The muscles of IL-6 transgenic mice suffer from atrophy. Experiments were carried out on these transgenic mice to elucidate activation of proteolytic systems in the gastrocnemius muscles and blockage of this activation by treatment with the anti-mouse IL-6 receptor (mIL-6R) antibody. Muscle atrophy observed in 16-wk-old transgenic mice was completely blocked by treatment with the mIL-6R antibody. In association with muscle atrophy, enzymatic activities and mRNA levels of cathepsins (B and L) and mRNA levels of ubiquitins (poly- and mono-ubiquitins) increased, whereas the mRNA level of muscle-specific calpain (calpain 3) decreased. All these changes were completely eliminated by treatment with the mIL-6R antibody. This IL-6 receptor antibody could, therefore, be effective against muscle wasting in sepsis and cancer cachexia, where IL-6 plays an important role.
An accurate wavelength meter (wavemeter) for cw lasers has been developed. The wavemeter is a Michelson-type fringe-counting two-beam interferometer operated in vacuum. A multicoincidence fringe counting technique has also been developed by which fringe fractions are determined with an uncertainty of 1/500 of a fringe. The result of wavelength comparisons between 612- and 633-nm I2 stabilized He-Ne lasers showed good agreement with the value recommended by CIPM 1983. The discrepancy was <4 x 10(-10) and the standard deviation of the comparison was 4 x 10(-10).
A 59-year-old man was admitted because of frequent vomiting and obtundation in February 1982. Neurological examination on admission revealed only slight impairment of consciousness. Papilledema, meningeal irritation sign and paralysis were not elicited. The plain CT scan was normal, but the CT scan with contrast material showed patchy enhancement in the left temporal lobe and around the third ventricle. Cerebral angiography showed a dural arteriovenous malformation (dural AVM) in the left transverse sinus fed by the left occipital artery, and the retrograde flow into the straight sinus. By the third day following admission, the level of consciousness became alert. The patient did not complain of headache, bruit and visual disturbance. He showed mild disorientation and memory disturbance. But his ordinary daily-living was independent. In August 1982, the patient gradually became inactive and apathetic. At times he lay in bed with moving his eyes, swallowing foods. At other times, he lay in bed with closing his eyes, immobile, and unresponsive except to strong painful stimuli. The patient was incontinent and required nursing care. During three month periods, the patient progressively became somnolent, speechless and immobile. Eventually, he was in a state of akinetic mutism. The patient became unresponsive. The state of consciousness fluctuated within a narrow range. The pupils were isocoric and did not react to light. He sometimes moved his eyes horizontally, but the vertical eye movement was limited. Deep tendon reflexes were hyperactive with Babinski reflex bilaterally. Passive mobilization of extremities revealed hypertonic. The CT scan disclosed the bilateral symmetrical infarction of the thalamus.(ABSTRACT TRUNCATED AT 250 WORDS)
To investigate the time course effect of sodium intake on release and synthesis of atrial natriuretic polypeptide (ANP), plasma and atrial content of ANP were measured in rats which had been fed either a high or a low salt diet for 1, 3, 7, 14 and 35 days. Plasma ANP in rats fed the high salt diet for one day was significantly higher than in those fed the low salt diet. However, there were no significant differences between the groups fed either the high or the low salt diet for 3 days or more. In contrast to the direction of change in plasma ANP, atrial content of ANP in rats fed the high salt diet for one day tended to be lower and was significantly lower in those fed for 3 and 7 days than in the low salt diet group, while there were no significant differences between both groups that were fed for 14 and 35 days. These results suggest that ANP is rapidly released into the circulation when sodium is loaded, however, the atrial storage of ANP remains depleted for about one week.
Apheresis platelets (APs) have gained favour over whole blood-derived platelets on the presumption that they are less likely to provoke alloimmunization to red-blood-cell antigens.
Non-D Rh antibodies appeared in three patients after apheresis platelet transfusion. Anti-C and anti-E arose in two female patients with previous antigen exposure. Both anti-c and anti-E arose in a male recipient with no prior transfusion history.
Fifty APs were analysed for residual RBCs and RBC-derived microparticles, using samples obtained from a local blood centre. Cells and microparticles were quantified with a flow cytometry gating scheme, using PE-labelled anti-CD235a (glycophorin A) and FITC-labelled anti-CD41a (platelet gp IIb/IIIa) to distinguish lineage.
