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Study question A prospective study to investigate the relationship between the composition of vaginal microbiota through next-generation sequencing and the efficacy of single frozen blastocyst transfer in the same cycle. Summary answer Dominant presence of lactobacillus and other lactate producing microbes in the upper vagina was highly correlated with implantation of transferred blastocyst in this pilot study. What is known already Next-generation sequencing of 16S rRNA detected microbes in the uterine cavity and recent studies indicated that dominant presence of Lactobacillus correlated highly with successful implantation of the transferred embryos. Aberrant vaginal microbiota has been known to cause poor obstetrical outcomes, however little is known for its effect on embryo implantation in assisted reproduction. Study design, size, duration A prospective study with 25 female subjects transferring a frozen blastocyst using autologous oocyte, over 14 months period in 2019-2020. Participants/materials, setting, methods 25 female patients without tubal and uterine pathology and no history of multiple miscarriages and implantation failures were recruited with consent at a private ART clinic. Transdermal estrogen was used to prepare endometrium. Upper vaginal fluid was obtained in follicular phase of the the same cycle and analyzed through next-generation sequencing, but the result was reported after pregnancy confirmation. Single frozen blastocyst transfer and standard luteal phase support were performed. Institutional IRB approved the protocol. Main results and the role of chance The mean age was 36.2 y.o.(range 29-41 y.o.), and 14 gestational sacs (implantation rate 56%), and 3 miscarriage (21.4%) were observed. Next-generation sequencing for 16S rRNA revealed average 69.2% presence of Lactobacillus (0-100%) and average 78.0% (0.2-100%) lactate producing microbes (LPM: Lactobacillus, Bifidobacterium, Streptococcus, and Enterococcus) in the vaginal fluid. Using 90% as cut-off, implantation rates were 11/15 (73.3%) and 3/10 (30%) with Lactobacillus dominant and non-dominant, 12/16 (75%) and 2/9 (22.2%) with LPM dominant and non-dominant microbiota, respectively. The difference in each group were not statistically significant. The relative risks for pregnancy were 2.63 (95%CI 1.03-6.67, P=0.04) for Lactobacillus and 3.11 (95%CI 1.24-7.79, P=0.02) for LPM. As for ROC analysis for embryo implantation and dominant microbes, AUC and associated criterion were 0.62 and 90.7% (sensitivity 78.6%, specificity 72.7%) for Lactobacillus, 0.69 and 96.6% (sensitivity 85.7%, specificity 72.7%) for LPM, respectively. The difference of AUC was not significant (P=0.24). Limitations, reasons for caution Despite prospective nature of the study, small sample size limited the analytical power of the study. Aneuploidy screening was not performed to remove confounding factor. Wider implications of the findings Our pilot study revealed possible relationship between vaginal microbiota and embryo implantation. Dominance of Lactobacillus or other lactate producing microbes may be advantageous for successful ART. Sampling vaginal fluid for microbe analysis is less invasive than endometrial sampling and can obtain more abundant RNA with possible higher accuracy of analysis. Trial registration number not applicable

The authors report a case of cerebral venous and sinus thrombosis (CVST) in a patient receiving a low-dose estrogen-progestin combination (oral contraceptives, OCs) for uterine adenomyosis. She was switched to gonadotropin-releasing hormone agonist (GnRHa) draw-back therapy, which was successfully administered long-term. Case The patient was a 38-year-old nulligravida with a history of smoking. She presented to this hospital with dysmenorrhea and postmenstrual lower abdominal pain. Adenomyosis was diagnosed using ultrasound and magnetic resonance imaging. She was instructed to stop smoking and was administered low-dose OCs. CVST occurred 18 months later. OC therapy was halted, and only antiplatelet therapy was administered. After six months, her chief complaint symptoms intensified, therefore GnRHa draw-back therapy was administered after obtaining informed consent. No uterine enlargement was observed, and the abdominal pain resolved. During 2.5 years of therapy, her bone density levels remained within normal limits. CVST did not recur and no other thromboses were observed.

The authors report a case of cerebral venous and sinus thrombosis (CVST) in a patient receiving a low-dose estrogen-progestin combination (oral contraceptives, OCs) for uterine adenomyosis. She was switched to gonadotropin-releasing hormone agonist (GnRHa) draw-back therapy, which was successfully administered long-term.The patient was a 38-year-old nulligravida with a history of smoking. She presented to this hospital with dysmenorrhea and postmenstrual lower abdominal pain. Adenomyosis was diagnosed using ultrasound and magnetic resonance imaging. She was instructed to stop smoking and was administered low-dose OCs. CVST occurred 18 months later. OC therapy was halted, and only antiplatelet therapy was administered. After six months, her chief complaint symptoms intensified, therefore GnRHa draw-back therapy was administered after obtaining informed consent. No uterine enlargement was observed, and the abdominal pain resolved. During 2.5 years of therapy, her bone density levels remained within normal limits. CVST did not recur and no other thromboses were observed.

