Interstitial lung disease associated with leflunomide.
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Biomedical subjects
Publications and source records attributed to Satoshi Ito.
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A 76-year-old man with autosomal dominant polycystic kidney disease (ADPKD) was admitted complaining of severe edema of bilateral lower extremities. Computed tomography (CT) of his abdomen revealed an enlarged hepatic cyst with intra-cystic hemorrhage, and massive thrombosis in the inferior vena cava (IVC). The extrinsic mechanical stress on the IVC seemed to induce thrombosis within the IVC, and the thrombosis was likely the cause of severe edema in lower extremities. In this report, we present a rare case of IVC thrombosis due to an enlarged cyst in ADPKD successful treated with anticoagulant therapy.
A case of renal cell carcinoma, found after skin metastasis is presented. A 79-year-old man visited Osaka JR hospital, complaining of a painless nodular mass on his right chest. The mass was resected and histopathological examination revealed a clear cell carcinoma (alveolar type, G1) with no involvement of the mammary gland. Abdominal ultrasound and magnetic resonance imaging revealed a heterogenous lower pole mass in the right kidney. Ultrasound-guided needle biopsy of the right renal mass was performed for histopathological diagnosis, which was clear cell carcinoma (alveolar type, G1). At that time, multiple metastases appeared in bilateral lung fields. The patient is currently receiving interferon-alpha therapy, without surgical treatment.
A 67-year-old man, who had smoked heavily for many years, was found in 1997 to have bladder tumors, and transurethral resection of the bladder tumor (TUR-Bt) was performed. Histopathological diagnosis was urothelial carcinoma (G2>G3, pTa, N0, M0, ly0, v0). In December, 1998, he noticed an oral cavity tumor. After preoperative radiation therapy (total 40 Gy, 17 times), surgical treatment was undertaken. Histopathological diagnosis was well differentiated squamous cell carcinoma (pT2, pN2b, M0). In February, 2000, gastric tumor was detected by endoscopic examination, and subtotal gastorectomy and Roux en Y operation were performed. Histopathological diagnosis was well differentiated adenocarcinoma (pT2, pN0, M0, P0, CY0). A chest computed tomographic (CT) scan revealed a solitary lung tumor in April, 2000. Partial peumonectomy was performed, and histopathological diagnosis was poorly differentiated adenocarcinoma (pT1, N0, M0, P0). In April, 2000, multiple lesions of bladder cancer in the neck of the urinary bladder and posterior urethra were found and radical cystoprostatourethrectomy combined with lymph node dissection and bilateral cutaneous ureterostomy were performed (urothelial carcinoma, G3, pT4a, pN2, M0, pL2, pV0, pR0). Since then, the patient has been followed carefully.
We report a case of stage I malignant melanoma of the penis (confined to the penis). A 74-year-old uncircumcised man noticed a nonhealing, painless black lesion in penile foreskin and visited our institute. As the lesion was confined to the prepuce, the patient underwent circumcision for treatment and histological diagnosis. Histological examination revealed a malignant melanoma composed of epithelioid melanocytes. Ten months later, he is currently alive, without recurrence or metastasis.
UNLABELLED: Several recent reports have described the judgment of chemotherapeutic effects on malignant lymphomas by use of (18)F-FDG PET as early as a few courses after the initiation of chemotherapy. However, the optimal timing of (18)F-FDG PET has yet to be clarified. Earlier (18)F-FDG PET, such as day 1 after chemotherapy, may be affected by inflammation or chemotoxicity in addition to chemotherapeutic effects, but the ways in which uptake is changed are as yet unclear. We therefore examined changes in (18)F-FDG PET results on day 1 after the initiation of chemotherapy for malignant lymphoma. METHODS: Twelve patients with non-Hodgkin's lymphoma were enrolled in this study. (18)F-FDG PET was performed before therapy to determine baseline results and then was repeated at day 1 and day 20 after the initiation of chemotherapy (just before the initiation of the second course of chemotherapy) and at the end of chemotherapy. We selected 1-9 regions of interest (ROIs) from each patient and calculated the corrected standardized uptake value (SUV(cor)) by subtracting the SUV of surrounding normal tissue for a semiquantitative analysis. From the ROIs in each patient, the representative SUV(cor) with the highest SUV(cor) at baseline was selected, and the mean representative SUV(cor)s for all 12 patients at baseline, day 1, day 20, and the end of chemotherapy were evaluated. Changes in the representative SUV(cor) were compared by use of paired t tests (2-tailed P values of <0.05 were considered statistically significant). RESULTS: All representative SUV(cor)s for each patient were lower on day 1 than at baseline, and the mean +/- SD representative SUV(cor) for all patients was significantly decreased from 10.7 +/- 7.9 at baseline to 5.8 +/- 5.8 at day 1 (P = 0.0002; paired t test). On day 20, the mean +/- SD SUV(cor) was 0.7 +/- 1.0, showing a further decrease from the value at day 1 (P = 0.01). Although the mean +/- SD SUV(cor) tended to decrease again to 0.4 +/- 0.7 by the end of chemotherapy compared with the value at day 20, no significant difference was identified (P = 0.37). CONCLUSION: (18)F-FDG uptake decreased as early as day 1 after the initiation of chemotherapy, indicating that (18)F-FDG PET for initial diagnosis or staging must be performed before the onset of chemotherapy, as scan results might already be severely compromised after the first day.
