1.Impact of mutation at V2 of gp120 on V3-specific neutralizing antibodies
Musang LIU ; Matsushita SHUZO ; Shibata JUNJI ; Weida LIU
Chinese Journal of Microbiology and Immunology 2011;31(7):613-617
Objective To study the impact of V2 mutations on neutralizing ability of HIV-1-specific neutralizing antibodies. Methods We tested the influence of L175P mutation to the neutralizing ability of V3-specific antibodies by pseudotype virus and the binding affinity of those V3-spesific antibodies to gpl20 monomer by ELISA. Results We found L175P mutation changed the neutralizing ability of V3-specific antibodies. However, L175P mutation showed no effects on the binding affinity of these antibodies to gpl20 monomer. Conclusion Our results revealed the L175P mutation at V2 loop changed the natural trimmer structure of gp120 and enhanced the neutralizing ability of V3-specific antibodies.
2.Impact of mutations in the V2 domain of HIV-1 envelop glycoprotein 120 on the recognition of neutralizing antibodies targeting the CD4-binding site
Musang LIU ; Matsushita SHUZO ; Shibata JUNJI ; Weida LIU
Chinese Journal of Dermatology 2012;45(10):731-734
Objective To investigate the impact of mutations in the V2 domain of HIV-1 envelop glycoprotein (gp) 120 gene on the recognition of neutralizing antibodies (NAbs) specific to the other domains of gp120.MethodsHIV-1 pseudoviruses (JR-FL) containing wild type or V2-mutant gp120 monomers were constructed,and the neutralization of CD4-binding site-specific and CD4-induced NAbs to the HIV-1 pseudoviruses was observed.Enzyme linked immunosorbent assay(ELISA) was performed to evaluate the binding affinity of CD4-binding site-specific and CD4-induced NAbs to wild type or V2-mutant gp120.Results Neither CD4-binding site-specific nor CD4-induced NAbs could neutralize the wild type JR-FL pseudoviruses,but both of them could neutralize pseudoviruses containg the gp120 V2 mutant at a low concentration.There was no significant difference in the binding affinity to CD4-binding site-specific NAbs between the wild type and mutant gp120,while the ELISA binding curves of wild type and mutant gp120 against CD4-induced NAbs were separate,and the affinity of CD4-induced NAbs to the mutant gp120 (L175P) was notably higher than that to the wild type gp120.Conclusion The mutations in the V2 domain of HIV-1 gp120 may affect the antiviral activity of NAbs.
3.Human immunodeficiency virus type 1(HIV-1)V2 L175P mutation increases the binding capability of neutralizing antibodies to HIV-1
Musang LIU ; Matsushita SHUZO ; Shibata JUNJI ; Weida LIU
Chinese Journal of Dermatology 2011;44(10):717-719
Objective To study the impact of HIV-1 V2 L175P mutation on the binding capability of anti-V3 neutralizing antibodies to HIV-1.Methods A series of eukaryotic cell expression plasmids were used to concatenate wild type and mutant env gene of HIV-1 and green fluorescent protein(GFP)gene.The recombinant plasmids were transfected into 293T cells to express HIV-1 gp120 protein on the surface of cells.The successfully transfected cells were screened by GFP florescence marker.Immunostaining and dual fluorescence flow cytometry were performed to test the binding affinity of several common V3 region specific neutralizing antibodies to wild type or mutant gp120 proteins.Results The mean fluorescence intensity(MFI)of mutant gp120-expressing 293T cells were significantly higher than that of negative control cells(expressing GFP).Flow cytometry showed that the curve for mutant gp120-expressing 293T cells was obviously different in shape and peak from that for the negative control,while most parts of the curve for the wild type gp120-expressing 293T cells overlapped with those for the negative control.Conclusion The V2 region mutation may increase the sensitivity of HIV-1 to the neutralization by V3 region specific antibodies.
4.One-year clinical efficacy and safety of indigo naturalis for active ulcerative colitis: a real-world prospective study
Yuichi MATSUNO ; Takehiro TORISU ; Junji UMENO ; Hiroki SHIBATA ; Atsushi HIRANO ; Yuta FUYUNO ; Yasuharu OKAMOTO ; Shin FUJIOKA ; Keisuke KAWASAKI ; Tomohiko MORIYAMA ; Tomohiro NAGASUE ; Keizo ZEZE ; Yoichiro HIRAKAWA ; Shinichiro KAWATOKO ; Yutaka KOGA ; Yoshinao ODA ; Motohiro ESAKI ; Takanari KITAZONO
Intestinal Research 2022;20(2):260-268
Background/Aims:
Recent studies suggested a favorable effect of indigo naturalis (IN) in inducing remission for refractory ulcerative colitis (UC), however, the maintenance effect of IN for patients with UC remains unknown. Therefore, we conducted a prospective uncontrolled open-label study to analyze the efficacy and safety of IN for patients with UC.
Methods:
Patients with moderate to severe active UC (clinical activity index [CAI] ≥ 8) took 2 g/day of IN for 52 weeks. CAI at weeks 0, 4, 8, and 52 and Mayo endoscopic subscore (MES) and Geboes score (GS) at weeks 0, 4, and 52 were assessed. Clinical remission (CAI ≤ 4), mucosal healing (MES ≤ 1), and histological healing (GS ≤ 1) rates at each assessment were evaluated. Overall adverse events (AEs) during study period were also evaluated. The impact of IN on mucosal microbial composition was assessed using 16S ribosomal RNA gene sequences.