Dietary iron absorption is regulated by duodenal cytochrome b (Dcytb), an integral membrane protein that catalyzes reduction of nonheme Fe3+ by electron transfer from ascorbate across the membrane. This step is essential to enable iron uptake by the divalent metal transporter. Here we report the crystallographic structures of human Dcytb and its complex with ascorbate and Zn2+. Each monomer of the homodimeric protein possesses cytoplasmic and apical heme groups, as well as cytoplasmic and apical ascorbate-binding sites located adjacent to each heme. Zn2+ coordinates to two hydroxyl groups of the apical ascorbate and to a histidine residue. Biochemical analysis indicates that Fe3+ competes with Zn2+ for this binding site. These results provide a structural basis for the mechanism by which Fe3+ uptake is promoted by reducing agents and should facilitate structure-based development of improved agents for absorption of orally administered iron. Ganasen et al. report the crystallographic structures of human duodenal cytochrome b and its complex with ascorbate and Zn2+. This study provides mechanistic insights into how reducing agents promote the uptake of orally administered iron and may facilitate the development of such interventions.

Faujasite-type zeolite films were prepared on foamed stainless steel by the in-situ crystallization method. Precursor solutions were prepared by dissolving water glass and NaAlO2in a NaOH solution and aged at room temperature for two days. The concentrations of the starting materials were varied from 0.29 to 2.3 M (in SiO2concentration) keeping the molar ratios of Na2O:SiO2:Al2O3fixed at 3.6:3.0:1.0. The foamed stainless steel substrate had about 90% of porosity and an average pore size of 600 μ m. It was dip-coated in the precursor solution four times, then hydrothermally treated at 80∘, 110∘ and 150∘C for 6–48 h. The XRD patterns and SEM photographs revealed that faujasite-type zeolite was formed predominantly at a SiO2concentration of 1.1 M, temperature of 110∘C and duration of 24 h, with a product particle size of 2–5 μ m. At higher concentrations of the precursor solution, hydroxylsodalite becomes the major product rather than faujasite-type zeolite. The adherence strength of the zeolite grains deposited on the foamed stainless steel is higher in the in-situ crystallization method than when a conventional solution method is used. Thus, the in-situ crystallization method is concluded to be effective for preparing zeolite films even on metal substrates.

This paper outlines the defect reduction measures performed during the development of a 130-nm Cu dual-damascene process. The test methodology, using short-loop test structures, included defect tracing, overlaying defect data and electrical measurement data, physical analyses based on these results, and analyses of defect size distribution. While the defect size distributions for large-scale integration processes are considered to depend on x/sup -k/, the distribution for the Cu dual-damascene process is found to be different and is instead characterized by a cumulative distribution described by the composition of several Lorentzian functions. Using these procedures, defect densities were successfully reduced by 50% in half the time taken previously and without the need for actual products.

Although previous retrospective reports have demonstrated the developmental course of several colorectal tumors, the natural history and progression of depressed carcinoma, especially in the early stage, remains obscure. We report a case of superficial depressed tumor in the transverse colon in a 71-year-old man, which did not change in size and gross configuration through prospective colonoscopic observation over a period of 19 months but which was finally diagnosed as early-stage submucosal invasive cancer. Most depressed cancers have been supposed to arise de novo and grow rapidly, showing aggressive behavior when 10 mm or less in size. However, this case report may suggest that even a depressed tumor may grow to approximately 10 mm within the mucosal layer over a few years and that the growth of colorectal tumors, whether they are polypoid or depressed in configuration, might be fairly slow.

Ceftazidime-resistant Enterobacter aerogenes was isolated from blood cultures of three patients with fever. DNA analysis using pulsed-field gel electrophoresis and ribosomal RNA gene restriction digest pattern analysis revealed that the strains were clonally similar to each other with a 79.3-96.0% homology. The same strain of E. aerogenes was isolated from a three-way stopcock connected to the indwelling catheter in one of the patients at a concentration of 45 cfu/mL. A similar strain was also isolated from the urine of one other patient on the same floor. The data suggest that E. aerogenes caused septicaemia via low bacterial contamination of a three-way stopcock in a peripheral drip intravenous infusion system in at least one patient, and that the outbreak of E. aerogenes infections was due to clonally-related strains.

