Diagnostic utility of galectin-3 and CD26/DPPIV as preoperative diagnostic markers for thyroid nodules

The aim of this study was to search for diagnostic markers that could correctly identify thyroid nodular lesions requiring urgent surgical treatment. We investigated whether galectin-3 and dipeptidyl peptidase IV (CD26/DPPIV) could be potential markers for improving the diagnostic accuracy of conventional cytology. Seventy-nine patients with histologically proven thyroid diseases were analyzed. The immunocytochemical staining results showed galectin-3 expression in neoplastic cells of all 37 papillary carcinomas, five of six follicular carcinomas, all three anaplastic carcinomas, one of three medullary carcinomas, and two of 14 follicular adenomas. All 16 adenomatous goiters were negative for galectin-3 immunostaining. On the other hand, all 37 papillary carcinomas, all six follicular carcinomas, and one of three anaplastic carcinomas revealed CD26/DPPIV expression, whereas all three medullary carcinomas were negative. Among benign thyroid lesions, four of 14 follicular adenomas and two of 16 adenomatous goiters exhibited varying degrees of immunoreactivity for CD26/DPPIV. RT-PCR analysis demonstrated overexpression of galectin-3 and CD26/DPPIV mRNAs in all six papillary and all three follicular carcinomas analyzed, whereas the mRNA expressions of these molecules were barely or not detectable in benign thyroid lesions and normal thyroid tissues, except for one case of follicular adenoma. In conclusion, we demonstrate that galectin-3 and CD26/DPPIV were consistently coexpressed at protein and mRNA levels in differentiated thyroid carcinomas. We propose that combined immunostaining for galectin-3 and CD26/DPPIV in the preoperative evaluation of thyroid nodules may play a role in accurate cytodiagnosis.     

Related Factors and Clinical Outcomes of Osteosarcopenia: A Narrative Review

Osteopenia/osteoporosis and sarcopenia are common geriatric diseases among older adults and harm activities of daily living (ADL) and quality of life (QOL). Osteosarcopenia is a unique syndrome that is a concomitant of both osteopenia/osteoporosis and sarcopenia. This review aimed to summarize the related factors and clinical outcomes of osteosarcopenia to facilitate understanding, evaluation, prevention, treatment, and further research on osteosarcopenia. We searched the literature to include meta-analyses, reviews, and clinical trials. The prevalence of osteosarcopenia among community-dwelling older adults is significantly higher in female (up to 64.3%) compared to male (8–11%). Osteosarcopenia is a risk factor for death, fractures, and falls based on longitudinal studies. However, the associations between osteosarcopenia and many other factors have been derived based on cross-sectional studies, so the causal relationship is not clear. Few studies of osteosarcopenia in hospitals have been conducted. Osteosarcopenia is a new concept and has not yet been fully researched its relationship to clinical outcomes. Longitudinal studies and high-quality interventional studies are warranted in the future.     

Successful Single-Lung Transplant for the Dominant Side: A Case Report

Although single-lung transplant on the side with better lung function is challenging in patients with significantly asymmetrical lung function between the right and left sides, it sometimes can be a realistic option because of the recipient's condition and from the viewpoint of organ sharing. We report our experience with a successful case of single-lung transplant on the side with a pulmonary perfusion ratio of 89%. The transplant was performed with the patient under central venoarterial extracorporeal membrane oxygenation through a clamshell incision, and the patient had an acceptable short- and long-term outcome with a remarkable improvement of lung function.     

Suppression of neointimal thickening by a newly developed HMG-CoA reductase inhibitor,BAYw6228, and its inhibitory effect on vascular smooth muscle cell growth

1. The aim of this study was to determine whether BAYw6228 (BAYw), a newly developed 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, could suppress an atherogenic process such as intimal thickening by a mechanism other than lowering the level of serum cholesterol.
2. First, we evaluated the in vitro effect of BAYw on the proliferation of vascular smooth muscle cells (SMC) from various species: Sprague-Dawley (SD) rats, New Zealand (NZ) white rabbits, intimal cells from Watanabe hereditary hyperlipidemic (WHHL) rabbit and SMC from the new-born human aorta. The increasing rate of total protein content of these cells was inhibited by the addition of BAYw in a dose-dependent fashion. In the presence of 2% foetal calf serum (FCS), the value of IC₅₀ was 1.0 μM in SD rats. 2.1 μM in NZ white rabbits, and 0.3 μM in WHHL rabbits. With human SMC, the value was 0.02 μM in the presence of 10% FCS and 0.2 μM with a mixture of growth factors.
3. Based on these above in vitro findings, we next examined the in vivo effect of the agent to determine whether it could suppress rabbit intimal thickening induced by balloon catheterization. A balloon catheter was inserted from a peripheral branch of the left external carotid artery to the aorta to denude the endothelium of the left common carotid artery in Japanese white rabbits. After 12 days they were divided into control and BAYw groups. The former were subcutaneously injected with saline and the latter with BAYw 1 mg kg⁻¹ day⁻¹. Two days after the beginning of treatment, a second balloon injury was performed to the previously injured left common carotid artery in both groups. After another two weeks, the left common carotid artery was removed and variously stained. Although the total serum cholesterol in the BAYw group was significantly lower than in the control (P<0.05), the difference was not enough to affect intimal thickening. In addition, the BAYw group had a smaller intima/media ratio than the control group, decreasing to 45% of control (P<0.05). By anti-α smooth muscle actin antibody staining, these intimal thickening areas were entirely occupied by SMCs, and their amount was attenuated by BAYw. By anti-rabbit macrophage antibody (RAM 11) staining, the number of positive cells in the intimal thickening was markedly decreased in the BAYw group compared to control (P<0.01).
4. These results indicate that BAYw has an inhibitory effect on intimal thickening by attenuating intimal SMC proliferation and infiltration of macrophages, suggesting that BAYw could be effective in the prevention of the progression of atherosclerotic plaque-like restenosis after angioplasty.

