Relationship between core temperature and skin blood flux in lower limbs during prolonged arm exercise in persons with spinal cord injury

The purposes of the present study were to examine the response of the skin blood flux (SBF) in the paralyzed lower limbs of persons with spinal cord injury (PSCI) and to clarify the relationship between the SBF and core temperature during prolonged arm exercise. Eight male PSCI with lesions from T6 to L5 and six male control subjects (CS) participated in this study. The subjects rested for 60 min and then performed arm-cranking exercise at 20 W for 30 min at 25 °C. The tympanic membrane temperature (T _ty) and SBF in the anterior thigh (SBFT) and in the posterior calf (SBFC) were continuously measured throughout the experiment. The SBFC did not change in either PSCI or CS during the experiment. The SBFT in four PSCI with high lesions (T6 to T12), remained unchanged during exercise. The SBFT in the other four PSCI with low lesions (T12 to L5, SBFT+) began to elevate markedly when the T t, exceeded a threshold temperature of 36.69 °C. The pattern of increase of SBFT in SBFT+ was similar to that in CS, although onset of the increase in SBFT was delayed and the peak of SBFT during exercise was significantly lower in comparison with the CS. We consider that these differences between the SBFT+ and CS were largely attributable to the lowerT _ty in the former group, which took a prolonged time to reach the threshold of 36.69 °C.     

Plasma brain natriuretic peptide and the evaluation of volume overload in infants and children with congenital heart disease

This study was designed to explore whether it was possible to evaluate the severity of VSD, PDA, and ASD by measuring brain natriuretic peptide (BNP) levels. We also investigated normal BNP levels in children to provide a baseline for our study. We measured BNP levels in 253 normal children, including 11 normal neonates, and in 91 VSD patients, 29 PDA patients, and 34 ASD patients. BNP levels showed no age-related differences in normal children (the mean value: 5.3 +/- 3.8 pg/ml). In the healthy neonates, BNP levels rose from 10.4 +/- 11.9 pg/ml in cord blood to 118.8 +/- 83.2 pg/ml on day 0, then fell to 15.3 +/- 7.8 pg/ml by day 7. In VSD and PDA patients, BNP levels correlated significantly with Qp/Qs, LVEDV, and peak RVP/LVP. In ASD patients, BNP levels correlated with Qp/Qs and RVEDV. Especially, in VSD patients, as an index corresponding to 1.5-2.0 of the Qp/Qs ratio, BNP levels of 20-35 pg/ml were found to be best with regard to both sensitivity and specificity. In the healthy neonates, BNP levels changed rapidly after birth. In VSD, PDA, and ASD patients, BNP levels were well-correlated with the severity of the disease. Especially, in VSD patients, it that appears BNP levels may be useful in evaluating surgical indications, with 20-35 pg/ml levels being the appropriate cut-off value.     

Lack of aberrations of the BMP4, BMP2, and PTX1 genes in a patient with pituitary hypoplasia,os odontoideum,renal dysplasia,and right leg anomalies

Hepatitis C virus (HCV) has been linked to extrahepatic manifestations such as oral lichen planus (OLP). In addition, anticardiolipin antibodies (aCL) and cryoglobulin have been demonstrated in chronic hepatitis C. The aim of this study was to investigate these prevalences in patients with HCV-associated OLP. The prospective study investigated the role of these factors in 133 subjects: 28 with OLP-HCV(+) (group 1), 22 with OLP-HCV(-) (group 2), 33 without OLP-HCV(+) (group 3), and 50 healthy volunteers matched for age and sex served as control group (group 4). Levels of immunoglobulin G (IgG) and IgM aCL antibodies, and cryoglobulin in serum were evaluated by enzyme-linked immunosorbent assay. The prevalence of aCL in groups 1, 2, 3, and 4 were 32.1, 18, 36.3, and 8%, respectively. The positive rate of aCL was significantly higher in groups 1 and 3 than that in the control group (group 1; p=0.02 vs. the control group, group 3; p<0.01 vs. the control group). There were no significant differences in cryoglobulin among the groups. The findings of the present study showed a high prevalence of IgG and IgM aCL in the serum of patients with HCV infectious diseases. A positive factor for aCL was determined by age, sex, the presence of OLP, and HCV infection.     

