[Lupoid thrombocytopenia].
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Biomedical subjects
Publications and source records attributed to K Shimizu.
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To analyze the radiographic characteristics of small adenocarcinomas of the lung that can be detected by computed tomography (CT), 46 resected small peripheral adenocarcinomas measuring less than 15 mm in diameter were retrospectively reviewed, and the marginal and internal findings and surrounding vessels of the tumors as shown on thin-section CT images were correlated with six histologic classifications (types A-F) as defined by Noguchi et al. The adenocarcinoma CT images were classified into two patterns: a solid-density type (n = 21) and an air-containing type (n = 25). The lesions of the air-containing type were further divided into two different growth patterns: a complete air-containing type (n = 12) and an incomplete air-containing type (n = 13). The solid-density adenocarcinomas shown in the CT images fell mainly into the C, D, F and Noguchi classifications. Although one sample in the complete air-containing category was type C, the rest were type A. The incomplete air-containing category included 4 type As and 9 type Bs. The CT findings for the 24 adenocarcinomas in the air-containing category (96%) showed an opaque ground-glass internal texture. Plural vascular involvement was observed in all 46 adenocarcinomas examined. Our results suggest that thin-section CT findings can play an important role in differentiating lung cancer and increasing our knowledge of the radiologic and pathologic correlations.
A 64-year-old female was hospitalized because of multiple liver metastasis, during the postoperative observation of chromophobe cell renal carcinoma. Injection of Epirubicin/Lipodol into the right hepatic artery followed by transcatheter arterial embolization was performed two times, and the metastatic foci responded favorably to this therapy. Since no new metastatic tumors were observed in the liver nor any other organs, a partial hepatectomy was thus performed. The liver tumor was pathologically diagnosed to be metastasis of the chromophobe cell renal carcinoma. The postoperative course has been uneventful and at present, 6 months after the operation, no further tumors have been observed.
Although a 76-year-old woman with a diagnosis of depression began a course of maprotiline, the drug was discontinued after 14 days when she developed a rash. She was started on lofepramine in substitution for maprotiline. Four years later, lofepramine treatment was stopped and to amoxapine treatment introduced due to the aggravation of depressive symptoms. On the second day of this regimen, she developed a pruritic rash. She stopped the medication immediately. Because the rash disappeared gradually, lofepramine treatment was restarted. But her recovery was restrained and new skin lesions developed. Again, she stopped the medication, and the rash cleared within several days. This case suggests the existence of cross-allergenicity between tricyclic antidepressants and maprotiline.
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A 60-year-old man who was diagnosed as having hepatic cell carcinoma by needle punch biopsy from the liver, underwent right hepatic lobectomy. However, no malignant components were detected in the removed tissue. It was suspected that he was the wrong patient and had undergone the operation unnecessarily. Individual identification was performed using paraffin blocks of his liver tissue taken by needle punch biopsy, that of liver tissue taken at surgery and his peripheral blood by genotyping several STR loci. All of these specimens had the same genotypes. Histological re-examination revealed that the biopsied sample contained no malignant component. The end result was that the initial biopsied liver specimen was misdiagnosed as hepatic cancer and the patient underwent an unnecessary operation due to misdiagnosis.
To increase the range of motion in the knee, posterior cruciate ligament-retaining total knee arthroplasty (TKA), which has a roll back (RB) mechanism, is used. The roll back mechanism is the complex movement of the femoral condyles relative to the tibial plateau, which results in translation of the tibiofemoral contact point posteriorly as the knee is flexed. This study was undertaken to assess the function of the posterior cruciate ligament (PCL) and posterior tibial tilt following PCL-retaining TKA. Eleven fresh-frozen cadaveric normal lower extremity specimens (average age: 75.4 years; range: 69 to 88 years) were obtained for this study. The test was performed on a loading frame after specimen preparation. The calcaneal bone was fixed on the rigid frame. A load of 9.5 kg was applied perpendicularly by the moving frame to femoral head through four casters. PCL strain and RB were measured before and following TKA by changing the posterior tilt of tibial component and the external rotation of femoral component. PCL strain at 105 degrees flexion in the 0 degree posterior tilt group (3.3% +/- 2.4%) was decreased in the 10 degrees posterior tilt group (0.6% +/- 0.5%), and this decrease was statistically significant (p < 0.05). RB was measured as anterior-posterior translation by using an arthroscopic probe. After TKA, RB was decreased in the medial compartment but was increased in the lateral component. These different movements of the tibiofemoral contact points consequently caused rotation in the flexion position. Posterior tilt of the tibial component decreased the efficiency of the PCL's function. Retaining the PCL physically is not the same as preserving the function of the PCL because of the lack of the ACL, the change of the joint line, the differences in articular geometry, and the balance of the ligaments.
