Establishment of a new cell line derived from human gastric adenocarcinoma, producing tumor markers.
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Adenocarcinoma↗
Biomedical subjects
T Shimada
Publications and source records attributed to T Shimada.
Double peroneal free flap for multiple skin defects of the hand.
Two or more relatively large skin defects of the hand and fingers were repaired in six cases by a double peroneal free flap with a flap attached to each of two cutaneous branches ramifying from a peroneal artery and vein. All the cases were either multidigital injuries or had injury to adjacent fingers, with skin defects ranging from 4 x 1.5 cm to 11 x 5 cm. The subcutaneous fat of the flap is thin with good elasticity, giving a good match for the finger. This procedure can be employed for two or more skin defects at any site in the finger and hand in one stage, with the added advantage of early rehabilitation.
Adult↗
Caudato-nigral transmission in the substantia nigra pars reticulata neurons changes with recovery from circling movements induced by microinfusion of ibotenic acid. I. Behavioral study.
Following creation of a unilateral circumscribed lesion in a portion of a cat substantia nigra pars reticulata by microinfusion of ibotenic acid, circling movements toward the contralateral side of the lesion appeared within 2 days and disappeared a few days later. After recovery, the circling movements reappeared when the cats were decerebrated at the premammillary and precollicular level, suggesting that brain centers rostral to the decerebration participate in compensating the circling movements.
Animals↗
Caudato-nigral transmission in the substantia nigra pars reticulata neurons changes with recovery from circling movements induced by microinfusion of ibotenic acid. II. Electrophysiological study on synaptic transmission.
Caudato-nigral synaptic transmission was examined by stimulation of the caudate nucleus while recording from nigral neurons in cats recovering from circling movements induced by a unilateral circumscribed lesion in the substantia nigra pars reticulata after microinfusion of ibotenic acid. Extra- and intracellular recording from neurons in lesion-spared areas of the substantia nigra pars reticulata indicated that the caudato-nigral synaptic action on the side ipsilateral to the lesion exhibited a shorter duration of inhibition and a larger amplitude of excitation as a means of compensating for the circling movements.
Action Potentials↗
Retroviral gp70 antigen in spontaneous mesangial glomerulonephritis of ddY mice.
We examined whether the retroviral envelope antigen, gp70, is a major nephritogenic antigen in ddY mice, a murine model of spontaneous mesangial glomerulonephritis associated with IgA and IgG deposition. Immunofluorescence microscopy revealed that the mesangial gp70 deposition increased with age in mice over 24 weeks old, as did the IgG and IgA deposits. Immunoelectron microscopy demonstrated the reaction products of gp70 superimposed on the electron dense deposits in the mesangial matrix. Various amounts of serum gp70 were detected in mice as young as 12 weeks without any apparent increase with age. There was no correlation between the serum level of gp70 and the extent of the glomerular gp70 deposition, whereas mice with heavier IgA deposition had higher mean levels of serum IgA. The absorption test demonstrated that significant amounts of serum gp70 composed immune complexes in 40 week-old ddY mice developing glomerulonephritis; however, this bound form of gp70 was not observed in 12 week-old mice without glomerulonephritis. Systemic examinations by immunofluorescence staining showed that gp70 was mainly localized in various lymphoid tissues. These findings suggest that the gp70 antigen, mostly derived from lymphoid cells, may circulate as immune complexes and accumulate in the mesangial area, thus contributing to the development of glomerulonephritis in these mice. In addition, the pathogenic role of the increased IgA production in these mice was discussed.
Animals↗
Regulation of viral expression of human immunodeficiency virus in vitro by an antisense phosphorothioate oligodeoxynucleotide against rev (art/trs) in chronically infected cells.
