Correlation between magnesium pre-loading and cisplatin-induced nephrotoxicity in 5-fluorouracil/cisplatin combination therapy for esophageal cancer.

The use of cisplatin may cause nephrotoxicity in patients. Hydration solutions supplemented with magnesium could reduce cisplatin-induced nephrotoxicity. In this study, we evaluated the preventive effect of magnesium pre-loading on cisplatin-induced nephrotoxicity in patients with esophageal cancer. We retrospectively evaluated the prevalence of, and risk factors for, nephrotoxicity in 160 patients with esophageal cancer treated with the 5-fluorouracil/cisplatin regimen from 2014 to 2016 with and without magnesium supplementation. Significant differences were observed between the magnesium and non-magnesium groups in terms of frequency of estimated creatinine clearance of grade 2 or higher that was at 4% (n = 3) and 13% (n = 10) (p = 0.027), respectively. The logistic regression analysis revealed that eCcr of grade 2 or higher was significantly associated with the non-magnesium regimen (odds ratio (OR), 4.175; 95% confidence interval (CI) = 1.061-16.430; p = 0.041) and age ≥ 65 years (OR, 13.951; 95% CI = 1.723-112.974; p = 0.014). This study suggests that 20 mEq magnesium pre-loading significantly reduces the prevalence of cisplatin-induced nephrotoxicity. Furthermore, when cisplatin is administered to individuals older than 64 years, a close observation for the onset of cisplatin-induced nephrotoxicity is crucial.

Histamine-2 receptor antagonists (H2RA) may negatively impact ADL assessment in patients on a convalescent rehabilitation ward.

Background/aim: In the convalescent rehabilitation ward, many elderly patients undergo rehabilitation. Histamine-2 receptor antagonists (H2RA), which is a one of the acid secretion inhibitors, is frequently prescribed for the patients as a peptic ulcer prevention measure. At present, H2RA are reported as being associated with factors that reduce cognitive function. However, little is known about the relationship H2RA and rehabilitation outcome. Therefore, this study examined the relationship between H2RA use and Functional Independence Measure (FIM) gain, which determines rehabilitation outcomes for patients admitted to the convalescent rehabilitation ward. Patients and methods: We retrospectively investigated FIM gain on discharge by both the administration group (H2RA (+)) (n = 118) and non-administration group (H2RA (-)) (n = 118). Results: The FIM gain scores of Motor FIM total, Cognition FIM total, and Total FIM were significantly lower in H2RA (+) than in H2RA (-) (Motor FIM total: 8.0 [4.0-16.0] [Inter-Quartile Range] vs. 12.0 [5.0-19.2], p =0.0217, Cognition FIM total: 3.0 [1.0-6.0] vs. 5.0 [2.0-7.0], p =0.0120, Total FIM: 11.5 [4.8-20.2] vs. 17.0 [8.0-27.0], p =0.0089). Conclusion: The administration of H2RA to elderly patients undergoing rehabilitation may prevent cognitive function maintenance or recovery by rehabilitation.

Computer-Assisted Detection of Cerebral Aneurysms in MR Angiography in a Routine Image-Reading Environment: Effects on Diagnosis by Radiologists.

BACKGROUND AND PURPOSE: Experiences with computer-assisted detection of cerebral aneurysms in diagnosis by radiologists in real-life clinical environments have not been reported. The purpose of this study was to evaluate the usefulness of computer-assisted detection in a routine reading environment. MATERIALS AND METHODS: During 39 months in a routine clinical practice environment, 2701 MR angiograms were each read by 2 radiologists by using a computer-assisted detection system. Initial interpretation was independently made without using the detection system, followed by a possible alteration of diagnosis after referring to the lesion candidate output from the system. We used the final consensus of the 2 radiologists as the reference standard. The sensitivity and specificity of radiologists before and after seeing the lesion candidates were evaluated by aneurysm- and patient-based analyses. RESULTS: The use of the computer-assisted detection system increased the number of detected aneurysms by 9.3% (from 258 to 282). Aneurysm-based analysis revealed that the apparent sensitivity of the radiologists' diagnoses made without and with the detection system was 64% and 69%, respectively. The detection system presented 82% of the aneurysms. The detection system more frequently benefited radiologists than being detrimental. CONCLUSIONS: Routine integration of computer-assisted detection with MR angiography for cerebral aneurysms is feasible, and radiologists can detect a number of additional cerebral aneurysms by using the detection system without a substantial decrease in their specificity. The low confidence of radiologists in the system may limit its usefulness.

