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Transfusion-related acute lung injury (TRALI) is a life-threatening adverse reaction to transfusion. It is characterized by non-cardiogenic pulmonary edema that develops during or within 6 h after transfusion. Transfusion of blood products or massive transfusion has long been known as a rare cause of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Because the main causes of ALI/ARDS are sepsis and/or pneumonia, little attention has been paid to transfusion as a cause of lung injury. Owing to indifference to and underrecognition of this complication, ALI after transfusion may be attributed to other causes. Moreover, physicians tend to attribute the cause of respiratory failure to more common complications of transfusion such as allergic reaction and circulatory overload. Even if an appropriate diagnosis of non-cardiogenic pulmonary edema is made, transfusion may not be identified as its cause. Although anti-leukocyte antibodies have been proved to be one of the main causes of TRALI, the precise mechanism of this syndrome is poorly understood. Anti-HLA and -HNA antibodies in labile blood products are reported to cause TRALI, and animal models of TRALI show that these antibodies induce lung injury under certain experimental conditions. We have recently showed that anti-CD36 antibody caused TRALI in two patients. This finding suggests that as-yet-unknown antibodies other than anti-HLA or -HNA antibodies might cause TRALI. According to current haemovigilance reports and previous look-back studies, the incidence of TRALI is not very high. This finding supports the concept of the two-hit theory of ALI, where certain patients’ clinical conditions are prerequisite in addition to transfusion for developing TRALI. A recent study in the ICU of a tertiary care medical centre has revealed a high incidence of suspected TRALI cases. This study revealed that female plasma, number of pregnancies in donors, number of donor units positive for anti-granulocyte antibodies and anti-HLA class II antibodies and concentration of lysophophatidylcholine in donor products are associated with developing TRALI. Our recent prospective study has revealed the predominance of male Fresh frozen plasma (FFP) FFP in post-transfusion respiratory function when comparing male only FFP and mixed FFP in surgical patients. The incidence of TRALI in the UK was successfully reduced by using preferentially male plasma. Although TRALI has a relatively better prognosis than ALI with other causes, TRALI has still been the leading cause of transfusion-related death in the United States in recent years. The prevention of TRALI caused by plasma products has been successful, but TRALI caused by apheresis platelets is still problematic. A recent study has suggested that the prevalence of anti-HLA antibodies in female donors increases with the number of pregnancies. Thus, screening for anti-HLA antibodies has emerged as an effective measure to prevent TRALI caused by apheresis platelets. At present, no single measure can thoroughly eliminate TRALI; however, early diagnosis and intervention may improve the outcome for patients with TRALI. Further study is required to elucidate the mechanisms of TRALI, which may lead to the development of preventive measures and treatment.

The superconducting magnetic separation system which separates ferromagnetic particles from powder mixture has been developed. It is required to remove the impurities from the powdered products without using chemical or heating processing. The impurities are usually powdered stainless steel from the piping which are deformed strongly and shows ferromagnetism. Magnetic separation using permanent magnets have been used for the separation. The conventional magnetic separation system has not shown the expected performance especially for the small sized impurities. To solve the problem, superconducting magnetic separation system was developed. We used the magnet with magnetic field up to 2 T. The boa size was 100 mm in diameter. Inside of the magnetic boa the magnetic filters are located to produce the high magnetic gradient. The performance of the separator was reported together with the design guideline.

Recently, evidence implicating the roles of the anti-human leucocyte antigen (HLA) class II antibody in the development of transfusion-related acute lung injury (TRALI), which is one of the most serious possible side effects of transfusion, has been accumulating. The aim of this study is to clarify the roles of the anti-HLA DR alloantibody in TRALI development. Cultured human lung microvascular endothelial (LME) cells were incubated with either HLA-DR15-positive or HLA-DR15-negative monocytes together with serum from a single multiparous donor previously implicated in a clinical case of TRALI and known to contain anti-HLA DR15 antibody. Production of soluble leukotriene B(4) (LTB(4)) was measured in the supernatant and found to be markedly increased in the presence of HLA-DR15-positive monocytes but not with the HLA-DR15-negative monocytes or in the absence of LME cells. The vascular cell adhesion molecule-1 expression in LME cells and leucocyte-function-associated molecule-1 (LFA-1) expression in HLA-DR15-positive monocytes were notably enhanced after combined culture of LME cells, HLA-DR15-positive monocytes and TRALI-inducing anti-HLA DR15 antibody-positive serum. In conclusion, anti-HLA DR alloantibodies may be implicated in LME dysfunction that leads to TRALI, in a monocyte-dependent manner.

