Different kinetics of antiviral and anticellular activities between human recombinant and natural interferon-gamma arising from different receptor-binding properties

Human recombinant interferon-gamma (ReIFN-gamma) and human natural interferon-gamma (IFN-gamma) showed significant differences in antiviral and anticellular activities. Namely, ReIFN-gamma exhibited antiviral activity against Sindbis virus and anticellular activity against HeLa S3 cells at significantly lower concentrations as compared with IFN-gamma at short exposure times of between 1 and 4 hr. This difference of activities was explicable in terms of different binding activities of the two IFNs to the receptors. The binding of 125I-ReIFN-gamma to the receptors was competitively decreased in a dose dependent manner by unlabeled ReIFN-gamma, whereas the competition by unlabeled IFN-gamma was significantly weaker. The results of pretreatment of the cells with unlabeled ReIFN-gamma or IFN-gamma suggested that the binding of IFN-gamma to the receptors was slower than that of ReIFN-gamma. ReIFN-gamma and IFN-gamma exhibited greater colony formation-inhibitory activity against HeLa S3 cells, as compared with IFN-alpha or ReIFN-beta. ReIFN-gamma also inhibited DNA, RNA and protein syntheses of HeLa S3 cells more potently than ReIFN-beta. However, the 2'-5' oligoadenylate (2'-5' A) synthetase activity in ReIFN-gamma-treated cells was significantly lower than that in ReIFN-beta-treated cells, suggesting that 2'-5' A synthetase does not play a major role in the anticellular activity of ReIFN-gamma, at least against HeLa S3 cells.     

Comparison of the production of cyclic AMP in response to parathyroid hormone in fibroblasts from aged subjects and young subjects: lack of an age-dependent decrease

An age-dependent effect on the ability to produce cyclic AMP in response to parathyroid hormone (PTH) stimulation was examined using culture skin fibroblasts from both young and elderly female subjects. The mean values of both absolute and comparative production of intracellular cyclic AMP due to various concentrations of PTH administration did not differ between the two age groups, although the mean serum PTH level was significantly higher in the elderly subjects. These results indicate that the decreased response of the target organ to PTH in aged subjects can be explained mainly by the decreased number of intact cells rather than a decreased response of individual cells to PTH.     

A clinical study of intraarterial infusion therapy with CDDP for primary osteosarcoma

Eleven patients with primary osteosarcoma were treated by intra-arterial infusion of cisplatin. Cisplatin (50-100 mg/m2) was infused slowly into tumor feeding artery or proximal-to-the-lesion artery. An antidote, sodium thiosulfate, was also administered intravenously in 10 cases and angiotensin II was simultaneously used in 2 cases. Symptoms of heat sensation and local pain were decreased or disappeared in almost all cases and histopathologic changes were observed in 7 cases. No viable tumor cells were seen in 3 cases.     

Two autopsied cases of arrhythmogenic right ventricular dysplasia

Autopsy studies of arrhythmogenic right ventricular dysplasia (ARVD) have rarely been reported, and its etiology remains unknown. The present report describes a detailed histopathological study of two autopsied cases of ARVD. Case 1: This 21-year-old man experienced palpitation accompanied by syncope. He died after ventricular tachycardia of right ventricular origin. The heart weighed 365 g and the right ventricular cavity was markedly dilated. The distribution of fatty tissue was roughly limited to the middle layer of the free wall, replacing the myocardium with fatty degeneration. Medial hyperplasia of the small arteries within the fatty tissue was also observed. Fibroelastosis was observed in the left ventricular endocardium. In the conduction system, fatty tissue was found in the sinus node. In addition, medial hypoplasia was observed in the pulmonary arteries. Case 2: This 32-year-old man who had had an arrhythmia for 10 years died of ventricular tachycardia of right ventricular origin. His older brother also died of heart disease. His heart weighed 515 g and both the right and left ventricles were dilated. Fatty tissue, unlike that in Case 1, was shown to markedly infiltrate from the epicardium into both the right and left ventricular walls. In the right ventricular wall, muscle layers disappeared in some portions. In the conduction system, fatty tissue was observed in the sinus node. Although ARVD may be considered a syndromic entity, individual cases are different in terms of pathological morphology, with possible variations in the etiology and pathogenesis.     

Mass Screening for Neuroblastoma in Japan

The present status of NB mass screening in Japan, which is the first national trial in the world, is presented. This program was conducted in cooperation with infants' mothers, local health centers, screening centers and hospitals. Three hundred and thirty-seven cases detected by the program, from the start in Kyoto in 1974 to the end of 1989, are analyzed. As many cases were detected at early stages, 97% of them were expected to be cured. Several clinical, technical and programmatic problems are also discussed.     

MR imaging of Sj?gren syndrome: correlation with sialography and pathology

Magnetic resonance (MR) imaging of the parotid glands were performed in 13 cases of Sj?gren syndrome to assess if there are any typical MR features. The MR findings were compared with sialography and pathology results. Signal intensity ratios of parotid (minus background noise) to skeletal muscle (minus background noise) were measured in these 13 cases as well as in 10 normal controls. Both T1- and T2-weighted images showed multiple hypointense mixed with hyperintense foci (salt-and-pepper appearance) throughout the glands in the six Sj?gren cases of intermediate severity (46%), inhomogeneous glands in five cases with early or advanced disease, and homogeneous glands in the remaining two cases with the earliest stage of disease. Mean intensity ratios in T2-weighted pulse sequences in patients with salt-and-pepper appearance and inhomogeneous glands were significantly smaller than those in normal controls (p less than 0.05 and p less than 0.001, respectively). Pathologic studies tend to indicate that focal lymphocytic aggregates associated with increased interlobular fibrosis are probably responsible for the hypointense foci and the decrease in intensity ratios. We think that the salt-and-pepper appearance is suggestive of Sj?gren syndrome and that the decreased intensity ratios combined with a typical clinical picture may lead to a highly probable diagnosis of this disorder.     

CT findings of endobronchial metastasis.

One hundred and sixty-one patients with pulmonary metastases were studied with CT. Six of them proved to have endobronchial (intraluminal) metastatic lesions by bronchoscopy. Retrospective analysis of the CT studies showed obstruction and/or narrowing of the bronchi in 5 cases while no lesion was observed in one patient. Although CT can not always demonstrate intraluminal lesions, it should be performed when an endobronchial metastasis from extrathoracic malignancy is seen by bronchoscopy because it will show hilar or mediastinal lymphadenopathy, or single or multiple pulmonary metastases other than the endobronchial lesion.