Kusafuka K, Baba S, Kitani Y
… +5 more, Hirata K, Murakami A, Muramatsu A, Arai K, Suzuki M
Med Mol Morphol
· 2022 Dec · PMID 35789287
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Intercalated duct lesions (IDLs) are usually asymptomatic. We report a case of IDL, in which a palpable mass formed. The patient was a 45-year-old Japanese male, who noticed a mass in the left parotid region. The nodular...Intercalated duct lesions (IDLs) are usually asymptomatic. We report a case of IDL, in which a palpable mass formed. The patient was a 45-year-old Japanese male, who noticed a mass in the left parotid region. The nodular lesion was well-circumscribed, but did not have a fibrous capsule or exhibit infiltrative growth. It contained a small cystic space and consisted of basaloid cells arranged in a cribriform pattern and inner ductal cells. It had some solid areas of nest-like proliferation displaying mild cellular atypia. Immunohistochemically, the luminal cells were positive for cytokeratin (CK)7 and epithelial membrane antigen, and the abluminal cells were positive for CK5/6, p63, and DOG1. S-100 protein-positive stromal cells were also seen. The lesion's cells were all positive for SOX10, and the nuclei of some basaloid cells were positive for β-catenin. The Ki-67 labeling index was 3.8%. The ductal cells contained diastase-digestion-resistant, Periodic acid Schiff-positive zymogen granules. Genetically, the lesion harbored a missense mutation in the CTNNB1 gene. We diagnosed the lesion as an IDL. As IDLs are usually small non-neoplastic lesions, symptomatic cases are rare. Based on its common immunohistochemical and genetic features, IDL may be a precursor of basal cell adenoma/adenocarcinoma, such as intercalated duct adenoma.
Sugita S, Sugawara T, Emori M
… +5 more, Aoyama T, Hosaka M, Segawa K, Fujita H, Hasegawa T
Med Mol Morphol
· 2022 Dec · PMID 35779129
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Atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) is a new entity of benign adipocytic tumor that spans a wide spectrum of histology from adipocytic to spindle cell/pleomorphic tumors. The latter non-adipocytic...Atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) is a new entity of benign adipocytic tumor that spans a wide spectrum of histology from adipocytic to spindle cell/pleomorphic tumors. The latter non-adipocytic component rarely shows sarcomatous features although ASPLTs are not thought to dedifferentiate. A 78-year-old woman with ASPLT in the left thigh had a sarcomatous component with high mitotic activity and Ki-67 labeling index (LI) mimicking dedifferentiated liposarcoma. The adipocytic component consisted of various-sized adipocytic cells with few lipoblasts. The sarcomatous component consisted of a fascicular proliferation of atypical spindle cells with scattered large bizarre and multinucleated giant cells. Mitotic figures including atypical mitoses were frequently observed. Immunohistochemically, the tumor cells were positive for cluster of differentiation 34 but not mouse double minute 2 homolog (MDM2), cyclin-dependent kinase 4 (CDK4), or retinoblastoma (Rb) protein. Ki-67 LI in the sarcomatous component reached 40%. MDM2 and CDK4 genes were not amplified and 13q14 including the RB1 locus was deleted according to fluorescence in situ hybridization. The patient is alive with no evidence of local recurrence or distant metastasis 3.5 years after surgery. As ASPLT may exhibit morphological variation, it is important to rule out dedifferentiated liposarcoma with careful pathological examination.
