Pancreatic mass lesions associated with raised concentration of IgG4

Autoimmune pancreatitis (AIP) is a recognized benign disease characterized by irregular narrowing of the pancreatic duct, swelling of parenchyma, lymphoplasmacytic infiltration and fibrosis, and a favorable response to corticosteroid treatment. In this condition, the whole pancreas is diffusely affected. Recently, however, a few cases with locally affected lesions were reported, with some of them showing features similar to cancer. We reviewed 138 patients with pancreatic mass lesion, of which 17 were not initially diagnosed despite examinations. Serum IgG4 levels were elevated in seven of them. Their biopsy specimens had a similar appearance to those of AIP. We considered that they should be diagnosed as AIP or conditions related to AIP. Among the 10 patients without elevated IgG4, 4 patients were diagnosed as pancreatic cancer after follow-up, 1 presented with an islet cell tumor, 1 presented AIP with sclerosing cholangitis, and the other 4 had chronic pancreatitis.     

A decrease in mother-to-child transmission of human T lymphotropic virus type I (HTLV-I) in Okinawa, Japan

To investigate the chronologic change of mother-to-child transmission of human T lymphotropic virus type I (HTLV-I) in Okinawa, Japan, the presence of antibody to HTLV-I was tested in 4,187 healthy residents between, 4,528 nursery school children, and 3,837 pregnant women between 1968 and 2000. The chronologic change of the feeding method and the length of the breast-feeding period among 1,117 healthy mothers from 1937 to 1995 were also obtained by interview. Age-adjusted prevalence of HTLV-I among healthy residents decreased from 9.1% in 1968-1970 to 7.8% in 1981-1984 and to 6.3% in 1996-1998. The crude prevalence of antibody to HTLV-I among healthy residents less than 20 years old decreased significantly from 4.6% in 1968-1970 to 0.1% in 1996-1998 (P < 0.0001). The prevalence of antibody to HTLV-I among nursery school children decreased significantly over the study period, from a high of 1.8% in 1984 to a low of 0.2% in 1998 (P = 0.03). The prevalence among pregnant women decreased significantly from 5.6% in 1989-1992 to 3.7% in 1997-2000 (P = 0.0275). Prior to 1967, all healthy mothers breast-fed their children. After 1968, the use of bottled and mixed milk (breast milk and bottled milk) increased, with bottled milk becoming predominant after 1990 (89%). The percentage of healthy mothers breast-feeding for more than one year significantly decreased from 68.3% in 1937-1947 to 0.4% in 1990-1995 (P < 0.0001). Infection with HTLV-I in Okinawa has decreased mainly due to a reduction in the number of mothers breast-feeding and a shortening of the breast-feeding period. However, because the mother-to-child transmission rate among non-breast-feeders decreased from 12.8% in 1986-1991 to 3.2% in 1995-1999, there may be other factors involved in the decrease in mother-to-child transmission.     

Cysticercosis/taeniasis in Asia and the Pacific

Three taeniid tapeworms infect humans in Asia and the Pacific: Taenia solim, Taenia saginata, and Taenia asiatica. Although there is continuing debate about the definition of a new species, phylogenetic analyses of these parasites have provided multiple lines of evidence that T. asiatica is an independent species and the sister species of T. saginata. Here we review briefly the morphology, pathology, molecular biology, distribution and control options of taeniasis/cysticercosis in Asia and the Pacific and comment on the potential role which dogs may play in the transmission of T. solium. Special attention is focused on Indonesia: taeniasis caused by T. asiatica in North Sumatra, taeniasis/cysticercosis of T. solium and taeniasis of T. saginata in Bali, and taeniasis/cysticercosis of T. solium in Papua (formerly Irian Jaya). Issues relating to the spread of taeniasis/cysticercosis caused by T. solium in Papua New Guinea are highlighted, since serological evidence suggests that cysticercosis occurs among the local residents. The use of modern techniques for detection of taeniasis in humans and cysticercosis in humans, pigs and dogs, with the possible adoption of new control measures will provide a better understanding of the epidemiology of taeniasis/cysticercosis in Asia and the Pacific and lead to improved control of zoonotic and simultaneously meat-borne disease transmission.     

Novel autoantibody to Cu/Zn superoxide dismutase in patients with localized scleroderma

Abnormal production of reactive oxygen species (ROS) induces tissue damage and superoxide dismutase (SOD) that converts superoxide radicals to hydrogen peroxide functions as defense against ROS. Cu/Zn SOD administration has been shown to be effective for various fibrotic conditions by inhibiting the fibrogenic effects of ROS. We hypothesized that autoimmune background in localized scleroderma induced anti-Cu/Zn SOD autoantibodies that inhibited SOD activity and thereby contributed to fibrosis by increasing ROS. ELISA using human purified Cu/Zn SOD revealed that IgG or IgM anti-Cu/Zn SOD Ab was detected in the serum of 89% of localized scleroderma patients, especially 100% of patients with generalized morphea, the severest form of localized scleroderma, but was positive only in the serum of less than 15% of patients with other autoimmune disorders, including systemic sclerosis, systemic lupus erythematosus, dermatomyositis, and autoimmune bullous disorders. The immunoblotting analysis confirmed the presence of IgG anti-Cu/Zn SOD Ab in sera from localized scleroderma patients. Remarkably, anti-Cu/Zn SOD autoantibody could inhibit Cu/Zn SOD enzymatic activity. Collectively, these results indicate that anti-Cu/Zn SOD Ab is a novel, major autoantibody in localized scleroderma, and also suggest that the autoantibody may play a role in the development of fibrosis by directly inhibiting SOD activity.     

