Biomedical subjects
Publications and source records attributed to K Takada.
A 1-year and 8-month-old girl admitted to our hospital because of wheeze and dyspnea. Echocardiogram and cardiac catheterization confirmed isolated congenital mitral insufficiency with pulmonary hypertension. She was treated with reconstructive surgery consisting of suture of clefted anterior mitral leaflet and annuloplasty. Her postoperative course was uneventual and mitral regurgitation was remarkably improved.
PURPOSE: To determine the MR characteristics of brain abnormalities in Fukuyama congenital muscular dystrophy (FCMD). METHODS: We reviewed 30 MR examinations of 21 patients with FCMD to assess cerebral and cerebellar cortical dysplasia, white matter changes, and miscellaneous abnormalities. RESULTS: On MR images, all patients had thick and bumpy cortices with shallow sulci corresponding to polymicrogyria, and 12 patients had pachygyric cortices with smooth surfaces, corresponding to type II lissencephaly. Both types of cortical dysplasia had characteristic distributions: the first type involved the frontal lobe in all 21 patients and also the parietotemporal lobe in 6 patients; the second type involved the temporooccipital lobes. Eighteen patients had prolonged T1 and T2 signal in the white matter, which was indistinct in neonates and seen infrequently in adolescents. In four patients, abnormal vessels were seen within the pachygyric cortices. CONCLUSION: MR studies of the brain show findings consistent with the known characteristics of FCMD. The MR detection of the two types of cerebral cortical dysplasia with characteristic distribution and cerebellar abnormalities is helpful in the differential and early diagnosis of FCMD.
We introduce a method for inspecting the function of the respiratory circuit of an anesthesia machine using "Valve Checker" devised by a manufacturer. With this method, the function of an inspiratory valve can be confirmed by the pressure not being removed when pressure is applied by connecting the "Valve Checker" directly with the inspiratory opening. Additionally, the function of an expiratory valve can be confirmed by the pressure being removed and also by the deflated bag being inflated when pressure is applied by connecting the "Valve Checker" directly with an expiratory opening. This is a method whereby a delicate cushioning of pressure by a hose is excluded and the function of the inspiratory valve and expiratory valve can be inspected independently and easily.
We treated four neonates with congenital abdominal wall defects and performed pulmonary function testing before and after closure of abdominal wall defects. Pulmonary mechanics were measured by passive occlusion technique. Static respiratory system compliance (Crs) was 0.61 +/- 0.16 ml.cmH2O-1 .kg-1 (mean +/- SD) preoperatively and decreased to 0.31 +/- 0.03 ml.cmH2O-1.kg-1 postoperatively. Two cases with a marked decrease in Crs after the abdominal wall closure seemed to have longer intubation time and N.P.O period and to have more complications than with the other two cases. Our experience provides an evidence that Crs measurement could be a useful index in decision-making of the treatment of neonates with congenital abdominal wall defects.
Two familial cases of myelodysplastic syndrome (MDS) are reported, one of whom had an abnormal karyotype of 45, XY, -7 (monosomy 7). Case 1 was a 60-year-old woman developed dizziness and nasal bleeding. She was treated with blood transfusion alone. About 11 months after diagnosis, she died of pneumonia. Case 2 was a 22 year-old man, who was the son of case 1, developed febrile disease because of recurrent skin and oral mucosa infections. He had a partial response to low-dose of cytarabine. Thirteen months after diagnosis, he died of severe pneumonia. Both cases were diagnosed as having refractory anemia with excess of blasts due to peripheral blood and bone marrow findings. Both patients had pancytopenia, erythroid hyperplasia in bone marrow, marked dyserythropoiesis, recurrent infectious diseases and severe pneumonia that resulted in death. These symptoms resembled to those reported for monosomy 7 syndrome. Familial MDS with monosomy 7 is rarely reported. These cases are of interest to investigate hereditary factors of MDS.
