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A 60-year-old female, diagnosed as scleroderma, was referred to our hospital because of symptoms of common cold and abnormal findings on a chest X-ray. The chest X-ray and CT scan revealed a mass in the left upper field, suspected to invade left anterior chest wall. Moreover, fibrotic changes were observed in the lung field. Cytology by bronchofiberscopy showed squamous cell carcinoma. Evaluation of pulmonary function, including unilateral pulmonary artery occlusion test (UPAO), revealed possibility of lung resection. Subsequently, pneumonectomy with combined resection of left 1st rib was performed. Postoperative course was uneventful and she was discharged. She was admitted again four months after the operation with appetite loss and body weight loss. Further examinations revealed arrhythmia, renal failure, pancreatitis and liver metastasis. Her general conditions grew worse and she died five months after the operation. In conclusion, UPAO was a useful method to determine the functional lung resectability for the case with scleroderma. However, effects of surgical stress for the development of scleroderma remain to be elucidated.

Multiseptate gallbladder is an extremely rare congenital anomaly. We report three cases of this clinical entity. The third patient, a 70-year-old male who was asymptomatic with this condition, also had a gallbladder carcinoma. The three surgically removed gallbladders had multiple thin septa with a honeycomb appearance. Histologically, the septa contained a muscular layer that was continuous with the gallbladder wall. Furthermore, in the third patient, mucinous cystadenoma with focal carcinomatous change in the epithelium was observed. To our knowledge, this is the first description of a multiseptate gallbladder with carcinoma.

Aplastic anaemia is characterized by reduced haematopoiesis resulting in pancytopenia. It has been speculated that there is an injury in haematopoietic stem cells in the bone marrow; however, the precise nature of the injury has not been elucidated. In this study, the levels of expression of mRNAs for three transcription factors, GATA-2, SCL and AML1, which function in the early stages of haematopoiesis, were examined by quantitative polymerase chain reaction in patients with aplastic anaemia, idiopathic thrombocytopenic purpura (ITP) and normal subjects. Among these factors, expression of GATA-2 mRNA in purified CD34-positive cells was markedly decreased in aplastic anaemia compared with that in ITP and in normal subjects. The expression levels of SCL and AML1 mRNA in CD34-positive cells in aplastic anaemia were not different from those in normal subjects. When the expression of GATA-2 protein in CD34-positive cells was examined by immunocytochemical analysis, the percentage of GATA-2-positive cells in aplastic anaemia was lower than that in normal subjects. These findings strongly suggest that there is an aberrant expression of transcription factors in stem cells in aplastic anaemia, which may be responsible for the development of the disease.

Release of cytochrome c from mitochondria to the cytosol is a critical step in apoptotic cell death after focal cerebral ischemia. The role of cytochrome c release on selective vulnerability and delayed death of hippocampal CA1 neurons after transient global ischemia is unknown and is the subject of this study. Global ischemia was induced by 10 min of bilateral common carotid artery occlusion and hypotension. Cytosolic expression of cytochrome c was evaluated by immunohisto- chemistry and Western blotting. Apoptosis after global ischemia was characterized by terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling (TUNEL) staining and genomic DNA gel electrophoresis. Immunohistochemistry showed cytosolic cytochrome c-positive cells exclusively in the vulnerable CA1 subregion of the hippocampus as early as 2 h after ischemia. Double fluorescent immunostaining confirmed that CA1 neurons and a small number of astrocytes expressed cytochrome c. Western blot analysis revealed a band (15kDa) of cytochrome c in the cytosolic fraction, and a corresponding decrease in the mitochondrial fraction. A significant number of TUNEL-positive cells appeared only in the CA1 pyramidal cell layer of the hippocampus, and DNA gel electrophoresis showed a significant amount of DNA fragmentation 3–5 days after ischemia. Our data provide the first evidence that cytochrome c was released to the cytosol from mitochondria in CA1 neurons after global ischemia, and that the release preceded DNA fragmentation. These findings suggest that cytochrome c may be involved in the delayed death of hippocampal CA1 neurons in rats after transient global ischemia.

C 36 H 18 cristallise dans P2 1 avec a=11.814, b=7.803, c=10.871A, β=91.41°, Z=2; affinement jusqu'a R=0.051. La molecule adopte une structure toit oblique, due a la presence de deux sites de recouvrement en forme de fjord, ce qui provoque une deformation vers une forme bateau du cycle central

To correlate retinal functional changes with structural changes in P23H rhodopsin transgenic rats as a model of autosomal dominant retinitis pigmentosa.P23H heterozygote (lines 1 and 3) and Sprague-Dawley control rats were studied at 4 to 29 weeks by retinal histology, electroretinogram (ERG), and a-wave transduction modeling.Both line 1 (faster degeneration) and line 3 (slower degeneration) showed progressive rod outer segment (ROS) shortening and outer nuclear layer (ONL) cell loss with age. ERG b-wave maximum amplitude (Vb(max)) decreased with age, but b-wave threshold remained constant within each line despite progressive ONL thinning and ROS shortening. The only exception was in line 1 at 29 weeks, which showed a slight threshold change relative to earlier ages. Va(max) and a-wave threshold changed more rapidly and were more sensitive than the b-wave in reflecting histologic degeneration. Va(max) was linearly proportional to the product of (ROS x ONL) across a two log unit range of data combined from both lines. The photopic b-wave was normal for both lines until the ONL thinned beyond 50%. Phototransduction sensitivity was normal for both lines, and dark-adaptation recovery after bleaching rhodopsin was normal.The P23H transgenic rat has a slow rod degeneration with initially normal cone function, consistent with clinical findings of P23H patients. However, the normal bleach recovery and the normal phototransduction sensitivity in this rat model are different from human P23H disease. a-Wave measures were more sensitive than the b-wave for tracking changes. b-Wave threshold was inexplicably poor for tracking degeneration. Although line 1 degenerated faster than line 3, the functional-structural correlates were the same. The tight linear relationship between saturated a-wave amplitude and the product of (ROS x ONL) indicates that the density of cGMP-gated channels per unit ROS plasma membrane area remains constant over a wide range of degenerations.