Fujimoto D, Fukuya M, Terao S
… +8 more, Irei I, Akiyama T, Watanabe A, Yasuda Y, Yoshioka D, Takada K, Hayakawa S, Moriya T
Med Mol Morphol
· 2022 Dec · PMID 35716257
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Patients with SARS-CoV-2 infection and with severe COVID-19 often have multiple coinfections, and their treatment is challenging. Here, we performed cytology analysis on sputum samples from two patients with severe COVID...Patients with SARS-CoV-2 infection and with severe COVID-19 often have multiple coinfections, and their treatment is challenging. Here, we performed cytology analysis on sputum samples from two patients with severe COVID-19. The specimens were prepared using the rubbing method and stained with Papanicolaou stain. In both cases, several cells with frosted nuclei were observed, and the cytological findings per 100 cells were evaluated. The infected cells were mononuclear to multinuclear, showing chromatin aggregation at the nuclear margins, intranuclear inclusion bodies, eosinophilic cytoplasmic inclusion bodies, and mutual pressure exclusion of the nuclei. Immunocytochemical staining revealed that the cells were positive for AE1/AE3 and negative for CD68 expression, indicating their epithelial origin. Furthermore, infected cells with frosted nuclei were positive for surfactant protein A (SP-A) in Case 2, suggesting infection of type II alveolar pneumocytes or Clara cells. Moreover, in Case 2, the infected cells were positive for herpes simplex virus (HSV) I + II and SARS-CoV-2 spike protein, confirming double infection in these cells. In conclusion, sputum cytology is an important tool for determining the diversity of viral infection, and additional immunocytochemistry can be used for definitive diagnosis.
Angioimmunoblastic T-cell lymphoma (AITL), a hematological malignancy, originates from follicular helper T cells. The primary site of AITL is the lymph nodes, but extranodal presentation is frequent in patients with adva...Angioimmunoblastic T-cell lymphoma (AITL), a hematological malignancy, originates from follicular helper T cells. The primary site of AITL is the lymph nodes, but extranodal presentation is frequent in patients with advanced stages. Here, we report a rare case of a patient with AITL presenting with rapidly progressive glomerulonephritis (RPGN). The patient underwent computed tomography, which showed systemic lymph node swelling. RPGN was noted at the time of admission. Livedo was observed in the lower limbs with purpura on the foot. The patient was diagnosed with AITL based on lymph node biopsy. Skin biopsy revealed vasculitis with immunoglobulin A (IgA) deposits. Renal biopsy revealed endocapillary proliferative glomerulonephritis with massive subendothelial deposits and intraluminal thrombi. Immunofluorescence showed IgA, IgG, and complement component 3c-predominant granular staining pattern in the capillary and mesangial areas. Electron micrographs demonstrated dense cylindrical-like deposits in the subendothelial space. Chemotherapy drugs were administered, but the patient's respiratory distress increased until death. Upon autopsy, membranoproliferative glomerulonephritis and extensive necrotizing cellular crescent formation were observed in the glomeruli. Taken together, this case is a rare combination of AITL and RPGN showing both cylinder-like deposits suggestive of cryoglobulinemic glomerulonephritis (CN) and IgA vasculitis.
Tumor-associated macrophages (TAMs) have protumor functions in various cancers. However, their significance in hepatoblastoma, the most common liver tumor in children, remains unclear. The aim of this study was to explor...Tumor-associated macrophages (TAMs) have protumor functions in various cancers. However, their significance in hepatoblastoma, the most common liver tumor in children, remains unclear. The aim of this study was to explore the potential roles of TAMs in hepatoblastoma. Immunohistochemical analysis revealed that the density of CD204-positive TAMs was significantly higher in the embryonal component than in other histological subtypes of hepatoblastoma. An in vitro co-culture study with Huh6 cells and human monocyte-derived macrophages (HMDMs) showed that macrophage-colony-stimulating factor receptor (M-CSFR) was strongly up-regulated in the Huh6 cells that were directly co-cultured with HMDMs. The expressions of M-CSFR ligands (interleukin-34 and M-CSF) were also increased by co-culture with HMDMs. The proliferation of HepG2 cells (another hepatoblastoma cell line expressing M-CSFR) was inhibited by an M-CSFR inhibitor. M-CSFR was found to be highly expressed in the embryonal component and in recurrent lesions. The number of CD204-positive macrophages was also higher in the M-CSFR-positive areas than in the M-CSFR-negative areas. Thus, M-CSFR expression appeared to be induced by cell-cell contact with macrophages in hepatoblastoma cells, and M-CSFR inhibitor is potentially effective against M-CSFR-positive hepatoblastoma, especially recurrent cases.
