Mechanism of inhibitory effect of dextran sulfate and heparin on human T-cell lymphotropic virus type I (HTLV-I)-induced syncytium formation in vitro: role of cell-to-cell contact.

Cell-to-cell contact is usually essential for syncytium formation by HTLV-I-infected cell lines. The present study was undertaken to determine the inhibitory effect of polyanionic compounds, dextran sulfate and heparin, on HTLV-I-induced syncytium formation, as demonstrated by the fusion of HTLV-I-infected cells with target cells. These two compounds almost completely blocked syncytium formation in the early phase of the reaction at a concentration of 125 micrograms/ml, but dextran, as a control, did not inhibit it at concentrations up to 625 micrograms/ml. 50% inhibition of syncytium formation was detected at a concentration of 2 micrograms/ml of dextran sulfate 5000, 3 micrograms/ml of dextran sulfate 8000 and 8 micrograms/ml of heparin. The binding of radiolabeled HTLV-I-infected cells (HCT-1) to the target cells was inhibited by addition of dextran sulfate and heparin, and the inhibitory effects were concentration-dependent. No marked changes were detected in the expression of adhesion molecules on the virus-infected cells and target cells, and in the expression of envelope proteins on the virus-infected cells after exposing them to the polyanionic compounds. These results suggest that the blocking of cell-to-cell contact by polyanionic compounds, probably independent of surface adhesion molecules, is important for their inhibitory effect on HTLV-I-induced syncytium formation.

Premature fat deposition in the salivary glands associated with Sjögren syndrome: MR and CT evidence.

PURPOSE: To investigate abnormal fat deposition in the major salivary glands associated with Sjögren syndrome. METHODS: We analyzed the fat deposition in the parotid and submandibular glands of 33 patients with Sjögren syndrome by using short-inversion-time inversion recovery (STIR) and fat-saturation MR sequences and CT values. RESULTS: All three in vivo techniques substantially confirmed premature deposition of fat in the major salivary glands in association with Sjögren syndrome. Furthermore, this change was characteristic of Sjögren syndrome, and the severity of fat deposition correlated well with the impaired rates of salivary flow in these patients. CONCLUSION: Monitoring of fat deposition might be useful for diagnosing Sjögren syndrome and assessing its progress in patients whose clinical and serologic findings are suggestive of the disease.

[A male case of primary Sjögren's syndrome with interstitial pneumonitis and interstitial tubulo-nephritis in the absence of dry eye and dry mouth: parotid gland MRI is a useful diagnostic method for Sjögren's syndrome].

Here we report a case of primary Sjögren's syndrome with hilar lymphadenopathy, interstitial pneumonitis and interstitial tubulo-nephritis. A 60-year old man was admitted to our hospital in May 1993 because of general fatigue and fever. He was noted to have hypergammaglobulinemia and had positive antibodies to nuclear antigens since 1990 in the absence of clinical manifestations. Since 9 months before admission, he presented with general fatigue, low grade fever and uveitis. On admission, chest X-ray and CT scan showed bilateral hilar lymphadenopathy and interstitial pneumonitis. The negative results for both serum angiotensin converting enzyme and histological findings of the cervical lymph node and the lung excluded the diagnosis of sarcoidosis. Serological examination exhibited marked elevation of polyclonal IgG level and anti-nuclear antibody, but neither anti-SS-A (Ro) nor anti-SS-B (La) antibody was detected. He did not have symptoms of xerophthalmia and xerostomia. Keratoconjunctivitis sicca was diagnosed by positive Schirmer's and rose bengal tests. His labial gland biopsy demonstrated severe mononuclear cell infiltration around the ducts. MRI findings of the parotid glands revealed heterogeneous and dotted high signal intensity similar to those in fat tissues in the T1- and T2-weighted images. These findings depicted that bilateral parotid gland was extensively destructed and was replaced by lipid tissue. Renal biopsy showed interstitial tubulo-nephritis. On the basis of the above findings, he was diagnosed to have primary Sjögren's syndrome and uveitis. Therefore, MR image of the parotid gland is considered to be a noninvasive and useful method for diagnosis of Sjögren's syndrome.

[Thyroid and radiation].

The topic "Thyroid and Radiation" is both an old and a new area to be solved by human beings. The thyroid is an organ that is usually susceptible to exposure to ionizing radiation, both by virtue of its ability to concentrate radioiodine (internal radiation) and by routine medical examination: Chest X-ray, Dental X-ray, X-irradiation of cervical lymphnodes etc. (external radiation). Iodine-131 is widely used for the therapy of Graves' disease and thyroid cancers, of which the disadvantage is radiation-induced hypothyroidism but not complications of thyroid tumor. The thyroid gland is comparatively radioresistant, however, the data obtained from Hiroshima, Nagasaki and Marshall islands indicates a high incidence of external radiation-induced thyroid tumors as well as hypothyroidism. The different biological effects of internal and external radiation remains to be further clarified. Interestingly, recent reports demonstrate the increased number of thyroid cancer in children around Chernobyl in Belarus. In this review, we would like to introduce the effect of radiation on the thyroid gland at the molecular, cellular and tissue levels. Furthermore the clinical usefulness of iodine-131, including the safety-control for radiation exposure will be discussed.