We investigated digestion of orally fed galactoglycerolipids such as monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) from wheat flour in the rat alimentary canal, especially focusing on the digestive fates of deacylated galactosylglycerol structures. After a single oral administration of MGDG (20 mg/rat), monogalactosylmonoacylglycerol and monogalactosylglycerol (MGG) were found to be major digestion products in the intestinal tract. Similarly, digalactosylmonoacylglycerol and digalactosylglycerol (DGG) were confirmed to be present in the intestinal tract after DGDG ingestion (20 mg/rat). In rats fed wheat flour glycolipids (42 mg MGDG and 81 mg DGDG per rat), completely deacylated galactosylglycerols (MGG and DGG) were not detected in portal plasma. Although the deacylated galactosylglycerols were not significantly decomposed by intestinal mucosa in vitro, they were hydrolyzed by cecal contents. The results demonstrated that orally ingested plant galactoglycerolipids in the rat alimentary canal are rapidly hydrolyzed into constituent fatty acids and that hydrophilic galactosylglycerols and the hydrophilic backbone galactosylglycerols are not absorbed from intestine or degraded into galactose and glycerol in the intestinal tract. Therefore, the presence of deacylated galactosylglycerols may affect the fermentative activity of enterobacteria in the cecum and colon.

This report describes two cases of Philadelphia chromosome-negative (Ph(-)) non-Hodgkin's lymphomas (NHLs) recognized in patients with chronic phase Ph-positive (Ph(+)) chronic myelogenous leukemia (CML). Lymph node biopsy of patient 1 was initially diagnosed as diffuse large B cell non-Hodgkin's lymphoma (NHL, T cell rich variant), but at relapse showed immunoblastic features with a marked decrease of admixed lymphocyte components. Patient 2 presented with thickened parietal pleura which revealed a CD30-positive anaplastic large cell lymphoma showing null cell phenotype and genotype with abundant admixed neutrophils and lymphocytes. At the time of lymphoma diagnosis, the patients had CML for 33 and 10 months, respectively. DNA obtained from bone marrow cells at the time of lymphoma diagnosis showed BCR/ABL gene rearrangements by both Southern blot analysis and reverse transcription polymerase chain reaction (RT-PCR), but lacked both immunoglobulin and T cell receptor gene rearrangements. BCR gene rearrangement and BCR/ABL fusion gene were also identified in lymph node and pleural biopsies by Southern blot and RT-PCR analysis, respectively. However, both biopsy specimens also contained reactive lymphocytes and neutrophils, and no fusion signals between BCR and ABL genes were identified in the hyperdiploid lymphoma cells of either case by fluorescence in situ hybridization (FISH). These data suggest the lymphoma cells in both cases were not genetically associated with BCR/ABL. Therefore, these cases were not diagnosed as an extramedullary localized blast crisis in CML, but as Ph(-) NHLs. This represents the first definitive demonstration of peripheral B cell lymphoma occurring by a separate genetic pathway, lacking BCR/ABL, in patients with Ph(+) CML. A review of the literature identified two different subtypes of malignant lymphomas arising in patients with an antecedent or concurrent diagnosis of CML. The most common are T cell lymphomas displaying an immature thymic phenotype, while peripheral B cell lymphomas are more rare. Our study shows, however, that 'Ph(+) NHL' occurring in CML or acute lymphocytic leukemia (ALL) may represent an unrelated neoplasm, even if standard cytogenetic analysis reveals a Ph(+) chromosome, and that FISH is required to confirm whether a localized lymphoid neoplasm is either a true extramedullary localized blast crisis or genetically distinct neoplasm. Leukemia(2000) 14, 169-182.

We encountered a 44-year-old woman with suspected chronic myelocytic leukemia (CML) in the acute phase that was difficult to be differentiate from Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). At disease onset, her bone marrow showed an increase in blasts that were negative for myeloperoxydase (MPO) and Positive for CD10, 19, 34, and HLA.DR. Standard type Ph was detected by chromosome analysis, and both major and minor BCR/ABL m-RNA were detected by reverse-transcriptase polymerase chain reaction (RT-PCR) methods. Neutrophil alkaliphosphatase (NAP) score was normal, and neither eosinophilia nor basophilia was observed in peripheral blood. Under a presumptive diagnosis of Ph-positive ALL (L2), the patient was given AdVP (doxorubicin, vincristine, and prednisolone) therapy followed by a regimen of LMVP (L-asparaginase, mitoxantrone, and VP), and obtained a complete remission 2 months later. At that time, FISH analyses of her bone marrow and blood cells no longer detected bone marrow Ph or BCR/ABL fusion gene. A month later, however, the leukemia relapsed with an increase in MPO-positive blasts in bone marrow, and the patient died soon thereafter. We finally concluded that her leukemia was not Ph-positive ALL, but CML in the acute phase at disease onset.

C 20 H 10 N 4 cristallise dans Pbcn avec a=14,53, b=10,007, c=20,033 A, Z=8; affinement jusqu'a R=0,059. Le cycle indenofluorene est plan, et on observe une grande deformation des angles et des longueurs des liaisons dans les deux groupements diazo bien situes. Des paires de molecules avec des orientations antiparalleles forment un empilement en aretes de poissons, propres aux hydrocarbures aromatiques polycondenses

We describe two patients with primary cardiac malignant lymphoma involving the right atrium and superior vena cava, resulting in intractable right cardiac failure and superior vena cava syndrome. Patients were diagnosed by surgical myocardial biopsy and were treated with combination chemotherapy for non-Hodgkin's lymphoma. Each attained a marked response, and hence avoided sudden death from tricuspid atresia. Both have remained alive for more than 21 and 34 months, respectively, and continue intermittent combination chemotherapy.

