Serum IgG levels demonstrate seasonal change in connective tissue diseases: a large-scale, 4-year analysis in Japanese

Hypergammaglobulinemia is often found in patients with autoimmune diseases, such as systemic lupus erythematosus (SLE), and its level may correlate with disease activity. However, it is unclear whether immunoglobulin G (IgG) displays seasonal changes. We analyzed the seasonal change in serum IgG by assessing 450 patients with connective tissue disease. The serum IgG levels in summer were compared with those in winter from 2006 to 2009. Independent samples from 355 patients were analyzed to confirm results in the first set. The differences in the IgG levels between the two seasons were analyzed in each disease and compared with disease activity. 488 patients without connective tissue disease were analyzed as reference instead of healthy people as control. We found that connective tissue disease patients tended to show higher levels of serum IgG in summer than in winter every year from 2006 to 2009, whereas patients without connective tissue disease did not demonstrate such a tendency. We observed this seasonal tendency in each disease. Seasonal changes weakly correlated with those of anti-DNA antibody in SLE patients and those of disease activity score in rheumatoid arthritis (RA) patients. Serum IgG levels of patients with connective tissue diseases display seasonal variations. Biological and clinical significance of these variations should be elucidated.     

Criteria for the glucagon provocative test in the diagnosis of gastrinoma

Introduction

The glucagon provocative test is useful for the diagnosis of gastrinoma. The aim of this study was to determine the criteria for the glucagon provocative test.

Methods

This study reviewed 8 patients that underwent the glucagon provocative test preoperatively and in whom the diagnosis was confirmed as gastrinoma histologically. The glucagon provocative test was performed by administering glucagon (20 μg/kg) intravenously, followed by 20 μg/kg h for the next 30 min, and plasma gastrin levels were measured 3 and 1 min before and 3, 5, 7, 10, 15, 20, and 30 min after the administration of glucagon. This study evaluated the peak value of plasma gastrin and the time required to reach the peak.

Results

Two of the 8 patients had multiple endocrine neoplasm type 1. The basal plasma gastrin levels ranged from 524 to 10,300 pg/ml. The time required to reach the peak was 3–10 min for all patients. The increase in the peak from the basal value was 235–8,920 pg/ml, and the percentage of increase was 38–337 %.

Conclusions

These results suggest that a diagnosis of gastrinoma should thus be made when plasma gastrin levels peak within 10 min after glucagon administration, with an increase of greater than 200 pg/ml and greater than 35 % of the basal value.     

Age-related production of osteoclasts and the changes of serum levels of vascular endothelial growth factor (VEGF) and receptor activator for nuclear factor (NF)-κB ligand (RANKL) in osteopetrotic (op/op) mice

ObjectiveExpression of osteoclasts in osteopetrotic (op/op) mice is substantially reduced by the absence of functional macrophage colony-stimulating factor (M-CSF). However, it has been reported that osteoclasts do gradually appear in the bones of op/op mice and spontaneously correct the osteopetrosis.DesignAge-related production of osteoclasts and the changes of serum levels of vascular endothelial growth factor (VEGF) and receptor activator for nuclear factor (NF)-κB ligand (RANKL) in op/op mice were examined.ResultsThe number of femoral osteoclasts, and the serum levels of VEGF, both gradually increased in op/op mice after birth and reached a peak in 120- and 60-day-old mice, respectively. However, the serum levels of RANKL showed an inverse relationship to osteoclast number.ConclusionsThese findings suggest that the appearance of osteoclasts may be influenced by the serum levels of VEGF and that the serum levels of RANKL may be influenced by the appearance of osteoclasts.     

Isolated pyramidal tract impairment in the central nervous system of adult-onset Krabbe disease with novel mutations in the GALC gene

This report describes a 60-year-old female patient with Krabbe disease who presented with slowly progressive gait disturbance due to mild spastic paraplegia. Brain magnetic resonance imaging showed high-intensity lesions along the upper parts of the bilateral pyramidal tracts in fluid-attenuated inversion recovery images. Central motor conduction time was prolonged both in the upper and the lower extremities, while central sensory conduction time was normal. The reduced lymphocyte galactocerebrosidase (GALC) activity and two novel mutations in the GALC gene, p.G496S and p.G569S, proved the diagnosis of Krabbe disease. Our findings show that adult-onset Krabbe disease is characterized by isolated pyramidal tract impairment in the central nervous system, both neurophysiologically and radiologically.     

Therapeutic time window of post-ischemic mild hypothermia and the gene expression associated with the neuroprotection in rat focal cerebral ischemia

Hypothermia is the only neuroprotective therapy proven to be clinically effective. Identifying the molecules that play important roles in the efficacy of hypothermia, we developed a multi-channel computer-controlled system, in which the brain temperatures of freely moving rats were telemetrically monitored and maintained below 35 degrees C, and examined the time window necessary to exert its significant neuroprotective effects. Eight-week-old SD rats were subjected to a 2h middle cerebral artery occlusion (MCAO) with an intraluminal filament, and post-ischemic hypothermia was introduced at 0, 2, 4, or 6h after reperfusion until the rats were killed 2 days after MCAO. Since a significant protection was observed when hypothermia was started within 4h after reperfusion, it was concluded that the therapeutic time window of mild hypothermia lasts for 4h after reperfusion in our model. On the basis of the window, comprehensive gene expression analyses using oligonucleotide microarrays were conducted and identified potential genes related to the efficacy of hypothermia, which included inflammatory genes like osteopontin, early growth response-1, or macrophage inflammatory protein-3alpha. Therefore, the neuroprotective effects of post-ischemic mild hypothermia were strongly suggested to be mainly associated with the reduction of neuronal inflammation.     