Comprehensive sequence analysis of translation termination sites in various eukaryotes.

Recent investigations into the translation termination sites of various organisms have revealed that not only stop codons but also sequences around stop codons have an effect on translation termination. To investigate the relationship between these sequence patterns and translation as well as its termination efficiency, we analysed the correlation between strength of consensus and translation efficiency, as predicted according to Codon Adaptation Index (CAI) value. We used RIKEN full-length mouse cDNA sequences and ten other eukaryotic UniGene datasets from NCBI for the analyses. First, we conducted sequence profile analyses following translation termination sites. We found base G and A at position +1 as a strong consensus for mouse cDNA. A similar consensus was found for other mammals, such as Homo sapiens, Rattus norvegicus and Bos taurus. However, some plants had different consensus sequences. We then analysed the correlation between the strength of consensus at each position and the codon biases of whole coding regions, using information content and CAI value. The results showed that in mouse cDNA, CAI value had a positive correlation with information content at positions +1. We also found that, for positions with strong consensus, the strength of the consensus is likely to have a positive correlation with CAI value in some other eukaryotes. Along with these observations, biological insights into the relationship between gene expression level, codon biases and consensus sequence around stop codons will be discussed.

Neuropathology of early-infantile epileptic encephalopathy with suppression-bursts; comparison with those of early myoclonic encephalopathy and West syndrome.

For the critical lesions and pathomechanism of early-infantile epileptic encephalopathy (EIEE) with suppression-bursts, we investigated the brains of EIEE, early myoclonic encephalopathy (EME), and West syndrome (WS) patients using immunohistochemical technique and neuropathological examination. We could compare with the results of these diseases. The EIEE patients had the most severe lesions, which were in the putamen, thalamus, hippocampus as well as the tegmentum of the brainstem. Among the syndromes, EIEE brains showed the most expanded lesions. Tyrosine hydroxylase-immunopositive cells and fibers were not demonstrated in EIEE, but were detected in WS. Reduced tyrosine hydroxylase immunoexpression in the EIEE brains was in the putamen, globus pallidus, and substantia nigra. Tryptophan hydroxylase immunoreactivity was reduced in the three epileptic syndromes, but especially in EIEE. Reduced expression of tyrosine hydroxylase and tryptophan hydroxylase may demonstrate dysfunction of the catecholaminergic and serotonergic neurons. From this study, the lesions in EIEE were widespread, including in the lower brainstem and cerebellum, compared with in EME and WS. Dysfunction of the catecholaminergic and serotonergic systems could be suggested. These characteristic changes may lead to the pathophysiology of EIEE.

Paroxysmal discharges on EEG in young autistic patients are frequent in frontal regions.

EEGs were recorded in 86 autistic patients during sleep. Epileptic discharges were observed in 37 cases (43%). Twenty-seven (73%) of these 37 cases had localized spikes, 8 had multiple spike foci, one had generalized spikes, and one had both multiple spike foci and generalized spikes. Forty-seven epileptic discharge foci were registered in 36 cases, the exception being one with generalized spikes. Thirty-six (76.6%) of the registered 47 epileptic discharge foci were in the frontal region, one (2.1%) in the temporal region, 7 (14.1%) in the centro-parietal region, and 3 (6.4%) in the occipital region. Twenty (55.6%) of the 36 frontal spikes were at midline (11 at Fz and 9 at Cz), 8 on the left side, and 8 on the right side. The dipole of midline spikes was in the deep midline frontal region. These results suggest that frontal dysfunctions are important in the mechanism of symptoms in autism.

Luminol chemiluminescence in unbuffered solutions with a cobalt(II)-ethanolamine complex immobilized on resin as catalyst and its application to analysis.

