HTL V-I from Iranian Mashhadi Jews in Israel is phylogenetically related to that of Japan,India, and South America rather than to that of Africa and Melanesia

A new endemic focus of human T-lymphotropic virus type I (HTL V-I) was recently reported among Mashhadi Jews, a group of immigrants from northeastern Iran to Israel. We extracted DNAs from fresh peripheral blood mononuclear cells (PBMCs) and/or gargle mouthwash from 10 HTL V-I carriers, who consisted of members of one family, and HTL V-I-associated myelopathy (HAM) and adult T-cell leukemia (ATL) patients. Long terminal repeat (LTR) regions of proviral DNAs were sequenced and analyzed phylogenetically. In a phylogenetic tree, all the Mashhadi HTL V-I isolates belonged to subtype A, one of the three subtypes of the cosmopolitan type of HTL V-I, and made a tight cluster distinct from the other isolates of subtype A from Japan, India, the Caribbean Basin, and South America. Although a few nucleotide substitutions were observed among the clones sequenced, no characteristic sequence variation was found in different disease manifestations, even in one family or different sources of DNA preparation.     

Involvement of cAMP response element-binding protein activation in salivary secretion.

OBJECTIVE: Saliva secretion is mediated by cAMP and the calcium signaling pathway in salivary acinar cells. The PKA signaling pathway plays an important role in protein secretion through the activation of cAMP, in fluid secretion through the elevation of intracellular calcium and in the activation of cAMP response element-binding protein (CREB), which is involved in these signaling cascades. In this study, we investigated whether the activation of CREB plays a part in the salivary secretion in mice. METHODS: We examined CREB activation by assessing phosphorylation at the serine-133 position using Western blotting. RESULTS: Carbachol (a muscarinic acetylcholine agonist) and isoproterenol (a beta-adrenergic agonist) markedly activated CREB in parotid acinar cells. Carbachol and isoproterenol-induced CREB phosphorylation was blocked by atropine (a muscarinic acetylcholine antagonist) and propranolol (a beta-adrenergic antagonist), respectively. The PKA inhibitor H89 inhibited CREB activation, but the PLC inhibitor U73122 did not. Moreover, carbachol- and isoproterenol-stimulated amylase secretion from parotid acinar cells was inhibited by H89 and adenoviral dominant-negative CREB. CONCLUSION: These results indicate that the muscarinic and beta-adrenergic activation of CREB was mediated through the PKA pathway and that CREB is involved in protein secretion from parotid acinar cells.     

Balloon cell nevus of the soft palate: an immunohistochemical and ultrastructural study

An ultrastructural analysis of oral balloon cell nevus of intramucosal type complemented with an immunohistochemical study was performed for the first time. The lesion was composed of large balloon cells with an admixture of small nevus cells and melanophages at the periphery. Balloon cells showed cytoplasmic accumulation of vacuoles of varying sizes and the presence of microgranular and vacuolated melanosomes were found. Residual cytoplasm contained no identifiable organelles. A spectrum of transitional forms between balloon cells and conventional nevus cells with microvacuoles was readily observed. Both cells exhibited intense immunoreactivity to multiple melanocytic markers. Ballooning phenomenon was not evident in melanophages containing a large amount of melanosome complex. It can be inferred, from the present and previous observations, that progressive vacuolization of melanosomes in nevomelanocytes may be responsible for the formation of peculiar ballooning appearance, suggesting an aberrant melanogenesis.     

The plasminogen activation system reduces fibrosis in the lung by a hepatocyte growth factor-dependent mechanism

Mice deficient in the plasminogen activator inhibitor-1 gene (PAI-1-/- mice) are relatively protected from developing pulmonary fibrosis from bleomycin administration. We hypothesized that one of the protective mechanisms may be the ability of the plasminogen system to enhance hepatocyte growth factor (HGF) effects, which have been reported to be anti-fibrotic in the lung. HGF is known to be sequestered in tissues by binding to extracellular matrix components. Following bleomycin administration, we found that HGF protein levels were higher in bronchoalveolar lavage fluid from PAI-1-/- mice compared to wild-type (PAI-1+/+) mice. This increase could be suppressed by administering tranexamic acid, which inhibits plasmin activity. Conversely, intratracheal instillation of urokinase into bleomycin-injured PAI-1+/+ mice to activate plasminogen caused a significant increase in HGF within bronchoalveolar lavage and caused less collagen accumulation in the lungs. Administration of an anti-HGF neutralizing antibody markedly increased collagen accumulation in the lungs of bleomycin-injured PAI-1-/- mice. These results support the hypothesis that increasing the availability of HGF, possibly by enhancing its release from extracellular matrix by a plasmin-dependent mechanism, is an important means by which activation of the plasminogen system can limit pulmonary fibrosis.     