The present paper describes the design concept and manufacturing of a new compact laminar flow heat exchanger with stainless-steel micro-tubes for helium refrigerators. In the temperature range of less than 20 K, aluminum plate fin type heat exchangers exhibit a remarkable fall of performance characteristics as a compact heat exchanger. We presented in a previous paper that some compact heat exchangers with good performance in the temperature range of less than 4 K are required for a subcooled He II refrigerator cycle to be worked with 3He turbo-compressors (F. Doty, et al., A new look at the closed brayton cycle, Proceedings, IECEC-90 Reno, NV, 1991, p. 116). For this requirement, we developed a micro-tube strip counter flow type heat exchanger, which consists of 12 elements with a total of 4800 stainless steel micro-tubes. Each element is formed with 400 tubes and a newly developed vacuum brazing method was applied for the bonding to the side plate. Each tube has an inner diameter of 0.5 mm, an outer diameter of 0.7 mm and is 310 mm long. We developed a cladding plate with two layers of gold brazing sheet sandwiched inside. In aerodynamic and thermal design of the element, the laminar flow conditions were adopted for the flows of inner and outer tubes to keep a high heat transfer rate and a low pressure loss.

CD138-positive and Kaposi's sarcoma-associated herpes virus (KSHV)-negative B cell lymphoma with serosal spreading of the body cavity and lymphadenopathy is presented. Our lymphoma cells showed pleomorphic morphology and a clonal immunoglobulin gene rearrangement. Immunophenotypically, they lacked B- and T-cell-associated antigens but expressed strong membranous CD138 antigen along the serosa. Although our case was not conventional primary effusion lymphoma (PEL) because of the absence of KSHV and the presence of lymphadenopathy, its unique phenotype and serosal spreading were consistent with those of PEL. Our case suggests that, irrespective of KSHV infection, some pleomorphic B cell lymphomas with membranous CD138 expression show a peculiar serosal spreading.

We report a case of complete remission of multiple hepatocellular carcinomas after oral administration of enteric-coated tegafur/uracil. A 77-yr-old woman was diagnosed as having recurrent hepatocellular carcinoma associated with decompensated liver cirrhosis. We administered enteric-coated tegafur/uracil to this patient. After 1 month of oral administration, there was a decrease in tumor markers. An image analysis showed disappearance of hepatocellular carcinoma. No recurrence of the hepatocellular carcinoma was recognized for 18 months up to the time of the patient's death, which was due to massive bleeding from a hemorrhagic rectal ulcer. At autopsy, the tumor lesion had necrotized. Oral administration of enteric-coated granules containing tegafur/uracil may provide an effective treatment for hepatocellular carcinoma.

A cooperative signal reception and down-link beam-forming algorithm is proposed for mobile communication systems employing phase-shift-keying (PSK) modulation. Down-link beam optimality is defined as maximizing the desired reference user's average received power while keeping the noise power plus total amount of average powers received by other users less than or equal to a certain constant level. The proposed algorithm requires neither the detection of other user's signals nor knowledge about the direction-of-arrivals (DOA)'s of the incident path components. Results of a series of exhaustive simulations are presented to demonstrate the overall performance of the proposed algorithm. For a hexagonal cell layout, the distribution of signal-to-interference power ratio (SIR) in a reference (central) cell with the optimal down-link beam is evaluated and compared with that with a unit gain omnidirectional antenna through computer simulations for an eight-element circular array. The beam-forming performances are also evaluated under several sets of practical parameter values with regard to the fading correlation.

Purpose:Our purpose was to select the proper chromosomes for preimplantation diagnosis based on aneuploidy distribution in abortuses and to carry out a feasibility study of preimplantation diagnosis for embryos using multiple-probe fluorescence in situ hybridization (FISH) on the selected chromosomes of biopsied blastomeres.

Conventional T cells (i.e. TCRhigh) are generated by the main stream of T-cell differentiation in the thymus. However, primordial T cells (i.e. TCRint) are generated by extrathymic pathways and an alternative intrathymic pathway. Since TCRint cells contain self-reactive clones, the diversity of the T-cell antigen receptor (TCR) complementarity-determining region (CDR) 3 was examined. The predominant Vbeta8.2+ clones among TCRint cells were selected for DNA sequencing. Thymectomized, irradiated mice subjected to bone-marrow transplantation (BMT) were used; graft-versus-host disease (GVHD), B6-->(B6xC3H/He)F1 and syngeneic BMT, B6-->B6. In these combinations, only TCRint cells were generated. Vbeta8.2+ cells with a low diversity of CDR3 of V-gene expanded in GVHD mice. Vbeta8.2+ cells of TCRint and TCRhigh cells in normal mice were polyclonal, showing that the former has a lower diversity of CDR3 than the latter. The clonality of activated TCRhigh cells was examined, in which CD3high cells (bml2 mice) were injected into 1 Gy-irradiated B6 nude mice. Some Vbeta8.2+ clones among TCRhigh cells were expanding but the diversity of CDR3 was greater than that of CD3int cells, despite the fact that the recognition site of the H-2 difference was smaller. Taken together with invariant usage of V alpha14, these results suggest that TCRint cells have a low diversity of CDR3 of Vbeta genes.

