A case report of a pedunculated uterine leiomyosarcoma.
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Biomedical subjects
Publications and source records attributed to N Ohara.
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BACKGROUND: Aortic aneurysm is a rare but life-threatening cardiovascular complication in patients with autoimmune disorders. The purpose of this study was to clarify the characteristic clinical features and the pathological mechanism of aneurysmal formation in those patients treated with corticosteroids. METHODS: Among 429 patients operated on for abdominal aortic aneurysm during the past 10 years, six patients with autoimmune diseases treated with corticosteroids (one with progressive systemic sclerosis, one with rheumatoid arthritis and four with systemic lupus erythematosus) were reviewed retrospectively. Their data were compared with those of 391 patients with atherosclerotic aneurysms with no autoimmune disorders. The resected aneurysmal walls of the six patients were also compared histopathologically with those of the last six consecutive patients in the control group. RESULTS: The average age of the patients with autoimmune disease was younger than that of the control group (53.8+/-16.6 vs 71.8+/-7.8 years; p<0.05). Patients with autoimmune disease had received long-term corticosteroid therapy for 15-32 years; mean 22.2+/-6.5 years. Pathological examination showed that the destructive change of the medial elastic lamina in the autoimmune disease group was wider than that in the controls. Most patients had no complications in the postoperative follow-up period (5.1+/-3.2 years), while one patient died of rupture of a dissecting aneurysm two years after operation. CONCLUSIONS: Prolonged corticosteroid treatment probably plays a major role in the disintegration of connective tissue of the media, possibly together with primary aortic wall involvement and/or vasculitic damage in patients with autoimmune disorders, which can result in aortic aneurysmal enlargement.
The proteins in culture filtrate derived from Bacillus Calmette-Guérin (BCG) were examined for protection against infection by Mycobacterium leprae. Immunization with the major secreted proteins, antigen 85 complex (Ag 85) A, B and C, induced effective protective immunity against multiplication of M. leprae in the foot pads of mice. The most effective protection was observed when mice were immunized with Ag 85A. A single immunization with Ag 85 could induce antigen-specific interferon gamma (IFNgamma) synthesis and more effective protection than live BCG vaccine. This study demonstrates that Ag 85 is an important immunoprotective molecule against leprosy infection.
The alpha antigen, which is an immunodominant antigen, is a 30 kDa protein secreted by mycobacterial species. The C-terminal regions of alpha antigens are quite divergent. We investigated the question of whether the C-terminal regions of Mycobacterium avium alpha antigen (A-alpha), M. intracellulare alpha antigen (I-alpha) and M. bovis BCG alpha antigen (B-alpha) contained species-specific B-cell epitopes. We investigated the reactions of these peptides with anti-A-alpha, anti-I-alpha and anti-B-alpha sera prepared from BALB/c in a Western blot assay and ELISA. The C-terminal regions of I-alpha reacted exclusively with anti-I-alpha serum. The results of the inhibition assay of antibodies binding to I-alpha by peptides of C-A-alpha, C-I-alpha, and C-B-alpha are that only C-I-alpha inhibited the binding of antibodies to C-I-alpha. We found that the C-terminal region was B-cell epitope-specific to I-alpha in BALB/c mice.
The ribosomes from BCG strongly induced delayed type hypersensitivity (DTH) skin reactions in guinea pigs immunized with live BCG or heat killed Mycobacterium tuberculosis H37Rv, and also induced lymphocyte proliferative response in mice immunized with ribosomes. In contrast, neither ribosomal proteins nor RNA alone induced both DTH skin reactions and lymphocyte proliferative responses. Particle form consisted of ribosomal proteins and RNAs might be absolutely required for the activation of immune responses.
We herein describe a 27-year-old male presenting with a pulmonary blastoma. The patient was admitted to our hospital with the chief complaints of fever and left back pain. Chest roentgenograms showed a tumor measuring 10 cm in diameter in a lower lobe of the left lung. Computed tomography and magnetic resonance imaging revealed a well demarcated and heterogeneously enhanced tumor. Although a histological diagnosis could not be obtained by a transbronchial biopsy, image analyses led us to suspect it to be malignant. The patient underwent a left lower lobectomy with lymph node dissection. A histopathological examination revealed the tumor to be a biphasic type of pulmonary blastoma. Because of the rapid progress of the tumor and the difficulty in making a preoperative diagnosis in such cases, an immediate surgical resection is therefore recommended in cases with even the slightest suspicion of malignancy.
