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Biomedical subjects

T Tomita

Publications and source records attributed to T Tomita.

At least 19 recordsLinked to original sources

[Adverse reactions to low osmolar iodine contrast media (second report)].

From January to December 1990, we performed a prospective survey of adverse reactions to contrast media at two different institutes of Juntendo University. We collected a total of 4555 case sheets during the period. The radiological procedures we investigated were computed tomography, intravenous urography, arteriography, venography and myelography. Low osmolar iodine contrast medium was used almost exclusively (except for five cases). The overall incidence of adverse reactions was 7.0%, and there were no severe or fatal reactions. The incidence of adverse reactions was higher in females (8.5%) than in males (6.1%). The incidence of adverse reactions increased according to the dose of contrast medium, especially when more than 101 ml was injected. Intra-arterial injection caused adverse reactions most often, followed by regular intravenous injections, followed by bolus intravenous injections. Adverse reactions occurred most often during injection. The next occurred in 5 minutes after injection, and then, 5-10 minutes after the injection of contrast medium. The incidence of adverse reactions was higher in patients with a history of allergy or previous reactions. Allergic adverse reactions were observed at a higher frequency. Pretesting was performed in 56.7% of the cases.

Adolescent

Reduced functions of intracellular Ca2+ in aggregation, secretion and protein phosphorylation of permeabilized platelets from stroke-prone spontaneously hypertensive rats.

Aggregation, secretion and 47kDa protein (P47) phosphorylation by various agonists such as thrombin, ADP and ionophore A23187 were markedly reduced in platelets from stroke-prone spontaneously hypertensive rats (SHRSP) compared with those of age-matched Wistar Kyoto rat (WKY) platelets, suggesting defective functions of intracellular Ca2+ in SHRSP platelets (Tomita et al. Hypertension 1989; 14: 304-315). To clarify the mechanism of the platelet hypofunctions, saponin permeabilized platelets were prepared to compare the responses of platelets from both rats in varying concentrations of extracellular Ca2+. The leakage of lactate dehydrogenase from saponin (15 micrograms/ml)-treated platelets was approx. 5% of total activity; the degree of the leakage in both platelets did not differ. In saponin-treated platelets, extracellular Ca2+ alone did not induce either aggregation or secretion in both strains. However, in the presence of 1-oleoyl-2-acetylglycerol (10 micrograms/ml), Ca2+ dose dependently stimulated both aggregation and secretion. Under this condition, Ca2+ sensitivity of aggregation, secretion and P47 phosphorylation in SHRSP platelets were significantly reduced compared with those in WKY platelets. These results strongly suggest that intracellular Ca2+ functions are impaired in SHRSP platelets.

Animals

Influence of membrane fluidity on the assembly of Staphylococcus aureus alpha-toxin, a channel-forming protein, in liposome membrane.

By use of multilamellar phosphatidylcholine (PC) liposomes of different acyl composition and cholesterol content as model membranes, we studied whether or not membrane fluidity affects the assembly process of Staphylococcus aureus alpha-toxin. Under conditions using fluid and solid membranes, we assayed accessibility (or hemolytic activity) of liposome-bound alpha-toxin to rabbit erythrocytes added, hexamerization of membrane-bound toxin using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under nondenaturating conditions, and susceptibility of liposome-bound toxin to trypsin digestion. Our data indicated 1) that alpha-toxin bound to PC membrane as a hemolytically active monomer (or reversibly bound state); 2) that when the membrane was fluidized either by phase transition of PC or by inclusion of cholesterol over 20 mol %, the hemolytically active monomer of the toxin was irreversibly converted to nonhemolytic monomer (and/or unstable oligomer) in a first-order kinetics with a t1/2 of about 1 min, and thereafter hexamerization of the toxin gradually proceeded in the following 60-90 min; 3) that alpha-toxin might have different topology and/or conformation in PC membrane, depending on the presence or absence of cholesterol in the PC membrane; and 4) that coexistence of unsaturated acyl chain-carrying PC and cholesterol was a prerequisite for efficient hexamerization of alpha-toxin in membrane. Thus, increase in membrane fluidity promoted the assembly process of S. aureus alpha-toxin.

