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Biomedical subjects

T Maeda

Publications and source records attributed to T Maeda.

At least 1,027 records · Page 57Linked to original sources

The computerized derivation of rate equations for enzyme reactions on the basis of the pseudo-steady-state assumption and the rapid-equilibrium assumption.

A computer program is developed for the derivation of the rate equation for enzyme reactions on the basis of the pseudo-steady-state assumption and the combination of the pseudo-steady-state and the rapid-equilibrium assumptions. The program not only has an easy input method, but also can obtain a complete rate equation in itself on only one run. The usefulness of the program is demonstrated by deriving the rate equations for some typical enzyme reactions. Details of the program have been deposited as Supplementary Publication SUP 50141 (42 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7QB, U.K., from whom copies may be obtained as indicated in Biochem. J. (1988), 249, 5.

Computer Simulation↗

[A case of chemical hyperthyroidism induced by antiarrhythmic agent amiodarone].

Amiodarone, an antiarrhythmic agent, is known to occasionally induce alterations in thyroid function because of its iodine content and ability to inhibit T4 5'-monodeiodination. We herein describe the drug-induced chemical hyperthyroidism in a diabetic patient with ventricular premature beats. A 46-year-old man with well controlled diabetes mellitus revealed neck swelling during a 4 months' treatment with amiodarone for his frequent occurrence of ventricular premature beats. Physical findings were unremarkable other than grade III diffuse struma. Routine laboratory studies were almost normal. The results of thyroid function studies showed hyperthyroidism, including increases in T4 and free T4, slight increases in T3 and free T3, a marked increase in reverse T3 and a decrease in 123I 24-h uptake. TSH was low and did not respond to TRH. Antithyroid antibodies and TSH receptor antibodies were negative. The findings of the thyroid biopsy were unremarkable except for a mild follicular hyperplasia. After cessation of the drug, T3 and free T3 were returned to normal within 2 weeks, T4 and free T4 within 2 months and reverse T3 after 6 months. These data suggest that the struma and chemical hyperthyroidism observed in our patient were induced by amiodarone treatment.

Amiodarone↗

Conformation of antithrombin III with defective biological functions derived from a thrombophilic patient.

Antithrombin III (AT III) with defective biological functions and altered antigenicity has been found in a thrombophilic patient. Circular dichroism (CD) spectra of antithrombin III purified from the patient's plasma were measured in near and far-ultraviolet (UV) wavelength regions. The far-UV CD spectrum of the patient's AT III was similar at room temperature to that of normal AT III derived from healthy adult males. Mean residue ellipticity at 221 nm of the patient's AT III, however, decreased its magnitude by 6% gradually as temperature increased up to 74 degrees C, whereas that of the normal AT III reduced its magnitude sharply at around 63-64 degrees C and by 18%. The near-UV CD spectrum of patient's AT III was different from that of normal AT III. These results indicate that the secondary structure of patient's AT III is similar to that of normal AT III at room temperature, while local conformation of aromatic amino acid residues in the abnormal protein is different from that in the normal one and that the secondary structure of the patient's AT III is heat-stable, while that of the normal one is heat-labile.

Antithrombin III↗

QT intervals as an index of high serum calcium in hypercalcemia.

The relationship between QT interval and serum calcium concentration (s-Ca) was examined in 9 hypercalcemic (s-Ca greater than 11 mg/dl) patients. Three QT intervals corrected by Bazett's formula were used for the analysis: the intervals from the beginning of the QRS to the onset (QoTc), the apex (QaTc), and the end of T wave (QeTc). The measurements of s-Ca and other electrolytes were made on the blood sample taken on the same day of the electrocardiogram (ECG) recordings. The normal range of s-Ca and three QTc intervals was determined in 50 outpatients with no cardiac disease. Three QT intervals in the hypercalcemic patients were significantly shortened with a diminution in the s-Ca. The QTc intervals showed significant negative correlation with s-Ca. Sensitivity of QoTc, QaTc, and QeTc in predicting high s-Ca was 83%, 57%, and 39%, respectively, and specificity was 100%, 100%, and 89%. The PQ interval tended to be prolonged in the case of hypercalcemia, but the change was statistically insignificant. These observations suggest that QT intervals can serve as an indicator of high s-Ca and that the QoTc seems to be a good indicator of the three QTc's.

Adult↗

Filiform papillae as a sensory apparatus in the tongue: an immunohistochemical study of nervous elements by use of neurofilament protein (NFP) and S-100 protein antibodies.

