Treatment of tubular damage in high-fat-diet-fed obese mice using sodium-glucose co-transporter inhibitors.

A long-term high-fat diet (HFD) causes obesity and changes in renal lipid metabolism and lysosomal dysfunction in mice, causing renal damage. Sodium-glucose co-transporter inhibitors, including phlorizin, exert nephroprotective effects in patients with chronic kidney disease, but the underlying mechanism remains unclear. A HFD or standard diet was fed to adult C57BL/6J male mice, and phlorizin was administered. Lamellar body components of the proximal tubular epithelial cells (PTECs) were investigated. After phlorizin administration in HFD-fed mice, sphingomyelin and ceramide in urine and tissues were assessed and label-free quantitative proteomics was performed using kidney tissue samples. Mitochondrial elongation by fusion was effective in the PTECs of HFD-fed obese mice under phlorizin administration, and many lamellar bodies were found in the apical portion of the S2 segment of the proximal tubule. Phlorizin functioned as a diuretic, releasing lamellar bodies from the apical membrane of PTECs and clearing the obstruction in nephrons. The main component of the lamellar bodies was sphingomyelin. On the first day of phlorizin administration in HFD-fed obese mice, the diuretic effect was increased, and more sphingomyelin was excreted through urine than in vehicle-treated mice. The expressions of three peroxisomal ß-oxidation proteins involved in fatty acid metabolism were downregulated after phlorizin administration in the kidneys of HFD-fed mice. Fatty acid elongation protein levels increased with phlorizin administration, indicating an increase in long-chain fatty acids. Lamellar bodies accumulated in the proximal renal tubule of the S2 segment of the HFD-fed mice, indicating that the urinary excretion of lamellar bodies has nephroprotective effects.

RNA-seq analysis, targeted long-read sequencing and in silico prediction to unravel pathogenic intronic events and complicated splicing abnormalities in dystrophinopathy.

Dystrophinopathy is caused by alterations in DMD. Approximately 1% of patients remain genetically undiagnosed, because intronic variations are not detected by standard methods. Here, we combined laboratory and in silico analyses to identify disease-causing genomic variants in genetically undiagnosed patients and determine the regulatory mechanisms underlying abnormal DMD transcript generation. DMD transcripts from 20 genetically undiagnosed dystrophinopathy patients in whom no exon variants were identified, despite dystrophin deficiency on muscle biopsy, were analyzed by transcriptome sequencing. Genome sequencing captured intronic variants and their effects were interpreted using in silico tools. Targeted long-read sequencing was applied in cases with suspected structural genomic abnormalities. Abnormal DMD transcripts were detected in 19 of 20 cases; Exonization of intronic sequences in 15 cases, exon skipping in one case, aberrantly spliced and polyadenylated transcripts in two cases and transcription termination in one case. Intronic single nucleotide variants, chromosomal rearrangements and nucleotide repeat expansion were identified in DMD gene as pathogenic causes of transcript alteration. Our combined analysis approach successfully identified pathogenic events. Detection of diseasing-causing mechanisms in DMD transcripts could inform the therapeutic options for patients with dystrophinopathy.

A nationwide survey of monocarboxylate transporter 8 deficiency in Japan: Its incidence, clinical course, MRI and laboratory findings.

BACKGROUND: Monocarboxylate transporter 8 (MCT8) deficiency is an X-linked recessive developmental disorder characterized by initially marked truncal hypotonia, later athetotic posturing, and severe intellectual disability caused by mutations in SLC16A2, which is responsible for the transport of triiodothyronine (T3) into neurons. We conducted a nationwide survey of patients with MCT8 deficiency to clarify their current status. METHODS: Primary survey: In 2016-2017, we assessed the number of patients diagnosed with MCT8 deficiency from 1027 hospitals. Secondary survey: in 2017-2018, we sent case surveys to 31 hospitals (45 cases of genetic diagnosis), who responded in the primary survey. We asked for: 1) perinatal history, 2) developmental history, 3) head MRI findings, 4) neurophysiological findings, 5) thyroid function tests, and 5) genetic test findings. RESULTS: We estimated the prevalence of MCT8 deficiency to be 1 in 1,890,000 and the incidence of MCT8 deficiency per million births to be 2.12 (95 % CI: 0.99-3.25). All patients showed severe psychomotor retardation, and none were able to walk or speak. The significantly higher value of the free T3/free T4 (fT3/fT4) ratio found in our study can be a simple and useful diagnostic biomarker (Our value 11.60 ± 4.14 vs control 3.03 ± 0.38). Initial white matter signal abnormalities on head MRI showed recovery, but somatosensory evoked potentials (SEP) showed no improvement, suggesting that the patient remained dysfunctional. CONCLUSION: For early diagnosis, including in mild cases, it might be important to consider the clinical course, early head MRI, SEP, and fT3/fT4 ratio.

