Phenotype for activated tissue macrophages in histiocytic necrotizing lymphadenitis

Macrophage polarization is divided into M1 and M2 type based on membrane receptors, cytokines, and chemokines. M1 expresses CD80, interleukin (IL)-6, IL-12, and chemokine receptor (CCR)7, while M2 expresses CD163, IL10, and chemokine ligand (CCL)22. The aim of the present study was to identify the properties of infiltrating tissue macrophages in histiocytic necrotizing lymphadenitis (HNL). Twenty patients with HNL were studied, and immunohistochemistry for CD68 (KP1), CD163, CCL22, CCR7, and CD123 was done, along with myeloperoxidase (MPO). To evaluate the phenotypes of tissue macrophages in HNL, the number of cells stained positively for CD163, CCL22, CCR7, CD123 and MPO concurrently with CD68 was counted, and the ratio was calculated for each antibody to CD68+ cells. There was a high rate of co-expression for CD163 (median, 78%) or CCL22 (80%) and a low rate for CCR7 (5%) in CD68+ cells. It is therefore conceivable that infiltration by M2 macrophages is dominant in HNL. Furthermore, some CD68+ tissue macrophages in HNL co-express MPO or CD123 (range, 5–80%; median, 23% and 40%, respectively). It is suggested that these characteristic tissue macrophages may be associated with the pathogenesis of HNL and that M2 macrophages may infiltrate to repair the lymphoid tissue injured by cytotoxic T cells in HNL.     

Radiotherapy for Japanese elderly patients with cervical cancer: preliminary survival outcomes and evaluation of treatment-related toxicity

Purpose  

To examine the preliminary survival outcomes and treatment-related toxicity for elderly patients with cervical cancer treated with radiotherapy (RT).     

A feasibility study of carboplatin and weekly paclitaxel combination chemotherapy in endometrial cancer: a Kansai Clinical Oncology Group study (KCOG0015 trial)

Objectives.

The optimal chemotherapy regimen for women with endometrial cancer has not been established. We assessed the feasibility, toxicity and clinical efficacy of combination triweekly carboplatin and weekly paclitaxel in women with endometrial cancer.

Methods.

Eligible patients had histologically confirmed primary advanced or recurrent endometrial cancer (Group A), or had localized high-risk features (Group B). All were treated with paclitaxel 80 mg/m² (days 1, 8 and 15) and carboplatin AUC 5 (day 1) each 21-day cycle. A minimum of 3 cycles was planned; if 75% or more of patients were able to receive at least 3 cycles with acceptable toxicity, the regimen was declared “feasible.”

Results.

Forty patients were enrolled and administered 163 cycles of therapy; 38 (95%) were chemo-naive. No patients received radiation previously. Group A (measurable disease) contained 15 patients (5 with recurrent disease, 7 receiving neo-adjuvant chemotherapy, and 3 treated adjuvantly following suboptimal cytoreduction). Group B (non-measurable disease) contained 25 patients (primary stage I:10, II:5, III:8, IV:1 and relapse 1). Hematological toxicities(G3/G4) were neutropenia (31%/33%) and thrombocytopenia (6%/0%). Reversible G3 hypersensitivity (5%) and G2 cardiotoxicity (3%) was uncommon. Thirty-one patients (78%) completed ≥ 3 cycles (median 4, range: 1-9). Thirteen of 15 (87%) measurable patients responded (3CR, 10PR). Eighty-seven percent of measurable patients were not progressive at 6 months. In Group A, QOL scores were significantly improved after 3 cycles of chemotherapy (p = 0.037), and at the completion of chemotherapy (p = 0.045). QOL scores in Group B did not change during therapy.

Conclusions.

This combination chemotherapy is feasible and effective for endometrial cancer patients.     

Conserved and divergent expression patterns of markers of axial development in the laboratory opossum,Monodelphis domestica

Background: Previous comparative studies suggest that the requirement for Nodal in epiblast and hypoblast development is unique to mammalians. Expression of anterior visceral endoderm (AVE) genes in the visceral endoderm and of their orthologs in the hypoblast may be unique to mammalians and avians, and is absent in the reptilian hypoblast. Axis formation in reptiles is signaled by the formation of the posterior marginal epiblast (PME), which expresses a series of primitive streak genes. To assess the phylogenetic origin of Nodal and AVE gene expression and axis formation in amniotes, we examined marker gene expression in gray short‐tailed opossum, a metatherian. Results: Nodal was expressed in neither epiblast nor hypoblast of opossum embryos. No AVE genes were expressed in the opossum hypoblast. Attainment of polarity in the embryonic disk was signaled by Nodal, Wnt3a, Fgf8, and Bra expression in the PME at 8.5 days post‐coitus. Conclusions: Nodal expression in epiblast or hypoblast may be unique to eutherians. AVE gene expression in visceral endoderm and hypoblast may have been independently acquired in eutherian and avian lineages. PME formation appears to be the event that signals axis formation in reptilian and metatherian embryos, and thus may be an ancestral characteristic of basal amniotes. Developmental Dynamics 245:1176–1188, 2016. © 2016 Wiley Periodicals, Inc.     

Topical ocular dexamethasone decreases intraocular pressure and body weight in rats

Background

Recently, topical dexamethasone-induced ocular hypertension and a consequent loss of retinal ganglion cells (RGCs) have been described in mice. This has been proposed as a model of steroid-induced glaucoma. In this study, we set up and evaluated a similar model in rats.

