Novel 4-bp Intronic Deletion (c.1560+3_1560+6del) in LEMD3 in a Korean Patient With Osteopoikilosis

Osteopoikilosis is an autosomal dominant bone disorder characterized by symmetric multiple osteosclerotic lesions throughout the axial and appendicular skeleton. Pathogenic variants in the LEMD3 have been identified as the cause of osteopoikilosis. LEMD3 encodes an inner nuclear membrane protein that interacts with bone morphogenetic protein (BMP) and transforming growth factor (TGF)-β pathways. We report the case of a 19-year-old man presenting with lower back pain and sciatica. His radiograph revealed bilateral and symmetrical multiple osteosclerotic bone lesions in both scapular areas. Sanger sequencing of LEMD3 revealed a four-base-pair deletion in intron 2 (c.1560+3_1560+6del), which was inherited from his father. We found that this four-base-pair deletion in intron 2 causes aberrant splicing and consequent deletion of exon 2. To the best of our knowledge, this is the first report of genetically confirmed osteopoikilosis in Korea.

Cytologic Characteristics of Thymic Adenocarcinoma with Enteric Differentiation: A Study of Four Fine-Needle Aspiration Specimens

Thymic adenocarcinoma is extremely rare. Although its histologic features have been occasionally reported, a lack of description of the cytologic features has hampered the prompt and accurate diagnosis of this condition. Herein, we describe the cytologic findings and histology of four aspiration cytology specimens of thymic adenocarcinoma. The specimens were obtained from primary tumors, metastatic lymph nodes, and pericardial effusions. All four specimens showed three-dimensional glandular clusters with a loss of polarity and nuclear overlapping. One specimen had extensive extracellular mucinous material. Three specimens contained tumor cells with intracytoplasmic vacuoles. While the specimen with extracellular mucin showed relatively mild cytologic atypia, other specimens exhibited more atypical cytologic changes: irregular nuclear membranes, a coarse chromatin pattern, and prominent nucleoli. The cytologic features were correlated with the histologic features in each case of enteric type thymic adenocarcinoma. The differential diagnosis included other thymic carcinomas, yolk sac tumors, and metastatic adenocarcinoma from the lung or colorectum.

Preparation of SUN5-specific polyclonal antibody for detection of SUN5 expression in human germ cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To prepare a specific polyclonal antibody against full-length SUN5 for detecting the expression of SUN5 in human germ cells.</p><p><b>METHODS</b>Bioinformatic methods were used to compare the full-length SUN5 and its variant SUN5β, and a short peptide was designed based on the differential region to prepare SUN5 antibody. The prepared antibody was used to detect the expression of SUN5 in Ntera-2 cells and in human germ cells by Western blotting and immunofluorescence assay.</p><p><b>RESULTS</b>The short peptide was correctly synthesized and SUN5 antibody was obtained and purified. Western blotting showed that the prepared antibody was capable of recognizing full-length SUN5 in Ntera-2 cells, and SUN5 expression was localized on the nuclear membrane and in the cytoplasm as shown by immunofluorescence assay. Using this antibody, we detected SUN5 expression in the spermatocytes, round spermatids and sperms in human germ cells.</p><p><b>CONCLUSION</b>We successfully prepared SUN5-specific antibody. SUN5 is expressed in the spermatocytes, round spermatids and sperms in human germ cells, suggesting its important role in spermatogenesis.</p>

Vitamin A supplementation modifies the antioxidant system in rats

BACKGROUND/OBJECTIVES: It has been shown that vitamin A supplementation has different effects on skeletal health and the antioxidant system. Deficiency or excess of this vitamin can lead to health problems. Vitamin A can work as either an antioxidant or prooxidant depending on its concentration. The present study was conducted to investigate the effects of different doses of vitamin A supplementation on the antioxidant system in rats. MATERIALS/METHODS: Forty Spargue-Dawley male rats were divided into four groups according to the dose of vitamin A received: 0 (A0), 4,000 (A1), 8,000 (A2), and 20,000 (A3) IU retinyl palmitate/kg diet. After a feeding period of 4 wks, lipid peroxide levels, glutathione concentration, antioxidant enzyme activities, and vitamins A and E concentrations were measured. Histopathological changes were observed in rat liver tissue using an optical microscope and transmission electron microscope. RESULTS: Lipid peroxide levels in plasma were significantly decreased in the A1 and A2 groups compared to the A0 rats. Erythrocyte catalase and hepatic superoxide dismutase activities of the A2 group were significantly higher than those of the A0 group. Hepatic glutathione peroxidase activity was significantly lower in the A3 group compared to the other groups. Total glutathione concentrations were significantly higher in the A1 and A2 groups than in the A0 group. Histological examination of liver tissue showed that excessive supplementation of vitamin A might lead to lipid droplet accumulation and nuclear membrane deformation. CONCLUSIONS: These results indicate that appropriate supplementation of vitamin A might have a beneficial effect on the antioxidant system in rats.