In isolated mesenteric arteries of rats, dose-dependent increase in perfusion pressure by adenosine 5'-triphosphate (ATP, 0.1 approximately 3000 nmole) diminished with age. ATP responses of both 4- and 32-week-old rats were enhanced by indomethacin (5 microM), and further by the combination of indomethacin and N(G)-nitro-L-arginine methyl ester (L-NAME, 5 microM). The enhancement with each of the treatments was less in 32-week-old rats than that in 4-week-old rats, and there was no enhancement in 75-week-old rats. The ATP response was enhanced by removing the endothelium only in 4-week-old rats. The constrictions in response to ATP (1000 nmole) in both 4- and 32-week-old rats were equally enhanced by reactive blue 2 (30 micromole) and were inhibited by pyridoxal-phosphate-6-azophenyl-2',4-disulphonic acid (PPADS, 30 microM) and alpha, beta-methylene ATP (alpha, beta-mATP, 100 nmole) to a similar extent. The increased tone which was produced by the perfusion with physiological solution containing 100 mM potassium chloride was greater in older animals. This age-related change in the vascular tone disappeared when the responses were potentiated by L-NAME. These results demonstrate that in rat mesenteric arteries, ATP-induced constriction decreases with age. The age-related decline of vasoconstriction is not likely to arise from the changes in the contractility of smooth muscle, from the counterbalancing regulation by the endothelium, or from the cooperation of P2 purinoceptor subtypes. The density of purinoceptors and some post-receptor signal transduction mechanisms in the vascular smooth muscle cells may change with age. The enhanced ATP response might have special physiological significance in rats during development.
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Two patients who had aortopulmonary fistula of postoperative origin with hemoptysis underwent successful repair by means of an endovascular stent graft procedure. One patient had undergone repeated thoracotomies two times, and the other one time to repair anastomotic aneurysms of the descending aorta after surgery for Takayasu's arteritis. A self-expanding stainless steel stent covered with a Dacron graft was inserted into the lesion through the external iliac or femoral artery. The patients recovered well, with no signs of infection or recurrent hemoptysis 8 months after the procedure. Endovascular stent grafting may be a therapeutic option for treating patients with aortopulmonary fistula.
Concerns over cancer development from exposure to environmental sources of densely ionizing, high linear energy transfer (LET) radiation, such as alpha-particles from radon, is a current public health issue. The study of tumors attributable to high LET irradiation would greatly augment our insights into the biological mechanisms of carcinogenesis. Chronic low-dose-rate internal exposure to alpha-radiation from thorium dioxide deposits following intravascular administration of the radiographic contrast agent Thorotrast is known to markedly increase the risk of cancer development, especially that of hepatic angiosarcomas and cholangiocarcinomas. Although the mechanism is hypothesized to be via cellular damage, DNA being a major target, wrought by the high LET alpha-particles, the specific genes and the actual sequence of events involved in the process of transforming a normal cell into a malignant one are largely unknown. To shed some light on the molecular mechanisms of cancer development during a lifetime exposure to alpha-radiation, we analyzed the most commonly affected tumor suppressor gene in humans, p53, in 20 Thorotrast recipients who developed cancer, mostly of hepatic bile duct and blood vessel origin. Of the 20 cases, 19 were found to harbor p53 point mutations. Moreover, the accompanying non-tumor tissues from these patients also had p53 mutations, albeit at lower frequency. The distribution pattern of the point mutations was significantly different between the non-tumor and tumor tissues, with most mutations in malignant tissues located in the highly conserved domains of the p53 gene. Our results support the idea that p53 mutations are important in the genesis of Thorotrast-induced tumors but that these point mutations are a secondary outcome of genomic instability induced by the irradiation. Additionally, non-tumor cells harboring p53 mutations may gain some survival advantage in situ but mutations in the domains responsible for the formation of structural elements critical in binding DNA may be necessary for a cell to reach full malignancy.