Imaging neural circuit pathology of autism spectrum disorders: autism-associated genes, animal models and the application of in vivo two-photon imaging.

Recent advances in human genetics identified genetic variants involved in causing autism spectrum disorders (ASDs). Mouse models that mimic mutations found in patients with ASD exhibit behavioral phenotypes consistent with ASD symptoms. These mouse models suggest critical biological factors of ASD etiology. Another important implication of ASD genetics is the enrichment of ASD risk genes in molecules involved in developing synapses and regulating neural circuit function. Sophisticated in vivo imaging technologies applied to ASD mouse models identify common synaptic impairments in the neocortex, with genetic-mutation-specific defects in local neural circuits. In this article, we review synapse- and circuit-level phenotypes identified by in vivo two-photon imaging in multiple mouse models of ASD and discuss the contributions of altered synapse properties and neural circuit activity to ASD pathogenesis.

Differentiating early clinical features of Panayiotopoulos syndrome from acute encephalopathy.

BACKGROUND: Panayiotopoulos syndrome (PS) is a common benign epilepsy in childhood, characterized by predominantly autonomic symptoms such as emesis, pallor, and seizures, which are often prolonged. In an emergency room (ER), particularly when unconsciousness is prolonged, differentiating PS from acute encephalopathy is challenging. In this study, we aimed to elucidate the differences in clinical features of patients with PS and acute encephalopathy who visited our ER. METHODS: We retrospectively reviewed 18 patients who were transferred to our ER because of status epilepticus later diagnosed as PS, and 30 patients with acute encephalopathy, between July 2012 and July 2017. We compared patient demographics, clinical characteristics, and treatment. RESULTS: Most patients (90%) with acute encephalopathy had convulsive seizures of greater than or equal to 15 min, whereas only three patients (17%) with PS had convulsive seizures of greater than or equal to 15 min (P < 0.001). In addition, seizures were treatable in all patients with PS with a small dose of midazolam (0.1 mg/kg), but all patients with acute encephalopathy required midazolam at 0.3 mg/kg or more (P < 0.001). More patients with PS had autonomic symptoms compared to those with acute encephalopathy (e.g., vomiting [78% vs. 3%, P < 0.001]). Non-convulsive status epilepticus was observed in 22% of PS patients, but not in any acute encephalopathy patients. In contrast, fever was observed in all patients with acute encephalopathy (100%), but less frequently in those with PS (11%, P < 0.001). CONCLUSION: PS was characterized by 1) convulsive seizures shorter than 15 min, 2) seizures treatable with small doses of midazolam, and 3) autonomic symptoms. PS could be differentiated from acute encephalopathy in the early stages of the syndrome.

Mechanism of transient photothermal inactivation of bacteria using a wavelength-tunable nanosecond pulsed laser.

There is a great demand for novel disinfection technologies to inactivate various pathogenic viruses and bacteria. In this situation, ultraviolet (UVC) disinfection technologies seem to be promising because biocontaminated air and surfaces are the major media for disease transmission. However, UVC is strongly absorbed by human cells and protein components; therefore, there are concerns about damaging plasma components and causing dermatitis and skin cancer. To avoid these concerns, in this study, we demonstrate that the efficient inactivation of bacteria is achieved by visible pulsed light irradiation. The principle of inactivation is based on transient photothermal heating. First, we provide experimental confirmation that extremely high temperatures above 1000 K can be achieved by pulsed laser irradiation. Evidence of this high temperature is directly confirmed by melting gold nanoparticles (GNPs). Inorganic GNPs are used because of their well-established thermophysical properties. Second, we show inactivation behaviour by pulsed laser irradiation. This inactivation behaviour cannot be explained by a simple optical absorption effect. We experimentally and theoretically clarify this inactivation mechanism based on both optical absorption and scattering effects. We find that scattering and absorption play an important role in inactivation because the input irradiation is inherently scattered by the bacteria; therefore, the dose that bacteria feel is reduced. This scattering effect can be clearly shown by a technique that combines stained Escherichia coli and site selective irradiation obtained by a wavelength tunable pulsed laser. By measuring Live/Dead fluorescence microscopy images, we show that the inactivation attained by the transient photothermal heating is possible to instantaneously and selectively kill microorganisms such as Escherichia coli bacteria. Thus, this method is promising for the site selective inactivation of various pathogenic viruses and bacteria in a safe and simple manner.