Although thiopental is known to potentiate halothane-epinephrine arrhythmias, the precise mechanism of this potentiation is obscure. The authors investigated the comparative role of alpha 1 and beta adrenergic actions in the thiopental-induced potentiation of halothane-epinephrine arrhythmias in dogs. Adult mongrel dogs were anesthetized with halothane alone (1.3%) or thiopental (20 mg kg-1) plus halothane and monitored continuously for systemic arterial pressures and for premature ventricular contractions. The arrhythmogenic doses of phenylephrine and isoproterenol were determined during the two anesthetic methods and the effect of thiopental on the arrhythmogenic action of alpha 1 and beta agonists was examined. Thiopental failed to exert a significant potentiation of arrhythmogenic effect of phenylephrine or isoproterenol, when these agents were administered separately. On the other hand, the potentiation of arrhythmogenicity by thiopental was remarkable in the case of combined administration of both the agonists, that is, thiopental enhanced the synergistic interaction between phenylephrine and isoproterenol for inducing arrhythmias during halothane anesthesia. In addition, the potentiation was more prominent when a low dose of isoproterenol and a high dose of phenylephrine was combined than that when a high dose of isoproterenol and a low dose of phenylephrine was given in combination. The results indicate that thiopental significantly potentiates the arrhythmogenic interaction of alpha 1 and beta adrenergic agonists administered concurrently, although individual potentiation of these agonists is not significant.
Tumor necrosis factor alpha (TNF-alpha) is released from cells of monocyte/macrophage lincage and mediates the development of a variety of clinical and pathomorphological features in various infectious diseases, autoimmune diseases and cancer. In the case of tuberculosis, it is suggested that the release of TNF-alpha in the affected regions and into the circulation could account for the pathological and clinical features such as the development of necrotic lesions and fever and weight loss in TB patients. In the present study, the levels of soluble TNF receptor type I (sTNFR type I) and type II (sTNFR type II) and TNF-alpha in the sera of patients with pulmonary TB were assayed, and we tried to know whether these levels have clinical significance in determining the disease activity in TB patients. The serum levels of both sTNFR types I and II were significantly higher in TB patients (n = 22) who were previously untreated than in the healthy control (n = 14): for sTNFR type I, 2.82 +/- 1.37 ng/ml vs. 1.40 +/- 0.33 ng/ml (p < 0.0001), and for sTNFR type II, 3.83 +/- 1.76 ng/ml vs. 1.62 +/- ng/ml (p < 0.0001). The serum levels of sTNFR types I and II in TB patients showed significant correlations with their serum levels of CRP. The serum levels of TNF-alpha in these TB patients was 2.21 +/- 1.72 pg/ml, whereas TNF-alpha was not detectable in the sera of 9 healthy control. The serum levels of sTNFR type I and II were significantly higher in cavitary TB (n = 17) than in non-cavitary TB (n = 5). When TB patients were treated with antituberculosis drugs and clinical improvements were achieved, the elevated levels of sTNFR type I and TNF-alpha in the sera of same 5 patients measured before starting treatment showed significant decline and the serum levels of sTNFR type II showed also declined, however, the decline was statistically not significant. From all the results obtained in this study, we conclude that the assay of the serum levels of sTNFR in TB patients is useful in the evaluation of the disease activity of TB.
The association of Epstein Barr virus (EBV) with Sjögren's syndrome (SS) is still in dispute. This study is aimed to investigate the existence of EBV genomes and their products in salivary glands of SS. Salivary gland samples were surgically obtained from Chinese patients. EBV DNA was detected in three of seven cases by dot blot hybridization and in four of seven cases by in situ hybridization. The EBV-encoded small RNA-1 (EBER1) was detected in two of seven cases by in situ hybridization. The immunohistochemical staining of EBV proteins showed that the EBV latent membrane protein-1 was detected in four of seven cases and that BZLF1, BALF2, and gp350/220 proteins associating with virus production were not expressed. In eight controls, no positive signal was observed by these methods. DNA in situ hybridization identified ERV on both epithelial cells and lymphocytes. On the other hand, EBER1-positive signals were exclusively localized on lymphocytes. These results indicate that two forms of EBV infection may exist in salivary glands of SS. One is EBER1-positive latency in lymphocytes, the other is EBER1-negative latency in epithelial cells. Frequent EBV detection in salivary glands of SS suggests that EBV plays a role in the genesis of SS.
A 57-year-old woman was diagnosed as having non-Hodgkin lymphoma (follicular mixed cell, B-cell type, Stage III) in February 1988. Since then, she had been treated with radiation and chemotherapy contained with alkylating agents and etoposide for 6 years. In April 1994, peripheral blood study disclosed leukocytosis with basophilia and thrombocytosis. Bone marrow was hypercellular. The karyotype of bone marrow cells was 46, XX, t(9:22) (q34:q11). Rearrangement of bcr was detected in bone marrow, but not in lymph node cells. On the basis of these findings, she was diagnosed as having the chronic phase of chronic myelogenous leukemia (CML) following the therapy for malignant lymphoma and treated with interferon-alpha (IFN-alpha) and hydroxycarbamide. Following this therapy, the lymphoadenopathy promptly disappeared and chromosome analysis showed disappearance of Ph chromosome positive cells. Although CML is rare in secondary leukemia, the present case seemed therapy-related CML and the treatment with IFN-alpha and hydroxycarbamide was effective for both CML and malignant lymphoma.