To achieve low conversion-loss and high image-rejection performance in the wide band for up and down conversion, an SSB subharmonically pumped mixer using an inphase RF divider/combiner is proposed. The SSB mixer monolithic microwave integrated circuit (MMIC) is integrated in a small area of 1.8/spl times/1.3 mm/sup 2/ and shows good performance at 21.6 to 30.8 GHz.

This paper describes novel high-isolation monolithic microwave/millimeter-wave integrated circuit (MMIC) field-effect transistor (FET) switches that have higher isolation characteristics than conventional switches without much insertion loss degradation. The newly developed switches consist of series/shunt FETs and T-shaped R-C-R circuit. Each FET switch utilizes the parasitic capacitive component of the FETs in the off-state to produce a band-rejection filter at the operating frequency. The design method of the newly proposed switches and their characteristics are described herein. With this method, the isolation characteristics are improved by more than 15 dB between 5.4 GHz and 6.4 GHz and more than 20 dB between 5.5 GHz and 6.1 GHz over conventional values.

The objective was to report the first pathologically confirmed case of partly functionally preserved medulla oblongata in a patient with catastrophic traumatic brain injury. A patient is described with epidural haematoma with normal breathing and blood pressure and a retained coughing reflex brought on only by catheter suctioning of the carina. Multiple contusions in the thalami and pons were found but the medulla oblongata was spared at necropsy. In conclusion, medulla oblongata function may persist despite rostrocaudal deterioration. This comatose state ("medulla man") closely mimics brain death.

To evaluate the specific reactivity of HLA Class I antibodies (HLA-I Abs) in acute non-hemolytic transfusion reactions (ANHTRs) using solid phase assays (SPAs) and conventional complement-dependent lymphocyte cytotoxicity test (LCT). ANHTRs are major issues in transfusion medicine. Anti-leukocyte antibodies have been implicated as one of the causative agents of transfusion-related acute lung injury (TRALI) and febrile reaction. Antibodies to HLA Class I and/or Class II (HLA Abs) have been intensively studied using SPAs for TRALI, but not for febrile reaction. About 107 patients and 186 donors associated with ANHTRs were screened for HLA Abs by SPAs such as enzyme-linked immunosorbent assay (ELISA) and the Luminex method. When HLA-I Ab was detected, its specific reactivity was evaluated by comparing its specificity identified by the Luminex method using recombinant HLA molecules and cognate HLA antigens (Ags), as well as LCT with or without anti-human globulin (AHG). The incidences of HLA Abs were as high as 32·7% of patients' serum samples and 16% of donors' serum samples. The incidence of HLA-I Abs did not differ significantly between cases of febrile and allergic reactions. However, HLA-I Abs associated with febrile reaction showed a significantly higher rate of possessing specific reactivity to cognate HLA Ags than those associated with allergic reactions. In addition, the Luminex method enabled the detection of HLA-I Abs much earlier than AHG-LCT in serum samples from a patient with febrile reaction and platelet transfusion refractoriness (PTR). SPAs seem more useful than AHG-LCT for evaluating reactivity of antibodies in ANHTR cases.

