Role of interleukin-17F in chronic inflammatory and allergic lung disease

IL-17 family members belong to a distinct category of cytokines that coordinate local tissue inflammation by inducing the release of pro-inflammatory and neutrophil-mobilizing cytokines. The importance of the IL-17 family in inflammatory and autoimmune disease is becoming increasingly apparent. IL-17F is a recently discovered member of the IL-17 family that has a number of biological activities through induction of various cytokines, chemokines, and mediators. IL-17A, the founding member of the IL-17 family, and IL-17F are produced by several inflammatory cells, including activated T cells, in response to infectious and antigenic stimuli. Overexpression of IL-17A or IL-17F in the lungs results in induction of CXC chemokines and neutrophil recruitment. In a case-control study of 1125 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in the third exon of the IL17F gene was shown to be associated with asthma and chronic obstructive pulmonary disease (COPD). Functionally, this variant failed to induce cytokines and chemokines, and interestingly, was able to antagonize the activity of wild-type IL-17F. These results provide an experimental basis for the observed genetic association with chronic inflammatory lung diseases, and also suggest the potential therapeutic utility of this antagonistic variant of IL-17F. Given that asthma and COPD are complex diseases involving a number of genetic and environmental factors, the genetic impact of IL-17F H161R with regard to the development of chronic airway inflammation likely varies among individuals with different genetic backgrounds and environmental exposures.     

Acute hemorrhagic colitis induced by the neuraminidase inhibitor oseltamivir]

A 23-year-old woman had lower abdominal pain, diarrhea and bloody stool was admitted and given a diagnosis of influenza B. Her home doctor had started treatment by neuraminidase inhibitor (oseltamivir) the previous day. Colonoscopic examination revealed an area of hemorrhage and erosion in the left transverse colon. After halting oseltamivir treatment these symptoms disappeared and her colonoscopic findings improved. A drug-induced lymphocyte stimulation test was positive for oseltamivir. This case is the first reported case of acute hemorrhagic colitis induced by oseltamivir.     

Left anterior hemiblock studied by computer graphic electrocardiography

In order to find the three-dimensional distribution of ventricular depolarization potentials in left anterior hemiblock (LAHB) diagnosed by the conventional scalar ECG, 7 subjects with LAHB aged 9 to 62 years old who were otherwise healthy were studied by computer graphic electrocardiography (CGECG).Two modes of the initial ventricular depolarization (IVD) were noted. (1) The IVD appeared irregularly and separately on the mid- to lower central region of the anterior body surface. (2) The IVD appeared in a form rather like a parallelogram on the central region of the anterior body surface. Both (1) and (2) potentials propagated toward the left middle, lower, and lateral regions of the anterior body surface as normally observed; however, they were far lower in voltage than those observed in intact subjects.From the results, it has been concluded that LAHB may be, not a block, but rather a defective ventricular septal conduction.Presented at the 34th Annual Congress, International College of Angiology, Budapest, Hungary, July 1992.     

A case of retroperitoneal venous aneurysm]

A case of retroperitoneal venous aneurysm is reported. A 73-year-old woman was referred to us with the chief complaint of left abdominal mass. A giant abdominal mass was palpable and diagnostic imaging examination including ultrasound tomography, excretory pyelography, computed tomography, magnetic resonance imaging and angiography revealed a giant cystic mass encircled by calcification in the left retroperitoneal space. Operation for this cystic mass was performed under the preoperative diagnosis of a giant left renal cyst. During operation the mass was located between the left kidney and the left adrenal gland. Because it was difficult to separate the mass from the left kidney the mass was removed with the left kidney. The extirpated tumor measured 15.5 x 15.0 x 9.5 cm and contained old blood clots and red-yellow colored fluid. A histological examination revealed that the tumor wall was composed of smooth muscle and elastic fibers. Therefore, pathological diagnosis was retroperitoneal venous aneurysm. Retroperitoneal venous aneurysm is very rare. To our knowledge, this is the 8th case of retroperitoneal venous aneurysm reported in Japan.     

Mechanism of hematuria. II. A scanning electron microscopic demonstration of the passage of blood cells through a glomerular capillary wall in rabbit Masugi nephritis

A model of hematuria was established in rabbits. An accelerated form of unilateral Masugi nephritis was induced in 10 New Zealand white rabbits by an intravenous injection of duck antirabbit kidney serum and by ligating the left renal artery immediately after the injection of the antibody. All 10 rabbits became hematuric 1-2 weeks after the injection of the antibody and red blood cell (RBC) casts were found in the urinary sediment of all these animals. An ultrastructural examination of renal glomeruli by transmission electron microscopy revealed the transcapillary passage of polymorphonuclear leukocytes through the gaps of the glomerular basement membrane (GBM). RBC were found in the urinary space in 50% of the glomeruli observed by scanning electron microscopy (SEM) and the passage of leukocytes and RBCs through the glomerular capillary wall was also observed. Gaps in the GBM became clearer after the removal of cellular components by detergents. In control rabbits, no RBCs could be observed in the urinary space, and isolated GBM were intact by SEM. These data further support the hypothesis that in rabbit Masugi nephritis hematuria is a result of the passage of RBCs through gaps in the GBM.     