Results

Ten-week old Sprague Dawley (SD) rats (N?=?12) were used to evaluate the effect of topical 0.1 % dexamethasone (50 μl) administered 3 times daily for 4 weeks. Sodium chloride (0.9 %) was used in another group of rats (N?=?12) that served as the controls. After 1 week, we observed a progressive decrease in body weight in the dexamethasone-treated rats compared both to the pre-treatment baseline and the vehicle-treated rats. In contrast to earlier work that showed elevated Intraocular pressure (IOP) following dexamethasone instillation in mice, IOP in the rats unexpectedly fell to 11.3?±?1.3 mmHg in the treated eyes, compared to 14.8?±?2.4 mmHg in the untreated eyes, after 3 weeks of topical dexamethasone (P?=?0.032). Blood tests performed after 4 weeks of treatment showed a 3.3-fold increase in both plasma cholesterol (P?<?0.001) and alanine transaminase (P?=?0.019) in the dexamethasone-treated rats compared to the control rats. Meanwhile, topical steroid did not induce changes in either plasma blood glucose or glycated hemoglobin (HbA1c). We also did not detect changes in the expression of RGC markers (with real-time PCR) following the treatment.

Conclusions

In contrast to mice, which previously showed increased IOP following the topical administration of dexamethasone, the rats displayed a paradoxical reduction in IOP following a similar treatment. This was accompanied by a loss of body weight without affecting the level of blood glucose.

     

Optical aggregometry of red blood cells associated with the blood-clotting reaction in extracorporeal circulation support

The aggregability of red blood cell (RBCs) is associated with the contribution of plasma proteins, such as fibrinogen and lipoproteids, to blood-clotting. Hence, we hypothesized that RBC aggregability reflects the blood-clotting reaction. A noninvasive optical monitoring method to measure RBC aggregability for the assessment of blood-clotting stage during mechanical circulatory support was developed. An in vitro thrombogenic test was conducted with a rotary blood pump using heparinized fresh porcine blood. Near-infrared laser light at a wavelength of 785 nm was guided by an optical fiber. The fibers for detecting incident, forward-, and backward-scattered light were fixed on the circuit tubing with an inner diameter of 1/4 inch. Because there is substantial RBC aggregation at low shear flow rates, a pulsatile flow was generated by controlling the pump rotational speed. The flow rate was changed from 0 to 8.5 L/min at a period of 40 s. The intensities of forward- and backward-scattered light changed dramatically when the flow stopped. The aggregability was evaluated by the increase ratio of the transmitted light intensity from the flow stopping in the low-flow condition. The experiment started when the anticoagulation was stopped by the addition of protamine into the circulating blood. Reduction in RBC aggregability was associated with a decrease in the amount of fibrinogen and the number of platelets. Continuous, noninvasive monitoring of thrombosis risk is possible using optical measurements combining pulsatile flow control of a rotary blood pump. RBC aggregometry is a potential label-free method for evaluating blood-clotting risk.     

New development of a cytological examination ordering system at Osaka National Hospital

Effective and rapid use of cytological data are issue in Japan. We addressed this problem by development of an ordering system for cytological examinations at Osaka National Hospital. This system is located in the department of pathology and is a client-server system that consisted of 1 server and 6 clients. Five of the 6 clients are related to cytology and there are connections to microscopes with digital cameras. One client is for acceptance of cytological specimens at the department of pathology. Through a local area network, 100 Mbps, this system is connected to the hospital information system, which is of the order-entry type. After a clinician orders a cytological examination, these data are sent to both the Accounts and Pathology departments. A small bar-code label is simultaneously printed out, which is stuck on the form. By checking this label at the department of pathology by using a label reader, relevant clinical information is sent to the pathology server. After the cytological diagnosis has been made by senior cytotechnologist and cytopathologist, data on the diagnosis and microscopic images are sent to the hospital information system. Thus, clinicians can review the cytological diagnosis together with the photomicrographs. This new cytology system has brought great benefits to both cytotechnologist and clinicians with regard to the rapid transfer of cytological examination, and it seems to contribute to more advanced and efficient medical care.     

Genetic association between interleukin-10 gene promoter region polymorphisms and type 1 diabetes age-at-onset

This study investigated whether interleukin-10 (IL-10) gene promoter region polymorphisms are associated with susceptibility to or clinical presentation of type 1 diabetes. The frequency of -1082G/A, -819C/T, and -592C/A polymorphisms was analyzed in 128 Japanese patients with type 1 diabetes and in 107 healthy control subjects in a case-controlled study. The allelic and haplotypic frequencies of the IL-10 gene promoter region polymorphisms were similar in patients with type 1 diabetes and in control subjects. However, the -819T and -592A allele were associated with adult-onset (>18 years) of the disease (p = 0.037). Furthermore, the frequency of ATA haplotype was increased in adult-onset patients than that in early-onset patients (< or =18 years; p = 0.037). Among the genotypes comprising ATA haplotype, the frequency of ATA/ATA was significantly higher in adult-onset patients than in early-onset patients (p = 0.004). These results suggest that the IL-10 gene promoter polymorphisms are associated with the age-at-onset in Japanese patients with type 1 diabetes.