OBJECTIVE The biological role of the adrenal sex steroid precursors - DHEA and DHEA sulphate (DS) and their decline with ageing remains undefined. We observed previously that administration of a 50 daily dose of DHEA for 3 months to age-advanced men and women resulted in an elevation (10%) of serum levels of insulin-like growth factor-I (IGF-I) accompanied by improvement of self-reported physical and psychological well-being. These findings led us to assess the effect of a larger dose (100 mg) of DHEA for a longer duration (6 months) on circulating sex steroids, body composition (DEXA) and muscle strength (MedX). SUBJECTS AND DESIGN Healthy non-obese age-advanced (50–65 yrs of age) men (n = 9) and women (n = 10) were randomized into a double-blind placebo-controlled cross-over trial. Sixteen subjects completed the one-year study of six months of placebo and six months of 100 mg oral DHEA daily. MEASUREMENTS Fasting early morning blood samples were obtained. Serum DHEA, DS, sex steroids, IGF-I, IGFBP-1, IGFBP-3, growth hormone binding protein (GHBP) levels and lipid profiles as well as body composition (by DEXA) and muscle strength (by MedX testing) were measured at baseline and after each treatment. RESULTS Basal serum levels of DHEA, DS, androsternedione (A), testosterone (T) and dihydrotestosterone (DHT) were at or below the lower range of young adult levels. In both sexes, a 100 mg daily dose of DHEA restored serum DHEA levels to those of young adults and serum DS to levels at or slightly above the young adult range. Serum cortisol levels were unaltered, consequently the DS/cortisol ratio was increased to pubertal (10:1) levels. In women, but not in men, serum A, T and DHT were increased to levels above gender-specific young adult ranges. Basal SHBG levels were in the normal range for men and elevated in women, of whom 7 of 8 were on oestrogen replacement therapy. While on DHEA, serum SHBG levels declined with a greater (P

Null points in magnetic fields destroy the adiabatic invariants of charged particle motion, resulting in a chaotic motion. The mixing effect of the chaos produces efficient collisionless heating of electrons. The entropy production is represented by an effective resistance in a macroscopic description. This ``chaos-induced resistance'' enables plasma production at a low gas pressure suitable for ultrafine plasma etching.

Recently, we reported that the thecal compartment of the human ovary contains a CRF system replete with gene expression and protein for corticotropin-releasing factor (CRF), CRF-Receptor 1 (CRF-R1), and the blood-derived high affinity CRF-binding protein (CRF-BP). Granulosa cells are devoid of the CRF system. The parallel increases in intensity of CRF, CRF-R1, and 17α-hydroxylase messenger ribonucleic acid (mRNA) and proteins in thecal cells with follicular maturation suggest that the intraovarian CRF system may play an autocrine role regulating androgen biosynthesis, with a downstream effect on estrogen production by granulosa cells. The functionality of the ovarian CRF system may be conditioned by the relative presence of plasma-derived CRF-BP by virtue of its localization of protein, but not transcript in thecal cells and its ability to compete with CRF for the CRF receptor.To further these findings, in the present study we have examined the effect of CRF on LH-stimulated 17α-hydroxylase (P450c17) gene expression and androgen production by isolated thecal cells from human ovarian follicles (11–13 mm). During the 48-h culture, addition of LH (10 ng/mL) to the medium increased by 5- and 6-fold dehydroepiandrosterone and androstenedione production by thecal cells. Remarkably, the LH-stimulated, but not basal, androgen production was inhibited by CRF in a time- and dose-dependent manner. The half-maximal (ID50) effect dose of CRF occurred at 5 × 10−8 mol/L, and at a maximal concentration of 10−6 mol/L, CRF completely inhibited LH-stimulated androgen production. This inhibitory effect of CRF became evident at 12 h (45%), and by 24 h the effect was more pronounced, with a 70% reduction from baseline. As determined by Northern analyses, CRF dose dependently decreased LH-stimulated P450c17 mRNA levels, with a maximal inhibition of 85% P450c17 gene expression at a CRF concentration of 10−6 mol/L. With the addition of 10−6 mol/L of the antagonist α-helical CRF-(9–41), the inhibitory effect of CRF was partially reversed for both P450c17 mRNA (75%) and androgen production (50%), indicating the CRF-R1-mediated event.In conclusion, the present study demonstrated a potent inhibitory effect of CRF on LH-stimulated dehydroepiandrosterone and androstenedione production that appears to be mediated through the reduction of P450c17 gene expression. Thus, the ovarian CRF system may function as autocrine regulators for androgen biosynthesis in the thecal cell compartment to maintain optimal substrate for estrogen biosynthesis by granulosa cells. Further studies to define the role of CRF-BP in the endocrine modulation of the intraovarian CRF system are needed.