Biosynthesis of acylceramide in murine epidermis: characterization by inhibition of glucosylation and deglucosylation, and by substrate specificity

We have investigated the physiological significance of the glucosylation of ceramides and the subsequent deglucosylation of glucosylceramide in the synthetic pathway of acylceramide. In this metabolic pathway using [14C]-serine in organ culture, newborn murine (BALB/c) epidermis synthesizes several types of ceramides, including acylceramide, as analyzed by thin-layer chromatography. When conduritol-B-epoxide, a specific inhibitor of beta-glucocerebrosidase, was added to the culture medium, the synthesis of acylceramide was significantly suppressed in concert with a significant increase in acylglucosylceramide. Furthermore, addition of d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of glucosyltransferase, also specifically abolished the synthesis of acylceramide whereas non-acylated ceramides were relatively less affected. We further determined whether the physiological substrate of glucosyltransferase is omega-hydroxyceramide (C30) or non-omega-hydroxylated ceramides. Of those, only non-omega-hydroxylated ceramides proved to be good substrates for glucosyltransferase in vitro. Our parallel in vitro study also demonstrated that murine epidermis contains enzymatic activity by which omega-hydroxyglucosylceramide or omega-hydroxyceramide can be converted to acylglucosylceramide or acylceramide. Collectively, these findings indicate that the majority of acylceramides found in the stratum corneum may be synthesized through a distinct sequence of enzymatic reactions consisting of the glucosylation of ceramides by glucosyltransferase, omega-hydroxylation of glucosylceramide, the acylation of omega-hydroxyglucosylceramide (possibly by an omega-acyltransferase), and the deglucosylation of acylglucosylceramide by beta-glucocerebrosidase.     

Impaired spatial learning after hypergravity exposure in rats

Most astronauts experience spatial disorientation after exposure to weightlessness, indicating that constant gravity is utilized as a stable external reference during spatial cognition. We attempted to elucidate the role of constant gravity in spatial learning using a radial arm maze test on rats housed in a hypergravity environment (HG) produced by a centrifuge device. Male Wistar rats were kept in 2G linear acceleration for 2 weeks before the spatial learning task, which lasted for 10 days. The control rats were placed close to the centrifuge device but not exposed to hypergravity. Spatial learning was evaluated by the accuracy and the re-entry rate, which were the rate of correct arm entries and the rate of entries into the arms that they had already visited, respectively. Locomotor activity was measured by number of entries per minute. The number of baits the animal took per minute was also measured. The results showed that accuracy was significantly inferior and the re-entry rate was significantly higher in the HG rats than in the controls, suggesting that animals use a constant gravity as a stable external reference in spatial learning. However, these differences disappeared at 5 days later, indicating that the HG rats learned the spatial task more rapidly than the controls. Locomotor activity was higher in the HG rats and there was no difference in number of baits per minute between the HG and control animals. In conclusion, if one sensory cue necessary for spatial cognition is disturbed by gravity change, animals can subsidize with other sensory cues such as proprioceptive and motor efference copy signals through increased locomotor activities.     

Oxidative stress and microglial activation in substantia nigra following striatal MPP+

The present study aims to study sequential alterations occurring in both dopaminergic neurons and microglia in substantia nigra (SN) following intrastriatal injection of 1-methyl-4-phenylpridium ion (MPP+) in rats. Heme oxygenase-1 (HO-1), a marker of oxidative stress, first appeared in dopaminergic neurons in SN at 1 day post-lesion. Subsequently, microglia in SN exhibited morphological changes indicative of activation. At 7 days post-lesion, those findings increased severity and 7a significant reduction in the number of dopaminergic neurons was observed. The present finding suggests that extensive oxidative stress and secondary-induced neuroinflammation play a relevant role in MPP(+)-induced retrograde dopaminergic neuron degeneration. We hope that this model will be useful in developing a disease modifying therapy of Parkinson's disease.     

Cortical processing of tactile language in a postlingually deaf-blind subject

We compared neural activation detected by magnetoencephalography (MEG) during tactile presentation of words and non-words in a postlingually deaf-blind subject and six normal volunteers. The left postcentral gyrus, bilateral inferior frontal gyri, left posterior temporal lobe, right anterior temporal lobe, bilateral middle occipital gyri were activated when tactile words were presented to the right hand of the deaf-blind subject. This set of activated regions was not observed in the normal volunteers, although activation of several combinations of these regions was detected. Positron emission tomography confirmed the location of the MEG-activated areas in the deaf-blind subject. Our results demonstrated that the deaf-blind subject is heavily involved in interpreting tactile language by enhancing cortical activation of cognitive and semantic processing.     

Migrating and myelinating potential of neural precursors engineered to overexpress PSA-NCAM

Polysialic acid (PSA) on NCAM is an important modulator of cell-cell interactions during development and regeneration. Here we investigated whether PSA overexpression influences neural cell migration and myelination. We stably expressed a GFP-tagged polysialytransferase, PSTGFP, in mouse neurospheres and induced prolonged PSA synthesis. Using a chick xenograft assay for migration, we show that PSA can instruct precursor migration along the ventral pathway. PSA persistence did not change neural precursor multipotentiality in vitro but induced a delay in oligodendrocyte differentiation. PSTGFP+ precursors showed widespread engraftment in shiverer brain, closely similar to that observed with control precursors expressing a fluorescent protein. Initially, myelination by oligodendrocytes was delayed but, eventually, down-regulation of PSTGFP occurred, allowing myelination to proceed. Thus down-regulation of polysialyltransferases takes place even in cells where its RNA is under the control of a heterologous promoter and engineering PSA overexpression in neural precursors does not cause irreversible unphysiological effects.