Results:
Thirty-three patients were enrolled. The rates of clinical remission at weeks 4, 8, and 52 were 67%, 76%, and 73%, respectively. The rates of mucosal healing at weeks 4 and 52 were 48% and 70%, respectively. AEs occurred in 17 patients (51.5%) during follow-up. Four patients (12.1%) showed severe AEs, among whom 3 manifested acute colitis. No significant alteration in the mucosal microbial composition was observed with IN treatment.
Conclusions
One-year treatment of moderate to severe UC with IN was effective. IN might be a promising therapeutic option for maintaining remission in UC, although the relatively high rate of AEs should be considered.
5.Treating Neurogenic Heterotopic Ossification around a Femur Following Paraplegia after an Open Surgery for Thoracoabdominal Aortic Aneurysm
Itaru HOSAKA ; Yutaka IBA ; Shingo TSUSHIMA ; Tsuyoshi SHIBATA ; Junji NAKAZAWA ; Tomohiro NAKAJIMA ; Nobuyoshi KAWAHARADA
Japanese Journal of Cardiovascular Surgery 2023;52(2):128-132
A 59-year-old man who was diagnosed with hypertension and a large thoracoabdominal aortic aneurysm was referred to our hospital for surgical treatment. He underwent open surgery and thoracic endovascular aneurysm repair in three stages. He developed paraplegia after the third surgery. Despite acute postoperative treatment and rehabilitation, his lower extremity motor function and bladder and bowel dysfunction did not improve. He was transferred to a recovery hospital 67 days after the third surgery. However, he was readmitted to our hospital about four months later for management of a refractory decubitus ulcer and recurrent urinary tract infections. Computed tomography revealed hematoma and calcification around the femur. Based on the clinical course and imaging findings, we diagnosed neurogenic heterotopic ossification associated with postoperative paraplegia in this patient. He had flap reconstruction for the ulcer. Finally, he was discharged 79 days after readmission. To date, no study has reported neurogenic heterotopic ossification associated with postoperative aortic aneurysm paraplegia. The mechanism underlying this condition is similar to the widely accepted process associated with traumatic spinal cord injury, and conservative treatment comprising pressure ulcer treatment and antibiotics was continued. Although acute rehabilitation is important after highly invasive aortic aneurysm surgery, rehabilitation is limited by the risk of neurogenic heterotopic ossification in patients with postoperative paraplegia, and recovery and maintenance of activities of daily living are challenging. To our knowledge, early diagnosis and prompt treatment for these complications are important considering neurogenic heterotopic ossification.
6.A Case of Antiphospholipid Syndrome Underwent Cardiac Surgery Performed Using Coagulation Management by Measuring Heparin Concentration during Extracorporeal Circulation
Riko UMETA ; Tomohiro NAKAJIMA ; Yutaka IBA ; Itaru HOSAKA ; Akihito OKAWA ; Naomi YASUDA ; Tsuyoshi SHIBATA ; Junji NAKAZAWA ; Nobuyoshi KAWAHARADA
Japanese Journal of Cardiovascular Surgery 2023;52(1):9-13
A 72-year-old female was diagnosed with systemic lupus erythematosus and antiphospholipid syndrome (APS) in 2014 and was followed up. Severe mitral regurgitation coexisted with APS, but the case was nonsymptomatic, and surgery involved high risk. Therefore, the physicians continued their observation. In 2020, the patient experienced rheumatic severe mitral stenosis and shortness of breath on exertion. Paroxysmal atrial fibrillation and coronary stenosis were also detected. Therefore, we planned mitral valve replacement, tricuspid annuloplasty, coronary artery bypass, pulmonary vein isolation and left atrial appendage closure. During extracorporeal circulation (ECC), we performed coagulation management based on blood heparin concentration using HMS PLUS. Because the APS patient showed prolonged activated clotting time (ACT), and coagulation therapy based on ACT is unreliable. She was discharged from our hospital on postoperative day 23. No complications, including bleeding and thrombosis, were observed 2 years after the operation. We experienced a case of APS who underwent cardiac surgery and performed coagulation management by measuring heparin concentration during ECC. We targeted a 3.5 U/ml heparin concentration, and her clinical course was uneventful.
7.A Successful Case of Redo-Tricuspid Valve Replacement for Prosthetic Valve Endocarditis Thirty-Two Years after Single Tricuspid Bioprosthetic Valve Replacement
Shuhei MIURA ; Yutaka IBA ; Kei MUKAWA ; Keitaro NAKANISHI ; Takakimi MIZUNO ; Ayaka ARIHARA ; Tsuyoshi SHIBATA ; Junji NAKAZAWA ; Tomohiro NAKAJIMA ; Nobuyoshi KAWAHARADA
Japanese Journal of Cardiovascular Surgery 2024;53(3):100-104
We present a successful case of redo-tricuspid valve replacement for tricuspid prosthetic valve endocarditis. A 78-year-old man who underwent tricuspid bioprosthetic valve replacement for severe tricuspid regurgitation thirty-two years earlier was referred to our institution with persistent high fever and back pain. The blood culture was positive for Streptococcus oralis, and echocardiography revealed a mobile vegetation attached to the tricuspid prosthetic valve with moderate tricuspid regurgitation. A clinical diagnosis of prosthetic valve endocarditis was established. Redo-tricuspid bioprosthetic valve replacement was performed following antibiotics therapy. The patient was discharged on postoperative day 49 after 6 weeks of additional antibiotic treatment, and had no recurrence of infection for 6 months after redo-surgery.