Genetic epidemiological analysis of hypouricaemia from 4993 Japanese on non-functional variants of URAT1/SLC22A12 gene.

OBJECTIVES: Up to 0.3% of Japanese have hypouricaemia. Most cases appear to result from a hereditary disease, renal hypouricaemia (RHUC), which causes exercise-induced acute kidney injury and urolithiasis. However, to what extent RHUC accounts for hypouricaemia is not known. We therefore investigated its frequency and evaluated its risks by genotyping a general Japanese population. METHODS: A cohort of 4993 Japanese was examined by genotyping the non-functional variants R90H (rs121907896) and W258X (rs121907892) of URAT1/SLC22A12, the two most common causative variants of RHUC in Japanese. RESULTS: Participants' fractional excretion of uric acid and risk allele frequencies markedly increased at lower serum uric acid (SUA) levels. Ten participants (0.200%) had an SUA level ≤2.0 mg/dl and nine had R90H or W258X and were likely to have RHUC. Logistic regression analysis revealed these URAT1 variants to be significantly and independently associated with the risk of hypouricaemia and mild hypouricaemia (SUA ≤3.0 mg/dl) as well as sex, age and BMI, but these URAT1 variants were the only risks in the hypouricaemia population (SUA ≤2.0 mg/dl). W258X was only a risk in males with SUA ≤3.0 mg/dl. CONCLUSION: Our study accurately reveals the prevalence of RHUC and provides genetic evidence for its definition (SUA ≤2.0 mg/dl). We also show that individuals with SUA ≤3.0 mg/dl, especially males, are prone to RHUC. Our findings will help to promote a better epidemiological understanding of RHUC as well as more accurate diagnosis, especially in males with mild hypouricaemia.

[Successful treatment with thalidomide-combined therapy in an amyloidosis-complicated multiple myeloma patient refractory to bortezomib, lenalidomide, and pomalidomide].

A 77-year-old man suffering from back and arm pain was referred for anemia to the hospital by an orthopedic clinic. Serum examination of the patient revealed monoclonal IgA, and he consulted the Sapporo Medical University Hospital, where he was diagnosed with multiple myeloma complicated with AL amyloidosis. He was then enrolled for a randomized double-blind study aimed to compare between melphalan-prednisone (MP) and thalidomide-melphalan-prednisone (MPT) treatments, which revealed the patient to be in the MP arm. This treatment induced a temporary partial response. After progression, he was treated with three variable combinations: 1) bortezomib and MP, 2) lenalidomide and dexamethasone, and 3) pomalidomide and dexamethasone. However, none of these treatments provided a stable response. Further, thalidomide in combination with bortezomib and dexamethasone was provided as the fifth-line treatment. After four cycles of this treatment, he achieved VGPR that lasted for 11 months. Our case report suggests that because there is a lack of a standard strategy for MM that is refractory to several agents, treatment should be selected on the basis of previous treatments and general condition of patients.

Effect of Single Nucleotide Polymorphisms of Toll-Like Receptor 4 (TLR 4) on Reproductive Performance and Immune Function in Dairy Cows.

In dairy cows, inflammatory diseases caused by infection with pathogenic bacteria post calving affect ovarian functions. This study examined the relationship between single-nucleotide polymorphisms (SNPs) of Toll-like receptor 4 (TLR4), reproductive performances [the number of artificial insemination (AI) application and days open], and immune cell functions (apoptosis and migration). Two hundred Holstein cows from the Obihiro University farm were included. The SNPs of TLR4 were genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP) method. Polymorphonuclear leukocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) were isolated from whole blood. The number of AI application in the animals with T/C genotype in the TLR4 exon3 was lower than that in animals with C/C genotype (1.6 ± 0.2 and 2.2 ± 0.2, respectively). Among the animals with TLR4 exon3 polymorphisms, the days open was shorter for the T/C cows than that for C/C cows (100.7 ± 6.9 days and 136.6 ± 9.0 days, respectively). The SNPs in the TLR4 intron did not affect the number of AI and days open. The apoptosis percentage of PMNs treated with lipopolysaccharide (LPS; 0.001 and 1 µg/ml) tended to be lower in the T/C genotype compared to that in the C/C genotype. The transmigration rates of PMNs, and IL-1ß production in PBMCs were tended to be higher for the animals with the T/C genotype compared to those for animals with the C/C genotype. Taken together, these results suggest that TLR4 polymorphisms offer a meaningful tool to judge the reproductive potential and immune activity in individual cows.

