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Biomedical subjects

M Komatsu

Publications and source records attributed to M Komatsu.

At least 19 recordsLinked to original sources

A novel low-density lipoprotein with large amounts of phospholipid found in the egg yolk of crustacea sand crayfish Ibacus ciliatus: its function as vitellogenin-degrading proteinase.

Low-density lipoprotein (LDL) with large amounts of phospholipid but not triacylglycerol was isolated from the egg yolk of crustacea sand crayfish Ibacus ciliatus as well as lipovitellin. LDL possessed vitellogenin-degrading proteinase activity. Hemolymph vitellogenin was degraded by incubating with LDL at pH 4.5 for 72 hr at 35 degrees C and apolipoprotein profiles of vitellogenin degraded by LDL were very similar to those of lipovitellin in the egg.

Animals

Nuclear DNA analysis of hyperplastic parathyroid glands in multiple endocrine neoplasia type I.

Twenty-four hyperplastic parathyroid glands from 11 patients with multiple endocrine neoplasia type I (MEN-I), and 36 hyperplastic parathyroid glands in 15 patients with sporadic primary hyperparathyroidism, ie, not associated with MEN, were analyzed for DNA by flow cytometry. Sixteen of 24 hyperplastic parathyroid glands from patients with MEN-I were DNA diploid, and eight were DNA aneuploid. Thirty-three of 36 hyperplastic parathyroid glands from patients without MEN were DNA diploid, and only three were DNA aneuploid. The mean percentage of 4c level (a measure of the G2M phase of the cell cycle) of DNA diploid hyperplastic parathyroid glands taken from patients with MEN-I was 8.1% +/- 4.5%, which is significantly higher than the 3.5% +/- 3.4% for those taken from patients without MEN. Our results show that there is a difference in nuclear DNA content between hyperplastic parathyroid glands in patients with MEN-I and those in patients without MEN.

Aneuploidy

Adenomatous goitre: therapeutic strategy, postoperative outcome, and study of epidermal growth factor receptor.

A total of 377 patients with histologically proven adenomatous goitre was operated on, 34 as a second operation, and assessed for postoperative outcome (including the incidence of unsuspected malignancy) and immunohistochemical localization of epidermal growth factor receptor. In primary surgery, enucleation of all the nodules was carried out. Patients requiring reoperation showed multicystic degenerate nodules involving one or both lobes. A coexistent cancer was observed in 18 patients (4.8 per cent). The immunohistochemically detected expression of epidermal growth factor receptor in adenomatous goitre was more evident in patients with multinodular lesions. Near-total lobectomy of the involved side(s) is desirable for the prevention of recurrence and complications after operation.

Adolescent

Abnormal molecular weight profile of urinary protein in rats with streptozotocin-induced diabetes.

A quantitative analysis of the molecular weight (MW) profile of urinary protein by SDS-PAGE was performed in streptozotocin (STZ)-injected, non-ketotic diabetic rats (DM group), diabetic rats receiving dipyridamole (DM-DIP group), normal rats (C group) and STZ-injected rats with near-normal glycemia due to insulin treatment (DM-INSULIN group). In the DM group, decrease of a small MW protein (SMWP) (MW 19.5 k) was found at 2.5 weeks, and an increase of larger MW proteins (LMWP) (MW 68 [albumin], 55 and 29 k) together with a decrease of SMWPs (MW 19.5 and 15 k) was found at 15 weeks, as compared to the C group: the MW profile of urinary protein in the DM-INSULIN and C groups was indistinguishable. At 15 weeks, creatinine clearance (Ccr) was significantly depressed and an increase in the mesangial matrix with electron dense deposits was evident in the DM group. The urinary protein abnormalities were partially corrected and the reduction of Ccr was absent in the DM-DIP group with no effect on glomerular morphology. STZ-induced diabetes in rats is accompanied by a reduction of urinary SMWP, and a subsequent increase of LMWP and depression of Ccr: dipyridamole ameliorates urinary protein abnormalities and prevents the reduction of Ccr.

Animals

Differential effects of body weight, hyperinsulinemia and oral glucose load on serum C-peptide/insulin molar ratio.

