We observed a fatal case of Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) with an abnormal karyotype. Increased levels of αβ T cells of the patient were investigated ...using an inverse polymerase chain reaction (PCR) of the T-cell receptor variable region gene, followed by Jβ-PCR and single-strand conformation polymorphism (SSCP) to confirm the clonality of specific αβ-T cell subsets. A high frequency (>15%) was recognized in Vβ9 at onset, but not in any Vβ and Vα families 2 weeks after chemotherapy. High levels (>20%) of some Jβ genes were detected in all Vβ families investigated, and the predominant bias of the Jβ2 gene relative to the Jβ1 gene (86.1% versus 13.9% at onset, and 77.4% versus 23.5% after chemotherapy) was recognized in pan-αβ T cells. When each Vβ–Jβ fragment was compared among the samples at onset and after chemotherapy by SSCP analysis, several distinct bands were observed that indicate a clonal evolution. Thus, the findings suggest that some of the αβ T cell clones could be associated with abnormal karyotypes in EBV-HLH. The present findings provide molecular evidence of the presence of oligoclonal T cells in pan-αβ-T cells and clonal evolution during a short clinical course in EBV-HLH with abnormal karyotypes.
This paper describes a pipe shape reconstruction technique directly from impulse response of an acoustic reflection dynamics. Proposed algorithm is aimed to detect a fault of telecommunication ...conduit by an abnormal changes of cross sectional area. Example of pipe shape reconstruction is given, for a numerical simulation. We also show the results of field trial by our prototype acoustic inspection system for a telecommunication conduit damaged by the earthquake.
A 49-year-old female cardiomyopathic patient with heart, hepatic, and renal failure and lactic acidosis was transferred to the intensive care unit without a unifying diagnosis. She was of short ...stature (145 cm tall), had difficulty in hearing, a past history of complete atrioventricular block, and had received a permanent pacemaker. She had been diagnosed and treated as dilated cardiomyopathy by her primary doctor. Treatment in the intensive care unit for 21 days including plasma exchange, continuous hemodiafiltration, artificial ventilation, and administration of catecholamine, carperitide, and a large amount of coenzyme Q10 (210 mg/day) improved the symptoms. Genetic analysis using mitochondrial DNA from leukocytes and sternocleidomastoid muscle revealed a 3243A>G mutation in the mitochondrial tRNA(Leu (UUR)) gene, which is related to mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). The patient recovered through intensive care and could be discharged from hospital without any sequelae. This case was mitochondrial cardiomyopathy diagnosed from the symptoms of multiple organ dysfunction syndrome. Cardiomyopathy due to the mutation of mitochondrial DNA is not a common disease. However, it should be considered as a possible cause of heart failure.
We successfull treated a patient with bilateral pulmonary arteriovenous fistulas (PANT) with Rendu-Osler-Weber disease by surgery and pulmonary artery embolization. A 56-year-old woman was referred ...to the hospital because of bilateral abnormal shadows in a chest radiograph. Chest CT and pulmonary angiography revealed pulmonary arteriovenous fistulas located in the right middle lobe (2 PAVFs, 2cm and 10cm in diameter respectively) and left lower lobe (1PAVF, 5cm in diameter). The patient had a history of recurrent epistaxis and showed telangiectasia of lips and tongue. She was diagnosed as Rendu-Osler-Weber disease with bilateral pulmonary arteriovenous fistulas. Right middle lobectomy and selective left pulmonary artery embolization was performed. In the treatment of bilateral multiple arteriovenous fistulas of the lung like this case, more effective therapeutic outcome can be expected by selecting either or both surgery or pulmonary artery embolization for each fistula.
3-Isopropylmalate dehydrogenase (IPMDH, EC 1.1.1.85) catalyzes an oxidation-decarboxylation reaction of (2R, 3S)-3-isopropylmalate (IPM) into 2-oxoisocaproate with the aid of NAD^+ in the penultimate ...step of the biosynthetic pathway of an essential amino acid L-leucine. We have been involved in the mechanistic and molecular recognition studies on IPMDH derived from the extremely thermophilic bacteria Thermus thermophlus HB8. The finding that 2-O-methyl-3-isopropylmalate (1) is an uncompetitive inhibitor of IPMDH, prompted to design conformationally restricted substrate analogs, in which the hydroxy oxygen is intramolecularly bound to an isopropyl carbon to form a ring structure. The oxirane 2 was the most inhibitory among those synthesized. IPMDH appeared to recognize preferentially the anticonformation of the butanedioic acid structure. (2R, 3S)-3-vinylmalic acid (VM) was designed, as a mechanism-based inhibitor. The synthesis of VM was pursued in 6 steps from diethyl (R)-malate. Besides its weak activity as a substrate, VM appeared to be a competitive and mechanism-based inhibitor (K_i values 25 nM) for IPMDH as deduced from the time-dependent and kinetic analyses. By GC-MS and ^1H-NMR analysis of the enzyme reaction of VM, 2-oxo-3-pentenoate (7) was detected as the product. Furthermore, we synthesized deuterium-labeled VM (VM-d_3) and monitored the enzyme reaction by ^2H-NMR spectroscopy. While the signals of VM-d_3 (at δ_D 5.1 and 5.8 ppm) disappeared by consumption of VM-d_3, the signals which derived from 7 emerged at δ_D 2.0 and 7.1 ppm. These results suggest that the transient covalent bond, which was formed between IPMDH and 7, inhibits the IPMDH reaction. Arg94Lys mutant of IPMDH was prepared by site-directed mutagenesis. The mutant enzyme had the same Km value as the native enzyme. But its catalytic efficiency lowered 10^<-2> times as compared with wild-type IPMDH. Arg94 of IPMDH appeared to stabilize the transition state of the IPMDH reaction and participate in the catalytic efficiency.