A Case of Reticulohistiocytoma Mimicking Primary Cutaneous CD 4 Positive Small/medium T-cell Lymphoma / 임상소아혈액종양

Reticulohistiocytoma is a rare, benign histiocytic proliferation of the skin or soft tissue. A 5-month-old healthy girl visited our clinic for an enlarging nodule on the center of her right palm. The clinical differential diagnosis included xanthogranuloma and primary cutaneous CD4 positive small/medium T-cell lymphoma. Histopathology of the nodule showed abundant eosinophilic and glassy cytoplasm. The nuclei were round to oval shaped, with focal irregular nuclear membrane, and mitotic figures were absent. Immunohistochemical study determined that the cells were positive for CD68 but negative for CD1a. She was finally diagnosed with reticulohistiocytoma (solitary epithelioid histiocytoma).

Gaps in Menopause Knowledge

The average middle aged woman goes through a volatile period of endocrine fluctuations as she passes through menopause and the stages that precede and follow it. Ovarian hormones are steroid hormones. They readily cross the cell and nuclear membranes and influence transcription of numerous genes. Such influences are tissue specific and state specific. In short, changes in ovarian hormones mean that a women will experience changes in her entire body systems. When an individual woman's constitutional factors, pathologic states, medications, environmental exposures are taken into consideration, the integrated changes become too complex to predict. Inter-study sampling differences with the complexities in the backdrop may have led to conflicting conclusions in menopause research. This paper reviews some of the controversies in the care of menopausal women.

A Case of Reticulohistiocytoma Mimicking Primary Cutaneous CD 4 Positive Small/medium T-cell Lymphoma / 임상소아혈액종양

Reticulohistiocytoma is a rare, benign histiocytic proliferation of the skin or soft tissue. A 5-month-old healthy girl visited our clinic for an enlarging nodule on the center of her right palm. The clinical differential diagnosis included xanthogranuloma and primary cutaneous CD4 positive small/medium T-cell lymphoma. Histopathology of the nodule showed abundant eosinophilic and glassy cytoplasm. The nuclei were round to oval shaped, with focal irregular nuclear membrane, and mitotic figures were absent. Immunohistochemical study determined that the cells were positive for CD68 but negative for CD1a. She was finally diagnosed with reticulohistiocytoma (solitary epithelioid histiocytoma).

Cytological Findings of the Micropapillary Variant of Urothelial Carcinoma: A Comparison with Typical High-Grade Urothelial Carcinoma

BACKGROUND: Micropapillary variant of urothelial carcinoma (MPUC) showed distinct pathologic features and aggressive behavior. The cytologic findings of MPUC are still indistinct. In this study, we evaluated the cytological findings of MPUC compared with those of high-grade urothelial carcinoma (HGUC). METHODS: The voided urine cytology of 8 cases of MPUC and 8 cases of HGUC was reviewed. Following cytological parameters were evaluated: cellularity, background, number of small, tight papillary clusters, small acinar structure, scattered single cells, cytoplasmic features, nuclear-to-cytoplasmic ratio, nuclear pleomorphism, nuclear membrane irregularity, hyperchromasia, chromatin pattern and nucleoli. RESULTS: Compared to that of HGUC, cytology of MPUC showed large numbers of small, tight papillary clusters, small acinar structure, few numbers of single cells, and hyperchromatic nuclei. Other parameters were similar between the two groups; both groups showed similar cellularity, dense or vacuolated cytoplasm, moderate to severe nuclear pleomorphism, irregular nuclear membrane, coarse granular chromatin, and small and prominent nucleoli. CONCLUSIONS: The urine cytology of MPUCs showed smaller and tighter papillary cell clusters, more small acinar structures, fewer numbers of scattered single cells, and more hyperchromatic nuclei than that of HGUC. These features can help to distinguish MPUC and HGUC and offer an early cytological diagnosis of MPUC.

