Report of the Fifth International Conference on Human Retrovirology: Human T-cell Lymphotropic Virus.
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Biomedical subjects
Publications and source records attributed to K Takatsuki.
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When B-cell chronic lymphocytic leukemia (B-CLL) cells derived from peripheral blood are cultured in vitro, a substantial proportion die spontaneously by programmed cell death (PCD). In this study, we reexamined this phenomenon with both B-CLL and T-CLL cells, using a serum-free culture system. After 48 h of culture, in B-CLL cells, 23.3% +/- 6.7% (mean +/- S.E.M., n = 3) of total DNA was fragmented, while in 2 cases of T-CLL, this value was 32% and 45%, respectively. Analysis by electrophoresis indicated that the DNA of the B-CLL and T-CLL cells had been cleaved into regular oligonucleosome fragments comprising approximately 180-200 base pairs. This process was significantly promoted by methylprednisolone and the protein kinase A (PKA) activator Sp-cAMPS in at least some cases. Since B-CLL and T-CLL cells often possess interleukin-2 (IL-2) receptors on their cell membranes, we assessed the effects of IL-2 on spontaneous PCD. After a 48-h culture PCD was inhibited by 100 units/ml IL-2 by 31.7% +/- 6.6% in B-CLL (n = 3) and by 47% in one of 2 cases of T-CLL. This protective effect of IL-2 against spontaneous PCD was dose- and time-dependent. These findings suggest that the viability of B-CLL and T-CLL cells in vivo is regulated both positively and negatively by intrinsic IL-2, glucocorticoids, and regulators of PKA activity. This process of cell death may be involved in the development of CLL.
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A 4-year-old boy was referred for treatment of papillary tumor at the urethral meatus. He was well until December 1990, when his mother noticed a tumor at the urethral meatus. The tumor was resected elsewhere. However, a similar tumor was noted again at the urethral meatus in May, 1991. The patient was admitted on September 16, 1991. Retraction of the phimotic foreskin revealed a well-demarcated papillary mass, approximately 2 x 2 mm in diameter, at the urethral meatus. There were no tumors on foreskin or glans. Under general anesthesia endoscopy was performed to locate other tumors at the urethra and bladder. No tumors were found elsewhere. Then the meatal tumor was resected surgically. Pathology was condyloma acuminatum. There was no recurrence one year after surgery. We also reviewed 24 boys with condyloma acuminatum, including 13 boys with a solitary condyloma at the urethral meatus, reported in Japan.
A seroepidemiological study was carried out to find out if human T-lymphotropic virus type I (HTLV-I) was closely associated with uveitis in two hospitals: one in an area where HTLV-I was highly prevalent (Miyakonojo, Miyazaki) and the other in an area where HTLV-I was less prevalent (Kurume). In the highly prevalent HTLV-I area, the seroprevalence in patients with idiopathic uveitis (78/206, 37.9%) was significantly higher than in patients with non-uveitic ocular diseases (73/380, 19. 2%) or in patients with uveitis with defined etiologies (8/80, 10.0%). A more striking finding was that the seroprevalence in the younger group (20-49 years) with idiopathic uveitis in the area was 40/82 (48.8%), but only 9/114 (7.9%) in the other two reference groups. The odds of contracting idiopathic uveitis for HTLV-I infected persons was estimated at 11.0 in the younger group, and 2.0 in the older group. Similar observations were recorded even in the less prevalent area (Kurume). These data thus suggest that HTLV-I infection is a risk factor for idiopathic uveitis.
The clinical features of human T-lymphotropic virus type (HTLV-I) uveitis, an idiopathic uveitis in HTLV-I seropositive patients, were analyzed in a hospital located in an area where HTLV-I was endemic (Miyakonojo, Miyazaki). A total of 61 patients (25 males and 31 females) with HTLV-I uveitis were the subjects of the analysis. Intermediate uveitis with moderate to severe vitreous opacities accompanied by mild iritis and retinal vasculitis was the most characteristic feature, and was observed in the majority of the patients (66% of all or 84% in young adult patients between 20 and 49 years of age). The uveitis affected one eye in 57% and both eyes in 43% of the patients, with subacute onset of floaters and foggy vision. The uveitis responded well to therapy with topical or systemic corticosteroids, but recurred in many cases. A significant number of patients (15% of all and 25% of female patients) had a previous history of Graves' disease with hyperthyroidism.
