Amide proton transfer and chemical exchange saturation transfer MRI differentiates between growing and non-growing intracranial meningiomas: a pilot study.

AIM: To differentiate between growing and non-growing intracranial meningiomas using magnetisation transfer ratio (MTR) values with amide proton transfer (APT) and chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). MATERIALS AND METHODS: Seventeen patients with suspected intracranial meningiomas who underwent APT-CEST MRI from November 2020 to April 2021 were evaluated retrospectively. MTR values on APT-CEST imaging as well as conventional MRI features were evaluated. These parameters were compared in growing meningiomas versus non-growing meningiomas and the findings compared with previous MRI examinations. ROC curve analysis was also performed to determine the diagnostic cut-offs for MTR. RESULTS: The cohort comprised 10 patients with growing meningiomas (two men [20%], eight women [80%]; mean age [standard deviation (SD)]: 59.9 years [16]) and seven patients with non-growing meningiomas (seven women [100%]; mean age [SD]: 63.9 years [18.6]). Significant differences were found in MTR values (0.0198 ± 0.0003 versus 0.0131 ± 0.0002; p<0.0001) between the growing meningiomas and non-growing meningiomas groups, respectively. The receiver operating characteristic (ROC) curve analysis showed that MTR values clearly differentiated between growing and non-growing meningiomas. At an area under the ROC curve (AUC) threshold of 0.0151, diagnostic sensitivity, specificity, positive predictive value, and negative predictive values for MTR were 100%, 85.7%, 90.9%, and 100%, respectively. CONCLUSION: Patients with growing meningiomas could be discriminated from patients with non-growing meningiomas, using the MTR values on post-growth tumour APT-CEST imaging.

Investigation of the thermal tolerance of silicon-based lateral spin valves.

Improvement in the thermal tolerance of Si-based spin devices is realized by employing thermally stable nonmagnetic (NM) electrodes. For Au/Ta/Al electrodes, intermixing between Al atoms and Au atoms occurs at approximately 300 °C, resulting in the formation of a Au/Si interface. The Au-Si liquid phase is formed and diffuses mainly along an in-plane direction between the Si and AlN capping layers, eventually breaking the MgO layer of the ferromagnetic (FM) metal/MgO electrodes, which is located 7 µm away from the NM electrodes. By changing the layer structure of the NM electrode from Au/Ta/Al to Au/Ta, the thermal tolerance is clearly enhanced. Clear spin transport signals are obtained even after annealing at 400 °C. To investigate the effects of Mg insertion in FM electrodes on thermal tolerance, we also compare the thermal tolerance among Fe/Co/MgO, Fe/Co/Mg/MgO and Fe/Co/MgO/Mg contacts. Although a highly efficient spin injection has been reported by insertion of a thin Mg layer below or above the MgO layer, these thermal tolerances decrease obviously.

Predictive models for conversion of prediabetes to diabetes.

AIM: To clarify the natural course of prediabetes and develop predictive models for conversion to diabetes. METHODS: A retrospective longitudinal study of 2105 adults with prediabetes was carried out with a mean observation period of 4.7years. Models were developed using multivariate logistic regression analysis and verified by 10-fold cross-validation. The relationship between [final BMI minus baseline BMI] (δBMI) and incident diabetes was analyzed post hoc by comparing the diabetes conversion rate for low (< -0.31kg/m2) and high δBMI (≥ -0.31kg/m2) subjects after matching the two groups for the covariates. RESULTS: Diabetes developed in 252 (2.5%/year), and positive family history, male sex, higher systolic blood pressure, plasma glucose (fasting and 1h- and 2h-values during 75g OGTT), hemoglobin A1c (HbA1c) and alanine aminotransferase were significant, independent predictors for the conversion. By using a risk score (RS) that took account of all these variables, incident diabetes was predicted with an area under the ROC curve (95% CI) of 0.80 (0.70-0.87) and a specificity of prediction of 61.8% at 80% sensitivity. On division of the participants into high- (n=248), intermediate- (n=336) and low-risk (n=1521) populations, the conversion rates were 40.1%, 18.5% and 5.9%, respectively. The conversion rate was lower in subjects with low than high δBMI (9.2% vs 14.4%, p=0.003). CONCLUSIONS: Prediabetes conversion to diabetes could be predicted with accuracy, and weight reduction during the observation was associated with lowered conversion rate.

