Hepatocellular carcinoma in a transplanted donor liver and colon cancer developing in a patient with a complex background: A case report.

The development of tumors in livers transplanted from hepatitis B virus (HBV)-negative donors to patients with hepatitis B and cirrhosis is rare. The present study describes the case of a woman in her 60s who developed hepatocellular carcinoma (HCC) in her grafted liver, 19 years after transplantation, as well as a metachronous colorectal tumor. The pathological findings, including clinical, immunohistochemical and molecular results, are described in the present case report. The liver tumor was a conventional HCC and the colorectal tumor comprised a tubular adenocarcinoma. Immunohistochemistry of both tumors showed a loss of expression of mutL homolog 1 and postmeiotic segregation increased 2 in the tumor cells, confirming microsatellite instability-high (MSI-H) status. Furthermore, a molecular study detected the presence of genes located on the Y chromosome in the normal and tumor tissues of the liver, proving that the HCC occurred in the grafted liver. The present report also discusses that prolonged use of immunosuppressive drugs to prevent post-transplant rejection, poorly controlled diabetes mellitus and MSI-H may have contributed to the risk of tumor development.

Giant retroperitoneal myolipoma mimicking liposarcoma: report of a resected case and review of the literature.

Myolipomas are rare tumors that are often difficult to differentiate from liposarcoma. Herein, we report a case of resected giant myolipoma preoperatively diagnosed as liposarcoma. A 63-year-old woman was suspected of having a large retroperitoneal liposarcoma on October 202X. The patient was referred to our department for tumor resection and a histological diagnosis. After consultation with the urology, obstetric and gynecology, and vascular surgery departments, tumor resection was planned, including the potential resection of other organs. Intraoperative findings revealed a large, elastic, soft tumor with a smooth surface and a capsule occupying the entire abdominal cavity. The tumor was adherent to the stomach, left colon, and uterine adnexa, and no invasion was observed. The tumor was completely resected, and organ resection was not necessary. The tumor was 40 cm in diameter and 4.0 kg in weight. Pathological examination and immunostaining confirmed a diagnosis of myolipoma. The patient's postoperative course was uneventful, and she was discharged on postoperative day 10 with no complications. Twelve months after surgery, the patient was doing well. To the best of our knowledge, we report a complete resection of the largest retroperitoneal myolipoma reported to date. Physicians should consider surgery, even for suspected large sarcomas that may be difficult to resect completely.

Rational in silico design identifies two mutations that restore UT28K SARS-CoV-2 monoclonal antibody activity against Omicron BA.1.

SARS-CoV-2 rapidly mutates and acquires resistance to neutralizing antibodies. We report an in-silico-designed antibody that restores the neutralizing activity of a neutralizing antibody. Our previously generated antibody, UT28K, exhibited broad neutralizing activity against mutant variants; however, its efficacy against Omicron BA.1 was compromised by the mutation. Using previously determined structural information, we designed a modified-UT28K (VH T28R/N57D), UT28K-RD targeting the mutation site. In vitro and in vivo experiments demonstrated the efficacy of UT28K-RD in neutralizing Omicron BA.1. Although the experimentally determined structure partially differed from the predicted model, our study serves as a successful case of antibody design, wherein the predicted amino acid substitution enhanced the recognition of the previously elusive Omicron BA.1. We anticipate that numerous similar cases will be reported, showcasing the potential of this approach for improving protein-protein interactions. Our findings will contribute to the development of novel therapeutic strategies for highly mutable viruses, such as SARS-CoV-2.

A Case Report of Anti-TIF1-γAntibody-Positive Dermatomyositis Concomitant with Small Cell Neuroendocrine Carcinoma of the Urinary Bladder.

Small cell neuroendocrine carcinoma is rare among urinary bladder cancer types, and to date, there are no case reports of concurrent antitranscriptional intermediary factor 1-γantibody-positive dermatomyositis. We describe the case of a 69-year-old Japanese man who presented with elevated creatine kinase levels and haematuria on medical examination. Approximately one month later, he developed dysphagia. Laryngoscopy confirmed laryngeal dysfunction. He also presented with muscle weakness and a skin rash. Magnetic resonance imaging of the upper extremities suggested bilateral brachial muscle myositis. He was diagnosed as having dermatomyositis and was later found to be positive for antitranscriptional intermediary factor 1-γ antibody. Computed tomography revealed an intravesical space-occupying lesion and right iliac lymphadenopathy, suggesting urinary bladder cancer. The patient was admitted to our hospital for treatment. Urinary bladder biopsy confirmed small cell neuroendocrine carcinoma because tumour cells were positive for synaptophysin, CD56, and chromogranin A. Thus, the patient was diagnosed as having an antitranscriptional intermediary factor 1-γantibody-positive dermatomyositis concomitant with urinary bladder small cell neuroendocrine carcinoma. The patient was treated with glucocorticoid and intravenous immune globulin therapy for dermatomyositis. Radiotherapy was selected for the carcinoma. Although muscle weakness and skin symptoms improved with treatment, dysphagia persisted. Furthermore, expression of the transcriptional intermediary factor 1-γ protein in tumour cells was also confirmed by immunohistochemistry, but the significance is unknown. It should be noted that antitranscriptional intermediary factor 1-γantibody-positive dermatomyositis can occur concomitantly with such a rare malignancy.

