Abrupt onset of severe Behçet's disease: preceding oral ulceration is not essential for diagnosis.
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Biomedical subjects
Publications and source records attributed to S Shimizu.
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A patient with idiopathic thrombocytopenic purpura (ITP) developed T-cell lymphoma while undergoing steroid therapy. We examined the relationship between the patient's serum thrombopoietin (Tpo) level, platelet count, megakaryocyte number and CFU-Meg number during the second 5 d course of chemotherapy for lymphoma in which megakaryopoiesis switched from ITP phase to amegakaryocytic phase. The patient's platelet count was temporarily elevated but CFU-Meg numbers were markedly suppressed, and megakaryocyte numbers were decreased in this period, whereas serum Tpo level was not suppressed despite an increased platelet count, indicating that serum Tpo level is mainly regulated by megakaryocyte mass.
Molecular mechanisms of neuronal cell death are still largely unknown. In the present study, the signal transduction pathway of cell death in cerebellar granule neurons was examined by employing various death-preventative agents. When death was induced by the depletion of serum and a depolarizing level of potassium, transient increase in active c-Jun, mitochondrial membrane potential (deltapsi) loss, activation of caspase-3 (-like) proteases, and nuclear condensation and fragmentation were observed. The protein synthesis inhibitor cycloheximide blocked all these phenomena, whereas RNA synthesis inhibitor actinomycin-D, survival factor such as insulin-like growth factor-1, brain-derived neurotrophic factor, high K+ (25 mM) and overproduced antiapoptotic protein Bcl-2, prevented deltapsi, loss, caspase activation, and nuclear change, but not an increase in active c-Jun. The caspase inhibitor z-Asp-CH2-DCB (carbobenzoxy-L-aspartyl-alpha-[(2,6-dichlorobenzoyl) oxy]methane) only inhibited activation of caspases and nuclear change. These results suggest that the death signal in cerebellar granule neurons is sequentially transduced in the order of c-Jun activation, de novo RNA synthesis, mitochondrial deltapsi loss, activation of caspase-3 (-like) proteases and nuclear change.
We have devised a new expansion process for the reconstruction of the cervical oesophagus with free revascularised jejunum in cases of hypopharyngeal cancer. The jejunal island flap is divided into three subislands and the major island of the caudal end is split partially at its oral end. The middle island is split, trimmed triangularly, and inserted into opened major island to expand the diameter of the oral end of the conduit for the cervical oesophagus and to make it funnel-shaped. The smallest island on the oral side is used as a circulation monitor for the transferred jejunum. Because the jejunal island patch is rotated around the root of mesentery like a folding fan and joined to the major island, there is neither shortening of the pedicle nor distortion. This method allows expansion of the oral end by up to 180% to facilitate end to end anastomosis in proximal pharyngeal defects.
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It is generally considered that perinidal edema in an arteriovenous malformation (AVM) is caused by a concomitant intracerebral hematoma. We report a rare case of AVM with perinidal massive edema which was possibly not due to hemorrhage, and discuss the pathophysiological mechanisms of such edema development. A 60-year-old woman presented with a sudden onset severe headache. Computed tomography (CT) scans obtained two hours after the onset showed an AVM-like lesion with a small hematoma in the right parieto-occipital lobe, and unexpectedly early development of massive edema adjacent to the hematoma. Angiograms demonstrated a medium-sized AVM, and severe stenosis in the draining vein which suggested the presence of venous hypertension at prestenotic sites. Repeated CT scans and magnetic resonance (MR) images in the chronic period after the hemorrhage demonstrated persistence of the perinidal edema with mass effect. Removal of the lesion was achieved 2 months after the onset. MR images 3 months after the operation showed marked reduction of perinidal edema. The time course of the perinidal edema suggests that its development was unrelated to the hemorrhage. The findings indicate that increased venous pressure secondary to severe stenosis of the draining vein may possibly contribute to the development of perinidal edema.