Selective sensitization of C-fiber nociceptors by hydrogen sulfide.

We examined the effects of intraplantar (i.pl.) administration of NaHS, an H2S donor, known to cause T-type Ca(2+) channel (T-channel)-dependent mechanical hyperalgesia, on responsiveness to electric stimulation with 5, 250 and 2000 Hz sine waves (SW) that selectively excites C, Aδ and Aß fibers, respectively. NaHS, given i.pl., caused behavioral hypersensitivity to SW stimulation at 5 Hz, but not 250 or 2000 Hz, in rats. NaHS also enhanced phosphorylation of spinal ERK following 5 Hz SW stimulation. Three distinct T-channel blockers abolished the NaHS-induced behavioral hypersensitivity to 5 Hz SW stimulation. Thus, H2S selectively sensitizes C-fiber nociceptors via T-channels.

[A case of primary mediastinal (Thymic) B-cell lymphoma successfully treated with the DA-EPOCH-R Regimen].

Primary mediastinal (thymic) B-cell lymphoma (PMBL) is resistant to treatment when compared with diffuse large B-cell lymphoma (DLBCL). Moreover, the optimal first -line treatment of PMBL has not yet been determined. Herein, we report a case of PMBL that was successfully treated with the dose adjusted (DA) etoposide, prednisolone, vincristine, doxorubicin, and cyclophosphamide with rituximab (EPOCH-R) regimen. A-29-year-old woman was referred to our hospital with an anterior mediastinal tumor. Eight months before admission, she had visited a clinic for pain in the chest and back, but no abnormalities were found. Subsequently, her chest pain got worse, and she went to another clinic, where she was detected with an anterior mediastinal tumor and was referred to our hospital. Tumor biopsy with a thoracoscope was performed, and a diagnosis of PMBL was made. The tumor diameter was 90 mm, with invasion to the lungs and superior vena cava. The tumor had a clinical stage of IEA, and the International Prognostic Index (IPI) was low risk. She was treated with the DA-EPOCH-R regimen for 8 courses, and a complete response was achieved. A recent retrospective study of DA-EPOCH-R treatment without radiotherapy for PMBL was recently published. It showed that the event-free survival rate was 93% and the overall survival rate was 97% during a median 5-year follow-up. Thus, DA-EPOCH-R may be a potential standard treatment for PMBL.

The effect of single nucleotide polymorphisms in the tumor necrosis factor-α gene on reproductive performance and immune function in dairy cattle.

The present study aimed to assess the effect of polymorphisms in the tumor necrosis factor α (TNF-α) promoter (A/A, A/G and G/G) and exons (T/T, T/C and C/C) on immune function and reproductive performance in dairy cows. The occurrence of the first postpartum ovulation within 3 weeks in the cows with the TNF-α promoter A/G and G/G genotypes was higher than in the A/A group. Among the different TNF-α exon genotypes, the occurrence of early first postpartum ovulation was higher in the T/C and C/C genotype groups than in the T/T group. Single nucleotide polymorphisms (SNPs) in the TNF-α gene did not affect the rate of artificial insemination (AI) or duration from parturition to next conception (days open). The apoptosis rate of polymorphonuclear leukocytes (PMNs) did not differ among the TNF-α promoter genotypes, but the PMN transmigration rate was significantly higher for the A/A and A/G genotypes than for the G/G genotype. Interleukin 8 (IL-8) mRNA expression in PMNs and peripheral blood mononuclear cells (PBMCs) before culture was significantly higher for the A/A genotype compared with the G/G genotype. There were no significant differences between the genotypes in the mRNA expression of TNF-α, IL-6, IL-1ß, and toll-like receptor 4 (TLR4) in PMNs and PBMCs before and 4 h after culture. IL-8 and IL-1ß production by PBMCs cultured for 4 h was significantly higher for the animals with the A/A genotype than for those with the G/G genotype. On the other hand, no significant difference was observed in IL-8 and IL-1ß production by PMNs among different TNF-α genotypes. Taken together, these results suggest that SNP in the TNF-α gene affects immune function and reproductive performance in dairy cows.