An Autopsy Case of Ruptured Hepatic Angiosarcoma Treated by Transcatheter Arterial Embolization.

An 80-year-old Japanese man presented to our hospital with intra-abdominal hemorrhage due to a ruptured liver tumor. Transcatheter arterial embolization (TAE) temporarily achieved hemostasis, but he died following re-rupture 4 days later. Based on autopsy findings, the liver tumor was diagnosed as hepatic angiosarcoma. Embolic agents used during embolization were identified within the hepatic small interlobular arteries. However, there were no findings of tumor cell necrosis or ischemic change in the angiosarcoma. In the present case, TAE alone did not induce ischemia-induced tumor necrosis, suggesting that TAE might be unsuitable to treat hepatic angiosarcoma. Treatment optimization for ruptured hepatic angiosarcoma is desired.

Nephrotic syndrome induced by aortic regurgitation with Takayasu arteritis: an autopsy case with long-term clinical follow-up.

Takayasu arteritis is a rare, chronic, and large-vessel vasculitis involving the aorta and its branches in a complex autoimmune reaction. Takayasu arteritis sometimes complicates aortic regurgitation and chronic kidney disease, but rarely accompanies nephrotic syndrome. We had a patient with Takayasu arteritis and concomitant aortic regurgitation. She had nephrotic syndrome that was refractory to immunosuppressive therapy but was promptly improved after surgical aortic valve replacement. In her kidney biopsy, glomeruli had mild mesangial proliferative changes without immune complex deposition. Her proteinuria remained negative until the recurrence of aortic regurgitation due to perivalvular leakage. Seventeen years after the surgery, she died suddenly. In her kidney autopsy, the arteriolar showed severe hyalinosis and the glomerulus showed mesangial proliferative changes with segmental mesangiolysis. Severe aortic regurgitation may have altered renal hemodynamics and caused glomerular lesions, resulting in nephrotic syndrome. We should be aware of the rare but critical comorbidity of nephrotic syndrome in patients with Takayasu arteritis and concomitant aortic regurgitation.

Preparation of Anti-Rabies Virus N Protein IgYs by DNA Immunization of Hens Using Different Types of Adjuvants.

DNA immunization has been used to study vaccination methods and for production of specific antibodies. The present study aimed to apply DNA immunization to prepare specific IgYs, which react against rabies virus N protein (RV-N) and can be used to research and diagnose rabies virus. The DNA sequence of RV-N was ligated into a pcDNA 3.1 plasmid for constructing pcDNA-N. Eight hens were divided into four groups. Group 1 comprised the control group (non-immunized). In Groups 2, 3, and 4, hens were injected intramuscularly with pcDNA-N (400 µg/hen). Eight injections were administered every other week. From the 4th week, an adjuvant was injected in addition to pcDNA-N. Freund's complete adjuvant (FCA) and λ-carrageenan were administered to Groups 3 and 4, respectively. Eggs were collected daily, and the specific antibody activities of egg yolks were measured by ELISA. IgYs were purified from pooled egg yolks at 16-19 weeks post-administration in each group. The detection sensitivities of the RV-N were compared using purified IgY as the primary antibody for ELISA, dot blotting, and western blotting. Egg yolks from one of the two hens in Group 2 (pcDNA-N alone) and all hens in Groups 3 (pcDNA-N + FCA) and 4 (pcDNA-N + λCarra) had increased ELISA values. The combined use of λ-carrageen in DNA immunization resulted in an adjuvant effect comparable to that of FCA. Each purified specific IgY detected RV-N in the ELISA, western blotting, and dot blotting; however, the detection sensitivity differed. Higher detection sensitivity of the +λCarra IgY was observed by ELISA, whereas there was higher detection sensitivity of +FCA IgY in western blotting and dot blotting. In summary, anti-rabies virus N protein IgY was prepared through DNA immunization of hens using FCA or λ-carrageenan as adjuvants and can be used as a primary antibody to detect rabies viruses.

