Spinal epidural lipomatosis in children with renal diseases receiving steroid therapy

Spinal epidural lipomatosis (SEL) in patients on steroid therapy may be explained by two hypotheses: (1) steroids induce SEL and (2) steroids cause the growth of a pre-existing SEL, especially in obese children. Steroid-induced SEL (SSEL) is rarely described in children, with only six cases reported elsewhere. However, we have already reported four nephrotic children with SSEL, including one child in another hospital, in addition to the six cases. We investigated the frequency of SSEL in 125 children with renal diseases treated with glucocorticoids in a single hospital over 16 years, and examined the risk factors in 62 patients with SSEL reported in the literature. When patients complained of symptoms at the early stage of SSEL, i.e., back pain or numbness, and patients were obese, we performed spinal magnetic resonance imaging (MRI). SSEL was detected in 5 of 125 children (4.0%). Of the 5 patients with SSEL, 3 had vertebral compression fractures, and all 5 patients were on methylprednisolone pulse therapy. Our study suggests that many more patients can be detected at the early stage of SSEL by performing spinal MRI for patients with early symptoms, obesity, and those who have received methylprednisolone pulse therapy.     

Evaluation of ischemic heart disease on a 1.5 Tesla scanner: combined first-pass perfusion and viability study

PURPOSE: We implemented a fast gradient echo (GRE) sequence with an echo-planar imaging (EPI) read-out (FGRE-ET) to conduct myocardial perfusion studies on a conventional scanner. The accuracy of combined perfusion and viability studies is evaluated in comparison with coronary angiography (CAG). MATERIALS AND METHODS: We enrolled 33 patients suspected of having coronary artery disease in this study. Short-axis perfusion images of the left ventricles were acquired following intravenous bolus injection of gadolinium-DTPA (0.05 mml/kg), both after myocardial loading by dipyridamole (0.56 mg/kg) and at rest. Viability studies were obtained using an inversion-recovery FGRE sequence. Radiologists performed blinded film readings. The findings with perfusion and the viability studies were compared with CAG on a segment-to-segment basis corresponding to the coronary arteries' territories. Stenosis equal to or greater than 75% in diameter was considered significant on CAG. The results were also compared with single photon emission computed tomography (SPECT) in 23 patients. RESULTS: The combination of perfusion and viability studies showed 85.7% sensitivity, 88.9% specificity, and 87.2% accuracy in comparison with CAG. SPECT revealed respective rates of 71.7%, 78.3%, and 73.9% in 23 patients of this group. CONCLUSION: Myocardial perfusion studies using FGRE-ET were feasible and accurate, even on a conventional scanner.     

PKC412 induces apoptosis through a caspase-dependent mechanism in human keloid-derived fibroblasts

There is no established pharmacological therapy for skin keloids, a wound healing disorder. In this study, we investigated the effect of N-benzoyl staurosporine (PKC412), a protein kinase C inhibitor, on human keloid-derived fibroblasts to examine whether this agent is applicable for the treatment of keloid formation. Although PKC412 induced apoptosis in keloid fibroblasts in a time- and dose-dependent manner, the effective concentration of this agent was much higher than that of staurosporine. Western blotting showed that both PKC412 (10 microM) and staurosporine (100 nM) cleaved pro-caspase-3 to active forms. An in vitro caspase assay also showed that PKC412 and staurosporine elevated caspase-3 activities. Carbobenzoxy-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-FMK), a caspase inhibitor with a broad spectrum, inhibited caspase-3 activities stimulated by PKC412 and staurosporine; however, only PKC412-induced apoptosis, but not staurosporine-induced apoptosis, was prevented by Z-VAD-FMK. These results suggested that PKC412-induced apoptosis, but not staurosporine-induced apoptosis, is mainly mediated by the caspase-dependent mechanism.     

Vascular Endothelial Growth Factor Concentrations in Follicular Fluid Obtained from IVF-ET Patients: A Comparison of hMG, Clomiphene Citrate, and Natural Cycle

Purpose: Evaluation of vascular endothelial growth factor (VEGF) concentrations of follicular fluid (FF) in accordance with an ovarian stimulation protocol and ovarian response. Methods: The subjects of this study were 38 patients undergoing IVF-ET in our hospital. They were divided into three groups according to ovarian stimulation protocols; Group 1: hMG cycles (n = 19), Group 2: clomiphene citrate cycles (n = 10), Group 3: natural cycles (n = 9). They reclassified into three groups according to the number of oocytes harvested. VEGF concentration was measured in FF, employing ELISAs. Results: Group 1 shows lower VEGF concentrations in FF than Group 2 or Group 3. Excluding high responders from Group 1, no difference was found among these three groups. As for the reclassified groups, group of highest number of oocytes havested showed lowest VEGF concentrations in FF. Conclusions: VEGF concentrations in FF might negatively correlate with the number of follicles, irrespective of the ovulation induction protocol.     