Long‐term observation of a Japanese mucolipidosis IV patient with a novel homozygous p.F313del variant of MCOLN1

Mucolipidosis type IV (MLIV) is an autosomal recessively inherited lysosomal storage disorder characterized by progressive psychomotor delay and retinal degeneration that is associated with biallelic variants in the MCOLN1 gene. The gene, which is expressed in late endosomes and lysosomes of various tissue cells, encodes the transient receptor potential channel mucolipin 1 consisting of six transmembrane domains. Here, we described 14‐year follow‐up observation of a 4‐year‐old Japanese male MLIV patient with a novel homozygous in‐frame deletion variant p.(F313del), which was identified by whole‐exome sequencing analysis. Neurological examination revealed progressive psychomotor delay, and atrophy of the corpus callosum and cerebellum was observed on brain magnetic resonance images. Ophthalmologically, corneal clouding has remained unchanged during the follow‐up period, whereas optic nerve pallor and retinal degenerative changes exhibited progressive disease courses. Light‐adapted electroretinography was non‐recordable. Transmission electron microscopy of granulocytes revealed characteristic concentric multiple lamellar structures and an electron‐dense inclusion in lysosomes. The in‐frame deletion variant was located within the second transmembrane domain, which is of putative functional importance for channel properties.     

Vinyl polymerization initiated with the lanthanum versatate/p-chlorobenzenediazonium tetrafluoroborate system

The system of lanthanum versatate ( 1 ) and p-chlorobenzenediazonium tetrafluoroborate ( 2 ) was found to induce effectively polymerizations of electron-accepting monomers such as methyl methacrylate ( 3 ) and di-2-ethylhexyl itaconate (DEHI). The polymerization rate (R_p) was expressed by R_p = k[ 1 / 2 ]^0,44 [ 3 ]^0,65 at 50°C fixing the mole ratio of 1 and 2 at unity. The overall activation energy of the polymerization was calculated to be 37, 1 kJ · mol^?1. The spin trapping result revealed that the initiator system produces p-chloropheneyl radicals. The polymerization system of DEHI was observed to involve ESR-observable propagating polymer radicals, indicating that the polymerization initiated with the 1/2 system proceeds through radical mechanism. During the polymerization, the ESR spectrum was changed in shape, suggesting that the propagating polymer radicals interact with some species formed by the initiation reaction. Interacting polymer radicals were also observed in the polymerizations of diethyl itaconate and N-dodecylmaleimide with the 1/2 system. The polymerization systems of MMA, styrene and butyl acrylate were also found to involve ESR-observable radicals, although it is vague whether they are propagating polymer radicals or not.     

The prevalence of TT virus (TTV) infection and its relationship to hepatitis in children

TT virus (TTV) is a newly discovered virus from a patient with post-transfusion hepatitis. We investigated the frequency and pathogenesis of TTV infection in children. A semi-nested PCR assay was used to amplify TTV-DNA in serum samples from 254 ambulatory children without liver disease, 20 with hepatitis of unknown etiology, and 18 transfusion recipients or hemophiliacs. In positive samples, TTV-DNA was quantified by real-time quantitative PCR using a fluorescent probe. We detected TTV-DNA in 20% of children with hepatitis of unknown etiology, which was not statistically different from the 23% prevalence in ambulatory children. In transfusion recipients or hemophiliacs, the frequency was higher (50%) than that in ambulatory children (P = 0.01). Among ambulatory children, TTV-DNA was frequently detected in children with acute gastroenteritis (36%). TTV-DNA was detected in 10% of the infants under 6 months old, and 20% of the children from 7 to 12  months old. The prevalence was constant after the age of 1 year; however, the copy number of TTV-DNA was significantly higher in children under 1 year of age (mean: 10^5.4 versus 10^3.8 copies/ml, P= 0.008). Finally, TTV-DNA was quantified serially in three children with chronic hepatitis who were positive for TTV-DNA. The presence or amount of TTV-DNA was unrelated to the serum alanine aminotransferase level. These results indicate that TTV infection is common in children. The larger quantity of TTV-DNA in infants and the high prevalence of TTV in children of all ages suggest that TTV may be transmitted in early childhood. Its relationship to hepatitis is doubtful in children. Received: 8 April 1999     

Gastric juvenile polyposis associated with germline SMAD4 mutation

We treated a 39-year-old woman with hypoproteinemia and anemia who had profuse gastric polyposis. Radiographic and endoscopic examination showed numerous polyps restricted to the stomach. The patient had pulmonary arteriovenous malformations in the left lung. Histological examination of the resected stomach revealed the gastric polyposis to be composed of cystic dilatation of the glands with small areas of adenocarcinoma. These findings were compatible with gastric juvenile polyposis (GJP) accompanied by gastric cancer. Analysis of genomic DNA revealed that the patient had truncating mutation of SMAD4, a responsible gene for juvenile polyposis (JP). Our case suggests that SMAD4 is possibly a responsible gene for GJP.     

Postanesthetic malignant hyperthermia with convulsions

Journal of Anesthesia -