The presence of proviral DNA of human T-lymphotropic virus type I (HTLV-I) in the inflammatory cells in the aqueous humor was examined by polymerase chain reaction. The proviral DNA was detected in all the tested patients (n = 9) with HTLV-I uveitis. On the other hand, the provirus was not detected in 2 out of 3 HTLV-I seropositive patients with other types of uveitis, i.e., Behçet's disease, toxoplasmosis and Vogt-Koyanagi-Harada's disease. None of the 11 seronegative patients with other types of uveitis or senile cataract had proviral DNA in the aqueous humor. Thus, the fact that HTLV-I-infected cells were present in the aqueous humor of all HTLV-I uveitis patients suggests significant involvement of HTLV-I in the pathophysiology of the uveitis.
The ocular manifestation of human T-cell lymphotropic virus type I (HTLV-I) infection has been recognized as a new clinical entity termed HTLV-I uveitis. In order to determine whether HTLV-I uveitis is associated with lymphocyte alveolitis, bronchoalveolar lavage (BAL) was carried out in 11 patients with HTLV-I uveitis, five asymptomatic HTLV-I carriers, 11 HTLV-I-negative patients with ocular sarcoidosis, and nine normal control subjects seronegative for HTLV-I. Six of the 11 patients with HTLV-I uveitis showed increased total cell counts, and T-lymphocytosis in BAL fluid. CD4+/CD8+ ratios of T-lymphocytes were decreased in three of these patients, and normal in three other patients. Such abnormalities of the lung were not found in asymptomatic HTLV-I carriers, and in normal control subjects. BAL findings in HTLV-I uveitis differed from those of patients with sarcoidosis in terms of the lymphocytic component. Interestingly, it was found that there was an increase of HTLV-I proviral deoxyribonucleic acid (DNA) load in peripheral blood mononuclear cells (PBMC) from seven patients with HTLV-I uveitis, and in the BAL cells from four patients with pulmonary involvement. These results provide further evidence in terms of HTLV-I tropism for the lung, and suggest that a systemic and local increase of HTLV-I proviral DNA load plays an important role in the pathogenesis of lymphocyte alveolitis in patients with HTLV-I uveitis.
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The authors present the results of an autopsy of a 67-year-old Japanese man with POEMS/Takatsuki/Crow-Fukase syndrome (P/T/CFS) diagnosed in 1972. Each component of the syndrome was gradually recognized after the resection of lumbar vertebral solitary plasmacytoma in 1967. The patient died in 1989 of generalized infection and renal failure. Autopsy revealed in the vertebral canal between the fifth and seventh thoracic vertebrae dorsal pachymeningeal fibrosis, with prominent amyloid deposition that oppressed the spinal cord. This condition was consistent with the final neurologic manifestation of the patient, bilateral motor and sensory disturbance below the sixth thoracic level. Myelopathy remained clinically unnoticed because neurologic disturbance had begun as peripheral polyneuropathy. Normocellular marrow with heterogeneously scattered lambda light chain-positive plasma cells and degeneration of the myelinated fibers of sciatic nerve also were observed. This is the first report of focal spinal amyloidosis associated with P/T/CFS.