Impact of weight gain on the evolution and regression of prediabetes: a quantitative analysis.

BACKGROUND/OBJECTIVES: The quantitative impact of weight gain on prediabetic glucose dysregulation remains unknown; only one study quantitated the impact of weight loss. We quantified the impact of weight gain on the evolution and regression of prediabetes (PDM). SUBJECTS/METHODS: In 4234 subjects without diabetes, using logistic regression analysis with a 4.8-year follow-up period, we analyzed the relationship between (1) δBMI (BMIfollow-up-basal) and the progression from normal glucose regulation (NGR) to PDM or diabetes, and (2) δBMI and the regression from PDM to NGR. RESULTS: Mean (±s.d.) δBMI was 0.17 (±1.3) kg/m2 in subjects with NGR and δBMI was positively and independently related to progression (adjusted odds ratio (ORadj) (95% CI), 1.24 (1.15-1.34), P<0.01). Mean (±s.d.) δBMI was -0.03 (±1.25) kg/m2 in those with PDM and δBMI was negatively related to the regression (ORadj, 0.72 (0.65-0.80), P<0.01). The relation of δBMI to the progression was significant in men (ORadj, 1.42 (1.28-1.59), P<0.01) but not in women (ORadj, 1.05 (0.94-1.19), P=0.36). Also, the negative impact of δBMI on the regression was significant only in men (men, ORadj, 0.65 (0.57-0.75), P<0.01; women, ORadj, 0.94 (0.77-1.14), P=0.51). CONCLUSIONS: In Japanese adults, an increase in the BMI by even 1 kg/m2 was related to 24% increase in the risk of development of PDM or diabetes in NGR subjects and was related to 28% reduction in the regression from PDM to NGR. In women, we did not note any significant impact of weight gain on the evolution or regression of PDM.

Quantification of Lung Perfusion Blood Volume by Dual-Energy CT in Patients With and Without Chronic Obstructive Pulmonary Disease.

Purpose: In chronic obstructive pulmonary disease (COPD), pulmonary vascular alteration is one of the characteristic features. Recently, software has been used for the quantification of lung iodine perfusion blood volume (iPBV) using dual-energy CT, allowing objective evaluation. The purpose of this study was to evaluate the quantification of lung PBV with and without COPD. Materials and Methods: This study was approved by the Institutional Review Board. Sixty-two subjects who had undergone a respiratory function test within one month underwent dual-energy CT angiography. The subjects were divided into two groups: with (n = 14) and without (n = 48) COPD. We evaluated the quantification of lung iPBV in the early phase and late phase using Syngo softwarepost contrast. Associations between lung iPBV and respiratory function (forced expiratory volume in 1 second/forced vital capacity; FEV1/FVC) and the percentage area of emphysema (%LAA-950) were also evaluated. Results: In the early phase, lung iPBV values were 20.1 ± 5.5 and 30.6 ± 7.6 Hounsfield Unit (HU) in those with and without COPD, respectively, with a significant difference between them (p < 0.0001). In the late phase, the values were 12.3 ± 3.7 and 15.3 ± 4.6 HU, respectively, with no significant difference (p = 0.051). However, this could be noticed as a trend. In the early phase, there was a weak significant correlation between lung iPBV value and FEV1/FVC (R = 0.26, p = 0.047). There were significant and moderate negative correlations between lung iPBV value and %LAA-950 in early and late phases (R = -0.57, p = 0.0002; R = -0.45, p = 0.005, respectively). Conclusions: Quantification of lung iPBV reflects reduced pulmonary perfusion in patients with COPD. It may be useful for objective evaluation of the pulmonary blood flow in patients with COPD.

Identification of proliferating human hepatic cells from human induced pluripotent stem cells.