Animals

Slope of the end-systolic pressure-volume relation derived from single beat analysis is not always sensitive to positive inotropic stimuli in humans.

Single beat estimation of the slope of the end-systolic pressure-volume relation assumes symmetric left ventricular pressure increase and decay and requires extrapolation of peak isovolumic developed pressure (Pmax) from the left ventricular pressure curve of an ejection contraction. To test the sensitivity of this slope to positive inotropic stimuli, biplane cineangiocardiography and simultaneous high-fidelity left ventricular pressure measurements were performed in 50 patients with heart disease. The end-systolic pressure-volume relations were assessed under baseline conditions and during norepinephrine infusion (n = 19) or after postextrasystolic potentiation (n = 24), or both (n = 7). Norepinephrine did not change left ventricular end-systolic volume despite significant elevations of end-systolic pressure. Postextrasystolic potentiation significantly decreased end-systolic volume in association with an unaltered left ventricular end-systolic pressure. The potentiation significantly decreased the pressure half-time of contraction, an index of the speed of the left ventricular pressure increase, while it increased the pressure half-time of relaxation, an index of the speed of the pressure decline, indicating asymmetric pressure increase and decay. The slope of the end-systolic pressure-volume relation increased from 3.3 to 4.4 mm Hg/ml/m2 (p less than 0.001) during norepinephrine infusion. In contrast, despite an augmented contractility, the slope decreased significantly from 3.2 to 2.4 mm Hg/ml/m2 (p less than 0.0001) after the potentiation. The slope showed a high correlation with Pmax (r = 0.86, p less than 0.0001, n = 107). Thus, the slope of the end-systolic pressure-volume relation derived from single beat analysis is not always sensitive to inotropic interventions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effect of fatty acyl domain of phospholipids on the membrane-channel formation of Staphylococcus aureus alpha-toxin in liposome membrane.

By use of carboxyfluorescein-loaded multilamellar liposomes prepared from synthetic phosphatidylcholine (PC) or sphingomyelin and cholesterol in a molar ratio of 1:1, we studied whether or not fatty acyl domain of the phospholipids affects the membrane-damaging action (or channel formation) of Staphylococcus aureus alpha-toxin on the phospholipid-cholesterol membranes. Our data indicated: (1) that toxin-induced carboxyfluorescein-leakage from the liposomes composed of saturated fatty acyl residue-carrying PC and cholesterol was decreased with increasing chain length of the acyl residues between 12 and 18 carbon atoms, although toxin-binding to the liposomes was not significantly affected by the length of fatty acyl residue; (2) that unsaturated fatty acyl residue in PC or sphingomyelin molecule conferred higher sensitivity to alpha-toxin on the phospholipid-cholesterol liposomes, compared with saturated fatty acyl residues; and (3) that hexamerization of alpha-toxin, estimated by SDS-polyacrylamide gel electrophoresis, occurred more efficiently on the liposomes composed of PC with shorter fatty acyl chain or unsaturated fatty acyl chain. Thus, hydrophobic domain of the phospholipids influences membrane-channel formation of alpha-toxin in the phospholipid-cholesterol membrane, perhaps by modulating packing of phospholipid, cholesterol and the toxin in membrane.

Diglycerides

Effects of ammonium chloride on membrane currents of acinar cells dispersed from the rat parotid gland.

In acinar cells freshly dispersed from rat parotid glands, the effects of ammonium chloride (NH4Cl) on membrane currents were studied using the whole-cell clamp method. When membrane currents were recorded with command pulses to 0 mV, applied at 2-s intervals from a holding potential of -70 mV, NH4Cl (5-20 mM) transiently decreased outward currents and then slowly increased both outward and inward currents. After reaching a peak in about 40-50 s, both outward and inward currents gradually decreased in the presence of NH4Cl and, on its wash-out, the currents returned to the control level. Butyrate (5-20 mM) had little effect on the resting membrane currents, but markedly inhibited the response to NH4Cl. Tetraethylammonium (5 mM) strongly reduced both the resting and NH4Cl-induced outward currents, whereas it slightly potentiated the NH4Cl-induced inward current without affecting the membrane current at the holding potential. Without ATP in the patch pipettes, carbachol-induced membrane currents were relatively resistant to Ca2+ removal from the external medium, but NH4Cl-induced currents were quickly abolished in the absence of Ca2+. We conclude that intracellular alkalinization with NH4Cl increases Ca2+ influx and activates Ca(2+)-dependent outward K+ and inward Cl- currents.