Nozawa Y, Ishida K, Maiko N
… +7 more, Takada-Owada A, Onozaki M, Takaoka M, Matsuyama K, Sakuraoka Y, Nakazato Y, Kubota K
Med Mol Morphol
· 2022 Sep · PMID 35596001
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A non-ampullary duodenal mixed adenoneuroendocrine carcinoma (MANEC), consisting of a conventional adenocarcinoma and a neuroendocrine carcinoma (NEC), is exceedingly rare. Moreover, mismatch repair (MMR) deficient tumor...A non-ampullary duodenal mixed adenoneuroendocrine carcinoma (MANEC), consisting of a conventional adenocarcinoma and a neuroendocrine carcinoma (NEC), is exceedingly rare. Moreover, mismatch repair (MMR) deficient tumors have recently attracted attention. The patient, a 75-year-old woman with epigastric pain and nausea, was found to have a type 2 tumor of the duodenum, which was diagnosed on biopsy as a poorly differentiated carcinoma. A pancreaticoduodenectomy specimen showed a well-defined 50 × 48 mm tumor in the duodenal bulb, which was morphologically composed of glandular, sheet-like, and pleomorphic components. The glandular component was a tubular adenocarcinoma, showing a MUC5AC-positive gastric type. The sheet-like component consisted of homogenous tumor cells, with chromogranin A and synaptophysin diffusely positive, and a Ki-67 index of 72.8%. The pleomorphic component was diverse and prominent atypical tumor cells proliferated, focally positive for chromogranin A, diffusely positive for synaptophysin, and the Ki-67 index was 67.1%. The sheet-like and pleomorphic components were considered NEC, showing aberrant expression of p53, retinoblastoma, and p16. Notably, all three components were deficient in MLH1 and PMS2. We diagnosed a non-ampullary duodenal MANEC with MMR deficiency. This tumor has a unique morphology and immunohistochemical profile, and is valuable for clarifying the tumorigenesis mechanism of a non-ampullary duodenal MANEC.
We investigated whether BMP4, FGF8, and/or WNT3a on neural crest-like cells (NCLC) derived from mouse induced pluripotent stem (miPS) cells will promote differentiation of odontoblasts-like cells. After the miPS cells ma...We investigated whether BMP4, FGF8, and/or WNT3a on neural crest-like cells (NCLC) derived from mouse induced pluripotent stem (miPS) cells will promote differentiation of odontoblasts-like cells. After the miPS cells matured into embryonic body (EB) cells, they were cultured in a neural induction medium to produce NCLC. As the differentiation of NCLC were confirmed by RT-qPCR, they were then disassociated and cultured with a medium containing, BMP4, FGF8, and/or WNT3a for 7 and 14 days. The effect of these stimuli on NCLC were assessed by RT-qPCR, ALP staining, and immunocytochemistry. The cultured EB cells presented a significant increase of Snai1, Slug, and Sox 10 substantiating the differentiation of NCLC. NCLC stimulated with more than two stimuli significantly increased the odontoblast markers Dmp-1, Dspp, Nestin, Alp, and Runx2 expression compared to control with no stimulus. The expression of Dmp-1 and Dspp upregulated more when FGF8 was combined with WNT3a. ALP staining was positive in groups containing BMP4 and fluorescence was observed in immunocytochemistry of the common significant groups between Dmp-1 and Dspp. After stimulation, the cell morphology demonstrated a spindle-shaped cells with long projections resembling odontoblasts. Simultaneous BMP4, FGF8, and WNT3a stimuli significantly differentiated NCLC into odontoblast-like cells.
