Roles of plasmablasts in IgG4-related disease and various immune-based diseases

IgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory disease with multiple organ disorders. Recently, in IgG4-RD, increased circulating plasmablasts have been found. The subsets of plasmablasts are negative for RP105 (CD180). A large population of B cells lacking RP105 (RP105-negative B cells) are found in patients with active with systemic lupus erythematosus and other systemic autoimmune diseases, including dermatomyositis, and Sjögren’s syndrome. In other conditions, such as neuromyelitis optica, Kawasaki’s disease, primary biliary cirrhosis and aging, RP105 expression on B cells and monocytes also alters. We review the basic science and clinical significance of RP105-negative B cells including plasmablasts in various immune-based diseases. RP105-negative B cells, especially plasmablasts, play crucial roles in both systemic and organ-specific autoimmune and inflammatory disorders.     

Detection of maleate-induced Fanconi syndrome by decreasing accumulation of125I-3-iodo-a-methyl-L-tyrosine in the proximal tubule segment-1 region of renal cortex in mice: A trial of separate evaluation of reabsorption

OBJECTIVE: Fanconi syndrome is a renal dysfunction characterized by various combinations of renal tubular transport dysfunction involving amino acids, glucose, protein and other substances. Most reabsorption of amino acids occurs in proximal renal tubule segment 1 (S1). The present study evaluated the possibility of early detection of drug-induced Fanconi syndrome, based on decreased renal accumulation of 125I-3-iodo-alpha-methyl-L-tyrosine (125I-IMT), an amino acid transport marker, in the S1 region of renal cortex. The present experimental model used maleate (MAL)-induced Fanconi syndrome in mice. Results were compared between 125I-IMT and 3 other clinical renal radiopharmaceuticals: 99mTc-2,3-dimercaptosuccinic acid (99mTc-DMSA); 99mTc-mercaptoacetylglycylglycylglycine (99mTc-MAG3); and 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA). METHODS: Male ddY mice (age, 6 weeks; body weight, 25 g) were used to create a Fanconi model of renal dysfunction. A single dose of maleate disodium salt was administered by intraperitoneal injection (6 mmol/kg). Hematoxylin and eosin (HE) staining of the renal cortex, renal autoradiography and measurement of renal radioactivity of labeled compounds were performed at 30, 60, 90 and 120 min after MAL injection. At 5 min after injection of labeled compounds (18.5 kBq for accumulation experiment, 670 kBq for autoradiography), animals were sacrificed by ether overdose and kidneys were removed. For the accumulation experiment, radioactivity was measured using a well-type scintillation counter. For autoradiography, 20-microm sections of frozen kidney were used with Bio-Imaging Analyzer. RESULTS: At 30 min after MAL injection, HE staining showed pyknosis in some proximal tubule cells. At that time, accumulations of 125I-IMT and 99mTc-DMSA in the S1 region were approximately 67% and 55% of control levels (p < 0.005). MAL increased accumulation of 99mTc-DTPA in the S1 region, but had no effect on accumulation of 99mTc-MAG3 in the S 1 region. CONCLUSIONS: Decreased accumulation of 123I-IMT in the S1 region appears to represent a useful marker for detection of MAL-induced Fanconi syndrome. In future, we plan to assess the efficacy of using 125I-IMT to monitor renal dysfunction induced by nephrotoxic clinical drugs.     

Stepwise decrease in VEP latencies and the process of myelination in the human visual pathway

To assess the progress in myelination in the developing human brain, a prospective longitudinal study of flash visual evoked potentials (VEPs) was performed in 22 healthy preterm infants with the same gestational age at birth (between 30 weeks 0 day and 31 weeks 0 day). The individual curves of the changes in the N1a peak latency (the early peak of the N1 wave) decrease not linearly but in a stepwise pattern in the preterm period. Twenty-one infants out of the 22 have one or more ‘acceleration week(s)' in which the latency decreases at a rate of more than 6 ms per week. These stepwise decreases in the latency may reflect a synchronized progress in myelination in several parts of the visual pathway. A detailed analysis of the ‘acceleration weeks' in relation to postmenstrual age (PMA) indicates that they most prominently occur at 37 weeks PMA. At 37 weeks an initiation of myelination in the optic radiation has been demonstrated in post-mortem studies. We propose that a longitudinal follow-up study of VEPs can be accepted as a functional in vivo evaluation of myelination in the developing human brain.     

Chemical structure of the carbohydrate moiety of fucose-rich glycopeptides from human pancreatic juice

Summary Human pancreatic juice, obtained from nine patients after partial excision of the pancreas for bile duct cancer, was fractionated in order to isolate its glycopeptides. Three glycopeptides were purified employing ion-exchange chromatography and gel filtration. All the glycopeptides were found to be free of sialic acid and galactosamine but to have an unusually high content ofl-fucose. The chemical structures of the three glyco-peptides were determined using 500-MHz [¹H]-NMR spectroscopy. One of them, glycopeptide, GP-4, possessed a biantennary structure with threel-fucose residues. The second glycopeptide, GP-3, had a triantennary structure with fourl-fucose residues, and the third one, G-2, had a tetra-antennary structure with fivel-fucose residues. The chemical compositions of these glycopeptides, including the absence of sialic acid and the highl-fucose content, indicate that they represent a new class of glycopeptide present in the normal human pancreas.     