Using a heterogeneous catalyst, Co(II)-ethanolamine complex sorbed on Dowex-50W resin, the chemiluminescence (CL) of luminol in unbuffered or weakly acidic solution was studied in the presence of H2O2. The maximum luminol CL wavelength at pH 5.7 was 448 nm, 23 nm longer than that in a basic solution (pH 10.5). Three different ligands, mono-, di-, and triethanolamine, and six transition metal ions, Co(II), Cu(II), Ni(II), Mn-(II), Fe(II), and Fe(III) were compared by CL measurements. The CL intensity decreased in the order mono- > di- > triethanolamine and Co(II) > Cu(II) > Ni(II) > Fe-(III) > Mn(II) > Fe(II). This heterogeneous CL system was developed as H2O2 and glucose flow-through sensors. Detection limits (S/N = 3) of H2O2 and glucose using Dowex-50W-X4-Co(II)-monoethanolamine as catalyst are 1 x 10(-7) M and 1 x 10(-6) M, respectively. On the basis of the studies of the CL, fluorescence, UV-vis and ESCA spectra and the effect of dissolved oxygen in luminol solution, a mechanism for CL emission in unbuffered solution was considered as the formation of a superoxide radical ion during the decomposition of H2O2 catalyzed by the Co(II)-ethanolamine immobilized resin. Then the superoxide radical ion acted on luminol and the CL was emitted. The applications of the proposed method to determine H2O2 in rainwater without any special pretreatment and glucose in human urine and orange juice samples give satisfactory results.

Mechanical ventilation care in severe childhood neurological disorders.

Forty-five patients underwent long-term life-sustaining mechanical ventilation care in the Child Neurology Ward, National Center Hospital for Mental, Nervous and Muscular Disorders from 1990 to 2000. Twenty patients had chronic respiratory insufficiency due to neuromuscular disorders, nine of whom underwent home mechanical ventilation care. Nineteen of the 45 patients had chronic respiratory insufficiency due to progressive central nervous system disorders, three of whom underwent home mechanical ventilation care. Six patients with chronic respiratory insufficiency due to the sequelae of transient events were on ventilation, two of whom underwent home mechanical ventilation care. In some patients, especially ones with neuromuscular disorders, mechanical ventilation care is very useful for improving their daily activity and quality of life. In other patients, however, mechanical ventilation care is merely a means of prolonging life without visible improvement of their quality of life. As medical resources are limited, home mechanical ventilation care is a recommended method for patients who need life-sustaining mechanical ventilation care. Considering an individual or social consensus, the indication of long-term life-sustaining mechanical ventilation care for chronic respiratory insufficiency due to severe childhood neurological disorders should be further discussed.

Diagnosis of Alexander disease in a Japanese patient by molecular genetic analysis.

Alexander disease is a leukodystrophy that is neuropathologically characterized by the presence of numerous Rosenthal fibers in astrocytes. Recently, mutations in the gene encoding glial fibrillary acidic protein (GFAP) were identified in patients with Alexander disease. We sequenced the GFAP gene of a Japanese girl who presented with typical symptoms of Alexander disease but in whom the diagnosis was not proven by histopathology. We identified a missense mutation, R239C, which is identical to the mutation previously reported to be most frequent. As was the case in previously described patients, our patient was also heterozygous for the de novo mutation. Interestingly, despite the fact that this is a de novo mutation, R239C was found to be common in different ethnic groups, implying that the site is a "hot spot" for mutagenesis. Molecular genetic analysis now makes the antemortem diagnosis of Alexander disease possible.

Molecular cloning and characterization of mouse Tspan-3, a novel member of the tetraspanin superfamily, expressed on resting dendritic cells.

Dendritic cells (DCs) are the most potent antigen-presenting cells and play an essential role for triggering T-cell-mediated immune responses. In search for novel cell surface molecules expressed on DCs involved in T cell priming by representational differential analysis, we identified a mouse homologue of Tspan-3 (mTspan-3), a novel member of the tetraspanin superfamily. The mTspan-3 consists of four hydrophobic, putative transmembrane regions, forming a small and a large extracellular loop, with short intracellular amino and carboxil tails. Although the mTspan-3 is expressed on a variety of immune cell types including resting DCs, its expression on DCs is downregulated during activation induced by cross-linking CD40 with anti-CD40 monoclonal antibody. These results suggest that mTspan-3 may be involved in the function of DCs in association with T cell stimulation.

NMR structure of the hRap1 Myb motif reveals a canonical three-helix bundle lacking the positive surface charge typical of Myb DNA-binding domains.