Liver fibrosis/cirrhosis is characterized by hyper-accumulation of fibrous tissue components and is commonly observed in later or terminal states of chronic hepatic diseases. In ongoing work, we found that the administration of human recombinant hepatocyte growth factor (hrHGF) suppressed the onset of liver fibrosis/cirrhosis in several distinct models and accelerated the recovery from liver fibrosis/cirrhosis in rats. Repeated administration of porcine serum for 10 weeks to rats induced liver fibrosis without any accompanying hepatocellular injuries; in addition, the intravenous (i.v.) administration of hepatocyte growth factor (HGF) to these rats suppressed increases in fibrous components and hydroxyproline contents in the liver, thus preventing the onset of liver fibrosis. Repeated administration of dimethylnitrosamine (DMN) for four weeks induced liver cirrhosis, as characterized by the hyper-accumulation of fibrous components, infiltration of mononuclear leukocytes, and hepatic dysfunction. When HGF was injected daily for four weeks along with DMN-treatment, the onset of DMN-induced hepatic fibrosis/cirrhosis was suppressed; the numbers of infiltrating mononuclear cells, fibrous tissue components, and hydroxyproline content in the liver were decreased. When HGF was injected for two weeks following four weeks of DMN-treatment, HGF accelerated the recovery from liver cirrhosis and prevented death due to hepatic dysfunction. Likewise, HGF-injection suppressed the onset of liver fibrosis, when liver fibrosis had been induced by long-term treatment with carbon tetrachloride (CCl4). Thus, the administration of HGF holds great promise for treating subjects with liver fibrosis/cirrhosis as a result of chronic hepatic injury.

Inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn disease (CD), may be induced by combined interactions of dysregulated immune reaction, environmental factors, and disease susceptibility genes. Under normal conditions, reactive oxygen species play an important role in protecting the body from invading microorganisms. However, excessive production of ROS mainly by neutrophils and macrophages may play a role in the pathogenesis of IBD. Antioxidants were found to be effective for ameliorating experimental colitis. Curcumin, superoxide dismutase, and fish oils were shown to be effective in the treatment of human IBD.

This paper describes the numerical analysis of the magnetization process of type II superconductors based on the Ginzburg-Landau theory. A computer code based on the finite difference method was developed and it was applied to simulate the magnetization process of type I and type II superconductors. As regards the time integration method, the CPU times required for the computation in some cases of GL-parameter were compared for two difference schemes, the backward and the forward schemes.

A novel tunable filter using a Fourier grating is studied and discussed. It consists of a Fourier grating, a collimator lens, single-mode fibers, and a computer controlled rotary actuator. It has very low polarization dependence of less than 0.3 dB, an insertion loss of less than 3 dB, and a narrow bandwidth of 1.5 nm. Wavelength selection was realized by rotating the grating, which was controlled by a computer. The device is able to select the light at the desired wavelength from more than 100 WDM optical data streams with 2 nm spacing in the range of 1.3-1.55 /spl mu/m.

Acquired factor XIII (FXIII) deficiency due to an autoantibody against FXIII is a very rare, yet potentially life-threatening bleeding disorder. As the standard coagulation tests (prothrombin time and activated partial thromboplastin time) are normal, the specialized tests are required to make an accurate diagnosis. Here, we report a case of acquired FXIII deficiency with severe bleeding symptoms. A 75-year-old man was referred to our hospital because of severe bleeding tendency after a tooth extraction. Laboratory findings showed that routine coagulation studies were normal, but factor XIII (FXIII) activity was low (3%). The presence of FXIII inhibitor was detected with dot blotting studies. Although the bleeding tendency was very severe, it was successfully controlled by infusion of FXIII concentrates combined with immunosuppressive treatment (oral prednisolone). Fibrin cross-linking study showed the significant delay of the γ-chain dimer and α-chain polymer formation. Western blotting revealed the marked decrease in FXIII-A level. The mixing study of FXIII activity measured using amine-incorporation assay showed the incomplete inhibition pattern. There seems to be little agreement as to the treatment strategy of acquired FXIII deficiency. In this patient, the use of FXIII concentrates was very useful in the initial treatment of bleeding symptom. The use of steroids was also effective in increasing FXIII activity without any serious complications.