Mass-scale production of hepatocytes from human induced pluripotent stem cells (iPSCs) with functional properties of primary hepatocytes is of great value in clinical transplantation for liver failure as well as in facilitating drug development by predicting humanized drug metabolism profiles. In this report, we generated human hepatocyte-like cells from human iPSCs with the use of a stepwise protocol. Aiming at future clinical and industrial application, it is important to determine the suitable stage of iPSC-derived hepatic cells that possess high proliferative capacity to intensively expand the hepatic cells. Ki67 immunostaining showed that human iPSC-derived hepatic endoderm cells contained Ki67(+) cells at the highest level in the middle stage of hepatic differentiation, suggesting that the abundance of proliferating hepatic progenitor cells exists in this stage. Extensive expansion and differentiation of human iPSC-derived hepatic progenitors will provide future perspectives in transplantation therapy and drug development.

Muscle atrophy in chronic inflammatory demyelinating polyneuropathy: a computed tomography assessment.

BACKGROUND AND PURPOSE: Muscle atrophy is generally mild in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) compared with the severity and duration of the muscle weakness. Muscle atrophy was evaluated using computed tomography (CT) in patients with CIDP. METHODS: Thirty-one patients with typical CIDP who satisfied the diagnostic criteria for the definite CIDP classification proposed by the European Federation of Neurological Societies and the Peripheral Nerve Society were assessed. The clinicopathological findings in patients with muscle atrophy were also compared with those in patients without atrophy. RESULTS: Computed tomography evidence was found of marked muscle atrophy with findings suggestive of fatty degeneration in 11 of the 31 patients with CIDP. CT-assessed muscle atrophy was in the lower extremities, particularly in the ankle plantarflexor muscles. Muscle weakness, which reflects the presence of muscle atrophy, tended to be more pronounced in the lower extremities than in the upper extremities in patients with muscle atrophy, whereas the upper and lower limbs tended to be equally affected in patients without muscle atrophy. Nerve conduction examinations revealed significantly greater reductions in compound muscle action potential amplitudes in the tibial nerves of patients with muscle atrophy. Sural nerve biopsy findings were similar in both groups. The functional prognoses after immunomodulatory therapies were significantly poorer amongst patients with muscle atrophy. CONCLUSIONS: Muscle atrophy was present in a subgroup of patients with CIDP, including patients with a typical form of the disease. These patients tended to demonstrate predominant motor impairments of the lower extremities and poorer functional prognoses.

Role of squalene synthase in prostate cancer risk and the biological aggressiveness of human prostate cancer.

BACKGROUND: We previously conducted a genome-wide linkage analysis of Japanese nuclear families affected with prostate cancer and showed that the susceptibility to prostate cancer was closely linked to D8S550 at 8p23. The role of farnesyl diphosphate farnesyltransferase (FDFT1), which is located under the peak marker D8S550 at 8p23, and squalene synthase, the enzyme encoded by FDFT1, in prostate cancer was studied. METHODS: The association among common variants of FDFT1 with prostate cancer risk, the promoter activities of FDFT1 with different genotypes and the effects of inhibition of squalene synthase were studied, and the FDFT1 transcript levels of human prostate samples were quantified. RESULTS: The A allele of rs2645429 was significantly associated with prostate cancer risk in a Japanese familial prostate cancer population. Rs2645429 was located in the promoter region of FDFT1, and the AA genotype showed significantly increased promoter activity. The knockdown of FDFT1 mRNA expression or squalene synthase inhibition led to a significant decrease in prostate cancer cell proliferation. Additionally, human prostate cancer specimens expressed significantly higher levels of FDFT1 mRNA compared with noncancerous specimens. Finally, aggressive cancers showed higher transcript levels. CONCLUSIONS: FDFT1 and its encoded enzyme, squalene synthase, may play an important role in prostate cancer development and its aggressive phenotypes.

Skin biopsy is useful for the antemortem diagnosis of neuronal intranuclear inclusion disease.

