Leukocyte and plasma N-laurylsphingosine deacylase (ceramidase) in Farber disease

Severe deficiency of acid ceramidase activity (4-5% of normal) was demonstrated in cultured skin fibroblasts, leukocytes and plasma from a 1-year-old boy who was diagnosed as being affected with Farber disease. Determination of ceramidase activity in plasma was achieved by a highly sensitive assay employing a ceramide substrate containing radiolabeled C12 N-acyl moiety (N-lauryl). The enzyme activity in the parents' leukocytes and plasma was found to be reduced to 18-47% of the respective normal values, and that determined in a plasma specimen from a patient with I-cell disease was about 4 times elevated above the normal level.     

Herpetic croup: two case reports and a review of the literature

Croup is an acute infectious illness usually occurring in children; it is characterized by brassy cough and stridor. The main pathogens include mainly parainfluenza and influenza viruses. Recently there have been reports of prolonged croup caused by the herpes simplex viruses. We report two cases of prolonged croup due to herpes simplex types 1 and 2. We also review and summarize the reported pediatric cases of herpetic croup.     

Optimum selection of an implantable secondary battery for an artificial heart by examination of the cycle life test

An implantable secondary battery is one of the key components in a total artificial heart system. Because a 2 year cycle life is required, the cycle life of the secondary battery as well as its charge and discharge properties are important parameters for selection of an appropriate battery. We carried out cycle life tests on four kinds of rechargeable batteries (a Ni-MH secondary battery, a Ni-Cd secondary battery, a Li-ion battery with a graphite anode, and a Li-ion battery with a nongraphitizable carbon electrode) to determine their suitability as implanted back-up batteries. Each of the batteries was charge/discharge cycled at 37 degrees C to 39 degrees C using a charge current of 1 C ampere, and they were each fully discharged under either pulsatile discharge loads, which mimicked pulsatile operation, or a nonpulsatile load equivalent to the average of the pulsatile loads. The two Li-ion batteries made by different manufacturers both met the minimum requirement of cycle life of more than 1,500 cycles, considering safety coefficient regardless of the discharge pattern. In addition, the temperature increase of these Li-ion batteries (3 degrees C) was lower than that of Ni-Cd and Ni-MH batteries (15-25 degrees C). Out of these four batteries, the two Li-ion batteries are the most suitable for use in a totally implantable artificial heart system.     

Polyglutamine aggregates stimulate ER stress signals and caspase-12 activation

Accumulation of unfolded and malfolded proteins causes endoplasmic reticulum (ER) stress, stimulating unfolded protein response (UPR) and c-Jun N-terminal kinase (JNK) activation and activating caspase-12 located on the ER. Little is known about the relationship between the ER stress and polyglutamine [poly(Q)] aggregates. Poly(Q)72 repeats [poly(Q)(72)] induced the stimulation of ER stress signals such as JNK activation, upregulation of Grp78/Bip and caspase-12 activation in C2C5 cells. We prepared antiserum against the cleavage site of mouse caspase-12 at D(318) (anti-m12D318), and showed that poly(Q)(72) with perinuclear aggregates, cytoplasmic inclusions and nuclear inclusions stimulated JNK activation and anti-m12D318 immunoreactivity, but poly(Q)(72) with dispersed aggregates and small nuclear aggregates showed a significantly less effect. Poly(Q)(72) and poly(Q)(11) dispersed in cytoplasm did not. Anti-m12D318-positive cells showed apoptotic features. Unlike anti-m8D387 immunoreactivity, the anti-m12D318 immunoreactivity was not coaggregated with poly(Q). Ac-IETD-fmk (caspase-8 inhibitor) and Ac-DEVD-CHO (caspase-3 inhibitor) did not prevent the anti-m12D318 immunoreactivity induced by poly(Q)(72) aggregates. Anti-m12D318 immunoreactivity was detected in caspase-8(-/-) and caspase-3(-/-) mouse embryonic fibroblasts expressing poly(Q)(72) aggregates. Thus, caspase-12 was activated by poly(Q)(72) aggregates via a pathway independent of caspase-8 and caspase-3 activation, and caspase-12 activation was closely associated with poly(Q) aggregate-mediated cell death. Stimulation of ER stress signals may be involved in the pathogenesis of neurodegenerative disorders with poly(Q) expansion.     