Prostaglandin F(2alpha), cytokines and cyclic mechanical stretch augment matrix metalloproteinase-1 secretion from cultured human uterine cervical fibroblast cells

Human uterine cervical tissue is composed mainly of fibroblast cells and the extracellular matrix in which collagen types I and III predominate. It is hypothesized that these collagens are degraded by matrix metalloproteinases (MMPs) in the initial step of uterine cervical ripening during parturition. Among the MMPs, MMP-1, -8 and -13 have substrate selectivity for collagen types I and III. In the present study, we examined the regulation of MMP-1 secretion from the human uterine cervix. Immunohistochemistry detected strong staining of MMP-1, but not of MMP-8 or -13, in stromal cells of the pregnant uterine cervix. The MMP-1 expression in the pregnant uterine cervix was further confirmed by Western blot analysis and RT-PCR. To clarify the regulation of MMP-1 production, we subsequently investigated the effects of prostaglandins, inflammatory cytokines and cyclic mechanical stretch on the secretion of MMP-1 from cultured human uterine cervical fibroblast cells. Treatment with prostaglandin (PG)F(2alpha) (10(-7) to 10(-5) mol/l) or interleukin (IL)-1alpha (0.01-1.0 ng/ml) or stimulation with cyclic mechanical stretch increased MMP-1 secretion from cultured human uterine cervical fibroblast cells, with maximal increases of 3.4-, 4.5- and 1.9-fold respectively (24 h of treatment, P < 0.05 for all comparisons). These data suggest that MMP-1 may play a significant role in the degradation of extracellular collagen types I and III in the pregnant uterine cervix during the process of cervical ripening, in response to various stimulations such as PGF(2alpha), IL-1alpha and mechanical stretch.     

Effect of ethanol treatment on metabolic activation and detoxification of esophagus carcinogenic N-nitrosamines in rat liver

In order to elucidate the mechanism underlying enhancement by ethanol of N-nitrosodiethylamine (DEN)- and N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in rats, hepatic levels of cytochrome P-450 (CYP) enzymes, mutagenic activation of several N-nitrosamines and three kinds of UDP-glucuronyltransferase (UDPGT) activities were assayed in F344 rats. Immunoblot analyses of microsomal CYP proteins revealed induction of CYP2E1 (approximately 2-fold), but not CYP2B1/2, 1A1/2 or 3A2, by treatment with 10% ethanol in the drinking water for 2 weeks. In contrast, s.c. treatment with 0.5 mg/kg NMBA three times per week for 2 weeks produced no significant alterations in the levels of these CYP species. Ethanol treatment also elevated the mutagenic activities of N-nitrosodimethylamine (DMN), DEN and N-nitrosopyrrolidine (NPYR) in strain TA100 up to 2.1-, 1.6- and 2.3-fold above each control, respectively. However, this was not the cases for four N-nitrosamines, including NMBA, in strain TA100 and two heterocyclic amines and aflatoxin B(1) in strain TA98. In addition, ethanol did not affect UDPGT activities towards 4-nitrophenol, bilirubin and testosterone. Hepatic CYP species responsible for mutagenic activation of selected N-nitrosodialkylamines were confirmed by use of specific CYP inducers and inhibitors with the liver from F344 and Wistar rats, indicating that DMN, DEN and NMBA are selectively activated by CYP2E1, predominantly by CYP2E1 with a slight contribution by CYP2B2 and selectively by CYP2B1/2, respectively. These results demonstrate that ethanol exerts an enhancing effect on mutagenic activation by CYP2E1 of DMN, DEN and NPYR, but does not affect that of NMBA and the other carcinogens by CYP2B1/2, 1A1/2 and 3A2 and UDPGT1A1, 1A6 and 2B1 activities. Consequently, this suggests that enhancement by ethanol of DEN-induced esophageal carcinogenesis in F344 rats can be attributed to an increase in hepatic activation during the initiation phase, but that of NMBA-induced tumorigenesis is not attributable to metabolic activation and inactivation via glucuronidation in liver.     

