Unexpected Resistance to X-Irradiation in a Strain of Hybrid Mammalian Cells

The radiosensitivities of a strain of mouse fibroblasts (Cl-1D), of rat pituitary cells (GH(1)2C(1)), and of a hybrid between the two (alpha-RST) have been studied. Their mean chromosome numbers were 50, 70, and 111, respectively. The hybrid cells were much more resistent to radiation than either of the parent strains. The range of the D(0) (reciprocal of the slope, and therefore a measure of radiosensitivity) for the linear portion of the survival curves for each cell line was: Cl-1D, 134-142 R; GH(1)2C(1), 154-170 R; and alpha-RST, 248-274 R. There were no significant differences in the magnitude of the shoulder or extrapolation number of the survival curves, nor in the ability of the three cell strains to accumulate and repair sublethal radiation damage. It appears unlikely that the unusual resistance of the hybrid strain is simply related to the increase in chromosome number; more likely, it involves some interaction between the two genomes. The study of somatic cell hybrids may offer further insight into the factors controlling the radiosensitivity of mammalian cells.     

Non-episodic angioedema associated with eosinophilia following <Emphasis Type="Italic">Mycoplasma pneumoniae</Emphasis> infection

Episodic angioedema with eosinophilia is characterized by recurrent angioedema, peripheral eosinophilia, fever, weight gain, elevated serum immunoglobulin M (IgM), and a benign course lacking any internal organ involvement. A non-episodic variant has also been reported which is limited to a single attack and normally is less severe than the episodic type. We report a case of Mycoplasma pneumoniae infection with dermatological manifestation that was followed by non-episodic angioedema with eosinophilia including fever, weight gain, and elevated serum IgM. Even though the patient’s clinical characteristics resemble episodic angioedema with eosinophilia as reported by Gleich, angioedema was non-episodic. This may be due to systemic corticosteroid treatment which was prescribed because of persistent skin manifestation following M. pneumoniae infection. The current report is the first observation suggesting that angioedema associated with eosinophilia may be triggered by atypical bacterial infection.     

Neuronal metabotropic glutamate receptor 8 protects against neurodegeneration in CNS inflammation

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with continuous neuronal loss. Treatment of clinical progression remains challenging due to lack of insights into inflammation-induced neurodegenerative pathways. Here, we show that an imbalance in the neuronal receptor interactome is driving glutamate excitotoxicity in neurons of MS patients and identify the MS risk–associated metabotropic glutamate receptor 8 (GRM8) as a decisive modulator. Mechanistically, GRM8 activation counteracted neuronal cAMP accumulation, thereby directly desensitizing the inositol 1,4,5-trisphosphate receptor (IP3R). This profoundly limited glutamate-induced calcium release from the endoplasmic reticulum and subsequent cell death. Notably, we found Grm8-deficient neurons to be more prone to glutamate excitotoxicity, whereas pharmacological activation of GRM8 augmented neuroprotection in mouse and human neurons as well as in a preclinical mouse model of MS. Thus, we demonstrate that GRM8 conveys neuronal resilience to CNS inflammation and is a promising neuroprotective target with broad therapeutic implications.     

FBXO28 causes developmental and epileptic encephalopathy with profound intellectual disability

Chromosome 1q41‐q42 deletion syndrome is a rare cause of intellectual disability, seizures, dysmorphology, and multiple anomalies. Two genes in the 1q41‐q42 microdeletion, WDR26 and FBXO28, have been implicated in monogenic disease. Patients with WDR26 encephalopathy overlap clinically with those with 1q41‐q42 deletion syndrome, whereas only one patient with FBXO28 encephalopathy has been described. Seizures are a prominent feature of 1q41‐q42 deletion syndrome; therefore, we hypothesized that pathogenic FBXO28 variants cause developmental and epileptic encephalopathies (DEEs). We describe nine new patients with FBXO28 pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and analyze all 10 known cases to delineate the phenotypic spectrum. All patients had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5 months (range 8 months to 5 years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features, albeit different to those typically seen in 1q41‐q42 deletion syndrome and WDR26 encephalopathy. We distinguish FBXO28 encephalopathy from both of these disorders with more severe intellectual impairment, drug‐resistant epilepsy, and hyperkinetic movement disorders.     