Apheresis platelets were found to contain a mean of 7·5×10(6) (95% C.I. [6·3-8·5×10(6) ]) RBCs on one manufacturer's device and 5·2×10(6) (95% C.I. [4·0-6·3×10(6) ]) RBCs on another's. RBC-derived microparticles averaged 210·7×10(6) (95% C.I. [166·2-254·2×10(6) ]) on one manufacturer's device and 232·3×10(6) (95% C.I. [194·3-272·9×10(6) ]) on another's. These counts all correspond to volumes of <1 μl.
Despite RBC contamination of APs below commonly accepted thresholds for Rh immunogenicity, AP transfusion can provoke non-D Rh antibody formation. RBC-derived microparticles, smaller but more numerous than RBCs, are volumetrically comparable and may be a hitherto underappreciated antibody stimulus. Further microparticle research will guide considerations of extended phenotypic matching of platelet components.
1. The urinary excretion of a metabolite of illudin S after oral administration to rat has been studied. 2. From an ethyl acetate extract of urine, metabolite 1, a cyclopropane ring-cleavage compound, was identified by liquid chromatographic-mass spectrometric analysis 3. A hplc method for determination of the metabolite in rat urine was developed with extraction using Sep-Pak C18 cartridge followed by liquid-liquid extraction. 4. The metabolite excreted during 3 days after administration of illudin S to rat amounted to approximately 10-19% of the dose as free form and 3-5% of the dose as glucuronide.
Osteosarcoma is the most frequent malignant bone tumor in children. It is highly invasive, however, the mechanisms behind osteosarcoma cell invasion are as yet still unknown. In the present study, treatment with TNFalpha enhanced the invasiveness of two human osteosarcoma cell lines, OST and MNNG. TNFalpha treatment also induced tumor cell motility, adhesion to laminin, the expression of matrix metalloproteinase 9 (MMP9), and the nuclear translocation of nuclear factor kappaB (NFkappaB) in the osteosarcoma cells. Moreover, antioxidants inhibited TNFalpha-induced osteosarcoma cell invasion, motility and NFkappaB nuclear translocation, but not adhesion to laminin or MMP9 expression. NFkappaB decoy, another NFkappaB inhibitor, also inhibited TNFalpha-induced osteosarcoma cell invasion and motility. Therefore, motility and NFkappaB activation were possibly related to TNFalpha-induced osteosarcoma cell invasion. However, adhesion to laminin or MMP did not demonstrate any correlation with TNFalpha-induced osteosarcoma cell invasion. Although NFkappaB is known to regulate TNFalpha-induced phenotypes, it may influence only motility and invasion, but not the MMP or laminin-mediated adhesion of these osteosarcoma cells.
A new computerized image processing system was developed and applied clinically for three-dimensional visualization and volume calculation of cardiac structures, which were recorded in more than seven original two-dimensional echocardiograms in parallel planes. Three-dimensional display of this series of original two-dimensional echocardiograms was performed automatically using an overlaid display with different gray levels designating depths. The limitation of the present study was in the recording of original two-dimensional echocardiograms in parallel planes.
Porous TiO2 film was prepared by sol-gel method from TiO2 sol containing polyvinylpyrolidone (PVP). Photocatalytic activity of the film was evaluated by the elimination rate of ethylene. Several adsorbents including zeolite and silica powders were incorporated into the TiO2 film. All the adsorbents enhanced the activity. The optimum adsorbent content was 0.005-0.01 g/ml of the coating sol solution. Silica provided better activity than zeolite. At high humidity and in dry air the activity decreased.
We treated 63 patients (pts) suffering from metastatic liver cancer with intra-arterial infusion chemotherapy, and analysed 44 of their for survival since the first treatment with regard to the primary foci of cancer and the method of intra-arterial therapy. Via the superficial femoral artery, we performed superselective hepatic catheterization by Seldinger's method. Three types of intraarterial therapy were used: Gelfoam embolization with mitomycin-C (MMC) in 12 pts (GS-TAE), capillary chemo-embolization with MMC-Lipiodol emulsion in 28 pts (LP-TAI) and "one-shot" slow infusion of MMC or cisplatinum in 4 pts. Fifty-percent survival was 189 days in pts with metastases from colo-rectal cancer (n = 20), 109 days from gastric cancer (n = 9), 100 days from pancreatobiliary cancer (n = 5) and 240 days from breast cancer (n = 7). More than one-year survival was obtained in 13 out of the 40 pts (32.5%). Survival of 12 pts, treated with GS-TAE regimen, was not significantly superior to that of 28 pts with LP-TAI regimen. Hence, we conclude that LP-TAI is the treatment of choice in chemo-embolization for unresectable liver metastases, because it causes less damage to the hepatic arterial beds, and facilitates repeat intraarterial therapy in these pts.