Allogeneic bone marrow transplantation in a patient with primary hepatic diffuse large B-cell lymphoma that relapsed after autologous stem cell transplantation.

A 64-year-old woman was admitted to our hospital due to a relapse of primary hepatic lymphoma (PHL). Three years previously, she had been referred to our hospital with a history of chronic hepatitis B for further examination of severe liver dysfunction, at which point a liver biopsy revealed PHL. She received conventional chemotherapy resulting in complete response (CR). An autologous stem cell transplantation was subsequently performed. However, 25 months after the transplantation, she suffered a relapse of PHL and was readmitted to our hospital. She achieved CR after treatment with salvage chemotherapy and then received an allogeneic bone marrow transplantation. CR has since been maintained for more than one year. This case provides insight about treatment choices in PHL.

Direct Comparison of the Effectiveness and Safety Among Direct Oral Anticoagulants and Warfarin in Japanese Patients: Nationwide Cohort Study in Japan.

Direct oral anticoagulant drugs (DOACs) are available in addition to warfarin for the treatment of patients with non-valvular atrial fibrillation (NVAF). Anticoagulants are useful for practical pharmacotherapy in Asian populations, but their responses are different from those in Caucasian populations. Therefore, we aimed to identify the most useful anticoagulant using a nationwide insurance claims database in Japan. We extracted information on patients with NVAF treated with DOACs or warfarin for the first time between September 2015 and February 2018 to conduct a retrospective observational cohort study using the claims database of Japan. We calculated hazard ratios (HR) of effectiveness and safety endpoints among DOACs or warfarin after adjusting for backgrounds by propensity scores (inverse probability weighting). Using negative control outcomes, we considered renal function as an unmeasured confounding factor. After adjusting for their backgrounds, patients treated with DOACs showed higher effectiveness endpoints (stroke or systemic embolism) than those treated with warfarin (HR; 0.72-0.81) and higher safety in terms of safety end points (clinically significant bleeding) (HR; 0.80-0.88). The net clinical benefit, which reflects the actual clinical usefulness, indicates the advantages of DOACs over warfarin (HR; 0.75-0.82). Dabigatran had lower usefulness than edoxaban and rivaroxaban in Japanese patients treated with NVAF, even after considering the unmeasured confounding factor of kidney function. Based on practical clinical data, edoxaban and rivaroxaban were the most useful anticoagulants in Japanese patients with NVAF.

Michael addition-aromatization reaction of dienylimines bearing a leaving group and its application to the preparation of thiol-selective labeling reagents capable of forming strong carbon-sulfur bonds.

The reaction of a dienylimine with thiols was found to proceed smoothly to afford the corresponding indolines bearing aromatic carbon-sulfur bonds as a result of a Michael addition-aromatization sequence. Furthermore, this reaction was applied to the development of fluorogenic dienylimines that could be used as thiol-selective fluorescent labeling reagents.

Epidemiology and predictors of hyponatremia in a contemporary cohort of patients with malignancy: a retrospective cohort study.