BACKGROUND Despite the use of the anti-c100-3 assay for blood donor screening, posttransfusion non-A,non-B hepatitis still occurred. A more sensitive assay should be developed to prevent this. STUDY DESIGN AND METHODS Stored serum specimens from 2020 healthy blood donors who were negative for c100-3 antibody to hepatitis C virus (HCV) were retrospectively screened for the presence of antibodies against a core protein of HCV using an enzyme-linked immunosorbent assay and Western blot analysis as part of a study on posttransfusion non-A,non-B hepatitis. RESULTS Eight (0.4%) of the 2020 donors were positive for HCV core antibody. Posttransfusion non-A,non-B hepatitis occurred in 5 of five patients known to have received blood that was positive for HCV core antibody and 1 of 141 patients transfused with blood that was negative for HCV core antibody. The total incidence of posttransfusion non-A,non-B hepatitis was 4.1 percent (6/146). The nucleotide sequence of the nonstructural 5 region of the HCV genome obtained from two donors and corresponding recipients was also analyzed. The HCV genome sequences were identical for one donor-recipient pair, and there was 99.4-percent homology for a second pair. CONCLUSION Anti-core-positive blood proved to be highly infectious for HCV, and this validated the use of the second-generation anti-HCV assay for blood donor screening.

Human α-1-antitrypsin (α-1-anti-T), one of the most important serum protease inhibitors, is a glycoprotein of mol wt 51,000 (1-3).α-1-anti-T neutralizes the activity of enzymes such as elastase, trypsin, and chymotrypsin The molecule consists of a single polypepide chain of 394 amino acids, with three sugar chains that are N-linked to asparagine residue at positions 46, 83, and 247 (2-4).The major chemical structures of the sugar chains have been reported to be biantennary and triantennary oligosaccharides (4,5) Genetic polymorphism of α-1-anti-T has been elucidated by many investigators. About 40 genetic variants have been recognized, implying considerable heterogeneity and polymorhism. These complexities include variations in the degree of sialylation on the sugar chains and complex formation with low molecular weight thiols by disulfide bridges of the reactive single cysteine (6) Hereditary deficiency of α-1-anti-T predisposes to degenerative lung disease and liver disease (7,8).Nucleotide sequence studies of α-1-anti-T have shown single or two-base substitution or dinucleotide deletion with subsequent single amino acid substitutions or deletions. In the common S and Z variants, A to T (264 Glu to Val) and G to A (342 Glu to Lys) mutations were identified (9).

These studies were undertaken to measure the kinetic constants that characterize the disappearance of a representative free fatty acid (FFA) from the plasma of fetal and newborn sheep. A bolus of albumin-complexed [14C]palmitic acid was infused intravenously, and during the next 8 min, 24 arterial samples were collected to characterize the disappearance curve. Palmitic acid disappearance from plasma was well described by a double-exponential model. When birth was simulated in utero, kinetic values were not changed by cooling. However, after intrauterine ventilation with O2, the volume of distribution of the FFA increased 29%, its plasma clearance rate decreased 26%, and its apparent half-life in the plasma lengthened from 0.8 to 1.2 min (all P < 0.01, n = 8). After umbilical cord occlusion, plasma clearance rate decreased a further 19% and half-life lengthened to 1.4 min. About 60% of the increase in FFA concentration during simulated birth is explained by increased release from adipose stores, and 40% is explained by decreased clearance. Further experiments tested the influence of FFA concentrations themselves. After infusion of unlabeled FFA, clearance of the tracer decreased 23% (P < 0.05, n = 5), a result consistent with a saturable membrane transporter of FFAs.

We examined the changes in plasma levels of endothelin-1 (ET-1), a potent vasoconstrictor peptide, in 47 cases of disseminated intravascular coagulation (DIC) to investigate the role of ET-1 in DIC and its relation to multiple organ failure (MOF). A significant elevation of plasma levels of ET-1 was observed in some cases of DIC, especially in patients with sepsis, blastic crisis of chronic myelogenous leukemia, and cancer. However, no such significant elevation was observed in patients with acute promyelocytic leukemia (APL), acute leukemias except for APL, or non-Hodgkin lymphoma. Plasma levels of ET-1 were higher in patients with DIC with MOF than in those without MOF. Although the levels of ET-1 were decreased or remained low with clinical improvement in most DIC patients, the levels were further increased or remained high in patients who showed no improvement in DIC. It is suggested that ET-1 must play an important role in further progression of MOF with the vasoconstriction and microcirculatory disorders. © 1992 Wiley-Liss, Inc.