Cardiomyocytes have been differentiated from various stem cells such as human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC), but it is difficult to produce mature cardiomyocytes. We showed rat hair...Cardiomyocytes have been differentiated from various stem cells such as human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC), but it is difficult to produce mature cardiomyocytes. We showed rat hair-follicle-associated pluripotent (HAP) stem cells have pluripotency and produced mature beating cardiomyocyte sheets differentiated from rat HAP stem cells. The upper parts of rat vibrissa hair follicles were cultured in 10% FBS DMEM and stained with antibodies of the ectoderm, mesoderm, endoderm system to show the differentiation of multiple cell types. Moreover, HAP stem cells were cultured under three different conditions to decide the most suitable culture conditions for making beating cardiomyocyte sheets. The beating cardiomyocyte sheets were shown to be mature by staining sarcomere structures. Isoproterenol alone and the combination of isoproterenol, activin A, bone morphogenetic protein 4 (BMP4) and basic fibroblast growth factor (bFGF) effectively induced beating long-fiber cardiomyocytes, which formed beating sheets, only in the presence of all four agents. Flexible substrates were essential for the differentiation of sheets of mature beating cardiomyocytes for HAP stem cells. The features of the cardiomyocytes differentiated from HAP stem cells demonstrate they have clinical potential for heart regeneration.
Female pattern hair loss (FPHL), a type of hair disease common in pre- and postmenopausal women, is characterized by thinning of hair to O-type, mainly at the crown. Although a mouse model of this disease has recently be...Female pattern hair loss (FPHL), a type of hair disease common in pre- and postmenopausal women, is characterized by thinning of hair to O-type, mainly at the crown. Although a mouse model of this disease has recently been established, its details are still unknown, and thus, warrants further analysis. In this study, 3 week-old and 7- to 8 week-old C57BL/6 female mice were divided into two groups: one group underwent ovariectomy (OVX), while the other underwent sham surgery. In the 3 week-old mice, the dorsal skin was collected at seven weeks of age, while in the 7- to 8 week-old mice, it was collected at 12 and 24 weeks of age. In the former group, both the pore size of the hair follicles (HFs) and diameter of the hair shaft of telogen HFs decreased upon OVX; while in the latter group, these factors increased significantly. Notably, the thickness of the dermis and subcutis increased significantly in the OVX group. It needs to be further elucidated whether OVX mouse could serve as an ideal mouse model for FPHL, but our results upon evaluation of skin thickness indicate that it could be used to establish a novel treatment for non-hair-related diseases, such as post-menopause-related skin condition.
Nakayama F, Miyoshi M, Kimoto A
… +5 more, Kawano A, Miyashita K, Kamoshida S, Shimizu K, Hori Y
Med Mol Morphol
· 2022 Sep · PMID 35475918
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Distant metastasis is a dismal prognostic factor of pancreatic cancer. Metastasis is established in several steps, but the mechanism underlying the very early stages remains unclear. Epithelial-mesenchymal transition (EM...Distant metastasis is a dismal prognostic factor of pancreatic cancer. Metastasis is established in several steps, but the mechanism underlying the very early stages remains unclear. Epithelial-mesenchymal transition (EMT) is involved in these stages. Although signaling molecules have been reported to induce EMT, the mechanism underlying their origin is unclear. In this study, we hypothesized that pancreatic cancer cell-derived exosomes induce EMT in cancer cells themselves, a notion we entertained because we found EMT in in vitro three-dimensional colonies of cancer cells, with vimentin-positive cells observed in some of the budding pancreatic cancer cells and in single cells outside the colony as well. First, we clarified that pancreatic cancer cell-derived exosomes induce EMT in cancer cells themselves. Next, we examined the involvement of transforming growth factor-β1 (TGF-β1), and TGF-β1 knock-down in pancreatic cancer cells with TGF-β1 siRNA significantly suppressed TGF-β1 gene expression in cancer cells, and exosomal TGF-β1 was significantly reduced in the secretory exosomes. Exosomes from TGF-β1 knock-down cells suppressed EMT induction in cancer cells themselves and TGF-β1 protein expression in target cells. Taken together, these findings suggest that TGF-β1 is involved in EMT induction via exosomes, results that may support the production of effective metastasis inhibitors.
