the presence of a CD28⁺, CD95 strongly positive CD8⁺ population, while disease progression is marked by the CD28⁻CD95⁺CD8⁺ subset. Purified CD8⁺ cells from LTNP retain their ability to produce IL-2, interferon-gamma (IFN-γ) and, to a lesser degree, to produce IL-10 and IL-4. In contrast, CD8⁺ cells from progressors are unable to secrete IL-2 and IL-10. Although CD8⁺ cytokine profile does not fit with the proposed T helper (Th)1/Th2 switch in progressive HIV infection, LTNP CD8⁺ T cells maintain their capacity to produce IL-2 and IL-10 (Th0-like), a pattern very similar to that observed in normal HIV healthy controls. We suggest that CD8⁺ cells expressing CD28, CD95 and having a Th0-like profile may be considered to be associated with long-term survival.     

Ventricular tachycardia as a complication of annular subvalvular ventricular aneurysm in a Caucasian woman

A Caucasian female patient with repetitive attacks of ventriculartachycardia and fibrillation caused by annular submitral leftventricular aneurysm is reported. During a follow-up periodof six years after aneurysmectomy, the patient remained symptom-free.     

In Situ Study of Haemopoiesis in Human Fetal Liver

The anatomy of haemopoietic cells in human fetal liver was examined using immunohistological techniques on frozen sections of 31 fetuses (10-28 weeks gestational age). The immunohistological findings were consistent with reported cell suspension data. With regard to the location of haemopoietic activity no particular relationship existed between the various haemopoietic cell lineages. A large number of proliferating cells was present; only a few of these were reactive with haemopoietic progenitor cell monoclonal antibodies (MoAb) CD34. A population of haemopoietic cells expressed CD43 antigen (MoAb MT1) alone or together with anti-vimentin MoAb reactivity; this population needs further delineation. Erythropoiesis and myelopoiesis occurred in clusters around sinusoids and portal triad vessels respectively. Lack of MoAb reacting exclusively with early developmental stages of erythropoiesis and myelopoiesis precluded dissection of these lineages. Lymphopoiesis occurred in a loosely scattered pattern without any sign of focal development. Pre-B and B-cell numbers increased with gestational age. Cells expressing markers of more mature B cells (surface IgD, CD35, and CD21) were rare. Also, few cells reacted with mature T-cell markers, but CD7+ cells were obviously present. This expression of CD7 on haemopoietic fetal liver cells suggests that T-cell precursors develop in fetal liver as well as B cells.     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

Diabetes and its Long-term Complications in General Practice: a Survey in a Well-defined Population

The aim of this study was to assess the prevalence of long-termcomplications in all patients with non-insulin-dependent diabetesmellitus, who were known to their general practitioners (GPs).During one year 19 GPs in the area of Hoogeveen in the Netherlandsexamined their non-insulin-dependent (NIDDM) patients, includingthose under specialist's care. A detailed protocol was used;the GPs were trained in the diagnostic procedures. Complicationswere either already known from the records or newly discoveredduring screening. In a population of 41940 14.5/1000 patientswith diabetes were identified: 12/1000 NIDDM and 2.5/1000 insulin-dependent-diabetesmellitus (IDDM). Of the 509 NIDDM patients, 387 (76%) couldbe screened for late complications. Signs and symptoms of latecomplications were found in many patients: retinopathy (14%),nephropathy (57%), neuropathy (68%) and macroangiopathy (53%).The prevalence of serious complications was: proliferative retino-and maculopathy (3.3%); diabetic foot (2.6%); renal failure(2.5%). The systemic screening revealed a high number of previouslyunknown cases. It is concluded that many patients with NIDDMdevelop signs and symptoms of late complications. Most casesare identified by systemic screening only. More long-term studiesof the prognosis of late com plications in NIDDM are needed.     

MODULATION OF ALCOHOL PREFERENCE BY NMDA ANTAGONISTS IN MALE RATS

Chronic alcoholization by alcohol inhalation was used to studythe properties of magnesium, a non-competitive NMDA receptorantagonist, and CGP 39551, a competitive NMDA receptor antagonist,on behavioural dependence as estimated by the free-choice paradigm[alcohol 10% (v/v) vs. water], on the hypermotility after alcoholwithdrawal, and finally on the cortical vascularization. Thefirst experimental group received the drugs per os during thewhole alcoholization period. Magnesium (20 mg/kg/day) decreasedthe alcohol dependence while CGP 39551 (5 and 10 mg/kg/day)increased, in a dose-dependent manner, the dependence to alcohol.A second group of animals received the same drugs at the samedosages, not simultaneously during chronic alcoholization, butimmediately after alcoholization in one shot i.p. injection.In this case, rats receiving 5 mg/kg CGP 39551 never showedany dependence towards alcohol, while 10 mg/kg CGP 39551 or20 mg/kg magnesium prolonged the number of days of alcohol dependence.These results thus indicate the close interaction between NMDAreceptor function and dependence for alcohol. Magnesium hadno effects on hypermotility, while CGP 39551-treated animalspresented a decrease in the hypermotility observed after alcoholwithdrawal. Neither drug affected the hypervasculanzation accompanyingthe chronic alcoholization.     

