Severe COVID-19 as a Possible Mediator of Autoimmunity and Sjögren's Syndrome.

We treated a 65-year-old man for COVID-19 who was hospitalized urgently due to life-threatening respiratory decompensation and later developed cardiac arrest, both of which were successfully treated. Three days prior to the patient's urgent hospitalization, he had a high fever of over 38.0°C. Viral infection was diagnosed by polymerase chain reaction (PCR) on the day of admission, which was negative on the 11th day. Blood analysis on the second day was strongly positive for COVID-19 IgG antibodies, which continued for one year. Because of the acute increase in viral IgG antibodies, we performed other immunological analyses; Sjögren's syndrome antigen A (SS-A) and Sjögren's syndrome antigen B (SS-B) antibodies were positive, although he had no history of autoimmune diseases. Subsequent salivary-gland biopsy and pathological analysis confirmed the diagnosis of Sjögren's syndrome. The severe clinical manifestations and early antibody seroconversion in this case suggest COVID-19 as a mediator of autoimmunity and Sjögren's syndrome.

[A case of leptomeningeal melanomatosis presenting with right abducens nerve palsy].

A 39 year-old man was admitted to this hospital because of severe headache and vomiting. He had been suffering from lumbago about one month previously, and diplopia ten days previously. The neurological examination revealed disturbance of right eye abduction, no nuchal rigidity. The cerebrospinal fluid (CSF) at the time of admission included erythrocytes (1,490/µl), white blood cell (62/µl) and increased level of protein (531 mg/dl), but no malignant cells were detected. He was treated as meningitis. Cranial magnetic resonance imaging (MRI) demonstrated heterogeneous intensity lesion in the left maxillary sinus and gadolinium enhancement of diffuse meninges and cranial nerves. Spine MRI showed gadolinium enhancement of lumbar spinal meninges and the cauda equina. Biopsy of the lesion in the left maxillary sinus was performed. The pathological findings demonstrated malignant melanoma. Because malignant cells were also observed in CSF, we diagnosed this case as leptomeningeal melanomatosis. Leptomeningeal carcinomatosis should be suspected when headache accompanied with pleomorphic clinical manifestations.

Molecular cloning and function of Oct-3 isoforms in cynomolgus monkey embryonic stem cells.

Oct-3 is a key molecule for maintaining self-renewal in mouse embryonic stem (ES) cells. The function of Oct-3 in ES cells of other species, however, especially primate ES cells, is not clear. In the present study, we cloned two splicing isoforms of Oct-3, Oct-3A and Oct-3B, from cynomolgus monkey ES cells, and found that they have high homology to human Oct-3A and Oct-3B. To examine their function, Oct-3A and Oct-3B were overexpressed in cynomolgus monkey ES cells. Transient Oct-3A overexpression induced ES cell differentiation into endodermal and mesodermal lineages and disrupted proliferation of undifferentiated monkey ES cells. In contrast, Oct-3B overexpression did not induce differentiation of monkey ES cells. These findings indicate that a certain Oct-3A expression level has an important role in sustaining self-renewal in non-human primate ES cells.

STAT3 is dispensable for maintenance of self-renewal in nonhuman primate embryonic stem cells.

The leukemia inhibitory factor (LIF)/glycoprotein 130 (gp130)/signal transducer and activator of transcription 3 (STAT3) pathway plays an essential role in the maintenance of self-renewal and pluripotency in mouse embryonic stem (ES) cells. However, in primate ES cells, including those from humans and monkeys, LIF alone is not sufficient to maintain self-renewal. The precise role of the LIF/gp130/STAT3 pathway for self-renewal in primate ES cells is still unclear. In this study, we found that stimulation of cynomolgus monkey ES cells with LIF or interleukin (IL)-6/soluble IL-6 receptor leads to STAT3 phosphorylation, an effect seen previously in murine ES cells. Concomitant with this notion, nuclear translocalization and transcriptional activation of STAT3 were observed in a LIF-dependent manner. Moreover, the analysis of a dominant interfering mutant, STAT3F, showed that even though the phosphorylation, nuclear translocalization, and transcriptional activation of endogenous STAT3 after LIF stimulation were completely abrogated by over-expressing STAT3F in monkey ES cells, they continued to proliferate in an undifferentiated state, retaining their pluripotency. These results demonstrate that the LIF/gp130/STAT3 pathway functions in cynomolgus monkey ES cells but is not essential for the maintenance of self-renewal. They also suggest that cynomolgus monkey ES cells, unlike murine ES cells, are maintained in an undifferentiated state through LIF/gp130/STAT3-independent signaling.