A Case of Nivolumab-Induced Severe Mononeuropathy Multiplex and Rhabdomyolysis

We report an 81-year-old man with multiple liver metastases after tumorectomy for primary mediastinal malignant melanoma, who experienced limb weakness and sensory disturbance after nivolumab monotherapy. He was diagnosed with nivolumab-induced mononeuropathy multiplex and rhabdomyolysis based on serologic examination, muscle biopsy, magnetic resonance imaging of the limbs, and a nerve conduction study. A course of intravenous methylprednisolone (mPSL) was initiated at 1 g/day for 3 days. After that, oral prednisolone (PSL) was started at 1 mg/kg/day and gradually tapered. Limb muscle strength improved, but when PSL was reduced to 0.3 mg/kg/day, the weakness recurred, and a nerve conduction study showed exacerbation of mononeuropathy multiplex. The patient was again administered intravenous mPSL (0.5 g/day for 3 days) followed by oral PSL at 0.5 mg/kg/day, and his neurological symptoms improved. Nivolumab, an immune checkpoint inhibitor, is used for the treatment of advanced melanoma and other cancers and causes various immune-related adverse events (irAEs). However, neurological irAEs related to nivolumab are rare. Furthermore, there are no reports of simultaneous nerve and muscle impairment. Unexpected irAEs affecting various organs should be recognized and treated appropriately

Urine and plasma levels of uroguanylin and its molecular forms in renal diseases

Urine and plasma levels of uroguanylin and its molecular forms in renal diseases. Uroguanylin activates the intestinal and possibly the renal guanylate cyclase C receptor, and stimulates Cl− secretion. We developed a sensitive radioimmunoassay (RIA) for human uroguanylin and measured its concentration in the urine and plasma. Twenty-four-hour urinary excretion of immunoreactive (ir-) uroguanylin for persons with a high-salt diet (10 g/day) was 137.8 ± 14.4 pmol/day, significantly higher than that for persons with a low-salt diet (7 g/day, 95.1 ± 16.3 pmol/day, P < 0.05). There were significantly positive correlations between the urinary excretion of ir-uroguanylin and Na+, Cl−, K+ or cyclic GMP (cGMP). We demonstrated the presence of messenger RNA of guanylate cyclase C in the medulla of human kidney. The concentration of plasma ir-uroguanylin significantly correlated with that of serum creatinine (r = 0.71, P < 0.001). Biologically active uroguanylin-16 accounted for 99% of the endogenous uroguanylin molecules in normal urine and 60% in plasma, the remainder being the 10kDa precursor. The precursor content increased in the urine and plasma as the severity of renal impairment increased. These findings suggest that bioactive uroguanylin-16 is involved in the regulation of electrolyte homeostasis and that the kidney participates in the metabolism and excretion of uroguanylin

Topological isomers of human uroguanylin: interconversion between biologically active and inactive isomers

AbstractThe solution structures of the two compounds of human uroguanylin (I and II), which were generated during disulfide bond forming reaction, were found to be topological isomers by 1H-nuclear magnetic resonance spectroscopy. These isomers are interconvertible in aqueous media at rates which vary with the pH and temperature of the solution. Because compound I is active in the cGMP producing assay, but compound II is not, this interconversion may be useful for evaluating the activity of human uroguanylin both in vivo and in vitro

Observing Supernova Neutrino Light Curves with Super-Kamiokande. III. Extraction of Mass and Radius of Neutron Stars from Synthetic Data

Neutrinos are guaranteed to be observable from the next Galactic supernova (SN). Optical light and gravitational waves are also observable, but may be difficult to observe if the location of the SN in the Galaxy or the details of the explosion are unsuitable. The key to observing the next SN is to first use neutrinos to understand various physical quantities and then link them to other signals. In this paper, we present Monte Carlo sampling calculations of neutrino events from Galactic SN explosions observed with Super-Kamiokande. The analytical solution of neutrino emission, which represents the long-term evolution of the neutrino light curve from SNe, is used as a theoretical template. It gives the event rate and event spectrum through inverse beta decay interactions with explicit model parameter dependence. Parameter estimation is performed on these simulated sample data by fitting least squares using the analytical solution. The results show that the mass, radius, and total energy of a remnant neutron star produced by an SN can be determined with an accuracy of ∼ 0.1 M⊙, ∼1 km, and ∼ 10⁵¹ erg, respectively, for a Galactic SN at 8 kpc

18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging evaluation of chorea

Chorea is thought to be caused by deactivation of the indirect pathway in the basal ganglia circuit. However, few imaging studies have evaluated the basal ganglia circuit in actual patients with chorea. We investigated the lesions and mechanisms underlying chorea using brain magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). This retrospective case series included three patients with chorea caused by different diseases: hyperglycemic chorea, Huntington’s disease, and subarachnoid hemorrhage. All the patients showed dysfunction in the striatum detected by both MRI and FDG-PET. These neuroimaging findings confirm the theory that chorea is related to an impairment of the indirect pathway of basal ganglia circuit

Molecular analysis of a variant type of familial amyloidotic polyneuropathy showing cerebellar ataxia and pyramidal tract signs

金沢大学がん研究所がん分子細胞制御A Japanese family with atypical type I familial amyloidotic polyneuropathy (FAP) in Iiyama, Japan, was studied. Most of the family members have dysfunctions of the central nervous system, in addition to typical symptoms of type I FAP. The transthyretin (TTR, also called prealbumin) gene of the atypical FAP (FAP-IY) was analyzed with recombinant DNA techniques and a RIA method. FAP-IY was found to have the mutation responsible for the methionine-for-valine substitution at position 30 of TTR, as in the case of typical type I FAP. However, analysis of DNA polymorphisms in the TTR locus showed that FAP-IY has a genetic background differing from that of the typical type I FAP. These observations lead to the consideration that a genetic factor(s) involved in the dysfunction of the central nervous system may locate in a chromosome region in close proximity to the TTR gene

Effect of octanoic acid-rich formula on plasma ghrelin levels in cachectic patients with chronic respiratory disease

<p>Abstract</p> <p>Background</p> <p>For cachectic patients with chronic respiratory disease (CRD), conventional enteral nutrition formula is an optional treatment to maintain energy balance. The molecular mechanisms by which enteral nutrition formula controls appetite and weight remain unknown. We examined whether enteral nutrition formula rich in octanoic acids would increase plasma levels of ghrelin, an appetite-stimulating hormone produced in the stomach, in cachectic patients with CRD.</p> <p>Methods</p> <p>Plasma ghrelin profiles in cachectic patients with CRD were assessed and compared with those in age- and sex-matched controls. Plasma levels of acyl-ghrelin, an active ghrelin modified by octanoic acids, and desacyl-ghrelin were measured separately. We examined changes in 24-h plasma ghrelin profiles before and after single administration of the formula. We also evaluated the effects of 2-week administration of the formula on plasma ghrelin levels and nutritional status in patients.</p> <p>Results</p> <p>The ratio of acyl-ghrelin to desacyl-ghrelin in plasma was lower in patients than in controls. Single administration of the formula did not change plasma desacyl-ghrelin levels, but induced an increase in acyl-ghrelin levels. Two-week treatment with the formula was effective in increasing weight and acyl-ghrelin, along with improving nutritional status in patients.</p> <p>Conclusion</p> <p>These results show that the formula contributes to increased weight, which may be associated with induction of acyl-ghrelin production in cachectic patients with CRD.</p