Ammonium Chloride

Induction of coronary artery spasm by intracoronary acetylcholine: comparison with intracoronary ergonovine.

To investigate the mechanism of coronary spasm, we compared the action of acetylcholine with that of ergonovine in 11 patients with vasospastic angina (group 1) and in 15 patients with chest pain (group 2). Coronary arteriography was performed immediately after the patients received intracoronary injections of titrated increments of each agent. In the patients in group 1 occlusive or near-occlusive (99% luminal narrowing) coronary spasm associated with angina and ischemic electrocardiographic ST changes was noted in nine of 11 patients receiving acetylcholine and in all 11 patients receiving ergonovine. The region and the degree of the most severe coronary spasm on coronary arteriograms evoked by the two agents were the same in nine of the 11 patients in group 1. In the other two patients in group 1, spontaneous focal coronary spastic stenosis in the baseline coronary arteriogram was relieved by the intracoronary injection of acetylcholine, and a focal coronary occlusive spasm in the same region was induced repeatedly by the subsequent intracoronary injection of ergonovine (paradoxic phenomenon). In contrast, occlusive or near-occlusive coronary spasm was not induced by either agent in any patient in group 2. These results suggest that the two provocative tests for coronary spasm that involve acetylcholine and ergonovine are clinically useful in the diagnosis of vasospastic angina, but testing with intracoronary ergonovine is needed when a spontaneous focal coronary spasm is relieved by the intracoronary injection of acetylcholine. The results also indicate that in many patients with vasospastic angina, nonspecific hypersensitivity to acetylcholine or ergonovine in a definite region of the coronary arteries generally plays an important role in the induction of coronary spasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

Processing of structural polypeptides of infectious flacherie virus of the silkworm, Bombyx mori: VP1 and VP4 are derived from VP0.

Infectious flacherie virus of the silkworm, Bombyx mori, contains five major polypeptides termed VP0, VP1, VP2, VP3, and VP4 in the order of descending molecular weight. Immunoblot analysis with specific antisera against each of these structural polypeptides showed that antisera against VP1 and VP4 unequivocally reacted with VP0 as well as their homologous structural polypeptides. Limited proteolysis of VP0 and VP1 by Staphylococcus aureus V8 protease gave several common polypeptide fragments. Amino acid sequence analysis showed that VP0 and VP4 shared a common NH2-terminal amino acid sequence. These results indicate that VP1 and VP4 are generated from VP0 and that VP4 occupies the NH2-terminal portion of VP0.

Amino Acid Sequence

31P nuclear magnetic resonance study of phospholipid metabolites in ischemic liver.

To assess the metabolic alterations induced by normothermic hepatic ischemia, 31P nuclear magnetic resonance analysis was performed on liver samples using perchloric acid extraction. In particular, phosphomonoesters and phosphodiesters, the intermediary metabolites of membrane phospholipid turnover, were characterized precisely and quantitated. Phosphocholine and phosphoethanolamine, the precursors of phospholipid anabolism, did not change, while the phosphodiesters decreased. In contrast, alpha-glycerophosphate, which is both a precursor of phospholipid synthesis and the intermediary product of phospholipid degradation, markedly increased following 30 min of normothermic ischemia. These findings suggest that cellular phospholipids are actively degraded during normothermic hepatic ischemia.

Adenosine Triphosphate

Pancreatic islets of obese hyperglycemic mice (ob/ob).

