Tetralogy of Fallot associated with chromosome 22q11 deletion.
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Abnormalities, Multiple↗
Biomedical subjects
A Takao
Publications and source records attributed to A Takao.
A clinical study of mortality due to asthma.
BACKGROUND: Despite identification of the pathophysiologic mechanisms of asthma and improvement in therapy, asthma mortality has not decreased in recent years. OBJECTIVE: The pathophysiology and asthma-related death preventive measures were investigated with a physician-based questionnaire survey. METHODS: Questionnaires were sent to physicians primarily involved in treating asthma in Nagasaki Prefecture, Japan. The clinical characteristics of 32 patients who died of asthma (fatal cases) from 1984 to 1992 were compared with those of 17 patients with severe asthma who survived as a result of treatment by mechanical ventilation (nearly fatal cases). RESULTS: The number of deaths due to asthma increased in the last 2 years. Fatal cases and nearly fatal cases included patients with severe asthma as well as patients with mild asthma. Analysis of the clinical histories of patients judged to have died suddenly revealed the presence of persistent wheezing in these patients for a few days prior to the fatal episode. Airway obstruction was more marked and bronchial hyperresponsiveness was greater in fatal cases compared with those of a group of 70 patients without a history of nearly fatal acute asthma. CONCLUSIONS: The following measures may help prevent asthma deaths. Both patients and physicians should realize that even mild episodes can lead to severe, even fatal acute asthma. The severity of asthma should be evaluated not only by symptoms and peak expiratory flow rates but also bronchial hyperresponsiveness. Treatment should include reduction of bronchial hyperresponsiveness using oral or inhaled corticosteroids.
Adult↗
[Pharmacokinetics of SK & F 104864 in experimental animals. I. Plasma level].
A camptothecin derivative, SK & F 104864 (topotecan), was injected for 30 minutes into the rabbit ear vein at a dose of 2 mg/kg or 5 mg/kg, and the plasma concentration was assayed by a HPLC method. The plasma level of SK & F 104864 (lactone form) decreased bi-exponentially with mean alpha and beta half-lives of 0.101 h and 0.849 h at 2 mg/kg, respectively, and 0.518 h and 7.57 h at 5 mg/kg, respectively. The AUCs were 0.846 micrograms.h/ml at 2 mg/kg and 2.14 micrograms.h/ml at 5 mg/kg. The plasma level of total topotecan (SK & F 104864 plus SK & F 105992) decreased bi-exponentially with mean alpha and beta half-lives of 0.696 h and 9.07 h at 2 mg/kg, respectively, and 0.795 h and 8.97 h at 5 mg/kg, respectively. The AUCs were 2.15 micrograms.h/ml at 2 mg/kg and 5.73 micrograms.h/ml at 5 mg/kg. The AUCs of lactone form were 39.3% of total topotecan at the 2 mg/kg dose and 37.3% at the 5 mg/kg dose, respectively. After intravenous bolus injection of SK & F 104864 at 20 mg/kg into Sarcoma 180 bearing mice, the alpha and beta half-lives of SK & F 104864 were 0.401 h and 3.99 h, respectively, and the AUC was 5.49 micrograms.hr/ml. The alpha and beta half-lives of total topotecan were 0.517 h and 4.27 h, respectively, and the AUC was 9.88 micrograms.hr/ml. The ratio of lactone form to total topotecan was 55.6%.
Animals↗
[Pharmacokinetics of SK & F 104864 in experimental animals. II. Tissue distribution].
After intravenous bolus injection of a camptothecin derivative, SK & F 104864 (topotecan), at 20 mg/kg into Sarcoma 180 bearing mice, the tissue concentration of total topotecan (SK & F 104864 plus SK & F 105992) in the mice decreased bi-exponentially, and the beta half-lives in most tissues were longer than those in plasma. The AUCs of total topotecan were extremely large in the kidney, that was followed by the pancreas > intestine > stomach > spleen > liver > thymus > lung > tumor > uterus > plasma. The concentration of total topotecan after 24 hours decreased to less than 2% of the peak level in most tissues except the kidney.
Animals↗
Molecular characterization of a novel atrial-specific myosin heavy-chain gene expressed in the chick embryo.