Stimulation of steroid-producing cells of the gonads and adrenals with tropic hormone results in a marked increase in steroid hormone synthesis within minutes. The rate-limiting step in this acute steroidogenic response is the transport of cholesterol from the outer to the inner mitochondrial membrane, where the first committed step in steroid synthesis is performed by the side-chain cleavage enzyme system. This process of cholesterol translocation is blocked by inhibitors of protein synthesis, suggesting that the effect of trophic hormones, acting through the intermediacy of cAMP, most likely involves the de novo synthesis of a protein that is rapidly inactivated. The recently identified steroidogenic acute regulatory (StAR) protein appears to be the most likely candidate for the "labile" protein, based on the following observations: 1) Expression of StAR in COS-1 cells engineered to contain the cholesterol side-chain cleavage system substantially augments pregnenolone formation; 2) StAR protein is expressed almost exclusively in steroid-producing cells, except the trophoblast of the human placenta, and its presence is correlated with steroid hormone production; 3) StAR mRNA increases in response to cAMP; 4) StAR is a target for serine phosphorylation mediated by protein kinase A, a process that is essential for maximizing StAR activity; and 5) lack of functional StAR causes the autosomal recessive disease, congenital lipoid adrenal hyperplasia, characterized by markedly impaired gonadal and adrenal steroid hormone synthesis. Studies on the mechanism of action of StAR revealed that import into mitochondria is not essential to its steroidogenesis-enhancing activity and more likely represents a means of rapidly inactivating StAR. Truncation mutations and site-directed mutations established that the C-terminus of the StAR protein contains the functionally important domains. The demonstration of steroidogenic activity of recombinant StAR protein on isolated mitochondria from bovine corpus luteum using protein that lacks the mitochondrial targeting sequence confirmed that StAR import is not essential for its steroidogenic activity and suggested that StAR acts directly on the outer mitochondrial membrane in the absence of intermediary cytosolic factors. Evidence that StAR functions as a cholesterol transfer protein raises the possibility that StAR acts directly on lipids of the outer mitochondrial membrane, probably stimulating cholesterol desorption from the sterol-rich outer membrane and its movement to the relatively sterol-poor inner membrane.

The purpose of this study was to compare the effect of premixed 5% dextrose in Ringer's acetate solution and premixed lidocaine with propofpl on the reduction of pain during injection of propofol in adult patients. We conducted a prospective, randomized, double-blinded trial. Ninety-six patients were randomly allocated to one of three groups according to the agents added to 1% propofol 20 ml; Group C, normal saline 2 ml, Group L, 2% lidocaine 2 ml, and Group A, 5% dextrose in Ringer's acetate solution 2 ml. The pain on injection was rated as none, mild, moderate, or severe. Seventy percent of patients in the C group experienced pain, while 33% and 25% of patients experienced pain in the A group and the L group, respectively. Forty-two percent of patients in the C group complained moderate to severe pain but only one patient in both A group and L group. In conclusion, 5% dextrose in Ringer's acetate solution premixed with 200 mg propofol significantly reduces incidence and severity of pain associated with propofol injection and is easier to use than premixed lidocaine.

Gallbladder carcinoma limited to the mucosa (pT1a) or muscularis proper (pT1b) with no lymph node metastasis (stage I) is defined as early carcinoma of the gallbladder. Eleven patients with early carcinoma of the gallbladder, treated by either simple or extended cholecystectomy (cholecystectomy plus wedge resection of the gallbladder bed of the liver and lymphadenectomy), were reviewed to determine the diagnostic capability and to clarify the rational resectional procedure for this stage of the disease. A definitive pre-operative diagnosis was made in only 2 patients with pT1b tumors. Most of the remaining 9 patients were diagnosed incidentally after cholecystectomy for polyps or stones. Among 7 patients with pT1a tumors, 5 underwent simple cholecystectomy and 2 underwent extended cholecystectomy. All 7 patients survived with a recurrence-free condition for 5 years or more following the operation. Two patients with pT1b tumors, however, died of a local recurrence or bile duct carcinoma following simple cholecystectomy. Two patients with pT1b tumors who were correctly diagnosed before the operation and underwent extended cholecystectomy survived without recurrence. It is concluded that patients with pT1a tumors can be successfully treated by simple cholecystectomy, while patients with pT1b tumors require extended cholecystectomy.

An analytical wave‐optics solution is derived for the modal structure of the Cerenkov second‐harmonic optical field in weakly guiding cylindrical fiber waveguides. Numerical results for the axially symmetric mode indicate that the second‐harmonic power significantly depends on the dimension of the core.

Systemic administration of melatonin can increase retinal light damage in the rat. The role of retinal melatonin receptors in modulating light-damage susceptibility was investigated by intravitreally injecting the melatonin receptor antagonist luzindole into rats.Nine Sprague-Dawley albino rats 8 to 9 weeks of age were kept in 50 lux cyclic light for at least 7 days before receiving an intravitreal injection of 1 microl 1 mM luzindole in one eye and 1 microl vehicle in the other eye. The injection was given just before the beginning of the normal 12-hour dark phase. At the end of this dark period, animals were exposed to constant light of 2500 lux for 48 hours. Animals were returned to dim cyclic light for 7 days, and dark-adapted electroretinograms (ERGs) were then recorded from the two eyes simultaneously. The eyes were processed for retinal morphology. Photoreceptor nuclei were counted in the outer nuclear layer (ONL), and the thickness of the ONL and that of the rod outer-segment plus inner-segment layer were measured at several points along sections through the vertical meridian. Two age-matched control rats were maintained in dim cyclic light but received no injections.Luzindole-treated eyes had ERG b-wave thresholds of 2.7 +/- 0.5 (mean +/- SEM) log candela (cd)/m2 lower than the fellow eyes injected with vehicle (P0.001), and the maximum b-wave amplitude was 1.0 +/- 0.2 log microV greater in luzindole-treated eyes (P0.001). Thresholds of the scotopic threshold response were 0.5 +/- 0.1 log cd/m2 lower than those in vehicle-injected eyes (P0.05). Luzindole-treated eyes on average had twice as many photoreceptor cells remaining (P0.005). In some areas, several rows of photoreceptor nuclei and outer segments remained in the luzindole-treated eye, whereas the fellow control eye showed cells only occasionally and no outer segments.Eyes pretreated with the melatonin receptor competitive antagonist luzindole before the dark phase preceding constant light exposure were substantially protected from light damage to the retinal photoreceptors. These results implicate the intraocular melatonin-dopamine system in the regulation of light-damage susceptibility.