We have generated a mouse model for hepatic ischemia in which surgical subcutaneous transposition of the spleen allows hepatic ischemia to be applied without affecting other tissues. Using this mouse model we investigated the relationship between the length of ischemic periods in the liver and subsequent liver function; furthermore, we assayed the activation of c-Jun N-terminal kinase (JNK) during ischemia and reperfusion. Although prior to this study only the activated form of JNK was known to be translocated to the nucleus, we found that JNK translocates to the nucleus during ischemia without activation and is then activated during reperfusion. These results suggest a novel mechanism of JNK activation.
Sonodynamically-induced cell damage and active oxygen generation enhanced by adriamycin (ADM) were compared in the same in vitro insonation set-up. Significant enhancement of the rates of both ultrasonically-induced cell damage and nitroxide generation was demonstrated with 40-160 microM ADM. Both rates correlated very well resulting in a correlation coefficient of more than 0.99. The enhancement of both rates was suppressed by 10 mM histidine. These results are consistent with the hypothesis that ultrasonically-generated active oxygen plays a major role in the sonodynamically-induced cell damage enhanced by ADM.
STUDY DESIGN: A description of the clinical picture of chylous leakage after spinal surgery. OBJECTIVES: To present the clinical course of three cases of chylous leakage after spinal surgery and to discuss the pathogenesis of the disease. SUMMARY OF BACKGROUND DATA: Chylous leakage is a rare complication after spinal surgery. It has been attributed to direct injury of a lymphatic trunk or one of its major tributaries by surgical maneuver. METHODS: Three cases of chylous leakage after circumferential thoracolumbar fusion for correction of kyphosis resulting from fracture were reported. RESULTS: All of the three cases were managed successfully; two cases of chyloretroperitoneum detected within 4 days after surgery were healed conservatively, but one case of chylothorax of which the onset was noticed 5 weeks after spinal surgery, required surgical ligation of the thoracic duct and pleurodesis. CONCLUSION: Early detection of this disease is important for a good prognosis. Retroperitoneal drainage is necessary for the detection and management of chyloretroperitoneum. The pathogenesis and management of the chylous leakage are discussed in this report.
In n-alkane-utilizing yeast, Candida tropicalis, two NADP-linked isocitrate dehydrogenase (NADP-IDH) isozymes are present, one in mitochondria (Mt-NADP-IDH) and the other in peroxisomes (Ps-NADP-IDH). Here we report the isolation, sequencing, and expression of the gene encoding Ps-NADP-IDH (CtIDP2), distinct from the Mt-NADP-IDH gene (CtIDP1). Based on the N-terminal amino acid sequence of purified Ps-NADP-IDH, a cDNA fragment specific for Ps-NADP-IDH was obtained by the 5'-RACE method. Using this fragment as a probe, the genomic CtIDP2 gene was isolated. Nucleotide sequence analysis of CtIDP2 disclosed that the region encoding CtIdp2p had a length of 1233 bp, corresponding to 411 amino acid residues. The deduced N-terminal amino acid sequence matched the results obtained from the purified protein. When this CtIDP2 was expressed in Saccharomyces cerevisiae using the C. tropicalis isocitrate lyase gene promoter (UPR-ICL), high intracellular NADP-IDH activity was observed. Comparison of amino acid sequences and phylogenetic tree analysis with NADP-IDH enzymes from all reported eukaryotic sources revealed that mammalian mitochondrial NADP-IDHs formed a cluster, as did plant NADP-IDHs. CtIdp2p and other yeast NADP-IDHs were not included in these clusters and seemed to diverge at an early stage from all other enzymes of higher eukaryotes. Ps-NADP-IDH had no typical C-terminal peroxisomal targeting signal and no processing was demonstrated at the N-terminus. However, we could find a region near the N-terminus of the protein with high similarity to both the putative N-terminal peroxisomal targeting signal sequence of Fox3p of S. cerevisiae and an internal region of Pox4p of C. tropicalis. The results of northern blot analysis indicated that the biosynthesis of CtIdp2p was induced in a medium containing alkanes as a carbon source, where profuse proliferation of peroxisomes is observed.