To investigate the effects of benzidine (BZ) and beta-naphthylamine (BNA) on the immune system in man, the activity of natural killer (NK) cells as well as the relative number (percentage) of Leu 11a positive cells in peripheral blood lymphocytes were measured in 63 dyestuff workers exposed to BZ and BNA (aromatic amines, AA). The cytotoxic potential per NK cell (unit NK cell activity) was approximated by dividing the NK activity per fixed numbers of unseparated mononuclear cells by the percentage of Leu 11a positive lymphocytes that mediated NK activity. Thirty one of these workers had previously been treated for bladder cancer and then cured (ex-cancer AA workers) whereas the remaining 32 had not been diagnosed as having bladder cancer (non-cancer AA workers). There was no significant difference in the gross NK activity per unseparated peripheral mononuclear cells among ex-cancer AA workers, non-cancer AA workers, and the control group (p greater than 0.05). The relative number of Leu 11a positive cells, on the other hand, was significantly higher in AA workers than in the control group (p less than 0.01). The unit NK cell activity, as a result, was significantly more reduced in both ex-cancer and non-cancer AA workers than in the control group (p less than 0.05 and p less than 0.01, respectively). Between ex-cancer and non-cancer AA workers, no significant difference was observed in terms of unit NK cell activity. These results indicated that the function of NK cells per se was impaired in AA workers whereas the number of circulating NK cells was relatively increased.

summary To study the relationship between antibodies detected in patients’ and/or donors’ sera and the clinical features of acute non-haemolytic transfusion reactions (ANHTRs), and to determine any gender-related difference. ANHTRs range from urticaria to transfusion-related acute lung injury (TRALI). Antibodies to human leukocyte antigen (HLA), granulocytes, platelets, and/or plasma proteins are implicated in some of the ANHTRs. A higher antibody positivity is expected for females than for males. A comparative study of ANHTRs for antibody positivity and their clinical features between females and males for both patients and donors is helpful for characterizing ANHTRs including TRALI more clearly, but such studies are few and outdated. Two hundred and twenty-three ANHTR cases reported by 45 hospitals between October 2000 and July 2005 were analysed. The patients and 196 donors of suspect blood products were screened for antibodies to HLA Class I, HLA Class II, granulocytes, and platelets. The patients were also screened for anti-plasma protein antibodies. The types and severity of ANHTR did not differ significantly between female and male patients. The frequency of the anti-HLA antibodies, but not that of the non-HLA antibodies, was significantly higher in females. Non-HLA antibodies were significantly associated with severe reactions in females. All the TRALI cases had predisposing risk factors for acute lung injury, and 60% of the cases showed anti-leucocyte antibodies. Although the anti-HLA antibodies were detected more frequently in females than males, no significant association of ANHTRs including TRALI with gender, not only for patients, but also for donors, could be shown in this study.

To measure total energy expenditure (TEE) for normal healthy Japanese by the doubly labelled water (DLW), and to compare the physical activity level (PAL) among categories classified by the categories used in daily reference intake (DRI), Japan and the International Physical Activity Questionnaire (IPAQ).A total of 150 healthy Japanese men and women aged 20- to 59-year-old living in four districts of Japan. TEE was measured by the DLW method, and the PAL was calculated from TEE divided by basal metabolic rate. Simultaneously with TEE measurement, the PAL was assessed employing the categories used in DRI, Japan and IPAQ.The average TEE and PAL were 10.78+/-1.67 MJ/day and 1.72+/-0.22 for males and 8.37+/-1.30 MJ/day and 1.72+/-0.27 for females, respectively. The subjects in the highly active categories assessed by both DRI and IPAQ showed significantly higher PAL compared with less active categories. However, PALs among light and moderate categories by DRI, and insufficient and sufficiently active by IPAQ were not significantly different.In developed countries, highly active subjects could be assessed by a simple questionnaire. However, the questionnaire should be improved to clarify the sedentary to moderately active subjects by assessing carefully very light to moderate physical activity.

A 70-year-old man presenting with a chief complaint of tongue swelling had been diagnosed with prostate cancer 1 year earlier. He had been on an oral angiotensin-converting enzyme inhibitor (ACE) inhibitor for hypertension for 20 years. Two months before the first of 4 episodes of tongue swelling within a period of 40 days, he had been prescribed oral estramustine phosphate (EMP) for the prostate cancer. He was admitted to our hospital for the evaluation after massive swelling of the tongue and epiglottis which necessitated tracheotomy. Food allergies, allergic reactions to environmental factors, and hereditary angioneurotic edema were excluded. Massive swelling of the tongue and epiglottis disappeared completely after EMP was discontinued. We concluded that angioedema was induced by EMP used concurrently with the ACE inhibitor.

