Human orbital fibroblasts are activated through CD40 to induce proinflammatory cytokine production

CD40 is an important signaling and activation antigen found oncertain bone marrow-derived cells. Recently, CD40 has also been shownto be expressed by nonhematopoietic cells, including certain humanfibroblasts, but not others. Little is known about the function of CD40on fibroblasts. The current study investigates the hypothesis that CD40is expressed on orbital fibroblasts and represents a pathway forinteraction between these fibroblasts and CD40 ligand-expressing cells,such as T lymphocytes and mast cells. We report here that orbitalconnective tissue fibroblasts, obtained from normal donors and frompatients with severe thyroid-associated ophthalmopathy (TAO), expressfunctional CD40. CD40 is upregulated ~10-fold by interferon- (500 U/ml) treatment for 72 h. These fibroblasts become activated throughtriggering of CD40 with CD40 ligand (CD40L). This is evidenced bynuclear translocation of nuclear factor-B and induction of theproinflammatory and chemoattractant cytokines interleukin-6 andinterleukin-8, respectively. These data support the concept thatcognate interactions between orbital fibroblasts and infiltrating Tlymphocytes, via the CD40-CD40L pathway, may promote the tissueremodeling observed in TAO and other inflammatory diseases of theorbit. Disruption of the CD40-CD40L interaction may represent atherapeutic intervention to reduce the inflammatory components of TAO,which remains a vexing clinical problem.

     

A Serum Bottle Modification of the Hungate Technique for Cultivating Obligate Anaerobes

The modification described utilizes a serum bottle closed with a butyl rubber stopper with a crimped metal seal for the growth of obligately anaerobic bacteria.     

Simplified Method for the Preparation of Silica Gel Media

A simplified and reliable method for the preparation of a variety of silica gel media is described. The growth of common microorganisms on these media was examined.     

Cellular energy metabolism during fetal development. II. Fatty acid oxidation by the developing heart

In view of the importance of fatty acids as substrates for the mature heart, fatty acid oxidation by fetal and calf heart mitochondria has been investigated. Free fatty acids of 10 carbon units or less which exhibit carnitine-independent transport into mitochondria were effective substrates for oxidative phosphorylation in both fetal and calf heart mitochondria. Efficient oxidative phosphorylation with these substrates was dependent upon the presence of bovine serum albumin in the assay medium to reverse the uncoupling effects of the fatty acids. In the presence of bovine serum albumin, ADP/0 ratios were in the range of 3 when short-chain fatty acids and carnitine esters of short- and long-chain fatty acids were substrates. Compared with calf heart mitochondria, fetal heart mitochondria showed decreased carnitine-dependent oxidation of palmityl-CoA. However, the oxidation of palmitylcarnitine was identical in both. These data suggest that the formation of palmitylcarnitine is rate limiting for palmityl-CoA oxidation by the fetal heart mitochondria and that long-chain fatty acids are not readily oxidized by the fetal heart.     

Studies on haptoglobin and transferrin types in Khatris and Aroras of Punjab,India

Summary Using horizontal starch gel electrophoresis along with the discontinuous buffer system, resolution of haptoglobin and transferrin bands has been obtained for 200 Khatris and Aroras of Punjab. One Khatri individual possessing Hp1-P variant and another Khatri individual possessing, as yet unclassified, Hp2-1(m) was found in this series. Common CC type transferrin bands characterise Khatris and Aroras.

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Zusammenfassung Mit Hilfe der horizontalen Stärkegel-Elektrophorese und eines diskontinuierlichen Puffer-Systems wurden die Haptoglobin- und Transferrin-Typen bei 200 Khatris und Aroras aus dem Punjab untersucht. In dieser Serie fand sich ein Khatri-Individuum mit einer Hp1-P-Variante und ein anderes Khatri-Individuum mit einer noch unklassifizierten Hp2-1(m)-Variante. Beide Bevölkerungen sind durch das ausschließliche Vorkommen des häufigen Transferrin CC-Typs charakterisiert.

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Earlier papers of the author are published in her maiden name of S. Anand.     

Vascular dynamics

A study, using the four-electrode impedance plethysmograph system, was completed to evaluate simultaneous variations in conduction of upper and lower body segments relative to displacement of blood volume during change in body position. Measurements of cardiac output were compared with simultaneous results by dye dilution methods as a means of assessing the use of impedance techniques to determine cardiac output during tilt table studies. Two groups, 48 healthy private pilots and 22 patients with diabetes mellitus, were tested and the results were compared.Control and test heart rate values were higher in the afternoon than in the morning for the same healthy subjects, and the blood pressure and heart rate changes paralleled the variations in stroke volume and calf blood pulse changes. The results in the patients with diabetes differed markedly in terms of the magnitude of the cardiovascular changes and indicated the value of the tilt table in assessing fatigue in the circulatory system as a result of metabolic disturbance. The change from horizontal to 65 degree head up position in the patients with diabetes showed a marked fall in thoracic stroke and conductive volume in contrast to the minimal decrease observed in healthy subjects.Symbols resistivity, ohm cm - L length or distance between detecting electrodesE ₁-E ₂, cm - E voltage, volts - I current, amps - R ₀ segmental resistance between detecting electrodesE ₁-E ₂, ohms - V ₀ segmental volume equivalent to (L ²/R ₀), ml - V change in volume, ml - R change in resistance, ohms Terms Impedance plethysmography Measurement of change in volume due to variation in electrical resistance of a segment to a 50 or 120 kHz signal. The impedance at these frequencies is primarily resistive - Four electrodes Two electrodes for introduction of the reference signal to the examined segment and two electrodes for detecting variation in conduction of the signal - Conduction The reciprocal of resistance measured in mohs. - Conductive volume The volume defined byV ₀=(L ²/R ₀) containing electrolytes including whole blood and plasma This project was supported by Contract NAS4-1321, NASA Flight Research Center, Edwards, California, U.S.A.