MR imaging of the parotid gland in Sjögren's syndrome: a proposal for new diagnostic criteria.

OBJECTIVE: Because classic diagnostic techniques for sjögren's syndrome (SS) are invasive and require radiation exposure, a noninvasive diagnostic method might benefit patients with SS. The purpose of this study was to determine whether quantitative analysis of MR images of the parotid gland can differentiate patients with SS from normal subjects. SUBJECTS AND METHODS: We performed quantitative analysis of MR images of the parotid gland for 40 patients with definite and probable SS, for 30 normal subjects matched by age and sex to the SS patients, and for 10 patients with parotid inflammation. MR images of teh parotid gland were assessed by calculating standard deviations (SD) of signal intensity. RESULTS: SD of signal intensity exclusively (p < .0001) separated MR images of the parotid glands of patients with definite SS from those of normal subjects. SD of signal intensity for the parotid glands of patients with probable SS also were significantly higher (p < .001) than those of normal subjects. Changes in signal intensity were specific for SS and did not occur with parotid inflammation. Tentative categorization on the basis of signal intensity patterns on MR images of the parotid glands of SS patients showed a high correlation with the results of labial gland biopsy (r = .834) and sialography (r = .936). CONCLUSION: Taken together, these results conclusively indicate that quantitative analysis of MR images for SD of signal intensity is useful method for diagnosing SS and can replace classic methods, which are invasive.

Prevalence of serum and salivary antibodies to HTLV-1 in Sjögren's syndrome.

There is accumulating evidence that human T-lymphotropic virus-1 (HTLV-1) infection contributes to the development of various inflammatory disorders. To elucidate the relation between the infection and Sjögren's syndrome, seroepidemiological and virological studies were conducted on patients with this syndrome in Nagasaki Prefecture, Japan, an area heavily endemic for HTLV-1. The HTLV-1 seroprevalence rate among the patients with Sjögren's syndrome (17/74, 23%) was significantly higher than that among blood donors (916/27,284, 3%), whereas the difference between patients with systemic lupus erythematosus and blood donors was insignificant. Moreover, among Sjögren's syndrome patients the seroprevalence was high irrespective of age, unlike that among blood donors, which rose with age. Titres of serum antibodies in the HTLV-1 seropositive patients with Sjögren's syndrome were similar to those among patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and significantly higher than those among healthy carriers. IgM class antibodies were commonly detected in the serum of patients with Sjögren's syndrome. However, unlike that in HAM/TSP patients, the viral load in peripheral-blood mononuclear cells was not necessarily high in the seropositive Sjögren syndrome group. Salivary IgA antibodies to HTLV-1 were common among seropositive patients with Sjögren's syndrome (5/7), which might be due to increased viral activity in the salivary glands. These antibodies were barely detectable in HAM/TSP patients (prevalence 1/10) or in healthy carriers (0/11). The findings strongly suggest that HTLV-1 is involved in the pathogenesis of the disease in a subset of patients with Sjögren's syndrome in endemic areas.

Heightened transmigrating activity of CD4-positive T cells through reconstituted basement membrane in patients with human T-lymphotropic virus type I-associated myelopathy.

We investigated the transmigrating activity of peripheral blood T cells of patients with human T-lymphotropic virus type I-associated myelopathy (HAM) through reconstituted basement membrane. The transmigrating activity of CD4+ T cells of HAM patients was increased significantly in comparison to that of anti-HTLV-I-seropositive carriers and HTLV-I-seronegative controls. However, the migrating activity of CD8+ T cells was not significantly different in HAM patients and controls. The activity of aminopeptidase-N in peripheral blood T cells of HAM patients also was increased significantly, as compared to that of controls. In addition, HTLV-I proviral load in transmigrating CD4+ T cells of HAM patients was increased significantly (two- to eight-fold), compared to that in nontransmigrating CD4+ cells. By contrast, no significant difference in HTLV-I proviral load was found between transmigrating and nontransmigrating CD4+ cells of HTLV-I-seropositive carriers, although copy numbers of HTLV-I proviral load were very low in them. The heightened transmigrating activity of CD4+ cells from HAM patients through reconstituted basement membrane is based on the increased activity of aminopeptidase-N. Collectively, these findings suggest that HTLV-I-infected CD4+ T cells play an important role in the early stage of the pathogenesis of HAM.