Background: Hyponatremia is associated with worse outcomes among patients with malignancy. However, contemporary cohort data on epidemiology and risk factors are lacking. Methods: In this single-centre, retrospective cohort study, patients who received intravenous antineoplastic agents from 2018 to 2020 at Nagoya City University Hospital were enrolled. Associations of demographics, antineoplastic agents, types of malignancy and concomitant medications with hyponatremia, defined as serum sodium concentration ≤130 mmol/l, were analysed by mixed-effects logistic regression and the machine learning-based LightGBM model artificial intelligence technology. Results: Among 2644 patients, 657 (24.8%) developed at least one episode of hyponatremia. Approximately 80% of hyponatremia was due to sodium wasting from the kidneys. Variables associated with hyponatremia both by mixed-effects logistic regression and the LightGBM model were older age, hypoalbuminemia and higher estimated glomerular filtration rate. Among antineoplastic agents, cisplatin {odds ratio [OR] 1.52 [95% confidence interval (CI) 1.18-1.96]}, pembrolizumab [OR 1.42 (95% CI 1.02-1.97)] and bortezomib [OR 3.04 (95% CI 1.96-4.71)] were associated with hyponatremia and these variables also had a positive impact on predicted hyponatremia in the LightGBM model. Conclusions: Hyponatremia was common among patients with malignancy. In addition to older age and poor nutritional status, novel antineoplastic agents, including immune checkpoint inhibitors and bortezomib, should be recognized as risk factors for hyponatremia.

Phosphorylation of human INO80 is involved in DNA damage tolerance.

Double strand breaks (DSBs) are the most serious type of DNA damage. DSBs can be generated directly by exposure to ionizing radiation or indirectly by replication fork collapse. The DNA damage tolerance pathway, which is conserved from bacteria to humans, prevents this collapse by overcoming replication blockages. The INO80 chromatin remodeling complex plays an important role in the DNA damage response. The yeast INO80 complex participates in the DNA damage tolerance pathway. The mechanisms regulating yINO80 complex are not fully understood, but yeast INO80 complex are necessary for efficient proliferating cell nuclear antigen (PCNA) ubiquitination and for recruitment of Rad18 to replication forks. In contrast, the function of the mammalian INO80 complex in DNA damage tolerance is less clear. Here, we show that human INO80 was necessary for PCNA ubiquitination and recruitment of Rad18 to DNA damage sites. Moreover, the C-terminal region of human INO80 was phosphorylated, and overexpression of a phosphorylation-deficient mutant of human INO80 resulted in decreased ubiquitination of PCNA during DNA replication. These results suggest that the human INO80 complex, like the yeast complex, was involved in the DNA damage tolerance pathway and that phosphorylation of human INO80 was involved in the DNA damage tolerance pathway. These findings provide new insights into the DNA damage tolerance pathway in mammalian cells.

Variants in the flavin-containing monooxygenase 3 (FMO3) gene responsible for trimethylaminuria in a Japanese population.

Loss-of-function mutations of flavin-containing monooxygenase 3 (FMO3), the enzyme responsible for trimethylamine N-oxygenation, cause the inherited disorder trimethylaminuria, or fish odor syndrome. The aim of this study was to further investigate the inter-individual variations of FMO3 activity in a Japanese cohort that we had studied previously. The subjects were 640 Japanese volunteers with self-reported trimethylaminuria; genomic DNA was sequenced in those that had 10-70% FMO3 metabolic capacity in urine tests. A heterozygote for the novel single nucleotide substitution p.Ile441Thr (proband 1) and a heterozygote for the novel single nucleotide substitution p.Ser195Leu (proband 2) were identified. The biological parents of probands 1 and 2 were heterozygous and had >90% trimethylamine N-oxygenation metabolic capacity. In addition, single nucleotide substitutions p.Val58Ile, p.Pro70Leu, and p.Gly421Val in FMO3 were found in probands 3-7. In the course of DNA sequencing, another FMO3 variant, p.Thr488Ala, was found in two unrelated heterozygous subjects. Variant FMO3 proteins recombinantly expressed in Escherichia coli membranes exhibited decreased activity toward typical FMO3 substrates. Although the allele frequencies of these six novel variants were low (<1%), the present results suggest that individuals homozygous or heterozygous for any of the six novel missense FMO3 variants or known nonsense mutations such as p.Cys197stop or p.Arg500stop may possess abnormal trimethylamine N-oxygenation.

