MR Relaxometry for Discriminating Malignant Ovarian Cystic Tumors: A Prospective Multicenter Cohort Study.

BACKGROUND: Endometriosis-associated ovarian cancer (EAOC) is a well-known type of cancer that arises from ovarian endometrioma (OE). OE contains iron-rich fluid in its cysts due to repeated hemorrhages in the ovaries. However, distinguishing between benign and malignant tumors can be challenging. We conducted a retrospective study on magnetic resonance (MR) relaxometry of cyst fluid to distinguish EAOC from OE and reported that this method showed good accuracy. The purpose of this study is to evaluate the accuracy of a non-invasive method in re-evaluating pre-surgical diagnosis of malignancy by a prospective multicenter cohort study. METHODS: After the standard diagnosis process, the R2 values were obtained using a 3T system. Data on the patients were then collected through the Case Report Form (CRF). Between December 2018 and March 2023, six hospitals enrolled 109 patients. Out of these, 81 patients met the criteria required for the study. RESULTS: The R2 values calculated using MR relaxometry showed good discriminating ability with a cut-off of 15.74 (sensitivity 80.6%, specificity 75.0%, AUC = 0.750, p < 0.001) when considering atypical or borderline tumors as EAOC. When atypical and borderline cases were grouped as OE, EAOC could be distinguished with a cut-off of 16.87 (sensitivity 87.0%, specificity 61.1%). CONCLUSIONS: MR relaxometry has proven to be an effective tool for discriminating EAOC from OE. Regular use of this method is expected to provide significant insights for clinical practice.

Transvenous embolization via the facial vein for intraorbital dural arteriovenous fistula: illustrative case.

BACKGROUND: Intraorbital arteriovenous fistula (IOAVF) is a rare type of intracranial fistula that presents with ocular signs similar to those of cavernous sinus dural arteriovenous fistula. The treatment of IOAVF is based on the vascular architecture of each case due to its infrequent occurrence. The authors report the case of an IOAVF that was successfully treated with embolization via the facial vein, with good outcomes. OBSERVATIONS: A 78-year-old woman presented with left eyelid swelling, pulsatile ocular protrusion, and left ocular conjunctival hyperemia. Ophthalmological evaluation revealed elevated intraocular pressure; time-of-flight magnetic resonance angiography revealed a dilated left superior ophthalmic vein. Digital subtraction angiography showed an arteriovenous shunt in the left superior orbital fissure, which was treated using transvenous coil embolization. The patient experienced immediate improvement in left ocular protrusion and conjunctival hyperemia. Ophthalmological evaluation 1 month after treatment showed normal intraocular pressure in the left eye. No neurological symptoms were observed, and there was no recurrence of the arteriovenous shunt 3 months postoperatively. LESSONS: The authors report a rare case of IOAVF treated with embolization via the facial vein with a good outcome. A thorough understanding of the vascular architecture using three-dimensional images is useful for determining endovascular access and procedures.

Efficacy of combined estrogen-progestin hormone contraception therapy for refractory coronary spastic angina in very young women.

Coronary spastic angina (CSA) in premenopausal women is rare, but has also been suggested to be associated with estrogen decline during the menstrual cycle. In this report, we describe the case of a young premenopausal patient with refractory CSA. She presented with ventricular fibrillation (VF) at the age of 15 years and was diagnosed as having CSA. She underwent implantation of an Implantable Cardioverter Defibrillator (ICD), and despite receiving systemic drug therapy at the maximum doses, she experienced a total of four appropriate ICD shocks over the subsequent six years. Based on careful history-taking, it was suspected that the angina episodes were closely related to the phase of the menstrual cycle. We started the patient on continuous combined estrogen-progestin hormone contraception therapy so as to prevent the reduction of the blood estrogen levels just prior to and during menstruation. After the start of this treatment, the patient became completely free of angina episodes. Although there are a few reports of the efficacy of hormone replacement therapy in premenopausal women with CSA, this is the first report of the efficacy of this therapy in a woman as young as 22 years old. .