In cases of personal identification of unknown skeletal remains, forensic scientists normally analyze an individual's genotype or phenotype by comparison with those of other family members such as patients. However, such genotyping does not necessarily provide conclusive proof of identity. In this study, we attempted personal identification by comparison of several short tandem repeat (STR) loci in samples from three corpses in various stages of decomposition with samples from personal articles of the respective individuals. The first victim had been found dead in a burned car. Almost 100% of his body was charred. The genotypes of the iliac bone from the burned body with regard to several STR loci were compared with those from a single hair recovered from the vacuum cleaner from the candidate's home. The second victim was found in a forest after more than 5 years. Several STR loci genotypes of skeletal bone were compared with those of the candidate's mummified umbilical cord kept in his parent's house. In the last case the victim was found in the sea after more than 7 months. The genotypes of the loci in the pubic bone of the corpse were compared with those of a menstrual bloodstain on the candidate's underwear left in the washing machine at her home. We succeeded in identification of the three cases by comparison of several VNTR and STR loci in the corpses with those in personal articles. In conclusion, personal identification can sometimes be performed more precisely by genotyping of personal articles than by comparison with the genotypes of relatives.
Serum-induced inactivation of retroviruses is the most critical limitation for in vivo gene transfer therapy. To solve this problem, we searched for reagents that protect retroviruses from inactivation. The effects of the protease inhibitors FOY-007 and FOY-305 and of an inhibitor of the complement pathway FUT-175, all of which have been used clinically, were investigated. All of these agents protected against the inactivation of retroviruses by human serum, with 1 microM FUT-175 providing the most effective protection. Thus, the co-administration of FUT-175 with retroviruses may make retrovirus-mediated in vivo gene transfer feasible for the treatment of patients. FUT-175 dose-dependently inhibited the classical pathway of complement in a hemolysis protection assay of sensitized sheep erythrocytes with guinea pig serum or by cell-lysis assay of mouse fibroblasts with human serum. However, increasing the FUT-175 concentration by 10-fold (10 microM) did not produce further protection against retroviral inactivation in most human sera. There was also no correlation between the serum-induced inactivation of retroviruses and either the amount of anti-alpha-galactosyl (anti-alpha-Gal) antibody or the complement activity in human serum. These results suggest that retroviruses are not inactivated by utilizing the same pathway leading to cell lysis by the classical complement system.
Fungal beta xylanases were screened for production of acidic xylooligomers from 4-O-methylglucuronoxylan. In situ reduced hardwood xylan was used as substrate because the products of neutral- and acidic-branched xylooligomers help define substrate specificity of the enzymes. Borohydride reduction in situ transformed 30% of 4-O-methyl-alpha-D-glucopyranosyluronic acid residues into 4-O-methyl-alpha-D-glucopyranosyl residues and reduced C-1 end groups in the xylan backbones. A total of ten beta-xylanase fractions from four fungi were partially purified by chromatography by anion exchange and molecular sieving, and graded qualitatively for enzymatic hydrolysis of the substrate. The yield of acidic xylooligomers was highly affected by whether alpha-glucuronidases were present in the beta-xylanase fractions. Some fractions gave free 4-O-methyl-alpha-D-glucopyranosyluronic acid, but none of the enzyme fractions could release free 4-O-methyl-alpha-D-glucose. Among the beta-xylanase fractions studied, xylanase II of Trichoderma viride was the best producer of aldotetraouronic acid [2-O-(4-O-methyl-alpha-D-glucopyranosyluronic acid)-D-xylotriose]. The results obtained suggested that there was a difference in the steric hindrance of the branch point on fungal beta-xylanases between 4-O-methyl-alpha-D-glucopyranosyl and 4-O-alpha-D-glucopyranosyluronic acid residues.