Sebaceous adenoma occurring within an intracranial dermoid cyst.

Among intracranial cystic lesions, dermoid cysts and epidermoid cysts are relatively common benign tumors. In a small number of these tumors, it is known that squamous cell carcinomas arise in the lining epithelium of the cysts. Among tumors derived from the appendage, only one case of hidradenoma within a dermoid cyst and no cases of sebaceous tumor have been reported previously. In the present case, a protruding lesion was present in the cystic wall, and it was composed of two cell types: sebaceous cells (sebocytes) and basaloid/germinated cells, being characteristic of this tumor. It is essential to distinguish it from other sebaceous lesions such as hyperplasia, sebaceoma, sebaceous carcinoma, and basal cell carcinoma with sebaceous differentiation derived from the epidermis. The critical distinguishing points in making a differential diagnosis among these lesions are the ratio of the two cell types and the presence or absence of other components such as hair sacs, invasion or cellular atypia. Immunohistochemical examination revealed that the tumor cells were positive for the epithelial markers, such as cytokeratin (CK)14, p63, p40, high-molecular CK, and adipophilin; these findings are peculiar to sebaceous adenoma. Although there have been several similar case reports of sebaceous tumors associated with dermmoid cysts in the ovaries, most of the intracranial lesions were squamous cell carcinomas that developed within the cysts, and there has been no precedent showing an association with a sebaceous tumor. The present report describes the first case of sebaceous adenoma that occurred in an intracranial dermoid cyst.

A Case of Dedifferentiated Melanoma With Lymph Node Metastasis Where Molecular Biological Tests Were Useful for Diagnosis.

Malignant melanoma is known to have an altered phenotype and loss of differentiation markers for melanoma due to metastasis. Here, we report a case in which the expression of the immunohistochemical markers for melanoma was changed due to lymph node metastasis of primary cutaneous malignant melanoma. The patient, a male in his 60s, was diagnosed with malignant melanoma after undergoing excision of a skin mass. The additional excision specimen showed a small number of tumor cell clusters infiltrating the dermis. The biopsied lymph node showed completely different histological findings from those of the skin lesion and consisted of spindle-shaped tumor cells. An immunohistochemical study revealed no significant positive reactions in the lymph node tissue indicative of melanoma. The additional genetic study revealed BRAF V600e mutations in both the primary tumor and a lymph node. Together with the histological findings, the diagnosis was of metastasis of dedifferentiated melanoma to a lymph node. In summary, there is a risk of underestimation or misdiagnosis of melanoma as undifferentiated sarcoma or other tumors when melanoma metastasizes to lymph nodes and findings show a dedifferentiated or undifferentiated tumor. Therefore, as in this case, it is necessary to add a genetic study in order to make a comprehensive judgment.

Epitope Mapping of A Viral Propagation-Inhibiting Single-Chain Variable Fragment Against Rabies Lyssavirus Phosphoprotein.

Rabies is a highly neurotropic disease caused by rabies lyssavirus (RABV). Human rabies vaccines exist for pre- and postexposure prophylaxis; however, after clinical symptoms appear, the disease has an ∼100% mortality rate with no effective treatments available. In our previous study, mouse neuroblastoma cells transfected with a plasmid coding one clone of a single-chain variable fragment (scFv), scFv-P19, against RABV phosphoprotein (RABV-P) derived from an scFv phage-display library, before infection, exhibited reduced viral propagation after infection with the RABV-fixed strain, CVS11. In this study, we conducted epitope mapping of scFv-P19 through indirect fluorescent assay and Western blotting analysis against full-length and N- or C-terminal truncated RABV-P. Our results suggest that scFv-P19 targets a portion containing amino acids 47-52 at the N-terminus, which partially overlaps with the N-terminal nuclear export sequences. This provides insights into the underlying mechanism associated with inhibition of RABV by scFv-P19, while allowing for the design of additional scFv-based therapeutic studies for RABV by integrating appropriate delivery and application systems. Furthermore, the results of this study suggest that scFv-P19 may serve as an effective tool for investigating nuclear trafficking of RABV-P to explore the roles of RABV-P isoforms in rabies pathogenesis.

Interleukin-32 regulates downstream molecules and promotes the invasion of pancreatic cancer cells.