Generation and characterization of new CCR5-tropic HIV-1rmt clones.

To develop effective non-human primate models for coping with numerous HIV-1/AIDS studies, rhesus macaque-tropic HIV-1 (HIV-1rmt) clones with a variety of biological properties are required. Such clones, if available, are powerful tools to experimentally elucidate HIV-1 replication and pathogenicity in host individuals, and also to develop anti-HIV-1 drugs/vaccines. However, only limited numbers of HIV-1rmt clones have been currently reported. In the present study, we generated new HIV-1rmt clones carrying various CCR5-tropic env (envelope) genes by standard recombinant DNA and intracellular homologous recombination techniques. Resultant virus clones contain the env sequences derived from an AIDS-inducible laboratory or two clinically isolated viral strains. We further constructed their variant clones bearing N160K, S304G, or G310R mutation in Env that potentially can change the viruses to better grow. Newly generated clones were analyzed for their virological properties such as Env expression, single-cycle infectivity, and multi-cycle replication ability. Out of a number of new clones examined, two were found to grow better in macaque cells than the previously constructed clone used for comparison. Our study described here constitutes the initial and essential step towards obtaining CCR5-tropic HIV-1rmt clones useful for various basic and clinical research projects on infected individuals. J. Med. Invest. 64: 272-279, August, 2017.

Phylogenetic Insights into the Functional Relationship between Primate Lentiviral Reverse Transcriptase and Accessory Proteins Vpx/Vpr.

The efficiency of reverse transcription to synthesize viral DNA in infected cells greatly influences replication kinetics of retroviruses. However, viral replication in non-dividing cells such as resting T cells and terminally differentiated macrophages is potently and kinetically restricted by a host antiviral factor designated SAMHD1 (sterile alpha motif and HD-domain containing protein 1). SAMHD1 reduces cellular deoxynucleoside triphosphate (dNTP) pools and affects viral reverse transcription step. Human immunodeficiency virus type 2 (HIV-2) and some simian immunodeficiency viruses (SIVs) have Vpx or Vpr to efficiently degrade SAMHD1. Interestingly, the reverse transcriptase (RT) derived from HIV-1 that encodes no anti-SAMHD1 proteins has been previously demonstrated to uniquely exhibit a high enzymatic activity. It is thus not irrational to assume that some viruses may have acquired or lost the specific RT property to better adapt themselves to the low dNTP environments confronted in non-dividing cells. This adaptation process may probably be correlated with the SAMHD1-antagonizing ability by viruses. In this report, we asked whether such adaptive events can be inferable from Vpx/Vpr and RT phylogenetic trees overlaid with SAMHD1-degrading capacity of Vpx/Vpr and with kinetic characteristics of RT. Resultant two trees showed substantially similar clustering patterns, and therefore suggested that the properties of RT and Vpx/Vpr can be linked. In other words, HIV/SIVs may possess their own RT proteins to adequately react to various dNTP circumstances in target cells.

Expression Profiles of Vpx/Vpr Proteins Are Co-related with the Primate Lentiviral Lineage.

Viruses of human immunodeficiency virus type 2 (HIV-2) and some simian immunodeficiency virus (SIV) lineages carry a unique accessory protein called Vpx. Vpx is essential or critical for viral replication in natural target cells such as macrophages and T lymphocytes. We have previously shown that a poly-proline motif (PPM) located at the C-terminal region of Vpx is required for its efficient expression in two strains of HIV-2 and SIVmac, and that the Vpx expression levels of the two clones are significantly different. Notably, the PPM sequence is conserved and confined to Vpx and Vpr proteins derived from certain lineages of HIV-2/SIVs. In this study, Vpx/Vpr proteins from diverse primate lentiviral lineages were experimentally and phylogenetically analyzed to obtain the general expression picture in cells. While both the level and PPM-dependency of Vpx/Vpr expression in transfected cells varied among viral strains, each viral group, based on Vpx/Vpr amino acid sequences, was found to exhibit a characteristic expression profile. Moreover, phylogenetic tree analyses on Gag and Vpx/Vpr proteins gave essentially the same results. Taken together, our study described here suggests that each primate lentiviral lineage may have developed a unique expression pattern of Vpx/Vpr proteins for adaptation to its hostile cellular and species environments in the process of viral evolution.