T lymphocytes express various glycosylphosphatidylinositol (GPI)-anchored surface proteins, such as Thy-1 and Ly-6A. However, functional contribution of GPI-anchored proteins in T cell activation is as yet poorly understood. Here we report the generation of mutant mice deficient in the expression of GPI-anchored molecules exclusively in their T cells. We established mice carrying three identically oriented lox-P sites within the Pig-a gene, which encodes a component essential for the initial step of GPI anchor biosynthesis. These mice were crossed with mice carrying the Cre recombinase gene driven by the T cell-specific p56lck proximal promoter. Offspring carrying both the lox-P-containing Pig-a gene and the Cre transgene exhibited almost complete loss of the surface expression of GPI-anchored molecules on peripheral T cells. Interestingly, those T cells deficient in GPI-anchored molecules were capable of responding to T cell receptor stimulation in vitro and in vivo. These results indicate that T cells lacking the expression of GPI-anchored molecules are functionally competent in exerting TCR-mediated immune responses.

We report a 63 year-old female with aplastic anemia (AA) who was complicated with hemophagocytic syndrome induced by systemic miliary tuberculosis. Two years before admission to our hospital, she was diagnosed as AA and had been treated with granulocyte colony-stimulating factor, erythropoietin and methenolone acetate. In May, 1996, She was transferred to our hospital because of high fever and exacervation of pancytopenia. She showed severe pancytopenia, and an increase in macrophages showing remarkable erythrophagocytosis and decrease in hemopoietic cells in the bone marrow. In initial examination, high titer of IgM antibody to herpes simplex virus type I was identified and methylprednisolone pulse therapy was started under the diagnosis of virus associated hemophagocytic syndrome. Ten days later, however, she died for intestinal hemorrhage followed by multiorgan failure. In autopsy, multiple epitheloid cell granulomas with acid-fast bacilli were found in bone marrow, lungs, liver, spleen and kidneys.

1. Alpha1B-adrenoceptors are localized at a steady state in the plasma membrane in untreated cells, and internalize to intracellular vesicles when exposed to agonist. Flow cytometry analysis with an anti-N-terminus-antibody (1B-N1-C, (Hirasawa et al., 1996)) facilitated the quantification of cell surface alpha1B-adrenoceptor. Also, the cellular distribution of alpha1B-adrenoceptors was visually monitored by immunocytochemical confocal microscopy. 2. Utilizing this combined approach, we have examined the molecular mechanism for cellular trafficking of alpha1B-adrenoceptors, including the process of sorting of the synthesized receptor protein to the cell surface, and the agonist-induced internalization. The two processes were separately examined by using alpha1B-adrenoceptor inducible DDT1MF-2 cells for the sorting process and CHO cells stably expressing alpha1B-adrenoceptors for the agonist-promoted internalization. 3. We examined the effects of cytochalasin D and mycalolide B (actin depolymerization agents), demecolcine (a microtubule disrupting agent), brefeldin A (an inhibitor of vesicular transport and Golgi function), bafilomycin A1 (a specific inhibitor of the vacuolar proton pump) or hyperosmotic sucrose treatment (that may inhibit clathrin-mediated endocytosis) on these processes. 4. We found that the agonist-promoted internalization was blocked by cytochalasin D and mycalolide B, while the cell surface sorting process was specifically blocked by brefeldin A, indicating that the two processes involve different components of the cellular endocytic machinery. 5. The experimental approach as exemplified in this study would provide a valuable system to study further the molecular mechanism(s) of cellular trafficking of G protein-coupled receptors.

We studied the reproducibility of multifocal electroretinography by repeated measurements in normal subjects. We also analyzed the amplitude and implicit time of the waves. Nine healthy eyes including myopic cases (-4.1 D on average) of 9 normal males, aged 19 to 42 years, were the objects of study. We used a (Visual Evoked Response Imaging System III (VERIS III), by TOMEY Corp.) for multifocal electroretinography. Each eye was examined 4 times on different days. The stimulus elements consisted of 103 hexagons. The net recording time was 4 minutes. We used the coefficient of variation (standard deviation/average) of 4 measurements of response density as index of reproducibility. Poor fixation and blinking were important factors that affected the reproducibility. In all the 9 eyes, reproducibility of multifocal electroretinography, expressed as average of the coefficient of variation of all regions, was 22% on average. In 6 eyes with good fixation and without blinking, the reproducibility was 15% on average. In 6 eyes with good reproducibility, we analyzed three parameters of the focal response waves: all traces, quadrants and rings, as well as the amplitude and latency of the waves. These data served as controls. Our studies showed that the response density correlated closely with the amplitude and not with the latency in normal subjects.

We studied relationships between maximal walking distance (WDmax) and frequency of both outing enumerated by the aim of each outing as well as by each outing per se in patients receiving home oxygen therapy (n = 109). The results were compared with those from members of a seniors' club (n = 434). A questionnaire was used to obtain WDmax, defined as the distance a subject could walk without rest on level ground. In the questionnaire, WDmax was classified into five groups including 50 m (the distance between two electric posts), 500 m, 1 km, 1.5 km and more than 1.5 km. Since few patients could walk 1.5 km or more, they were included into the "can walk 1 km or more group". Outing frequency was measured using a 4-week diary which showed eight aims of outings including shopping, seeing a doctor, visiting friends or relatives, doing a hobby practicing something, participating in a seniors' club and neighborhood meetings or events, traveling, work and others. The subjects checked the diary each time they went out. True outing frequency was defined as the number of outings. If a subject left home to shop and visited a friend on the way home, the outing frequency enumerated by aims was two, while the true outing frequency was one. The mean and SE (1/4 weeks/one subject) of true outing frequency for patients (21.4 +/- 2.2) was significantly less than that of seniors' club members (45.6 +/- 1.4). Even in patients with a WDmax of 1 km or more, the frequency of travel was significantly lower than in seniors' club members. Although outing frequencies for shopping, seeing friends or relatives, doing a hobby and work were not significantly different between the two groups at a WDmax of 1 km or more, the outing frequency for work of patients was significantly lower at a WDmax of 500 m, and outing frequencies for the remaining three aims became significantly lower at a WDmax of 50 m. We demonstrated that in patients receiving home oxygen therapy, outing frequency was limited. A new modality is necessary to increase the outing frequency and to improve the quality of life for these patients.