Mammalian telomeres are composed of long tandem arrays of double-stranded telomeric TTAGGG repeats associated with the telomeric DNA-binding proteins, TRF1 and TRF2. TRF1 and TRF2 contain a similar C-terminal Myb domain that mediates sequence-specific binding to telomeric DNA. In the budding yeast, telomeric DNA is associated with scRap1p, which has a central DNA-binding domain that contains two structurally related Myb domains connected by a long linker, an N-terminal BRCT domain, and a C-terminal RCT domain. Recently, the human ortholog of scRap1p (hRap1) was identified and shown to contain a BRCT domain and an RCT domain similar to scRap1p. However, hRap1 contained only one recognizable Myb motif in the center of the protein. Furthermore, while scRap1p binds telomeric DNA directly, hRap1 has no DNA-binding ability. Instead, hRap1 is tethered to telomeres by TRF2. Here, we have determined the solution structure of the Myb domain of hRap1 by NMR. It contains three helices maintained by a hydrophobic core. The architecture of the hRap1 Myb domain is very close to that of each of the Myb domains from TRF1, scRap1p and c-Myb. However, the electrostatic potential surface of the hRap1 Myb domain is distinguished from that of the other Myb domains. Each of the minimal DNA-binding domains, containing one Myb domain in TRF1 and two Myb domains in scRap1p and c-Myb, exhibits a positively charged broad surface that contacts closely the negatively charged backbone of DNA. By contrast, the hRap1 Myb domain shows no distinct positive surface, explaining its lack of DNA-binding activity. The hRap1 Myb domain may be a member of a second class of Myb motifs that lacks DNA-binding activity but may interact instead with other proteins. Other possible members of this class are the c-Myb R1 Myb domain and the Myb domains of ADA2 and Adf1. Thus, while the folds of all Myb domains resemble each other closely, the function of each Myb domain depends on the amino acid residues that are located on the surface of each protein.

[Three cases of Costello syndrome presenting with intractable epilepsy and profound psychomotor retardation/regression].

We report three cases of Costello syndrome (CS) presenting with intractable epilepsy and profound psychomotor retardation/regression. Previous reports on CS described mild to moderate psychomotor retardation, and epilepsy in only 8% of the cases. The details of these neurological complications have not been reported so far. All the present cases had intractable epilepsies and profound psychomotor retardation/regression. Two of them had symptomatic localization-related epilepsies and the other had Lennox-Gastaut syndrome following West syndrome. Unusual complication of profound psychomotor retardation/regression in our cases seems to be caused by intractable epilepsy. It should be noted that CS patients with epilepsy may have more severe central nervous symptoms than those previously reported.

[Life-sustaining mechanical ventilation care for children with progressive or degenerative brain disorders].

In the past 10 years, we have treated 25 patients with chronic respiratory insufficiency due to a progressive or degenerative brain disorder. Ten patients died and the other 15 survived. Five of the former and 12 of the latter received life-sustaining mechanical ventilation care. Even in the terminal stage of progressive or degenerative brain disorders, patients can survive for a longer period than previously, if life-sustaining mechanical ventilation care is given. In Japan we do not have a guideline for medical indication or decision-making for children with progressive or degenerative brain disorders. Whenever we see such patients, we have great difficulty in making a decision. It may therefore be necessary to discuss whether we should have such a guideline.

Mitochondrial respiration as an early marker of viability in cardiac-arrested rat lungs.