Effects of fluoride release from bis-GMA/TEGDMA resin regulated by gamma-methacryloxypropyltrimethoxysilane on demineralization of bovine enamel

We previously demonstrated that fluoride release from resins could be regulated by the polysiloxane coating of the fluoride additives. The present study investigated the effects of regulated fluoride release from resin on enamel demineralization in vitro. Bovine enamel cavities were restored with bis-GMA/TEGDMA resins containing 50 wt% NaF powders treated with or without gamma-methacryloxypropyltrimethoxysilane. Specimens were immersed in distilled water that was changed daily to measure the amount of fluoride released over 40 days, and thereafter subjected to pH-cycling. Microradiographic observations were performed to determine total mineral loss (AZ) and lesion depth (Ld) on the enamel. In addition, fluorine distribution was analyzed using EPMA. The resin containing untreated NaF exhibited high-rate and short-term fluoride release, whereas the resin containing treated NaF released low concentrations of fluoride over a longer period. The former showed high fluorine uptake in the adjacent enamel. In contrast, the latter showed high fluorine uptake not only in the adjacent enamel, but also in a wider area of enamel surface. The latter also showed lower AZ and Ld values in the surrounding enamel, indicating a high inhibitory effect on caries formation. Therefore, it is suggested that regulated fluoride release from the resin based on polysiloxane coating is effective in preventing caries formation.     

Cytomegalovirus infections following umbilical cord blood transplantation using reduced intensity conditioning regimens for adult patients.

Cytomegalovirus (CMV) infection is a major complication after allogeneic hematopoietic stem cell transplantation (Allo-HSCT); however, we have little information on the clinical features of CMV reactivation after cord blood transplantation using reduced-intensity regimens (RI-CBT) for adults. We reviewed medical records of 140 patients who underwent RI-CBT at Toranomon Hospital between January 2002 and March 2005. All the patients were monitored for CMV-antigenemia weekly, and, if turned positive, received preemptive foscarnet or ganciclovir. Seventy-seven patients developed positive antigenemia at a median onset of day 35 (range, 4-92) after transplant. Median of the maximal number of CMV pp65-positive cells per 50,000 cells was 22 (range, 1-1806). CMV disease developed in 22 patients on a median of day 35 (range, 15-106); 21 had enterocolitis and 1 had adrenalitis. CMV antigenemia had not been detected in 2 patients, when CMV disease was diagnosed. CMV disease was successfully treated using ganciclovir or foscarnet in 14 patients. The other 8 patients died without improvement of CMV disease. In multivariate analysis, grade II-IV acute graft-versus-host disease was a risk factor of CMV disease (relative risk 3.48, 95% confidential interval 1.47-8.23). CMV reactivation and disease develop early after RI-CBT. CMV enterocolitis may be a common complication after RI-CBT.     

Cytoskeletal modulation of the response to mechanical stimulation in human vascular endothelial cells