Campylobacter fetus subspecies fetus rarely causes celluitis associated with bacteremia in debilitated hosts. We have identified this infection in two patients with systemic lupus erythematosus and in one with liver cirrhosis. All three patients had eaten raw beef, liver, or improperly cooked pork before the manifestations of the illness. C. fetus subspecies fetus was recovered from blood and feces from the three patients. This organism was also isolated from a subcutaneous aspirate of the cellulitis lesion in one patient. DNA macrorestriction endonuclease profiles analyzed by pulsed field gel electrophoresis differed for the isolates from the three patients but were identical for the blood and fecal isolates or the aspirate and fecal isolates from each patient. These findings suggest that cellulitis associated with bacteremia arises from ingestion of C. fetus subspecies fetus organisms and that clinicians and microbiologists should be aware of this infection in debilitated hosts.
A 42-year-old female with a mediastinal tumor and massive pleural effusion ws admitted to our hospital in June 1993. Biopsy revealed lymphoblastic lymphoma. She had no evidence of distant metastasis except pleural effusion. Bone marrow examination revealed a normal karyotype (46, XY). The patient had been progression-free for more than 1 year after achieving complete remission by induction, consolidation and maintenance therapy according to the standard chemotherapy and involved-field radiation for lymphoblastic lymphoma. From May 1996 progressive leukopenia and thrombocytopenia developed. The diagnosis of refractory anemia with excess of blasts (RAEB) was made. Subsequently, in November 1996, she developed acute myelogenous leukemia (AML), M4 type by FAB classification. The karyotype of MDS and AML clones involved inversion (3) (q21q26) and monosomy 7. The EVI 1 gene was examined and was proved to be rearranged and activated. This may be the first case among the therapy-related cases of MDS/AML reported whose karyotypes were followed and in which the mRNA expression of EVI 1 gene involved was directly proved in the leukemogenesis process of chemotherapy-induced secondary MDS and AML.
Apical dominance is a phenomenon in which a terminal bud grows predominantly and the growth of the axillary buds is suppressed. Here, we investigated the molecular mechanisms associated with cell cycle control that occur in pea axillary buds as a result of decapitation. Proliferating cell nuclear antigen (PCNA) protein was detected in both dormant and growing buds, while PCNA mRNA was absent in dormant buds. Pissa; CycB1;2 and Cdc2 proteins were undetectable during dormancy. To analyze an interaction between PCNA and Pissa;CycD3;1, we performed anti-PCNA immunoaffinity column chromatography. Pissa;CycD3;1 protein was detected in the eluate prepared from the dormant buds, but not in the eluate prepared from the growing buds. Furthermore, we performed anti-Pissa;CycD3;1 immunoaffinity column chromatography. PCNA protein was detected in the eluate prepared from the dormant buds, but not in the eluate prepared from the growing buds. These results indicated that PCNA associated with Pissa;CycD3;1 only during dormancy. In addition, the interaction between PCNA and Pissa;CycD3;1 was confirmed by a yeast two-hybrid system.
Axillary buds of pea (Pisum sativum L. cv. Alaska) do not grow on intact plants. Dormant axillary buds can be stimulated to grow rapidly after decapitation. Here, we isolated cDNAs of PCNA, cyclinB, cyclinD, and cdc2 from pea. The mRNA expression levels of these genes were very low in dormant axillary buds, whereas they remarkably increased after decapitation. Based on the mRNA accumulation patterns of these genes, we found that most cells in dormant axillary buds are arrested at the G1 phase in the cell cycle. There are four buds at the second node on pea seedlings. After decapitation, mRNAs became abundant in the large and small buds and were kept during the following 3 d. After 4 d, mRNAs were still present in the large bud, but not in the small bud. However, after removal of the large bud, the mRNA levels started to increase again in the small bud. These mRNA accumulation patterns were the same as those after the first decapitation. These results suggested that most cells in axillary buds at the second node are arrested at the G1 phase again and have the capacity to undergo multiple cycles of dormancy and growth. Moreover, in situ hybridization analyses demonstrated that PCNA mRNA increased in all parts of the axillary buds after decapitation.
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Multiple endocrine neoplasia type 1 (MEN1) is a familial cancer syndrome inherited as an autosomal dominant trait. Various heterozygous germline mutations of the responsible gene, MEN1, have been identified within its exons in many, but not all, affected individuals. We here demonstrate, by DNA polymorphism analysis and gene dosage analysis with polymerase chain reaction (PCR), a large heterozygous germline MEN1 deletion in a kindred with MEN1, in whom no mutation could be detected in the PCR-amplified exons. The deletion spanned an at least 7 kb region containing the entire MEN1 gene. These findings indicate that a large germline deletion of the MEN1 gene, which escapes detection in PCR-based sequence analysis, should be considered as a potential cause of MEN1.