In this report, we demonstrate the sequence-specific suppression of viral expression in T cells chronically infected with human immunodeficiency virus 1 (HIV-1), using antisense phosphorothioate oligodeoxynucleotides. As a target for antisense intervention, we used the HIV-1 gene rev, which is essential for viral replication and regulates the expression of virion proteins, in part, by affecting the splicing of the viral mRNA. A phosphorothioate oligomer complementary to the initiation sequence of HIV-1 rev had a significant and selective inhibitory effect on the production of several viral proteins in chronically HIV-1-infected T cells and drastically reduced the unspliced (genomic) viral mRNA transcripts, with relative sparing of smaller (spliced) transcripts. By contrast, the antisense sequence with unmodified normal phosphodiester linkages as well as phosphorothioate oligomers containing sense, random, homopolymeric sequences, or antisense sequence with N3-methylthymidine residues did not have an inhibitory effect on viral expression. Thus, sequence specificity and nuclease resistance were critical for the anti-viral-gene regulatory effect of the antisense molecules. The altered HIV-1 mRNA profile induced by the antisense phosphorothioate oligomer suggests that the mechanism for the inhibition of viral expression is due to an interference with the regulatory gene, rev, by translation arrest.
Base Sequence↗
A genetically engineered cell line that produces empty capsids of B19 (human) parvovirus.
B19 parvovirus is pathogenic in humans, causing the common childhood exanthem fifth disease and bone-marrow failure, both acute (transient aplastic crisis of hemolysis) and chronic (pure erythrocyte aplasia in immunodeficiency). The virus is tropic for a human red cell progenitor cell, and failure to culture B19 in a cell line has limited its clinical study. We cotransfected the right half of the cloned B19 genome and a minigene derived from the human dihydrofolate reductase gene (DHFR) into dhfr--Chinese hamster ovary cells and screened selected clones by RNA analysis; after amplification in methotrexate, clones were tested for capsid protein expression. A cell line, designated 3-11-5, stably expressed nearly full-length transcripts for the two capsid proteins. These cells produced the major and minor structural protein species in natural proportions that self-assembled into virion capsids. Capsids from 3-11-5 cells could be separated from virions by sucrose gradient sedimentation and had the density on cesium chloride isopycnic sedimentation of empty parvovirus capsids. Capsid protein was present in both nuclei and cytoplasm on immunofluorescence study but fractionated with the cytosol on purification. Empty capsid production was equal to or greater than virion production by infected bone-marrow cells, 1000-2000 capsids per cell, but cell growth was not diminished by capsid production. This cell line will be useful in developing practical assays for B19 parvovirus antibody and a vaccine for the virus, as well as potentially serving as a packaging cell line for gene therapy.
Animals↗
Evidence for cytochrome P-450NF, the nifedipine oxidase, being the principal enzyme involved in the bioactivation of aflatoxins in human liver.
In vitro studies with human liver indicate that the major catalyst involved in the bioactivation of the hepato-carcinogen aflatoxin B1 (AFB1) to its genotoxic 2,3-epoxide derivative is cytochrome P-450NF (P-450NF), a previously characterized protein that also catalyzes the oxidation of nifedipine and other dihydropyridines, quinidine, macrolide antibiotics, various steroids, and other compounds. Evidence was obtained using activation of AFB1 as monitored by umuC gene expression response in Salmonella typhimurium TA1535/pSK1002 and enzyme reconstitution, immunochemical inhibition, correlation of response with levels of P-450NF and nifedipine oxidase activity in different liver samples, stimulation of activity by 7,8-benzoflavone, and inhibition of activity by troleandomycin. Similar results were obtained when levels of 2,3-dihydro-2-(N7-guanyl)-3-hydroxyaflatoxin B1 formed in DNA were measured. P-450NF or a closely related protein also appears to be the major catalyst involved in the activation of aflatoxin G1 and sterigmatocystin, the latter compound being more genotoxic than AFB1 in these systems. Several drugs and conditions are known to influence the levels and activity of P-450NF in human liver, and the activity of the enzyme can be estimated by noninvasive assays. These findings provide a test system for the hypothesis that a specific human disease state (liver cancer) is linked to the level of oxidative metabolism in populations in which aflatoxin ingestion is high.
Aflatoxin B1↗
Function, characterization and autoradiographic localization and quantitation of beta-adrenoceptors in cardiac tissues.