It is well known that atrial fibrillation (AF) is one of the most important diseases that predispose patients to thrombosis. We have attempted to identify patients with AF in the hypercoagulable state by measuring molecular markers such as thrombin-antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (PTF) and determining the effect of antithrombotic therapy on these markers; 83 patients with AF were studied. Increased levels of plasma TAT and PTF were more frequently observed in patients with AF and associated mitral stenosis than in patients with AF alone. In cases of AF without mitral stenosis, plasma levels of TAT and PTF were significantly lower in those patients receiving antithrombotic agents (aspirin or warfarin) than in those receiving no antithrombotic agents. Furthermore, plasma levels of PTF were significantly lower in patients given warfarin than in those receiving aspirin. These results suggest that (1) patients with AF and mitral stenosis who are not given warfarin are in an extremely hypercoagulable state and (2) some patients with AF without mitral stenosis who are not given antithrombotic agents are also moderately hypercoagulable. In vivo activation of blood coagulation was more effectively controlled in patients receiving warfarin than in those taking aspirin.

Mg+ ions were implanted into highly pure InP grown by the liquid encapsulated Czochralski (LEC) method in which the Mg concentration [Mg] was varied between 1×1015 cm−3 and 3×1020 cm–3. Two annealing methods were used: furnace annealing (FA) up to 740° C and flash lamp annealing (rapid thermal annealing, RTA) up to 900° C. For characterization, photoluminescence (PL) spectra were measured between 2K and room temperature together with Raman scattering measurements at room temperature. An emission designated by g, which was attributed to a novel energy state of an isolated acceptor, was found to be produced for a rather low value of [Mg]. In addition, a broad emission denoted by [g−g], which was ascribed to acceptor-acceptor pairs, was observed below bound exciton emissions for moderate values of [Mg]. These features were quite similar to those previously observed in acceptor-doped GaAs when the background concentration of donors is extremely low. Two additional novel emissions located far below the band-to-acceptor emission were also obtained, and each showed a remarkable energy shift towards lower energy with increasing [Mg]. The binding energies of these emissions were estimated from the temperature dependence of PL spectra and the results suggest that they are complex-type radiative recombination centers, presumably donor-acceptor-type centers. A strong broad emission centered near the band-to-acceptor emission was observed for [Mg]=3×1020 cm−3. This observation indicates a formation of a new material between In, P and Mg, which was also attested by the appearance of a new TO-like Raman signal for [Mg] greater than 1×1019 cm−3. A substantial difference of PL and Raman spectra was revealed for the two annealing methods, suggesting that the annealing behaviour of ion-implanted InP should be investigated more extensively in order to establish reliable annealing procedures.

Ion-implantation of magnesium into extremely pure InP grown by the liquid-encapsulated Czochralski method was carried out with magnesium concentrations [Mg] ranging from 1 × 1015 to 3 × 1020 cm−3 with a maximum energy of 400 keV. Low temperature photoluminescence and Raman scattering measurements were performed on these samples. A new state of excitions bound to what was presumed to be a new type of acceptor g and an emission attributed to acceptor-acceptor pairs [g-g] were found below the bound exciton emission series. Two novel emissions located far below the band-to-acceptor emissions were also observed, and these showed remarkable energy shifts towards the lower energy side with increasing [Mg]. With heavily implanted samples, a strong broad emission of a new type was observed in the vicinity of the band-to-acceptor emissions.

OBJECTIVE The biological role of the adrenal sex steroid precursors - DHEA and DHEA sulphate (DS) and their decline with ageing remains undefined. We observed previously that administration of a 50 daily dose of DHEA for 3 months to age-advanced men and women resulted in an elevation (10%) of serum levels of insulin-like growth factor-I (IGF-I) accompanied by improvement of self-reported physical and psychological well-being. These findings led us to assess the effect of a larger dose (100 mg) of DHEA for a longer duration (6 months) on circulating sex steroids, body composition (DEXA) and muscle strength (MedX). SUBJECTS AND DESIGN Healthy non-obese age-advanced (50–65 yrs of age) men (n = 9) and women (n = 10) were randomized into a double-blind placebo-controlled cross-over trial. Sixteen subjects completed the one-year study of six months of placebo and six months of 100 mg oral DHEA daily. MEASUREMENTS Fasting early morning blood samples were obtained. Serum DHEA, DS, sex steroids, IGF-I, IGFBP-1, IGFBP-3, growth hormone binding protein (GHBP) levels and lipid profiles as well as body composition (by DEXA) and muscle strength (by MedX testing) were measured at baseline and after each treatment. RESULTS Basal serum levels of DHEA, DS, androsternedione (A), testosterone (T) and dihydrotestosterone (DHT) were at or below the lower range of young adult levels. In both sexes, a 100 mg daily dose of DHEA restored serum DHEA levels to those of young adults and serum DS to levels at or slightly above the young adult range. Serum cortisol levels were unaltered, consequently the DS/cortisol ratio was increased to pubertal (10:1) levels. In women, but not in men, serum A, T and DHT were increased to levels above gender-specific young adult ranges. Basal SHBG levels were in the normal range for men and elevated in women, of whom 7 of 8 were on oestrogen replacement therapy. While on DHEA, serum SHBG levels declined with a greater (P