Histochemical organization of the Caudata olfactory system remains largely unknown, despite this amphibian order showing phylogenetic diversity in the development of the vomeronasal organ and its primary centre, the accessory olfactory bulb. Here, we investigated the glycoconjugate distribution in the olfactory bulb of a semi-aquatic salamander, the Japanese sword-tailed newt (Cynops ensicauda), by histochemical analysis of the lectins that were present. Eleven lectins showed a specific binding to the olfactory and vomeronasal nerves as well as to the olfactory glomeruli. Among them, succinylated wheat germ agglutinin (s-WGA), soya bean agglutinin (SBA), Bandeiraea simplicifolia lectin-I (BSL-I) and peanut agglutinin showed significantly different bindings to glomeruli between the main and accessory olfactory bulbs. We also found that s-WGA, SBA, BSL-I and Pisum sativum agglutinin preferentially bound to a rostral cluster of glomeruli in the main olfactory bulb. This finding suggests the presence of a functional subset of primary projections to the main olfactory system. Our results therefore demonstrated a region-specific glycoconjugate expression in the olfactory bulb of C. ensicauda, which would be related to a functional segregation of the olfactory system.
Portopulmonary venous anastomosis is a potential channel for systemic arterial embolization during embolization procedures for bleeding esophageal varices. To document the presence of such anastomoses, 15 patients with esophageal varices were studied by real-time contrast echocardiography combined with transhepatic cineportography. Cinefluorographic technique, which was applied for this purpose, occasionally failed to demonstrate the dynamic events in the left atrium because of rapid dilution of contrast medium. Echocardiography after the injection of dextrose solution into the gastric coronary vein allowed two-dimensional real-time images of contrast echoes in the left cardiac chambers. By combining these two methods, more reliable diagnostic information was obtained in five of the 15 patients studied.
Medium-chain and long-chain acyl-CoA dehydrogenases from rat liver have been purified in two forms, holoenzymes containing FAD and apoenzymes which do not contain this cofactor. In contrast, short-chain acyl-CoA dehydrogenase can only be isolated as the holoenzyme. Marked differences in the reactivity to organic sulfhydryl reagents were observed between the apo and holo forms of these enzymes. While the two apoenzymes were severely inactivated by N-ethylmaleimide (NEM), p-chloromercuribenzoate (pCMB), and iodoacetate (IAA), the two corresponding holoenzymes were not susceptible to these reagents. The inactivation of the two apoenzymes by NEM followed pseudo-first order kinetics. Incubation of the apoenzymes with FAD completely prevented the inactivation by the organic sulfhydryl reagents. Methylmercury halides (iodide or chloride) inactivated both the apo and holo forms of medium-chain and long-chain acyl-CoA dehydrogenases. On the other hand, holo-short-chain acyl-CoA dehydrogenase behaved somewhat differently from the other two holoenzymes in that it was inactivated by pCMB (but not NEM or IAA) following a pseudo-first order process. The titration of the two apoenzymes with [14C]NEM and that of the holo-short-chain acyl-CoA dehydrogenase with [14C]pCMB indicated that all three acyl-CoA dehydrogenases contain a single essential cysteine residue/subunit. In the inactivation of holo-medium-chain and holo-long-chain acyl-CoA dehydrogenases with methylmercury halide, the same essential cysteine residue was modified without perturbing or releasing the enzyme-bound FAD. The inactivations of the three holoenzymes by appropriate organic sulfhydryl reagents were prevented by prior incubation with substrate. These experimental results indicate that the essential cysteine residue is located in the vicinity of the FAD- and substrate-binding sites within the active center of the enzymes. It appears, however, that this cysteine residue does not participate directly in FAD binding.
Through extensive training, humans can become "visual experts, " able to visually distinguish subtle differences among similar objects with greater ease than those who are untrained. To understand the neural mechanisms behind this acquired discrimination ability, adult monkeys were fully trained to discriminate 28 moderately complex shapes. The training effects on the stimulus selectivity of cells in area TE of the inferotemporal cortex were then examined in anesthetized preparations. Area TE represents a later stage of the ventral visual cortical pathway that is known to mediate visual object discrimination and recognition. The recordings from the trained monkeys and untrained controls showed that the proportion of TE cells responsive to some member of the 28 stimuli was significantly greater in the trained monkeys than that in the control monkeys. Cell responses recorded from the trained monkeys were not sharply tuned to single training stimuli, but rather broadly covered several training stimuli. The distances among the training stimuli in the response space spanned by responses of the recorded TE cells were significantly greater in the trained monkeys than those in the control monkeys. The subset of training stimuli to which individual cells responded differed from cell to cell with only partial overlaps, suggesting that the cells responded to features common to several stimuli. These results are consistent with a model in which visual expertise is acquired through the development of differential responses by inferotemporal cells to the images of relevant objects.