Cleidocranial dysplasia (CCD) is a hereditary disorder associated with skeletal dysplasia and dental abnormalities. CCD arises from heterozygous loss of function mutations in the Runt-related transcription factor 2 (RUNX...Cleidocranial dysplasia (CCD) is a hereditary disorder associated with skeletal dysplasia and dental abnormalities. CCD arises from heterozygous loss of function mutations in the Runt-related transcription factor 2 (RUNX2) gene. Osteoporosis is often observed in CCD patients and conventional vitamin D supplementation is recommended. However, sufficient evidences have not been presented yet. This study investigated the role of RUNX2 in osteoblastic differentiation and sought to identify potential target genes for the treatment of osteoporosis associated with CCD, using induced pluripotent stem cell (iPSC) technology. We successfully established Runx2, Runx2 and wild-type miPSCs from litter-matched mice and found poor Vdr expression in Runx2cells. Significant down-regulation of osteoblastic differentiation in Runx2 miPSCs was observed. Gene expression array revealed unexpected results such as remarkable increase of Rankl expression and decrease of Vdr in Runx2 cells. Insufficient response to vitamin D in Runx2 cells was also observed. Our results suggest that RUNX2 functions as a regulator of Rankl and Vdr and thereby controls bone density. These findings also suggest that conventional vitamin D supplementation may not be as effective as previously expected, in the treatment of osteoporosis associated with CCD, and that inhibiting RANKL function might be worth considering as an alternative treatment strategy.
Taki Y, Fuku A, Nakamura Y
… +18 more, Koya T, Kitajima H, Tanida I, Takaki T, Nozaki K, Sunami H, Hirata H, Tachi Y, Shimasaki T, Masauji T, Yamamoto N, Ishigaki Y, Shimodaira S, Shimizu Y, Ichiseki T, Kaneuji A, Osawa S, Kawahara N
Adipose-derived stem cell (ADSC) sheets have potential to be effective in various therapies. In this study, we first demonstrated that a cell sheet composed of human ADSCs could be created using a new temperature-respons...Adipose-derived stem cell (ADSC) sheets have potential to be effective in various therapies. In this study, we first demonstrated that a cell sheet composed of human ADSCs could be created using a new temperature-responsive culture dish from the DIC Corporation. The dish can cause detachment of adherent cells due to temperature changes, but a few morphological analyses have evaluated the presence or absence of damage on the detached surface of cell sheet. To characterize our ADSC sheet, we tried to observe the surface of ADSC sheets with scanning electron microscope (SEM) using the ionic liquid, which enables the rapid preparation of samples. No damage was found on the surface of the ADSC sheets on the side that had been in contact with the surface of the culture dishes. In addition, when the transcriptomes of the harvested cell sheets were compared with those of monolayer cultures, no up-regulation of cell death related genes were detected. These results propose that the detachment from temperature-responsive culture dish causes no serious damage on the prepared ADSC sheet. It is also suggested that the SEM with ionic liquids is a useful and rapid method for the analysis of ADSC sheets for therapy.
