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Sézary syndrome involving the intestinal tract (j,k) Histological investigation of the specimens of the subtotal colon excision showed submucosal infiltration of atypical lymphocytes with mitotic figures without lymphoepithelial lesion. Histopathological examination of biopsy specimens from erythema on the back showed superficial and perivascular infiltration of mononuclear cells with mild atypia in the dermis (Fig. c, d). [Extracted from the article]

We present pathology of the peripheral nerves of a patient with Adult-onset Charcot-Marie-Tooth disease 4F caused by periaxin gene mutation p.D651N. The patient was a 72-year-old woman. She had hoarseness and underwent continuous positive airway pressure therapy at night due to sleep apnea. The patient died abruptly. Remarkable demyelination with tomacula formation was found in the phrenic nerve, vagal nerve, recurrent laryngeal nerve, and oculomotor nerves. The cause of death could have been insufficient reactivity to the aspiration or sudden onset of bilateral vocal cord palsy. We must pay attention to respiratory function and cranial nerve palsies in hereditary demyelinating neuropathies., Competing Interests: None., (© 2021 The Authors.)

A 72-year-old man was followed as an outpatient at our hospital for 6 years after surgery for small cell carcinoma of left adrenal gland origin. Follow-up abdominal computed tomography showed a 6-cm mass in the left lower mesentery. The patient underwent open laparotomy. The histological diagnosis was sclerosing mesenteritis. The previous specimens of the left adrenal mass were then re-examined with a microscope, and panniculitis was found around the small cell carcinoma. Both lesions were histologically similar to IgG4-related disease (RD), but they did not completely meet the diagnostic criteria of IgG4-RD clinically or histologically.

A fundic gland polyp (FGP) is a common gastric polyp. Intraepithelial neoplasia in FGPs, referred to as FGP with dysplasia, is often seen in patients with familial adenomatous polyposis (FAP). In sporadic FGPs, low-grade dysplasia (LGD) is rare, and high-grade dysplasia (HGD) or carcinoma arising from sporadic FGPs is extremely rare. Because of this rarity, the prognosis and appropriate management of these lesions have not been clarified. In the present case, a sporadic FGP with LGD did not develop into invasive carcinoma, but contained foci of HGD 14 years after diagnosis. The biopsy specimen of the polyp taken at the first esophagogastroduodenoscopy 15 years earlier was diagnosed as FGP without dysplasia. At the second histological examination, LGD was found. Because the polyp increased in size during proton pump inhibitor therapy for 14 years, endoscopic mucosal resection was performed. The pathological diagnosis of the resected specimen was FGP with HGD mixed in LGD, with no invasive carcinoma. Dysplasia in FGPs might have less malignant potential regardless of dysplasia or size., (© 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Objectives: A key challenge in diagnosis and treatment of thymic epithelial tumors (TET) is in improving our understanding of the genetic and epigenetic changes of these relatively rare tumors., Methods: Methylation specific PCR (MSP) and immunohistochemistry were applied to 66 TET to profile the methylation status of DNA repair gene O6-methylguanine DNA methyltransferase (MGMT) and its protein expression in TET to clarify the association between MGMT status and clinicopathological features, response to chemotherapy and overall survival., Results: MGMT methylation was significantly more frequent in thymic carcinoma than in thymoma (17/23, 74% versus 13/44, 29%; P<0.001). Loss of expression of MGMT protein was significantly more frequent in thymic carcinoma than in thymoma (20/23, 87% versus 10/44, 23%; P<0.0001). There is a significant correlation between of MGMT methylation and loss of its protein expression (P<0.0003). MGMT methylation and loss of expression were significantly more frequent in advanced thymic epithelial tumors (III/IV) than in early tumors (I/II)., Conclusion: MGMT methylation plays a soul role in development of TET, especially in thymic carcinoma. Therefore, translation of our results from basic molecular research to clinical practice may have important implication for considering MGMT methylation as a marker and a target of future therapies in TET., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Our previous studies revealed a variety of genetic changes in lung cancers from chromate-exposed workers (chromate lung cancer). In the present study, we examined epigenetic changes in chromate lung cancers. Nested-methylation-specific PCR was employed in studying the methylation of CpG islands in the APC, MGMT, hMLH1 genes in 36 chromate lung cancers and 25 nonchromate lung cancers. Methylation in chromate lung cancers was detected at 86% for APC, 20% for MGMT, and 28% for hMLH1. Whereas, it occurred at lower frequencies in nonchromate lung cancers, particularly in APC (44%) and hMLH1 (0%) genes. Our previous study showed that methylation of p16 gene in chromate lung cancer and nonchromate lung cancer was 33% and 26%, respectively. The mean methylation index (MI), a reflection of the overall methylation status, was significantly higher in chromate lung cancers than nonchromate lung cancers (0.41 vs. 0.21, P=0.001). Methylation of multiple genes (particularly hMLH1, p16, and APC genes) had experienced more than 15 yr of chromate exposure in chromate lung cancer (MI: <15 yr; 0.19, ≥ 15 yr, 0.42). There is a significant correlation of p16 and hMLH1 methylation with the expressional decrease or loss of the corresponding gene products (P=0.037 and 0.024) respectively, and an inverse correlation between APC and MGMT methylation (P = 0.014). This study provides a novel evidence for the chromium carcinogenesis that chromate lung cancer is linked to the progressive methylation of some tumor suppressor genes, which may be related to genomic instability., (Copyright © 2010 Wiley-Liss, Inc.)