Chlorethylclonidine (CEC) inactivation has been used as one criterion to subclassify the alpha1-adrenoceptors (AR); however, the extent of CEC inactivation can vary depending on the CEC treatment. By constructing the FLAG-tagged (N-terminus) and green fluorescent protein (GFP)-fused (C-terminus) alpha1-ARs, we have determined the relationship between CEC sensitivity and the cellular localization of alpha1-AR subtypes using COS-7 cells. In GFP-expressing cells, flow cytometry analysis with anti-FLAG N-terminus antibody detected strong fluorescent signals in most of alpha1B-AR-expressing cells, but low signals in alpha1A-AR-expressing cells. Further examination with confocal microscopy showed that fluorescent signals densely localized intra-cellularly in alpha1A-AR-expressing cells, while most of alpha1B-AR localized on the cell surface. Furthermore, radioligand binding studies with [125I]HEAT showed that CEC (10 microM) treatment of intact cells inactivated approximately 30-40% of alpha1A-AR and90% of alpha1B-AR, while the CEC treatment of membrane preparations resulted in80% decrease in the alpha1A-AR density and90% of alpha1B-AR density, respectively. The results showed that the hydrophilic alkylating agent CEC inactivated only alpha1-AR on the cell surface irrespective of its subtype, and that the subtype-specific sorting is a major determinant for CEC inactivation of alpha1-AR. Subtype-specific cellular localization suggests a new class of functional properties that may explain the signal and functional diversity of homologous alpha1-AR (as well as other G protein-coupled receptors) subtypes.

We examined family APGAR scores in patients on home oxygen therapy (n = 101) and their main caregivers (n = 91), and compared them with those obtained from members of a seniors' club who were not on home oxygen therapy themselves, nor had any family members on home oxygen therapy. Furthermore, the relationship between the main caregivers recognition of the patients' mental state and the patients' CESD score was examined. Family APGAR scores for the main caregivers were significantly lower than those of the patients (p0.002), or the seniors' club members (p0.004). Since most the main caregivers were women, we compared family APGAR scores of the female main caregivers and the age-matched female members of the seniors' club, revealing that the satisfaction of the female main caregivers with the "adaptation" component of the APGAR score (the component dealing with support given when something troublesome happens), was significantly lower than that of the members of the seniors' club (p0.0001). The CESD of the patients whom the main caregivers recognized as depressed was significantly higher. Thus, we concluded that satisfaction of the main caregivers with family function who were family members was low, and that the role of the main caregivers is important in alleviating the depression of patients on home oxygen therapy.

A dimeric form of C60 is selectively synthesized by squeezing organic molecular crystal (ET)2C60 at 5GPa and 200 °C. Characterizations by Raman, infrared, and chromatographical studies provide unambiguous evidences for the dimeric form connected by 2+2 cycloaddition. Differential scanning calorimetry analysis showed that the heat of formation for the dimeric C60 is the largest among several polymeric phases of C60.

We described an autopsy case of a ruptured aneurysmal subarachnoid hemorrhage treated with endovascular embolization by interlocking detachable coils. An 85-year-old male presented with sudden onset of severe subarachnoid hemorrhage. Cerebral angiogram revealed a right internal carotid-posterior communicating artery aneurysm. Post-operative angiogram revealed complete obliteration of the aneurysm, except for its orifice. Following the embolization of the aneurysm, tissue plasminogen activator was intrathecally perfused for anti-vasospasm treatment. Follow-up angiogram showed stable obliteration of the aneurysm, and no particular findings of cerebral vasospasm. The patient had been recovering without any neurological deficits, but died from pneumonia on the 25th day after the embolization. Autopsy findings revealed the disappearance of the subarachnoid hemorrhage, and no visible finding of cerebral infarction or edema. The inner lumen of the aneurysm was occupied by a mixture of the coils and the clots. The surface of the embolized coils was directly observed through the orifice of the aneurysm without any membranous substance from the inner lumen of the internal carotid artery. This pathological finding is different from the previously reported animal models in which the surface of the embolized coils was covered with endothelial membrane 2 weeks after embolization. Further examinations are required to clarify the pathogenesis of the endothelial regrowth.

We report a case of large cystic acoustic neurinoma. A 52-year-old male was admitted to hospital with a history of progressive dysphagia, gait disturbance and diplopia for 2 months. On admission, neurological examinations revealed Bruns' type nystagmus to the left side, hypesthesia in the distribution of the second and third divisions of the left trigeminal nerve, and partial paresis of cranial nerves IX, X, and XII on the left side, and truncal ataxia. A pure-tone threshold audiogram indicated the presence of 32 dB hearing loss in the left ear. Speech discrimination was 80%. Caloric vestibular responses were absent on the left side. Skull radiographs with polytomographs of the internal auditory canal (IAC) were normal. Bony changes in the IAC were not found by high-resolution bone-window computed tomography (CT) scan. A plain CT scan revealed a large low-attenuated cystic mass in the left cerebellopontine angle (CPA), which was associated with displacement of the fourth ventricle. An enhanced CT scan demonstrated a thin rim-enhancement in the cyst wall. Magnetic resonance imaging (MRI) scans disclosed a large rim-enhanced cystic mass extending superiorly into the tentorial incisura and inferiorly into the foramen magnum. At surgery via a left suboccipital approach, a large cystic mass was found at the left CPA arising from the VIIIth nerve, and compressing the Vth, VIth, VIIth and lower cranial nerves. The cyst was filled with a xanthochromic fluid and was firmly attached to the internal auditory meatus (IAM). However no tumor extension into the IAM was confirmed. The tumor was excised completely. The postoperative course was uneventful, except for impairment of the VIIth and VIIIth nerves. At 6 months after the first operation, the facial nerve had improved up to grade III (Hause-Brackmann stage). Histological examinations revealed a typical benign acoustic neurinoma with predominant representation of Antoni B tissues. The cyst wall contained numerous abnormal sinusoid and telangiectasia-like vessels which showed occasional thromboses. The vessel walls displayed endothelial proliferations and were frequently hyalinized. Hemosiderin deposits and hemosiderin-containing phagocytes were also found near these vessels. Myxoid degeneration and necrosis were evident in vast areas. These degenerative changes appeared to be the principal causes of the large cystic formation. 16 cases including our case have been reported. The broad characteristics of the clinical symptoms and radiological findings of these tumors are discussed.