Kaku N, Shimada T, Hosoyama T
… +1 more, Tsumura H
Med Mol Morphol
· 2022 Jun · PMID 35244781
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This study aimed to examine the ultrastructure of the arteries of the synovium, acetabular labrum, and ligamentum teres of the hip joint using light, scanning electron, and transmission electron microscopes to identify f...This study aimed to examine the ultrastructure of the arteries of the synovium, acetabular labrum, and ligamentum teres of the hip joint using light, scanning electron, and transmission electron microscopes to identify features of early arteriosclerosis. Tissues collected from three patients (under 40 years of age) with osteonecrosis of the femoral head were immersed in 8 N HCl at 60 °C for 20 min to digest collagen fibers for scanning electron microscopy. Tortuous arterioles and arteries were noted in the joint components, including the synovium, acetabular labrum, and ligamentum teres. The ultrastructure of the arterioles appeared normal; however, intimal thickening was found in most arteries. The thickened intima had abundant elastic fibers and many smooth muscle cells (which were of a synthetic phenotype because they had a few actin filaments and well-developed rough endoplasmic reticulum). This study illustrates that arteriosclerotic changes are present in tortuous arteries in the synovium, acetabular labrum, and ligamentum teres of the hip joint even from a relatively young age and suggests that meandering blood vessels may be the preferred foci of arteriosclerosis.
Nakajima Y, Yamazaki Y, Gao X
… +5 more, Hashimoto M, Nio M, Wada M, Fujishima F, Sasano H
Med Mol Morphol
· 2022 Jun · PMID 35238992
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Biliary atresia (BA) is a cholestatic disease with extrahepatic bile duct obstruction that requires early surgical intervention and occasionally liver transplantation (LT). Accumulation of toxic bile acids induces oxidat...Biliary atresia (BA) is a cholestatic disease with extrahepatic bile duct obstruction that requires early surgical intervention and occasionally liver transplantation (LT). Accumulation of toxic bile acids induces oxidative stress that results in cell damage, such as cell senescence, mitochondrial dysfunction and others. However, details of their reciprocal association and clinical significance are unexplored. Therefore, we used immuno-localization of markers for cell senescence (p16 and p21), nuclear double-strand DNA damage (γH2AX), autophagy (p62), and mtDNA damage (mtDNA copy number) in patients with BA who underwent Kasai portoenterostomy (KP) and LT. We studied liver biopsy specimens from 54 patients with BA, 14 who underwent LT and 11 from the livers of neonates and infants obtained at autopsy. In hepatocytes, p21 expression was significantly increased in KP. In cholangiocytes, p16 expression was significantly increased in LT, and p21 expression was significantly increased in KP. p62 expression was significantly increased in the KP hepatocytes and LT cholangiocytes. Furthermore, mtDNA copy number significantly decreased in KP and LT compared with the control. Cell senescence and mitochondrial DNA damage progression were dependent on the BA clinical stages and could possibly serve as the markers of indication of LT.
Med Mol Morphol
· 2022 Jun · PMID 35137264
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Subarachnoid hemorrhage (SAH) is a complicated and deadly disorder. Dysregulation of miRNAs in SAH has been widely reported. This investigation elucidated the function of miR-23a-3p in the in vivo and in vitro models of...Subarachnoid hemorrhage (SAH) is a complicated and deadly disorder. Dysregulation of miRNAs in SAH has been widely reported. This investigation elucidated the function of miR-23a-3p in the in vivo and in vitro models of SAH. The miR-23a-3p and VCAN levels in SAH rats and sham controls were detected by RT-qPCR. The SAH rats were intracerebrally administrated with miR-23a-3p antagomir. Morphological changes and brain function were assessed. The isolated brain microvascular endothelial cells (BMECs), identified by immunofluorescence staining, were used as the model of SAH in vitro. The viability and apoptosis of BMECs were evaluated using MTT, flow cytometry, and western blotting analyses. Targeted relationship between miR-23a-3p and VCAN was predicted in miRDB and validated by a luciferase reporter assay. We found that the miR-23a-3p level was upregulated in rats after SAH, while VCAN was downregulated. Silencing miR-23a-3p attenuated neurological deficits and neuronal apoptosis in rats after SAH. VCAN was verified to be targeted by miR-23a-3p. Functionally, miR-23a-3p downregulation or VCAN overexpression inhibited BMEC apoptosis and promoted cell activity. Moreover, knockdown of VCAN eliminated the influence of miR-23a-3p inhibition in BMECs. Overall, suppression of miR-23a-3p improves cognitive function after SAH by targeting VCAN.