Relationships between the first ovulation postpartum and polymorphism in genes relating to function of immunity, metabolism and reproduction in high-producing dairy cows.

The decrease in fertility and conception rates of high-producing dairy cows is one of the major negative impacts for today's producers. The recovery of ovarian activity postpartum is affected by the status of immunity, metabolism and reproduction and plays a critical role in subsequent fertility after parturition in the cow. In the present study we investigated the relationships between polymorphisms in genes relating to the above functions and the first postpartum ovulation as a marker of the recovery of ovarian function in the cow. In immune function related-factors, the occurrence of first postpartum ovulation within 3 weeks in the C/C genotypes of tumor necrosis factor α (TNFα) exon (55.4%) and the A/G genotypes of TNFα promoter (55.4%) was significantly higher than that in T/T genotypes of TNFα exon (14.3%) and A/A genotypes of TNFα promoter (14.3%). Moreover, anovulatory cows with the T/T genotype of TNFα exon and the A/A genotype of TNFα promoter tended to have a prolonged days open compared with those of the other genotypes of TNFα polymorphisms. In metabolic function-related factors, ovulatory and anovulatory cows had a different distribution for alleles of the growth hormone receptor, but there were no significant differences in genotype and allele frequency of insulin-like growth factor-I polymorphism. No significant relationships were found between ovarian function after parturition and polymorphisms for reproduction-related genes. In conclusion, polymorphisms of TNFα gene both in exon and promoter regions have a strong association with the early first ovulation within 3 weeks after parturition in the high-producing dairy cow. Taken together, polymorphisms of TNFα gene could be strongly related to early first ovulation after parturition, thus being an effective tool of selection for improving reproductive performance in the high-producing dairy cow.

Irinotecan as the key chemotherapeutic agent in second-line treatment of metastatic gastric cancer after failure of first-line S-1 or S-1/CDDP therapy.

BACKGROUND: S-1, an oral fluoropyrimidine, is one of the standard chemotherapeutic agents for the treatment of metastatic gastric cancer(MGC). However, the most effective second-line regimen after failure of treatment with first-line agents such as S-1 is yet to be determined. The aim of this study was to investigate the various second-line chemotherapy regimens in MGC patients. METHODS: We retrospectively studied patients with MGC who received second-line treatment after failure of the first-line S-1 or S-1/cisplatin treatment. The overall survival times with each second-line regimen were determined using the Kaplan-Meier method, and the effect on overall survival was analyzed using Cox regression analysis. RESULTS: The median survival time for all patients was 14. 2 months(95% confidence interval(CI): 12. 88-15. 43 months)with a 1-year survival rate of 60. 4%. Kaplan-Meier analysis revealed that the second-line regimens containing irinotecan significantly improved the median survival time as compared to regimens without irinotecan(median survival time: 16. 5 and 13. 8 months, respectively). Cox regression analysis showed that irinotecan-containing regimens were associated with improved overall survival(hazard ratio: 0. 165; 95% CI: 0. 041-0. 665). CONCLUSION: The use of irinotecan-containing regimens as second-line chemotherapy after failure of first-line S-1 therapy may be beneficial for MGC patients.

Phosphorylation of ERK in the spinal dorsal horn following pancreatic pronociceptive stimuli with proteinase-activated receptor-2 agonists and hydrogen sulfide in rats: evidence for involvement of distinct mechanisms.