For the induction of mucosal immune responses by intranasal vaccination, cholera toxin B subunits (CTB) and Escherichia coli heat-labile toxin (LT) are often administered as mucosal adjuvants in order to enhance immune responses to mucosally co-administered bystander antigens. However, these toxin also are the causative agents of diarrhea. There is a demand for the establishment of an effective and safer adjuvant or vaccine that elicits mucosal immunity, but does not require the use of CTB or LT adjuvants. In order to induce protective mucosal immune responses in the nasal area against influenza virus infection, we have examined the recombinant protein composed of the complement component, C3d, which is fused to the secreted form of hemagglutinin (sHA-mC3d3) in the influenza-BALB/c mouse model. The fusion protein sHA-mC3d3, the secretory form of hemagglutinin, and the transmembrane form of HA (tmHA) from the influenza virus were intranasally administered to the mice with or without CTB containing a trace amount of holotoxin (CTB*) as an adjuvant. After intranasal administration of these proteins with CTB*, all mice produced nasal IgA and serum IgG antibodies (Abs) against the viral HA. In addition, viral infection was completely inhibited in these mice. In contrast, in the absence of the adjuvant, only sHA-mC3d3-induced locally secreted IgA and serum IgG Abs and provided complete protection against the influenza virus challenge. Thus, C3d fused to the influenza HA antigen is an effective and safe tool for mucosal vaccination.
A 24-year-old woman was admitted to Toyosaka Hospital with proteinuria, hematuria, lymphopenia, hypocomplementemia, positive anti-nuclear antibody (ANA), and elevation of anti-streptolysin O (ASO). Renal biopsy specimen revealed diffuse mesangial and endocapillary glomerulonephritis with crescent formation and duplication of the capillary loop on light microscopic examination. Mild to moderate proliferation of mesangial matrix and cells were observed. On immunofluorescence (IF) examination, deposition of IgG, IgA, IgM, C1q, C3, and C4 to the mesangium and capillary wall were observed. By electron microscopy (EM), mesangial, subendothelial, and subepithelial deposits were recognized. However, microtubular structure in glomerular endothelial cells, fingerprint structures, and circumferential mesangial interposition were not observed by EM. The patient was referred to our hospital, but there was no change in her proteinuria 3 weeks after admission. The elevation of ASO, hypocomplementemia, and endocapillary proliferation suggested acute glomerulonephritis, while lymphocytopenia, positive ANA, the persistent hypocomplementemia, and various deposits detected by IF and EM suggested lupus nephritis; however, she did not fulfill the classification criteria of systemic lupus erythematosus. We started prednisolone (40 mg/day) with the diagnosis of chronic glomerulonephritis revealing diffuse mesangial and endocapillary proliferative glomerulonephritis, but it was not effective for the proteinuria. Quinapril (10 mg/day) and losartan (25 to 50 mg/day) were administered and the proteinuria decreased. It is possible that this use of an angiotensin converting-enzyme inhibitor and an angiotensin II receptor antagonist was effective in reducing the proteinuria in this patient.
Telemedicine was used for taking ocular fundus images of diabetic patients, which were subsequently sent by electronic mail to experienced ophthalmologists at a university hospital. The ophthalmologists provided reports on the patients to the internists. The objective of the study was to evaluate the effectiveness of this telemedicine system. A total of 279 diabetic patients were admitted to the Third Department of Internal Medicine of Yokohama City University Hospital, School of Medicine, for blood sugar control or for education on lifestyle between April, 1999, and October, 2000. The subjects did not have eye disease nor diabetic retinopathy when evaluated by an ophthalmologist (at either Yokohama City University Hospital or other facility) within 3 months before enrollment in the study. After dilation of the pupil, fundus images were taken of each eye from four angles using a nonmydriatic fundus camera. The images were transmitted by electronic mail to the Division of Ophthalmology of Tokyo University Branch Hospital along with other patient information. The ophthalmologists there evaluated the images on the screen according to Fukuda's classification of diabetic retinopathy. They sent ophthalmologic reports to the internists at the Third Department of Internal Medicine of Yokohama City University Hospital, School of Medicine, and recommended whether the patient should be seen by his/her regular ophthalmologist earlier than the next scheduled visit. Fundus images were obtained at the time of admission, at 1, 3, and 6 months after discharge, and at every 6 months thereafter. Out of the images of 1170 eyes obtained at various time points from the 279 patients, 1076 (92.0%) were successfully evaluated by the ophthalmologists at the University of Tokyo, while 60 (5.1%) could not be evaluated and there was a communication problem for the images of 34 eyes. The ophthalmologists determined that 5 eyes of 3 patients required further evaluation by the patient's regular ophthalmologist based on the images transferred by telemedicine. No patient dropped out during the study period.