Prophylactic Insulin Treatment of Diabetes-prone BB/OK Rats by Application of a Sustained Release Insulin Implant

Normoglycemic diabetes-prone BB/OK rats aged 33, 45 or 75 days were subjected to prophylactic insulin treatment by means of a single subcutaneous application of a sustained release insulin implant. The single application of a sustained release insulin implant decreased the incidence of diabetes or delayed the onset of the disease in BB/OK rats of all treatment groups. Prophylactic insulin administration caused a transient hypoglycemic period accompanied by an inhibition of glucose stimulated insulin secretion and a decrease of the insulin content of Langerhans' islets as detectable in vitro . Compared to islets of normoglycemic controls pancreatic islets isolated from hypoglycemic BB/OK rats within 7-21 days after the insulin application at 45 days of age displayed a decreased susceptibility of the cells to complement-dependent cytotoxicity of the monoclonal islet cell surface antibody (ICSA) K14D10 but not to the cytotoxic effect of the ICSA M3aG8. The appearance of complement-dependent antibody-mediated cytotoxicity to islet cells and pancreatic exocrine cells in serum regarded as a sign of immune dysregulation in BB/OK rats seems not to be affected by insulin prophylaxis and was detectable during hypoglycemia as well as in the subsequent normoglycemic state. In conclusion, BB/OK rats of different age can be protected from diabetes by a single application of a sustained release insulin implant. Insulin and/or hypoglycemia seem to influence the expression of cell surface antigens, thus render the islets of Langerhans less vulnerable to immune cytolysis, whereas the appearance of humoral immunological abnormalites is not affected.     

Diagnostic yield of capillary compared to venous glucose in the diagnosis of hypoglycorrhachia in children: A prospective,observational study

IntroductionThe ratio of cerebrospinal fluid (CSF) glucose and blood glucose is of major relevance, conducting to the diagnosis of hypoglycorrhachia, which is a sign of neuroinfection, as well as a number of neurological diseases of genetic or neoplastic etiology. Glucose in capillary sample (glucometry) is a low cost, readily available technique, as compared to venous glucose. This study aims to compare glucometry to venous glucose in the diagnosis of hypoglycorrhachia in pediatric population.MethodsProspective cross-sectional study based on data obtained from lumbar punctures in the period from February 2017 to January 2019 in a specialized pediatric institution in Colombia.Results97 patients were analyzed, aged 1 month to 17 years old, mean 7.67 years, 52 (53.61%) were female. 26 (26.8%) were diagnosed with hypoglycorrhachia. Pearson correlation coefficient for absolute venous and capillary glucose was 0.54, and 0.55 for the ratios of CSF glucose/venous glucose and CSF glucose/glucometry, which support a linear correlation between the variables in both, absolute values and ratios. Intraclass correlation coefficient was calculated for both, the venous glucose and glucometry ratios, which was 0.52, revealing a moderate agreement among the tests. Sensitivity and specificity of CSF glucose/glucometry, as compared to gold standard are 73.1% and 60.6% respectively; whereas predictive positive value (PPV) and negative predictive value (NPV), were 40.4% and 86.0%.ConclusionGlucometry cannot replace the glucose in venous sample in the diagnosis of hypoglycorrhachia in children.     

Swedish Universities Scales of Personality: Relation to Other Personality Instruments

ObjectiveTo investigate associations between Swedish universities Scales of Personality (SSP) and scales of the following personality instruments: Structured Clinical Interview for DSM-III-R axis II screening questionnaire (SCID-II screen), revised NEO personality inventory (NEO-PI-R), revised Chapman scales (Chapman) and the psychotic traits questionnaire (STQ). MethodsHealthy individuals (n=406) completed self-report personality questionnaires including SSP and at least one more personality inventory. Correlations were calculated between the 13 different SSP subscales as well as SSP’s three factors and factors and scales/subscales in SCID-II screen, NEO-PI-R, Chapman and STQ. The main factors of the various instruments were factor analysed. ICC were calculated. ResultsSSP Neuroticism factor correlated with SCID-II cluster C (r=0.71), NEO Neuroticism (r=0.80) and Chapman Social anhedonia (r=0.62). SSP Extraversion factor correlated with NEO Extraversion (r=0.63) and SSP Aggressiveness factor with NEO Agreeableness (r=-0.62). Strong correlations between SSP factors and scales and scales of the other instruments were sparse, although weaker correlations were common. ConclusionSSP is a useful investigation tool when measuring personality traits related to temperament-like features. SSP partly correlates well to especially three of the NEO-PI-R factors. The different personality inventories are not completely comparable to each other. Instead, they measure personality aspects in partly different ways.