An analysis on biomedical effects of bipolar electric pulses at different central frequency / 生物医学工程学杂志

Adopting the cell model of multilayer spherical symmetry and the circuit analysis, the present paper gives the calculated results of the voltages on each of several parts of malignant Tonsillar B-cells and Jurkat T lymphocytes when the first-order Gaussian pulses at different central frequency apposed on them. The relationship between the central frequency and the transmembrane voltages of plasma membrane is also given. The optimum frequency causing electroporation in nuclear envelope is given as well. The paper discusses the reasons of electroporation in membrane and DNA degradation in nuclear. The work provides a reference for usage of transient bipolar electric pulses in cancer treatment.

Fine Needle Aspiration Cytology of Metastatic Adenocarcinoma of the Gingiva from the Lung: A Case Report

Metastases of malignant tumors to the oral region from distant sites are uncommon. A 45-year-old man with painless gingival swelling was diagnosed with adenocarcinoma of the lung. On cytology, clusters of tumor cells on mucous background revealed enlarged nuclei, indistinct cell borders, and irregular nuclear membranes. Some cells showed nuclear inclusions, nuclear grooves and small nucleoli. These findings are indicative of metastatic adenocarcinoma. We present a case of gingival metastasis from a lung adenocarcinoma.

Liquid-Based Cytology of Villoglandular Adenocarcinoma of the Cervix: A Report of 3 Cases

Villoglandular adenocarcinoma (VGA) is a rare subtype of cervical adenocarcinoma with a more favorable prognosis compared to conventional adenocarcinomas. Although the tumors are usually recognized on colposcopic examination due to the mainly exophytic growth pattern, they may be underdiagnosed as benign lesions by cytology because of their minimal cytologic atypia. We report the liquid-based cytology (LBC) findings of three histologically confirmed VGAs which we have recently identified. They were characterized by hypercellular smears on low-power examination with smooth-bordered three-dimensional papillary fragments. The nuclei were relatively uniform with irregular nuclear membranes. Nucleoli were small but distinct and macronucleoli were also seen. The abnormal architectural patterns such as papillary structures and nuclear overlapping and nuclear hyperchromasia are important clues to the diagnosis of VGA. In addition, nuclear membrane irregularity and prominent nucleoli can be recognized on LBC specimens, further facilitating its diagnosis.

Electric pulse duration and windows effect of nuclear envelope / 生物医学工程学杂志

Nuclear envelope voltages of T cells were analyzed with a lumped circuitry for cells in combination with frequency domain power density of Gaussian pulses and monocycle pulses. According to the differences in geometric and electric parameters between normal and malignant T cells, circuitry analysis was performed. Theoretical evaluations indicated that apoptosis of malignant T cells was of feasibility, which could be applied in cancer therapy. The evaluations were in accord with the published experimental findings.

Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer / 癌症

Through advances in technology, the genetic basis of cancer has been investigated at the genomic level, and many fundamental questions have begun to be addressed. Among several key unresolved questions in cancer biology, the molecular basis for the link between nuclear deformation and malignancy has not been determined. Another hallmark of human cancer is aneuploidy; however, the causes and consequences of aneuploidy are unanswered and are hotly contested topics. We found that nuclear lamina proteins lamin A/C are absent in a significant fraction (38%) of human breast cancer tissues. Even in lamin A/C-positive breast cancer, lamin A/C expression is heterogeneous or aberrant (such as non-nuclear distribution) in the population of tumor cells, as determined by immunohistology and immunofluorescence microscopy. In most breast cancer cell lines, a significant fraction of the lamin A/C-negative population was observed. To determine the consequences of the loss of lamin A/C, we suppressed their expression by shRNA in non-cancerous primary breast epithelial cells. Down-regulation of lamin A/C in breast epithelial cells led to morphological deformation, resembling that of cancer cells, as observed by immunofluorescence microscopy. The lamin A/C-suppressed breast epithelial cells developed aneuploidy as determined by both flow cytometry and fluorescence in situ hybridization. We conclude that the loss of nuclear envelope structural proteins lamin A/C in breast cancer underlies the two hallmarks of cancer aberrations in nuclear morphology and aneuploidy.