Case-control association study of rare nonsynonymous variants of SCN1A and KCNQ2 in acute encephalopathy with biphasic seizures and late reduced diffusion.

PURPOSE: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized by prolonged febrile seizures at onset and subsequent damage to the cerebral cortex of infants and children. The pathogenesis is suspected to be excitotoxicity leading to neuronal death. SCN1A and KCNQ2 are causative genes of genetic epilepsy including Dravet syndrome and Ohtahara syndrome. Here we conducted a case-control rare-variant association study of the two genes in AESD. METHODS: The coding regions of SCN1A and KCNQ2 were sequenced by the Sanger method for 175 and 111 patients, respectively, with AESD. As control subjects, we used genetic data from 3554 subjects provided by the Integrative Japanese Genome Variation Database (iJGVD). Then we performed a case-control association study of rare missense and splice region variants (minor allele frequency < 0.005) of each gene with AESD using Weighted Sum Statistics (WSS) and Sequence Kernel Association Test (SKAT). RESULTS: SCN1A rare variants had a significant association with AESD after correction for multiple tests (WSS, permutated p value 4.00 × 10-3: SKAT, p value 2.51 × 10-4). The association was more significant when we focused on deleterious variants (WSS, permutated p = 9.00 × 10-4; SKAT, p = 4.99 × 10-5). Although KCNQ2 rare nonsynonymous variants tended to be more frequent in patients than in controls, there was no significant difference. CONCLUSION: Our study provided statistical evidence of an association between SCN1A and AESD for the first time, and established SCN1A as one of the susceptibility genes for AESD.

Early administration of vitamins B1 and B6 and l-carnitine prevents a second attack of acute encephalopathy with biphasic seizures and late reduced diffusion: A case control study.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most prevalent encephalopathy in Japanese children. AESD is characterized by a prolonged febrile seizure on day 1 followed by secondary seizures and MRI abnormality on days 4-6, resulting in high incidence of neurological sequelae. We aimed to clarify whether early administration of vitamins (vitamin B1, vitamin B6, and l-carnitine) would improve the clinical course of AESD. METHODS: We retrospectively reviewed 34 patients with acute encephalopathy who were admitted to our hospital between January 2009 and August 2016. Of the retrospectively registered 34 patients, 22 (65%) since 2011 were treated with the drug cocktail (prescription group) within 24 h of onset, whereas 12 (35%) before 2011 were not (non-prescription group). We compared clinical course, laboratory data, and MRI findings historically in both groups. RESULTS: The two groups did not differ in terms of laboratory findings except for blood lactate values. There were no differences between the two groups regarding duration of ICU admission, intubation, or the duration of seizures. Among the prescription group, two patients developed AESD while 20 had mild encephalopathy (single phasic). In contrast, seven patients inthe non-prescription group developed AESD while five did not. The incidence of AESD was lower in the prescription group (P = 0.004). As for outcomes, the rate of developmental delay and epilepsy was significantly lower in the prescription group. CONCLUSIONS: Our data suggested that early administration of vitamins would improve the clinical course of acute encephalopathy. Mitochondrial rescue and neuroprotection are thought to be responsible for the favorable results.

A case of Niemann-Pick disease type C with neonatal liver failure initially diagnosed as neonatal hemochromatosis.