Noxious stimuli cause prompt phosphorylation of extracellular signal-regulated kinase (ERK) in the spinal dorsal horn that contributes to facilitation of pain sensation and is often used as an immediate marker for excitation of spinal neurons following somatic and colonic nociception. Here we asked whether two distinct pronociceptive stimuli with proteinase-activated receptor-2 (PAR2) agonists and hydrogen sulfide (H(2)S) in the pancreas cause phosphorylation of ERK in the spinal dorsal horn and also examined involvement of their possible downstream signaling molecules, transient receptor potential vanilloid-1 (TRPV1) and T-type Ca(2+) channels, respectively. Capsaicin (a TRPV1 agonist), trypsin (an endogenous PAR2 agonist), SLIGRL-NH(2) (a PAR2-activating peptide), and NaHS (an H(2)S donor) were infused into the pancreatic duct in anesthetized rats, and phosphorylated ERK in the spinal cord was detected by immunohistochemistry. Intraductal administration of capsaicin and trypsin caused prompt phosphorylation of ERK in the superficial layers of T9, but not T5 or T12, spinal dorsal horn. SLIGRL-NH(2) and NaHS, administered in the same manner, also produced ERK phosphorylation in the corresponding spinal regions. Mibefradil, a T-type Ca(2+) channel blocker, abolished the phosphorylation of ERK caused by intraductal NaHS but not SLIGRL-NH(2). In contrast, capsazepine, an inhibitor of TRPV1, suppressed the phosphorylation of ERK caused by intraductal SLIGRL-NH(2) but not NaHS. Our data thus demonstrate that pancreatic pronociceptive stimuli with PAR2 agonists and H(2)S cause ERK phosphorylation in the spinal dorsal horn, through activation of TRPV1 and T-type Ca(2+) channels, respectively, and that those two pronociceptive pathways are independent of each other.

L-Ascorbate Biosynthesis Involves Carbon Skeleton Rearrangement in the Nematode Caenorhabditis elegans.

Ascorbate (AsA) is required as a cofactor and is widely distributed in plants and animals. Recently, it has been suggested that the nematode Caenorhabditis elegans also synthesizes AsA. However, its biosynthetic pathway is still unknown. To further understand AsA biosynthesis in C. elegans, we analyzed the incorporation of the 13C atom into AsA using gas chromatography-mass spectrometry (GC-MS) in worms fed with D-Glc (1-13C)-labeled Escherichia coli. GC-MS analysis revealed that AsA biosynthesis in C. elegans, similarly to that in mammalian systems, involves carbon skeleton rearrangement. The addition of L-gulono-1,4-lactone, an AsA precursor in the mammalian pathway, significantly increased AsA level in C. elegans, whereas the addition of L-galactono-1,4-lactone, an AsA precursor in the plant and Euglena pathway, did not affect AsA level. The suppression of E03H4.3 (an ortholog of gluconolactonase) or the deficiency of F54D5.12 (an ortholog of L-gulono-1,4-lactone oxidase) significantly decreased AsA level in C. elegans. Although N2- and AsA-deficient F54D5.12 knockout mutant worm (tm6671) morphologies and the ratio of collagen to non-collagen protein did not show any significant differences, the mutant worms exhibited increased malondialdehyde levels and reduced lifespan compared with the N2 worms. In conclusion, our findings indicate that the AsA biosynthetic pathway is similar in C. elegans and mammals.

Elevation of Plasmin-α2-plasmin Inhibitor Complex Predicts the Diagnosis of Systemic AL Amyloidosis in Patients with Monoclonal Protein.