Malignant lymphoma (ML) induction in rabbits by Epstein-Barr virus (EBV)-related herpesvirus of cynomolgus (Cyno-EBV) is reported. Twenty-seven of 30 (90%) rabbits inoculated intravenously with Cyno-EBV-producing simian (cynomolgus) lymphocyte cell line (Ts-B6) cells developed ML between 45 and 115 days after inoculation. The peroral inoculation of Ts-B6 cells induced ML in only 2 of 10 (20%) rabbits (75 to 85 days). Five of 6 (83%) rabbits injected with cell-free pellets from Ts-B6 cultures also developed ML (27 to 122 days). Antibody response to the viral capsid antigen of EBV was also detected in sera from rabbits inoculated with Ts-B6. ML of the large cell or mixed type infiltrated diffusely in many organs, frequently involving the spleen, liver, kidneys, heart, and less frequently the lungs, lymph nodes, brain, eyes, gastrointestinal tract, thymus, and bone marrow. A chromosomal analysis of five lymphoma cell lines established from tumor-bearing rabbits revealed the rabbit karyotype. Three of these cell lines showed the chromosomal abnormalities with 12q- or t (7p+:12q-). EBV-encoded small RNA-1 and EBV-associated nuclear antigen 1 were expressed in Ts-B6 cells, the tumor tissues, and all rabbit cell lines by in situ hybridization and by immunofluorescence tests, respectively. EBV DNA was also detected in Ts-B6 cells and rabbit lymphoma cell lines by polymerase chain reaction and Southern blot analysis. The Southern blots of EBV termini revealed oligoclonal bands in the Cyno-EBV-induced rabbit lymphomas. No lymphoma was induced by the inoculation of B95-8 (EBV-producing cells) or peripheral leukocytes from normal cynomolgus (controls). These data suggest that the high rate of lymphoma induction in rabbits may be caused not by human EBV (B95-8) but by Cyno-EBV from Ts-B6 cells. A sequence analysis of the IR1 (BamHIW) region of Cyno-EBV revealed that this region is quite similar to that of herpesvirus Macaca fascicularis 1, which is a causative agent for a monkey model of AIDS-related lymphomas. The present rabbit model of lymphoma with specific chromosomal abnormalities is very useful to clarify the role of EBV in human EBV-associated lymphoma and provides a means for studying prophylactic and therapeutic regimens.
alpha,beta-Methylene ATP (alpha, beta-mATP), ATP and UTP dose dependently increased the perfusion pressure of rat mesenteric arteries with a potency order of alpha, beta-mATP >> ATP > UTP. In the veins, while alpha, beta-mATP did not affect the pressure, both ATP and UTP equi-potently increased it. The arterial ATP response was attenuated to some degree by suramin (100 microM), but markedly and to a similar extent by pyridoxal-phosphate-6-azophenyl-2',4-disulphonic acid (PPADS 30 microM) and alpha, beta-mATP (100 nmol). The venous response was not affected by PPADS or alpha, beta-mATP, but was slightly attenuated by suramin. Thus, ATP seems to elicit arterial constriction predominantly by stimulating P2X, but venous constriction by stimulating P2U purinoceptors.
Age-related changes of norepinephrine response were studied in isolated perfused mesenteric arteries and veins of rats at 4, 32 and 75 weeks of age. Norepinephrine (0.1-100 nmole) significantly and dose-dependently increased perfusion pressure of the arteries, whereas it only slightly changed that of the veins. The arterial response increased, but the venous response decreased with age. Indomethacin at 5 x 10(-6) M did not change the arterial response at any of the ages. The combination of indomethacin and NG-nitro-L-arginine methyl ester (L-NAME) at 5 x 10(-6) M, and endothelium denudation similarly augmented the response in 4-week-old rats, but neither of these affected the responses in 32- and 75-week-old rats. At raised tone by 100 mM potassium chloride, acetylcholine-induced decrease in perfusion pressure and inhibition of the response by L-NAME were attenuated gradually with age. The raised tone in 75-week-old rats was higher than that in either 4- or 32-week-old rats, but the difference disappeared in the presence of L-NAME. These results demonstrate that the arterial portion is predominant in norepinephrine response and the arterial and venous responses change oppositely with age. It is also suggested that neither prostanoids nor endothelial nitric oxide regulate the arterial response in mature animals, while only in 4-week-old rats, nitric oxide may counteractively regulate the response. Additionally, the roles of nitric oxide in the regulation of transient norepinephrine response, in the regulation of the potassium-induced tonic contracture, and in the vasodilation through muscarinic receptor stimulation seem to change somewhat differently with age.