BACKGROUND: Niemann-Pick type C (NPC) is a lysosomal lipid storage disease with mutation of NPC1/NPC2 genes, which transport lipids in the endosome and lysosome, and various neurological symptoms. NPC patients also develop hepatosplenomegaly or liver disorder in the neonatal period, and 10% suffer severe liver failure. Neonatal hemochromatosis (NH) is a liver disorder characterized by hepatic and extrahepatic siderosis. Although the etiology of NH is unclear, recent reports suggest that the gestational alloimmune mechanism is the cause of NH. Herein, we report a Japanese NPC patient initially diagnosed as NH. CASE REPORT: A 5-day-old boy was transferred to our hospital with severe cholestatic liver failure. Congenital infections and metabolic screening were negative, and NH was suspected. However intra and extrahepatic siderosis were not found. As his liver deteriorated rapidly, liver transplantation was performed at 19 days old. The explanted liver showed cirrhosis, and strong C5b-9 complex staining of hepatocytes, so NH was diagnosed. From the age of one and a half years, he developed regression, vertical supranuclear gaze palsy and cataplexy. Fibroblast filipin staining was strong, blood oxysterol was high, and there were compound heterozygous mutations in NPC1,p.[(F288L)];[(K1206N)]. The patient was then diagnosed as NPC and started on miglustat. CONCLUSION: Neonatal liver failure was initially diagnosed as NH. Later, the patient developed various neurological symptoms characteristic of NPC. Neurological follow-up of children who develop NH is required.

Prolonged mild disturbance of consciousness and acute encephalopathy.

BACKGROUND: Acute encephalopathy (AE) is defined by the Japanese guidelines as the acute disturbance of consciousness (Glasgow coma scale [GCS] score ≤11) that persists for >24 h. We have often encountered, however, cases of prolonged mild disturbance of consciousness (PMDC) with GCS score >11, meaning that they do not fit the guideline definition of AE. The reports of these cases have been relatively sparse, and the nosological position, prognosis, and other characteristics remain unknown. To clarify the characteristics of PMDC we compared cases of PMDC with cases of AE. METHODS: This study was a retrospective observational study at a tertiary children's hospital in Japan. We studied children with a diagnosis of AE or PMDC between January 2011 and August 2016. RESULTS: Thirteen cases of PMDC and 19 cases of AE were identified during the study period. PMDC patients more frequently had hyponatremia (P < 0.01), paradoxical arousal response on electroencephalogram (P = 0.010), normal computed tomography (CT; P = 0.025), and normal magnetic resonance imaging (MRI; P < 0.01) than the AE patients. Sequelae were more frequently observed in AE than in PMDC patients (P = 0.011). CONCLUSIONS: PMDC has different characteristics to AE with regard to hyponatremia, paradoxical arousal response, CT or MRI findings, and prognosis. Despite the differences, PMDC might also be regarded as being a milder member of the wide variety of AE and related diseases.

Severe anti-GAD antibody-associated encephalitis after stem cell transplantation.

BACKGROUND: General features of anti-glutamic acid decarboxylase (GAD) antibody-associated limbic encephalitis are seizures, cognitive impairment, and imaging findings at the medial temporal lobes. We report a patient affected with remarkably severe anti-GAD antibody-positive encephalitis after hematopoietic stem cell transplantation (HSCT). CASE REPORT: A 5-year-old girl received HSCT due to pineoblastoma. Thirteen months after HSCT, she showed seizure clustering and altered mental status. Her anti-GAD antibody level was high, 65,100 U/mL (reference range < 1.5 U/mL). Her disease was diagnosed as autoimmune encephalitis and she received intravenous immunoglobulin (IVIG) and methylprednisolone. After the therapy, she partially recovered. Encephalitis later relapsed, however, and she showed extremely high anti-GAD antibody, 27 months after HSCT. Although lesions were located in the temporal and occipital lobes by MRI at 5 days after the relapse, very severe whole brain encephalitis was revealed at 13 days after the relapse. Seizures and abnormal encephalogram were resistant to IVIG and methylprednisolone. After plasma exchange, these findings were resolved. MRI revealed diffuse cerebral atrophy, 57 months after the relapse. No relapse has occurred for the past 5 years with decreased anti-GAD antibody after starting bimonthly administration of IVIG. CONCLUSION: This may be the first case of severe and recurrent anti-GAD antibody-associated autoimmune encephalitis after HSCT with specific MRI findings. No relapse has occurred since starting maintenance IVIG.

A Simplified Electroencephalogram Monitoring System in the Emergency Room.