The aim of the study was to investigate the increase in myocardial (99m)Tc-methoxyisobutylisonitrile (sestamibi) retention in humans during pharmacologic vasodilation.For calculation of the increase in (99m)Tc-sestamibi retention during hyperemia, baseline and adenosine triphosphate (ATP)-induced hyperemic stress sestamibi studies were performed using a same-day rest-stress protocol. On the injection of sestamibi, left ventricular dynamic data were obtained for 90 s. The increase in sestamibi retention from baseline to hyperemia was calculated by the formula [abstract: see text] where Cm(h)(t) and Cm(b)(t) are myocardial counts on the tomographic image, and Cb(b)(tau) and Cb(h)(tau) are the left ventricular blood-pool counts during the first transit of sestamibi at baseline and during hyperemia, respectively. Coronary flow increase during intravenous ATP stress was measured using intracoronary Doppler flow guide wire and compared with the scintigraphic results of 28 measurements in 22 patients.Sestamibi retention increased as coronary flow velocity increased but plateaued at2.5-3 times baseline flow velocity. The relationship between the increase in sestamibi retention (Y) and the increase in flow (X) is expressed as follows: Y = 0.44 + 0.60X - 0.068X(2) (r = 0.82).In humans, the increase in (99m)Tc-sestamibi myocardial retention underestimates coronary flow reserve, particularly at high flow rates. Knowledge of these tracer retention characteristics will contribute to a more comprehensive understanding of the manner and interpretation of stress sestamibi imaging.

The asialoglycoprotein receptor is an abundant hetero-oligomeric endocytic receptor that is predominantly expressed on the sinusoidal surface of the hepatocytes. A number of physiological and pathophysiological functions have been ascribed to this hepatic lectin (HL), the removal of desialylated serum glycoproteins and apoptotic cells, clearance of lipoproteins, and the sites of entry for hepatotropic viruses. The assembly of two homologous subunits, HL-1 and HL-2, is required to form functional, high affinity receptors on the cell surface. However, the importance of the individual subunits for receptor transport to the cell surface is controversial. We have previously generated HL-2-deficient mice and showed that the expression of HL-1 was significantly reduced, and the functional activity as the asialoglycoprotein receptor was virtually eliminated. However, we failed to detect phenotypic abnormalities. To explore the significance of the major HL-1 subunit for receptor expression and function in vivo, we have disrupted the HL-1 gene in mice. Homozygous HL-1-deficient animals are superficially normal. HL-2 expression in the liver is virtually abrogated, indicating that HL-1 is strictly required for the stable expression of HL-2. Although these mice are almost unable to clear asialo-orosomucoid, a high affinity ligand for asialoglycoprotein receptor, they do not accumulate desialylated glycoproteins or lipoproteins in the plasma.

Introduction This study aimed to elucidate the relationship of night duty, on-call duty, average working hours and job stress to insomnia among hospital doctors. Methods Questionnaires including job factors and the Brief Job Stress Questionnaire, were sent to all alumni of Asahikawa Medical University (n=2937). Of the 568 medical doctors who responded, 430 were hospital doctors; 424 questionnaires were analysed after excluding six because of missing values. Insomnia was estimated using the Athens Insomnia Scale (≥6 points). Explanatory variables were sex, age, specialty, location, night duty, on-call duty, average working hours, job effort, level of job control, support from supervisors, support from co-workers and support from family/friends. Logistic regression analysis was used; sex, age and specialty were forced into the model and other variables were entered into the model in a reverse stepwise manner. Results In the stepwise logistic regression analysis, night duty had a significantly higher OR for insomnia (OR=2.00; 95% CI 1.24 to 3.27). A high levels of job control and high job support had a significantly lower ORs (OR=0.76, 95% CI 0.68 to 0.86; OR=0.88, 95% CI 0.79 to 0.98, respectively). Average working hours was selected in final model but the relationship was not significant. The other variables were not selected in the final model. Conclusion Night duty may induce insomnia, but a high level of job control and a high level of support from co-workers may have a protective effect against insomnia among hospital doctors.

