Genotypes at chromosome 22q12-13 are associated with HIV-1-exposed but uninfected status in Italians

OBJECTIVE: Despite multiple and repeated exposures to HIV-1, some individuals possess no detectable HIV genome and show T-cell memory responses to the viral antigens. HIV-1-reactive mucosal IgA detected in such uninfected individuals suggests their possible immune resistance against HIV. We tested if the above HIV-1-exposed but uninfected status was associated with genetic markers other than a homozygous deletion of the CCR5 gene. METHODS: Based on our mapping in chromosome 15 of a gene controlling the production of neutralizing antibodies in a mouse retrovirus infection, we genotyped 42 HIV-1-exposed but uninfected Italians at polymorphic loci in the syntenic segment of human chromosome 22, and compared them with 49 HIV-1-infected and 47 uninfected healthy control individuals by a closed testing procedure. RESULTS: A significant association was found between chromosome 22q12-13 genotypes and a putative dominant locus conferring anti-HIV-1 immune responses in the exposed but uninfected individuals. Distributions of linkage disequilibrium across chromosome 22 also differed between the exposed but uninfected and two other phenotypic groups. CONCLUSIONS: The data indicated the presence of a new genetic factor associated with the HIV-1-exposed but uninfected status.     

PET Imaging Analysis of Vitamin B<Subscript>1</Subscript> Kinetics with [<Superscript>11</Superscript>C]Thiamine and its Derivative [<Superscript>11</Superscript>C]Thiamine Tetrahydrofurfuryl Disulfide in Rats

Purpose

Thiamine is an essential component of glucose metabolism and energy production. The disulfide derivative, thiamine tetrahydrofurfuryl disulfide (TTFD), is better absorbed than readily-available water-soluble thiamine salts because it does not require the rate-limiting transport system required for thiamine absorption. However, the detailed pharmacokinetics of thiamine and TTFD under normal and pathological conditions have not yet been clarified. C-11-labeled thiamine and TTFD were recently synthesized by our group. In this study, to clarify the differences in pharmacokinetics and metabolism of these probes, a quantitative PET imaging study and radiometabolite analysis of C-11-labeled thiamine and TTFD were performed in the rat heart.

Procedures

Positron emission tomography (PET) imaging with [¹¹C]thiamine and [¹¹C]TTFD was performed in normal rats to determine the pharmacokinetics of these probes, and the radiometabolites of both probes from the blood and heart tissue were analyzed by thin-layer chromatography.

Results

Accumulation of [¹¹C]TTFD was significantly higher than that of [¹¹C]thiamine in the rat heart. Moreover, as a result of the radiometabolite analysis of heart tissue at 15 min after the injection of [¹¹C]TTFD, thiamine pyrophosphate, which serves as a cofactor for the enzymes involved in glucose metabolism, was found as the major radiometabolite and at a significantly higher level than in the [¹¹C]thiamine-injected group.

Conclusions

PET imaging techniques for visualizing the kinetics and metabolism of thiamine using [¹¹C]thiamine and [¹¹C]TTFD were developed in this study. Consequently, noninvasive PET imaging for the pathophysiology of thiamine-related cardiac function may provide novel information about heart failure and related disorders.

     

Construction of an infectious cDNA clone of radish mosaic virus, a crucifer-infecting comovirus

Radish mosaic virus (RaMV) is a crucifer-infecting comovirus that has been detected worldwide. Here, we report the successful construction of a full-length infectious cDNA clone of RaMV. The full-length cDNA clones corresponding to RNA1 and RNA2 of a Japanese isolate of RaMV were cloned into the pBlueScript plasmid or the binary vector pCAMBIA1301 downstream of the cauliflower mosaic virus 35S promoter. Mechanical inoculation or agroinoculation of Nicotiana benthamiana with these vectors resulted in systemic RaMV infections causing symptoms similar to those caused by the wild-type parental virus. The presence of progeny virus was verified by western blot analysis and electron microscopy.     

Latent abnormal fatty acid metabolism in apparently normal perfusion during stress in patients with restenosis after coronary angioplasty: assessment by exercise stress thallium-201 and iodine-123-labeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid-dual myocardial single-photon emission computed tomography

Restenosis is a major problem in patients undergoing coronary angioplasty. Reduced uptake of iodine-123-labeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (I-BMIPP-123) relatively to thallium-201 (Tl-201) has been attributed to the metabolic damage in the myocardium in patients with coronary artery disease. Therefore, we performed exercise stress Tl-201 and I-BMIPP-123 dual myocardial single-photon emission computed tomography (SPECT) to detect coronary restenosis in 48 patients (35 men and 13 women, mean age 66 +/- 8 years), followed by coronary angiography at follow-up. Patients were divided into 2 groups: those with (n = 24) and without (n = 24) restenosis. Redistribution of Tl-201 was seen more frequently in the restenosis group than in no-restenosis group (58% [14 of 24] vs 8% [2 of 24], p <0.05). Five of 10 patients (50%) with restenosis but without Tl-201 redistribution had Tl-201/I-BMIPP-123 discrepancy during stress. In patients without restenosis, only 1 patient had this discrepancy during stress. Incorporation of Tl-201/I-BMIPP-123 uptake discrepancy during stress significantly improved the sensitivity (58% [14 of 24] to 79% [19 of 24]) with preserved specificity (92% [22 of 24] to 88% [21 of 24]). Exercise stress Tl-201 and I-BMIPP-123 dual myocardial SPECT revealed that latent abnormal fatty acid metabolism may exist in apparently normal perfusion during stress in patients with restenosis after coronary angioplasty. Use of I-BMIPP-123 together with Tl-201 during stress SPECT substantially improved the diagnostic accuracy of restenosis based on Tl-201 redistribution (from 75% to 83%).     

Amebic colitis in asymptomatic subjects with positive fecal occult blood test results: clinical features different from symptomatic cases

Amebiasis is a common parasitic infectious disease in developing countries. In developed countries, it is occasionally encountered in travelers to the tropics and in homosexual males. During the past eight years, we detected four cases of amebic colitis among 5,193 subjects who underwent colonoscopy because of positive fecal occult blood test results in a mass screening. All four cases did not have any abdominal symptoms. Ulcerative lesions were observed only in the cecum and ascending colon; another portion of the colon and rectum appeared normal. We may encounter amebic colitis during colonoscopic examination even in subjects who are asymptomatic.     

Plasma Exchange Therapy to Reduce Mortality in Japanese Patients With Diffuse Alveolar Hemorrhage and Microscopic Polyangiitis

Diffuse alveolar hemorrhage (DAH) is well known as a serious complication of microscopic polyangiitis (MPA). We examined the effectiveness of plasma exchange (PLEX) therapy to reduce mortality in Japanese DAH patients with MPA. This retrospective, double‐center, observational cohort study included 20 DAH patients with MPA who were admitted to Juntendo University Hospital or Juntendo Koto Geriatric Medical Center between April 1998 and March 2018. The primary outcome was non–disease‐specific mortality. The 1‐year survival rate of patients with PLEX therapy (N = 4) was higher than that of patients with conventional therapy (N = 16, 75% and 13%, respectively, P = 0.037). Higher values of the 1996 Five‐Factor Score (FFS) and 2009 FFS were associated with increased mortality, with hazard ratios of 2.29 (P = 0.040) and 2.41 (P = 0.043), respectively, by Cox univariate analysis. We investigated PLEX therapy for reducing mortality in DAH patients with MPA, and the 1996 FFS and 2009 FFS were both independent prognostic factors.