CSF hypocretin-1 (orexin-A) levels in childhood narcolepsy and neurologic disorders.
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Adolescent↗
Biomedical subjects
T Shimizu
Publications and source records attributed to T Shimizu.
Expression of Notch in a case of osteosarcoma of the maxilla.
In this immunohistochemical examination, the expression of Notch1 peptide was detected in neoplastic cells in a case of osteosarcoma of the maxilla of a 31-year-old Indonesian male patient. Notch1 peptide appeared in the cytoplasm of neoplastic cells of comparatively well-differentiated areas of the osteosarcoma, an osteoblastic area containing osteoid and/or immature bone tissues. The results suggest that Notch1 is closely related to cytological differentiation or acquisition of cytological characteristics in neoplastic cells of osteosarcoma.
Adult↗
The dural tail of intracranial meningiomas on fluid-attenuated inversion-recovery images.
We evaluated the "dural tail" associated with 48 intracranial meningiomas on fluid-attenuated inversion-recovery (FLAIR) and contrast-enhanced T1-weighted images. In 30 (62.5%), a dural tail was observed on contrast-enhanced T1-weighted images, and thickening of the dura mater and abnormal signal were identified in the corresponding region on FLAIR images. Thus, FLAIR imaging was useful for showing dural abnormality associated with meningiomas without the needed for contrast medium.
Adult↗
N10 component in median nerve somatosensory evoked potentials (SEPs) is not an antidromic motor potential.
OBJECTIVE: To test the hypothesis that the N10 far-field potential in median nerve somatosensory evoked potentials is generated by the motor axons by examining patients with amyotrophic lateral sclerosis (ALS). METHODS: Subjects were 5 ALS patients showing pronounced or complete denervation of median-innervated small hand muscles. We evaluated N10 over scalp, and proximal plexus volleys (PPVs) at lateral or anterior cervical electrode. RESULTS: N10 and PPVs were definitely preserved for every ALS subject. N10 amplitudes of ALS subjects were even significantly larger than control subjects. In one ALS patient completely lacking motor axons, N10 was larger than the largest one among control subjects. CONCLUSIONS: Present results clearly indicate that N10 is not predominantly generated by motor axons but by the whole median nerve dominated by sensory axons. We propose a theory that N10 is a junctional potential generated by the entrance of the median nerve into bone at the intervertebral foramen, producing a positive pole at the non-cephalic reference electrode. Significantly larger N10 in ALS subjects may be due to the lack of cancellation by slower motor axons. SIGNIFICANCE: The hypothesis that N10 is generated by motor axons is refuted, and a new theory of its generation is presented.
Aged↗
Spaceflight alters the fiber composition of the aortic nerve in the developing rat.
Hydrostatic pressure gradients due to the gravitational force in blood vessels disappear under conditions of microgravity during spaceflight, and the ability of the baroreceptor reflex to control arterial pressure and blood distribution may be altered. We hypothesized, on the basis of the results obtained in our previous experiments using the head-down tilt method in rats and rabbits, that the range of increase in arterial pressure caused by animal behavior narrows under conditions of microgravity, affecting the development of high-threshold unmyelinated fibers in the rat aortic nerve which sends signals from baroreceptors located in the aortic wall to the reflex center. We verified this hypothesis using 9-day-old rat neonates housed with their dams for 16 days on the space shuttle Columbia in outer space (STS-90, Neurolab Mission). Age-matched neonatal rats with the dams remained on the ground as controls. After breeding was carried out in the three experimental groups (FLT, spaceflight; AGC, asynchronous ground control; VIV, vivarium ground control), specimens of the 25-day-old rats were excised and five left aortic nerves in each group were examined by electron microscopy. The number of aortic unmyelinated fibers was significantly less in the FLT group than in each ground control (mean+/-S.D.; 139+/-37 in the FLT, 207+/-36 in the AGC, 283+/-121 in the VIV; P<0.05), which may be related to the weakness of the baroreceptor reflex under conditions of microgravity in space. This result may contribute to understanding of the several cardiovascular issues which occur under microgravity and after reexposure to gravity in human.
Analysis of Variance↗
A Japanese patient with distal myopathy with rimmed vacuoles: missense mutations in the epimerase domain of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene accompanied by hyposialylation of skeletal muscle glycoproteins.