Myelination of a fetus with Pelizaeus-Merzbacher disease: immunopathological study

We report an autopsied case of a 21-gestational-week fetus with duplication of the proteolipid protein (PLP) gene (PLP1). An immunohistochemical study, which can detect the specific expression of PLP, myelin basic protein, myelin-associated glycoprotein, and platelet-derived growth factor receptor alpha subunit in brain tissues, showed that the myelination was almost the same as that of age-matched controls. This result suggests that the development and migration of the oligodendrocyte is normal in Pelizaeus-Merzbacher disease until midgestation. To our knowledge, this is the first report of the myelination of a fetus with duplication of the PLP1 gene.     

Characteristic developmental expression of amyloid beta40, 42 and 43 in patients with Down syndrome

We immunohistochemically studied the expression of beta-amyloid precursor protein (APP), Abeta40, Abeta42, and Abeta43 in the frontal lobes of 20 Down syndrome (DS) patients and 13 controls. The immunoreactivity for each antibody was different in the degree of intensity and the chronological pattern of expression. APP and Abeta43 immunoreactivity was increased in neurons initially, and then Abeta43 and 42 immunoreactivity appeared in diffuse plaques from 32 years of age. APP and Abeta43 were characteristically observed in axons around senile plaques. Finally, Abeta40 immunoreactivity was detected in the cores of senile plaques. This time course of immunoreactive expression may be related to the pathogenetic process of Alzheimer-type dementia in DS, and the axonal damage in senile plaques may lead to the formation of neurofibrillary tangles (NFT) or neuronal death through axonal flow disturbance and accumulation of Abeta43 in cortical neurons.     

Association of osteopontin with ischemic axonal death in periventricular leukomalacia

Osteopontin (OPN) is a bone matrix protein expressed my macrophages and related to the process of tissue calcification, and is also known to protect ischemic cells. To understand how OPN is involved in the process of ischemic axonal death in periventricular leukomalacia (PVL), we examined the immunoreactivity of OPN and ionized calcium binding adaptor molecule 1 (Iba1; microglia/ macrophage marker) at various stages of PVL. OPN immunoreactivity paralleled the number of Iba1-positive foam cells; a finding which suggests the production of OPN protein by foam cells. OPN immunoreactivity was not found in either normal white matter or acute PVL lesions, but was detected at the subacute and chronic stages in swollen and calcified axons bordering the ischemic zone. These findings suggest that OPN is closely associated with death of swollen axons at the periphery of the ischemic zone, regulating the presence or absence of calcification. Received: 20 January 1999 / Revised, accepted: 21 September 1999     

Developmental expression of myotonic dystrophy protein kinase in brain and its relevance to clinical phenotype

To investigate the pathophysiologic role of myotonic dystrophy protein kinase (DMPK) in the brain in myotonic dystrophy (MD), the developmental characteristics of DMPK immunoreactivity in the central nervous system and its alteration with disease were studied. Eleven patients’ brain with MD (5 congenital form, 6 adult form) were examined by immunohistochemistry using a specific antibody against synthetic DMPK peptides, anti-peptide DM1, and compared with 30 control brains, including 16 age-matched controls. In controls, DM1-immunoreactive neurons appeared in the early fetal frontal cortex and cerebellar granule cell layer, persisting through 29 weeks of gestation and then disappearing. In contrast, immunoreactive neurons continued to persist in the cerebral cortex and cerebellar granule cell layer of MD patients. When we counted DM1-immunoreactive neurons, the increase over controls was greater in the congenital form of MD than in the adult form, and was greater in the cerebrum than in the cerebellum in both forms of MD. DM1 immunostaining was predominantly nuclear, mirroring Western blotting of subcellular fractions. Differences in DM1 expression related to development and to the two forms of MD may be closely related to the pathogenesis of mental retardation in this disease. Received: 30 July 1999 / Revised: 21 January 2000 / Accepted: 1 February 2000