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     

Two patients with chromosome 6q terminal deletions with breakpoints at q24.3 and q25.3.

We report on 2 patients with de novo terminal deletion of 6q. The first was a 4-month-old boy whose karyotype was 46,XY,del(6)(q24.3); the second a 2-year-old girl whose karyotype was 46, XX, del(6)(q25.3). The main anomalies in both patients included mental retardation, minor craniofacial and cerebral anomalies, and cardiac defects. The characteristic manifestations were imperforate anus in the first patient, and retinitis proliferans and a triatrial heart in the other. Comparison of clinical findings of our 2 patients with those of 18 previously reported patients with similar phenotypes suggests that terminal deletion of the 6q23 or 6q25 band is critical in producing the main anomalies of del(6q) syndrome.     

Pulmonary complications in patients with adult T-cell leukemia

A survey of 360 patients with various hematologic diseases revealed a high frequency of respiratory complications in patients with adult T-cell leukemia (ATL) compared to others. Among 29 patients with ATL, pulmonary complications were seen in 26 patients; leukemic pulmonary infiltration in 13, bleeding in 1, interstitial pneumonitis in 1, and pulmonary infection in 13. The incidence of Pneumocystis carinii and bacterial pneumonias were high despite adequate neutrophil count. Even in chronic and smoldering ATL, respiratory diseases were found in high frequency. Many of those were leukemic cell infiltration. In ten of 13 patients with pulmonary infiltration it occurred in the early stage and 6 of them were diagnosed as having "chronic lung disease" before the diagnosis of ATL. Its histology was accompanied by fibrosis in greater or lesser degree in almost all cases. Transbroncheal lung biopsy (TBLB) is of value in diagnosis (8 of 13 cases).     

Evaluation of the test method “activated sludge, respiration inhibition test” proposed by the OECD

The test method of "activated sludge, respiration inhibition test" proposed by the OECD was critically carried out and compared with other test methods. Investigation of test conditions showed that the moderate deviation from the test conditions defined by the OECD Test Guidelines did not have much effect on the result, and some modifications were proposed to improve the method. This method had a poor detection limit compared with the LC50 test with Oryzias latipes and EC50 of the growth inhibition test with Tetrahymena pyriformis. The susceptivity of the method was particularly poor for the chemicals which were highly toxic in the other two tests.     

Comparison of Intrinsic Connectivity in Different Areas of Macaque Monkey Cerebral Cortex

We have used small injections of biocytin to label and comparepatterns of intreareal, laterally spreading projections of pyramidalneurons in a number of areas of macaque monkey cerebral cortex.In visual areas (V1, V2, and V4), somatosensory areas (3b, 1,and 2), and motor area 4, a punctate discontinuous pattern ofconnections is made from 200-µm-diameter biocytin injectionsin the superficial layers. In prefrontal cortex (areas 9 and46), stripe-like connectivity patterns are observed. In allareas of cortex examined, the width of the terminal-free gapsis closely scaled to the average diameter of terminal patches,or width of terminal stripes. In addition, both patch and gapdimensions match the average lateral spread of the dendriticfield of single pyramidal neurons in the superficial layersof the same cortical region. These architectural features ofthe connectional mosaics are constant despite a twofold differencein scale across cortical areas and different species. They thereforeappear to be fundamental features of cortical organization.A model is offered in which local circuit inhibitory "basket"interneurons, activated at the same time as excitatory pyramidalneurons, could veto pyramidal neuron connections within eithercircular or stripe-like domains; this could lead to the formationof the pattern of lateral connections observed in this study,and provides a framework for further theoretical studies ofcerebral cortex function.     

MR imaging of internal carotid artery occlusion

Five patients with internal carotid artery occlusion were studied with MR imaging at 0.22 T. At the carotid siphon, occluded vessels showed absence of flow void in three patients. But two cases had "partial flow void" which mimicked small arterial caliber. In these patients angiography showed collateral circulation to the carotid siphon. So the partial flow void in the carotid siphon suggested internal carotid artery occlusion with collateral circulation.     