Hereditary inclusion body myopathy and distal myopathy with rimmed vacuoles are both caused by mutations of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. Here we report a Japanese patient with compound heterozygous missense mutations in the epimerase domain of GNE gene, 89 G to C and 578 A to T. Biochemical analysis demonstrated decreased reactivity of skeletal muscle glycoproteins with the lectins recognizing sialic acid residues. The results suggest that hyposialylation of glycoproteins may be involved in the pathogenesis of muscle dysfunction in this patient.
Adult↗
Efficacy of IgM anti-blood type antibody monitoring by enzyme-linked immunosorbent assay after renal transplantation across the blood barrier: high-dose immunoglobulin administration blocks IgM rather than IgG anti-blood type antibodies.
We used an enzyme linked immunosorbent assay (ELISA) to investigate the presence of subtypes of anti-blood-type antibodies in patients with biopsy-proven humoral rejection after ABO-incompatible renal transplantation. High agglutinin IgG and IgM anti-blood type antibodies from 12 ABO-incompatible recipients with vascular rejection were separately assessed using an ELISA. Patients who exhibited excellent renal function despite high agglutinin titers of anti-blood-type antibodies(n = 8) were also examined. All 12 rejection patients exhibited highly elevated titers of IgG and IgM, while the eight stable patients exhibited only slightly elevated IgG titers, but not IgM. IgG and IgM titers did not change after plasmapheresis and steroid pulse therapy, whereas IVIg treatment significantly blocked both IgG and IgM, with IgM being blocked to a larger extent than IgG. Blocking of IgM seems to play an important role in improving ABO-incompatible grafts.
Antibodies, Anti-Idiotypic↗
Impact of positive PRA on the results of ABO-incompatible kidney transplantation.
INTRODUCTION: Due to the continuing shortage of cadaveric donors in Japan, ABO-incompatible living kidney transplantation (LKT) is being performed. It is well known that highly sensitized patients with positive panel reactive antibodies (PRA) often present with acute rejection. Therefore, we examined the impact of a positive PRA on the results of ABO-incompatible LKT. MATERIALS AND METHODS: One hundred seventy-seven recipients underwent ABO-incompatible LKT between January 1989 and March 2003. Of these patients, 37 who had been examined for PRA before transplantation were included in this study. There were 25 men and 12 women of mean age 37.3 years. Plasmapheresis was performed to remove anti-ABO antibodies before transplantation. During the induction phase, methylprednisolone, azathioprine, or mycophenolate mofetil and cyclosporine or tacrolimus were used for immunosuppression. Splenectomy was performed at the time of kidney transplantation in all patients. PRA was measured using FlowPRA by flow cytometer. RESULTS: Eight of the 37 patients had a positive PRA before transplantation (class I, 5; class II, 1; class I and class II, 2). The incidence of acute rejection was 37.9% in the patients with a negative PRA and 37.5% in patients with a positive PRA. One patient with a negative PRA and one patient with a positive PRA lost grafts due to acute rejection. CONCLUSIONS: Positive PRA may not increase the incidence of acute rejection in ABO-incompatible LKT because plasmapheresis and splenectomy are performed to eliminate anti-ABO antibody.
ABO Blood-Group System↗
Analysis of cause of death with a functioning graft: a single-center experience.
INTRODUCTION: After the introduction of new immunosuppressants, such as tacrolimus and mycophenolate mofetil, we have achieved excellent results for kidney transplantation with a low acute rejection rate. Currently, nonimmunological factors are considered to be the main cause of graft loss for long-term transplant patients. In this study, we analyzed the cause of death with a functioning graft. PATIENTS AND METHODS: We performed 1375 cases of living kidney transplantation (LKT) and 219 cases of cadaveric kidney transplantation (CKT) between January 1983 and December 2002. Of these patients, 86 LKT patients and 19 CKT patients died with a functioning graft. RESULTS: The mean duration of graft function was 4.8 +/- 4.5 years. The incidence of the causes of death were: infection, 24%; stroke, 17%; cardiovascular disease, 16%; malignant disease, 15%; hepatic failure, 11%; gastric ulcer, 4%; and accident/suicide 2%. Five- and 10-year graft survivals for LKT were 80.2 and 62.0%, respectively. The corresponding values for patients (with the exception of the patients who died with a functioning graft) was 83.0% and 66.1%, respectively. The 5- and 10-year graft survival rates for cadaveric kidney transplants were 70.8% and 48.9%, respectively. The corresponding values for patients (with the exception of the patients who died with a functioning graft) were 75.3% and 52.6%, respectively. CONCLUSION: To prevent death with a functioning graft, management of vascular disorders such as stroke and cardiovascular disease, malignant disease, and infectious disease is crucial for kidney transplant patients.