The development of the obesity-associated hyperglycemic syndrome in ob/ob mice, genetically determined, was observed over time by a combined functional and structural study of pancreatic islets. Islet areas increased with advancing age in ob/ob mice from 2 times at 1 month to 30 times at 6 months of age the size of lean mouse islets. Islet areas apparently increased more than pancreatic insulin content in ob/ob mice. Glucose and insulin tolerance tests were performed to study in vivo responses to glucose and insulin, respectively, in 1-, 3-, and 6-month-old mice. With ob/ob mice, glucose tolerance tests revealed more elevation of plasma glucose than in lean mice, the lean mice revealing more elevated plasma insulin than the obese mice. In insulin tolerance tests, lean mice presented marked hypoglycemia, whereas ob/ob mice revealed slightly higher plasma glucose at 1 month of age but three to four times higher amounts than that of lean mice at 6 months of age. Thus, increasing insulin resistance in ob/ob mice older than 3 months is associated with progressively increasing islet area, which contains proportionally less insulin than that of lean mouse pancreas. The data suggest that insulin resistance in ob/ob mice progressively develops up to 6 months of age and that marked islet hyperplasia is likely in response to sustained hyperglycemia, leading to hyperinsulinemia and eventual marked obesity.

Animals

C-cell hyperplasia in secondary hyperparathyroidism.

Calcitonin is a hypocalcaemia producing hormone and is secreted by C-cells of the thyroid. The current study was undertaken on a hypothesis that C-cell hyperplasia may develop in the secondary hyperparathyroidism of chronic renal failure in response to sustained hypercalcaemia. With an immunoperoxidase staining method for calcitonin, C-cell hyperplasia was noted in four of six cases of autosomal dominant polycystic kidney disease and in three of six cases of acquired renal cystic disease, an overall incidence of 58% compared with an incidence of 36% (five of 14) in cases of primary hyperparathyroidism with parathyroid adenoma. Thus, both primary and secondary hyperparathyroidism may trigger C-cell hyperplasia in an attempt to produce a hypocalcaemic effect.

Adult

Effects of intracellular ATP on calcium current in freshly dispersed single cells of guinea-pig portal vein.

In smooth muscle cells freshly dispersed from the guinea-pig portal vein, inward currents were recorded with the whole-cell clamp method in the presence of 2.4 mM Ca2+ under the condition in which outward K+ currents were suppressed and the effects of ATP in patch pipettes were studied. There was a large variation of the rate of current decay, the half-decay time ranging from 20 to 80 ms, but it was difficult to demonstrate clearly the presence of fast (T-type) and slow (L-type) Ca2+ channels based on threshold, the effects of changing holding potential, and of nicardipine, a dihydropyridine Ca2+ channel blocker. Intrapipette ATP had a weak potentiating effect on inward current, but did not seem to influence the correlation between peak current amplitude and current configuration. Cyanide (0.5 mM) reduced inward currents, particularly when ATP concentration was low and only limited recovery was observed. It was concluded that the amplitude and the rate of current decay of inward currents are not only determined by intracellular ATP, but also significantly influenced by some other factor, such as that involved in 'run-down' of Ca2+ currents.

Action Potentials

Phospholipid metabolism in platelets from stroke-prone spontaneously hypertensive rats and Wistar Kyoto rats.

Platelets from stroke-prone spontaneously hypertensive rats (SHRSP) show severe hypofunctions accompanied by defective protein (P47) phosphorylation. To examine the mechanism of platelet hypofunctions, phospholipid metabolism in SHRSP was compared with that in Wistar Kyoto rats (WKY). Phosphatidylinositol (PI) content was 20% less in SHRSP than in WKY, but no changes were observed in other phospholipids. Incorporation of [3H]-arachidonic acid (AA) into PI and phosphatidylethanolamine (PE) was 12% and 11% lower, and that into phosphatidylcholine (PC) was 6% higher in SHRSP than in WKY. Thrombin-induced diacylglycerol and phosphatidic acid formation were similar in both groups of platelets. Thrombin-induced release of [14C]-AA from the labeled platelets and its metabolism to eicosanoids occurred at similar rates. These results suggest that reduced formation of diacylglycerol, an activator of protein kinase C (PKC), does not cause defective phosphorylation of P47, a substrate of PKC, in SHRSP. However it remains unclear how the lower PI content and the altered distribution of AA in PC and PE is related to SHRSP platelet hypofunctions.

