CT findings in 11 patients with TAFRO syndrome: a variant of multicentric Castleman's disease.

AIM: To assess detailed computed tomography (CT) findings in patients with the recently described thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome, in order to contribute to imaging interpretation in the challenging diagnosis of this disease. MATERIALS AND METHODS: The institutional review board approved this retrospective study and waived the need for informed consent. Eleven patients (six men, five women; mean age, 52.5 years) with confirmed TAFRO syndrome were included in this study. Chest-to-pelvis CT images were analysed for the presence of anasarca, organomegaly, bone lesions, and lung lesions. RESULTS: Anasarca was present in all patients and involved multiple cavities and tissues; pleural effusion and ascites were found in 100% of patients; pericardial effusion in 64%; periportal collar in 91%; gallbladder wall oedema in 78%; subcutaneous oedema in 91%; retroperitoneal oedema in 100%; and mesenteric oedema in 100%. Organomegaly involved multiple organs: hepatomegaly in 73%, splenomegaly in 82%, lymphadenopathy in 100%, and enlarged anterior mediastinum in 64% (solitary, well-circumscribed mass, 0%; infiltrative mass, 0%; non-mass-forming infiltrative lesion, 64%). Bone lesions were present in 91% patients and all bone lesions had ground-glass density with diffuse distribution. None of the patients had any lesions in their lungs. CONCLUSION: The present study revealed that the findings of anasarca, organomegaly, and diffuse bony ground-glass appearance were observed in detail on CT in patients with TAFRO syndrome. A "matted" appearance of the enlarged anterior mediastinum is the characteristic CT finding of TAFRO syndrome, and it is possible to diagnose TAFRO syndrome from the combination of several CT findings.

Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients.

To clarify the cooperative roles of recurrently identified mutations and to establish a more precise risk classification system in acute myeloid leukemia (AML), we comprehensively analyzed mutations in 51 genes, as well as cytogenetics and 11 chimeric transcripts, in 197 adult patients with de novo AML who were registered in the Japan Adult Leukemia Study Group AML201 study. We identified a total of 505 mutations in 44 genes, while only five genes, FLT3, NPM1, CEBPA, DNMT3A and KIT, were mutated in more than 10% of the patients. Although several cooperative and exclusive mutation patterns were observed, the accumulated mutation number was higher in cytogenetically normal AML and lower in AML with RUNX1-RUNX1T1 and CBFB-MYH11, indicating a strong potential of these translocations for the initiation of AML. Furthermore, we evaluated the prognostic impacts of each sole mutation and the combinations of mutations and/or cytogenetics, and demonstrated that AML patients could be clearly stratified into five risk groups for overall survival by including the mutation status of DNMT3A, MLL-PTD and TP53 genes in the risk classification system of the European LeukemiaNet. These results indicate that the prognosis of AML could be stratified by the major mutation status in combination with cytogenetics.

Fabrication and optical properties of Pb(Mg(1/3)Nb(2/3))O(3)-PbTiO(3) thin films on Si substrates using the PLD method.

Epitaxial 0.67Pb(Mg(1/3)Nb(2/3))O(3)-PbTiO(3)-0.33PbTiO(3) (PMN-PT) thin films with electro-optic effects were fabricated on (PMN-PT) thin films with electro-optic effects were fabricated on (La0(0.5)Sr0(0.5))CoO(3) (LSCO)/CeO(2)/YSZ-buffered Si(001) substrates using double-pulse excitation pulsed laser deposition (PLD) method with a mask placed between the target and the substrate. Epitaxial growth of PMN-PT thin films was undertaken using the two-step growth method of PMN-PT film. The PMN-PT seed layer was deposited at 500 degrees C on the LSCO/CeO(2)/YSZ/Si, which temperature was the same as that used for LSCO deposition. The PMN-PT thin films were deposited on the PMN-PT seed layer at 600 degrees C, which enables growth of high-crystallinity PMN-PT films with smooth surfaces. We obtained optimum fabrication conditions of PMNPT film with micrometer-order thickness. Resultant films showed high crystallinity with full width at half maximum (FWHM) = 0.73 deg and 1.6 mum thickness. Electro-optic properties and the refractive index value were measured at 633 nm wavelength using the prism coupling method. The obtained refractive index was 2.59. The electro-optic coefficients r(13) and r(33) were determined by applying the electrical field between a semitransparent, thin top electrode of Pt and a bottom LSCO electrode. The electro-optic coefficient was r(13) = 17 pm/V at transverse electric field (TE) mode and r(33) = 55 pm/V at transverse magnetic field (TM) mode.