Adult↗
Impact of HLA-identity on results of ABO-incompatible living kidney transplantation.
INTRODUCTION: Due to the continuing shortage of cadaveric donors in Japan, ABO-incompatible living kidney transplantation is being performed. Our previous studies showed that the long-term graft survival in ABO-incompatible living kidney transplantation was comparable to that in ABO-compatible living kidney transplantation. However, the impact on HLA-identity on the results of ABO-incompatible living donor kidney transplantation had not been investigated previously. MATERIALS AND METHODS: One hundred twenty-seven recipients underwent ABO-incompatible living kidney transplantation between January 1989 and December 2000. Five were grafted from HLA-identical sibling donors group (I). The remaining 122 recipients received grafts from an HLA-nonidentical donor (group N). Both groups were similar in terms of recipient age, donor age, warm ischemic time, and total ischemic time. Three or four sessions of plasmapheresis were performed prior to transplantation. Cyclosporine or tacrolimus, methylprednisolone, and azathioprine or mycophenolate mofetil were used for immunosuppression. Splenectomy was done at the time of kidney transplantation in all patients. RESULTS: Graft loss was seen in one of the five HLA-identical recipients due to chronic rejection. Five- and 10-year graft survival rates were 80.0% I vs 72.0% N, and 80.0% I vs 54.2% N, respectively. The incidence of acute rejection in the HLA-identical recipients was lower than that in the HLA-nonidentical recipients (20% I vs 67.2% N). In conclusion, long term graft survival among ABO-incompatible kidney transplants from HLA-identical sibling donors was much better than that from HLA-nonidentical sibling donors.
ABO Blood-Group System↗
Retroperitoneoscopic live donor nephrectomy: extended experience in a single center.
INTRODUCTION: Retroperitoneoscopic live donor nephrectomy (RPLDN) was performed because it is considered to be less invasive than open live donor-nephrectomy (OLDN) or transperitoneal laparoscopic live donor nephrectomy. PATIENTS AND METHODS: Between July 2001 and May 2003, 118 consecutive live donor kidney grafts were procured using RPLDN or OLDN. The patients who underwent RPLDN were divided into 2 groups: an initial group 1 (n = 38) and a subsequent group 2 (n = 48).Thirty-two patients who underwent OLDN during the same period were used as controls (group 3). The patients were placed in the lateral position. Three retroperitoneoscopic ports were inserted. The kidneys were retrieved through a 5-cm flank incision just below the 11th rib in group 1. In group 2, a 5-cm Pfannenstiel incision was used to extract the kidney. RESULTS: The operative time was 307 +/- 88 minutes, 245 +/- 42 minutes, and 215 +/- 70 minutes in groups 1, 2, and 3, respectively (group 1 vs group 2 or 3, P < .01). The mean postoperative pentazocine (painkiller) requirements were 12 mg, 4.4 mg, and 22 mg in groups 1, 2, and 3, respectively (group 2 vs group 1 or 3, P < .01). The hospital stay was 6.6 +/- 1.6, 4.9 +/- 0.7, and 7.0 +/- 0.1 days in groups 1, 2, and 3, respectively (group 2 vs group 1 or 3, P < .01). There were no serious complication, such as massive bleeding or bowel injury. CONCLUSIONS: RPLDN may be safer and less invasive than open donor nephrectomy.
Humans↗
Comparative roles of macrophages and NK cells in the host innate resistance of mice to Mycobacterium fortuitum infection.
OBJECTIVES: Profiles of host innate resistance to Mycobacterium fortuitum (MFT) infection in mice and the roles of macrophages (Mphis) and NK cells in host resistance to MFT infection were studied. METHODS: MFT-infected mice with or without the treatments to reduce Mphis and NK cells were examined for survival and the bacterial loads in the kidneys during the course of infection. RESULTS: A unique profile of strain difference was found in the innate resistance of mice to MFT. A/J, C3H/He and DBA/2 mice were susceptible, while BALB/c, B10A and C57BL/6 mice were resistant, in terms of survival after MFT infection. Such profiles of host resistance to MFT were essentially correlated with the ability of individual strain mice to prevent the bacterial growth in the early periods after infection. These profiles were different from the strain difference controlled by Bcg gene. Studies using carrageenan, anti-asialo GM1 antibody, and NK cell-deficient beige mice indicated the important roles of Mphis and NK cells in the host innate defense against MFT. CONCLUSIONS: These findings suggest that Bcg gene does not control the host resistance to MFT and that both Mphis and NK cells play crucial roles in the host innate resistance to MFT infection.