Seroepidemiologic, clinical, and virologic studies were performed to determine whether human T-cell lymphotropic virus type I was closely associated with uveitis in two hospitals. One hospital was in an endemic area of the virus (Miyakonojo, Miyazaki) and the other hospital was in a less endemic area (Kurume). In the endemic area, the seroprevalence of the virus in patients with uveitis without defined causes (35.4%, 62 of 175 patients) was significantly higher than that in patients with nonuveitic ocular diseases (16.1%, 42 of 261 patients), or in patients with uveitis with defined causes (10.3%, eight of 78 patients). The seroprevalence in younger patients (20 to 49 years of age) with uveitis without defined causes in the area was 44.8% (30 of 67 patients), whereas it was only 9.3% (ten of 107 patients) in the other two groups. A similar observation was recorded even in the less endemic area (Kurume). Because the seroprevalence of the virus in the general population is known to be low in younger patients and to increase with age, these findings were interpreted to indicate that the association of human T-cell lymphotropic virus type I with uveitis was significant. Most patients, particularly those aged 20 through 49 years, had an intermediate uveitis characterized by a moderate inflammation in the vitreous body accompanied by an iritis and retinal vasculitis. The ocular symptoms in the patients differed from those of other types of uveitis common in Japan (Behçet's disease, Vogt-Koyanagi-Harada's disease, and toxoplasmosis, for example).(ABSTRACT TRUNCATED AT 250 WORDS)
We report a case of chronic myeloid leukemia (CML) in myelomonocytic transformation associated with bone marrow (BM) eosinophilia. At diagnosis, all BM cells showed a Ph chromosome. At the time of blastic phase, more than 50% of Ph+ cells had a pericentric inversion of chromosome 16, inv(16)(p13q22). This case confirms that blastic transformation of CML can involve any committed progenitor, and myelomonocytic leukemia with BM eosinophilia is specifically associated with rearrangement of chromosome 16 at band p13 and q22.
Although the possible occurrence of systemic fibrinogenolysis has been suggested in patients with metastasising prostatic cancer (MPC), direct evidence is lacking. We report on a patient with MPC whose laboratory data were consistent with hyperfibrinolysis: marked decrease of alpha 2-antiplasmin (AP) level (less than 50% of normal), increase of plasmin-alpha 2-antiplasmin complex, D-fragment of fibrin and fibrinogen degradation products [FDP(D)] and cross-linked fibrin degradation products (XDP). The patient neither showed laboratory nor clinical evidence for consumption coagulopathy except for a slight increase in thrombin-antithrombin III complex level. Immunoblotting of the patient's serum using an anti-fibrinogen antibody revealed the presence of a 250 kDa protein in addition to DD fragments. Following reduction of this protein by 2-mercaptoethanol after extraction from SDS-PAGE gel, gamma-chain of fibrinogen (47 kDa) was found by immunoblotting using a monoclonal antibody recognising a 86-302 residue of the gamma-remnant of fibrinogen. Moreover, the 250 kDa protein did not bind to Sepharose 4B to which a monoclonal antibody recognising the N-terminus of fragment D was conjugated. These findings indicated that this protein was not fragment DY, but rather fibrinogen fragment X. With the retraction of the prostatic tumour by an effective therapy, the patient's AP level increased gradually. When the plasma AP level rose to 60% of normal, the fragment X was no longer detectable. These findings suggested that systemic fibrinogenolysis occurred in the patient with MPC only when AP levels were markedly decreased.
The antigenic profile of basal cell carcinoma (BCC) cells was analyzed by immunoperoxidase staining of 27 surgically removed BCC lesions with antiganglioside, antiadhesion molecule, and antihistocompatibility locus antigen (HLA) monoclonal antibodies (MoAb). The large majority of BCC lesions were stained by antiganglioside MoAb; among the latter the anti-GD3 ganglioside MoAb R24 displayed the broadest reactivity. The GD3 ganglioside expression by BCC cells, which was corroborated by thin layer chromatography immunostaining with MoAb R24, appears to be a proliferation dependent phenomenon. Among the adhesion molecules tested vitronectin receptor and CDw44 were found in up to 70% of the lesions tested, while intercellular adhesion molecule 1 (ICAM-1) was detected in only a low percentage of BCC cells in one lesion. ICAM-1 was not induced on BCC cells in five and three lesions removed 24 and 48 h, respectively, following the intralesional injection of gamma-interferon. The latter enhanced HLA Class I antigen expression and induced ICAM-1 expression by the surrounding keratinocytes; furthermore gamma-interferon induced HLA Class II antigen expression by a small percentage of BCC cells in three lesions. These results suggest that malignant transformation of keratinocytes is associated with a selective loss of susceptibility to induction by cytokines of ICAM-1 expression. Besides confirming the low HLA Class I and Class II antigen expression by BCC cells, the present investigation has shown a differential expression of distinct monomorphic determinants of HLA Class I antigens and a lower expression of HLA-A antigens than of HLA-B antigens by BCC cells. Furthermore, the present study has shown that HLA Class II antigens can be induced on BCC cells by cytokines.