Background: Serum proteins that non-specifically bind with human S100A8/A9 (h-S100A8/A9) have been proposed. Our aim was to isolate and identify these proteins, and verify their clinical significance for monitoring the postoperative condition of liver recipients, and further to discuss the transportation of human fibronectin (h-FN) with h-S100A8/A9 and its functional role in vivo., Methods: To isolate the serum proteins, recombinant human S100A8, S100A9 and S100A8/A9 affinity columns were used. Proteins were identified by mass spectrometry. Two enzyme-linked immunosorbent assays (ELISA) were used to measure h-S100A8/A9 and h-FN in the sera of liver recipients. Flow cytometry was employed to detect h-S100A8/A9 and h-FN on immunological cells. Western blotting was used to confirm serum constituents using antibodies specific to each constituent., Results: One of the proteins was identified with h-FN, and its fluctuation pattern in the serum of the recipient was in contrast to that of CRP. Flow cytometry showed a positive reaction for h-S100A8/A9 and h-FN on neutrophils and monocytes, indicating that both proteins exist on these cells., Conclusions: The h-FN could be transported with S100A8/A9 in blood and/or on immunological cells, and effectively prevent further attack by various internal oxidants or repair damaged liver tissue in vivo., (2010 Elsevier B.V. All rights reserved.)

We have described a possible mechanism for the regulation of excessive inflammatory responses with S100A8/A9 protein in damaged rat livers. Recombinant human S100A8(r-S100A8) and S100A9 (r-S100A9) were expressed in E. coli cells, and their heterodimer (r-S100A8/A9) with 90% approximate purity was also prepared successfully. The effect of the r-S100A8/A9 on suppression of acute inflammatory changes in rat livers with LPS-induced damage was microscopically observed. Indeed, the liver damage diminished as the dose of the r-S100A8/A9 increased, and the minimum requirement of the protein was estimated to be 1,000 microg/rat in this study. Observation of superoxide anions was positively observed in control rats treated with LPS alone, but almost not in the livers of rats treated with the r-S 100A8/A9 1h after injection of LPS. This fact strongly suggests that the r-S100A8/A9 could indirectly suppress production of such internal oxidants according to unknown pathway (s) in acute inflammation. Expression of mRNAs of several kinds of inflammatory cytokines, such as TNF-alpha, IL-6 and IL-1beta, was also significantly suppressed, which was of much note. Therefore, the possibility that the r-S100A8/A9 partly inhibits the process of signal transduction of inflammatory responses in the immunological cells leading to down regulation of inflammatory changes in vivo was suggested in this study. Conclusively, S100A8/A9 is not necessarily an inflammatory-induced factor, and preferably effective on suppression of excessive inflammatory reaction in vivo dose-dependently, although the mechanism is still unclear.

We previously hypothesized that S100A8/A9 binds with several kinds of proinflammatory cytokines, such as TNF-alpha, IL-6 and IL-1beta, to form the S100A8/A9-proinflammatory cytokine complexes in vivo in acute inflammation, leading to subsidence of inflammatory responses. Our goal was to verify the presence of these complexes in liver tissues of rats with lipopolysaccharide (LPS) induced damage. We firstly prepared two kinds of the full-length cDNA encoding amino acid sequences of human S100A8 and S100A9 proteins, and constructed their pCold-I expression vectors. The recombinant S100A8 and S100A9 were successfully expressed in E. coli, and then purified by Ni-agarose columns, respectively. The S100A8/A9 was noncovalently synthesized in 2.0 mol/1 Tris-NaOH solution (pH 12) using the purified S100A8 and S100A9. After purification, this heterodimer (1 mg) was intraperitoneally injected into a rat 1h after injection of LPS. Two kinds of ELISA systems were used to detect the S100A8/A9-inflammatory cytokine complexes in the rat liver tissue. As determined by the ELISA-A and B, the reaction was apparently positive and quantitative. Immunohistochemistry provided such complexes-positive cells in the liver with damage. The S100A8/A9-positive cells almost corresponded to the cytokines-positive ones morphologically, strongly suggested the presence of the S100A8/A9-proinflammatory cytokine complexes. In conclusion, the possibility that these complexes were formed in vivo and accumulated to the immunological cells, such as macrophages and/or activated neutrophils, was indicated. Our effort is currently addressed to isolate the S100A8/A9-proinflammatory cytokine complexes using biochemical techniques, and to comprehensively resolute their clinical significance in the differential diagnosis of inflammatory diseases.