We report a rare case of a giant thrombosed fusiform aneurysm at the branch of left middle cerebral artery presenting with intramural hemorrhage of the aneurysm. A twenty-year-old man with familial and past history of migraine presented sudden temporalgia on August 13, 1995. Computed tomography (CT) scan on the day of the first attack revealed a well delineated high density area at the left Sylvian fissure, 2.5cm in diameter. Angiogram showed avascular area corresponding to the lesion, but no visualization of the aneurysm. On October 18, this patient presented sudden temporalgia again. CT scan on the day of the second attack indicated new intramural hemorrhage and surgery was performed on October 31. No evidence of subarachnoid hemorrhage was shown during the operation, and the lesion was proven to be a thrombosed fusiform aneurysm at the branch of the middle cerebral artery. The parent artery was clipped at both proximal and distal sides of the aneurysm, and the aneurysm was totally removed with success. Histological finding further supported the idea that the attacks mentioned were due to intramural hemorrhage of the thrombosed aneurysm. Postoperative course was uneventful and the patient was discharged without any neurological deficit. Intramural hemorrhage of a giant fusiform aneurysm is relatively rare, only reported in several autopsy cases. Furthermore, we failed to discover any comparable cases of giant fusiform aneurysm presenting symptoms directly caused by intramural hemorrhage of the aneurysm.

We report a case of 53-year-old man with acute myelogenous leukemia (M2) showing a karyotype of t(7;11) (p15;p15), del(10) (q11;q12), who was complicated with perforation of a duodenal ulcer during the antileukemic chemotherapy using behenoyl ara-C, daunorubicin, 6-mercaptopurine and prednisolone. As his bone marrow still showed high cell density and leukemic proliferation at the time of intestinal perforation, the therapeutic regimen was changed to a combination of behenoyl are-C and mitoxantrone, and daily rhG-CSF was concurrently administered for the purpose of early establishment of bone marrow hypoplasia. On the 8th day after the therapeutic regimen had been changed, his bone marrow became nearly aplastic, and complete remission was obtained on the 24th day. This case may indicate that the concurrent administration of cell-cycle specific antileukemic drugs and rhG-CSF is available for AML patients with emergent need of leukemic cell reduction.

Thin films of rare earth (RE)-doped BiFeO3 (where RE=Sm, Ho, Pr and Nd) were grown on LaAlO3 substrates by using the pulsed laser deposition technique. All the films show a single phase of rhombohedral structure with space group R3c. The saturated magnetization in the Ho- and Sm-doped films is much larger than the values reported in the literature, and is observed at quite a low field of 0.2 T. For Ho and Sm doping, the magnetization increases as the film becomes thinner, suggesting that the observed magnetism is mostly due to a surface effect. In the case of Nd doping, even though the thin film has a large magnetic moment, the mechanism seems to be different.

We investigated the effect of nicardipine (NC), a calcium antagonist, on retinal ischemia-reperfusion injury. Electroretinogram (ERG) was recorded from rabbit eyes before and after ischemia produced by increasing intraocular pressure to 140 mmHg for 90 min after giving 0.01% NC (0.1 ml) intravitreally (n = 4). ERGs from intact (non-ischemic) rabbit eyes after injecting NC intravitreally was also recorded (n = 4) (NC group). The recovery rate of b-wave amplitude after reperfusion was significantly higher in the NC group than in the control group which was given saline without NC (p0.05). There were no significant differences between the NC and the control groups in a-wave amplitude and implicit time of the b-wave. No significant changes were detected in the a-wave or b-wave amplitude after intravitreal injection of NC into the intact eyes. We suggest that NC can prevent ischemia-reperfusion injury of the rabbit retina and could be considered for clinical use.

The intestinal walls of the irradiated pelvic tumor cases of 20 patients were studied. CT manifestations of the irradiated intestinal wall were examined at the early vascular phase (examined 40 seconds after the injection of contrast medium by helical scan) and at the delayed equilibrium phase (examined 4 to 5 minutes after the injection of contrast medium by rapid sequence scan). Two characteristics were identified: intestinal wall thickening and a three-layered pattern. The former was better depicted on equilibrium phase, whereas the latter was clearer on early vascular phase. Differences in visualization of the wall thickening on vascular phase and delayed phase were statistically significant. The three-layered pattern was considered to suggest severe inflammatory edematous change of the intestinal wall. Early enhancement of the mucosal and muscular-serosal layers with less enhancement of the submucosal layer, and homogeneous distribution of the contrast medium to the interstitium on delayed phase were considered to be the reason.