Nervous elements supplying the filiform papillae of the tongue of cattle and rats were investigated using immunohistochemistry against neurofilament protein (NFP) and glia-specific S-100 protein. The rod-shaped bovine filiform papillae were heavily keratinized along their entire length and lacked the connective tissue core that occurs in other mammals. Instead, the core was located posterior to the filiform papilla. The base of the bovine filiform papillae was invaded vertically by laminar connective tissue papillae. The core contained a large number of NFP-positive nerve fibers, most of them terminating as free endings in its anterior margin. NFP-positive nerves gathered around the anterior ridge of the epithelium at the base of the core and occasionally penetrated into the epithelium. The laminar connective tissue papillae at the base of the filiform papilla also contained NFP-positive nerve fibers. The core contained S-100-immunoreactive lamellated corpuscles, which were identified as "simple corpuscles" in electron micrographs. The structure and innervation of the bovine filiform papilla suggest that they represent a specialized sensory apparatus. The pyramidal filiform papillae of the rat were smaller, each containing a simple connective tissue core. Few NFP-positive nerve fibers from the nerve plexus entered the core. Filiform papillae are thus less specialized in rats than in cattle.

Animals↗

Innervation of periodontal ligament and dental pulp in the rat incisor: an immunohistochemical investigation of neurofilament protein and glia-specific S-100 protein.

Nervous elements in the periodontal ligament and dental pulp of rat incisors were investigated by means of immunohistochemistry for neurofilament protein (NFP) and glia-specific S-100 protein. The periodontal ligament in the incisors was densely innervated by NFP-immunoreactive nerve fibers; the distribution of the nerve fibers and their terminations differed markedly from those in molars. NFP-positive, thick nerve bundles entered the lingual periodontal ligament through slits located in the mid-region of the alveolar socket, and immediately formed numerous Ruffini-like corpuscles. In the labial periodontal ligament, all of the NFP-immunoreactive nerve fibers terminated in free endings. The restricted location of the stretch receptor, Ruffini-like corpuscle, in the lingual periodontal ligament appears to be an essential element, because this region is regularly extended during mastication. The nervous elements were restricted to the alveolar half of the periodontal ligament in every region; they avoided the dental half of the periodontal ligament, which presumably moves continuously with the tooth. Pulpal nerve fibers in incisors also showed a characteristic distribution different from those in molars; individual nerve fibers with beaded structures ran in the center of the pulp toward the incisal edge, and did not form the subodontoblastic nerve plexus of Raschkow. Immunostaining for S-100 protein revealed a distribution pattern of nervous elements similar to that for NFP, suggesting that the nerves supplying the periodontal ligament and dental pulp were mostly covered by a Schwann sheath.

Animals↗

Experimental study on "delay" phenomenon in relation to flap width and ischaemia.

The present investigation was designed to clarify what induces circulatory enhancement in the delay procedure. Two different sizes of a bipedicle flap were prepared in rats and the blood flow was measured at the centre of the flaps. The delay effect, that is, elongation of the survival length, was significantly less in the wide flap than in the narrow flap, though the two flap groups had almost identical levels of central ischaemia when averaged for each group. On the basis of ischaemic level, the flaps, regardless of size, were classified into two groups: more and less ischaemic than the mean. The delay effects noted in the more ischaemic flaps were not significantly different from those in the less ischaemic flaps. These results indicate that flap width has more influence on the delay effect than the degree of ischaemia.

Animals↗

Class switching from gamma 3 to gamma 2b in a murine pre-B cell line.

Class switching from gamma 3 to gamma 2b production at pre-B cell stage was observed in an Abelson virus-transformed murine immature cell line that is able to perform VH to DJH recombinations followed by class switch recombinations. A series of Southern blotting experiments indicates that the class switching from gamma 3 to gamma 2b was mediated by the deletion mechanism of the intervening CH genes on the expressed chromosome and that the break points in the switch recombinations might be different from each other among six independent switching events from gamma 3 to gamma 2b. This in vitro switching system should provide us with much information on the mechanisms of class switch recombination.

Abelson murine leukemia virus↗

Parasympathetic innervation of cutaneous blood vessels by vasoactive intestinal polypeptide-immunoreactive and acetylcholinesterase-positive nerves: histochemical and experimental study on rat lower lip.