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in neuronal and somatic cells. Because of the variety of clinical manifestations, antemortem diagnosis of NIID is difficult. METHODS: Seven skin biopsy samples from patients with familial NIID were evaluated histochemically, and the results were compared with those of skin samples from normal control subjects and from patients with other neurologic diseases. We also examined skin biopsy samples from patients with NIID by electron microscopy. RESULTS: In NIID skin biopsy samples, intranuclear inclusions were observed in adipocytes, fibroblasts, and sweat gland cells. These inclusions were stained with both anti-ubiquitin and anti-SUMO1 antibodies. Electron microscopy revealed that the features of the intranuclear inclusions in adipocytes, fibroblasts, and sweat gland cells were identical to those of neuronal cells. Approximately 10% of adipocytes showed intranuclear inclusions. No intranuclear inclusions were identified in the skin samples from normal control subjects and patients with other neurologic diseases. CONCLUSIONS: Skin biopsy is an effective and less invasive antemortem diagnostic tool for NIID.

Single nucleotide polymorphism of TAG-1 influences IVIg responsiveness of Japanese patients with CIDP.

OBJECTIVE: Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized by immune-mediated peripheral demyelination. Although corticosteroid, IV immunoglobulin (IVIg) and plasma exchange have been established as the most effective therapeutics, subpopulations of patients show little or no response to either of these therapies. In this study, we examined whether particular genetic factors influence the therapeutic responsiveness of patients with CIDP. METHODS: One hundred Japanese patients categorized as responders or nonresponders to IVIg therapy participated in our study. We performed an association analysis with single nucleotide polymorphisms (SNPs) and haplotype studies between the IVIg responders and nonresponders. RESULTS: Two separate SNPs, corresponding to TAG-1 (transient axonal glycoprotein 1) and CLEC10A (C-type lectin domain family 10, member A), showed strong significant differences between responders and nonresponders. Haplotype analysis of a series of expanded SNPs, from TAG-1 or CLEC10A, showed that only TAG-1 included a significant haplotype within 1 linkage disequilibrium block, which accommodates IVIg responsiveness. Diplotype analysis of TAG-1 also supported this observation. CONCLUSIONS: Transient axonal glycoprotein 1 is a crucial molecule involved in IV immunoglobulin responsiveness in Japanese patients with chronic inflammatory demyelinating polyneuropathy.

[Off-pump coronary artery bypass grafting for angina pectoris with coronary artery aneurysm due to kawasaki disease: report of a case].

We report a 27-year-old woman who underwent off-pump coronary artery bypass grafting (OPCAB) for angina pectoris with coronary artery aneurysm due to Kawasaki disease. At the age of 3, she was diagnosed as Kawasaki disease with coronary artery aneurysms in the right coronary artery and the left anterior descending artery. She was medically followed-up since then Because an enlarged aneurysm and a stenotic lesion were recognized in the right coronary artery, operation was indicated. In operation, the right coronary artery was ligated at the inflow and the outflow of the aneurysm. OPCAB was also conducted with the right internal thoracic artery anastomosed to the right coronary artery. Postoperative course was uneventful, and she was discharged at the day 5 after operation. Revascularization using arterial grafts, especially the internal thoracic arteries, may be the choice for young patients to expect a good patency rate in the long-term.

[Off-pump coronary artery bypass grafting as standard operation; surgical strategies and results].

We report the clinical results of 799 cases of isolated coronary artery bypass grafting (CABG) performed during the recent 5 years. We performed off-pump CABG (OPCAB) as standard operation, in which arterial grafts were mainly used. The mean number of distal anastomoses was 3.6 +/- 1.4 per patient Four hundred and fifty-five cases (57.0%) were done only with arterial grafts. Bilateral internal thoracic arteries were used in 326 cases. The mean number of saphenous vein grafts was 1.6 +/- 0.8 per patient. Continuous hemodiafiltraion (CHDF) was performed in 22 cases (2.8%) postoperatively. Among the OPCAB cases, 10 cases (1.3%) were converted to on-pump CABG. There were 7 cases (0.9%) of hospital death. The mean length of postoperative hospital stay was 10.2 +/- 5.3 days. The ratio of the patients with left main trunk disease and that of the patients who required postoperative CHDF increased year by year. The mean length of postoperative hospital stay decreased every year, and the reduced length was 2.7 days in the 5 years (8.7+/- 3.6 days in 2007). It is expected that patients who have severe calcified lesions or who are on hemodialysis may increase in the near future. In such cases, CABG rather than percutaneous catheter intervention may be suitable for revascularization. Therefore, not only appropriate choice of treatment strategies, but also accurate surgical techniques may become more importance.