The prevention of left ventricular aneurysm formation and left ventricular remodeling by percutaneous transluminal coronary angioplasty (PTCA) performed 24 to 48 hours after onset of acute myocardial infarction was investigated. Left ventriculography and coronary angiography were performed in 25 patients within 24 hours of onset of acute myocardial infarction. The patients were divided into two groups; reperfusion group (n = 17) and successful PTCA group (n = 8). The reperfusion group and the PTCA group included patients whose infarct-related coronary arteries were successfully reperfused to 99%, Thrombolysis in Myocardial Infarction (TIMI) grade II or III, immediately after coronary thrombolysis. However, the reperfusion group did not include the patients with spontaneous reperfusion or reperfusion after PTCA. The PTCA group consisted of patients who underwent successful PTCA performed within 24 to 48 hours after onset of infarction (mean 28.4 +/- 6.0 hours). Non-reperfusion in the acute phase was defined as TIMI grade 0-I. The size of the ventricular aneurysm in the PTCA group was significantly reduced compared with the reperfusion group (PTCA group 4.2 +/- 8.7%, reperfusion group 27.2 +/- 6.6%; p < 0.01). The increase of left ventricular end-diastolic volume (delta LVEDVI) from the acute to chronic phases was calculated to estimate left ventricular remodeling. There was a significant difference between the two groups in delta LVEDVI (PTCA group 4 +/- 19 ml/m2, reperfusion group 19 +/- 17 ml/m2; p < 0.05). PTCA performed within 24 to 48 hours after onset in patients with acute myocardial infarction and infarct-related coronary arteries, resulting in reperfusion to 99% TIMI grade II or III immediately after coronary thrombolysis, prevents left ventricular aneurysm formation and remodeling.
Cytologic methods for detection of early cancers of the uterine cervix, lung and various other organs are discussed. The scraping smear method using a spatula is more effective than the cotton swab or vaginal pool smear method for detection of preinvasive intraepithelial lesions, such as, carcinoma in situ and dysplasias of various degrees of the uterine cervix. The use of sputum specimens pooled for three to five days is recommended for cytologic examination in population screening of lung cancer. Good cytopreparatory techniques, suitable screening and cytodiagnostic classifications of malignancy are also described and emphasized, especially, the importance of properly fixed cytologic material for correct cytopathological diagnosis.
A sandwich ELISA has been developed to measure intracellular levels of multi-ubiquitin chains. The mixture of multi-ubiquitin chains, prepared in vitro by incubation of ubiquitin (plus 125I-ubiquitin) and lysozyme with ubiquitin-ligating enzymes and ATP, was partially purified and established as a standard named the multi-ubiquitin-chain reference preparation 1 (MUCRP1). The concentration of MUCRP1 was calculated from the recovered radioactivity of 125I-ubiquitin. All measurements by the ELISA were expressed in terms of MUCRP1. The ELISA showed good sensitivity (98 pg/ml), precision (intra-assays < 6%) and reproducibility (interassay < 9%). In addition, there was no substantial cross-reaction with mono-, di- and tri-ubiquitin, or mono-ubiquitinated and di-ubiquitinated lysozyme in the ELISA, and large multi-ubiquitin chains (n > approximately 6) may be fully reactive. These results combined with excellent results in the recovery and dilution tests guarantee accurate measurement of multi-ubiquitin chains in cell extracts prepared with a lysis buffer (water soluble) or the buffer supplemented 8 M urea (urea soluble). The level of the water-soluble multi-ubiquitin chains in reticulocytes was lower than that of erythrocytes, but the urea-soluble chain level was higher in the reticulocytes. Heat-shock treatment of HeLa cells increased the urea-soluble multi-ubiquitin chains. These data indicate that this ELISA provides a useful and reliable approach to the study of intracellular multi-ubiquitin-conjugate turnover.