Possible interactions of cytoskeletal elements with mechanically induced membrane currents and Ca²⁺ signals were studied in human endothelial cells by using a combined patch-clamp and Fura II technique. For mechanical stimulation, cells were exposed to hypotonic solution (HTS). The concomitant cell swelling activates a Cl^– current, releases Ca²⁺ from intracellular stores and activates Ca²⁺ influx. To interfere with the cytoskeleton, cells were loaded either with the F-actin-stabilizing agent phalloidin (10 mol/l), or the F-actin-depolymerizing substance cytochalasin B (50 mol/l). These were administered either in the bath or the pipette solutions. The tubulin structure of the endothelial cells was modulated by taxol (50 mol/l), which supports polymerization of tubulin, or by the depolymerizing agent colcemid (10 mol/l) both applied to the bath. Immunofluorescence experiments show that under the chosen experimental conditions the cytoskeletal modifiers employed disintegrate the F-actin and microtubuli cytoskeleton. Neither of these cytoskeletal modifiers influenced the HTS-induced Cl^– current. Ca²⁺ release was not affected by cytochalasin B, taxol or colcemid, but was suppressed if the cells were loaded with phalloidin. Depletion of intracellular Ca²⁺ stores by thapsigargin renders the intracellular [Ca²⁺] sensitive to the extracellular [Ca²⁺], which is indicative of a Ca²⁺ entry pathway activated by store depletion. Neither cytochalasin B nor phalloidin affected this Ca²⁺ entry. We conclude that F-actin turnover or depolymerization is necessary for Ca²⁺ release by mechanical activation. The tubulin network is not involved. The Ca²⁺ release-activated Ca²⁺ entry is not modulated by the F-actin cytoskeleton.     

Early induction of neuronal lipocalin-type prostaglandin D synthase after hypoxic-ischemic injury in developing brains

Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is up-regulated in oligodendrocytes (OLs) in mouse models for genetic neurological disorders including globoid cell leukodystrophy (twitcher) and GM₁ and GM₂ gangliosidoses and in the brain of patients with multiple sclerosis. Since L-PGDS-deficient twitcher mice undergo extensive neuronal death, we concluded that L-PGDS functions protectively against neuronal degeneration. In this study, we investigated whether L-PGDS is also up-regulated in acute and massive brain injury resulting from neonatal hypoxic-ischemic encephalopathy (HIE). Analysis of brains from human neonates who had died from HIE disclosed that the surviving neurons in the infarcted lesions expressed L-PGDS. Mouse models for neonatal HIE were made on postnatal day (PND) 7. Global infarction in the ipsilateral hemisphere was evident at 24 h after reoxygenation in this model. Intense L-PGDS immunoreactivity was already observed at 10 min after reoxygenation in apparently normal neurons in the cortex, and thereafter, in neurons adjacent to the infarcted area. Quantitative RT-PCR revealed that the L-PGDS mRNA level of the infarcted hemisphere was 33-fold higher than that of the sham-operated mouse brains at 1 h after reoxygenation and that it decreased to the normal level by 24 h thereafter. Furthermore, in both human and mouse brains, many of L-PGDS-positive cells were also immunoreactive for p53; and some of these expressed cleaved caspase-3. The expression of L-PGDS in degenerating neurons implies that L-PGDS functions as an early stress protein to protect against neuronal death in the HIE brain.     

Neural fibrolipoma of the superficial peroneal nerve in the ankle: a case report with immunohistochemical analysis

This report presents a case of neural fibrolipoma arising from the superficial peroneal nerve in the ankle. A 28-year-old woman was referred with a soft tissue mass in the anterior aspect of the right ankle, which had been gradually enlarging for the past 10 years. Magnetic resonance imaging showed a mass lesion, measuring approximately 8 x 3 x 2 cm, with high to partially low signal intensity on both T1- and T2-weighted images. A band of low signal intensity within the lesion, which is indicative of coexistence with the tumor and the superficial peroneal nerve, could be detected on both T1- and T2-weighted images. The patient underwent an excisional biopsy. The specimen microscopically consisted of nerve bundles and fibro-fatty proliferation with abundant collagen fibers. Immunoreactivity for CD34 antigen antibody was detected in fibrous spindle cells. This is the first report to present an immunohistochemical profile of neural fibrolipoma. Neural fibrolipoma should be considered as a differential diagnosis when a lipomatous lesion is encountered in the foot or ankle as well as in the upper extremities.