Transient low level of IgG3 induced by sepsis

Staphylococcus aureus sepsis developed in a 14 year old girl. Immunological evaluation revealed low level of IgG3, although total IgG level was normal. The level of IgG3 increased gradually along with the recovery from sepsis. Immunoglobulin replacement therapy might have been useful in this patient, even though the total immunoglobulin level was within normal limits.     

A mild case of nesidioblastosis with diagnostic and therapeutic difficulty

A female infant with nesidioblastosis who showed mild clinical symptoms is reported. In this patient, insulin levels and insulin to glucose ratios (IRI/G) were often normal. Regular milk feedings supplemented with continuous glucose infusion (0.7-2 mg/kg per min) or oral glucose feedings (4.5 mg/kg per min) prevented hypoglycemia. As leucine-sensitivity was diagnosed at 2 months of age, she was started on diazoxide. This was, however, ineffective, and adverse effects appeared. Subtotal pancreatectomy (95%) was therefore attempted at 5 months of age, and persistent normoglycemia as well as normal growth and development followed up to 3 years after the operation. The pancreas showed characteristic signs of nesidioblastosis. The above clinical observation suggests that a patient with nesidioblastosis whose blood glucose level is easily controllable may develop an unexpected episode of hypoglycemia in the presence of a leucine sensitivity. In such a patient, diazoxide or, when it is of no avail, surgical intervention should promptly be instituted to prevent possible neurologic sequelae induced by hypoglycemia.     

Human T cell responses to recombinant mite antigens of Dermatophagoides farinae

We studied T cell responses to four glutathione S transferase (GST)-fused mite antigens prepared in our laboratory using peripheral blood lymphocytes from mite-sensitive patients with bronchial asthma. Of the four recombinant antigens, purified GST-Mag3 had the strongest ability to cause patients' lymphocytes to proliferate, and its potency was almost comparable to that of crude mite bodies (Dfb) and faeces (Dff) antigens and a purified major antigen, Der f 2. The responder lymphocytes were mainly T cells, because the proliferative response was depleted by the treatment of lymphocytes with anti-CD3 antibody and complement, but not with anti-CD20 antibody and complement. The responsiveness of lymphocytes to GST-Mag3 correlated with that to Der f 2, but GST-Mag3 displayed slightly higher activity to stimulate lymphocytes than Der f 2. Simultaneously, the levels of Dff- and GST-Mag3-specific IgE antibodies correlated with the responsiveness of lymphocytes to GST-Mag3. These results suggest that Mag3 is a new valuable antigen for the response of T cell proliferation in mite-sensitive patients.     

Epstein-Barr Virus-induced Lymphoblastoid Cell Lines from Patients with Primary Immunodeficiency Diseases

Peripheral lymphocytes from eight patients with congenital immunodeficiency diseases were infected with Epstein-Barr virus (EBV) in an attempt to establish B lymphoblastoid cell lines (LCL). These patients included three boys with congenital agammaglobulinaemia, two girls with hypogammaglobulinaemia, one boy with common variable immunodeficiency, one boy with severe combined immunodeficiency with adenosine deaminase deficiency, and one boy with DiGeorge syndrome. Five of the patients bore no surface immunoglobulins (slg) on their peripheral lymphocytes. LCL were established from seven of the eight patients. All the LCL established formed rosettes with EAC3 and had the ability to produce cytoplasmic immunoglobulins (clg) of various classes. Culture supernatants concentrated up to 100-fold developed precipitin bands by Ouchterlony's method with antisera to human Ig in all the established LCL. These results suggested that both slg^-, clg^- and C3⁺ cells and slg⁺, clg^- and C3⁺ cells might be the target cells for EBV and that slg^-, clg^- and C3⁺ cells might be the precursor cells of B lymphocytes.     

Neuropeptide Y regulates rat renal tubular Na,K-ATPase through several signalling pathways

Neuropeptide Y (NPY) has at least three receptors (Y₁, Y₂ and Y₃) through which it influences different mechanisms in many cell types. Previous data suggest that the Y₂ receptor may be divided into prejunctional and postjunctional subgroups. We have examined the intracellular signalling pathways of the postjunctional Y₂ receptor in rat renal proximal tubules. The results indicate that NPY regulates Na⁺,K⁺-ATPase through several signalling pathways: (1) In proximal tubule (PT) cells NPY increased intracellular calcium. The response was blocked by removing extracellular calcium and was also blocked by using nifedipine. This suggests that calcium was increased by influx from the extracellular space through L -type calcium channels. (2) NPY increased Na⁺,K⁺-ATPase activity in PT segments and this effect was also blocked by nifedipine. CaMKII-Ala²⁸⁶[281–302] a blocker of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) inhibited the NPY-stimulated Na⁺,K⁺-ATPase activity. This implies that increased intracellular calcium activates CaMKII which subsequently increases Na⁺,K⁺-ATPase activity. CaMKII thus appear to act similar to what has been proposed for protein phosphatase 2B. (3) Calphostin C, an inhibitor of protein kinase C (PKC), did not inhibit NPY-stimulated Na⁺,K⁺-ATPase activity. PKC is, therefore, unlikely to be involved. (4) Y₂ receptors are negatively coupled to the cAMP pathway. NPY attenuated forskolin-stimulated cAMP production in renal tubules and exogenous cAMP counteracted the NPY-stimulated Na⁺,K⁺-ATPase activity. This illustrated the importance of NPY for the regulation of renal sodium handling. We also propose that the renal tubule cell is a good model for studying the function and mechanisms of postjunctional Y₂ receptors.     