Dependence of the Molecular Mobility and Protein Stability of Freeze-Dried γ-Globulin Formulations on the Molecular Weight of Dextran

Purpose. The effect of the molecular weight of dextran on the molecular mobility and protein stability of freeze-dried serum -globulin (BGG) formulations was studied. The stabilizing effect of higher molecular weight dextran is discussed in relation to the molecular mobility of the formulations. Methods. The molecular mobility of freeze-dried BGG formulations containing dextrans of various molecular weights was determined based on the free induction decay of dextran and water protons measured by proton NMR. The protein stability of the formulations was determined at temperatures ranging from 20 to 70°C by size exclusion chromatography. Results. Changes in the molecular mobility of freeze-dried formulations that occurred at temperatures below the glass transition temperature could be detected as the molecular mobility-changing temperature (T_mc), at which dextran protons started to exhibit a Lorentzian relaxation decay due to higher mobility in addition to a Gaussian relaxation decay. T_mc increased as the molecular weight of dextran increased. The proportion of dextran protons which exhibited the higher mobility relaxation process (P_hm) at temperatures above T_mc decreased as the molecular weight of dextran increased. Protein stability was closely related to molecular mobility. The temperature dependence of the denaturation rate changed at around T_mc, and denaturation in the microscopically liquidized state decreased as P_hm decreased with increasing molecular weight of dextran. Conclusions. The effect of the molecular weight of dextran on the protein stability of freeze-dried BGG formulations could be explained in terms of the parameters obtained by ¹H-NMR such as T_mc and P_hm. These parameters appear to be useful in preformulation and stability prediction of freeze-dried formulations.     

Physical Stability and Protein Stability of Freeze-Dried Cakes During Storage at Elevated Temperatures

The relationship between physical stability of freeze-dried cakes and protein stability during storage was studied using -galactosidase as a model protein and inositol as an excipient. Amorphous samples freeze-dried from solutions containing the enzyme and various concentrations of inositol in sodium phosphate buffer (50 mM, pH 7.4) were stored for 7 days over P₂O₅ at 40 to 70°C. Structural collapse and inositol crystallization were observed in some of the samples, depending on the formulation and storage temperature. The physical stability of freeze-dried samples was also studied by differential scanning calorimeter (DSC). Inositol showed a protein-stabilizing effect when its amorphous form was retained during storage, regardless of structural collapse. However, crystallization of inositol during storage removed its stabilizing effect. Addition of water-soluble polymers such as dextran, Ficoll and carboxymethyl cellulose sodium salt (CMC-Na) preserved activity of the enzyme by preventing inositol crystallization.     

Breast parenchymal activity on scintimammography: Comparison between bone-seeking agents and99mTc-sestamibi

The aim of this study was to evaluate breast parenchymal activity on scintimammography with bone-seeking agents and 99mTc-MIBI. Scintimammography was performed with bone-seeking agents in 61 patients and with 99mTc-MIBI in 33 patients. Activity in the breast parenchyma contralateral to the suspected lesion was visually assessed by two independent observers. Increased breast parenchymal activity was shown in 19 of 61 patients examined with bone-seeking agents, while it was demonstrated in only two of 33 patients examined with 99mTc-MIBI. Breast parenchymal activity of bone-seeking agents was higher in patients aged 50 years or younger than in those older than 50. Increased parenchymal activity of bone-seeking agents may disturb visualization of primary breast cancer especially in relatively young patients. Low parenchymal activity is suggested to be a favorable characteristic of 99mTc-MIBI as a scintimammographic agent.     

Regulation of phosphatidylcholine biosynthesis by mGluR1alpha expressed in human embryonic kidney 293 cells--A 31P-NMR study

A recent report has demonstrated that inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release plays a crucial role in neurite growth. Here, using 31P-NMR, we examine whether activation of the metabotropic glutamate receptor 1 (mGluR1), which induces the production of IP3, could modulate phospholipid metabolism in human embryonic kidney 293 cells. mGluR1alpha- but not ionotropic glutamate receptor 1-expressing cells stimulated with glutamate exhibited a drastic reduction in the phosphorylcholine level, with corresponding increases in the level of phosphatidylcholine, a major phospholipid component. Quantitative analysis of cell growth revealed that mGluR1alpha-expressing cells cultured with 100microM glutamate were statistically significantly longer than the nontransfected cells. The effect was no longer observed following coincubation with a metabotropic glutamate receptor antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine. These results suggest that mGluR1alpha activation triggers phosphatidylcholine biosynthesis and may contribute to neurite extension.