One-month oral toxicity of (S)-10-[(S)-(8-amino-6-azaspiro[3,4] octan-6-yl)]-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de] [1,4]benzoxazine-6-carboxylic acid hemihydrate (CAS 151390-79-3, DV-7751a) a new quinolone antibacterial agent was investigated in Sprague-Dawley rats at doses of 12.5, 50, 200 and 800 mg/kg/d and in cynomolgus monkeys at 10, 30 and 100 mg/kg/d. Rats receiving 200 mg/ kg showed abnormal urine crystals, enhanced deposition of lipid in hepatocytes and exacerbation of osteochondrotic lesions in the femoral condyle. In addition, dosing at 800 mg/kg induced decrease in body weight gain and increased levels of serum alkaline phosphatase (ALP), cholinesterase, leucine aminopeptidase and total cholesterol. Monkeys receiving 100 mg/kg showed abnormal urine crystals and increases in serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and ALP levels. The non-toxic doses of DV-7751a in rats and monkeys were 50 and 30 mg/kg, respectively, under the present experimental conditions.

We report a case of intraorbital conjunctival cyst following a penetrating orbitocranial injury. The patient was a 28-year-old male who was hospitalized with exophthalmos, retrobulbar pain and upper gaze disturbance of his left eye. When he was 4 years old, a thin iron rod had penetrated intracranially through the inner angle of his left orbit. He was hospitalized and treated conservatively for about two weeks. The left eye ball was intact and visual acuity was normal, although bloody fluid had continuously flowed out from the left inner angle of the conjunctival wound for a few days. He had been febrile to 39 degrees C and complained of headache for one week. Subsequentry, the symptoms gradually improved through conservative therapy. When he was a junior high school student, he noticed exophthalmos of his left eye. However, he had never been examined closely, until he was 28 years old. We suspect that he had suffered from meningitis caused by the penetrating orbitocranial injury, and had fortunately improved under the conservative therapy. On admission to our hospital, a craniogram showed fracture of the left orbital roof, and coronal and three-dimensional computed tomography (CT) scans clearly demonstrated the orbital fracture. CT revealed a cystic mass in the retrobulbar space, and a porencephalic cyst in the medial basal frontal lobe. On magnetic resonance imaging (MRI) scans, both cysts were of low intensity on T1-weighted imaging, and of high intensity on T2-weighted images. Coronal and sagittal MRI scans showed that the two cysts were connected with each other through the fracture in the orbital roof. We diagnosed therefore that the orbital cyst was a herniated porencephalic cyst of the frontal lobe. Surgery was performed by a transcranial approach. The porencephalic cyst adhered to the fractured lesion of the frontal base but did not extend into the orbita. The intraorbital cyst was totally removed by opening the orbital roof including the fractured lesion. The cyst contained milky fluid. Postoperatively, the exophthalmos, retrobulbar pain and upper gaze disturbance showed gradual improvement. On histological examination, the cyst was found to be lined by non-keratinized stratified squamous epithelium and was diagnosed as a conjunctival cyst. This case was considered to be one of traumatic conjunctival cysts caused by a penetrating orbitocranial injury. Orbital conjunctival cysts have been reported to comprise about 10% of orbital epidermoid and dermoid cysts. Of these cysts, traumatic conjunctival cysts are rare, and only a few cases have been described. The etiology and therapy of orbital conjunctival cysts are discussed.

A therapeutic trial of interleukin-3 (IL-3) was carried out in four patients with aplastic anemia refractory to the prior therapies. Daily subcutaneous doses of 2.5, 5.0 or 7.5 micrograms/kg was given for 7 or 14 days. In a patient who had co- and immediate boost-administration of granulocyte colony-stimulating factor (G-CSF) and/or erythropoietin (Epo) and another who had sequential administration of G-CSF and Epo two weeks after IL-3, definite hematological response was obtained during the course after IL-3. In one patient, moderate to severe side effects consisting of facial edema, conjunctival bleeding, chills and fever, were observed after two days' administration of IL-3. Co- or sequential administration of other hemopoietic factor(s) may be essential in IL-3 therapy for aplastic anemia.

We encountered a 71-year-old female with acute myelogenous leukemia (AML, M1), who maintained a steady hematological state for 22 months under ubenimex monotherapy. At the first medical examination in our hospital, the marrow cellularity was approximately 40% containing leukemic myeloblasts of 41.4% in the total nucleated cells, and the marrow cytogenetic study revealed 47, XX, + 8 in 13 of 20 cells analyzed. Nineteen months later, the bone marrow showed definite hypoplasia with leukemic blasts of 39.8% and chromosome finding of 46, XX, ins (10;?) (q11;?) in all cells analyzed. During the course, the patient has been doing well without transfusion of red blood cells or platelets.

Steroidogenic acute regulatory protein (StAR) plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone. We determined the organization of the StAR structural gene, mapped to 8p11.2. The gene spans 8 kb and consists of seven exons interrupted by six introns. The 1.3 kb of DNA upstream from the transcription start site directed expression of a luciferase reporter gene in mouse Y-1 adrenal cortical tumor cells but not in BeWo choriocarcinoma cells. Reporter gene expression in the Y-1 cells was increased more than 2-fold by 8-Br-cAMP, indicating that the 1.3 kb DNA fragment contains sequences that confer tissue-specific expression and cAMP regulation. The sequence of a related StAR pseudogene, mapped to chromosome 13, lacks introns and has an insertion, numerous substitutions, and deletions. Expression of StAR in COS-1 cells cotransfected with cholesterol 27-hydroxylase (P450c27) and adrenodoxin resulted in a 6-fold increase in formation of 3 beta-hydroxy-5-cholestenoic acid, demonstrating that StAR's actions are not specific to steroidogenesis but extend to other mitochondrial cholesterol-metabolizing enzymes.

We present here an interesting case of multiple dural arteriovenous shunts (dAVS) in different locations at the same time. There have been very few reports on multiple dAVS. A 63-year-old man was admitted with a sudden onset of headache and vomiting. CT scan showed a typical subarachnoid hemorrhage (Fisher Group 3). Cerebral angiogram (6 vessel study) revealed two dural arteriovenous shunts at the same time. One was located on the anterior fossa fed by the anterior ethmoidal artery, and the other was located on the posterior fossa near the marginal sinus fed by the left ascending pharyngeal and occipital arteries. At first, transarterial embolization was performed for dAVS located on the posterior fossa. Radical operation was performed for both anterior and posterior fossa dAVS. Both dAVS had disappeared on postoperative angiograms.