Antiinflammatory properties of the new antirheumatic agent 4-acetylaminophenylacetic acid

The antiinflammatory activity of 4-acetylaminophenylacetic acid (MS-932) was investigated. MS-932 did not suppress the acute inflammation of carrageenin-induced paw edema in rats or of primary swelling in adjuvant arthritic rats. However, prophylactic treatment with MS-932 inhibited secondary inflammation in adjuvant arthritic rats. MS-932 also restored to normal the weight of the spleen and the serum albumin/globulin ratio of adjuvant arthritic rats. In addition to its prophylactic effect, MS-932 had a therapeutic effect on adjuvant arthritis. In in vitro tests, MS-932 did not inhibit prostaglandin E2 biosynthesis from arachidonic acid by sheep seminal vesicle microsomal enzyme or superoxide generation by guinea pig neutrophils stimulated with opsonized zymosan. MS-932 had no analgesic effect in mice and no antipyretic effect in rats. These results indicate that MS-932 suppresses adjuvant arthritis through modulation of the immune system.     

Using adiabatic inversion pulses for long-T2 suppression in ultrashort echo time (UTE) imaging.

Ultrashort echo time (UTE) imaging is a technique that can visualize tissues with sub-millisecond T(2) values that have little or no signal in conventional MRI techniques. The short-T(2) tissues, which include tendons, menisci, calcifications, and cortical bone, are often obscured by long-T(2) tissues. This paper introduces a new method of long-T(2) component suppression based on adiabatic inversion pulses that significantly improves the contrast of short-T(2) tissues. Narrow bandwidth inversion pulses are used to selectively invert only long-T(2) components. These components are then suppressed by combining images prepared with and without inversion pulses. Fat suppression can be incorporated by combining images with the pulses applied on the fat and water resonances. Scaling factors must be used in the combination to compensate for relaxation during the preparation pulses. The suppression is insensitive to RF inhomogeneities because it uses adiabatic inversion pulses. Simulations and phantom experiments demonstrate the adiabatic pulse contrast and how the scaling factors are chosen. In vivo 2D UTE images in the ankle and lower leg show excellent, robust long-T(2) suppression for visualization of cortical bone and tendons.     

Clinical significance of 201Tl reverse redistribution in patients with aorto-coronary bypass surgery

Detection of myocardial ischemia by the stress thallium scan has traditionally been performed using transient defect analysis on exercise, followed by redistribution studies. Worsening of the ²⁰¹Tl myocardial image from exercise to redistribution is referred to as reverse redistribution. In this study, we found reverse redistribution in 10 (21%) of 48 angina pectoris patients who had undergone aortocoronary bypass surgery. The clinical significance of this phenomenon in these patients was investigated in relation to angiographic and surgical findings. Reverse redistribution was found to occur in regions which were supplied by bypass grafts. These areas showed increased coronary blood flow and rapid thallium washout. Our results indicate that a perfusion defect in the bypass region of the redistribution image might be caused by relatively rapid washout in the bypass graft region compared to the adjacent normal myocardium. These results should be considered in the clinical interpretation of stress thallium scans.     

Pericardial fibrosarcoma demonstrated by Ga-67 scintigraphy

A case of malignant fibrosarcoma originated from pericardium was reported. A 31 year-old female who complained of general fatigue and back pain showed dilated cardiac shadow in chest X-ray. Cardiac blood pool scan with 99mTc-RBC revealed avascular mass in pericardial cavity which push the heart up and left side. It was suspected to be malignant, since the mass had increased 67Ga uptake. CT and MRI also demonstrated that the tissue characterization of the pericardial mass was irregular, and the mass compressed venous return. The large mass originated from pericardium caused the right sided cardiac failure. In 12 years ago, she had a history of operation which resected benign hemangioma in the same space (pericardium). We could suspect the malignant transformation between the two rare pericardial tumors; benign hemangioma and malignant fibrosarcoma.     

Noradrenergic excitatory inputs to median preoptic neurones in rats.

Extracellular single-unit activity was recorded from 21 median preoptic nucleus (MnPO) neurones, antidromically identified as projecting to the hypothalamic paraventricular nucleus (PVN), in urethane-anaesthetized male rats. Of these identified MnPO neurones, 14 displayed an excitatory response in neuronal excitability following electrical stimulation (5 Hz, 600 microA) of the A1 noradrenergic region of the ventrolateral medulla, while the remaining neurones were unresponsive. The excitatory response of MnPO neurones was blocked by microiontophoretically applied phentolamine, an alpha-adrenoceptor antagonist, but not by timolol, a beta-adrenoceptor antagonist. These results suggest that the A1 region acts to enhance the activity of MnPO neurones projecting to the PVN via an alpha-adrenoceptor mechanism.