BACKGROUND: Leukocyte Fc receptors for immunoglobulin G (FcgammaR) play a major role in the handling of immune complexes and pathogens in systemic lupus erythematosus (SLE) and periodontitis. Both diseases have been shown to be partly influenced by genetic components including FcgammaR genotype. The aim of this study was therefore to evaluate whether FcgammaR gene polymorphisms are associated with periodontitis risk in SLE patients. METHODS: The study subjects consisted of 42 SLE patients with periodontitis (SLE/P), 18 SLE patients without periodontitis (SLE/H), 42 healthy subjects with periodontitis (H/P), and 42 healthy subjects without periodontitis (H/H), who were all unrelated Japanese non-smokers. Genomic DNA was isolated from peripheral blood, and FcgammaR genotypes for 3 biallelic polymorphisms (FcgammaRIIa-R131/H131, FcgammaRIIIa-158V/158F, FcgammaRIIIb-NA1/NA2) were determined by allele-specific polymerase chain reactions. RESULTS: The SLE/P group was found to have more mild levels of periodontal destruction than the H/P group (P < 0.01). There was a significant difference in the distribution of FcgammaRIIa genotypes between SLE/P and H/H groups (P = 0.004). A significant overrepresentation of the FcgammaRIIa-R131 allele was found in the SLE/P group compared to the H/H group (SLE/P versus H/H: odds ratio [OR] 3.13, 95% confidence interval [CI] 1.46-6.77, P = 0.0013). Furthermore, the prevalence of periodontitis was found to be 70% in SLE patients. The FcgammaRIIa-R131 allele was also found to be overrepresented in the SLE/P group compared to the SLE/H group (SLE/P versus SLE/H: OR 3.40, 95% CI 1.18-10.25, P = 0.011). CONCLUSION: These results show the FcgammaRIIa-R131 allele to be associated with periodontitis risk in SLE patients.
We treated a case of adult-onset severe-form anaphylactoid purpura. This case had been diagnosed as anaphylactoid purpura pathologically by skin biopsy. However, his clinical manifestations were atypical in view of complicated massive gastrointestinal hemorrhage. Intensive therapy including corticosteroid and cyclophosphamide transiently improved his condition. Nevertheless, the beta-D-glucan value in peripheral blood was gradually elevated. Prophylactic use of fluconazole failed to prevent contraction of invasive mycosis. Finally, he suddenly suffered from diffuse cerebral hemorrhage. Postmortem examination revealed systemic invasive aspergillosis as the cause of death.
A 40-year-old woman with a history of fever and arthralgia since age 17 had received long-term prednisolone (PSL) therapy. She was diagnosed with Takayasu's arteritis in 1980 and given PSL. The symptoms were well controlled until she developed itching in 1998. Laboratory tests showed elevated levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, total cholesterol, and immunoglobulin M (IgM). She tested positive for anti-mitochondria antibody and for both IgG and IgM anti-pyruvate dehydrogenases. Liver biopsy findings were typical of primary biliary cirrhosis (PBC). Our patient's clinical course suggested that an adequate amount of PSL to control Takayasu's arteritis does not necessarily prevent the development of PBC.
Two cases of spontaneous rupture of cystic craniopharyngioma without chemical meningitis are described. A 70-year-old woman complained of headache and visual field disturbance in July 1993. The tumor was extirpated in November 1993 and again in December 1996. After regular periodic follow-up evaluation, she was hospitalized for reoperation because of expansion of the cyst on magnetic resonance (MR) imaging in November 1998. However, preoperative MR imaging taken 8 weeks later revealed spontaneous reduction of the cyst. A 69-year-old woman noticed deteriorating vision and bitemporal hemianopsia in November 1998. The tumor was removed in December 1998, and 50.4 Gy postoperative radiotherapy was administered. MR imaging in May 2000 demonstrated an enlargement of the cyst, so she was hospitalized again for operation. However, preoperative MR imaging taken 7 weeks later showed spontaneous reduction of the cyst. Neither of the cases of cyst rupture were accompanied by symptoms of chemical meningitis. The signal intensity of the tumors on T1-weighted MR imaging declined after cyst reduction. Thereafter, the cysts increased in size again at 7 months and 5 months. Regular follow-up on MR imaging is necessary, since the cyst size can increase rapidly, even after spontaneous rupture.