1. This paper demonstrates the use of organ bath, radioligand binding and autoradiography to detect beta 1- and beta 2-adrenoceptors in human and guinea-pig cardiac tissues. 2. In organ bath experiments, non-selective and beta 1- and beta 2-adrenoceptor selective agonists produced concentration-dependent inotropic responses in human right atrial appendage. Both subtypes mediate inotropic responses. In guinea-pig right atria chronotropic responses were mediated predominantly through beta 1-adrenoceptors. 3. Receptor binding studies using (-)[125I]-cyanopindolol (CYP) and beta 1- and beta 2-adrenoceptor selective antagonists showed that beta 2-adrenoceptors comprised 25% of the total population of beta-adrenoceptors in guinea-pig right atria. In human right atria the proportion is higher (40%). 4. Quantitative autoradiography was used to determine the location and densities of beta 1- and beta 2-adrenoceptors in guinea-pig heart. Both beta 1- and beta 2-adrenoceptors were distributed on myocardium. The atrioventricular conducting system had a higher density of beta 2-adrenoceptors compared with myocardium.
Adrenergic beta-Agonists↗
Morphology of lymphatics of the mammalian heart with special reference to the architecture and distribution of the subepicardial lymphatic system.
The subepicardial lymphatic system in the rat and dog heart has been investigated by means of scanning electron microscopy. Following application of hydrogen peroxide, the epicardium was removed with a forceps under a dissecting microscope. The subepicardial region contained a well-developed lymphatic system which consisted of the main lymphatic trunks and lymphatic capillaries. The lymphatic trunks of large diameters ran from the apex of the heart to its base. The subepicardial lymphatic capillaries were ramified and anastomosed with each other to form a relatively dense network which extended over the entire surface of both ventricles. These networks joined the main lymphatic trunks. Further, some similar networks were connected with the underlying myocardial lymphatic capillaries.
Animals↗
Isovolumic relaxation period as an index of left ventricular relaxation under different afterload conditions--comparison with the time constant of left ventricular pressure decay in the dog.
In order to determine whether isovolumic relaxation period (IRP) reflects left ventricular relaxation under different afterload conditions, 17 anesthetized, open chest dogs were studied, and the left ventricular pressure decay time constant (T) was calculated. In 12 dogs, angiotensin II and nitroprusside were administered, with the heart rate constant at 90 beats/min. Multiple linear regression analysis showed that the aortic dicrotic notch pressure (AoDNP) and T were major determinants of IRP, while left ventricular end-diastolic pressure was a minor determinant. Multiple linear regression analysis, correlating T with IRP and AoDNP, did not further improve the correlation coefficient compared with that between T and IRP. We concluded that correction of the IRP by AoDNP is not necessary to predict T from additional multiple linear regression. The effects of ascending aortic constriction or angiotensin II on IRP were examined in five dogs, after pretreatment with propranolol. Aortic constriction caused a significant decrease in IRP and T, while angiotensin II produced a significant increase in IRP and T. IRP was affected by the change of afterload. However, the IRP and T values were always altered in the same direction. These results demonstrate that IRP is substituted for T and it reflects left ventricular relaxation even in different afterload conditions. We conclude that IRP is a simple parameter easily used to evaluate left ventricular relaxation in clinical situations.
Angiotensin II↗
Relationship between the coronary diameter and occurrence of vasospastic angina in patients with normal coronary arteries.
Coronary artery diameters were measured after various interventions in 30 patients without angina pectoris (group 1) and in 15 with angina pectoris (group 2: rest, or rest and effort angina) who had normal coronary arteries. The coronary artery diameters were significantly smaller in many coronary segments in group 2 than in group 1 during a control state, after exercise and ergonovine, but became nearly identical after isosorbide dinitrate in both groups. Patients in group 1 had diffuse narrowing but no focal vasoconstriction after ergonovine and all the segments had a diameter of more than 50% of that after isosorbide dinitrate. The change of coronary artery diameter in group 2 patients who had no vasospasm by ergonovine was the same as that in group 1. Patients in whom vasospastic angina was induced had local vasoconstriction or severe diffuse narrowing (less than 45%). These results indicate that angina pectoris patients with normal coronary arteries had an acceleration of coronary arterial basal tone, but vasospastic angina pectoris was not induced just by the general response of the coronary artery to various interventions in addition to the accentuated basal tone. For vasospastic angina to occur, local abnormal response to various interventions must be present.
