An infant case of bilateral small kidneys with both proximal and distal tubular dysfunction

Abstract A male infant with bilateral small kidneys associated with both proximal and distal tubular dysfunction, who showed chronic renal failure soon after birth, is reported. He was also noted to have both proximal and distal type of renal tubular acidosis. The small kidneys were thought to be due to renal hypodysplasia associated with bilateral severe vesicoureteral reflux, by radiological findings. An alkalization therapy with chemo-prophylaxis seemed to be of benefit in slowing the progression of renal failure in this case.     

Suppression of IFN-gamma production in atopic group at the acute phase of RSV infection

Several studies have suggested that respiratory syncytial virus (RSV) bronchiolitis induced the change of cytokine production profile in childhood. We sought to determine whether the RSV-induced cytokine production was affected by the patient's atopic background. We quantified interferon-gamma (IFN-gamma) and interleukin (IL)-4 in the supernatant of peripheral blood mononuclear cells (PBMCs) cultured for 24 h and in the presence of phytohemaglutinin (PHA), IL-12, or IL-18, from 14 infants who were divided into two groups, those who are non-atopic and an atopic group. In RSV-infected infants with atopic diseases, IFN-gamma production from IL-12- or especially IL-18-stimulated PBMCs was subtotally suppressed in the acute phase, whereas in RSV-infected infants without atopic diseases IFN-gamma production was not suppressed on acute phase. The IFN-gamma suppression observed in the atopic group is not caused by the immaturity of an infant's immune system since reduced IFN-gamma production to RSV is not observed in the infants of non-atopic group. IFN-gamma suppression in regard to RSV infection might be caused by some genetic factor involved in the development of atopic disease such as IL-18 signal cascade.     

Veno-venous bypass to prevent myocardial ischemia during right heart bypass operation in PA, IVS, and RV dependent coronary circulation

There is a risk of myocardial ischemia in patients with pulmonary atresia and intact ventricular septum associated with right ventricle dependent coronary circulation, especially during open heart operation. Cardiopulmonary bypass unloads the right ventricle, and thereby reduces the coronary perfusion pressure in an area that is wholly or partly dependent on the right ventricle. We present a veno-venous bypass technique to keep the right ventricle beating and ejecting to supply the oxygenated blood into the right ventricle dependent myocardium and consequently to prevent myocardial ischemia during right heart bypass operation.     

Metabolite alterations in basal ganglia associated with psychiatric symptoms of abstinent toluene users: a proton MRS study.

Long-term toluene abuse causes a variety of psychiatric symptoms. However, little is known about abnormalities at the neurochemical level in the living human brain after long-term exposure to toluene. To detect neurochemical changes in the basal ganglia of subjects with a history of long-term toluene use, proton magnetic resonance spectroscopy (1H MRS) was performed in 12 abstinent toluene users and 13 healthy comparisons with no history of drug abuse. N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr + PCr), choline-containing compounds (Cho), and myo-inositol (MI) levels were measured in the left and right basal ganglia. The Cho/Cr + PCr ratio, a marker of membrane metabolism, was significantly increased in the basal ganglia of toluene users in comparison to that of the control subjects. Furthermore, the increase in the Cho/Cr + PCr ratio was significantly correlated with the severity of residual psychiatric symptoms. These findings suggest that long-term toluene use causes membrane disturbance in the basal ganglia, which is associated with residual psychiatric symptoms that persist even after long-term abstinence from toluene use.     

Immunophilin ligands: from immunosuppressants to neuroprotective drugs]

Non-immunosuppressive immunophilin ligands (NI-IPLs) are attracting attention as new candidate drugs for neuroprotection and/or neurorestoration, particularly since they do not have the adverse effects of immunosuppressants. However, it is not yet enough to understand that NI-IPLs are useful drugs for treating neurological disorders. In particular, the molecular mechanism of NI-IPL activity in target cells in the brain remains obscure. In this review, we focused on the molecular basis of the neuroprotective properties of IPLs. Our findings suggest that IPLs have neuroprotective effects mediated by multiple beneficial properties such as a glutathione (GSH)-activating effect, a neurotrophic factor (NTF)-activating effect, and an anti-apoptotic effect, but not by an immunosuppressive effect, both in cell cultures and in vivo. In particular, the GSH-activating effect and the NTF-activating effect of NI-IPLs may be essential to the expression of their neuroprotective properties. Thus, NI-IPLs might have a potentially beneficial effect by ameliorating neurological disorders, since they do not cause serious side effects such as immune deficiency.     

Functional regulation of serotonin transporter, a molecule involved in the pathogenesis of anxiety disorder]

The serotonin transporter (SET) is a member of the Na+/Cl(-)-dependent neurotransmitter transporter family and functions as a membrane protein which terminates the serotonergic neuronal transmission by re-uptaking serotonin into the pre-synaptic terminal. SET is thought to be involved in the pathogenesis of affective disorders, drug abuse and anxiety disorder. We have focused on SET regulation by phosphorylation/dephosphorylation since SET has many putative phosphorylation sites in its intracellular region. Our previous studies have revealed that phorbolesters, activators of PKC, decreased in SET uptake activity. Based on a mutagenesis analysis of PKC phosphorylation sites and an in vivo phosphorylation study of SET, we have concluded that PKC regulates SET activity via an indirect mechanism, probably via alternating actin cytoskeleton status. Recent reports and our investigation have demonstrated that the SET C-terminal region interacts with actin binding proteins, suggesting the crucial roles of this region in functional regulation of SET.     

Hepatocyte growth factor overexpression ameliorates liver inflammation and fibrosis in a mouse model of nonalcoholic steatohepatitis

Background  

Hepatocyte growth factor (HGF) is a potent growth factor involved in liver regeneration that has various effects on epithelial and nonepithelial cells. Although it has been demonstrated that HGF can reduce liver inflammation or fibrosis caused by pharmaceutical or chemical insult, no examination of its effect on liver injury in nonalcoholic steatohepatitis (NASH) has been reported.