In-plane and out-of-plane ferroelectric instabilities in epitaxial SrTiO3 films.

The in-plane and out-of-plane ferroelectric instabilities in compressed (100)-epitaxial SrTiO3 films were examined by infrared reflection spectroscopy. The strongly stiffened in-plane soft mode frequency softened very slowly on cooling. On the other hand, the silent mode appeared at around 150 K, indicating an out-of-plane ferroelectric transition. This behavior points to a split of in-plane and out-of-plane ferroelectric instability temperatures due to the lowered symmetry of the SrTiO3 lattice caused by mechanical misfit strain. Infrared spectroscopy provides a possibility to detect such an effect in the strained epitaxial ferroelectric films.

Life-threatening bleeding and acquired factor V deficiency associated with primary systemic amyloidosis.

Acquired factor X deficiency has been described in patients with amyloidosis but acquired factor V deficiency is quite rare. We report here a case of life-threatening bleeding and acquired factor V deficiency associated with primary amyloidosis. A 50-year-old man who had no previous hemorrhagic diathesis was referred to our hospital because of recurrent epistaxis, gingival bleeding and hemospermia. The laboratory examination revealed that both the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) were significantly prolonged, and factor V activities were markedly decreased to 14-39% of the normal value. Other coagulation factors such as fibrinogen, prothrombin, factor VII, factor VIII, factor IX and factor X were subnormal and normal. Transaminases were slightly elevated but serological tests of hepatitis B and hepatitis C were negative. Mild hepatosplenomegaly was noted without sign of liver cirrhosis. The PT and aPTT obtained 8 years ago when he received a cholecystectomy due to cholecystitis were both normal. Specific assays for the detection of factor V inhibitor were repeatedly performed but no factor V inhibitor was found. Furthermore, a significant recovery of the infused factor V was noted shortly after an intravenous administration of 5-10 U fresh frozen plasma, but it did not last more than 6 h. Melena, bleedings into the left shoulder and buttock, and finally mortal retroperitoneal hemorrhage developed despite repeated infusions of large amounts of fresh frozen plasma. Acquired factor V deficiency associated with primary amyloidosis was suspected but histological diagnosis was not obtained because of the severe bleeding tendency. Autopsy revealed hepatosplenomegaly and massive deposits of AL amyloid in the liver, spleen, heart and other parenchymal organs. Perivascular amyloid deposition and factor V deficiency are both thought to be the cause of the severe hemorrhagic tendency seen in this patient.

Induction of urokinase-type plasminogen activator by the anthracycline antibiotic in human RC-K8 lymphoma and H69 lung-carcinoma cells.

Current evidence has suggested the possible involvement of ROS as signaling messengers in IL-1beta- or LPS-induced gene expression. We previously reported that both IL-1beta and LPS induce uPA in RC-K8 human lymphoma cells. Here, we provide evidence that ROS-generating anthracycline antibiotics, including doxorubicin and aclarubicin, upregulate uPA expression in 2 human malignant cell lines, RC-K8 and H69 small-cell lung-carcinoma cells. Both doxorubicin and aclarubicin markedly increased uPA accumulation in RC-K8- and H69-conditioned medium in a dose-dependent manner. In each case, maximal induction was observed at a sublethal concentration, i.e., at a concentration where cell growth was slightly inhibited. Both doxorubicin and aclarubicin increased uPA mRNA levels, and induction in each case reached the maximal level 9 hr after stimulation. Doxorubicin barely changed the half-life of uPA mRNA and activated uPA gene transcription. Antioxidants such as NAC and PDTC inhibited doxorubicin-induced uPA mRNA accumulation. Microarray analysis, using Human Cancer CHIP version 2 (Takara Shuzo, Kyoto, Japan), in which 425 human cancer-related genes were spotted on glass plates, revealed that uPA is 1 of 3 genes that were clearly upregulated in H69 cells by doxorubicin stimulation. These findings suggest that the anthracycline induces uPA in human malignant cells by activating gene transcription in which ROS may be involved. Therefore, by upregulating uPA expression, the anthracycline may influence many biologic cell functions mediated by the uPA/plasmin system.