Pancreatic cancer is a malignant neoplasm with high invasiveness and poor prognosis. In a previous study, a highly invasive pancreatic cancer cell line was established and found to feature enhanced interleukin-32 (IL-32) expression. However, whether IL-32 promotes the invasiveness by enhancing or suppressing the expression of IL-32 through regulating downstream molecules was unclear. To investigate the effect of IL-32, cells were established with high levels of expression or downregulated IL-32; their invasive ability was measured using a real-time measurement system and the expression of some candidate downstream molecules involved in invasion was evaluated in the two cell types. The morphological changes in both cell types and the localization of IL-32 expression in pancreatic cancer tissues were studied using immunohistochemistry. Among the several splice variants of IL-32, cells transfected with the ε isoform had increased invasiveness, whereas the IL-32-suppressed cells had reduced invasiveness. Several downstream molecules, whose expression was changed in the two cell types, were monitored. Notably, changes of E-cadherin, CLDN1, CD44, CTGF and Wnt were documented. The morphologies of the two cell types differed from the original cell line. Immunohistochemically, the expression of IL-32 was observed only in tumor cells and not in normal pancreatic cells. In conclusion, IL-32 was found to promote the invasiveness of pancreatic cancer cells by regulating downstream molecules.

Protein-losing Enteropathy Complicated with Primary Intestinal Follicular Lymphoma.

Protein-losing enteropathy (PLE) is a rare syndrome characterized by hypoproteinemia due to gastrointestinal (GI) protein loss. Primary intestinal follicular lymphoma (PIFL), a specific variant of follicular lymphoma with essential only GI involvement, has not been reported as an etiology of PLE. We herein report a case of PLE complicated with PIFL that was successfully treated with rituximab, resulting in rapid improvement of PLE and a complete response of PIFL. Macroscopic findings of ulcerative lesions with diffuse involvement, which were precisely described by capsule and double-balloon enteroscopy at the diagnosis, also improved following the treatment. This case provides a clue suggesting factors that promote PLE in PIFL.

The potential diagnostic significance of crypt differentiation in gastric dysplasia.

AIMS: This study investigated the relationship between the differentiation of tumour cells into crypts, which is determined by cell differentiation into Paneth and neuroendocrine cells, and tumour infiltration in gastric dysplasia. METHODS AND RESULTS: The lesions were endoscopically biopsied low-grade dysplasia (LGD), endoscopically resected high-grade dysplasia (HGD) or cancer with submucosal invasion. LGD (n = 32) displayed crypt differentiation across the entire width of the tumour in all cases. Crypt differentiation was identified as a characteristic of tumours with low biological malignancy. HGD (n = 40) included tumours with a mixture of areas with and without crypt differentiation (n = 25) and tumours with crypt differentiation throughout the entire width (n = 15). Of the cancers with submucosal invasion (n = 30), the morphological progression of the HGD area with crypt differentiation, the HGD area without crypt differentiation and invasive cancer without crypt differentiation was confirmed for 23 samples. In two lesions, invasive cancer without crypt differentiation developed from HGD without crypt differentiation throughout the tumour width. In five samples, well-differentiated tubular adenocarcinoma with crypt differentiation developed from HGD with crypt differentiation and invaded with lamina propria-like stroma. CONCLUSIONS: Loss of crypt differentiation could be an objective indicator of infiltration in the progression of HGD to invasive cancer. The invasive potential of dysplasia depends upon the presence or absence of crypt differentiation.

Central mucoepidermoid carcinoma of the maxilla developing from a calcifying odontogenic cyst: A rare case report.

Intraosseous mucoepidermoid carcinoma of the jaw is a rare lesion that has been suggested to originate from the odontogenic epithelium. We report an unusual case of central mucoepidermoid carcinoma in an 18-year-old Japanese man with an odontogenic cyst.

Effect of Continuous Feeding of Ayu-Narezushi on Lipid Metabolism in a Mouse Model of Metabolic Syndrome.

Ayu-narezushi, a traditional Japanese fermented food, comprises abundant levels of lactic acid bacteria (LAB) and free amino acids. This study aimed to examine the potential beneficial effects of ayu-narezushi and investigated whether ayu-narezushi led to improvements in the Tsumura Suzuki obese diabetes (TSOD) mice model of spontaneous metabolic syndrome because useful LAB are known as probiotics that regulate intestinal function. In the present study, the increased body weight of the TSOD mice was attenuated in those fed the ayu-narezushi-comprised chow (ayu-narezushi group) compared with those fed the normal rodent chow (control group). Serum triglyceride and cholesterol levels were significantly lower in the Ayu-narezushi group than in the control group at 24 weeks of age. Furthermore, hepatic mRNA levels of carnitine-palmitoyl transferase 1 and acyl-CoA oxidase, which related to fatty acid oxidation, were significantly increased in the ayu-narezushi group than in the control group at 24 weeks of age. In conclusion, these results suggested that continuous feeding with ayu-narezushi improved obesity and dyslipidemia in the TSOD mice and that the activation of fatty acid oxidation in the liver might contribute to these improvements.