OBJECTIVES: The study aims to assess the clinical usefulness and related limitations of our simplified emergency electroencephalography (eEEG) as an assessment tool of lethal abnormal brain waves in the emergency room (ER). METHODS: Electrodes were placed on 4 places: bilateral frontal poles and parietal regions. The derivations to judge consisted of only 2 bipolar leads on the left and right. Abnormal wave was defined as either persistent rhythmic waves or persistent high-amplitude slow waves (<2 Hz). The indications of eEEG were as follows: prolonged impairment of consciousness, suspected subclinical or subtle seizure, and requirement of evaluation of consciousness or seizure during administration of muscle relaxants for endotracheal intubation. RESULTS: We performed eEEG for 86 patients between July 2013 and February 2014. The persistent rhythmic waves were observed in 7 (8.1%), whereas high-amplitude slow waves were observed in 10 (11.6%). Among 69 patients with normal eEEG, 2 were diagnosed with encephalopathy after hospitalization. The mean time taken to attach electrodes was 5.4 minutes. CONCLUSIONS: For the ER physician, the simple EEG, such as eEEG, is useful as a biological monitor because it enables quick assessment of lethal abnormal brain waves in the ER. The clinical usefulness and limitations of our eEEG method should be investigated further in a large population.

Timothy syndrome-like condition with syndactyly but without prolongation of the QT interval.

Timothy syndrome is characterized by a unique combination of a prolongation of the corrected QT interval of the electrocardiogram and bilateral cutaneous syndactyly of the fingers and the toes and is caused by heterozygous mutations in CACNA1C, a gene encoding a calcium channel. After the discovery of the CACNA1C gene as the causative gene for Timothy syndrome, patients with CACNA1C mutations with QT prolongation but without syndactyly were described. Here, we report a 5-year-old female patient with cutaneous syndactyly, developmental delay, and pulmonary hypertension. Exome analysis showed a previously undescribed de novo heterozygous mutation in the CACNA1C gene, p.Arg1024Gly. To our knowledge, this patient is the first to exhibit syndactyly and to carry a CACNA1C mutation but to not have QT prolongation, which has long been considered an obligatory feature of Timothy syndrome.

A case report of reversible generalized seizures in a patient with Waardenburg syndrome associated with a novel nonsense mutation in the penultimate exon of SOX10.

BACKGROUND: Waardenburg syndrome type 1 (WS1) can be distinguished from Waardenburg syndrome type 2 (WS2) by the presence of dystopia canthorum. About 96% of WS1 are due to PAX3 mutations, and SOX10 mutations have been reported in 15% of WS2. CASE PRESENTATION: This report describes a patient with WS1 who harbored a novel SOX10 nonsense mutation (c.652G > T, p.G218*) in exon 3 which is the penultimate exon. The patient had mild prodromal neurological symptoms that were followed by severe attacks of generalized seizures associated with delayed myelination of the brain. The immature myelination recovered later and the neurological symptoms could be improved. This is the first truncating mutation in exon 3 of SOX10 that is associated with neurological symptoms in Waardenburg syndrome. Previous studies reported that the neurological symptoms that associate with WS are congenital and irreversible. These findings suggest that the reversible neurological phenotype may be associated with the nonsense mutation in exon 3 of SOX10. CONCLUSIONS: When patients of WS show mild prodromal neurological symptoms, the clinician should be aware of the possibility that severe attacks of generalized seizures may follow, which may be associated with the truncating mutation in exon 3 of SOX10.

Acute myeloid leukemia-associated DNMT3A p.Arg882His mutation in a patient with Tatton-Brown-Rahman overgrowth syndrome as a constitutional mutation.

DNA methylation plays a critical role in both embryonic development and tumorigenesis and is mediated through various DNA methyltransferases. Constitutional mutations in the de novo DNA methyltransferase DNMT3A cause a recently identified Tatton-Brown-Rahman overgrowth syndrome (TBRS). Somatically acquired mutations in DNMT3A are causally associated with acute myeloid leukemia (AML), and p.Arg882His represents the most prevalent hotspot. So far, no patients with TBRS have been reported to have subsequently developed AML. Here, we report a live birth and the survival of a female with the TBRS phenotype who had a heterozygous constitutional DNMT3A mutation at the AML somatic mutation hotspot p.Arg882His in her DNA from peripheral blood and buccal tissue. Her characteristic features at birth included hypotonia, narrow palpebral fissures, ventricular septal defect, umbilical hernia, sacral cyst, Chiari type I anomaly. At the age of 6 years, she exhibited overgrowth (> 3 SD) and round face and intellectual disability. This report represents the first documentation of the same variant (DNMT3A p.Arg882His) as both the constitutional mutation associated with TBRS and the somatic mutation hotspot of AML. The observation neither confirms nor denies the notion that mutations responsible for TBRS and those for AML might share the same mode of action. Larger data sets are required to determine whether TBRS patients with constitutional DNMT3A mutations are at an increased risk for AML. © 2016 Wiley Periodicals, Inc.