Effect of hypothermia on the in vitro potencies of neuromuscular blocking agents and on their antagonism by neostigmine

The effect of temperature on the potencies of neuromuscularblocking agents remains unclear. This study was undertaken toexamine the effects of different neuromuscular blocking agentsat 37 and 27 °C at a constant carbon dioxide content ( statprinciple). The effect of neostigmine 1 µmol litre^–1induced antagonism of these agents was also investigated. Phrenicnerve-hemidiaphragm preparations of rats were mounted in modifiedKrebs solution, maintained at 37 CC and aerated with a 5% carbondioxide-95% oxygen gas mixture, and at 27 °C with 4% carbondioxide to maintain the carbon dioxide content of the solutionconstant. Phrenic nerves were stimulated with 0.1 -Hz supra-maximalimpulses of 0.2-ms duration and the elicited tension of thediaphragm recorded. The potencies of the steroidal neuromuscularblocking agents (rocuronium, vecuronium, pancuronium and pipecuronium)increased significantly at 27 °C (P<0.05), while thepotencies of the benzyliso-quinolinium agents (tubocurarineand dimethyl-tubocurarine) did not change. Neostigmine-inducedantagonism of the steroidal agents did not differ significantlybetween each other but differed significantly from the benzylisoquinoliniumagents (P<0.05) at both temperatures. The ratios of IC₅₀(inhibitory concentration, 50%) with and without neostigmineat hypothermia were slightly higher for the steroidal agents,indicating slight enhancement of antagonism by neostigmine at27 °C. In contrast, the ratios were significantly greaterat 27 °C (P<0.05) for isoquinolinium agents, implyingsignificant enhancement of antagonism. Our results indicatethat at 27 °C the potency of all steroidal agents increasedand neostigmine-induced antagonism was slightly enhanced. Withthe isoquinolinium agents, hypothermia caused no change in potencyalthough neostigmine-induced antagonism was enhanced significantly.These findings suggest that the relative effects of steroidaland isoquinolinium agents on the neuromuscular junction aredifferent or that they have a different mechanism of actionon the neuromuscular junction.     

False Tendon‐Related Polymorphic Ventricular Tachycardia

A 39‐year‐old woman showed nonsustained polymorphic ventricular tachycardia (PVT) during light physical activity. Cardiac multidetector row computed tomography demonstrated false tendons, one of which proved to be the focus triggering premature ventricular contraction (PVC) in electrophysiological studies. The triggered PVC arose during the diastolic period, which might have caused tension in the false tendon. Radiofrequency catheter ablation targeting the triggered PVC by pace mapping was performed and proved partially effective against PVT. (PACE 2012;35:e341–e344)     

Physiological and psychological responses induced by expressing empathy with others

Aim: To assess the physical and mental burdens associated with expressing empathy with another person's stress. Methods: Nine female subjects listened to their partner's negative emotions aroused by a stress task (Stroop color‐word test) under two conditions. In the first, the subject reacted empathetically to their partner (“with empathy”); in the second, the subject offered no response (control). Electroencephalograms and skin temperature of the second finger were recorded during the test. Subjective stress was estimated using a visual analog scale, whereas the level of cognition was expressed on a five‐point ranking. Responses during and after expressions of empathy were examined by comparisons with control or by correlation. Results: Sympathetic nerve tone increased under both conditions (i.e. the skin temperature of the second finger fell). Subjective stress was not recognized by the subject while listening “with empathy”, although it did increase significantly after the subject has listened “with empathy”. Subjective stress was not felt under the control conditions. Right temporal activity while listening showed a significantly positive correlation with the level of cognition of feeling the same emotion as the stressed partner, whereas bilateral frontal activity after listening was significantly negative correlated with the level of cognition of understanding the emotions of the stressed partner. Conclusion: Expressing empathy with another person's negative emotion led to increased physiological activity and subjective stress. Physiological responses to empathy depended on cognition of the different subjective factors. Cognition of sharing negative emotions activated the right temporal region of the brain, whereas cognition of understanding negative emotions inhibited bilateral frontal activities.     

Comparison between famciclovir and valacyclovir for acute pain in adult Japanese immunocompetent patients with herpes zoster

Famciclovir is a guanine analog antiviral drug used commonly for herpes zoster. Efficacy of famciclovir treatment has been reported to be comparable to valacyclovir treatment. Both of these medications reduce the time to complete cessation of zoster‐associated pain including post‐herpetic neuralgia, as compared to acyclovir. We conducted a multicenter, randomized, open clinical trial in order to evaluate the extent of pain relief afforded by these two antiviral drugs during the acute disease phase of herpes zoster. The study group comprised 86 immunocompetent adult patients suffering from herpes zoster, who were treated with either famciclovir or valacyclovir for 7 days. Of these, 55 patients enrolled in this study within 72 h of the onset of the rash and 31 patients after 72 h of the onset. There was a significant reduction in acute herpes zoster pain with famciclovir on day 7 and at 2–3 weeks in both of these patient groups, while with valacyclovir, there was not significant reduction in pain on day 7. Of patients aged 50 years or older, there was a significantly earlier reduction in pain with famciclovir than with valacyclovir. In addition, a significant reduction in the number of patients with pain was observed as early as days 3–4 with famciclovir treatment as compared with valacyclovir treatment. We conclude that famciclovir was superior to valacyclovir in the relief of acute pain of herpes zoster. Accordingly, famciclovir is recommended for herpes zoster patients with moderate symptoms and a visual analog scale score of under 50 mm.