Granulomatous interstitial nephritis associated with atypical drug-induced hypersensitivity syndrome induced by carbamazepine

We report the case of a 70-year-old female patient with granulomatous interstitial nephritis (GIN) induced by carbamazepine (CBZ). The patient had a 22-year history of bipolar disorder. Approximately 50 days before admission to our hospital, she was switched from valproic acid to 200 mg/day CBZ for mood swings. Forty days later, she presented with mild transient platelet depletion and liver dysfunction along with a C-reactive protein (CRP) level of 2.65 mg/dL. At that time, she discontinued CBZ without consulting the doctor. She subsequently developed high fever and a pruritic maculopapular rash. Laboratory tests revealed an elevated CRP level (11.98 mg/dL) and serum creatinine (sCr) of 1.6 mg/dL. Hence, she was admitted to our hospital, where she showed eosinophilia and immunoglobulin suppression. She was diagnosed with atypical drug-induced hypersensitivity syndrome (DIHS). All drugs prescribed by the previous doctor were discontinued. A lymphocyte transformation test showed CBZ positivity; a renal biopsy revealed many granulomatous lesions connected to arterioles, without angionecrotic findings. The patient had no history of allergic disorders or tuberculosis. Because of psychological instability, we treated her conservatively without steroid administration. She had a good recovery except for mild residual renal insufficiency (sCr, 1.0 mg/dL). Although granuloma formation has been observed in kidney biopsy specimens of rare cases with DIHS, no previous studies have reported on the relationship between arterioles and granuloma formation

Behavioral analysis of relaxin-3 deficient mice

Relaxin-3 is a neuropeptide belonging to the relaxin/insulin superfamily. Studies using rodents have revealed that relaxin-3 is predominantly expressed in neurons in the nucleus incertus of the pons, projecting axons to forebrain regions including the hypothalamus. There is evidence that relaxin-3 is involved in several functions, including food intake and stress responses. We generated relaxin-3 gene knockout (KO) mice and examined them using a battery of behavioral tests of sensory/motor functions and emotion-related behaviors. Relaxin-3 KO mice exhibited normal growth and appearance. There was no difference in bodyweight among genotypes in both normal and high fat diet feeding. In addition, there were no significant differences between wild-type and KO mice in social interaction, depression-like behavior, and short memory test. However, in the elevated plus maze test, KO mice exhibited a robust increase in the tendency to enter open arms, although they exhibited normal performance in a light/dark transition test and showed no difference from wild-type mice in the open field test. Taken together, these results indicate that relaxin-3 KO mice exhibit mild anxiolytic characteristics relative to wild-type mice, suggesting that this peptide is involved in anxiety-related behavior

The Possible Role of TASK Channels in Rank-Ordered Recruitment of Motoneurons in the Dorsolateral Part of the Trigeminal Motor Nucleus.

Because a rank-ordered recruitment of motor units occurs during isometric contraction of jaw-closing muscles, jaw-closing motoneurons (MNs) may be recruited in a manner dependent on their soma sizes or input resistances (IRs). In the dorsolateral part of the trigeminal motor nucleus (dl-TMN) in rats, MNs abundantly express TWIK (two-pore domain weak inwardly rectifying K channel)-related acid-sensitive-K(+) channel (TASK)-1 and TASK3 channels, which determine the IR and resting membrane potential. Here we examined how TASK channels are involved in IR-dependent activation/recruitment of MNs in the rat dl-TMN by using multiple methods. The real-time PCR study revealed that single large MNs (>35 μm) expressed TASK1 and TASK3 mRNAs more abundantly compared with single small MNs (15-20 μm). The immunohistochemistry revealed that TASK1 and TASK3 channels were complementarily distributed in somata and dendrites of MNs, respectively. The density of TASK1 channels seemed to increase with a decrease in soma diameter while there were inverse relationships between the soma size of MNs and IR, resting membrane potential, or spike threshold. Dual whole-cell recordings obtained from smaller and larger MNs revealed that the recruitment of MNs depends on their IRs in response to repetitive stimulation of the presumed Ia afferents. 8-Bromoguanosine-cGMP decreased IRs in small MNs, while it hardly changed those in large MNs, and subsequently decreased the difference in spike-onset latency between the smaller and larger MNs, causing a synchronous activation of MNs. These results suggest that TASK channels play critical roles in rank-ordered recruitment of MNs in the dl-TMN

Intraocular Pressure Readings Obtained through Soft Contact Lenses using Four Types of Tonometer

To compare the reliability and accuracy of intraocular pressure (IOP) measured while wearing soft contact lenses (SCLs) using a non-contact tonometer (NCT), Goldmann applanation tonometer (GAT), iCare rebound tonometer (RBT) and the Tono-Pen XL. Twenty-six healthy subjects were examined. The IOP was measured using NCT, GAT, RBT, and the Tono-Pen XL, while the subjects wore SCLs −5.00 D, −0.50 D and +5.00 D. Bland–Altman plots and a regression analysis were used to compare the IOPs obtained with those instruments and the IOPs of the naked eyes measured using GAT (the standard IOPs in this study). The IOPs obtained by the Tono-Pen XL while the subjects were wearing −5.00 D, −0.50 D, and +5.00 D SCLs were significantly higher than those of the naked eyes obtained using GAT. RBT showed that the IOPs were similar to the GAT standard IOPs under all conditions. The IOPs measured with NCT and GAT while the subjects were wearing −5.00 D and −0.50 D SCLs were similar to the GAT standard IOPs. The IOPs obtained with RBT and NCT while the subjects were wearing −5.00 D and −0.50 D SCLs exhibited a good correlation with the standard IOPs. The NCT and RBT are best when measuring IOP through hydrogel SCLs