Natural Single-Nucleotide Variations in the HIV-1 Genomic SA1prox Region Can Alter Viral Replication Ability by Regulating Vif Expression Levels.

UNLABELLED: We previously found that natural single-nucleotide variations located within a proximal region of splicing acceptor 1 (SA1prox) in the HIV-1 genome could alter the viral replication potential and mRNA expression pattern, especially the vif mRNA level. Here, we studied the virological and molecular basis of nucleotide sequence variations in SA1prox for alterations of viral replication ability. Consistent with our previous findings, variant clones indeed expressed Vif at different levels and grew distinctively in cells with various APOBEC3G expression levels. Similar effects were observed for natural variations found in HIV-2 SA1prox, suggesting the importance of the SA1prox sequence. To define nucleotides critical for the regulation of HIV-1 Vif expression, effects of natural SA1prox variations newly found in the HIV Sequence Compendium database on vif mRNA/Vif protein levels were examined. Seven out of nine variations were found to produce Vif at lower, higher, or more excessive levels than wild-type NL4-3. Combination experiments of variations giving distinct Vif levels suggested that the variations mutually affected vif transcript production. While low and high producers of Vif grew in an APOBEC3G-dependent manner, excessive expressers always showed an impeded growth phenotype due to defects in single-cycle infectivity and/or virion production levels. The phenotype of excessive expressers was not due primarily to inadequate expression of Tat or Rev, although SA1prox variations altered the overall HIV-1 mRNA expression pattern. Collectively, our results demonstrate that HIV SA1prox regulates Vif expression levels and suggest a relationship between SA1prox and viral adaptation/evolution given that variations occurred naturally. IMPORTANCE: While human cells possess restriction factors to inhibit HIV-1 replication, HIV-1 encodes antagonists to overcome these barriers. Conflicts between host restriction factors and viral counterparts are critical driving forces behind mutual evolution. The interplay of cellular APOBEC3G and viral Vif proteins is a typical example. Here, we demonstrate that naturally occurring single-nucleotide variations in the proximal region of splicing acceptor 1 (SA1prox) of the HIV-1 genome frequently alter Vif expression levels, thereby modulating viral replication potential in cells with various ABOBEC3G levels. The results of the present study reveal a previously unidentified and important way for HIV-1 to compete with APOBEC3G restriction by regulating its Vif expression levels. We propose that SA1prox plays a regulatory role in Vif counteraction against APOBEC3G in order to contribute to HIV-1 replication and evolution, and this may be applicable to other primate lentiviruses.

Single-amino acid mutation 66SR in Gag-matrix enhances viral single-cycle infectivity of R5-tropic HIV-1rmt.

We recently constructed two rhesus macaque-tropic human immunodeficiency virus type 1 (HIV-1rmt) clones with CXCR4 or CCR5 tropism, but a CCR5-tropic HIV-1rmt clone grew more poorly than a CXCR4-topic clone. It has been demonstrated that interaction between viral Gag-matrix (MA) and Env-gp41 cytoplasmic tail is important for virion-incorporation of Env. Concordantly, Gag-MA mutations (62QR and 66SR) that rescue defects in virion-incorporation of Env/viral replication were reported. In this study, we analyzed effects of these Gag-MA mutations on R5-tropic HIV-1rmt replication potentials. While introduction of 62QR into three HIV-1rmt clones tested reduced their multi-cycle replication ability in rhesus lymphocytes or abolish single-cycle infectivity for luciferase reporter cells, three R5-tropic HIV-1rmt clones carrying 66SR exhibited similar growth kinetics to those of their parental clones. One such clone, 66SR+5gtu, appeared to induce stronger cytopathic effects than parental clone 5gtu. We therefore investigated effects of 66SR mutation on viral replication in more detail. Single-cycle infectivity of 66SR+5gtu was enhanced relative to that of 5gtu, but 66SR+5gtu virion production was significantly decreased compared to the 5gtu level. Gag-MA 66SR mutation may be useful to improve growth potentials of the R5-tropic HIV-1rmt clones.