Previous abdominal colectomy affects functional results after ileal pouch-anal anastomosis

We assessed the effect of previous abdominal colectomy on functional results after ileal J pouch-anal anastomosis (IPAA) in patients with ulcerative colitis. Twenty-five patients with colectomy prior to IPAA were compared with 22 patients who underwent noncolonic abdominal operations prior to IPAA. No differences were observed in pre- or postoperative resting anal sphincter pressure, squeeze pressure, or rectal inhibitory reflex. Previous colectomy was associated with a greater incidence of postoperative small bowel obstruction. Mean ± SEM daily stool frequency at 1 and 12 months postoperatively, respectively, was 8.9±0.8 and 5.7±0.3 for patients who had undergone previous colectomy, and 8.2±0.7 and 6.0±0.5 for the no previous colectomy group (p=not significant). At the same postoperative intervals, nocturnal stool frequency was 1.9±0.3 and 1.1±0.2 for the colectomy group and 1.5±0.3 and 0.6±0.1 for the no colectomy group (p=0.05 at 1 year). More patients in the previous colectomy group had greater than or equal to 1 nocturnal stool after 1 year (71% versus 33%,p=0.03). Although pouch capacity at 1 year was not different in the 2 groups, pouch capacity was directly related to stool frequency in the no colectomy group (r²=0.48,p=0.01), but not in the previous colectomy group (r²= 0.08,p=not significant). We conclude that previous abdominal colectomy may be associated with a higher overall incidence of small bowel obstruction. Moreover, previous colectomy is a determinant of postoperative nocturnal stool frequency after IPAA, most likely due to altered ileal pouch function. When possible, single-stage colectomy, mucosal proctectomy, and endorectal ileal pouch-anal anastomosis should be performed in patients requiring colectomy for ulcerative colitis.

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Resumen Hemos valorado el efecto de una colectomía abdominal previa sobre los resultados funcionales después de anastomosis ileoanal de bolsa en J (AIAB) en pacientes con colitis ulcerativa. Veinticinco pacientes con colectomía previa a la AIAB fueron comparados con 22 pacientes sometidos a operaciones abdominales no colónicas antes de la AIAB. No se hallaron diferencias en cuanto a la presión en reposo del esfínter anal (preoperatoria o postoperatoria), a la presión de compresión, o al reflejo rectal inhibitorio. La colectomía previa apareció asociada con una mayor incidencia de obstrucción del intestino delgado. La frecuencia de defecación diaria a 1 y a 12 meses postoperatorios, respectivamente, fue 8.9±0.8 y 5.7±0.3 para los pacientes que habían sido sometidos a colectomía previa, y 8.2 ±0.7 y 6.0±0.5 para el grupo sin colectomía previa (p=NS). En los mismos períodos postoperatorios la frecuencia de defecación nocturna fue 1.9±0.3 y 1.1±0.2 para el grupo con colectomía previa y 1.5±0.3 y 0.6 ±0.1 para el grupo sin colectomía (p=0.05 a 1 año). Más pacientes en el grupo de colectomía previa presentó más de una o una deposición nocturna después de un año (71% versus 33%, p=0.03). Aunque la capacidad de la boisa a un ano no apareció diferente en los 2 grupos, la capacidad de la bolsa apareció directamente relacionada con la frecuencia de la deposición en el grupo sin colectomía (r²=0.48,p=0.01), pero no en el grupo con colectomía previa (r²=0.08,p=NS). Nuestra conclusión es que una colectomía abdominal previa puede estar asociada con una mayor incidencia de obstrucción del intestino delgado. Además, la colectomía previa aparece como un factor determinante de la frecuencia de defecación nocturna después de AIAB, muy probablemente por alteración de la función de la bolsa ileal. En cuanto sea posible, se debe realizar la colectomía, proctectomía mucosal, y anastomosis ileal endorrectal en una sola etapa en los pacientes que requieran colectomía por colitis ulcerativa.

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Résumé Nous avons chercher à savoir si le fait d'avoir déjà effectué une colectomie retentissait sur les résultats de fonctionnement de l'anastomose iléo-anale avec réservoir en J (AIAR) chez le patient avec rectocolite hémorragique. Vingt cinq patients ayant eu une colectomie avant d'être opérés de leur AIAR ont été comparés à 22 patients ayant une intervention abdominale sans colectomie avant d'être opérés de leur AIAR. Aucune différence dans la pression sphinctérienne au repos pré ou post-opératoire, dans la pression de contraction ou dans le réflexe inhibiteur rectal n'a été observée. La colectomie préalable était associée à une incidence élevée d'occlusion intestinale post-opératoire. Le nombre de selles à 1 et à 12 mois post-opératoires était de 8.9±0.8 et 5.7±0.3, respectivement, chez le patient sans chirurgie colique antérieure (NS). Aux mêmes intervalles, la fréquence de selles nocturnes était de 1.9 ±0.3 et de 1.1±0.2 pour le groupe à colectomie préalable et de 1.5±0.3 et 0.6±0.1 pour le groupe sans chirurgie colique préalable (p=0.05 à un an). Dans le groupe à colectomie préalable, il y avait plus de patients qui avaient une ou plusieurs selles nocturnes après la première année (71% versus 33%;p= 0.03). Bien que la capacité du réservoir ne différait pas à 1 an entre les 2 groupes, la capacité était directement en rapport avec la fréquence des selles dans le groupe sans chirurgie colique préalable (r²=0.48; p=0.01), mais sans rapport dans le groupe avec chirurgie colique préalable (r²=0.08, p=NS). Nous concluons que la colectomie préalable est asscoiée à une incidence d'occlusion post-opératoire supérieure. De plus, la colectomie préalable est associée à une fréquence plus élevée de selles nocturnes après AIAR, probablement liée à un dysfonctionnement du réservoir. Lorsque la colectomie totale avec mucosectomie rectale, avec anastomose iléo-anale et réservoir est indiquée chez le patient ayant une rectocolite hémorragique, il vaut mieux la faire en un seul temps.

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Presented at the Société Internationale de Chirurgie, Toronto, Ontario, Canada, September, 1989.