Two novel gene mutations in type I antithrombin deficiency.

We studied the molecular basis of type I antithrombin (AT) deficiency in 2 Japanese families, in which affected persons had histories of recurrent venous thrombosis and low (about 50% of normal) levels of AT protein according to measurements by both functional and antigen assays. Southern blotting of DNA isolated from peripheral leukocytes revealed no abnormalities in all the cases examined. Direct sequencing of the polymerase chain reaction (PCR) products from case I suggested a novel heterozygous nonsense mutation in exon 4 (GAG-->TAG at nucleotide position 7627, leading to Glu306 stop). The sequencing of the subclones of the patient's exon 4 products confirmed the nonsense mutation. No other sequence abnormalities were detected in the rest of the PCR products. The same mutation was detected in this patient's brother, who had a history of recurrent venous thrombosis and a reduced level of AT activity. In case 2, the direct sequencing of PCR products suggested a novel heterozygous 9-bp deletion in exon 3a (-CACTTC at nucleotide position 5354-5362, leading to the deletion of 3 amino acids, His120, Phel21, and Phe122). The 9-bp deletion mutation in the region of a unique quasi palindrome was confirmed by sequencing several of the subclones of the patient's exon 3a from the PCR products. No other mutations were found by direct sequencing of the rest of the coding regions. The 2 mutations found in this study are novel. The use of PCR and the sequencing of the PCR product subclones has simplified and confirmed the detection and characterization of the various AT mutations.

Production of hepatocyte growth factor from human lung microvascular endothelial cells induced by interleukin-1beta.

To investigate the possible role of hepatocyte growth factor (HGF) in the reconstruction process following inflammatory damage in lung tissue, we compared HGF production of human lung microvascular endothelial cells (HLWECs) and human umbilical vein endothelial cells (HUVECs) after stimulation by interleukin(IL)-1beta. In an HLMEC-conditioned medium, large amounts of total (single and 2-chain) HGF were detected, and were 26- to 28-fold higher than those in HUVECs or human lung fibroblasts. The production of total HGF increased in a dose-dependent manner (4.7 to 9.2 times) with IL-1beta. In contrast, the amount of HGF in an HUVEC-conditioned medium was unaffected by IL-1beta treatment. The amount of cell-associated HGF also showed a dose-related increase (140% to 160%) in HLMECs, but not in HUVECs with IL1beta. In addition, HGF and c-met (HGF receptor) mRNAs in HLMECs and HUVECs were examined by the RT-PCR method. HGF and c-met mRNAs were clearly detected in HLMECs before and after treatment with IL-1beta, but not in HUVECs. These results suggest that increases in HGF production from HLMECs may play a role in the reconstruction process following inflammatory damage in lung tissue.

Insight into acid-mediated asymmetric spirocyclization in the presence of a chiral diol.

Asymmetric spirocyclization based on intramolecular conjugate addition using a combination of a Lewis acid and an optically active cyclohexane-1,2-diol has been studied in connection with 1) the effect of substituents on the cyclohexane-1,2-diol and 2) the effect of substituents on the substrate. This reaction was found to be both thermodynamically and kinetically controlled under restricted conditions.

Heterologous enzyme immunoassay for serum androstenediol.

A heterologous enzyme immunoassay for serum androstenediol (Adiol: 3beta, 17beta-dihydroxy-androst-5-ene) was established. The combination of anti-Adiol antiserum raised in rabbit against Adiol 7-O-(carboxymethyl)oxime (Adiol 7-CMO) conjugated bovine serum albumin (Adiol 7-CMO-BSA) and Adiol 7-iminomethylcarboxylic acid conjugated alkaline phosphatase was used for the assay. The sensitivity of the heterologous assay system was superior to that of a homologous assay system in which an antibody raised in rabbit against Adiol 7-CMO-BSA and enzyme labeled antigen, Adiol 7-CMO conjugated alkaline phosphatase, were used. The minimal amount of Adiol detected was 0.4 ngml(-1) and the measurable range was from 0. 4 to 150 ngml(-1). Intra-assay coefficients of variation (C.V.) were 8.6% (1.52+/-0.13 ngml(-1), mean+/-S.D., n=10) and 6.7% (13.4+/-0.9 ngml(-1), n=10). Inter-assay C.V. were 12.9% (1.63+/-0.21 ngml(-1), n=8) and 11.5% (12.2+/-1.4 ngml(-1), n=8). A linear relation was observed between the serum sample dilution and the Adiol concentration. For recovery study, authentic Adiol was added to serum sample (original concentration: 1.43 ngml(-1)). The calculated final Adiol concentration was 2.99 ngml(-1). The recovery was 98.6% (n=5). The Adiol concentrations in healthy subjects measured by the proposed assay (male: 1.1+/-0.3 ngml(-1) (mean+/-S.D.), range: 0.7-1. 7 ngml(-1), age: 22-50, n=10; female: 0.6+/-0.4 ngml(-1), range: 0. 2-1.6 ngml(-1), age: 23-48, n=20) were consistent with reported values.