Minimally invasive total knee arthroplasty requires subluxation of patella laterally without eversion. The anatomy of the vastus medialis oblique muscle (VMO), which affects the surgical exposure of minimally invasive total knee arthroplasty, was investigated. There was no significant difference between men and women with respect to any parameter. The average fiber angle relative to the rectus femoris muscle was 52.9 degrees on anteroposterior view and 49.7 degrees on lateral view. The average insertion height and the distal portion of VMO belly were 17.3% and 38.4% of the patella length from the upper pole of patella, respectively. Female patients had lower VMO attachment and VMO belly, and a significant sex difference was demonstrated. All patients had attachments beneath the upper pole of the patella.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) was used for the measurement of relative proteoglycan depletion of articular cartilage in the patellofemoral (PF) joint following a proprietary protocol, which was compared with the X-ray images, proton density weighted MR images (PDWI) and arthroscopic findings. The study examined 30 knees. The ages ranged from 16 to 74 (average 40.3) years. The Gd-DTPA(2-)containing contrast medium was used in a single dose. The subjects were made to exercise the knee joint for 10 min; and MR images were taken 2 h after intravenous injection of contrast medium. T1-calculated images were produced and the region of interest (ROI) was set as follows. (1) ROI1: entire articular cartilage in a slice through the center of the patella. (2) ROI2: low signal region in T1-calculated images, which were set in a blind fashion by two observers. (3) ROI3: articular cartilage on one side that includes ROI2 where low signal region were detected (medial or lateral). ROI3 was set to examine the contrast of ROI2 with surrounding articular cartilage. The average T1 values of ROI1 was 393.5+/-33.6 ms for radiographic grade 0 and 361.3+/-11.1 ms for grade I, which showed a significant difference (P=0.036). The T1 value of ROI2 was 351.6+/-28.2 ms for grade I, 361.9+/-38.3 ms for grade II, 362.1+/-67.7 ms for grade III, and 297.8+/-54.1 ms for grade IV according to arthroscopic Outerbridge classification. All cases, that demonstrated decrease of T1 values on dGEMRIC (ROI2), showed abnormal arthroscopic or direct viewing findings. The ratio (ROI3/ROI2) in cases of only slight damage classified as Outerbridge grade I (6 cases) was an average of 1.04+/-0.02 and was 1.0 or greater in all cases, thereby indicating well-defined contrast with the surrounding cartilage. The diagnosis of damage in articular cartilage was possible in all 16 cases with radiographic K-L grade I on dGEMRIC, while the intensity changes were not found in 10 of 16 cases on PDWI. The dGEMRIC with a single-dose would be useful on a diagnosis of the area demonstrating early relative proteoglycan depletion in the articular cartilage of the PF joint prior to any discernible changes in the subchondral bone on X-ray images and exceeds to plain MR images for examining deterioration of articular cartilage.

The relationships among expression of cytochrome p450 aromatase (p450arom) mRNA in the mediobasal hypothalamus (MBH), ovarian aromatase activity, and estrogen secretion were examined throughout the estrous cycle in beagle bitches. Using polymerase chain reaction (PCR) analysis we were able to detect p450arom gene transcripts in the canine MBH. The level of hypothalamic p450arom mRNA increased during the progression of anestrus and declined thereafter. Ovarian p450arom activity, as measured by a (3)H2O assay, were low in anestrus, increased in proestrus, and declined thereafter. Ovarian p450arom activity and plasma estradiol-17beta levels were positively correlated (r=0.77, P<0.05). These results suggest that enhancement of hypothalamic p450arom gene expression is associated with termination of anestrus.

The occlusal surfaces of upper first molars of Australian Whites were measured in three dimensions with the aid of moiré contourography. The dental casts had been collected from Australian White twins who were considered to be of European stock and the casts housed in the Department of Dentistry, The University of Adelaide, South Australia. In the present study, our first aim was to describe the three-dimensional features of occlusal surfaces of molars in Australian whites. One cast was selected from each monozygotic twin pair at random. A total of 24 males and 15 females were photographed. The results obtained in the present study were compared with those of other human populations previously reported. Cusp height of Australian Whites showed intermediate mean values among 8 populations, but mean intercuspal distances were smaller. This feature, such as small size of occlusal surface but relatively high cusps, also found in Dutch and Asiatic Indian. Mean cusp heights in this population of showed similar values between sexes. Mean differences were insignificant as in Asiatic Indian, Australian Aboriginals, and Bantu unlike the Mongoloid, Japanese and Eskimo populations, where there were significant sex differences in cusp heights. This sexual dimorphism in cusp height among human populations is discussed phylogenetically and functionally.