COVID-19 pneumonia in a patient with adult T-cell leukemia-lymphoma.

Although some patients with COVID-19 develop only mild symptoms, fatal complications have been observed among those with comorbidities. As patients with cancer are immunocompromised, they are thought to have a high risk of severe illness associated with COVID-19. We report a COVID-19 patient with adult T-cell leukemia-lymphoma (ATL) who was treated using favipiravir. A 69-year-old woman with lymphoma-type ATL was treated using cyclophosphamide, doxorubicin, vincristine, prednisolone and mogamulizumab (M-CHOP) with substantial efficacy. However, in cycle 4 of M-CHOP therapy, she developed fever with mild cough. The patient was admitted to the hospital and CT revealed bilateral ground-glass opacities. SARS-CoV-2 was detected by RT-PCR and the patient was diagnosed with COVID-19. Considering severe immunosuppression caused by ATL, we initiated favipiravir therapy. Subsequently, the fever improved without antipyretics and her C-reactive protein level decreased rapidly. SARS-CoV-2 PCR tests were negative on days 17 and 18 of favipiravir therapy, and the patient was discharged without residual disease on the final CT. This is the first documented case of COVID-19 in a patient with ATL. Although severe immunosuppression caused by ATL was present, severe COVID-19 pneumonia did not develop. The immunosuppressed condition caused by hematological malignancy may not always be a risk factor for severe illness associated with COVID-19. Further accumulation of data regarding COVID-19 in patients with hematological malignancies is warranted to clarify the risk factors for severe illness, the best-in-class antiviral agent, and the optimal treatment strategy in this population.

Immunolocalization of aquaporin-5 in normal human skin and hypohidrotic skin diseases.

Aquaporin (AQP)-5 has been shown to be expressed in the secretory parts of mouse, rat and horse sweat glands. However, the precise localization of AQP-5 in normal and diseased human skin has not been fully determined. The aim of the present study was to further clarify the immunolocalization of AQP-5 in normal human skin and hypohidrotic skin diseases. Normal human scalp skin and biopsies from skin affected by hypohidrotic diseases were analyzed for AQP-5 and/or dermcidin expression by immunohistochemistry, immunofluorescence and/or immunoelectronmicroscopy. AQP-5 was expressed on the apical and basolateral plasma membranes of the clear cells in eccrine sweat coils, but not in ductal components or apocrine glands. Numbers of AQP-5-positive coils in the secretory part of eccrine sweat glands were decreased in Sjögren's syndrome, but not in skin affected by idiopathic segmental anhidrosis or idiopathic pure sudomotor failure. AQP-5 was mostly localized to the plasma membranes of clear cells in the secretory coils of eccrine sweat glands, suggesting that it plays a role in producing the primary sweat fluid.

Immunocytochemical studies of aquaporin 4, Kir4.1, and α1-syntrophin in the astrocyte endfeet of mouse brain capillaries.

One of the most important physiological roles of brain astrocytes is the maintenance of extracellular K(+) concentration by adjusting the K(+) influx and K(+) efflux. The inwardly rectifying K(+) channel Kir4.1 has been identified as an important member of K(+) channels and is highly concentrated in glial endfeet membranes. Aquaporin (AQP) 4 is another abundantly expressed molecule in astrocyte endfeet membranes. We examined the ultrastructural localization of Kir4.1, AQP4, α1-syntrophin, and ß-spectrin molecules to understand the functional role(s) of Kir4.1 and AQP4. Immunogold electron microscopy of these molecules showed that the signals of these molecules were present along the plasma membranes of astrocyte endfeet. Double immunogold electron microscopy showed frequent co-localization in the combination of molecules of Kir4.1 and AQP4, Kir4.1 and α1-syntrophin, and AQP4 and α1-syntrophin, but not those of AQP4 and ß-spectrin. Our results support biochemical evidence that both Kir4.1 and AQP4 are associated with α1-syntrophin by way of postsynaptic density-95, Drosophila disc large protein, and the Zona occludens protein I protein-interaction domain. Co-localization of AQP4 and Kir4.1 may indicate that water flux mediated by AQP4 is associated with K(+) siphoning.