Serum C-peptide immunoreactivity (CPR)/immunoreactive insulin (IRI) molar ratio was determined in 136 subjects without renal, hepatic and thyroid disorders, at fasting, and during the initial period of 75 g-oral glucose tolerance test. The subjects were divided into 4 groups based on their body weight and age; Group A, young (< 55 years) and normal body weight (body mass index [BMI, kg/m2] < or = 25) subjects; Group B, young and overweight (BMI > 25) subjects; Group C, aged (> or = 55 years) and normal body weight (BMI < or = 25) subjects; Group D, aged and overweight subjects. Fasting CPR/IRI ratio and absolute CPR level negatively correlated in Groups B and D but not in A and C. After oral glucose load with elevation of insulin, CPR/IRI ratio invariably declined in all groups and significant negative correlation between CPR/IRI and CPR was found in Groups A, B and D but not in C. Slope of the regression lines obtained for correlation between CPR/IRI ratio and CPR were significantly steeper at fasting compared to the post-stimulation phase. CPR/IRI ratio is affected by hyperinsulinemia and oral glucose load but not by obesity alone. Assuming that CPR/IRI ratio reflects hepatic extraction of insulin, the insulin clearance at fasting is progressively reduced with increasing insulin secretion in overweight subjects: failure to detect such phenomenon in normal body weight subjects may be due to a narrower CPR range in this population. Insulin metabolism at fasting and during glucose stimulation is likely to be regulated by distinct factors.

Aged

Intraocular kinetics of ceftazidime (Modacin).

The concentration of ceftazidime was determined in the aqueous humor and the vitreous body of normal, vitrectomized and aphakic/vitrectomized eyes and in the serum of albino rabbits 1 h after intravenous injection of 100 mg/kg ceftazidime. The intravitreal ceftazidime concentration was low (0.1-0.2 microgram/ml) in normal eyes 1 h after intravenous injection, and high (8.7 +/- 8.5 micrograms/ml) in vitrectomized and aphakic/vitrectomized eyes when injected immediately after surgery. The ceftazidime concentration was also determined in the aqueous humor and the vitreous body of normal eyes and in the serum of albino rabbits 3, 6, 12, 24 and 48 h after intravitreal injection of 200 micrograms. The intravitreal ceftazidime concentration after intravitreal injection decreased exponentially for 12 h (half-life about 7.4 h). It decreased more slowly thereafter and remained at 13.0 micrograms/ml (mean) even 48 h after injection. This concentration exceeded the minimum inhibitory concentrations against common gram-positive and gram-negative organisms causing endophthalmitis.

Animals

Mastoparan-induced hormone release from rat pancreatic islets.

Mastoparan, a tetradecapeptide purified from wasp venom, stimulates insulin and glucagon release by rat pancreatic islets in a dose-related manner. In perifusion experiments, mastoparan produces monophasic hormone release, which ceases within 10 min of removal of the peptide. After exposure of the isles to mastoparan, glucose-induced insulin release is clearly retained. In incubation experiments, mastoparan-induced insulin release is greatly blocked by pretreatment of the islets with pertussis toxin or neomycin (inhibitor of phosphoinositide turnover) or by lowering the ambient temperature to 17 C. Pretreatment of the islets with nifedipine (calcium channel blocker), H-7 (inhibitor of A- and C-kinase), somatostatin, or divalent cation-free medium does not affect the response to mastoparan. Pretreatment with parabromophenacylbromide (phospholipase-A2 inhibitor) does not block the response induced by a high concentration of (58 microM) mastoparan. The peptide does not stimulate insulin synthesis during 30 min of incubation. Mastoparan raises the cytosolic free Ca2+ concentration, measured by fura-2, in isolated islet cells at normal (1.9 mM) and very low (6.5 microM) extracellular Ca2+ concentrations. Intravenous administration of mastoparan in rats causes a significant elevation of both insulin and glucagon. Together with the previous data, we conclude that mastoparan stimulates islet hormone release through a temperature-dependent process mediated by pertussis toxin-sensitive GTP-binding protein(s). Activation of phospholipase-C and liberation of intracellular Ca2+ are likely to be coupled to exocytosis. Ca2+ influx through the Ca2+ channel and protein kinase-A and -C appear not to be involved in mastoparan's hormone-releasing action. Phospholipase-A2 may be involved in the hormone release induced by low, but not high, concentrations of the peptide.

Animals

Evidence of intrathyroidal accumulation of TSH receptor antibody in Graves' disease.

To clarify the intrathyroidal accumulation of TSH receptor antibody (TR-ab) produced in the thyroid, adrenalin was injected directly into the thyroid artery of patients with Graves' disease during surgery, allowing serial determination of the TR-ab levels in the thyroidal venous blood. Nine surgical patients (3M and 6F) with Graves' disease and receiving anti-thyroid drugs preoperatively for a period of one to four years were enrolled in this study. Comparison between pre- and posttreatment TR-ab levels revealed continuous increments from the pretreatment levels within 15 min of the injection in five (55.6%) of the nine patients. In three of the five patients, TR-ab levels that had been negative before adrenalin injection became positive 1 min after injection. It is assumed that the increase in the TR-ab level is due to adrenalin-induced constriction of the capillaries in the thyroid tissues, resulting in a voluminous flow of the TR-ab retained in the thyroid into the vein. These findings indicate that the TR-ab level in the peripheral blood does not necessarily reflect precisely the abnormal immunological condition in the Graves' thyroid.