Arterial stiffness after successful renal transplantation.

Cardiovascular disease is a major barrier to the long-term survival of transplant recipients. The aim of this study was to determine whether successful renal transplantation improves the arterial stiffness resulting from chronic renal failure. This study involved a group of 9 recipients (23-56 years) who underwent successful renal transplantation at our clinic. The brachial-ankle pulse wave velocity and--intima-media thickness of the bilateral common carotid arteries were measured in each patient before and 1 year after successful renal transplantation. One year after renal transplantation, the 9 patients showed a mean serum creatinine level of 1.41 mg/dL. Assessment of arterial stiffness in this group revealed that the mean brachial-ankle pulse wave velocity was reduced after renal transplantation, but there was no reduction in the mean intima-media thickness of the bilateral common carotid arteries. There was a significant correlation between the variance ratios of pulse wave velocity and median blood pressure. The more effective blood pressure control provided by renal transplantation may functionally improve arterial stiffness. However, organic arterial stiffness remained unchanged 1 year after transplantation.

Neuropathic pain correlates with myelinated fibre loss and cytokine profile in POEMS syndrome.

OBJECTIVE: To reveal characteristic clinicopathological correlates of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome. METHODS: The clinical features of 22 patients with POEMS syndrome were investigated and correlated with the histopathological features of sural nerves and serum cytokine profiles. RESULTS: More than half of the patients complained of pain in the lower extremities, which is closely related to hyperalgesia. Assessment of the total nerve fibre population using complete transverse sural nerve cross-sections, excluding the marked enlargement of endoneurial areas due to intrafascicular oedema, showed that myelinated fibres, especially small myelinated fibres, were reduced, whereas unmyelinated fibres were preserved. Uncompacted myelin lamellae and segmental demyelination were seen more frequently in the small, rather than the large, myelinated fibres. The presence of hyperalgesia was electrophysiologically associated with a reduction of sensory nerve action potentials in the sural nerve (p<0.05) and histopathologically associated with myelinated fibre loss (p<0.01). Serum levels of proinflammatory cytokines (interleukin-1beta, interleukin-6 and tumour necrosis factor-alpha), but not their soluble receptors, were significantly elevated in patients with hyperalgesia (p<0.05-0.01). CONCLUSIONS: Hyperalgesia seen in patients with POEMS syndrome is closely related with a reduction in the myelinated, but not unmyelinated, fibre population. Elevation of proinflammatory cytokines is also correlated with hyperalgesia. The painful symptoms in POEMS syndrome may be generated by well-preserved unmyelinated C-fibres due to the lack of inhibitory myelinated A-fibres, along with cytokine sensitisation.

Prevalence and incidence rates of chronic inflammatory demyelinating polyneuropathy in the Japanese population.

OBJECTIVE AND METHODS: To characterise the epidemiological features of chronic inflammatory demyelinating polyneuropathy (CIDP) in the Japanese population, this study performed a nationwide assessment of the prevalence and incidence rates in Japan. RESULTS: The prevalence rate per 100 000 was 1.61 in the total population; 2.01 in males and 1.23 in females. The age dependent prevalence rates were 0.23 in juveniles (<15 years old), 1.50 in young adults (15-55 years) and 2.31 in elderly adults (>55 years). The sex and age dependent prevalence rates were 0.22 in males and 0.24 in females in juveniles, 1.81 in males and 1.19 in females in young adults, and 3.12 in males and 1.64 in females in elderly adults. The annual incidence rate per 100 000 was 0.48 in the total population, 0.58 in males and 0.38 in females. The age dependent incidence rate was 0.06 in juveniles, 0.40 in young adults and 0.73 in elderly adults. The sex and age dependent incidence rate was 0.05 in males and 0.08 in females in juveniles, 0.50 in males and 0.30 in females in young adults, and 0.93 in males and 0.58 in females in elderly adults. Both the prevalence and incidence rates were very similar throughout the eight geographical areas studied, from the northern to the southern parts of Japan. CONCLUSIONS: The prevalence and incidence rates were similar to those reported in the Caucasian population. The pathogenic background is suggested to be common throughout the different races and geographic areas, while gender and age effects should be taken into account in the pathogenesis of CIDP.