The distribution and origin of perivascular acetylcholinesterase-active and vasoactive intestinal polypeptide-immunoreactive nerve fibers were studied in the rat lower lip by means of acetylcholinesterase histochemistry and vasoactive intestinal polypeptide immunohistochemistry. The perivascular nerve fibers stained intensely with both histochemical techniques and were widely distributed on small arteries and arterioles of the lower lip, especially in the transitional zone between the hairy skin and the mucous membrane. The distributions of the two types of fibers were very similar and most of them showed overlapping coloration, on consecutive staining for vasoactive intestinal polypeptide and acetylcholinesterase. Both acetylcholinesterase-positive and vasoactive intestinal polypeptide-immunoreactive fibers were completely lost on removal of the otic ganglion, while they were not affected by sympathetic ganglion removal or sensory nerve sectioning. In the otic ganglion, most cells exhibited acetylcholinesterase activity, and about 60% of the cells showed light to heavy vasoactive intestinal polypeptide immunoreactivity. These findings indicate that vessels in the rat lip are innervated by parasympathetic fibers originating from the otic ganglion and support the view that vasoactive intestinal polypeptide is present in cholinergic neurons. This may suggest the possible control by the parasympathetic nervous system of cutaneous blood vessels through vasoactive intestinal polypeptide-containing cholinergic neurons, in general or at least in the facial area.

Acetylcholinesterase↗

Change in membrane elastic modulus on activation of glucose transport system of brush border membrane vesicles studied by osmotic swelling and dynamic light scattering.

The cell membrane having a transport system is inferred to be flexible when its function is being activated. For the brush border membrane vesicles prepared from rat small intestine, which have the co-transport system of Na+ and glucose, the membrane elasticity was measured as a function of the d-glucose concentration in the presence of Na+ ions. The elastic modulus of the vesicle membrane was obtained by an osmotic swelling method. Osmolality was changed by diluting the extravesicular d-mannitol concentration. The change in the diameter of the membrane vesicle in response to an osmolality change was measured by the dynamic light-scattering method. The elastic modulus of the vesicle membrane decreased from 150 dyn/cm to 80 (45) dyn/cm with the increase of d-glucose, from 0 mM to 10(30) mM in the presence of 10 mM Na+ ions. On the other hand, in the presence of 1 mM phlorizin, a glucose-transport inhibitor, the elastic modulus remained at a constant value of 160 dyn/cm in the same range of the d-glucose concentration. This indicates that the vesicle membrane becomes flexible when its transport function is activated. In a broad osmolality range, the brush border membrane vesicle showed cycles of "swell-burst-reseal". The vesicle membrane became flexible after every cycle, namely, the modulus was 150, 120, and 55 in units of dyn/cm in the presence of 1 mM d-glucose and 50 mM Na+ ions.

Alkaline Phosphatase↗

Changes in prolactinomas and somatotropinomas in humans treated with bromocriptine.

Effects of bromocriptine (CB) on human prolactin (PRL)-secreting adenomas (PRLomas) and growth hormone-secreting adenomas (GHomas) were analyzed morphologically and morphometrically. Treatment with CB for 2 weeks brought about a variety of changes in PRLomas, including cell shrinkage, degenerative and necrotic changes and fibrosis. Secretory granules within a cell increased in number but not in volume. However, the exocytosis of the granules increased remarkably. Single-cell necrosis was occasionally seen in the tumor nests, whereas breakdown of tumor cells occurred in clusters predominantly in the periphery of the nests. At 1 week after cessation of CB, PRLomas showed two distinct, divergent histological appearances; more advanced destructive changes and the regrowth. These findings suggest that human PRLomas consist of two populations, i.e., those sensitive and resistant to the cytocidal actions of CB. In contrast, treatment with CB produced almost no change in GHomas except for an increase in the stromal tissue volume. Vacuolation and single-cell necrosis were occasionally observed in a few GHomas.

Bromocriptine↗

Interactions between transplanted pituitary tumor and gonads in nude mice.

More pronounced hyperprolactinemia occurred in the male nude mice bearing a transplantable rat pituitary tumor than in the female nude mice, although the hyperprolactinemia in rats bearing the identical tumors was more prominent in the females than in the males. PRL levels in castrated nude mice of both sexes bearing tumor were almost the same as those in the intact female nude mice. PRL levels in the tumor tissues in each group paralleled relative abundance of PRL-secreting cells in the tumors. Supplement with testosterone or estrogen to the castrated mice recovered the PRL concentrations to the same or higher levels than those in intact male mice. Reproductive organs in the tumor-bearing male nude mice showed no alterations, whereas those in the female nude mice were markedly atrophic. Tumors had receptors for estrogen but not for androgen. Insufficient estrogen secretion due to the ovarian atrophy caused by the PRL from the tumors seemed responsible for the failure in growth of PRL-secreting tumor cells and consequent low PRL production by the tumor.

Animals↗

Lack of carcinogenicity of phenytoin in (C57BL/6 x C3H)F1 mice.