Poly-proline motif in HIV-2 Vpx is critical for its efficient translation.

Human immunodeficiency virus type 2 (HIV-2) carries an accessory protein Vpx that is important for viral replication in natural target cells. In its C-terminal region, there is a highly conserved poly-proline motif (PPM) consisting of seven consecutive prolines, encoded in a poly-pyrimidine tract. We have previously shown that PPM is critical for Vpx expression and viral infectivity. To elucidate the molecular basis underlying this observation, we analysed the expression of Vpx proteins with various PPM mutations by in vivo and in vitro systems. We found that the number and position of consecutive prolines in PPM are important for Vpx expression, and demonstrated that PPM is essential for efficient Vpx translation. Furthermore, mutational analysis to synonymously disrupt the poly-pyrimidine tract suggested that the context of PPM amino acid sequences is required for efficient translation of Vpx. We similarly analysed HIV-1 and HIV-2 Vpr proteins structurally related to HIV-2 Vpx. Expression level of the two Vpr proteins lacking PPM was shown to be much lower relative to that of Vpx, and not meaningfully enhanced by introduction of PPM at the C terminus. Finally, we examined the Vpx of simian immunodeficiency virus from rhesus monkeys (SIVmac), which also has seven consecutive prolines, for PPM-dependent expression. A multi-substitution mutation in the PPM markedly reduced the expression level of SIVmac Vpx. Taken together, it can be concluded that the notable PPM sequence enhances the expression of Vpx proteins from viruses of the HIV-2/SIVmac group at the translational level.

Species tropism of HIV-1 modulated by viral accessory proteins.

Human immunodeficiency virus type 1 (HIV-1) is tropic and pathogenic only for humans, and does not replicate in macaque monkeys routinely used for experimental infections. This specially narrow host range (species tropism) has impeded much the progress of HIV-1/acquired immunodeficiency syndrome (AIDS) basic research. Extensive studies on the underlying mechanism have revealed that Vif, one of viral accessory proteins, is critical for the HIV-1 species tropism in addition to Gag-capsid protein. Another auxiliary protein Vpu also has been demonstrated to affect this HIV-1 property. In this review, we focus on functional interactions of these HIV-1 proteins and species specific-restriction factors. In addition, we describe an evolutional viewpoint that is relevant to the species tropism of HIV-1 controlled by the accessory proteins.

Is the diameter or chirality distribution of single-walled carbon nanotubes selected in the synthesis process?

Based on recent theoretical photoluminescence intensity calculations, the population densities of sixteen semiconducting single-walled carbon nanotubes grown by alcohol catalytic chemical vapor deposition were estimated for two different temperatures. The profiles of population density merely as functions of tube-diameter or chiral angle are found to be widely scattered. However, systematic profiles are detectable when separately split into (2n + m), (n + 2m) and (n - m) family arrays. Apart from these well-knit family behaviors, the population densities of the group of nanotubes forming another three possible series [viz. constant-n, constant-m and constant-(n + m)] also show evidence of good correlations. Hence, a two-dimensional chiral-zone selective growth principle is hypothesized.

Quadricuspid aortic valve: report of three cases.

Quadricuspid aortic valve (QAV) is a very rare congenital malformation. We have encountered three patients with QAV, of whom one patient may be the eldest reported patient with this particular anatomical abnormality. In another of our patients, there was aortic regurgitation, aortic stenosis, and healed infective endocarditis, with adhesion of the tips of the cusps. In all three patients, the cusps were all of equal size. Until now, there has been very little documented evidence about the anatomical variations in QAV or its relationship with infective endocarditis. From the available literature, we conclude that the anatomical variations in patients with QAV are similar to those in patients with quadricuspid pulmonary valve, and infective endocarditis may not be an uncommon complication.