Primitive Neuroectodermal Tumors of the Central Nervous System

Controversial issues relating to the pathobiology and classification of central nervous system primitive neuroectodermal tumors (PNETs) have plagued neuropathologists for more than 70 years. Hypotheses advanced in the mid-1920's have remained as fixed concepts in contemporary literature, largely consequent to repetitious support by a small number of neuropathologists despite a growing body of information discrediting these ideas from neuroembryologists, oncologists, neuroscien-tists and pathologists.
Attention has largely focused upon PNETs arising in the cerebellum (commonly known as medul-loblastomas [MBs]), because about 80% of central nervous system (CNS) PNETs originate in this site. It has been asserted that the 20% which do not are biologically different, although most individuals agree that the histological features of PNETs that occur in different sites throughout the CNS are indistinguishable from those growing in the cerebellum.
The historical aspects of this controversy are examined in the face of evidence that there is, in fact, a unique class of CNS tumors which should appropriately be regarded as primitive neuroectodermal in nature. Specifically, a number of different approaches to the problem have yielded data supporting this hypothesis. These approaches include the identification of patterns of expression among a variety of cellular antigens (demonstrated by the use of immunopathological techniques), molecular analyses of cell lines derived from these tumors, experimental production of PNETs and molecular genetic analyses.
Differences of opinion among surgeons, oncologists and radiotherapists are typically resolved by conducting cooperative studies of patients with these tumors who are diagnosed and treated at multiple centers.     

An 8-cM interstitial deletion on 4q21-q22 in DNA from an infant with hepatoblastoma overlaps with a commonly deleted region in adult liver cancers

We performed molecular analysis of a germline interstitial deletion of chromosome 4 [del(4)(q21.22q23)], which had been observed in a male infant manifesting early-onset hepatoblastoma (HBL). The chromosomal anomaly in this child was associated with a unique congenital syndrome including HBL, atrial septal defect, ventricular septal defect, patent ductus arteriosus, mental retardation, and seizures. However, the patient did not exhibit a megalencephaly typical of 4q21-22 deletions. His HBL was associated with an increasing serum alpha-fetoprotein level and rapid growth. To define the chromosomal deletion at the molecular level in this child, we analyzed his lymphoblasts with fluorescence in situ hybridization, using as probes a panel of BAC/PAC genomic clones containing STS markers covering the 4q12-27 region. The analysis revealed that the affected chromosome had an 8-cM deletion within 4q21-q22, flanked by markers D4S2964 and D4S2966. This microdeletion overlaps with the commonly deleted region at 4q21-q22 that was recently defined in adult hepatocellular carcinomas.     

Glycogen storage disease type III with muscle involvement: reappraisal of phenotypic variability and prognosis.

A review of the case histories of 19 Japanese patients with enzymatically proven glycogen storage disease (GSD) III who developed muscular symptoms at various ages illustrates the phenotypic variability of this disease. There seem to be 4 subgroups of GSD III with muscle involvement according to the clinical symptoms. The first group of patients is characterized by the childhood onset of muscle weakness and hepatic disorders. The second group of patients develops muscular symptoms in adult years while the liver symptoms start in childhood. The third group includes the patients whose muscle weakness started in adult years long after liver symptoms in childhood had disappeared. The fourth group shows only muscular symptoms as adults without any sign or history of liver dysfunction since childhood. The prognosis for each subgroup seems to be different; however, none of them appears to be better than that for GSD I, as has been suggested previously.