Animals↗
Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice.
Fragile X syndrome (FXS) is the most common single gene (FMR1) disorder affecting cognitive and behavioral function in humans. This syndrome is characterized by a cluster of abnormalities including lower IQ, attention deficits, impairments in adaptive behavior and increased incidence of autism. Here, we show that young males with FXS have profound deficits in prepulse inhibition (PPI), a basic marker of sensorimotor gating that has been extensively studied in rodents. Importantly, the magnitude of the PPI impairments in the fragile X children predicted the severity of their IQ, attention, adaptive behavior and autistic phenotypes. Additionally, these measures were highly correlated with each other, suggesting that a shared mechanism underlies this complex phenotypic cluster. Studies in Fmr1-knockout mice also revealed sensorimotor gating and learning abnormalities. However, PPI and learning were enhanced rather than reduced in the mutants. Therefore, these data show that mutations of the FMR1 gene impact equivalent processes in both humans and mice. However, since these phenotypic changes are opposite in direction, they also suggest that murine compensatory mechanisms following loss of FMR1 function differ from those in humans.
Acoustic Stimulation↗
Cytokines in the gastric mucosa of children with Helicobacter pylori infection.
AIM: Few studies have looked at the cytokine profile in gastric mucosa in children with Helicobacter pylori infection. This study investigated cytokines and their effects on histological abnormalities in the gastric mucosa of children with H. pylori infection. METHODS: The levels of interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and IL-8 proteins were measured in biopsy specimens from the gastric antrum and corpus of children with H. pylori infection, and related to inflammatory cell infiltrations. RESULTS: The antral and corporal mucosal levels of IFN-gamma and IL-8 proteins were significantly higher in children with H. pylori infection than in uninfected children, but there was no such difference in the levels of IL-4 protein. The antral mucosal level of IL-8 protein was significantly higher than the corporal mucosal level of IL-8 protein in the infected children. Inflammatory cell infiltration was significantly higher in the infected children than in the uninfected children, but there were no significant correlations between mucosal cytokine levels and inflammatory cell infiltrations. CONCLUSION: The results suggest that the predominant Th1 cytokine response and enhanced IL-8 production in the mucosa may be involved in the gastric inflammation seen in children infected with H. pylori, as well as in adult patients.
Adolescent↗
A case of interstitial granulomatous drug reaction due to sennoside.
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Anthraquinones↗
Cetirizine, an H1-receptor antagonist, suppresses the expression of macrophage migration inhibitory factor: its potential anti-inflammatory action.
BACKGROUND: H1-receptor antagonists are often effective in the treatment of allergic disorders such as atopic dermatitis. Cetirizine, a putative H1-receptor antagonist, has recently been shown to have anti-inflammatory properties through the inhibition of leucocyte recruitment and activation, and by the reduction of ICAM-1 expression on keratinocytes. OBJECTIVE: To further elucidate the anti-inflammatory properties of cetirizine, we first examined its effects on antigen-induced eosinophilia and neutrophila in vivo. We then examined the anti-inflammatory effects of cetirizine on a human keratinocyte A431cell line. METHODS: Mice were sensitized subcutaneously with ragweed pollen and were challenged intraperitoneally with the allergen. Cetirizine diluted in sterile water (0-20 mg/kg) or only sterile water was administered orally. Peritoneal cells were obtained at 8 and 24 h after challenge. The eosinophilia and neutrophilia induced by ragweed pollen extract were quantitated. Macrophage migration inhibitory factor (MIF), macrophage inflammatory protein 2 (MIP-2) and eotaxin contents of peritoneal fluid were also measured by mouse ELISA. The effects of cetirizine on MIF-induced IL-8 production in A431 cells were examined by ELISA. The effects of cetirizine on MIF expression and production in A431 cells were examined by human MIF ELISA and Northern blot analysis. RESULTS: Eosinophilia and neutrophilia induced by ragweed pollen extract were found to be significantly reduced in cetirizine-treated mice (20 mg/kg). MIF, a pleuripotent cytokine, was significantly decreased at 8 and 24 h in the peritoneal fluid by cetirizine treatment. MIP-2 and eotaxin were also decreased 8 and 24 h, respectively, after challenge in the peritoneal fluid with cetirizine treatment. MIF stimulates IL-8 production in A431 cells. We found that MIF production in A431 cells was inhibited by 10 microm cetirizine. Consistent with this, cetirizine significantly inhibited MIF-induced IL-8 production. CONCLUSION: These results suggest that cetirizine exerts its anti-inflammatory effects by inhibiting MIF as well as IL-8 production, such as those involved in inflammatory allergic skin disease, suggesting a broad spectrum of action beyond its mere H1-receptor-antagonistic function.