[Evaluation of post intraocular lens implantation detrition of clear corneal incisions using an injector system in porcine eyes].

PURPOSE: To evaluate the detrition of clear corneal incisions (CCIs) after intraocular lens (IOL) implantation using an injector system in porcine eyes. METHODS: Group A: after CCIs were performed with 1.8, 2.0, 2.2, 2.4, and 2.65 mm wide slit knives, a Y-60 H (HOYA) IOL was implanted in the anterior chamber using an injector system. Group B: after CCIs were performed with 2.4, 2.65, 2.8, 3.0, and 3.2 mm wide slit knives, a PY-60 R (HOYA) IOL was implanted in the anterior chamber using an injector system. Group C: after CCIs were performed with 2.8, 3.0, 3.2, 3.4 mm wide slit knives, a SN 60 AT (Alcon) IOL was implanted in the anterior chamber using an injector system. CONTROL: CCIs were performed with 3.0 mm wide slit knives. Each group used five porcine eyes for each slit knife (Group A 25 eyes; Group B 25 eyes; Group C 20 eyes; CONTROL 5 eyes). The detrition of the CCIs was evaluated on three different aspects using a scanning electron microscope: a) external expansion at both edges of CCIs; b) rupture of the collagen fibers; c) expansion between the collagen fibers. Aspects a, b and c were given a score of 0, 1, and 2, respectively, and the total points were compared statistically between test and control groups. RESULTS: The degree of CCIs detrition was significantly reduced in CCIs with a width of more than 2.4 mm of CCIs width in Group A, more than 3.0 mm in Group B, and more than 3.2 mm in Group C. CONCLUSIONS: Minimizing the detrition of corneal incisions after IOL implantation needs a larger than the recommended width of corneal incision.

Immunohistochemical detection of dysbindin at the astroglial endfeet around the capillaries of mouse brain.

Dysbindin was first identified by the yeast two hybrid assay as a binding partner of dystrobrevin which is a cytoplasmic member of dystrophin glycoprotein complex. Immunolocalization of dystrobrevin in the astrocyte endfeet and endothelial cells in the rat cerebellum was reported. Therefore, we were interested in the expression and localization of dystrobrevin binding protein dysbindin in the mouse brain capillary wall and its surrounding astroglial endfeet. We examined whether the dysbindin expression is present in astroglial endfeet and/or capillary endothelial cells at light and electron microscopic levels. Using brain samples from five normal mice (C57BL/6ScSn), we prepared the anti-dysbindin antibody stained brain samples with immunoperoxidase method at light microscopic level and with immunogold method at ultrastructural level. Immunohistochemistry showed that dysbindin was located in the brain capillary at light microscopic level. Immunogold electron microscopy revealed that dysbindin signal was observed at the inside surface of plasma membrane of glial endfeet which surrounded the brain capillary endothelial cells and pericytes.

Actin -related protein 3 (Arp3) is mutated in proteinuric BUF/Mna rats.

The BUF/Mna strain of rat is a model of focal and segmental glomerulosclerosis (FSGS) in which a quantitative trait locus (QTL) for proteinuria, Pur1, has been identified. The aim of the present study was to identify candidates for the Pur1 gene. To narrow the Pur1 QTL, we performed fine QTL mapping and single nucleotide polymorphism (SNP) genotyping. To identify candidate genes, sequencing and gene-expression analyses of all genes contained in the narrowed locus were conducted. The narrowed Pur1 region contained 25 genes. Among these genes, only the Arp3 gene was mutated in the BUF/Mna strain; it contained a missense mutation that caused an (L)111(F) substitution. This leucine is conserved across species. Gene-expression analysis failed to identify any other candidate genes for Pur1. Arp3-mediated actin assembly abnormalities were visible in immunohistochemical and electron microscopic examinations of podocytes in old BUF/Mna rats. Taken together, these data suggest that Arp3 is a candidate for the Pur1 gene. This observation is consistent with our growing recognition that abnormal signaling-induced assembly of actin in podocytes leads to the development of FSGS.