Kuro A, Morimoto N, Hara T
… +5 more, Matsuoka Y, Fukui M, Hihara M, Kusumoto K, Kakudo N
Med Mol Morphol
· 2022 Jun · PMID 35129664
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Supercooling preservation below 0 °C allows the storage of the transplantable sources in an unfrozen state. This can improve the safety and efficacy of storage by improving the inhibition of metabolism and organ preserva...Supercooling preservation below 0 °C allows the storage of the transplantable sources in an unfrozen state. This can improve the safety and efficacy of storage by improving the inhibition of metabolism and organ preservation in comparison with conventional preservation at 4 °C. We have developed a supercooling technique using a voltage-applied apparatus without perfusion. We examined the preservation effects of our supercooling preservation technique in a rat model of artery transplantation. Our technique produces a supercooled state at - 2 °C with application of 1000 V. The viability of tissue cells from rat arteries was found to be higher with storage using the proposed method than that under ordinary conditions. Damage to the vascular endothelium of the femoral artery preserved by voltage-applied supercooling at - 2 °C was reduced compared to storage under ordinary conditions. Artery graft revival was successfully achieved with graft patency after supercooling preservation, and 1 week outcomes for post-transplanted grafts, including thrombosis, were better with supercooling preservation than with conventional 4 °C preservation. Supercooling artery preservation at - 2 °C with 1000 V promises to greatly prolong preservation time and improve post-transplant outcomes.
Med Mol Morphol
· 2022 Jun · PMID 35122146
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Purple urine bag syndrome (PUBS) is seen in the prolonged indwelling bladder catheters, and the mechanism of its onset was investigated using low vacuum scanning electron microscopy (LVSEM), which enables us to study the...Purple urine bag syndrome (PUBS) is seen in the prolonged indwelling bladder catheters, and the mechanism of its onset was investigated using low vacuum scanning electron microscopy (LVSEM), which enables us to study the 3D structure of urinary sediments and urine bag walls. The urinary sediment and urine bags of 2 cases of PUBS were observed by LVSEM. The urine was brown turbid urine with a pH of 8.5, and magnesium phosphate stones and granules were observed in the urinary sediment together with Gram-positive and Gram-negative bacilli. Bacteria that moved by Brownian motion were observed with a dark-field microscope. LVSEM showed granular crystals around the bacilli, cocci, or mycelium that adhered to the walls of the bag. Granular crystals were dissolved in chloroform and presumed to be a mixture of the bacterial metabolites indigo blue and indirubin red. LVSEM also detected unusual tubular and honeycomb-like graphene in the urinary sediments, which were derived from the inner layer of the silicon elastomer-coated rubber catheter. LVSEM revealed purple crystals produced by bacteria or fungi attached to the urine bag that caused PUBS.
Cai M, McNamara K, Yamazaki Y
… +5 more, Harada N, Miyashita M, Tada H, Ishida T, Sasano H
Med Mol Morphol
· 2022 Jun · PMID 35103835
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We attempted to explore the possible involvement of the in situ availability of mineralocorticoids and mineralocorticoid receptor (MR) in the pathogenesis of mammary ductal carcinoma. We also explored their individual pr...We attempted to explore the possible involvement of the in situ availability of mineralocorticoids and mineralocorticoid receptor (MR) in the pathogenesis of mammary ductal carcinoma. We also explored their individual profiles among different subtypes of invasive ductal carcinomas of no special type (IDC-NST) by evaluating the status of MR, Glucocorticoid receptor (GR), and 11β hydroxysteroid dehydrogenase (HSD) 1/2 at each stage of the putative cascade of the mammary ductal proliferative disorders. In this study, IDC-NST, ductal carcinoma in situ (DCIS), atypical ductal hyperplasia (ADH), and non-pathological breast tissues were all evaluated by immunohistochemistry. MR was significantly lower in ADH than in DCIS or IDC-NST. 11βHSD2 was significantly lower in ADH than normal breast tissue and 11βHSD1 was significantly higher in DCIS than normal, ADH, or IDC-NST. MR in progesterone receptor (PR)-positive IDC-NST cases tended to be associated with the Ki-67 labeling index. Results of the present study demonstrated that the status of MR and GR in conjunction with the 11βHSDs was correlated with the development of low-grade proliferative disorders in mammary glands. In addition, the potential crosstalk between MR and PR could also influence cell proliferation of breast carcinoma cells but further investigations are required for clarification.