CellprepPlus(R) Liquid-based Smear in Sono-guided Thyroid Fine Needle Aspiration: A Comparison of Conventional Method and CellprepPlus(R) Liquid-based Cytology

BACKGROUND: Fine needle aspiration (FNA) of the thyroid is a useful tool for the evaluation of benign or malignant thyroid nodules. The improvements in the quality of cytological preparations using the liquid-based cytology (LBC) method have been well-documented. The principal objective of this study was designed to evaluate the diagnostic adequacy, sensitivity, and specificity of the thyroid FNA comparing a conventional smear with the LBC adapted with the filtration method described herein. METHODS: One hundred ninety eight cases of FNA samples obtained from May 2009 to September 2009 were included in this study. All patients were subjected to ultrasound-guided aspiration twice at a target lesion by a radiologist and two types of slides were prepared using conventional smear and LBC. RESULTS: When compared with conventional method, the cellularity was reduced in LBC. However, the malignant tumor cells evidenced the larger and more vesicular nuclei, prominent nucleoli, and distinct nuclear membranes in LBC. Thirty two cases (16.16%) of conventional smear were inadequate, but 96 cases (48.49%) of LBC were inadequate. CONCLUSIONS: Most of the slides using CellprepPlus(R) LBC evidenced lower cellularity and clearer background. However, the conventional smears were found to generate much more applicable samples than CellprepPlus(R) LBC.

Model of chromosome associations in Mus domesticus spermatocytes

Understanding the spatial organization of the chromosomes in meiotic nuclei is crucial to our knowledge of the genome's functional regulation, stability and evolution. This study examined the nuclear architecture of Mus domesticus 2n=40 pachytene spermatocytes, analyzing the associations among autosomal bivalents via their Centromere Telomere Complexes (CTC). The study developed a nuclear model in which each CTC was represented as a 3D computer object. The probability of a given combination of associations among CTC was estimated by simulating a random distribution of 19 indistinguishable CTC over n indistinguishable "cells" on the nuclear envelope. The estimated association frequencies resulting from this numerical approach were similar to those obtained by quantifying actual associations in pachytene spermatocyte spreads. The nuclear localization and associations of CTC through the meiotic prophase in well-preserved nuclei were also analyzed. We concluded that throughout the meiotic prophase: 1) the CTC of autosomal bivalents are not randomly distributed in the nuclear space; 2) the CTC associate amongst themselves, probably at random, over a small surface of the nuclear envelope, at the beginning of the meiotic prophase; 3) the initial aggregation of centromere regions occurring in lepto-zygotene likely resolves into several smaller aggregates according to patterns of preferential partitioning; 4) these smaller aggregates spread over the inner face of the nuclear envelope, remaining stable until advanced stages of the meiotic prophase or even until the first meiotic division.

Comparison of Liquid-based (SurePath(TM)) and Conventional Preparations in Thyroid Fine Needle Aspiration

BACKGROUND: The aim of this study was to evaluate differences in cytologic findings between conventional preparation (CP) and SurePath(TM) liquid-based preparation (LBP) in thyroid fine needle aspiration (FNA). METHODS: We analyzed cytological features on a total of 182 thyroid FNAs (83 CP and 99 LBP) that were histologically confirmed as nodular hyperplasia (NH) or papillary carcinoma (PAC). RESULTS: LBP was superior in cellular preservation and cellularity than CP. Interestingly, in LBP, cellularity of NH was similarly high compared to that of PAC. The three-dimensional pattern was more prominent in LBP than in CP. The presence of follicle structures was more frequently found in LBP than in CP in the PAC group. Dispersed single cells in the background were more prominent in LBP than in CP. In the PAC group, contrast of the nuclear membrane was more distinctive in CP than in LBP. CONCLUSIONS: In thyroid FNA, LBP is better for cellular preservation, cellularity, background and nuclear detail than CP. However, some features in LBP such as high cellularity in NH, prominent dispersed single cells, and frequent follicle patterns were unfamiliar findings in CP. Hence, we should be aware of these cytomorphologic features in LBP to make a proper diagnosis.