Groups of 50 B6C3F1 mice of each sex were given 0.012% or 0.006% phenytoin in their powdered diet for 78 wk and were then fed a basal diet for 8 wk. Control groups of 50 mice of each sex were fed powdered basal diet for 86 wk. Mean total intakes of phenytoin per mouse were 301 and 150 mg in males, and 292 and 154 mg in females, respectively. The survival rates of each group at week 86 were 72-86% in males, and 86-94% in females. Liver-cell tumors, alveolar tumors, and Harderian-gland adenomas in male mice, malignant lymphomas and/or leukemias in female mice, and a few tumors in other organs of both sexes were found. The total number of hepatocellular tumors in mice treated with the high dose of phenytoin was significantly smaller than that of control mice in males (p less than 0.05). However, hepatocellular carcinomas developed 15 to 3 wk earlier in a few mice of phenytoin-treated males than in the controls. In other organs, no significant increase of any particular tumor type was observed in the treated groups of both sexes. Thus, phenytoin was not carcinogenic in B6C3F1 mice in this study.

Administration, Oral↗

Hyperthermic enhancement of the antitumor effect of natural human tumor necrosis factor-alpha and -beta: an in vitro and in vivo study.

A synergistic antitumor effect of natural human tumor necrosis factor-beta (TNF-beta) in combination with hyperthermia was found, in comparison with that of TNF-alpha, using an in vitro antiproliferative assay on a human colon cancer cell line (RPMI4788) and an in vivo tumor growth inhibition assay on Meth A sarcoma cells. In vitro combined treatment with TNF-beta (10,000 U/ml) and hyperthermia (at 43 degrees for 60 min) synergistically inhibited the proliferation of the cells. Combined effects of TNF-alpha or natural human interferon-alpha or -gamma (IFN-alpha, -gamma) and hyperthermia were also examined, and furthermore, the combinations of TNFs and IFNs were examined in combination with hyperthermia at 42 degrees; their antiproliferative effects were further augmented by hyperthermia. In vivo growth of Meth A sarcoma cells (5 x 10(5)), transplanted subcutaneously into BALB/c mice, was inhibited significantly (P less than 0.05) with the combination of TNF-alpha or -beta (2 x 10(5) U/mouse) and hyperthermia (at 43 degrees for 60 min) as compared to either a single intravenous injection of TNF-alpha or -beta alone or the hyperthermia alone. The influence of TNF-beta and hyperthermia on the cell cycle was examined. Flow cytometric analysis showed that RPMI4788 cells treated with TNF-alpha or -beta accumulated in the S phase of the cell cycle, and that hyperthermia (at 42 degrees for 60 min) alone had no influence on the cell cycle and did not augment the S phase accumulation of the cells treated with TNF-alpha or -beta.

Animals↗

Three cases of delivery under sodium valproate--placental transfer, milk transfer and probable teratogenicity of sodium valproate.

Here is a report of three cases of delivery from women who have taken sodium valproate (VPA). One neonate was born with polydactylism, and we reviewed the congenital malformations in children of mothers who have taken VPA. In the other two cases, we also examined the levels of VPA in the cord serum and breast milk. The levels of VPA in the cord serum were 50 micrograms/ml at 12 hours after the last maternal dose and 75 micrograms/ml at 14 hours after the last maternal dose. The blood levels of VPA in the two mothers were 48-59 micrograms/ml and 55-85 micrograms/ml in their late pregnancy, respectively. The levels of VPA in the breast milk were 2.0-3.5 micrograms/ml and the ratio of VPA in the breast milk to blood was 2-3%. These results suggest the high rate of placental transfer and the low rate of milk transfer of VPA.

Abnormalities, Drug-Induced↗

Captopril-induced metabolic acidosis with hyperkalemia.

Hyperreninemic hypoaldosteronism was diagnosed in a 34-year-old woman with hypertension who was receiving captopril therapy. Renal biopsy revealed an advanced stage of IgA nephropathy, and her creatinine clearance was 40 ml/min. Elevation of serum potassium from 4.7 to 5.8 mEq/l and development of hyperchloremic metabolic acidosis with laboratory findings of pH 7.285, HCO3- 13.5 mEq/l, Na 141, and Cl 114 mEq/l were observed after captopril therapy. When captopril was withdrawn, elevated serum potassium levels and metabolic acidosis returned to normal. Challenge with captopril resulted in a decrease in plasma aldosterone levels, an increase in plasma renin activity, and development of hyperkalemic, hyperchloremic metabolic acidosis which is corrected with mineralocorticoid replacement. This case study demonstrates that captopril can cause hyperreninemic hypoaldosteronism with the laboratory finding of hyperkalemic, hyperchloremic metabolic acidosis.

Acidosis↗