[Scintigraphic imaging in the diagnosis of failed intrathecal baclofen therapy: a case report of a 7-year-old boy with ventriculoperitoneal shunt].

Intrathecal baclofen (ITB) therapy is popular for the management of intractable spasticity. In 2007, the indications of ITB therapy expanded to include spasticity of children in Japan. In this report, we assessed the utility of radioisotopic scintigraphy in the diagnosis of failed ITB therapy. A 7-year-old boy with schizencephaly, hydrocephalus, and spastic quadriplegia had an ITB pump implanted. In his infancy, he had undergone ventriculoperitoneal shunt implantation. One month after the ITB operation, the ITB therapeutic effect diminished. Several examinations confirmed that the pump function was normal and catheter failure had not occurred. However, radioisotopic scintigraphy revealed that the baclofen had been washed out to blood circulation more rapidly than is typically observed. We considered two possible causes for this; obstruction of the cerebrospinal space due to kyphosis and excessive washout of celebrospinal fluid through the ventriculoperitoneal shunt. The catheter was moved to a more caudal site surgically, and his spasticity improved. The use of radioisotopic scintigraphy to identify the distribution of baclofen is an effective technique for investigation of baclofen pump system malfunction.

Missense mutations in sodium channel SCN1A and SCN2A predispose children to encephalopathy with severe febrile seizures.

OBJECTIVE: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a childhood encephalopathy following severe febrile seizures. The pathogenesis of AESD is considered to be fever-induced seizure susceptibility and excitotoxicity, which may be caused by sodium channel dysfunction in some cases. Here we studied whether mutations in genes encoding sodium channels, SCN1A and SCN2A, predispose children to AESD. METHODS: We recruited 92 AESD patients in a nationwide survey of acute encephalopathy in Japan from 2008 to 2011. We collected their genomic DNA samples, and sequenced the entire coding region of SCN1A and SCN2A. RESULTS: Five out of 92 patients (5.4%) had missense mutations either in SCN1A or SCN2A. After a preceding infection with fever, all the patients showed status epilepticus at the onset. Hemiconvulsion-hemiplegia was recognized in three patients during the acute/subacute phase. One patient had taken theophylline for the treatment of bronchial asthma just before the onset of AESD. Familial history was not remarkable except one patient with a SCN1A mutation (G1647S) whose mother had a similar episode of AESD in her childhood. A different substitution (G1674R) at the same amino acid position, as well as two other SCN1A mutations found in this study, had previously been reported in Dravet syndrome. Another SCN1A mutation (R1575C) had been detected in other types of acute encephahlitis/encephalopathy. One patient had SCN2A mutation, F328V, which had previously been reported in Dravet syndrome. Another SCN2A mutation, I172V, was novel. None of the patients were diagnosed with Dravet syndrome or genetic (generalized) epilepsy with febrile seizure plus in the following-up period. CONCLUSIONS: Mutations in SCN1A and SCN2A are a predisposing factor of AESD. Altered channel activity caused by these mutations may provoke seizures and excitotoxic brain damage.

Computational Study of the Rate Coefficients for the Reactions of NO2 with CH3NHNH, CH3NNH2, and CH2NHNH2.

The reactions of NO2 with cis-/trans-CH3NHNH, CH3NNH2 and CH2NHNH2 have been studied theoretically by quantum chemical calculations and steady-state unimolecular master equation analysis based on RRKM theory. The barrier heights for the roaming transition states between nitro (RNO2) and nitrite (RONO) isomerization reactions and those for the concerted HONO and HNO2 elimination reactions from RNO2 and RONO, affect the pressure dependences of the product-specific rate coefficients. At ambient temperature and pressure, the dominant product of the reactions of NO2 with cis-/trans-CH3NHNH and CH2NHNH2 would be expected to be HONO with trans-CH3NNH and CH2NNH2, respectively, whereas it is CH3N(NH2)NO2 for CH3NNH2 + NO2. The product-specific rate coefficients for the titled and related reactions on the same potential energy surfaces were proposed for kinetics modeling.