Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.     

Living domino liver transplantation in an adult with congenital absence of portal vein.

Congenital absence of the portal vein (CAPV) is a rare malformation of the splanchnic venous system. Although CAPV is usually detected in the pediatric age group, our patient was a 35-year-old woman. She had been diagnosed with CAPV in 1996 when she was 27 years old. In 1998, she was placed on hemodialysis due to chronic renal failure. After several episodes of encephalopathy in 2002, liver transplantation (LT) was recommended to her and her family. Since there was no suitable living donor candidate, she was put on the waiting list for a deceased donor liver transplant in Japan. In 2004, her ammonia level increased to around 300 microg/dl, and she went into a coma lasting for three days. After recovering from this event, she underwent a living domino transplantation using a whole liver donated by a familial amyloid polyneuropathy (FAP) patient. Her portal vein, which had drained directly into the inferior vena cava (IVC), was transected together with a cuff of the IVC wall and anastomosed to the graft liver portal vein in an end-to-end fashion. In conclusion, liver transplantation proved to be a safe and effective way to save this patient and improve her quality of life.     

Recovery functions of somatosensory vertex potentials in man: interaction of evoked responses from right and left fingers.

Somatosensory vertex potentials (SVPs) were examined in 12 healthy subjects in response to painful electrical stimulation of the finger. SVPs consisted of N1, P1, and N2. The average latencies of the 3 peaks were 150, 225, and 350 msec, respectively. The latency and amplitude of each potential were reproducible for each subject. Recovery functions of the SVPs were analyzed in 10 subjects. A pair of stimuli were delivered to the right or left finger with interstimulus intervals (ISIs) of 50, 100, 150, 200, 350, 500 and 650 msec. SVPs partially recovered with the shortest ISI (50 msec). Full recovery could not be obtained even with the longest ISI (650 msec). Differences in recoveries within 650 msec of ISI were not observed between right and left stimulations. To examine the interaction between SVPs evoked by right and left finger stimulation, recovery functions from prior contralateral finger stimulation were analyzed with the same ISIs. SVP recoveries for right after left or left after right patterns of stimulus delivery were nearly the same as those for ipsilateral ones. It is suggested that SVPs are generated at nearly the same site in the sensory pathway regardless of the side stimulated.     

Effect of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic, on the cardiac function of hamsters

Cardiovascular effects of (2'R)-4'-O-tetrahydropylanyladriamycin X HCl (THP) and doxorubicin (adriamycin, ADM) were studied in hamsters. In experiments to observe acute effects, THP was administered intravenously at a dose of 12.5, 25.0 or 50.0 mg/kg, and ADM at 1.56, 3.13 or 6.25 mg/kg was given to different subjects. The THP caused slight ECG alterations at a dose of 12.5 mg/kg. At a dose of 25.0 mg/kg or 50.0 mg/kg, THP caused moderate to remarkable alterations in ECG like a widening of PR and PRc interval, A-V block, ST segment depression and T wave flattening. The ADM caused moderate to remarkable alterations in ECG at a dose of 3.13 mg/kg or 6.25 mg/kg, including arrhythmia, bradycardia, A-V block, ST segment changes and T wave flattening. These changes caused by THP and ADM recovered within 5 approximately 10 minutes after injection. Alterations in the ultrastructure of the myocardium caused by THP at a dose of 50.0 mg/kg included some cells with slight changes like swelling of mitochondria, focal intracellular edema, and enlargement of myofibrils. The ADM, at a dose of 3.13 mg/kg, induced severer swelling of mitochondria than THP, dilatation of sarcoplasmic reticulum, intracellular edema, and disorganization of myofilaments. At a dose of 6.25 mg/kg of ADM, these changes became more pronounced. In experiments to observe subacute effects, hamsters were treated with THP or ADM by daily intraperitoneal injections for 15 consecutive days, and then allowed to be recovered for 15 days. Dose levels of THP or ADM were 0.125, 0.25, 0.5 and 1.0 mg/kg. General toxicity, ECG, hematological and blood biochemical analysis, and electron microscopic examination were studied. In the ECG study, THP-treated hamsters showed a reversible elevation of R wave amplitude at a daily dose of 0.5 mg/kg. Widening of PR and PRc interval, elevation of R and S wave amplitude, and reduction of T wave amplitude were observed at a daily dose of 1.0 mg/kg of THP. Hamsters treated with ADM showed increase of heart rate, reduction of T wave amplitude, and shortening of PR and PRc interval at a daily dose of 0.5 mg/kg. Severe changes were observed at a daily dose of 1.0 mg/kg of ADM including an increase of heart rate, elevation of R wave amplitude, reduction of S and T wave amplitude, and shortening of QT interval. The electron microscopic examination revealed that THP-treated hamsters showed separation of intercalated discs, formation of myelin structure, and dilatation of T-tubules at a daily dose of 1.0 mg/kg. Similar changes were caused by ADM at a daily dose of 0.25 to 1.0 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS)     

Maturation of Pulmonary Metastases of Wilms' Tumor after Therapy: A Case Report

A case is reported of Wilms' tumor associated with multiple pulmonary metastases histologically showing maturation of the tumor cells at 9 years after the resection of the primary tumor and intensive therapy. A huge tumor of a 22-month-old patient's right kidney was resected. The tumor was diagnosed as Wilms' tumor of mesenchymal type (stage 1), which consisted of predominantly immature mesenchymal tissue including rhabdomyoblasts, smooth muscle and fibrous tissue, and few blastemal and epithelial components. Intensive preoperative and postoperative chemotherapy with actinomycin D and vincristine and postoperative irradiation therapy totaling 16 Gy were carried out. The patient was regularly followed up uneventfully until 9 years after the surgery. On routine chest x ray at the age of 10 years 11 months, multiple pulmonary nodules were found. The excised nodules from the bilateral lungs disclosed similar histology, exclusively composed of dense collagen bundles and fibrocytes intermingled with mature striated muscle bundles. No immature tumor components were detected. The possible effect of intensive therapy in this maturation was stressed, although spontaneous benign differentiation of tumor cells cannot be excluded.     