A gas-chromatographic method for urinary organic acid analysis is described, designed to be used routinely for the diagnosis of organic aciduria. It involves extraction of urine with ethyl acetate, dehydration of extract residues, and trimethylsilylation. Organic acids are identified by using an extensive list of retention indices published in the accompanying paper (this issue). Quantitative values are given for organic acids in urines from 50 ostensibly normal subjects. Typical chromatograms of urinary organic acids from patients with eight well-established organic acidurias are also shown.
Glial cell line-derived neurotrophic factor (GDNF), neurturin (NTN) and their receptors (GFRalpha1, GFRalpha2 and Ret) play an important role in the survival of neurons in the central and peripheral nervous system. For example, GDNF as well as other trophic factors promotes photoreceptor survival during retinal degeneration. Recent studies have proposed that part of neurotophic rescue of photoreceptors may be indirect, mediated by interaction of the neurotrophic factors with other cell types, that in turn release secondary factors that act directly on photoreceptors. In the present study, we examined the GDNF receptor expression in control and light-damaged retina, and found that GFRalpha2 protein is upregulated in retina-specific Müller glial cells during photoreceptor degeneration. We also examined the effect of GDNF or NTN on cultured Müller cells. Exogenous GDNF increased brain-derived neurotrophic factor, basic fibroblast growth factor and GDNF, but not NTN mRNA production. On the other hand, NTN increased NTN, but not GDNF mRNA production in cultured Müller cells. These observations suggest that GDNF, NTN and their receptors are involved in the regulation of trophic factor production in retinal glial cells, and that functional glia-neuron network may utilize GDNF family for the protection of neural cells during retinal degeneration.
The heat shock protein ClpB in Escherichia coli is a protein-activated ATPase and consists of two proteins with sizes of 93 and 79 kDa. By polymerase chain reaction-aided site-directed mutagenesis, both the proteins have been shown to be encoded by the same reading frame of the clpB gene, the 93-kDa protein (ClpB93) from the 5'-end AUG translational initiation site and the 79-kDa protein (ClpB79) from the 149th codon (an internal GUG start site). Both the purified ClpB93 and ClpB79 proteins behave as tetrameric complexes with a very similar size of about 350 kDa upon gel filtration on a Superose-6 column. Both appear to be exclusively localized to the cytosol of E. coli. Both show inherent ATPase activities and have an identical Km of 1.1 mM for ATP. The ATPase activity of ClpB93 is as markedly stimulated by proteins, including casein and insulin, as that of wild-type ClpB, but the same proteins show little or no effect on ClpB79. Because ClpB79 lacks the 148 N-terminal sequence of ClpB93 but retains the two consensus sequences for adenine nucleotide binding, the N-terminal portion appears to contain a site(s) or domain(s) responsible for protein binding. Furthermore, ClpB79 is capable of inhibiting the casein-activated ATPase activity of ClpB93 in a dose-dependent manner but without any effect on its inherent ATPase activity. In addition, ClpB93 mixed with differing amounts of ClpB79 behave as tetrameric molecules, although its protein-activated ATPase activity is gradually reduced. These results suggest that tetramer formation between ClpB93 and ClpB79 may be responsible for the inhibition of the activity.
Although living donor liver transplantation for small pediatric patients is increasingly accepted, its expansion to older/larger patients is still in question because of the lack of sufficient information on the impact of graft size mismatching.
A total of 276 cases of living donor liver transplantation, excluding ABO-incompatible, auxiliary, or secondary transplants, were reviewed from graft size matching. Forty-three cases were highly urgent cases receiving intensive care preoperatively. Cases were categorized into five groups by graft-to-recipient weight ratio (GRWR): extra-small-for-size (XS; GRWR<0.8%, 17 elective and 4 urgent cases), small (S; 0.8< or =GRWR< 1.0%, 21 and 7), medium (M; 1.0< or =GRWR<3.0%, 119 and 19), large (L; 3.0< or =GRWR<5.0%, 67 and 10), and extra-large (XL; GRWR> or =5.0%, 9 and 3).