Allergens↗
The role of B7 molecules in the cell contact-mediated suppression of T cell mitogenesis by immunosuppressive macrophages induced with mycobacterial infection.
We found previously that immunosuppressive macrophages (Mphis) induced by Mycobacterium intracellulare infection (MI-Mphis) transmitted their suppressor signals to target T cells through cell contact with target T cells. In this study, we examined what kinds of Mphi surface molecules are required for such cell-to-cell interaction. First, it was found that a B7-1-like molecule (B7-1LM) recognizable with one of three test clones of anti-B7-1 monoclonal antibodies (mAbs) was required for expression of the Mphi suppressor activity. Neither anti-B7-2, anti-ICAM-1, nor anti-VCAM-1 mAb blocked the Mphi suppressor activity. Second, MI-Mphis increased the expression of B7-1LM in parallel with the acquisition of the suppressor activity. Moreover, MI-Mphis bound with target T cells in a B7-1LM-dependent fashion. Third, mAb blocking of CTLA-4 on target T cells did not reduce the suppressor activity of MI-Mphis, suggesting the role of a putative molecule on target T cells other than CTLA-4 as the receptor for B7-1LM of MI-Mphis. Fourth, concanavalin A (Con A) stimulation of MI-Mphis was needed for effective cell contact with target T cells and subsequent expression of the suppressor activity of MI-Mphis. Fifth, the Con A-induced increase in the suppressor activity of MI-Mphis was inhibited by KN-62 but not by herbimycin A, H-7, nor H-88, indicating that Con A-induced up-regulation of MI-Mphi function is mediated by calmodulin-dependent protein kinase II or ATP/P2Z receptors, but independent of protein tyrosine kinase, protein kinase C, and protein kinase A. These findings indicate that a B7/CTLA-4-independent mechanism is needed for the transmission of the suppressor signals from MI-Mphis to target T cells.
Animals↗
Histological analysis of late renal allografts of antidonor antibody positive patients with C4d deposits in peritubular capillaries.
The association of humoral immunity with late renal allograft dysfunction has recently been recognized, and many reports have revealed C4d deposits in peritubular capillaries (C4d in PTC), and the presence of serum antidonor HLA antibody in patients suffering from graft dysfunction, long time after transplantation. In this study, morphological changes in renal allograft biopsies more than 1 year after transplantation in 14 patients with C4d in PTC and serum antidonor antibody were investigated for the presence of chronic rejection (CR). In addition to the light microscope study, an electron microscope study was done to evaluate the multilayering of the peritubular capillary basement membrane (MLPTC). Histologically, only seven of 14 patients met the criteria of CR, and 71.4% (5/7) of CR patients had episodes of acute humoral rejection (AHR), coexisting with acute tubulointerstitial rejection. Peritubular capillaritis was observed in all patients, although it differed in severity. Transplant glomerulitis and interstitial inflammation were also observed in many patients: 71.4% (10/14) and 92.9% (13/14) respectively. MLPTC was observed in 12 patients (85.7%), but the severity of the MLPTC did not reflect the severity of peritubular capillaritis or any other histological features. The long-term outcomes of the patients CR, especially those with episodes of AHR, were poor, and two of them lost their graft functions. On the other hand, patients without CR had relatively favourable outcomes. In conclusion, we confirmed the diverse morphological changes of late renal allografts, which cannot be categorized as chronic humoral rejection (CHR), and such patients who do not have typical morphological changes such as CHR, should be followed-up on a long-term basis in order to clarify the significance of C4d on PTC in late renal allografts.
Adolescent↗