Ataxic vs painful form of paraneoplastic neuropathy.

OBJECTIVE: To characterize the clinicopathologic features of ataxic and painful forms of paraneoplastic neuropathy. METHODS: Clinical, electrophysiologic, and histopathologic findings were assessed in 17 patients with paraneoplastic neuropathy. RESULTS: Clinical features can be categorized into two groups: one group (13 patients) with predominantly deep sensory disturbance and a second group (4 patients) with predominantly superficial sensory disturbance. The former group showed severe sensory ataxia and predominantly large myelinated fiber loss in the sural nerve. The latter group showed marked pain, in particular, severe mechanical hyperalgesia, and predominantly small myelinated and unmyelinated fiber loss. Nerve conduction assessment indicated an axonal neuropathy pattern in both groups, while sensory action potentials were more markedly diminished in the sensory ataxic form. Anti-Hu antibodies were detected in half of the patients in both groups. Treatment for cancer was effective to improve or stabilize neuropathic symptoms in some cases from both groups. Immunotherapy was effective only for a short time. CONCLUSIONS: Paraneoplastic neuropathy can be characterized into two groups by the presence of sensory ataxia or severe spontaneous pain and severe mechanical hyperalgesia. Preferential small myelinated and unmyelinated fiber loss correlated to the cases of severe pain.

Intravenous immunoglobulin therapy markedly ameliorates muscle weakness and severe pain in proximal diabetic neuropathy.

A 57-year-old man with type 2 diabetes mellitus for 10 years showed progressive loss of muscle strength in both legs, pain and muscle atrophy in the femoral region and significant weight loss. On admission, he could not stand alone and used a wheelchair. He also complained of severe pain in the lower extremities. He was diagnosed with proximal diabetic neuropathy (PDN) by characteristic clinical and electrophysiological features. Intravenous immunoglobulin therapy (IVIg 0.4 g/kg x 5 days) markedly reduced the severe pain and muscle weakness in the legs. Eventually, pain assessed by the Visual Analogue Scale was relieved by 80% and muscle strength was also well recovered, thereby enabling the patient to walk with a cane. The present case suggests that IVIg therapy may be effective for the relief of pain in PDN.

Relationship between tooth contacts in the retruded contact position and mandibular positioning during retrusion.

We conducted a series of studies with the purpose to investigate the locations of tooth contacts in the retruded contact position (RCP) and to discuss their significance in the stomatognathic system. In the present study, the relationship between the locations of RCP contacts and mandibular positioning during retrusion was examined. Thirty dentists and clinical residents were selected as subjects. One specialist in prosthetic dentistry examined each subject for the location of the RCP contacts. The mandibular positioning during retrusion was measured using a mandibular movement analysis system with six degrees of freedom. Originally programmed software was developed. Five reference points were selected: the central lower incisor (point I), the first molars on both sides (points RM and LM) and the condyles on both sides (points RC and LC). Tooth contact was observed most frequently at the second molar, followed by the first premolar. Points I, RM and LM all moved in an inferior-posterior direction, whereas points RC and LC moved in various directions ranging from superior-posterior to inferior-posterior. When the subjects were divided into two groups according to the most anterior tooth of occlusion in the RCP, the condylar positioning tended to be more superior in the group with molar contact than that with premolar contact. These results suggest that the locations of RCP contacts could be an important factor in jaw guidance during retrusion.