Cervical lymphadenitis caused by Mycobacterium avium in a patient treated with Janus kinase inhibitors.

A woman diagnosed with rheumatoid arthritis and treated with Janus kinase (JAK) inhibitors presented with a gradually enlarging bilateral submandibular lymph nodes swelling that had lasted several weeks. A lymph node biopsy showed epithelioid granulomatous lymphadenitis with caseous necrosis. Mycobacteria grew in acid-fast bacteria culture and were identified as Mycobacterium avium by polymerase chain reaction. The patient was diagnosed with cervical lymphadenitis caused by M. avium. A computed tomography scan showed no evidence of a mass or infection at other sites, including the lungs; therefore, the mass was excised without any antimicrobial treatments. Her neck mass had not recurred at 9 months after the excision. JAK inhibitors have emerged as an important new class of oral therapy for rheumatoid arthritis and other diseases. Physicians should be aware of the relatively rare complications, such as cervical lymphadenitis caused by nontuberculous mycobacteria, when using JAK inhibitors.

A Case of Primary Systemic Amyloidosis Involving the Sinonasal Tract.

We present a case of primary systemic amyloidosis diagnosed by endoscopic sinus surgery. A 75-year-old woman had blurred vision in her left eye; computed tomography and magnetic resonance imaging showed shadows of the bilateral paranasal sinuses. Endoscopic sinus surgery was performed, and amyloidosis was diagnosed by histopathology. She had previously been diagnosed with amyloidosis of the stomach, and therefore, she was diagnosed with primary systemic amyloidosis. A systemic workup for additional amyloid deposits revealed no evidence of other diseases. The patient remained under follow-up without further treatment, as no further amyloid deposition or progression of the lesions was seen. Amyloidosis is a rare condition characterized by the deposition of abnormal protein filaments in the extracellular tissue. Generally, systemic amyloidosis does not involve the head and neck region, and the presence of amyloid in the nasal and paranasal sinus mucosa is more likely to be indicative of a localized process. However, in our patient, the lesions were located in both the sinonasal tract and the stomach, indicating systemic amyloidosis. To our knowledge, there have been no previous reports of systemic amyloidosis involving the sinonasal tract, and therefore, we consider this case to be extremely rare.

Intracellular Cl- Regulation of Ciliary Beating in Ciliated Human Nasal Epithelial Cells: Frequency and Distance of Ciliary Beating Observed by High-Speed Video Microscopy.

Small inhaled particles, which are entrapped by the mucous layer that is maintained by mucous secretion via mucin exocytosis and fluid secretion, are removed from the nasal cavity by beating cilia. The functional activities of beating cilia are assessed by their frequency and the amplitude. Nasal ciliary beating is controlled by intracellular ions (Ca2+, H+ and Cl-), and is enhanced by a decreased concentration of intracellular Cl- ([Cl-]i) in ciliated human nasal epithelial cells (cHNECs) in primary culture, which increases the ciliary beat amplitude. A novel method to measure both ciliary beat frequency (CBF) and ciliary beat distance (CBD, an index of ciliary beat amplitude) in cHNECs has been developed using high-speed video microscopy, which revealed that a decrease in [Cl-]i increased CBD, but not CBF, and an increase in [Cl-]i decreased both CBD and CBF. Thus, [Cl-]i inhibits ciliary beating in cHNECs, suggesting that axonemal structures controlling CBD and CBF may have Cl- sensors and be regulated by [Cl-]i. These observations indicate that the activation of Cl- secretion stimulates ciliary beating (increased CBD) mediated via a decrease in [Cl-]i in cHNECs. Thus, [Cl-]i is critical for controlling ciliary beating in cHNECs. This review introduces the concept of Cl- regulation of ciliary beating in cHNECs.

Enhancement of ciliary beat amplitude by carbocisteine in ciliated human nasal epithelial cells.

OBJECTIVE: Carbocisteine (CCis), a mucoactive agent, is used to improve the symptoms of sinonasal diseases. However, the effect of CCis on nasal ciliary beating remains uncertain. We examined the effects of CCis on ciliary beat distance (CBD, an index of amplitude), and ciliary beat frequency (CBF) in ciliated human nasal epithelial cells (cHNECs) in primary culture. METHODS: The cHNECs were prepared from the nasal tissue resected from patients required surgery for chronic sinusitis (CS) or allergic rhinitis (AR). CBD and CBF were measured using videomicroscopy equipped with a high-speed camera. RESULTS: CCis increased CBD by 30%, but not CBF, and decreased intracellular Cl- concentration ([Cl- ]i ) in cHNECs. The CCis' actions were mimicked by the Cl- -free NO3- solution. In contrast, prior treatment of NPPB (20 µM) or CFTR(inh)-172 (1 µM), which increased [Cl- ]i by 20%, decreased CBF by 10% and CBD by 25% and inhibited the CCis' actions. However, prior treatment of T16Ainh-A01 (10 µM) did not inhibit the CCis' actions, although it decreased [Cl- ]i by 10% and CBD by 15%. Thus, CCis stimulates Cl- channels including cystic fibrosis transmembrane conductance regulator (CFTR). Moreover, CCis enhanced the transport of microbeads driven by the beating cilia in cHNECs. The CCis actions were similar in cHNECs from both types of pateints. CONCLUSION: CCis increased CBD by 30% in cHNECs via an [Cl- ]i decrease stimulated by activation of Cl- channels, including CFTR. CCis may stimulate nasal mucociliary clearance by increasing CBD in patients contracting CS or AR. LEVEL OF EVIDENCE: NA. Laryngoscope, 130:E289-E297, 2020.