Aspiration Cytology of the Osteoclastic Variant of Anaplastic Thyroid Carcinoma: with Special Emphasis on the Undifferentiated Mononuclear Cells

Anaplastic thyroid carcinoma (ATC) is an uncommon aggressive malignant tumor, and the osteoclastic variant of ATC is extremely rare. We report here on the fine needle aspiration cytology of the osteoclastic variant of ATC in an 83-year-old woman. The smear was composed of many oval to slightly elongated undifferentiated mononuclear cells admixed with multinucleated osteoclast-like giant cells. The mononuclear tumor cells revealed inconspicuous nuclear pleomorphism and the nuclei were characterized by vesicular chromatin and an indented or lobulated nuclear membrane with conspicuous nuclear grooves. A few epithelial clusters suggestive of a papillary carcinoma component were also observed. Making the proper cytological diagnosis of the osteoclastic variant of ATC is helpful to determine the proper treatment modality for these patients.

Fine Needle Aspiration Biopsy of a Myxoid Leiomyosarcoma with Epithelioid Features and It Metastasized to the Abdominal Wall: A Case Report

We present the cytologic findings observed in a fine needle aspiration biopsy specimen of a rare myxoid variant of leiomyosarcoma with epithelioid features and the tumor had metastasized to the abdominal wall. The aspirate showed hypercellularity in a hemorrhagic background. Some large 3-dimensional aggregates of spindle cells were observed. Each cell had a solitary ovoid-to-elongated nucleus with finely granulated chromatin, one or two small distinct nucleoli and an irregular nuclear membrane. There were irregular fascicles of spindle cells with cigar-shaped, blunt-ended nuclei admixed with inflammatory cells. Epithelioid cells with a rather narrow, dense cytoplasmic rim and a well-defined cell border were embedded in a myxoid matrix in a cord-like and cluster arrangement. The matrix appeared as a pale green substance with sharply defined edges. There were very few mitoses. These cytologic features were the same as those of a uterine myxoid leiomyosarcoma that was surgically excised 7 years ago, and immunohistochemical staining revealed the smooth muscle origin of the tumor.

The Fine Needle Aspiration Cytology of a Metastatic Pulmonary Adrenocortical Carcinoma Mimicking Primary Large Cell Carcinoma of the Lung

Adrenocortical carcinoma is a rare neoplasm and it has an invariably lethal prognosis. We report here on the fine needle aspiration cytologic findings of a solitary metastatic pulmonary adrenocortical carcinoma in a 24-year-old woman. The aspirate smears were very cellular and they were composed of a monomorphic population of large polyhedral cells with abundant granular or vacuolated cytoplasm, and the cells were predominantly singly scattered in a necrotic background. Multinucleated pleomorphic tumor cells were also found. Pleomorphic nuclei with thickened nuclear membranes were impinging on the cell membranes. Mitotic activity was occasionally seen. The cytologic findings of pleomorphic cells with microvacuolated cytoplasm and the presence of vague gland-like sheets, as well as the patient's history of undergoing adrenalectomy for primary adrenocortical carcinoma helped the pathologist reach the diagnosis of metastatic adrenocortical carcinoma. Here, we focus on the cytologic differential points of metastastic pulmonary adrenocortical carcinoma and primary pulmonary carcinoma, especially large cell carcinoma.

The Fine Needle Aspiration Cytology of a Metastatic Pulmonary Adrenocortical Carcinoma Mimicking Primary Large Cell Carcinoma of the Lung

Adrenocortical carcinoma is a rare neoplasm and it has an invariably lethal prognosis. We report here on the fine needle aspiration cytologic findings of a solitary metastatic pulmonary adrenocortical carcinoma in a 24-year-old woman. The aspirate smears were very cellular and they were composed of a monomorphic population of large polyhedral cells with abundant granular or vacuolated cytoplasm, and the cells were predominantly singly scattered in a necrotic background. Multinucleated pleomorphic tumor cells were also found. Pleomorphic nuclei with thickened nuclear membranes were impinging on the cell membranes. Mitotic activity was occasionally seen. The cytologic findings of pleomorphic cells with microvacuolated cytoplasm and the presence of vague gland-like sheets, as well as the patient's history of undergoing adrenalectomy for primary adrenocortical carcinoma helped the pathologist reach the diagnosis of metastatic adrenocortical carcinoma. Here, we focus on the cytologic differential points of metastastic pulmonary adrenocortical carcinoma and primary pulmonary carcinoma, especially large cell carcinoma.