Effect of additives on transesterification activity of Rhizopus chinensis lipase.

The transesterification activity of powder lipase prepared from the purified lipase of Rhizopus chinensis cells by freeze-drying was quite low compared with that of acetone-dried cells. Additives which could enhance the transesterification activity of the freeze-dried powder lipase were screened. The freeze-dried lipases prepared with certain fatty acid methylesters or certain types of surfactants exhibited high transesterification activity. It was shown that not only the solubility of the freeze-dried lipase in n-hexane but also the organic solvent-stability was enhanced when methyl stearate was added to the lipase solution at the freeze-drying step.

[Effect of Nippostrongylus brasiliensis induced alterations in T helper cell subsets on Plasmodium berghei infection in mice].

OBJECTIVE: To observe the anti-P. berghei ability of C57BL/6 mice after infected with Nippostrongylus brasiliensis alterations in T helper cell subsets in the course of Plasmodium infection, and the effect of the alteration on host's prognoses. METHODS: C57BL/6 mice were infected with Nippostrongylus brasiliensis subcutaneously, 3 wk later, the mice were injected with Plasmodium berghei intraperitoneally. The parasitemia was monitored daily. On days 0, 3 and 9, RNA from the spleens of infected mice was prepared for PT-PCR to analyse the changes of IFN-gamma and IL-4 mRNA during the infection course. RESULTS: Compared with control group, the peak-reaching time of parasitemia in the experiment group was delayed, and the bearing capacity of mice to malaria infection and the surviving time increased obviously. The IL-4 level in the experiment group was higher than that in the control group on day 0 of P. berghei infection, but all raised abnormally in both groups at the early stage of the infection; while IFN-gamma level in the experiment group was higher than that in the control group on day 3 after infection, and then began to reduce to some extent on day 9 of the infection in the experiment group. CONCLUSION: T helper cell subsets play an important role in antimalarial immunoregulation in mice.

[Development of factor VIII inhibitor in three non-hemophiliac patients].

Infrequently, inhibitors against factor VIII can develop in non-hemophiliac patients and cause serious bleeding. In the last year, we have experienced 3 non-hemophiliac patients who developed factor VIII inhibitors. Here, we describe the clinical courses of the three patients and the characteristics of the inhibitors. Case 1: A 69-year-old man underwent a partial gastrectomy because of early gastric cancer, and one month later developed signs of a bleeding tendency such as hematemesis, tarry stools and intramuscular hemorrhage. Blood coagulation tests revealed prolongation of the activated partial thromboplastin time (aPTT), which had been normal on admission. Case 2: A 78-year-old woman with no previous disease history developed generalized subcutaneous purpura. Blood coagulation tests performed on admission revealed a prolonged aPTT. Case 3: A 30-year-old man was admitted to an emergency hospital because of left intrapleural hemorrhage and liver injury caused by a traffic accident. Two months later, a hematoma developed at the site of drainage in the left chest, and blood coagulation tests revealed prolongation of the aPTT, which had been normal on admission. Plasma factor VIII procoagulant activities in cases 1, 2 and 3 were 3%, 1% and 5%, respectively. The respective factor VIII inhibitor titers were 78, 870 and 0.5 Bethesda units/ml. The immunoglobulin class and subclass of the inhibitors examined by an ELISA method were: case 1, IgG1 and 4; case 2, IgG2 and 4 (dominant); case 3, IgG4. In cases 1 and 3, the patients recovered after glucocorticoid therapy, but in case 2 the patient died of intraperitoneal hemorrhage despite receiving two courses of methylprednisolone pulse therapy. The above clinical experience suggests that patients, who develop high titers of inhibitors may be refractory to ordinary immunosuppressive therapy, and therefore more aggressive therapy such as plasma exchange and/or bypass therapy using activated prothrombin complex concentrates or an activated factor VII preparation should be considered.