16;21 translocation is a recurrent primary abnormality in acute myeloid leukemia (AML). The genes involved in this translocation are ERG on chromosome 21 and TLS/FUS on chromosome 16. The rearrangement of the two chromosomes forms the TLS/FUS-ERG fusion gene and produces a consistent chimeric transcript on the der (21) chromosome. In this study, we analyzed the clinical characteristics of 19 patients with t(16;21)-AML, including 2 patients who evolved from myelodysplastic syndrome, and detected the chimeric transcripts of the TLS/FUS-ERG fusion gene in the patients during various clinical stages by the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. We found that the patients with t(16;21) are characterized by a relatively younger age (median age, 22 years old), involvement of various subtypes of French-American-British classification and a poor prognosis: 18 of the 19 patients died of the disease (median survival was 16 months). Four types of TLS/FUS-ERG chimeric transcripts including a novel type were noted in the RT-PCR analysis. The novel transcript contained an additional 138 nucleotides consisting of TLS/FUS exon 8 and ERG exons 7 and 8 and had an in-frame fusion. These chimeric transcripts were consistently detectable in the samples obtained not only at diagnosis and relapse but also in short and long complete remission, suggesting that t(16;21)-AML is resistant to conventional chemotherapy. Thus, we recommend that t(16;21) should be monitored by RT-PCR even in clinical remission and the patients should be treated by other more powerful modality like stem-cell transplantation in the first remission.
The translocation t(8;21)(q22;q22) is found in 40% of cases of acute myeloid leukemia (AML) designated as the subtype M2 in the French-American-British (FAB) classification. The 8;21 translocation is clinically of interest because patients with this subtype have a good prognosis. We describe a masked type of the translocation, t(8;12;21)(q22.1;q24.1;q22.1). The translocation was first interpreted as t(8;12)(q22;q24) based on cytogenetics, but was reevaluated as a result of Southern blot and fluorescence in situ hybridization (FISH) analyses.
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A compound, SCH 28080 (2-methyl-8-(phenylmethoxy)imidazo [1,2-a]pyridine-3-acetonitrile), reversibly inhibits gastric and renal ouabain-insensitive H+,K+-ATPase, but not colonic ouabain-sensitive H+,K+-ATPase. By using the functional expression system and site-directed mutagenesis, we analyzed the putative binding sites of SCH 28080 in gastric H+,K+-ATPase alpha-subunit. It was previously reported that the binding site of SCH 28080, which is a K+-site inhibitor specific for gastric H+,K+-ATPase, was in the first extracellular loop between the first and second transmembrane segments of the alpha-subunit; Phe-126 and Asp-138 were putative binding sites. However, we found that all the mutants in the first extracellular loop including Phe-126 and Asp-138 retained H+, K+-ATPase activity and sensitivity to SCH 28080. Therefore, amino acid residues in the first extracellular loop are not directly involved in the SCH 28080 binding nor indispensable for the H+, K+-ATPase activity. Here we propose a candidate residue that is important for the binding with SCH 28080, Glu-822 in the sixth transmembrane segment. Mutations of Glu-822 to Asp and Ala (mutants termed E822D and E822A, respectively) decreased the ATPase activity to about 45% and 35% of the wild-type enzyme, respectively, while the mutations to Gln and Leu abolished the activity. Mutant E822A showed a significantly lower affinity for K+ than the wild-type enzyme, indicating that Glu-822 is involved in determining the affinity for K+. The sensitivity of mutant E822D to SCH 28080 was 8 times lower than that of the wild-type enzyme. The counterpart of Glu-822 in gastric H+,K+-ATPase is Asp in Na+,K+-ATPase and other colonic ouabain-sensitive H+,K+-ATPase, which are insensitive to SCH 28080. These results suggest that Glu-822 is one of important sites that bind with SCH 28080.