A 1.2 kb fragment of a myosin heavy-chain (MHC) gene was isolated from the complementary DNA (cDNA) library derived from embryonic day 15 (E15), Hamburger and Hamilton (H.H) stage 41 chick embryonic ventricle, using a fragment of human beta-cardiac MHC cDNA as a probe. DNA sequence analysis determined that the gene (CCSV2) encoded the amino acid sequence of the rod portion (part of S2 and light meromyosin) of the chick atrial-specific MHC gene. The nucleotide sequence of CCSV2 was slightly different (90% homologous) from a previously reported atrial-specific MHC (AMHC1) expressed in chick embryo. Northern blot analysis, with the CCSV2 fragment (1.2 kb) used as a probe, showed that the gene is expressed intensively in the developing chick atrial muscle, but weakly in the ventricle and pectoralis muscle. S1-nuclease mapping analysis, with CCSV2 used as a probe, demonstrated a fully protected fragment in the atrium and ventricle. In this study, no intensive signal of a partially protected fragment was detected in the atrium. On the other hand, not only a fully protected fragment, but also four partially protected fragments were observed in the pectoralis muscle. Whole-mount in situ hybridization was performed in developing chick heart at H.H. stages 19, 21 and 30. The hybridization signal was intensive in the primitive atrium (H.H. stages 19 and 21) and in the atrial appendages derived from the primitive atrium (H.H. stage 30). Weak signals were detected in the primitive ventricle (H.H. stages 19 and 21), the ventricle (H.H. stage 30) and in the somites (H.H. stages 19 and 21).(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Confirmation that the conotruncal anomaly face syndrome is associated with a deletion within 22q11.2.
The so-called "conotruncal anomaly face syndrome" (CTAFS) is characterized by a peculiar facial appearance associated with congenital heart disease (CHD), especially cardiac outflow tract defects such as tetralogy of Fallot (TOF), double outlet right ventricle (DORV), and truncus arteriosus (TAC). CTAFS and the DiGeorge anomaly (DGA) have many similar phenotypic characteristics, suggesting that they share a common cause. In many cases DGA is known to be associated with monosomy for a region of chromosome 22q11.2. Fifty CTAFS patients and 10 DGA patients, 11 parents couples and 10 mothers of CTAFS patients, and 3 parents couples and 2 mothers of DGA patients were examined by fluorescent in situ hybridization (FISH) using the N25 (D22S75) DGCR probe (Oncor). Monosomy for a region of 22q11.2 was found in 42 CTAFS, 9 DGA, 4 mothers, and 1 father who had CTAF without CHD. The remaining 8 CTAFS patients 1 DGA patient and 1 mother who had questionable CTAF without CHD, showed no such chromosome abnormality. For the control, 60 patients who had CHD without CTAF or other known malformation syndromes were examined and had no deletion of 22q11.2. Therefore, we conclude that CTAFS is a part of the CATCH 22 syndrome; cardiac defects, abnormal faces, thymic hypoplasia, cleft palate, and hypocalcemia (CATCH) resulting from 22q11.2 deletions.
Abnormalities, Multiple↗
Rapid induction of vascular endothelial growth factor expression by transient ischemia in rat heart.
Vascular endothelial growth factor (VEGF or vascular permeability factor), a direct-acting, endothelial cell-specific mitogen, has been suggested to be involved in development and maintenance of vasculatures in tumor neovascularization and in normal tissues. To investigate possible roles of VEGF in ischemic hearts, we studied induction of VEGF mRNA by ischemia and hypoxia using coronary artery-ligated hearts in vivo and perfused hearts and cultured myocardial cells in vitro. VEGF mRNA was potently induced by ischemia in the heart in vivo. In perfused hearts, maximum expression was rapidly induced (within 30 min) by transient reversible ischemia (5-10 min of ischemia) and lasted at least 3 h. Induction was also caused by hypoxia, which was confirmed in perfused hearts and cultured myocardial cells. These results suggest that induction of VEGF mRNA is upregulated by oxygen deprivation in the heart and that not only infarction but also chronic ischemia in the clinical setting could induce VEGF as a potent angiogenesis factor to stimulate coronary collateral formation.
Animals↗
Disposition of gemcitabine in rat and dog after single and multiple dosings.
1. The disposition of radioactivity has been studied in rat and dog after intravenous administration of a single 10 mg/kg dose or multiple 1 mg/kg/day doses of 14C-gemcitabine. 2. Radioactivity was eliminated from the blood in a biphasic manner with half-lives of approximately 2 and 15 h in both the male and female rat. The concentration of radioactivity in the blood 24 h after the fifth dose was 4.4 times higher than that found after the first dose. In the male dog, the concentration of radioactivity in the blood showed a plateau during the first 2 h post-dose administration. 3. Radioactivity was rapidly and widely distributed throughout the body in both the male and female rat at 5 min after administration. Radioactivity was rapidly eliminated from the tissues with no evidence of accumulation. 4. After 120h, male rat excreted 95.2 and 1.9% of the dose in the urine and faeces respectively. Similar excretion patterns were observed in female rat and male dog. In rat, excretion of radioactivity in the urine 24 h after daily dosing was nearly constant, but excretion of radioactivity in the faeces slightly increased with increasing number of doses.