Difference in plasma metabolite concentration after ingestion of lemon flavonoids and their aglycones in humans

The concentrations of metabolites in human plasma after ingestion of flavanone glycosides (FG) and their aglycones (FA) in lemon were examined. FG consisting abundantly of eriocitrin were prepared from lemon peel and FA consisting abundantly of eriodictyol were prepared from FG by treatment with beta-glucosidase. Eriodictyol, homoeriodictyol, and hesperetin in plasma up to 4 h after ingestion of FG with water or FA with water by subjects were not detected in plasma of non-enzyme treatment but in plasma after treatment with beta-glucronidase and sulfatase. Metabolites in plasma after ingestion of FG and FA in humans were shown to exist as the glucuro- and/or sulfo-conjugates of eriodictyol, homoeriodictyol, and hesperetin. After ingestion of FA, the concentration of metabolites in plasma exhibited a high maximum peak at 1 h. The AUC (area under the blood concentration time curve) level of metabolites of FA was higher than that of FG. FA were suggested to be absorbed faster and in higher amounts than FG. The AUC of metabolites in subject plasma after ingestion of FG with flavonoid-depleted lemon juice was shown to change to a low level in comparison with that of FG with water. The maximum concentration peak of metabolites in plasma was faster at 0.5 h than FA with water but the AUC level was similar to FA with water, when subjects ingested FA with vodka (40%, ethanol). The absorption hour of FG and FA was shown to be affected by the co-existing solution.     

Cerebral blood flow and cerebral hematocrit in patients with cerebral ischemia measured by single-photon emission computed tomography

Abstract– Single-photon emission computed tomography (SPECT) was used for the measurement of regional cerebral blood flow (CBF), cerebral blood volume (CBV) and cerebral hematocrit (Hct). CBF was measured using N-isopropyl-p-I-123-Iodoamphetamine. CBV was measured by both RBC tracer (Tc-99m RBC) and plasma tracer (Tc-99m human serum albumin) and cerebral hematocrit (Hct) was calculated. In normals, the cerebral-to-large vessel Hct ratio was 75.9%. Isovolemic hemodilution in patients with high Hct tended to increase the cerebral-to-large vessel Hct ratio. Low CBF, high CBV and slow cerebral blood mean transit time (MTT by dynamic CT scanning) was seen during the acute stage of completed infarction and during the symptom-free interval of TIA. Cerebral Hct was increased in the ischemic region of poor prognosis.     

Well-differentiated HCC manifesting hyperattenuation on CT during arterial portography

A rare case of well-differentiated minute hepatocellular carcinoma (HCC) with hepatitis C virus-related cirrhosis, with unusual radiologic features, is presented. A 10-mm hypoechoic nodule disclosed by ultrasound in segment six showed hypoattenuation on computed tomography hepatic arteriography and hyperattenuation on computed tomography during arterial portography, indicating that the portal vein may have been the dominant vascularity of the nodule. Contrast-enhanced ultrasound revealed hypovascularity in the early arterial phase, isovascularity in the late vascular phase, and the same perfusion as that surrounding the liver parenchyma in the post-vascular phase, with the same pattern observed on the two imaging techniques. These findings were considered not compatible with those of well-differentiated HCC. Ultrasound-guided biopsy showed histological features of well-differentiated HCC with over two-fold the cellularity of the non-tumorous area with a high nuclear/cytoplasmic ratio, increased cytoplasmic eosinophilia, slight atypia and fatty change with an irregular thin trabecular pattern. Further studies may provide insights into the correlation between tumor neovascularity in multistep hepatocarcinogenesis and dual hemodynamics, including the artery and the portal vein.     

Effects of intravenous magnesium infusion on in vivo release of acetylcholine and catecholamine in rat adrenal medulla

We applied microdialysis technique to the left adrenal medulla of anesthetized rats and examined the effects of intravenous Mg^2 + infusion on presynaptic acetylcholine (ACh) release and postsynaptic catecholamine release induced by electrical stimulation of splanchnic nerves. The dialysis probes were perfused with Ringer's solution containing neostigmine. Low-dose MgSO₄ (25 μmol/kg/min for 30 min i.v.) increased mean plasma Mg^2 + concentration to 2.5 mM; the administration suppressed norepinephrine (NE) release by approximately 30% and epinephrine (Epi) release by approximately 20%, but did not affect ACh release. High-dose MgSO₄ (50 μmol/kg/min for 30 min i.v.) increased mean plasma Mg^2 + concentration to 3.8 mM; the administration suppressed ACh release by approximately 25%, NE release by approximately 60% and Epi release by approximately 45%. Administration of Na₂SO₄ (50 μmol/kg/min for 30 min i.v.) did not change the release of ACh, NE or Epi. Local administration of nifedipine (200 μM) suppressed NE release by approximately 40% and Epi release by approximately 30%, but did not affect ACh release. In the presence of nifedipine, low-dose MgSO₄ did not suppress the release of ACh, or further suppress NE or Epi compared to nifedipine alone, but high-dose MgSO₄ suppressed ACh release by approximately 25% and further suppressed NE release by approximately 60% and Epi release by approximately 50% compared to nifedipine alone. In conclusion, intravenous administration of Mg^2 + inhibits both presynaptic ACh release and postsynaptic catecholamine release in the adrenal medulla, but L-type Ca^2 + channel-controlled catecholamine release may be more sensitive to Mg^2 + than non-L-type Ca^2 + channel-controlled ACh release.