Adolescent

Ten-year follow-up of Japanese overweight subjects with impaired glucose tolerance: identification of a diabetes-prone subpopulation.

Ninety-four overweight subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) were followed for 10 years. No one from the NGT group developed diabetes, however 32% of the IGT subjects did develop diabetes. Initial data of the IGT subjects who developed diabetes were significantly different from those who did not develop diabetes. Fasting, peak and/or sigma plasma glucose (PG), IRI and CPR at 180 minutes and CPR/IRI at 0 and 180 minutes were increased, and the peak time of PG was delayed; also the prevalence of a positive family history was higher, and the body weight heavier. Seventy-nine percent of IGT subjects with the initial sigma PG of greater than or equal to 40 mM or a positive family history developed diabetes whereas only 3% of those with sigma PG of less than 40 mM and a negative family history developed diabetes. Therefore, it might be considered that among the overweight adults with IGT, those with sigma PG of greater than or equal to 40 mM or a positive family history are diabetes prone and those with sigma PG of less than 40 mM and a negative family history are diabetes resistant.

Adult

Dual functional role of membrane depolarization/Ca2+ influx in rat pancreatic B-cell.

Transient exposure of rat pancreatic B-cell to 50 mM K+ ([K+50]) makes exocytosis unresponsive to further depolarization, i.e., stimulation with 100 mM K+ or 1 uM glyburide, which closes the ATP-sensitive K+ (K+ATP) channel, simultaneously with [K+50] does not produce any greater insulin secretion compared with [K+50] alone. In sharp contrast, 16.7 mM glucose ([G16.7]) applied simultaneously with [K+50] elicits an insulin response markedly greater than that produced by [K+50] alone, which is not attenuated by 100 uM diazoxide, an inhibitor of K+ATP channel closure. [G16.7]-induced insulin secretion at the basal K+ concn of 4.7 mM was greatly (93%) suppressed by 100 uM diazoxide. Insulin secretion induced by [K+50] plus [G16.7] ([K+50 + G16.7]) was markedly suppressed (70%) by 1 uM nifedipine, a Ca(2+)-channel blocker and was completely abolished by 2 mM 2-cyclohexen-1-one, which reportedly decreases reduced glutathione level and blocks glucokinase. This finding indicates that insulin release induced by [K+50 + G16.7] is not due to leakage produced by toxic stimuli but to activation of exocytosis. When graded concentrations (25 and 50 mM) of K+ were applied simultaneously with [G16.7] in the presence of 100 uM diazoxide, insulin response was clearly dependent on K+ concentration, indicating that the physiological range of membrane depolarization also activates the glucose-responsive effector. Membrane depolarization/Ca2+ influx directly stimulates hormone exocytosis on one hand and activates the K+ATP channel-independent glucose-responsive effector or effectors on the other in the B-cell. The nature of the glucose-responsive effector or effectors remains to be established.

Adenosine Triphosphate

Effect of intravitreal injection of norfloxacin on the retina in pigmented rabbits.

The effect of an intravitreal injection of norfloxacin on the retina was evaluated by in-vivo electroretinogram (ERG) and histological examination in pigmented rabbits. The intraocular pharmacokinetics after an intravitreal injection of norfloxacin were also investigated. An intravitreal injection of 50 micrograms norfloxacin produced no significant change in the ERG. An injection of 500 micrograms norfloxacin decreased the amplitude of the oscillatory potentials, and delayed their peak latencies 3 hours after the injection, but these changes recovered within 7 days. A marked suppression of the c-wave was noted in one pigmented rabbit. Neither 50 micrograms nor 500 micrograms norfloxacin caused any apparent changes in the visual evoked potential and in the retinal histology 7 days after the injection. The intraocular pharmacokinetic study showed that the concentration of norfloxacin in the choroid-retina was almost the same level as that in the vitreous body 3 hours after the injection. However, the former was higher than the latter 7 days after the injection, suggesting the persistency of norfloxacin in the choroid-retina. An intravitreal injection of 50 micrograms norfloxacin could be used without retinal toxicity. A high dose-intravitreal use of norfloxacin needs careful attention with respects to its persistency in the pigmented ocular tissues.

Animals

ATP-sensitive K+ channel-independent, insulinotropic action of glucose in the B-cells.