Animals

Direct injection method for quantitation of delta-aminolevulinic acid in urine by high-performance liquid chromatography.

A highly sensitive and simple method for determining delta-aminolevulinic acid (ALA) in urine was established, using direct injection of urine into a high-performance liquid chromatographic column, with fluorometric detection after post-column derivatization with o-phthalaldehyde (OPA). The recovery of ALA was about 100% and ALA was completely separated on an ion exchange column (retention time, 38 min). The detection limit for ALA was 10 pmol (S/N = 2). The mean levels of urinary ALA of 10 healthy volunteers, 4 patients with acute intermittent porphyria, and 2 workers occupationally exposed to lead were 0.76, 5.25, and 23.54 mg/l, respectively. Because of its simplicity, the method is considered to be suitable for routine analysis of urinary ALA in the clinical laboratory.

Aminolevulinic Acid

Inheritance and breeding of the waltzing mutant in the musk shrew (Suncus murinus, Insectivora) characterized by the circling and head-shaking behaviors.

A behavioral mutant was found in the laboratory-bred musk shrew (Suncus murinus). The affected shrews were characterized by the behaviors of tight circling in both directions and frequent head shaking in horizontal. They could definitely be identified by at least day 10 after birth. These abnormal behaviors were steady and permanent through life. Mating experiments demonstrated that the mutant character is expressed by a single autosomal recessive gene in homozygote with complete penetrance. The pedigree analysis indicated that the gene was derived from one heterozygous male captured in Ginowan city, Okinawa. The name, waltzing, was proposed for this mutant character with the gene symbol wz. An abnormality of the balance organ was predicted for a cause of the abnormal behaviors, since, besides the circling and head shaking behaviors, the affected shrews could not keep the body stretching but twisted it frequently when they were held up by the tail and further they could not keep the head on the water surface at all. Nevertheless, the affected shrews were almost normal in gestation period, litter size, weaning ratio and body weight in comparison with the phenotypically normal ones. The mutant shrews have been maintained as a closed colony, the WZ line involved more than 30 individuals at every one generation.

Animals

Kinky coat, a new autosomal recessive mutation in the musk shrew, Suncus murinus.

A kinky-coat mutant was discovered at the fifth generation of the BAN strain originating from wild musk shrews (Suncus murinus) in Bangladesh. Mating experiments indicated that the kinky-coat character is controlled by a single autosomal recessive gene designated kc (kinky coat), which is not allelic to the gene ch (curly hair) previously reported in the Tr strain derived from wild musk shrews on Taramajima Island, Japan. Because the kc/kc homozygotes were fully fertile and viable, the kc gene should be useful as a genetic marker in linkage studies. In external appearance, homozygotes were characterized by curly vibrissae, somewhat unkept coat hair, and wavy long hair on the tail. Both the length and width of coat hair did not differ significantly between homozygous and normal shrews. Light microscopic observations showed that shafts of the kc coat hair are wavy and often have small swellings with disorganization of the medullary structure. Scanning electron microscopic examinations further revealed that the shafts of the vibrissae, coat hair, and tail hair have abnormalities such as longitudinal fissures, twists, and hollows. It is clear that these modifications caused waviness or curling of the shafts of the three kinds of hairs observed.

Alleles

Lung cancer accompanied by erythema.

Skin manifestations associated with malignant diseases are designated syndroma dermatotumorale. A case of lung cancer combined with atypical erythema is reported. A 70-year-old man was admitted to hospital because of a 4-month history of atypical erythema of unknown origin. A nodule in the right lung was revealed on chest roentgenogram which was diagnosed as lung cancer. After right upper lobectomy, the erythema regressed gradually and disappeared completely in 7 days. It is suggested that the erythema was a manifestation associated with the lung cancer.

Adenocarcinoma