Objective The complication of systemic immunoglobulin light chain (AL) amyloidosis in patients with monoclonal immunoglobulin affects the prognosis, but amyloid deposition in tissues is sometimes difficult to detect due to bleeding tendencies and preferential distributions. However, fibrinolysis is known to be exacerbated in patients with systemic AL amyloidosis specifically. We therefore explored new biomarkers for predicting a diagnosis of systemic AL amyloidosis focusing on coagulation and fibrinolysis markers. Methods We reviewed the clinical features and treatment outcomes of patients with serum monoclonal protein, including primary systemic AL amyloidosis and multiple myeloma (MM), treated at our hospital between January 2008 and December 2014. Results Among several biomarkers, only the serum level of plasmin-α2-plasmin inhibitor complex (PIC) in patients with systemic AL amyloidosis (n=26) at the diagnosis was significantly higher than in patients with MM without AL amyloidosis (n=26) (mean±standard deviation, 3.69±2.82 µg/mL vs. 1.23±0.97 µg/mL, p<0.01). The cut-off for predicting a diagnosis of systemic AL amyloidosis in patients with serum monoclonal protein was 1.72 µg/mL with 84.6% sensitivity and 80.8% specificity. Hepatic involvement resulted in a significantly higher PIC level than no involvement in patients with systemic AL amyloidosis. The serum PIC level was also associated with the hematological response of systemic AL amyloidosis. Conclusion PIC is a useful biomarker for the diagnosis and management of patients with systemic AL amyloidosis.

DEC1 promotes hypoxia-induced epithelial-mesenchymal transition (EMT) in human hepatocellular carcinoma cells.

Differentiated embryonic chondrocyte (DEC) 1 has been reported to be involved in cell differentiation, hypoxia response, and cancer progression. Recent studies have demonstrated that hypoxia-inducible factor (HIF)-1α induces epithelial-mesenchymal transition (EMT) in carcinoma cells to facilitate cell invasiveness and metastasis. However, it remains unclear whether DEC1 participates in hypoxia-mediated EMT processes. In the present study, we reported that hypoxia induced DEC1 expression in hepatocellular carcinoma (HCC) HepG2 cells, and DEC1 negatively regulated expression of HIF-1α and E-cadherin in transcriptional/translational levels. Cell morphological changes were evaluated with hematoxylin and eosin (H-E) staining. Exposure to hypoxia caused spindle-like shape in some of the HepG2 cells, and DEC1 overexpression furthered these changes. In conclusions, DEC1 is involved in hypoxia-induced EMT processes via negatively regulating E-cadherin expression in HepG2 cells.

Other Iatrogenic Immunodeficiency-associated Lymphoproliferative Disorder Presenting as Primary Bone Lymphoma in a Patient with Rheumatoid Arthritis.

Primary bone lymphoma (PBL) is a rare disorder. We herein present a case of other iatrogenic immunodeficiency-associated lymphoproliferative disorder (OIIA-LPD) presenting as PBL. A 63-year-old woman was diagnosed with rheumatoid arthritis and had been treated with methotrexate for seven years. Two months before admission, she suffered from pain in the limbs. Magnetic resonance imaging revealed multiple irregular lesions in the bones of the limbs, which showed an uptake of (18)F-FDG on positron emission tomography. A biopsy of the right radius revealed diffuse large B-cell lymphoma, leading to the diagnosis of OIIA-LPD. She received rituximab-containing regimens resulting in a complete response.

[A case of bronchial foreign body due to citrus fruit seed aspiration showing multiple pulmonary infiltration repeatedly].

We report a case of a bronchial foreign body in a 76-year-old citrus fruit farmer. The patient was detected patchy infiltration (ground-glass attenuation) of the right upper lung field on the chest X-ray on Dec. 26th, 2003. The shadow tended to disappear after treatment with antibiotics. The same shadow was detected again 10 months later and the patient underwent a bronchoscopic examination. A foreign body was found lodged in the center of the right upper bronchus, associated with bronchial stenosis due to mucosal edema. The abnormal shadow disappeared after the foreign body, which we decided was a citrus fruit seed, was removed. From the time course of the present illness and a retrospective evaluation of previous chest X-rays, the patient had aspirated the foreign body 18 months prior to his admission for bronchoscopy. We should be careful of the possibility of foreign bodies even when the elderly do not present a history of foreign body aspiration. It is important to consider the possibility of a bronchial foreign body in patients with repeated pneumonia, and to perform bronchoscopy aggressively.