Histiocytoid breast carcinoma (HBC) is a rare variant of breast carcinoma and often causes a diagnostic dilemma because of its histological similarities to some types of breast cancer and benign lesions. To elucidate the incidence of HBC and its biological properties, histological specimens from 1010 breast cancer patients treated at Yokohama Minami Kyosai Hospital between 1972 and 1996 were reviewed. Three cases of pure HBC and three cases of combined HBC (two with pleomorphic lobular carcinoma and one with apocrine ductal carcinoma) were found, yielding an incidence of 0.3% for each. Two of the three pure HBC cases contained foci of in situ lobular carcinoma. Targetoid and Indian file invasive patterns, the features characteristic of lobular carcinoma, were present in all three pure HBC cases and in two of the three combined HBC with pleomorphic lobular carcinoma. These results, together with those of previous studies, suggested that the majority of HBC are of lobular origin, although the apocrine ductal origin is also possible in a small number of HBC. Diastase-resistant periodic acid-Schiff-positive granules and granular immunoreactivities for gross cystic disease fluid protein-15 (GCDFP-15) were characteristic of the histiocytoid tumor cells in both the pure and combined HBC, suggesting the apocrine differentiation of tumor cells. All three pure HBC cases were in stage 1 and were free of the disease for up to 5 years and 1 month after the lumpectomy. Thus, the prognosis of HBC appears to be dependent on the stage of the disease and may not always be poor, as indicated by the original report mentioning a preferential eyelid metastasis.
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Pleomorphic carcinoma is a rare variant of pancreatic exocrine carcinoma. The aim of this communication is to reappraise surgical resection of pleomorphic carcinoma of the pancreas. Clinicopathological findings of four Japanese patients with pleomorphic carcinoma of the pancreas were reviewed and compared with those of 24 Japanese patients with adenocarcinoma of the pancreas to clarify possible surgical implications of pleomorphic carcinoma. Of the four patients, three were female and one male, aged 64, 65, 66, and 74 yr, respectively. Two carcinomas were located in the head of the pancreas, one in the body, and the other in the tail. Ultrasonography demonstrated a well defined hypoechoic mass measuring 5-10 cm, with central necrotic area in all of the patients. Computed tomography showed a low density tumor with sharp margin and heterogeneous internal structure in all. On angiography, three tumors were hypervascular and another was hypovascular. Extensive vascular encasement was observed in all. Pancreatoduodenectomy was done in two patients and distal pancreatectomy in the other two. Multiple liver metastases occurred 1 month after surgical resection in two patients and local recurrence 1 month in one and 2 months in the other, leading to death either 2 (2 patients) or 3 months (2 patients) after pancreatectomy. Significantly differentiating features of the four pleomorphic carcinomas of the pancreas and the 24 adenocarcinomas of the pancreas were the mean diameter (6.6 +/- 1.3 cm vs 3.5 +/- 0.3 cm, p = 0.0007), margin of the tumor (expansive in the four pleomorphic carcinomas versus infiltrative in 21 of the 24 adenocarcinomas, p = 0.003) and vascularity on angiography (hypervascular in three of the four pleomorphic carcinomas versus hypovascular in 21 of the 23 adenocarcinomas, p = 0.013). The 1-yr and 3-yr survival rates of the four patients with pleomorphic carcinoma were 0% and 0%, whereas those of the 24 patients with adenocarcinoma of the pancreas were 42% and 13%, respectively (p < 0.0001). These findings suggest that the clinical course of patients with pleomorphic carcinoma of the pancreas is so poor even after surgical resection that pleomorphic carcinoma of the pancreas is not a candidate for pancreatectomy despite its locally expansive growth.