Autoimmune diseases are known to be induced in some donor-recipient combinations of mice undergoing the graft-vs-host reaction (GVHR). In this paper, we report on the development of primary biliary cirrhosis (PBC)-like hepatic lesions and also on pancreatic insulitis in (B6 x bm12)F1 mice injected with B6 CD4+ T cells. At the sites of these lesions, cellular infiltration around ductal structure was observed. Immunohistochemical studies revealed that both CD4+ and CD8+ T cells were present in the lesions of the liver and pancreas. To clarify the role of the CD8+ T cells, which were probably of host origin, we used a mAb against the Lyt-2 molecule. Both the PBC-like hepatic lesions and pancreatic insulitis were exacerbated by eliminating CD8+ T cells from mice with MHC class II GVHR. Also, autoantibodies against the pyruvate dehydrogenase-E2 component, which has been recently found to contain an immunodominant site (autoepitope) for B cell reactivity in patients with PBC, were detected in the sera of these mice by ELISA and their presence was confirmed by immunoblotting procedures. Our findings suggest that similar mechanisms as in GVHR caused by MHC class II disparity are active in the development of PBC. It should also be noted that, in addition to the hepatic lesions, insulitis closely resembling that seen in the nonobese diabetic mouse was induced in our experimental system. The results suggest that our model provides a unique opportunity to study organ-specific autoimmune diseases. Because the effector in our experimental system was defined to be CD4+ T cells responding to Iabm12 Ag, our findings support the hypothesis that an excessive immune response directed against Ia Ag can produce autoimmune disease.

Dichroism analysis of polyenes produced in PVA films was carried out for films stretched (at 80°C) after heat treatment (at 170°C) and films heat-treated after stretch. The relation between Rs (stretch ratio of the film) and Rd,n (dichroic ratio of n conjugated polyene) in the former case fitted the theoretical curves, but in the latter, high Rd,n values regardless of Rs were observed. Stretching of the film might promote both polyene formation and cross-linking dehydration, especially on the segments oriented in the stretch direction.

A novel external-cavity semiconductor laser with a focusing grating mirror (FGM), which enables a single-mode oscillation at a specified wavelength, is proposed. The optical properties of the FGM, which is a computer-generated holographic grating with chirp and bend structure, are numerically analyzed. An optimally designed FGM for realizing laser oscillation at a specific wavelength of 1.30 mu m is fabricated by using a computer-controlled electron-beam writing system. The fabricated FGM with grating area of 1*1 mm/sup 2/ is combined as an external feedback mirror with an InGaAsP-InP semiconductor laser of 1.3 mu m wavelength range, and the lasing characteristics are experimentally measured. Stable and single-mode oscillations with spectral line width less than 10 MHz are observed. >

We recently cloned mouse Thy28 cDNA (mThy28), which is highly conserved among vertebrates and plants. The mThy28 mRNA is highly expressed in testis, liver, kidney, brain, with moderate expression in thymus, spleen, and heart. In the present study, characteristics of mouse Thy28 protein expression were examined using rabbit anti-mThy28 polyclonal antibody (Ab). Levels of mThy28 protein expression were highest in testis, with moderate expression in liver, spleen, and thymus. The Thy28 protein was mainly located in the nucleus, which was revealed by immunofluorescence microscopy and Western blotting using anti-mThy28 Ab, and transient expression of the mThy28/EGFP fusion gene. Engagement of membrane immunoglobulin with anti-IgM induced down-regulation of human Thy28 expression at both mRNA and protein levels, accompanied by induction of apoptosis in Ramos B lymphoma cells. Expression of protein and mRNA and induction of apoptosis were evaluated by flow cytometry/Western blotting, reverse transcription-polymerase chain reaction, and propidium iodide staining, respectively. Anti-IgM also down-regulated the promoter activity of the mThy28 gene, as demonstrated by luciferase assay. Thus, the anti-IgM-induced down-regulation of the nuclear Thy28 expression appears to correlate with the induction of apoptosis in Ramos B lymphoma cells.

A process that enables good gate-oxide integrity (GOI) in W/barrier/poly-Si gates and thermally stable low-resistivity source/drain (S/D) CoSi/sub 2/ electrodes has been developed for high-speed logic circuits with large-scale embedded DRAMs that use Ta/sub 2/O/sub 5/ high-k capacitors for high-density memory cells. Spin-on-glass (SOG)-based films were used to fill in narrow spaces between wordlines, and were also directly formed on silicide films. We prevented the oxidation of silicide during the SOG-based interlayer dielectric (ILD) formation. By using these CoSi/sub 2/ electrodes, we were able to obtain contact resistance ten times lower than that of conventional non-silicide electrodes.