The binding motifs of the immunodominant antigen (Ag) alpha-Ag (Ag 85 complex B) of Mycobacterium kansasii for human fibronectin were examined using digested fragments. We defined two fibronectin-binding epitopes on 27 amino acids from 84 to 110 and on 20 amino acids from 211 to 230. The epitopes were almost conserved in the closely related Ag 85 complex of other mycobacteria species. Inhibition of fibronectin binding to intact alpha-Ag molecules was observed with peptide-(84-110), but not with peptide-(211-230). Peptide-(84-110) could also inhibit fibronectin binding to all components of the Ag 85 complex of Bacillus Calmette-Guérin (Ag 85A, Ag 85B, and Ag 85C). Further study with synthetic peptides defined 11 residues from 98 to 108 as the minimum motif. Six residues (98FEWYYQ103) were critical for interacting with fibronectin. The motif revealed no homology to other known prokaryotic and eukaryotic fibronectin-binding proteins. The defined motif of alpha-Ag is novel and unique for mycobacteria.
We report a case of primary iliopsoas abscess successfully treated by ultrasonographically guided percutaneous drainage. A 56-year-old man presented at our hospital with lumbago, right-sided back pain, fever (temperature 38.5 degrees C) and chills. On physical examination, we found dark red skin, swelling, and tenderness localized at the right side at the back of his waist. Laboratory examination showed leukocytosis (white blood cell count 9700/mm3) with a leftward shift and elevated C-reactive protein (5.2 mg/dl). Ultrasonography (US), computed tomography (CT), and magnetic resonance imaging revealed a hypodense lesion in the right iliopsoas muscle extending to the subcutaneous tissue. About 50 ml of thick yellow pus was obtained by ultrasonographically guided aspiration drainage. A drain catheter was inserted in the abscess cavity. Laboratory findings improved and clinical symptoms abated rapidly after drainage. On the twenty-first day after drainage, US and CT showed that the abscess was no longer present. The patient was discharged after 32 days of hospitalization. As possible primary diseases causing iliopsoas abscess, such as digestive tract disease, tuberculosis, and osteomyelitis, were not found, we diagnosed the disease as primary iliopsoas abscess. Although surgical drainage has been performed in most reported cases of iliopsoas abscess, this case report shows that ultrasonographically guided percutaneous drainage is also effective for treating primary iliopsoas abscess if it is diagnosed early enough.
A 16-kDa protein, identical to the alpha-crystallin-like stress protein, was induced under O2-deficient culture conditions and bound principally to the 30S ribosomal subunits of Mycobacterium bovis BCG substrain Tokyo (BCG). The 16-kDa protein was shown to be tightly associated with the ribosome.
Mapping of B-cell epitopes on alpha antigen of Mycobacterium kansasii (K-alpha) was carried out by using recombinant truncated K-alpha fusion peptides. We observed that two immunodominant B-cell epitopes (amino acids 222-268 and 267-306) and one minor epitope (amino acid 249-286) were located in the C-terminal region of K-alpha. The other three minor B-cell epitopes were mapped in N-terminal (amino acids 80-98 and 99-166) and central (amino acid 174-204) regions of K-alpha. All defined epitopes were common to Mycobacterium tuberculosis and M. kansasii. Besides these common epitopes, a region in K-alpha (amino acid 290-319) revealed different reactivities between antibodies against K-alpha and alpha antigen of M. tuberculosis. These findings may provide a basis for development of serodiagnosis that can distinguish between M. kansasii and M. tuberculosis infections.