Animals↗
Placental transfer, lacteal transfer and plasma protein binding of gemcitabine.
1. The placental transfer, lacteal transfer and plasma protein binding of gemcitabine have been studied in rat and dog after single intravenous administration of 10 mg/kg 14C-gemcitabine. 2. Radioactivity was distributed to the foetuses at 5 min after administration to rat on days 12 and 18 of gestation. The concentrations of radioactivity in the foetal liver, lung and kidney on day 18 of gestation were 4.0-6.4 times higher than in the maternal blood at 4 h after administration. Relatively high levels of radioactivity were noted in foetal tissues 24 h after administration, indicating slow elimination from the foetus. 3. The concentration of radioactivity in milk reached a maximum at 15 min after administration to the lactating rat on day 10 after delivery, then declined in a biphasic manner, and was below the detection limit at 48 h. The concentrations of radioactivity in milk were lower than plasma concentrations of radioactivity. 4. Plasma protein binding ratios were 10-16 and 1-7% between 5 min and 8 h after administration to the male rat and dog respectively. When fresh plasma from male rat, dog and adult man was spiked with 14C-gemcitabine at concentrations of 0.1-25 micrograms/ml, the plasma protein binding ratios were about 7% in both rat and dog, and 10% in man.
Animals↗
[Six cases of allergic bronchopulmonary aspergillosis].
Six cases of allergic bronchopulmonary aspergillosis (ABPA) were evaluated. In four cases, diagnosis and steroid therapy were delayed, which resulted in irreversible pulmonary dysfunction. The important points for early diagnosis were: (1) Differentiation from pulmonary tuberculosis, (2) the presence of bronchial asthma was not essential for diagnosis, and (3) fungi other than Aspergillus fumigatus might cause this syndrome.
Adult↗
[Pharmacokinetics of paclitaxel in experimental animals. Part 1. Blood level].
The plasma disposition of paclitaxel in rabbits (7 mg/kg, 1 h i.v. inf.) was biphasic with half-lives of 0.36 and 6.36 h, and AUC was 9.46 micrograms.hr/ml. K12 value was larger than K21 and V2 was larger than V1, suggesting that paclitaxel had a favorable distribution profile in tissues. In S 180 bearing male ICR mice (30 mg/kg, i.v. bolus), the biphasic plasma disposition was also observed. The half-lives and AUC were 0.25 h, 2.23 h and 117.93 micrograms.hr/ml. Paclitaxel distributed widely in plasma rather than blood cells. The biliary level of paclitaxel in the enlarged gallbladder of ICR mice was markedly high, about 10-fold higher than the urinary level and 100-fold higher than the plasma level. The bioavailability with oral administration to ICR mice was poor. AUC(oral)/AUC(i.v.) ratio in the bile, liver, tumor and plasma was 18.91, 6.71, 0.83 and 0.45%, respectively.
Administration, Oral↗
[Pharmacokinetics of paclitaxel in experimental animals. Part 2. Tissue distribution].
In S 180 bearing male mice, paclitaxel was rapidly distributed to various tissues within 10 minutes. The highest AUC was seen in the liver, and relatively high in the pancreas, kidney, thymus, intestine, stomach and lung. The concentration of paclitaxel in tumor tissue was not so high early time after administration, but was sustained for a long time with a half life of 12.3 hr. Elimination from the testis and thymus was also slow. The drug level in the brain was very low. In M 109 bearing female CDF1 mice, the distribution and elimination profile of paclitaxel was comparable to that in S 180 mice. The concentration of paclitaxel in the ovary, lung and uterus decreased slowly. In M 109 tumor, which was very sensitive to paclitaxel, the drug had a higher and long lasting distribution compared with S 180 tumor. In S 180 tumor bearing mice pretreated with CCl4, the paclitaxel level was found to be lower in the liver and higher in the other tissues including tumor, plasma, urine and bile than in non-treated mice.
Animals↗
Human smooth muscle myosin heavy chain gene mapped to chromosomal region 16q12.