We reported a very rare case of an epidural hematoma soon after nose blowing. A 22-year-old male visited our hospital complaining of severe headache and nausea soon after he blew his nose. Thirteen years ago, he had a ventriculo-peritoneal (V-P) shunt operation for a pineal region tumor which had not recurred after irradiation. His left auditory tube had been patent. He hit his head about 3 months ago. On his arrival, his consciousness was almost clear but we observed slight right hemiparesis. Computed tomography of his head obtained on the first day showed the air in the hematoma in the left parietal epidural space which penetrated his petrosal bone from the mastoid air cells. Removal of his epidural hematoma was performed the next day and there was no abnormality of his parietal bone, dura and meningeal arteries. We supposed that nose blowing was what triggered his epidural hematoma. From pressure of nose blowing, the air of his nasopharyngeal space passed through his patent auditory tube into the tympanic cavity, and entered into the epidural space penetrating a microfracture or dissociation in the petrosal bone. In addition to this, V-P shunt system and the looser adhesion of dura to the skull in the young promoted entrance of air. Associated with formation of epidural hematoma in this case were four factors, "patency of auditory tube", "defect or microfracture of petrosal bone", "V-P shunt", "younger age" and triggered by nose blowing.

Muramyl dipeptide-Lys(L18) given by daily subcutaneous injection for 14 days induced arthritis in male Lewis, Fischer and nude rats, to a lesser degree in the last two than in the first strain. On the other hand, a single intradermal administration of Freund's complete adjuvant induced arthritis in Lewis and Fischer but not nude rats. Cyclosporin A (CsA) co-administered for 14 days markedly exacerbated the muramyl dipeptide-Lys(L18) induced arthritis (MIA) in rats of all three strains, but completely blocked the development of the adjuvant induced arthritis (AIA) in Lewis rats. Furthermore, AIA was transferred to recipient Lewis rats through spleen cells obtained from the donors with AIA, whereas MIA was not. Antibodies against type II collagen and DNA were not detected in sera from MIA or AIA rats. These data show a clear difference between MIA and AIA in the pattern of development of arthritis and suggest that delayed hypersensitivity reactions may be involved in the pathogenetic mechanisms of AIA, but not in MIA.

To examine the involvement of lymphocytes in the development of MDP-Lys(L18)-induced arthritis (MIA) in rats and the exacerbation of MIA by cyclosporin A (CsA), we analysed the spleen lymphocyte subset using monoclonal antibodies and flow cytometry during the development of arthritis and compared the results with those found in adjuvant-induced arthritis (AIA). Subcutaneous injection of MDP-Lys(L18) 4 mg/kg to male Lewis rats for 14 days caused very slight and quite clear increases in tarsal joint thickness on days 8 and 15, respectively. This increase was significantly enhanced by co-administration of CsA 10 mg/kg on both of these days. Adjuvant intracutaneously injected once increased the thickness only on day 15, and this was completely inhibited by CsA. The populations of CD4+ and CD8+ cells were increased and decreased, respectively, increasing the CD4+/CD8+ ratio, from day 8 in MIA. CsA enhanced the MDP-Lys(L18)-induced changes in these populations and caused additional decreases in the number of CD5+ cells. Only the CD4+ cell population was increased on day 15 in AIA, and this increase was inhibited by CsA. These results suggest that the spleen lymphocyte subsets in MIA have a different role from those in AIA, and that the contribution of enhancement of the subset changes to the exacerbating effect of CsA on MIA.

A 72-year-old female patient presented to our clinic with the chief complaint of gross hematuria and urinary frequency on September 6, 1990. Cystoscopic examination revealed a thumb's head size nonpapillary tumor. The tumor was located adjacent to the orifice of the left ureter. Histological findings of the tumor by transurethral resection (TUR) indicated transitional cell carcinoma with partial signet ring cell carcinoma. No other malignant findings in any other organs including the gastrointestinal tract were noted. Total cystectomy was performed and Indiana pouch was constructed. Histopathological staging was pT1 N0 M0. The patient died of multiple metastasis of the signet ring cell carcinoma on June 22, 1992. This is the thirty-second case of signet ring cell carcinoma of urinary bladder reported in the medical literature in Japan. We investigated 19 alive or unknown cases as follow up and briefly discussed the treatment and outcome of the primary signet ring cell carcinoma of the urinary bladder. The outcome appeared to be somewhat better than previous reports. Total cystectomies were performed in 18 of the 32 cases (56.3%). As noted in past reports, the treatment of our patient consisted of total cystectomy. Twenty-two patients died of signet ring cell carcinoma. Recurrence to the pelvic area was observed in 18 of the 22 (81.8%) patients who died. Because of this high rate of recurrence, we recommend a thorough assessment of the pelvic area of the patients diagnosed with signet ring cell carcinoma of urinary bladder.

We report a case of hypereosinophilia which was associated with the onset of anginal attacks. A 64-year-old man progressed to end-stage renal failure due to diabetic nephropathy, and was treated with continuous ambulatory peritoneal dialysis (CAPD). He had no past history of angina pectoris nor hypereosinophilia. Three weeks after the initiation of CAPD, the eosinophil count in peripheral blood increased (up to 4093/mm3). Two weeks later, he suffered from an anterior chest pain attack, and angina pectoris was diagnosed. As a result of treatment with isosorbide dinitrate and prednisolone, hypereosinophilia disappeared rapidly and repeated episodes of anginal attacks also disappeared. After an interval of 3 months, however, hypereosinophilia (up to 15190/mm3) and anginal attacks recurred. He underwent coronary angiography, in which no stenotic change was observed. The administration of prednisolone was effective in the treatment of these episodes. Although a close relationship between hypereosinophilia and anginal attack has been reported, it has not been known in CAPD patients as described here. Attention should be paid to these relationships in CAPD patients, because hypereosinophilia is frequently observed in maintenance peritoneal dialysis patients.