Expression of laminin-5 gamma 2 chain predicts invasion of extramammary Paget's disease cell.

Extramammary Paget's disease (EMPD) is a rare malignant skin neoplasm characterized by intraepidermal proliferation of tumor cells. The tumor cells of EMPD may sometimes invade into the dermis or metastasize into the regional lymph nodes. Several studies have proposed mechanisms underlying the increased invasiveness of EMPD; however, molecular markers indicating invasiveness have yet to be well characterized. Laminin-5 (Lam-5), a heterotrimer composed of three chains (α3, ß3, and γ2), is a major component of the basement membrane in many tissues. One of the chains, Lam-5 γ2, is a marker of invasion, because it often develops as a monomer in malignant neoplasms. We investigated the expression of Lam-5 γ2 and its role for the invasiveness in EMPD. Paraffin-embedded specimens of EMPD obtained from 36 patients were examined immunohistochemically for Lam-5 γ2. The cases adopted into this study comprised 16 cases of intraepidermal lesions and 20 cases with dermal invasion. The basement membrane seen in normal skin disappeared in one-third of non-invasive cases and in most invasive cases. The disappearance of Lam-5 γ2 in the basement membrane and its cytoplasmic expression was more observed in the invasive cases than non-invasive cases. Expression of Lam-5 γ2 may be a biological marker to predict invasiveness of EMPD.

Diagnosis by molecular pathology of an early and atypical histoplasmosis lesion in the duodenum of an immunocompromised patient: A case report.

Histoplasmosis is a fungal infection caused by Histoplasma capsulatum (HC), which can occasionally be aggressive resulting in the formation of granulomatous lesions. These are usually located in the lungs; however, immunocompromised patients may occasionally develop disseminated lesions in other organs as well. Human immunodeficiency virus (HIV) primarily infects cells of the immune system expressing CD4 molecules. Not only does HIV multiply within these cells, but it can also kill them or otherwise cause loss of cellular function, leading to an immunocompromised state. As a result, in an immunocompromised patient, infection with HC can have serious implications, often the development of visceral histoplasmosis in different organs. Although several types of lesions are formed in HC-infected organs, it may be difficult to distinguish the causative organism from other pathogens based on morphology alone. The present case report describes the case of a 57-year-old woman, from South America, who may have been infected with HC >20 years previously, remaining asymptomatic over the years. She later developed a lesion in the duodenum associated with immunodeficiency caused by HIV infection. The differential diagnosis of this case was made on the basis of several specific morphological findings using histopathological analysis and molecular pathological techniques. The pathogenesis of characteristic lesions caused by HC in the presence of HIV infection was also reviewed.

Opposite modulations of corticospinal excitability by intermittent and continuous peripheral electrical stimulation in healthy subjects.

Peripheral electrical stimulation (PES) modulates the excitability of the corticospinal tract (CST). This modulation of CST excitability depends on the PES intensity, defined by the amplitude and the width of each pulse, the total pulse number, the stimulation frequency, and the intervention duration. Another key PES parameter is the stimulation pattern; little is known about how PES pattern affects CST excitability, as previous studies did not control other PES parameters. Here, we investigated the effect of the net difference in PES pattern on CST excitability. We use three controlled PESs, intermittent PES (30 Hz) (stimulation trains at 30 Hz with pauses), continuous PES (12 Hz) (constant stimulation at 12 Hz without pauses), and continuous PES (30 Hz) with the same stimulation frequency as the intermittent PES (30 Hz), to compare the effect of the stimulation frequency. The motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs) of healthy subjects were recorded before and after these three types of PESs in separate sessions. We found that intermittent PES (30 Hz) increased MEP amplitudes, whereas continuous PES (12 and 30 Hz) decreased amplitudes. A significant change in subcortical SEP component occurred during continuous PES (12 and 30 Hz), but not intermittent PES (30 Hz), whereas cortical SEP components showed similar behavior in three types of PESs. We conclude that (1) opposing modulations of CST excitability were induced by the differences in the PES pattern, and (2) these modulations appear to be mediated through different processes in the sensorimotor system. Our findings suggest the possibility that it may be preferable to select the PES pattern in therapeutic interventions based on the putative desired effect and the neural structure being targeted.