The partial nucleotide sequence encoding the rod portion of the entire amino acid sequence of human smooth muscle myosin heavy chain (MHC) which corresponds to MYH11, according to Human Gene Mapping nomenclature, has been determined by cloning a complementary DNA (cDNA) and sequencing the cDNA (UMYHSM). Northern blot analysis with the UMYHSM fragment (4.3 Kb) showed that the smooth muscle MHC of the human umbilical artery is expressed in the human umbilical artery, bladder, esophagus and trachea. Southern blot analysis of human genomic DNA from human-mouse or human-Chinese hamster somatic cell hybrids demonstrated that the human smooth muscle MHC was mapped to human chromosome 16. Regional mapping of UMYHSM was performed using human cell lines with partial deletion and trisomy of chromosome 16. As a result, the human smooth muscle MHC gene segregated with 16p11-q12. In situ hybridization of biotin-labeled human smooth muscle MHC probe (UMYHSM fragment) to normal human metaphase chromosome independently showed that the human smooth muscle MHC gene (MYH11) is assigned to chromosome region 16q12. Analysis of early metaphase chromosomes showed that hybridization signals were in 16q12.1. In the human, although skeletal, cardiac, smooth muscle, and nonmuscle MHC genes are mapped to chromosomes 17, 14, 16, and 22, respectively, structural similarities of these MHC genes strongly suggest the common origin of these genes.
Amino Acid Sequence↗
Case report: immunoglobulin A deficiency in patients with juvenile rheumatoid arthritis treated with aspirin.
In three patients with juvenile rheumatoid arthritis, serum IgA concentrations were within the normal limit at the onset of disease and before aspirin administration. After aspirin administration, their serum IgA levels gradually decreased. After discontinuation of aspirin, their serum IgA levels gradually increased. These results suggest that IgA deficiency may be due to aspirin administration in such patients. The IgA production in vitro of peripheral blood mononuclear cells from a patient taken 3 months of discontinuation of aspirin was markedly inhibited by preincubation with aspirin. Since the patients' serum IgG and IgM levels hardly changed the heavy chain class switching may be influenced by aspirin through some undefined mechanisms.
Arthritis, Juvenile↗
Immunoglobulin secreting cells in lymphocytes of patients with IgA deficiency or hyper-IgA.
To assess the ability of immunoglobulin production in vivo, we enumerated the immunoglobulin secreting cells in the peripheral blood of patients with an IgA deficiency and of those with hyper-IgA-emia. All seven patients with primary IgA deficiency and two of the three patients with secondary IgA deficiency had low numbers of IgA secreting cells. In all five patients with hyper-IgA the number of IgA secreting cells was increased. Our results suggest that measurement of immunoglobulin secreting cells in PBMCs is useful in the assessment of ability of immunoglobulin production in vivo.
Antibody-Producing Cells↗
Right aortic arch with aberrant retroesophageal innominate artery: a report of 2 cases and review of the literature.
We describe two patients of right aortic arch associated with aberrant retroesophageal innominate artery. One case was associated with tetralogy of Fallot and a tortuous left common carotid artery originating from the retroesophageal innominate artery. Tetralogy of Fallot associated with this kind of aortic arch anomaly has never before been reported. The other case was associated with a perimembranous ventricular septal defect. Symptoms such as dyspnea, dysphagia and recurrent respiratory infection due to the compression by the vascular anomaly were not noted in these two cases. The morphological findings are indicative of a double aortic arch with an interruption of the left arch proximal to the common carotid artery.
Aorta, Thoracic↗
Conotruncal anomaly face syndrome is associated with a deletion within chromosome 22q11.
The conotruncal anomaly face syndrome was described in a Japanese publication in 1976 and comprises dysmorphic facial appearance and outflow tract defects of the heart. The authors subsequently noted similarities to Shprintzen syndrome and DiGeorge syndrome. Chromosome analysis in five cases did not show a deletion at high resolution, but fluorescent in situ hybridisation using probe DO832 showed a deletion within chromosome 22q11 in all cases.
Abnormalities, Multiple↗
[Linkage analysis in a Japanese long QT syndrome family].
Romano-Ward syndrome is an autosomal dominant trait disease, which is characterized by QT prolongation and normal hearings and shows predisposal to sudden death from cardiac arrhythmia. Recently, Keating et al. reported that Harvey ras-1 locus (H-ras-1) was closely linked to long QT syndrome (LQTS), being located on the short arm of chromosome 11. In this study we have examined a three-generation Japanese family whose members had recurrent fainting with prolongation of the QT interval on electrocardiogram. Using the H-ras-1 probe as DNA marker, we could not determine that the H-ras-1 gene was linked to LQTS. LQTS seems to be a genetically heterogeneous disease. Further study is needed to clarify the chromosomal location of the LQTS.
Adult↗