Adult↗
Treatment of chronic osteomyelitis of the leg by peroneal myocutaneous island flap transfer.
We treated 11 patients with chronic osteomyelitis of the tibia or the foot by local excision and transfer of a peroneal myocutaneous island flap. This flap, pedicled proximally or distally on the peroneal artery and veins, provides viable muscle to fill the dead space in bone and skin to close the defect. Ten patients reviewed more than three years after operation were all free of drainage with no clinical or radiographic evidence of recurrence.
Adult↗
Pseudohypoparathyroidism showing positive phosphaturic and negative cyclic AMP excretion response to parathyroid hormone.
We report a patient with pseudohypoparathyroidism (PHP) in whom parathyroid hormone (PTH) infusion failed to produce an increase in urinary adenosine 3', 5' monophosphate (cAMP) excretion in spite of the positive urinary phosphate excretion. The dbcAMP infusion test showed almost the same increase in phosphate as in the E-H test, although high urinary cAMP excretion was detected. Furthermore, a PTH infusion test in combination with calcium antagonist (diltiazem) administration markedly increased phosphate excretion, whereas the response of urinary cAMP excretion also remained negative. After treatment with 1 alpha(OH)D3, phosphaturic response increased by at least 14.3 mg/2 h compared with that in the pretreatment period. Therefore, intra and extra cellular calcium seem to affect the phosphaturic response induced by PTH.
Adult↗
[A case of congenital intercoronary communication].
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Cardiac Catheterization↗
[Two sisters with pseudoidiopathic hypoparathyroidism presenting extensive intracranial calcification].
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Adult↗
Unaffected electrogenic Na-K pump activity in "diseased" human atrial fibers, as assessed by intracellular K+ activity.
To investigate the role of the electrogenic Na-K pump in the resting membrane of "diseased" or "depolarized" human atrial muscles, intracellular K+ activity (aiK) and resting membrane potential (Vm) were simultaneously measured using double-barreled K(+)-selective microelectrodes. Under perfusion with normal Tyrode's solution (37 degrees C) containing 5.4 mM [K]o, Vm averaged -43.9 +/- 1.4 mV, and aiK was 99.7 +/- 1.3 mM (mean +/- S.E., n = 33). The aiK was comparable to that of atrial muscles obtained from other intact mammalian species. In 5.4 mM [K]o, dihydro-ouabain (DHO) at concentrations of 10(-6) and 10(-5) M significantly decreased aiK and depolarized Vm. Similar decreases in aiK were observed when [K]o was decreased from 5.4 to 0.5 mM or when the temperature of the perfusing solution was decreased from 37 to 22 degrees C. Upon returning [K]o from 0.5 to 5.4 mM at 37 degrees C, aiK increased, Vm hyperpolarized markedly for about 3 min, and this was followed by less marked levels of hyperpolarization in the steady state. The high [K]o-induced increases in aiK were inhibited in the presence of DHO, and at low temperature (22 degrees C). Isoproterenol (10(-7) M) increased aiK and hyperpolarized Vm. Acetylcholine (10(-5) M) hyperpolarized Vm with no change in aiK. The rate of reduction of Na(+)-efflux during application of DHO (10(-5) M) was calculated based on the change in aiK and surface-to-volume ratio of the cell measured electronmicroscopically in the same tissue, and estimated to be 2.6 to 3.8 pmol/(cm2.s), close to the value reported for Purkinje fibers excised from intact animals. We conclude that the Na-K pump functions normally even in "diseased" human atrial muscles, thereby keeping aiK within a physiological range.
Adolescent↗
[Loneliness of homebound senior citizens].
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Aged↗