Classification of human liver transplant recipients by their preoperative CD8+ T cell subpopulation and its relation to outcome.

The primed status of T cells is markedly different among liver transplant recipients, due to a lifetime of antigen exposure and reduced thymopoiesis by aging, and diseases. This study aims to characterize the preoperative immunological status of CD8+ T cell subpopulations and relate it to the outcome for liver transplant recipients. We classified 112 liver transplant recipients into 5 groups, based on hierarchical clustering of the CD8+CD45 isoform proportion of T cells. In Groups I and II (pediatric), the naive T cell proportion was more than 50%. In adult recipients, Group III was characterized by a naive T cell proportion of 50%, Group IV had the greatest effector/memory T cells (EM), and Group V had the greatest proportion of effector T cells. In Groups IV and V, the effector T cell proportion was considerably higher, and was accompanied by marked downregulation of the CD27+CD28+ subsets and upregulation of interferon gamma (IFN)-gamma, tumor necrosis factor-alpha, and perforin expression. Group V recipients tended to be complicated postoperatively, with a significantly reduced survival rate (1 yr, 66.8%) and markedly reduced Eastern Cooperative Oncology Group performance status.     

Effect of alpha 2-adrenergic receptor antagonist (midaglizole) on gastrointestinal motility in conscious dogs

To clarify the physiological role of the mechanism that adrenergic nerve inhibits Ach release from intramural cholinergic nerve endings, the influence of Midaglizole, alpha 2-adrenergic receptor antagonist, to postprandial gastrointestinal motilities in conscious dogs was investigated. Postprandial motilities of gastric antrum, duodenum, ileum, and colon were significantly enhanced by Midaglizole (3.0-5.0 mg/kg body weight, i.v.). These excitatory responses were abolished by atropine (0.05-0.1 mg/kg body weight, i.v.). On the other hand, in most cases (29 cases out of 32), when Midaglizole was administered during quiesent phase of IMC, no change occurred in gastrointestinal motility. However, after subliminal dose of pentagastrin or cisapride, which stimulated Ach release from intramural cholinergic neuron without development of motility, was administered, Midaglizole induced phasic, postprandial motility-like contraction in gastrointestinal tract. Even in the fasted state, when Midaglizole was administered intragastrically, irregular contractions with high amplitude occurred in every regions from gastric antrum to colon. And these excitatory responses were abolished by atropine. Similar reaction was observed also in truncal vagotomized dogs. These results suggest that it is the physiological mechanism that adrenergic nerve presynaptically inhibits Ach release from intramural cholinergic neuron, which is the main mechanism of development of postprandial motility, acting on alpha 2-adrenergic receptor, and has tonic control of postprandial motility.     

Aminergic and cholinergic afferents to REM sleep induction regions of the pontine reticular formation in the rat

Microinjection of cholinergic agonists in a dorsolateral part of the mesopontine tegmentum has been shown to induce a rapid eye movement (REM) sleep-like state. Physiological evidence indicates that not only acetylcholine but also various amine transmitters, including those implicated in behavioral state regulation, affect neuronal activity in this region of the pontine reticular formation. In the present study, sources of select aminergic and cholinergic inputs to this REM sleep induction zone were identified and quantitatively analyzed by using fluorescence retrograde tracing combined with immunofluorescence in the rat. In addition to previously demonstrated cholinergic projections from the pedunculopontine and laterodorsal tegmental nuclei, the REM sleep induction zone received various aminergic inputs that originated in widely distributed regions of the brainstem and hypothalamus. Serotoninergic afferents represented a mean of 44% of all aminergic/cholinergic source neurons projecting to the REM sleep induction zone, which was comparable to the mean percentage of 39% represented by cholinergic afferent neurons. The serotoninergic afferents originated from the raphe nuclei at all brainstem levels, with heavier projections from the pontine than from the medullary raphe nuclei. Unexpectedly, an additional major serotoninergic input was provided by serotoninergic neurons in the nucleus prosupralemniscus (B9). Noradrenergic afferent neurons represented a mean of 14% of all aminergic/cholinergic source neurons, which was only about one-third of the mean percentage of either cholinergic or serotoninergic source neurons. These noradrenergic projection neurons were located not only in the locus ceruleus (8%) but also in the lateral tegmentum, including the A5 (4%) and A7 (2%) cell groups. Histaminergic neurons in the tuberomammillary hypothalamic nucleus represented a minor group of afferent neurons (3%), and a still smaller input came from adrenegic C1 neurons. The pattern of these transmitter-specific afferent connections appeared to be similar regardless of the longitudinal level within the REM sleep induction zone. The present results are consistent with previous behavioral and physiological evidence for a role of the pontine REM sleep induction zone in triggering REM sleep. The regulation of REM sleep induction would be best understood in terms of a state-dependent interplay of cholinergic, serotoninergic, and other inputs all acting convergently upon neurons in the REM sleep-inducing region of the pontine reticular formation.