Although closure of the ATP-sensitive K+ (K+ ATP) channel produced by glucose metabolism in the B-cell has been considered mediating the major signal for glucose-induced insulin release, evidences indicating the existence of the K+ ATP channel-independent, insulinotropic action of glucose have recently been accumulated. Namely, glucose stimulates insulin release by the B-cell with a full inhibition of the K+ ATP channel closure by diazoxide, a K+ ATP channel opener, provided cytosolic calcium is elevated. Glucose clearly elicits insulin release even if the K+ ATP channel is maximally inhibited by high concentration of sulfonylurea. In this case, glucose-induced insulin release is associated with net increase, not decrease, of K+ outflow, indicating glucose is opening K+ channels. Thus, closure of the K+ ATP channel is highly unlikely to be the mechanism responsible for the insulinotropic action of glucose under these conditions. The K+ ATP channel-independent glucose action is dependent upon physiological glucose concentration (2-30 mM) and the degree of cytosolic calcium elevation. The K+ ATP channel-independent, glucose-induced insulin release shows gradually increasing monophasic pattern which temporally resembles the second phase response of glucose-induced insulin release. The role of glucose metabolism in the K+ ATP channel-independent glucose action remains to be established. Glucose action at the B-cell can now be subdivided into two classes: one is the K+ ATP channel-dependent and the other is the K+ ATP channel-independent. The two branches may be mutually interrelated to cause normal, biphasic insulin secretion.

Adenosine Triphosphate

Marinesco-Sjögren syndrome with reduced cytochrome c oxidase in muscle.

The present study deals with the sisters of Marinesco-sjögren syndrome without parental consanguinity. Cranial MRI of sisters in a 0.5T superconducting magnet revealed the cerebellar hypoplasia or atrophy, especially in vermis and tonsils with dilatation of IVth ventricle. Microscopic findings of muscle biopsy indicated moderate variation of fibers with phagocytosis, rimmed vacuoles and no ragged red fibers with markedly decreased cytochrome C oxidase activity. 1H-NMR study of urine indicates the secondary decreased turnover rate in urea cycle due to high concentration of 3-hydroxy-n-butyrate.

Biopsy

Thyroid function in premature infants.

The present study was performed using the simultaneous assays of free T4 and TSH levels in dried blood spots of filter paper for mass-screening of inborn errors of metabolism in order to clarify the thyroid function of premature infants. The subjects were divided in three groups: A group infants less than 1500 g at birth (n = 34, 27.4 +/- 2.6 weeks of gestational age), B group infants from 1500 to 2500 g at birth (n = 104, 35.6 +/- 2.4 weeks) and C group infants over 2500 g at birth (n = 490, 39.0 +/- 1.2 weeks). TSH levels were 4.51 +/- 3.03, 2.62 +/- 2.24 and 2.84 +/- 2.06 microU/ml in A, B and C group respectively and significant difference was recognized in group A and C. Free T4 levels were 0.71 +/- 0.42, 1.81 +/- 0.96 and 2.15 +/- 0.67 ng/dl, in group A, B and C respectively, and significant differences were recognized in all three groups. There was positive correlation between free T4 levels and gestational ages (Y = -2.413 +/- 0.11725X, r = 0.206, p less than 0.05).

Humans

[A clinical study of the significance of the gradient between feeding arterial tissue polypeptide antigen (TPA) and draining venous TPA in assessing the risk for recurrent breast cancers].

The incidence of postoperative recurrence of primary breast cancers in 73 patients was correlated with the blood levels of tissue polypeptide antigen (TPA) in peripheral veins (V-TPA), feeding arteries (A-TPA), draining veins (V-TPA) and the gradient between the TAP levels in draining veins and feeding arteries (V-A TPA). With progression in the stage of the cancers, all parameters were increased. In stages II and III, the mean level of V-TPA was significantly higher than the mean level of A-TPA (p less than 0.05). In each stage, each parameter was increased in the patients with recurrences when compared with the levels in the patients with no recurrences. In patients with V-A TPA gradients greater than 30 U/L, the rate of recurrence was significantly higher when compared with patients with gradients less than 30 U/L (p less than 0.05). The clinical significance of this finding is that patients with V-A TPA gradient greater than 30 U/L should be closely followed because of the increased risk of recurrences.

Breast

[An autopsied case of papillary thyroid carcinoma showing DNA heterogeneity-comparison of DNA content between primary focus and metastatic focus].

A 56-year-old female case of papillary thyroid carcinoma is reported. Nuclear DNA analysis using flow cytometry and immuno-histological staining with thyroglobulin, CA19-9 and CA125 of the primary and metastatic foci from the autopsy specimens were performed. Correlation between ploidy patterns and immuno-histological staining was not found. Although two histogram patterns namely DNA diploid (DP) and aneuploid (AP) with DNA index of 1.3 were seen in primary, sternal and lung metastatic foci, only DP pattern was seen in the lymph node metastatic foci.

Antigens, Tumor-Associated, Carbohydrate