Since the expression of genes for platelet-derived growth factor (PDGF)-A and PDGF beta-receptor are reciprocally regulated in vascular wall cells after balloon injury, we have investigated the ability of specific vasoactive molecules or growth factors to reproduce the injury pattern of gene expression in cultured rat smooth muscle cells (SMCs) and assessed the effect of inactivating alpha-thrombin on injury-induced expression of PDGF-A mRNA by vascular wall cells in vivo. The molecules investigated, to which vascular SMCs may be locally exposed after mechanical injury, included vasoactive factors (alpha- and beta-adrenergic agonists, serotonin, histamine, angiotensin II, and endothelin) and growth factors (PDGF-AA, PDGF-BB, basic fibroblast growth factor, insulin-like growth factor, epidermal growth factor, and alpha-thrombin). In cultured rat SMCs, only alpha-thrombin (0.1-100 nM), among these compounds, produced the pattern of transiently increased PDGF-A and decreased PDGF beta-receptor mRNA. PDGF-B chain mRNA levels remained undetectable in these cultured SMCs. The dependence of these changes in gene expression on the proteolytic activity of alpha-thrombin was shown by the interruption of altered gene expression or DNA synthesis after incubating the cultured SMCs with covalently inactivated alpha-thrombin using D-Phe-Pro-Arg chloromethyl ketone, a synthetic direct active-site irreversible inhibitor of alpha-thrombin. Continuous intravenous infusion of this synthetic antithrombin into baboons for 6 hours (100 nmol/kg per minute maintaining constant plasma levels of 3.0 +/- 0.5 microns/ml) after inducing balloon-catheter arterial injury also prevented the threefold increase in expression of PDGF-A mRNA characteristically exhibited by untreated mechanically injured vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

In the presence of a monoclonal antibody raised against the human thrombin-antithrombin III complex, the reaction between thrombin and antithrombin III proceeded to form preferentially a two-chain form of the inhibitor rather than to follow the major pathway of stable acyl complex formation. We thus propose the term "switching antibody" for an antibody that switches the enzyme-inhibitor reaction (Asakura, S., Matsuda, M., Yoshida, N., Terukina, S., and Kihara, H. (1989) J. Biol. Chem. 264, 13736-13739). By analyzing a CNBr fragment of the thrombin-antithrombin III complex that reacts with the antibody we localized the epitope for the antibody to a strongly hydrophobic residue 382-386 peptide segment, Ala-Ala-Ala-Ser-Thr, of the inhibitor, which is also contiguous with a hydrophobic amino acid Ala at its carboxyl terminus. This particular region should be cryptic in nascent antithrombin III, but could have been exposed to provide the reactive site for the antibody at an early stage of the reaction. Thereby a conformational change may have been induced at or near the reactive site of the complex, facilitating hydrolysis of the inhibitor by the enzyme. Interestingly, this hydrophobic region is highly conserved among members of the serpin family.

The propagation loss characteristics of silica-based optical waveguides with various bending curvatures fabricated on 5 inch Si wafers are investigated. Low loss waveguides more than lm long with a Δ of 0.75% are successfully fabricated and the loss is found to be independent of the curvature radius over 5mm. A minimum loss of 3.5dB/m at ∼1.55 μm is obtained in a waveguide 1.6 m long.

Diltiazem, verapamil and nifedipine suppress sinoatrial (SA) nodal function in the excised rabbit heart. Clinically, however, their suppressive effect on the SA node is modified considerably by the reflex increase in sympathetic tone as a result of the fall in blood pressure caused by the vasodilating action of the calcium antagonists. Diltiazem, verapamil and nifedipine suppress atrioventricular (AV) nodal conduction and prolong refractory periods in the excised rabbit AV node. Clinically, diltiazem and verapamil exert a similar suppressive effect on the AV node and are useful for treating and preventing AV nodal reentrant tachycardia. Nifedipine, in clinically practical doses, has no antiarrhythmic properties, probably because of reflex activation of the sympathetic system secondary to its hypotensive effect, which is greater than that of the other two calcium antagonists. Diltiazem and verapamil may sometimes worsen AV conduction, especially in patients with conduction disturbances. Nifedipine, on the other hand, can be used as a coronary vasodilator with the least untoward effect on AV conduction.