Hemoglobin concentration changes in the contralateral hemisphere during and after theta burst stimulation of the human sensorimotor cortices

Using near infrared spectroscopy and repetitive transcranial magnetic stimulation (rTMS), we studied interhemispheric interactions between bilateral motor and sensory cortices in humans. RTMS consisted of a triple-pulse burst (50 Hz) repeated every 200 m for 2 s (10 bursts, 30 pulses); one kind of theta burst TMS (TBS) (Huang et al. in Neuron 45:201–206, 2005). The hemoglobin concentration changes were recorded at the right prefrontal cortex, premotor area (PM), primary hand motor area (M1) and primary sensory area (S1) during and after TBS over the left PM, M1 and S1 or sham stimulation in eight normal volunteers. In addition, motor evoked potentials (MEPs) to TMS over the right M1 were recorded from the left first dorsal interosseous muscle after the conditioning TBS over left S1. TBS over PM induced a significant oxy-Hb decrease at the contralateral PM. TBS over M1 elicited a significant oxy-Hb decrease at the contralateral S1, and TBS over S1 significant oxy-Hb decreases at the contralateral M1 and S1. MEPs to TMS of the right M1 were significantly suppressed by the conditioning TBS over the left S1. These results suggest that there are mainly inhibitory interactions between bilateral PMs and bilateral sensorimotor cortices in humans. Those are partly compatible with the previous findings. In addition to between the primary motor cortices, bilateral connection is requisite for smooth bimanual coordination between the sensory cortices or premotor cortices.     

Evoked-cerebral blood oxygenation changes in false-negative activations in BOLD contrast functional MRI of patients with brain tumors

Blood oxygenation level dependent contrast functional MRI (BOLD-fMRI) has been used to define the functional cortices of the brain in preoperative planning for tumor removal. However, some studies have demonstrated false-negative activations in such patients. We compared the evoked-cerebral blood oxygenation (CBO) changes measured by near-infrared spectroscopy (NIRS) and activation mapping of BOLD-fMRI in 12 patients with brain tumors who had no paresis of the upper extremities. On the nonlesion side, NIRS demonstrated a decrease in deoxyhemoglobin (Deoxy-Hb) with increases in oxyhemoglobin (Oxy-Hb) and total hemoglobin (Total-Hb) during a contralateral hand grasping task in the primary sensorimotor cortex (PSMC) of all patients. On the lesion side, NIRS revealed a decrease in Deoxy-Hb in five patients (Deoxy-decrease group), and an increase in Deoxy-Hb in seven patients (Deoxy-increase group); the Oxy-Hb and Total-Hb were increased during activation in both groups, indicating the occurrence of rCBF increases in response to neuronal activation. BOLD-fMRI demonstrated clear activation areas in the PSMC on the nonlesion side of all patients and on the lesion side of the Deoxy-decrease group. However, in the Deoxy-increase group, BOLD-fMRI revealed only a small activation area or no activation on the lesion side. Intraoperative brain mapping identified the PSMC on the lesion side that was not demonstrated by BOLD-fMRI. The false-negative activations might have been caused by the atypical evoked-CBO changes (i.e. increases in Deoxy-Hb) and the software employed to calculate the activation maps, which does not regard an increase of Deoxy-Hb (i.e., a decrease in BOLD-fMRI signal) as neuronal activation.     

Aqueous Fibronectin Correlates With Severity of Macular Edema and Visual Acuity in Patients With Branch Retinal Vein Occlusion: A Proteome Study

PurposeLarge-scale protein analysis may bring important insights into molecular changes following branch retinal vein occlusion (BRVO). Using proteomic techniques this study compared aqueous humor samples from patients with BRVO to age-matched controls.MethodsAqueous humor samples from treatment naive patients with BRVO complicated by macular edema (n = 19) and age-matched controls (n = 18) were analyzed with label-free quantification nano liquid chromatography – tandem mass spectrometry (LFQ nLC-MS/MS). The severity of macular edema was measured as central retinal thickness (CRT) with optical coherence tomography. Control samples were obtained prior to cataract surgery. Proteins were filtered by requiring quantification in at least 50% of the samples in each group without imputation of missing values. Significantly changed proteins were identified with a permutation-based calculation with a false discovery rate at 0.05.ResultsIn BRVO, 52 proteins were differentially expressed. Regulated proteins were involved in cell adhesion, coagulation, and acute-phase response. Apolipoprotein C-III, complement C3, complement C5, complement factor H, fibronectin, and fibrinogen chains were increased in BRVO and correlated with CRT. Fibronectin also correlated with best corrected visual acuity (BCVA) and vascular endothelial growth factor (VEGF). Monocyte differentiation antigen CD14 (CD14) and lipopolysaccharide-binding protein (LBP) were upregulated in BRVO. Contactin-1 and alpha-enolase were downregulated in BRVO and correlated negatively with CRT.ConclusionsMultiple proteins, including complement factors, fibrinogen chains, and apolipoprotein C-III, correlated with CRT, indicating a multifactorial response. Fibronectin correlated with BCVA, CRT, and VEGF. Fibronectin may reflect the severity of BRVO. The proinflammatory proteins CD14 and LBP were upregulated in BRVO.