Smaller-for-size grafts were associated not only with larger and older recipients, but also with rather older donors. Posttransplant bilirubin clearance was delayed and aspartate aminotransferase corrected by relative graft size was higher in XS and S. Posttransplant hemorrhage and intestinal perforation were more frequent in XS and S, and vascular complications and acute rejection were more frequent in larger-for-size grafts. Consequently, graft survival in XS (cumulative 58% and actuarial 42% at 1 year) and S (76% and 74%) was significantly lower compared with that in M (93% and 92%) in elective cases. Graft survival in L (83% and 82%) and XL (75% and 71%) did not reach statistical significance.
The use of small-for-size grafts (less than 1% of recipient body weight) leads to lower graft survival, probably through enhanced parenchymal cell injury and reduced metabolic and synthetic capacity. Although large-for-size grafts are associated with some anatomical and immunological disadvantages, the negative impact is less pronounced.
During S phase, chromatid cohesion is established only between nascent sisters and with faithful pairing along their entire region, but how this is ensured is unknown. Here we report that sister chromatid cohesion is formed and maintained by a unique mechanism. In fission yeast, Eso1p, functioning in close coupling to DNA replication, establishes sister chromatid cohesion whereas the newly identified Cohesin-associated protein Pds5p hinders the establishment of cohesion until counteracted by Eso1p, yet stabilizes cohesion once it is established. Eso1p interacts physically with Pds5p via its Ctf7p/Eco1p-homologous domain.
This study was undertaken to compare the contribution of both the anaerobic threshold (AT) and onset of blood lactate accumulation (OBLA) with endurance performance in eleven non-endurance trained active male adults. AT determination was based upon both blood lactate and gas exchange criteria, while OBLA was determined as the point corresponding to a blood lactate concentration of 4 mmol X 1(-1). A dependent t-test revealed significantly higher values for OBLA related variables as compared with corresponding AT related variables, thereby validating the comparison of these two categories of variables in relation to endurance performance. Approximately 67, 60, 37, and 50% of the variance in endurance performance were accounted for by AT-VO2 (ml X kg-1 X min-1), AT-WR, OBLA-VO2 (ml X kg-1 X min-1), and OBLA-WR, respectively. When AT-HR (X2) was added to the AT-VO2 (X1) as another predictor, the contribution of these variables to endurance performance increased appreciably to 84%. The resultant multiple regression equation was Y = -4.564 X1 + 2.68 IX2 + 90.6 (SEE = 9.9 s). Consequently, it is suggested that variables related to an abrupt increase in blood lactate, together with several gas exchange responses, could explain endurance performance in a shorter distance to a greater extent than variables related to a rigid threshold of 4 mmol X 1(-1).
A new operative method, encephalo-duro-arterio-synangiosis, for the surgical treatment of pediatric moyamoya disease has been developed. The rationale of the operation is to help promote the natural tendency of this disease to develop cerebrovascular collaterals. The method is to transplant a scalp artery with a strip of galea, leaving the distal as well as the proximal arteries intact, to a narrow linear dural opening made under an osteoplastic craniotomy. A representative case is described and the operative procedure is outlined. Our new method is compared with other surgical treatments of this disease.
Chromosome translocations involving band 12p13 are known to be involved in a variety of hematologic malignancies, some of them resulting in rearrangement of the ETV6/TEL gene. Applying the fluorescence in situ hybridization (FISH) method, we found a cryptic translocation t(12;15)(p13;q25) in an adult acute myeloid leukemia (AML) patient. Hybridization with cosmid probes showed that the ETV6 gene was rearranged in this translocation. A patient-specific cDNA library was screened with ETV6 cDNA, and a novel fusion transcript was identified between the ETV6 and TRKC/NTRK3 gene located on 15q25. TRKC is a receptor tyrosine kinase that is activated by neurotrophin-3 (NT-3). It is known to be expressed broadly in neural tissues but not in hematologic cells, so far. ETV6-TRKC chimeric transcript encoded the pointed (PNT) domain of the ETV6 gene that fused to the protein-tyrosine kinase (PTK) domain of the TRKC gene. Two types of fusion transcript were determined, one that included the entire PTK domain of TRKC and the other in which the 3'-terminal 462 bp of TRKC was truncated within the PTK domain. Western blot analysis showed the expression of both chimeric proteins of 52 and 38 kD in size. Our results suggest that chimeric PTK expressed in the leukemic cells may contribute to cellular transformation by abnormally activating TRK signaling pathways. Moreover, this is the first report on truncated neurotrophin receptors associated in leukemia.