We designed new evaluation method using histogram of regional standardized uptake value (SUV) of every pixels of box shape volume of interest (VOI) on 18F-FDG PET. We evaluate lung and liver of normal volunteers and also the lesions of 4 cases of patients with non Hodgikin's malignant lymphoma using this method. SUV of pixels of pretreatment lesions shows log-normal distribution, whereas SUV of lung and liver show normal shape distribution. The next day of chemotherapy, 2 cases of them showed changes of distribution pattern from long-normal to normal with decrease of component of higher SUV values. No remarkable changes of distribution pattern were observed on other 2 cases, whereas decrease of regional mean values and max values of SUV were observed. And these findings were continued to 3 weeks later. These findings suggest that regional evaluation using histograms of SUV gives additional and predictive information for tumor therapies soon after the end of course.
Recently, the use of magnetic-resonance-guided navigation to improve the safety and effectiveness of surgical procedures has shown great promise. The purpose of the present study was to develop and demonstrate an imaging strategy that allows surgeons to continue operating without delays caused by imaging. The phase-scrambling Fourier-imaging technique has two prominent characteristics: localized image reconstruction and holographic image reconstruction. The combination of these characteristics allows images to be observed even during the data-acquisition period, because the acquired signal is converted into a hologram and the image is reconstructed instantly in the coherent optical image-processing system. Experimental studies have shown that the phase-scrambling Fourier-imaging technique enables the motion of objects to be imaged more quickly than the standard fast imaging. The proposed running reconstruction strategy can be easily implemented in the well-established magnetic-resonance imaging equipment that is currently in use.
BACKGROUND: Cancer cells express higher levels of glucose transporter proteins (Gluts) than do normal cells. Glut-1 overexpression is associated with invasiveness. Because matrix metalloproteinase-2 (MMP-2) is also overexpressed in cancer cells and is associated with invasiveness, we tested the hypothesis that Glut-1 may regulate MMP-2 expression. METHODS: We transiently transfected Glut-1 complementary DNA (cDNA) or Glut-1 antisense oligonucleotides in the human rhabdomyosarcoma cell line RD and analyzed MMP-2 mRNA expression and cell invasiveness. Empty vector and sense oligonucleotides were used for controls. We analyzed MMP-2 promoter activity in transfectants with a luciferase reporter assay and with p53 and Ets-1 gel mobility shift assays. Eight human cancer cell lines and 80 human cancer specimens were analyzed for coexpression of Glut-1 and MMP-2 by western blot and immunohistochemical analyses, respectively. RESULTS: Overexpression of Glut-1 in RD cells increased MMP-2 expression 4.3-fold (95% confidence interval [CI] = 3.7-fold to 4.9-fold) and invasiveness 3.2-fold (95% CI = 2.6-fold to 3.8-fold) relative to control transfected cells. Conversely, suppression of Glut-1 expression by antisense oligonucleotides decreased MMP-2 expression by 71.5% (95% CI = 71.1% to 71.9%) and invasiveness by 53.0% (95% CI = 47.5% to 58.5%). Glut-1-mediated MMP-2 expression involved the binding of the transcription factor p53 but not Ets-1. All eight human cancer cell lines coexpressed Glut-1 and MMP-2 by western blotting, and 45 of 80 human tumor tissues coexpressed Glut-1 and MMP-2 by immunohistochemistry. CONCLUSIONS: MMP-2 expression and cell invasiveness are tightly associated with Glut-1 expression in human cancer cell lines. Because suppression of Glut-1 decreased MMP-2 expression and cancer cell invasion, Glut-1 could be a target for therapy of various cancers that overexpress Glut-1.
A 44-year-old man was admitted to our hospital because of recurrent thrombosis. Laboratory findings showed that he had antiphospholipid antibody syndrome (APS) associated with systemic lupus erythematosus. Plasminogen activity was reduced (21%), but its antigenic level was rather elevated (16.4 mg/dl). The discrepancy of plasminogen activity and antigen levels was also found in his three daughters. Gene analysis revealed a homozygous missense mutation (Ala601-->Thr) at exon 15 of the plasminogen gene in the patient and a heterozygous mutation in his three daughters, suggesting that the patient has dysplasminogenaemia, which was reported as "plasminogen Tochigi." Although it still remains controversial whether both dysplasminogenaemia and plasminogen deficiency are relevant independent thrombotic risk factors, the combination of this deficiency and APS should be considered as a strong predisposition to thrombosis in this patient.
We have developed a 920-MHz NMR system and performed the proton NMR measurement of H(2)O and ethylbenzene using the superconducting magnet operating at 21.6 T (920 MHz for proton), which is the highest field produced by a superconducting NMR magnet in the persistent mode. From the NMR measurements, it is verified that both homogeneity and stability of the magnet have a specification sufficient for a high resolution NMR.