BACKGROUND: To evaluate the possibility of using pulmonary mitochondrial respiratory functions as early markers of ischemic lung viability in non-heart-beating donors, we investigated the roles of the mitochondria in ischemia-reperfusion injury of cardiac-arrested rat lungs. MATERIALS AND METHODS: Male Lewis rats were exposed to various periods of postmortem warm ischemia (0, 1, and 2 h at 21 degrees C). After a pulmonary artery flush and cold preservation (1 h at 4 degrees C), the rat lungs were reperfused using an isolated rat lung model. Each experimental group consisted of three subgroups (n = 7 in each subgroup) to examine pulmonary functions and biochemical measurements. RESULTS: The pulmonary functions after reperfusion were exacerbated after a 1-h postmortem warm ischemia and worsened after a 2-h warm ischemia following cardiac arrest. The mitochondrial respiratory control ratios already significantly decreased after a 1-h warm ischemia compared with nonischemic rat lungs, at which time the value was almost equivalent to that after a 2-h ischemia. There were no significant changes in the state 3 and 4 respiration of the mitochondria, the pulmonary lactate levels, or the lipid peroxide levels in the lung tissues and mitochondria during the first 1-h period of warm ischemia. The adenine nucleotide levels significantly decreased with the prolongation of the period of warm ischemia, but did not seem to be practical, because their determination required a much longer time than that of the mitochondrial respiratory control ratio. CONCLUSION: These results suggested that the mitochondrial respiratory control ratio may be a useful early marker for lung viability after cardiac arrest.

"Chemical preconditioning" by 3-nitropropionate reduces ischemia-reperfusion injury in cardiac-arrested rat lungs.

BACKGROUND: Chemical preconditioning was defined as the induction of resistance to massive disruption of energy metabolism through prior chemical suppression of oxidative phosphorylation, by which phenomena similar to those resulting from increased ischemic tolerance as a result of ischemic preconditioning can be induced. It could be induced by the inhibitor of either mitochondrial complex I or II. We investigated whether or not chemical preconditioning by 3-nitropropionate (an inhibitor of the mitochondrial complex II) can suppress ischemia-reperfusion injury in cardiac-arrested lungs, which will be the major problem in lung transplants donated from non-heart-beating cadavers. METHODS AND RESULTS: In an isolated rat lung perfusion model with fresh rat blood as perfusate, administration of 3-nitropropionate (20 mg/kg) immediately before the induction of cardiac arrest attenuated pulmonary dysfunction during reperfusion after 1 hr postmortem warm ischemia and 1 hr cold preservation. 3-Nitropropionate administration reduced the mitochondrial respiratory functions (state 3 and state 4 respiration, and the respiratory control ratio) before cardiac arrest and kept them at a lower level of activity than when decreased by ischemia alone. 3-Nitropropionate administration also reduced the ATP levels immediately after drug administration. However, 3-nitropropionate did not significantly reduce lipid peroxidation in the lung tissue and mitochondria. CONCLUSIONS: These results demonstrated that chemical preconditioning by 3-nitropropionate administration immediately before cardiac arrest suppressed succinate-related oxidation during postmortem warm ischemia and reduced ischemia-reperfusion injury in cardiac arrested rat lungs.

Single-photon emission computed tomography of the brain in autism: effect of the developmental level.

Brain single-photon emission computed tomography was performed in 22 autistic and 10 nonautistic disabled patients. The regional cerebral blood flow in both laterotemporal and dorso-medio-lateral frontal areas decreased significantly in the autistic group compared with in nonautistic group. In the autistic group, the regional cerebral blood flow was significantly higher in the right temporal and right parietal lobes than that in the left ones. Inversely, the regional cerebral blood flow in the frontal and occipital lobes was significantly higher on the left side than on the right side. In the nonautistic group, except for in the dorso-medio-lateral frontal lobes (left > right), there was no difference in the regional cerebral blood flow in either cerebrum or cerebellum. A positive correlationship between regional cerebral flow and development quotient (intelligence quotient) was observed in the left laterotemporal and both dorso-medio-lateral frontal areas, and a negative one was observed in the cerebellar vermis area. These results suggest that the regional cerebral blood flow decrease in the temporal and frontal areas relates to not only the brain mechanism of autism reported previously but also intelligence levels.

Siblings of Schwartz-Jampel syndrome with abnormal muscle computed tomographic findings.

Schwartz-Jampel syndrome (SJS) is a disorder characterized by myotonia, joint contractures, skeletal abnormalities, facial dysmorphism and growth retardation. We present two boys of ages 4 and 8 years with SJS. Their clinical, electromyographic and histopathological findings were similar to those described, except for computed tomography (CT) images that revealed diffuse high attenuation in sternocleidomastoid muscles and low attenuation in the paraspinal, quadriceps, sartorius, soleus and gastrocnemius muscles. This is the first report describing abnormal muscle CT findings associated with SJS. Additional studies of muscle CT might help to improve understanding of the pathogenesis of SJS.