IFN-gamma is a crucial mediator in the induction of cell-mediated Th1-type responses but is predominantly a negative regulator of B cell differentiation and proliferation. This cytokine is therefore a key factor in determining Th1 vs Th2 differentiation. This study investigates the action of IFN-gamma in modulation of HLA-DR expression and Ag presentation by EBV-transformed human B cell lines. In contrast to its action on the monocyte/macrophage, IFN-gamma down-regulates surface MHC expression on these B cells, and this regulation is posttranscriptional. In parallel with MHC down-regulation, there is a reduced capability to process and present exogenous protein and peptide Ag to T cell hybridomas. IFN-gamma does not change the rates of fluid phase endocytosis or exocytosis in this model system but correlates with an up-regulation of the lysosomal enzymes cathepsins B and D.

Animals↗

PubMed1999

Vectorial function of major histocompatibility complex class II in a human intestinal cell line.

This study explores the expression and the function of major histocompatibility complex class II in the intestinal epithelial cell line CaCo-2, which has been widely used as a model for the human gastrointestinal epithelium. Human leucocyte antigen (HLA)-DR expression on CaCo-2 cells is induceable by interferon-gamma (IFN-gamma), but responsiveness to IFN-gamma is dependent on cell differentiation and IFN-gamma availability at the basolateral cell surface. HLA-DR expression is concentrated in apical cytoplasmic vesicles and on the basolateral cell surface. Invariant chain is expressed in apical vesicles but is absent from the cell surface. Immunoprecipitation studies show a slow rate of dissociation of HLA-DR from Ii. Double labelling shows some overlap between HLA-DR expression and basolateral endosomal markers but no overlap with apical endosomal markers. Functional studies show processing and presentation of lysozyme endocytosed from the basolateral, but not apical surfaces. CaCo-2 cells may provide a useful model with which to dissect the antigen-processing pathways in polarized epithelial cells. The regulated access of antigens taken up from the gut lumen to the processing compartments may prevent overloading the immune system with antigens derived from normal gut contents.

Antigen Presentation↗

PubMed1998

In vivo priming of T cells against cryptic determinants by dendritic cells exposed to interleukin 6 and native antigen.

T cells recognizing poorly displayed self determinants escape tolerance mechanisms and persist in the adult repertoire. The process by which these T cells are primed is not clear, but once activated, they can cause autoimmunity. Here, we show that dendritic cells treated with interleukin 6 (IL-6) process and present determinants from a model native antigen in a qualitatively altered hierarchy, activating T cells in vitro and in vivo against determinants that were previously cryptic because of poor display. IL-6 does not induce conventional maturation of dendritic cells but alters the pH of peripheral, early endosomal compartments and renders the cells more susceptible to killing by chloroquine. Acidification of endosomes by ouabain mimics the effect of IL-6 and allows processing of the same cryptic determinant. These results suggest that cytokines such as IL-6 could initiate and help to propagate an autoimmune disease process by differentiating dendritic cells into a state distinct from that induced by normal maturation.

Animals↗

PubMed1996

Ceratomyxa drepanopsettae in the gallbladder of Atlantic halibut, Hippoglossus hippoglossus, from the northwest Atlantic Ocean.

Trophozoites of Ceratomyxa drepanopsettae Averintsev, 1907 (Myxosporea: Ceratomyxidae) containing prominent refractile granules were found in the gallbladders of all but one of eight halibut, the exception being a single juvenile. They ranged in shape and size from globular forms 5-10 micron in diameter, to rounded structures with pseudopodia and one or more processes that were up to 500 micron in length and packed with refractile granules. Some trophozoites were free in the bile, while others were attached to the epithelium of the gallbladder wall by pseudopodia which extended between the microvilli. Many free trophozoites were attached to each other by septate junctions between their pseudopodia. There were small cylindrical papillae on the surface of the trophozoites, and the rounded portions contained two vegetative nuclei, generative cells (some attached by junctions) and, in many cases, feeding vacuoles. During sporogony, a binucleate sporoplasmic cell and the capsulogenic cells of some sporoblasts were engulfed by valvogenic cells before they began to differentiate; whereas other sporoblasts consisted of six cells attached to each other, two being capsulogenic cells containing external tubes, two sporoplasmic cells and two valvogenic cells. There was a septate junction around the opening of the rounded polar capsule of the spore, between the capsulogenic and valvogenic cell. Sporoplasmosomes appeared to form in smooth membraned vesicles, possibly part of the Golgi apparatus. Spores had thin, delicate membrane, and elongate shell-valves, most of which were asymmetric, and bent or folded. A sporoplasm extended on either side of the distinct, straight suture line, but did not penetrate into the valves.

Animals↗

PubMed1994

The use of botulinum toxin for treatment of acquired nystagmus and oscillopsia.