To investigate the function of a basic and neutral amino acid transporter-like protein (rBAT) which is a candidate gene for cystinuria, we analysed the rBAT gene in cystinuric patients. Patient 1 is a compound heterozygote with mutations in the rBAT gene causing a glutamine-to-lysine transition at amino acid 268, and a threonine-to-alanine transition at amino acid 341, who inherited these alleles from his mother (E268K) and father (T341A), respectively. Injection of T341A and E268K mutant cRNAs into oocytes decreased transport activity to 53.9% and 62.5% of control (L-cystine transport activity in oocytes injected with wild-type rBAT cRNA), respectively. Co-injection of E268K and T341A into oocytes strongly decreased amino acid transport activity to 28% of control. On the other hand, co-injection of wild-type and mutant rBAT did not decrease transport activity. Furthermore, immunological studies have demonstrated that the reduction of amino acid transport is not due to a decrease in the amount of rBAT protein expressed in oocyte membranes. These results indicate that mutations in the rBAT gene are crucial disease-causing lesions in cystinuria. In addition, co-injection experiments suggest that rBAT may function as a transport activator or regulatory subunit by homo- or hetero-multimer complex formation.
The growth transforming potential of Epstein-Barr virus (EBV) for Burkitt's lymphoma and nasopharyngeal carcinoma is now extended to other neoplasia, such as Hodgkin's disease, peripheral T-cell tumor and gastric cancer. We have generated an EBV recombinant with a selectable marker at the viral thymidine kinase locus. Recombinant EBV was successfully infected into a human T-cell line, MT-2. Following incubation in the selective medium, drug resistant MT-2 cell clones were isolated and proved to be infected with recombinant EBV. EBV-infected MT-2 cell clones expressed EBNA 1 and LMP 1 and very little of EBNA 2, showing the BamHI F promoter-driven latency II form of infection, which is seen in non-B-cell tumors. This is the first report of in vitro generation of latency II type EBV infection. The present system of persistent EBV infection in T cells should be a good model for investigating the pathogenic role of EBV in non-B-cell tumors.
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KNI-272 is a tripeptide drug that has a strong pharmacological potential for treating human immunodeficiency virus type 1 (HIV-1). We have already reported the pharmacokinetic characteristics of KNI-272 after intravenous and intraduodenal (ID) administrations to rats. In this study, KNI-272 was administered to rats as a solution and the effect of four kinds of solvent on the bioavailability (BA) of KNI-272 was determined using rats. The mixtures included propylene glycol (PG) and water (70% PG), a solution of PG (100% PG), a solution of Tween 80 (Tween 80), and a mixture of PG and HCO60, a polyoxyethylated, 60 mumol, castor oil derivative (PG:HCO60 = 7:3). After ID administration to rats at a dose of 50.0 mg kg-1, the mean peak plasma concentrations, Cmax, were 2.58 +/- 0.53 (SE) (70% PG), 3.28 +/- 0.51 (100% PG), 3.15 +/- 0.51 (Tween 80), and 4.66 +/- 0.68 micrograms mL-1 (PG:HCO60). The highest BA, 44.6%, was obtained after ID administration of KNI-272 dissolved in PG:HCO60. On the other hand, after intragastric (IG) administration of KNI-272 solution in which the drug was dissolved with PG:HCO60, the Tmax, the Cmax, and the BA were 1.25 +/- 0.60 h, 2.33 +/- 0.65 micrograms mL-1, and 24.2%, respectively. The Cmax and BA values were equal to half of the values obtained after ID administration of KNI-272 dissolved in the same solution. In this study, as the PG concentration in the solution increased and the other additives (Tween 80 and HCO60) were coadministered, the BA of KNI-272 after ID administration increased. These results suggest that, for the development of an oral dosage form of KNI-272, a non-ionic surfactant that dissolves in the duodenum or small intestine and that enhances the absorption of this drug from the gastrointestinal tract into the enterocytes is needed.
Mycophenolate mofetil (MPM), a new immunosuppressant, is a morpholinoethyl ester of mycophenolic acid (MPA). The enzymatic and non-enzymatic hydrolysis was studied in an artificial digestive fluid, rat plasma, and tissue homogenates. MPM was chemically stable in the artificial digestive fluid. In rat tissue homogenates and plasma, MPM was rapidly hydrolysed to MPA. The conversion rate of MPM to MPA in various rat tissue homogenates was in the order of liver > kidney > plasma > small-intestine epithelial cells. After the intravenous injection of MPM at 16.7 mg kg-1, the terminal elimination half-life, t1/2 beta, was 4.74 +/- 0.33 (mean +/- SD)h, and the area under the plasma concentration versus time curve, AUC, was 48.78 +/- 6.01 micrograms h mL-1. After intraduodenal (ID) administration of MPM at 16.7 mg kg-1, t1/2 beta was 3.92 +/- 1.05 h, and the AUC was 38.08 +/- 8.30 micrograms h mL-1. The systemic availability of MPA after ID MPM dosing was 1.52 times higher than that after ID administration of MPA. This result supports the usefulness of MPM as an oral prodrug of MPA as a new oral immunosuppressant.