An attempt has been made in this review to cover recent information on the structure of metallic glasses (amorphous metals) obtained by X-ray diffraction. Based on the experimental data, the partial structure factors of a binary metallic glass are given. Various characteristics such as crystallization processes, thermal effects and alloying effects are also discussed.

The physicochemical properties of the purified calf thymus poly(ADP-ribose) polymerase were investigated. The enzyme purified to homogeneity was shown to contain about 10% DNA on a weight basis and its activity to be DNA independent. After removing this fragment of DNA, called the sDNA fraction, the enzyme becomes DNA dependent. The activity of this enzyme preparation was entirely dependent on, and completely restored by, added calf thymus DNA or sDNA. However, the calf thymus DNA concentration needed was a hundred times higher than that of sDNA. The properties of the two enzyme preparations, DNA independent and DNA dependent, were essentially the same. They both reacted against the specific antibody obtained with the DNA-independent poly(ADP-ribose) polymerase. The pH optimum was around 8; the activity was stimulated by Mg2+, Mn2+ and Ca2+, and inhibited by high ionic strength, p-chloromercuribenzoate, ADP-ribose, AMP and polylysine. Nicotinamide, thymidine and NADP were shown to be competitive inhibitors. The enzymatic activity was stimulated by histone H1 when the ratio of DNA to histone H1 was 2. Histones H2A, H2B, H3 and H4 had little effect on the DNA-independent enzyme activity, but were strongly inhibitory for the DNA-dependent enzyme. This inhibitory effect could be reversed by allowing the DNA-dependent enzyme to react with the sDNA fraction before adding histone subfractions. The apparent Km for NAD of the DNA-dependent poly(ADP-ribose) polymerase was shown to vary with the DNA concentration. It was minimum when the amount of sDNA was 10% of that of the enzyme. The ratio of the apparent Km for sDNA to the enzyme concentration was constant at any enzyme concentration. The minimum estimation of the number of base pairs of sDNA required for maximal activation of one enzyme molecule was 16. For calf thymus DNA, this estimation was of 640. These results suggest that the activation of the enzyme needs the formation of some complex between the protein and a specific part of the DNA. This complex was preserved in the DNA-independent enzyme preparation.

A processing protease has been purified from the matrix fraction of rat liver mitochondria. The purified protease contained two protein subunits of 55 kd (P-55) and 52 kd (P-52) as determined by SDS-PAGE. The processing protease was estimated to be 105 kd in gel filtration, indicating that the two protein subunits form a heterodimeric complex. At high ionic conditions, the two subunits dissociated. The purified processing protease cleaved several mitochondrial protein precursors destined to different mitochondrial compartments, including adrenodoxin, malate dehydrogenase, P-450(SCC) and P-450(11 beta), but the processing efficiencies were different each other. The endoprotease nature of the processing protease was confirmed with the purified enzyme using adrenodoxin precursor as the substrate; both the mature form and the extension peptide were detected after the processing. The processing activity of the protease was inhibited by metal chelators, and reactivated by Mn2+, indicating that the protease is a metalloprotease.

The fat embolism syndrome is a well-defined clinical entity that can usually be recognized in patients who have long-bone fractures. Cerebral symptoms of restlessness, confusion, stupor, and coma correlate with the autopsy findings of fat in the brain, but the amount of fat or amount of petechial hemorrhage cannot be quantitated with the severity of the cerebral symptoms. There is a correlation between the clinical manifestations of dyspnea and tachypnea and the autopsy findings in the lungs, which are heavy from edema and alveolar hemorrhage; however, we cannot correlate the degree of pathologic change in the lung, including lung weights, with the severity of findings clinically.