Ciliary beating amplitude controlled by intracellular Cl- and a high rate of CO2 production in ciliated human nasal epithelial cells.

The ciliary transport is controlled by two parameters of the ciliary beating, frequency (CBF) and amplitude. In this study, we developed a novel method to measure both CBF and ciliary bend distance (CBD, an index of ciliary beating amplitude) in ciliated human nasal epithelial cells (cHNECs) in primary culture, which are prepared from patients contracting allergic rhinitis and chronic sinusitis. An application of Cl--free NO3- solution or bumetanide (an inhibitor of Na+/K+/2Cl- cotransport), which decreases intracellular Cl- concentration ([Cl-]i), increased CBD, not CBF, at 37 °C; however, it increased both CBD and CBF at 25 °C. Conversely, addition of Cl- channel blockers (5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and 4-[[4-Oxo-2-thioxo-3-[3-trifluoromethyl]phenyl]-5-thiazolidinylidene]methyl] benzoic acid (CFTR(inh)-172)), which increase [Cl-]i, decreased both CBD and CBF, suggesting that CFTR plays a crucial role for maintaining [Cl-]i in these cells. We speculate that Cl- modulates activities of the molecular motors regulating both CBD and CBF in cHNECs. Moreover, application of the CO2/HCO3--free solution did not change intracellular pH (pHi), and addition of an inhibitor of carbonic anhydrase (acetazolamide) sustained pHi increase induced by the NH4+ pulse, which transiently increased pHi in the absence of acetazolamide. These results indicate that the cHNEC produces a large amount of CO2, which maintains a constant pHi even under the CO2/HCO3--free condition.

Daidzein-Stimulated Increase in the Ciliary Beating Amplitude via an [Cl-]i Decrease in Ciliated Human Nasal Epithelial Cells.

The effects of the isoflavone daidzein on the ciliary beat distance (CBD, which is a parameter assessing the amplitude of ciliary beating) and the ciliary beat frequency (CBF) were examined in ciliated human nasal epithelial cells (cHNECs) in primary culture. Daidzein decreased [Cl-]i and enhanced CBD in cHNECs. The CBD increase that was stimulated by daidzein was mimicked by Cl--free NO3- solution and bumetanide (an inhibitor of Na⁺/K⁺/2Cl- cotransport), both of which decreased [Cl-]i. Moreover, the CBD increase was inhibited by 5-Nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, a Cl- channel blocker), which increased [Cl-]i. CBF was also decreased by NPPB. The rate of [Cl-]i decrease evoked by Cl--free NO3- solution was enhanced by daidzein. These results suggest that daidzein activates Cl- channels in cHNECs. Moreover, daidzein enhanced the microbead transport driven by beating cilia in the cell sheet of cHNECs, suggesting that an increase in CBD enhances ciliary transport. An [Cl-]i decrease enhanced CBD, but not CBF, in cHNECs at 37 °C, although it enhanced both at 25 °C. Intracellular Cl- affects both CBD and CBF in a temperature-dependent manner. In conclusion, daidzein, which activates Cl- channels to decrease [Cl-]i, stimulated CBD increase in cHNECs at 37 °C. CBD is a crucial factor that can increase ciliary transport in the airways under physiological conditions.

Spontaneous oscillation of the ciliary beat frequency regulated by release of Ca2+ from intracellular stores in mouse nasal epithelia.

Ciliary beating frequency (CBF) was investigated in ciliated nasal epithelial cells (cMNECs) isolated from mice using video microscopy equipped with a high-speed camera. In cMNECs, a spontaneous CBF oscillation was observed. The CBF oscillation was abolished by BAPTA-AM but not by Ca2+-free solution. The addition of thapsigargin, which depletes Ca2+ from internal stores, also abolished CBF oscillation. Moreover, the intracellular Ca2+ concentration [Ca2+]i, spontaneously oscillated even with the Ca2+-free solution. Moreover, 2APB (an inhibitor of the IP3 receptor) abolished CBF oscillation in cMNECs. Overall, these findings suggest that the CBF oscillation in cMNECs is triggered by the release of Ca2+ from the IP3-sensitive internal stores. Moreover, IBMX, an inhibitor of phosphodiesterase, did not affect CBF oscillation in cMNECs, although it slightly increased CBF. These results suggest that CBF oscillations were induced by [Ca2+]i oscillation controlled via the release of Ca2+ from IP3-sensitive stores, rather than via cAMP accumulation. CBF oscillation possibly plays a crucial role in maintaining an efficient mucociliary clearance in the nasal epithelia.