PURPOSE: To evaluate the role of botulinum toxin A (BTA) in treating patients with diminished visual acuity secondary to acquired nystagmus and oscillopsia. METHODS: Twelve patients with acquired nystagmus causing oscillopsia and reduced vision were treated with injection of BTA. Botulinum toxin A was injected directly into the horizontal recti in three patients, and in nine patients retrobulbar BTA was administered. Injections were given at 3- to 4-month intervals and repeated as long as patients noted improvement in their quality of life. RESULTS: Improvement in visual function varied, and not all patients benefited from the procedure. However, 8 of 12 patients demonstrated a measurable improvement in visual acuity. Transient ptosis was the most common side effect. CONCLUSION: Retrobulbar BTA provides a simple and safe alternative in managing a condition for which alternative treatments are typically unsatisfactory.

Adult↗

PubMed1994

Soft tissue cervical metastases of squamous carcinoma of the head and neck.

Some 497 of 3085 patients with squamous cell carcinoma of the head and neck treated between 1963 and 1990 had a later radical neck dissection at some time after initial treatment. The histological slides were all reviewed, firstly to confirm the presence of squamous cell carcinoma within the neck, and secondly to ascertain whether the metastasis was to soft tissue, to a lymph node or to both. The presence of extracapsular rupture in lymph node deposits was also assessed. Of the 497 patients, 138 had soft tissue deposits only, and 359 had nodal deposits only. Of the patients with nodal deposits 165 had extracapsular rupture and 194 did not. The 5-year survival of the 138 patients with soft tissue metastases was 27% compared with 33% for patients with extracapsular rupture and 50% for patients with no extracapsular rupture. Weighted logistic regression showed that soft tissue deposits were significantly more common in patients in poor general condition, plus poorly differentiated squamous cell carcinoma plus T4 tumours (P < 0.005), and in patients with poorly differentiated squamous cell carcinoma plus T4 tumours (P < 0.025). Cox's multivariate analysis with backward elimination showed that gender, histological differentiation, site of primary tumour and age of patient had no statistically significant effect on survival. The number of nodes (P < 0.0001), the presence of extracapsular rupture (P < 0.0001) and the presence of soft tissue free metastases (P < 0.001) were all highly significant. The N-status at recurrence also reached statistical significance (P < 0.0001).

Carcinoma, Squamous Cell↗

PubMed1992

Osseous expansion of the cranial vault by craniotasis.

A study of cranial vault lengthening using a custom expandable fixation-distraction (craniotatic) appliance was performed in the young-adult rabbit model. Ten 24-week-old rabbits underwent circumferential suturectomy plus expansion (expanded group), 10 underwent circumferential suturectomy without expansion (sham control group), and 10 served as normal controls. The appliance was lengthened at a rate of 2.5 mm per week for 5 weeks. Serial lateral cephalometry, comparative dry-skull anthropometric measurements, and histologic examinations were performed. The expanded group demonstrated a significantly longer skull, cranial vault, anterior cranial base, posterior face, and orbit as compared with the control groups (p less than 0.05). Callus bone filled the distracted suturectomy and united the frontofacial complex to the posterior cranium. In conclusion, skull lengthening by distraction osteogenesis is possible in the rabbit model and offers a new technique for future investigation in the treatment of coronal synostosis.

Analysis of Variance↗

PubMed1991

Hemitonic seizures: etiological and diagnostic considerations.

Intermittent unilateral tonic posturing of the limbs may relate to focal motor epilepsy, intermittent dystonia or hysteria, and diagnosis may be difficult. Five patients are presented who illustrate two distinct hemitonic syndromes which we believe to be epileptic, namely forced elevation of one arm and paroxysmal hemispasm. It is suggested that these attacks follow an irritative lesion involving the supplementary motor cortex and a deep lesion involving striatothalamic projections respectively. Brevity of episodes, their stereotyped nature and rapid response to anticonvulsant drugs supports an epileptic etiology. The term paroxysmal hemidystonia may not be appropriate for patients with intermittent stereotyped disorders of limb posture, where the clinical features support an epileptic basis and we suggest the designation hemitonic seizures.

Adult↗

PubMed1989

The Noonan syndrome/cherubism association.

Noonan syndrome is characterized by short stature, unusual facies, congenital heart disease, chest deformity, mild mental retardation, and cryptorchidism in males. It may be sporadic or inherited as an autosomal dominant trait and occurs between 1 in 1000 and 1 in 2500 live births. Cherubism is a giant cell lesion of the jaws thought to be transmitted as an autosomal dominant trait. It is usually recognized by age 7 years, follows a variable course, and is not known to be related to other genetic disorders. We herein report on four patients with Noonan syndrome, all of whom had cherubism. Two other probable cases are cited in the literature for a total of six known cases.

Cherubism↗

PubMed1989

Transient compartment syndrome of the forearm resulting from venous congestion from a tourniquet.