Endogenous agonist–bound S1PR3 structure reveals determinants of G protein–subtype bias

脂質受容体の新たな活性化機構を解明 --脂質がまっすぐ伸びて活性化--. 京都大学プレスリリース. 2021-06-10.Sphingosine-1-phosphate (S1P) regulates numerous important physiological functions, including immune response and vascular integrity, via its cognate receptors (S1PR1 to S1PR5); however, it remains unclear how S1P activates S1PRs upon binding. Here, we determined the crystal structure of the active human S1PR3 in complex with its natural agonist S1P at 3.2-Å resolution. S1P exhibits an unbent conformation in the long tunnel, which penetrates through the receptor obliquely. Compared with the inactive S1PR1 structure, four residues surrounding the alkyl tail of S1P (the “quartet core”) exhibit orchestrating rotamer changes that accommodate the moiety, thereby inducing an active conformation. In addition, we reveal that the quartet core determines G protein selectivity of S1PR3. These results offer insight into the structural basis of activation and biased signaling in G protein–coupled receptors and will help the design of biased ligands for optimized therapeutics

Case Report Fabella Syndrome as an Uncommon Cause of Posterolateral Knee Pain after Total Knee Arthroplasty: A Case Report and Review of the Literature

The fabella is a sesamoid bone that is located in the lateral head of the gastrocnemius muscle and has been identified on magnetic resonance imaging in 31% of Japanese people. In the present case, a 65-year-old woman experienced posterolateral knee pain, accompanied by a clicking "sound" during active knee flexion, after undergoing total knee arthroplasty for knee osteoarthritis. Eight months of conservative therapy failed to produce an improvement, with progressive osteoarthritic change of the fabella identified on plain radiography. Based on this evidence, a diagnosis of fabella syndrome was made and the patient underwent a fabellectomy. Fabellectomy provided immediate resolution of posterolateral knee pain and the clicking sound with knee flexion, with the patient remaining symptom-free 18 months after fabellectomy and with no limitations in knee function. Fabellectomy eliminated symptoms in all of five case reports that have been previously published and is regarded as an effective first choice for treating fabella syndrome after total knee arthroplasty

Observer agreement for the diagnosis of intestinal acute graft‑vs.‑host disease based on the presence of villous atrophy in the terminal ileum

Intestinal graft‑vs.‑host disease (GVHD) is a serious complication of allo‑hematopoietic stem cell transplantation (allo‑HSCT). Villous atrophy in the terminal ileum is considered a useful diagnostic indicator for GVHD. However, the inter‑ and intra‑observer agreement regarding the ileocolonoscopic findings indicative of acute intestinal GVHD, i.e., villous atrophy in the terminal ileum, are currently insufficient in multiple institutions. Thus, the present study aimed to investigate the incidence of villous atrophy in the terminal ileum to diagnose acute intestinal GVHD and determine the inter‑ and intra‑observer agreement regarding this result for experienced endoscopists from multiple institutions. Consecutive patients who underwent allo‑HSCT were referred to our institution between May 2008 and September 2015. A total of 54 patients underwent total ileocolonoscopy after allo‑HSCT due to suspected intestinal acute GVHD. Subsequently, three observers from different institutions evaluated the cases for the presence of villous atrophy in the terminal ileum. In this study, the pathology results were a gold standard to evaluate the predictive value of ileocolonoscopy detection. Definitive pathological and non‑pathological GVHD was diagnosed in 22 and 32 cases, respectively. The results of examining whether villous atrophy could predict GVHD were as follows. For three observers (A, B and C), the sensitivity of villous atrophy in the terminal ileum was 86.4, 77.3 and 79.2%, respectively, whereas the specificity was 62.5, 62.5 and 86.7%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of villous atrophy for GVHD were as follows: The PPV of appearance was 61.3, 58.6 and 82.6%, respectively, whereas the NPV was 87.0, 80.0 and 83.9%, respectively. Kappa coefficients for the inter‑observer reliability were 0.85, 0.63 and 0.63 for observers A and B, A and C, and B and C, respectively. The intra‑observer kappa coefficient was 0.88 for observer A, 0.73 for observer B and 0.75 for observer C. A substantial observer agreement was achieved for the analysis of villous atrophy in the terminal ileum and the agreement for the predictive histological diagnosis was also excellent. Based on the results of the present study, identification of villous atrophy in the terminal ileum was a clinically effective diagnostic parameter, even if different endoscopists were involved in the diagnosis at multiple institutions. The present study was registered as a trial with the University Hospital Medical Information Network (UMIN; registration no. UMIN000025390)