Transient factor VIII inhibitor in a hemophilia patient after staphylococcal septic shock syndrome.

We report a transient type I factor VIII inhibitor that arose in a 30-year-old hemophilia patient just after staphylococcal septicemia. This situation usually occurs early in the course of substitution therapy with factor VIII concentrate in hemophilia patients. Although disseminated intravascular coagulation and acute respiratory distress syndrome developed after septic shock, the patient recovered following intravenous administration of antibiotics (meropenem and gentamycin), an antithrombin preparation, high-dose methylprednisolone, and recombinant factor VIII concentrate (rFVIII). During this therapy, however, activated partial thromboplastin time gradually lengthened. On the seventh day of hospitalization, intracranial hemorrhage occurred with right hemiplegia, even though the substitution therapy had continued at the same dosage (30 U/kg per day) of rFVIII. At that point, 4 Bethesda units of the type I inhibitor against factor VIII were detected in the plasma. Increased amounts (46 U/kg per day) of rFVIII and prednisolone were administered, and hypothermic therapy was initiated. Following these treatments, the patient's general condition gradually improved, and within 25 days the inhibitor titer dropped to undetectable levels and did not recur during treatment. These clinical findings suggest that the staphylococcal septic shock may have acted as a trigger in the development of transient factor VIII inhibitor in this patient.

[Anesthetic management of a patient with Coffin-Lowry syndrome].

Coffin-Lowry syndrome (CLS) is characterized by mental retardation, a peculiar face and deformities of the thorax and spine. A 33-year-old female with Coffin-Lowry syndrome (CLS), further complicated with atrial septal defect and ventricular tachycardia, underwent elective surgery for anterior cervical cyst. As difficult intubation had been anticipated, anesthesia was induced with continuous administration of propofol. After confirming that she could be ventilated by mask, vecuronium bromide, midazolam and fentanyl were given. The operation and anesthesia were conducted uneventfully. No complications occurred postoperatively. The use of propofol for slow induction of anesthesia was advantageous for hemodynamic stability in this case.

[A case of Morgagni's foramen hernia difficult to differentiate from lipoma].

A 61-year-old woman was admitted for chest discomfort. She had been admitted before, in March 1995, because of a lesion detected on chest roentgenograms. At that time, she was given a diagnosis of mediastinal lipoma based on the findings of chest computed tomography (CT) and magnetic resonance imaging (MRI), but was discharged without active intervention due to lack of subjective symptoms. During follow-up, the patient again reported chest discomfort beginning in March 1998. Because chest radiography disclosed. The tumor had enlarged, the patient was admitted to the hospital by our department. Chest MRI disclosed a mass with a signal intensity equal to that of subcutaneous fat in the pericardial space on both T1-weighted and T2-weighted images. Although sagittal images demonstrated continuity of the mass into intraperitoneal fat, a conclusive diagnosis of diaphragmatic hernia could not be made at that time. On April 30, 1998, a thoracotomy was performed on the basis of a preoperative diagnosis of mediastinal lipoma. During surgery, a hernial ring was observed slightly to the right and behind the sternum. The hernia consisted only of greater omentum, and was diagnosed as Morgagni's foramen hernia.

[Motor neuron disease with respiratory insufficiency as primary manifestation].

A 66-year-old man with dyspnea on exertion suffered a cardiac arrest and was referred to our hospital after emergency room intubation. Chest X-ray films detected no abnormalities. Blood gas analysis showed hypoxemia with normal A-aDO 2, and pulmonary function tests revealed combined ventilatory impairment. Chest fluoroscopy revealed weakness of diaphragmatic motion. No other abnormalities were found on initial examination. It was difficult to wean the patient off mechanical ventilation and identify the cause of alveolar hypoventilation. On the 60th hospital day, a neurological examination and electromyography disclosed fasciculation and denervation of the left biceps and pectoralis major muscle. These findings supported the diagnosis of motor neuron disease (MND). Although respiratory insufficiency as an initial symptom of MND is unusual, physicians should be aware of the possibility of MND in cases of alveolar hypoventilation of unknown etiology.