The purpose of this study was to examine the effect of tetrahydrobiopterin, a co-factor of nitric oxide synthase, on H2O2-induced endothelial cell injury. Pretreatment with sepiapterin, a precursor of tetrahydrobiopterin biosynthesis, increased tetrahydrobiopterin content of endothelial cells, and reduced H2O2-induced endothelial cell injury, which was measured by leakage of lactate dehydrogenase. Both the increase in tetrahydrobiopterin content and the protective effect of sepiapterin were prevented by co-pretreatment with N-acetylserotonin, an inhibitor of sepiapterin reductase. Although Ca2+ ionophore ionomycin-induced nitric oxide synthesis was increased by pretreatment with sepiapterin, the protective effect of sepiapterin was not affected by an inhibitor of nitric oxide synthesis. On the other hand, pretreatment with sepiapterin also reduced H2O2-induced rat foetal lung fibroblast cell injury via an increase in tetrahydrobiopterin content, despite rat foetal lung fibroblast cells lacking nitric oxide synthase. Moreover, increase in tetrahydrobiopterin strongly reduced H2O2-induced intracellular oxidative stress. These findings indicate that sepiapterin reduces H2O2-induced endothelial cell injury via an increase in tetrahydrobiopterin content. Although increase in endothelial tetrahydrobiopterin content stimulated nitric oxide production, the protective effect of tetrahydrobiopterin against H2O2-induced endothelial cell injury is unlikely to be related to the stimulation of nitric oxide release from nitric oxide synthase. The protective effect of tetrahydrobiopterin may involve reactive oxygen species-scavenging activity.
A low-specificity L-threonine aldolase (L-TA) gene from Pseudomonas sp. strain NCIMB 10558 was cloned and sequenced. The gene contains an open reading frame consisting of 1,041 nucleotides corresponding to 346 amino acid residues. The gene was overexpressed in Escherichia coli cells, and the recombinant enzyme was purified and characterized. The enzyme, requiring pyridoxal 5'-phosphate as a coenzyme, is strictly L specific at the alpha position, whereas it cannot distinguish between threo and erythro forms at the beta position. In addition to threonine, the enzyme also acts on various other L-beta-hydroxy-alpha-amino acids, including L-beta-3,4-dihydroxyphenylserine, L-beta-3,4-methylenedioxyphenylserine, and L-beta-phenylserine. The predicted amino acid sequence displayed less than 20% identity with those of low-specificity L-TA from Saccharomyces cerevisiae, L-allo-threonine aldolase from Aeromonas jandaei, and four relevant hypothetical proteins from other microorganisms. However, lysine 207 of low-specificity L-TA from Pseudomonas sp. strain NCIMB 10558 was found to be completely conserved in these proteins. Site-directed mutagenesis experiments showed that substitution of Lys207 with Ala or Arg resulted in a significant loss of enzyme activity, with the corresponding disappearance of the absorption maximum at 420 nm. Thus, Lys207 of the L-TA probably functions as an essential catalytic residue, forming an internal Schiff base with the pyridoxal 5'-phosphate of the enzyme to catalyze the reversible aldol reaction.
Ets-1 is a transcription factor that activates expression of matrix-degrading proteinases such as collagenase and stromelysin. To study the control of ets-1 gene expression in rat vascular smooth muscle cells (VSMC), cells were exposed to factors known to regulate VSMC migration and proliferation. Platelet-derived growth factor-BB (PDGF-BB), endothelin-1 (ET-1), and phorbol 12-myristate 13-acetate (PMA) induced a dose-dependent expression of ets-1 mRNA. These effects were abrogated by inhibition of protein kinase C (PKC) by H-7 or chronic PMA treatment. Ets-1 mRNA was superinduced by PDGF-BB and ET-1 in the presence of cycloheximide. The chelation of intracellular Ca2+ by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester and the depletion of endoplasmic reticulum intracellular Ca2+ concentration ([Ca2+]i) by thapsigargin inhibited PDGF-BB- and ET-1-induced ets-1 mRNA, whereas ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid had no effect. However, [Ca2+]i release alone was not sufficient to increase ets-1 mRNA. Forskolin blocked ET-1-, PDGF-BB-, and PMA-induced ets-1 mRNA, as well as inositol phosphate formation, consistent with an effect through impairment of PKC activation. Inhibitors of ets-1 gene expression, such as H-7 and herbimycin A, inhibited the ET-1 induction of collagenase I mRNA. We propose that ets-1 may be an important element in the orchestration of matrix proteinase expression and of vascular remodeling after arterial injury.