A case of transient compartment syndrome of the forearm resulting from faulty tourniquet function is described. The patient was followed with serial compartmental pressure measurements. Signs and symptoms subsided within a few hours of limb elevation. Thus, conservative care in the early stages may be therapeutic. Early recognition of tourniquet malfunction, systematic assessment of the source of engorgement, and prompt correction can avoid this post-operative complication.

Compartment Syndromes↗

PubMed1972

Photoreceptor-pigment epithelial cell relationships in rats with inherited retinal degeneration. Radioautographic and electron microscope evidence for a dual source of extra lamellar material.

Protein synthesis and displacement in photoreceptor and pigment epithelial cells of inbred normal (Fisher) and mutant (RCS) rats with inherited retinal degeneration has been studied by light and electron microscope radioautography. Groups of animals 14, 15, 17, 19, 27, 35, and 50 days of age were injected with amino acids-H(3) and killed at subsequent time intervals. In normal rats, radioactive protein synthesized in the rod inner segments was incorporated into outer segment saccules and displaced outward; the total renewal time of outer segments at all ages was approximately 9 days. In RCS photoreceptors, outer segment displacement was slowed from the normal rate before day 17 and at all subsequent stages. Most of the newly synthesized protein appeared to migrate only into the basal third of the outer segments. Labeling of pigment epithelial cells in RCS rats was always heavier than in controls. Labeled protein was displaced as early as 1 hr postinjection from pigment epithelial cell somas into the apical processes, and by 2 hr postinjection was located in the adjacent lamellar whorls characteristic of the mutant rat retina. After 1 day, radioactivity was present in the 14, 15, 17, and 19 day series of RCS rats in the apical third of the outer segment layer (occupied mainly by extra lamellar material) while there were few silver grains in the middle third of the layer (occupied mainly by distal parts of outer segments). The RCS pigment epithelial cells thus have an unusual synthetic role and appear to be a source of the extra lamellar material. Electron microscope examination revealed that many intact pigment epithelial cell processes were incorporated into the large whorls of extra lamellae. In addition, many disorganized outer segment saccules were observed in continuity with longer membranous lamellae and large lamellar whorls. The extra lamellar material therefore appears to be derived from both rod outer segments and pigment epithelial cells.

Age Factors↗

PubMedDate not supplied

[Investigation of electrophysical properties of Listeria monocytogenes cells during the interaction with monoclonal antibodies].

An electrooptical approach was used in studies of Listeria monocytogenes-antibody binding. An electrooptical analyzer, which has been developed at the State Research Center for Applied Microbiology (Obolensk, Russia), was used as a basic instrument for electrooptical measurements. The analyzer consists of the following modules: a sample preparation module, a mixer, an AC field generator, an EO-flow cell, a microcontroller for transfer of liquid, a thermal system, an operator interface, and an image processor. The sample preparation module includes a unit for an automatic filter changing device and a hydraulic system. Since the AC electrokinetic effects depend on the dielectric properties of bioparticles, their composition, morphology, phenotype, the medium, and the frequency of applied electrical field, the electroorientational spectra were used for discrimination of different types of bacteria, a given type being "controlled" (and identified) by the selective choice of binding agents (antibodies). The measurements were performed using a discrete set of frequencies of the orienting electric field (10, 100, 250, and 500 kHz). During biospecific interactions, an antibody is bound to the microorganism, causing a change in the dielectric properties of the microorganism-antibody complex, and the electrooptic signal reaches its maximum at 100-200 kHz. It was shown that the biospecific interactions of Listeria monocytogenes cells with anti-Listeria antibody in the presence of E. coli K-12, and A. brasilense sp7 significantly change the electrooptical signals. Thus, the determination of the presence of particular bacteria within a mixed sample may be achieved by selection and matching of antibodies specific to individual bacterium types and by comparing the spectra of bacterium in the presence and in the absence of specific binding agent (antibody).

Antibodies, Monoclonal↗

PubMedDate not supplied

[The electrooptical parameters of suspensions of Escherichia coli XL-1 cells interacting with helper phage M13K07].

The electrophysical properties of Escherichia coli XL-1 cells interacting with helper phage M13K07 were studied as a function of the phage-to-cell ratio and the contact time. The electro-optical signal of bacterial cells changed considerably as soon as 10 min after the onset of their incubation with phage particles, presumably due to phage adsorption on the cell surface. The maximum changes in the orientational spectra of cell suspensions were observed when the phage-to-cell ratio was 20. Selectivity studies showed that E. coli XL-1 cells interacting with the helper phage M13K07 in the presence of foreign microflora, such as E. coli K-12 or Azospirillum brasilense Sp7, can be identified by using their electrophysical properties. Changes in the orientational spectra of cell suspensions are interpreted with the stage of phage-bacterium interaction taken into account. The results obtained can probably be used to devise a new rapid method for identification of microorganisms and to study the particular stages of cell infection by bacteriophages.

Bacteriophage M13↗