     

Syntheses of hydroxyamino, nitroso and nitro derivatives of Trp-P-2 and Glu-P-1, amino acid pyrolysate mutagens, and their direct mutagenicities towards Salmonella typhimurium TA98 and TA98NR

Hydroxyamino, nitroso and nitro derivatives of 3-amino-1-methyl-5H-pyrido[4,3-b]indole(Trp-P-2) and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole(Glu-P-1), mutagens-carcinogens produced on pyrolysis of aminoacids, were synthesized from Trp-P-2 and Glu-P-1. 3-Hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole(N-OH-Trp-P-2) and 2-hydroxyamino-6-methyldipyrido[l,2-a:3',2'-d]imidazole (N-OH-Glu-P-1) were obtained with good yieldsby controlled catalytic reduction of 3-nitro-l-methyl-5H-pyrido[4,3-b]indoleand 2-nitro-6-methyldipyrido[1,2-a:3',2'-d]imidazole. Subsequentoxidation of N-OH-Trp-P-2 and N-OH-Glu-P-1 with -manganese dioxideyielded 3-nitroso-1-methyl-5H-pyrido[4,3-b]indole and 2-nitroso-6-methyldipyrido[1,2-a:3',2'-d]imidazole.All six synthesized compounds were mutagenic to Salmonella typhimuriumTA98 without mammalian activation systems. The mutagenic activitiesof hydroxyamino and nitroso derivatives were identical for bothS. typhimurium TA98 and TA98NR, the nitroreductase deficientstrain. However, nitro derivatives were essentially mutageniconly towards S. typhimurium TA98.     

A crucial role of uridine/cytidine kinase 2 in antitumor activity of 3'-ethynyl nucleosides.

The antitumor 3'-ethynyl nucleosides, 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)cytosine (ECyd) and 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)uridine (EUrd), are potent inhibitors of RNA polymerases and show excellent antitumor activity against various human solid tumors in xenograft models. ECyd is being investigated in phase I clinical trials as a novel anticancer drug possessing a unique antitumor action. ECyd and EUrd require the activity of uridine/cytidine kinase (UCK) to produce the corresponding active metabolite. The UCK family consists of two members, UCK1 and UCK2, and both UCKs are expressed in many tumor cells. It was unclear, however, whether UCK1 or UCK2 is responsible for the phosphorylation of the 3'-ethynyl nucleosides. We therefore established cell lines that are highly resistant to the 3'-ethynyl nucleosides from human fibrosarcoma HT-1080 and gastric carcinoma NUGC-3. All the resistant cell lines showed a high cross-resistance to ECyd and EUrd. As a result of cDNA sequence analysis, we found that UCK2 mRNA expressed in EUrd-resistant HT-1080 cells has a 98-base pair deletion of exon 5, whereas EUrd-resistant NUGC-3 cells were harboring the point mutation at nucleotide position 484 (C to T) within exon 4 of UCK2 mRNA. This mutation was confirmed by genome sequence analysis of the UCK2 gene. Moreover, the expression of UCK2 protein was decreased in these resistant cells. In contrast, no mutation in the mRNA or differences in protein expression levels of UCK1 were shown in the EUrd-resistant HT-1080 and NUGC-3 cells. These results suggest that UCK2 is responsible for the phosphorylation and activation of the antitumor 3'-ethynyl nucleosides.     

Bufadienolide and spirostanol glycosides from the rhizomes of helleborusorientalis

The rhizomes of Helleborus orientalis have been analyzed for the bufadienolide glycoside and spirostanol saponin constituents, resulting in the isolation of a new bufadienolide rhamnoside (1), along with two known bufadienolide glycosides (2 and 3) and five new spirostanol saponins (4-8). The structures of the new compounds were determined on the basis of extensive spectroscopic analysis, including 2D NMR, and the results of hydrolytic cleavage. The isolated compounds were evaluated for their cytotoxic activities against cultured tumor and normal cells.     

Insulin resistance in nonobese Japanese women with polycystic ovary syndrome is associated with poorer glucose tolerance,delayed insulin secretion,and enhanced insulin response

PurposeTo determine the prevalence of insulin resistance (IR) and impaired glucose tolerance (IGT) in PCOS patients, the optimal screening method, and to compare our findings between nonobese and obese Japanese women with PCOS.MethodsNinety‐eight PCOS patients were included in this research from 2006 to 2013. Glucose tolerance test (OGTT) was performed. Serum glucose and insulin concentration were assayed before and 30, 60, and 120 min after taking 75 g of glucose.ResultsAll examined metabolic parameters were significantly favorable in the nonobese subjects, below 25 kg/m². HOMA‐IR, fasting insulin, glucose₁₂₀, and insulin₁₂₀ showed strong correlations with BMI. A total of 1.4 % of nonobese women had IR based on fasting insulin or HOMA‐IR. However, 15.5 % (11/71) of nonobese women had IR as determined by a continuous increase of serum insulin level in OGTT. In comparison, the prevalence of IR among the obese women ranged from 41 to 59 %. AUC_glucose, glucose₆₀, glucose₁₂₀, and insulin₁₂₀ in nonobese women with a continuous insulin increase were higher than those without such a continuous increase.ConclusionsAll examined metabolic parameters were significantly correlated with BMI. As the presence of a continuous increase of insulin level reflects to some degree poorer glucose tolerance, delayed insulin secretion, and enhanced insulin response compared with non‐continuous insulin increase, OGTT might not been excluded to determine IR and IGT for nonobese women with PCOS.