Med Mol Morphol
· 2022 Jun · PMID 35048195
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Both fascin and fibronectin are known to play important roles in cell adhesion and migration. They are noted as tumor markers or inhibiting target for tumor treatment. In this study, embryonic rat livers were obtained to...Both fascin and fibronectin are known to play important roles in cell adhesion and migration. They are noted as tumor markers or inhibiting target for tumor treatment. In this study, embryonic rat livers were obtained to examine the expression of fascin and fibronectin during liver development. Then, the effect of fibronectin on fascin expression was investigated. At embryonic day (ED) 10.5, when the foregut endoderm began to form the liver bud and spread into the septum transversum, fibrous extracellular matrix was observed between the space where the liver bud and the septum transversum merged. At ED11.5, fibronectin was observed surrounding the cluster of fascin-positive hepatoblasts. At ED13.5, hematopoietic cells emerged and both fibronectin and fascin expression started to decline. Fascin and fibronectin appeared temporarily and disappeared by ED 14.5. Their expression was chronologically synchronized. Subsequently, the effect of fibronectin on fascin was examined by cultivation of hepatoblasts that were isolated from the ED13.5 rat liver. As a result, with fibronectin, fascin was positive in most hepatoblasts, although, without fibronectin, fascin expression was remarkably declined. Presently, there are few studies about the relationship between fascin and fibronectin. Our findings suggest that fibronectin could regulate fascin expression in rat hepatoblasts.
Nasu K, Aoyagi Y, Zhu R
… +3 more, Okamoto M, Kai K, Kawano Y
Med Mol Morphol
· 2022 Jun · PMID 34846581
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Endometriosis is a benign tumor that affect 6-10% women of reproductive age. To date, it is suggested that the aberrant microRNA (miRNA) expressions play important roles in the pathogenesis of endometriosis. Reviewing th...Endometriosis is a benign tumor that affect 6-10% women of reproductive age. To date, it is suggested that the aberrant microRNA (miRNA) expressions play important roles in the pathogenesis of endometriosis. Reviewing the literature, we found nine overexpressed miRNAs, which were thoroughly investigated in the context of endometriotic tissues and cells. Most of the overexpressed miRNAs induced endometriosis-specific characteristics including inhibition of apoptosis and decidualization, upregulation of fibrogenesis, invasion, migration, cell proliferation, attachment to extracellular matrix, inflammation, and angiogenesis in the endometriotic cells. Then, we found that the downstream target molecules of these miRNAs, such as early growth response protein-1, extracellular signal-regulated kinase, matrix metallopeptidase 1, signal transducer and activator of transcription 3, cyclooxygenase-2, phosphoinositide 3-kinase, AKT, mammalian target of rapamycin, and vascular endothelial growth factor-A are promising for the therapeutic targets of endometriosis. Recent findings suggest that complex molecular mechanisms leading to development and progression of endometriosis by miRNAs may exist in endometriosis. The meticulous balance between tumorigenic miRNAs and tumoristatic miRNAs may destine the natural course and response to the surgical, medical, and hormonal treatments of this disease. Further investigations into endometriosis-associated miRNAs may elucidate the pathogenesis of endometriosis and help to develop novel therapeutics.