Association of the −173 G/C polymorphism of the macrophage migration inhibitory factor gene with ulcerative colitis

Background Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine and has been shown to be involved in the development of chronic murine colitis. In the +173G/C polymorphism of the MIF gene, the presence of C creates the binding motif of activator protein 4. This study explored the association of this polymorphism with ulcerative colitis (UC).Methods Genotyping was carried out, with a tetra-primer polymerase chain reaction (PCR) method, for 659 DNA specimens from 438 healthy volunteers and 221 patients with UC. Genotype distribution between cases and controls and the association of patients genotypes with clinical parameters were statistically evaluated.Results No significant difference in genotype distribution was found between UC patients and healthy controls. However, when the relation of the C/C genotype to clinical parameters in UC patients was evaluated by Fishers exact test, it was found that the frequency of the C/C genotype was higher in patients with pancolitis type than in those with other types restricted to the distal or left-sided colon (odds ratio [OR], 10.781; 95% confidence interval [CI], 1.342–86.619; P = 0.0074).Conclusions These data suggest that the MIF –173G/C polymorphism may be related to the extent of disease in UC in a Japanese population.     

Relapsing polychondritis presenting as encephalitis

Relapsing polychondritis (RP) is a rare, generalized autoimmune disorder that is characterized by recurrent inflammation of various cartilaginous structures. Involvement of the central nervous system is rarely observed in RP. Here we report a case of encephalitis associated with RP. A 60-year-old man presented with headache and bilateral ear swelling. Three weeks later, he came to our hospital because of the acute onset of a speech impediment. A non-contrast computed tomography scan of the head showed slight high-density areas in his left frontal lobe, but he refused to be admitted and went home. On the next day, he developed acalculia, agraphia, right-left disorientation, and mild right hemiparesis. Brain MRI revealed hyperintensity areas in the left frontal sulcus on fluid-attenuated inversion recovery (FLAIR) images, and these hyperintensity areas were enhanced by gadolinium. Therefore, the patient's symptoms were diagnosed as focal epilepsy caused by meningoencephalitis. Other examinations, including laboratory blood tests, cerebrospinal fluid tests, and a cerebral angiography, were all negative. Therefore, a brain biopsy of the left frontal cortex was performed 5 days after the patient's admission. Pathological findings revealed chronic inflammation of the meninges, so prednisone was administered. After receiving oral prednisone, the patient's bilateral ear swelling dramatically improved and the lesions apparent on cranial MRI gradually subsided. The patient was diagnosed with RP by a neurologist after discharge from the hospital. In this study, early diagnosis and steroid treatment is recommended for patients with neurological complications due to RP.     

Genomic determinants impacting the clinical outcome of mogamulizumab treatment for adult T-cell leukemia/lymphoma

In order to identify genomic biomarkers for the outcome of mogamulizumab-containing treatment, an integrated molecular analysis of adult T-cell leukemia/lymphoma (ATL) was conducted on 64 mogamulizumab-naïve patients. Among driver genes, CCR4 and CCR7 alterations were observed in 22% and 11% of the patients, respectively, both consisting of single nucleotide variants (SNV)/insertion-deletions (indels) in the C-terminus. Patients with CCR4 alterations or without CCR7 alterations exhibited a more favorable clinical response (complete response [CR] rate 93%, 13/14; P=0.024, and CR rate 71%, 40/56; P=0.036, respectively). Additionally, TP53, CD28, and CD274 alterations were identified in 35%, 16%, and 10% of the patients, respectively. TP53 alterations included SNV/indels or copy number variations (CNV) such as homozygous deletion; CD28 alterations included SNV, CNV such as amplification, or fusion; CD274 alterations included CNV such as amplification, or structural variants. Univariate analysis revealed that TP53, CD28 or CD274 alterations were associated with worse overall survival (OS) (hazard ratio [HR]: 2.330, 95% confidence interval [CI]: 1.183-4.589; HR: 3.191, 95% CI: 1.287-7.911; HR: 3.301, 95% CI: 1.130-9.641, respectively) but that CCR4 alterations were associated with better OS (HR: 0.286, 95% CI: 0.087-0.933). Multivariate analysis indicated that in addition to performance status, TP53, CCR4 or CD274 alterations (HR: 2.467, 95% CI: 1.197-5.085; HR: 0.155, 95% CI: 0.031-0.778; HR: 14.393, 95% CI: 2.437-85.005, respectively) were independently and significantly associated with OS. The present study contributes to the establishment of precision medicine using mogamulizumab in ATL patients.     

Aortocoronary saphenous vein graft aneurysm in redo coronary artery bypass grafting: Report of a case

(Received for publication on Oct. 14, 1996; accepted on Mar. 4, 1997)     

Analyses of serum lipoprotein(a) and the relation to phenotypes and genotypes of apolipoprotein(a) in type 2 diabetic patients with retinopathy.

To elucidate the association of lipoprotein(a) (Lp(a)) with diabetic retinopathy (DR), we studied the serum Lp(a) concentrations (n = 412), apolipoprotein(a) (apo(a)) phenotypes expressed by the number of kringle 4 (K4) repeats (n = 150), apo(a) gene genotypes (n = 161) of type 2 diabetes with or without DR. The 5'-untranslated region of apo(a) gene was classified into seven haplotypes (A to G) and 18 genotypes by PCR-RFLP at three distinct sites. The serum Lp(a) concentrations were significantly higher in diabetic patients than in normal controls. Furthermore, the patients with DR, especially proliferative retinopathy showed higher serum Lp(a) concentrations than those without DR. Although a negative correlation was found between the serum Lp(a) concentrations and the number of K4 repeats in total diabetic patients, no difference was seen in the distribution of the number of K4 repeats between those with and without DR. In the same apo(a) phenotypes, the patients with DR had higher Lp(a) concentrations than those without DR. Among the genotypes, type CC showed significantly higher serum Lp(a) concentrations than the other genotypes. However, there was no difference in the ratios of the type CC between the patients with and without DR. In conclusion, other factors than phenotypes and genotypes in the 5'-untranslated region of apo(a) may be responsible for the elevation of serum Lp(a) in diabetic patients with retinopathy.