[Acceleration plethysmogram].
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Diabetic Foot↗
Biomedical subjects
K Kosugi
Publications and source records attributed to K Kosugi.
[Prolonged neuromuscular blockade with vecuronium in patient with triple pregnancy treated with magnesium sulfate].
A 33 year-old parturient with triplet pregnancy underwent emergency cesarean section at 35 week of gestation under general anesthesia. The patient had received magnesium sulfate to prevent uterine contraction immediately before the cesarean section. Although serum magnesium value was not beyond therapeutic levels (3.3 mEq.l-1), the neuromuscular blocking effects with vecronium were strengthened. It was not likely that volatile anesthetic enhanced neuromuscular blockade produced by vecuronium because the onset time of vecuronium had already been faster than that in pregnant patients untreated with magnesium before she was exposed to isoflurane. In addition, it is possible that magnesium could interfere with postpartum uterine contractions because of its tocolytic properties. Magnesium sulfate therapy has several implications to anesthetic agents. We, anesthesiologists, should know about the biophysiological effects of magnesium and control the interaction between anesthetic agents and this electrolyte.
Adult↗
Supernumerary head of biceps brachii and branching pattern of the musculocutaneus nerve in Japanese.
Out of 546 upper limbs (273 cadavers), supernumerary heads of the biceps brachii were found in 75 limbs (13.7%) of 58 cadavers (21.3%). The form, origin, and insertion of the supernumerary heads, and branching pattern of the musculocutaneus nerve were studied. In addition, the dimensions of the heads were measured. In many cases, the supernumerary head arose from the humerus, between the insertion of the coracobrachialis and the upper part of the origin of the brachialis, and/or from the medial intermuscular septum. In a few cases, a supernumerary head arose from the tendon of the pectoralis major or the deltoid, or from the articular capsule, or from the crest of the greater tubercle. The supernumerary heads typically joined the common belly, or the aponeurosis of the biceps brachii. Some heads joined the belly of the long head or that of the short head. In the examination of the branching pattern of the musculocutaneus nerve, communication between the musculocutaneus nerve and the median nerve was found in 43 out of the 75 limbs (57.3%). The communicating branch ran from the musculocutaneus nerve to the median nerve in 24, from the median nerve to the musculocutaneus nerve in 12, in both directions in 5, or in another type of pattern in 2 out of 43 limbs. Sometimes a branch of the musculocutaneus nerve ran around a supernumerary head and then fused with the present trunk. The presence of a supernumerary head seemed to affect the course and branching of the musculocutaneus nerve.
Arm↗
Hyperlipidemia and atherosclerosis in experimental insulinopenic diabetic monkeys.
Chronic insulinopenic diabetes was induced by i.v. streptozotocin in the non-human primate Macaca fuscata. Five diabetic monkeys were kept for 8-19 months and nine for 24-48 months without any insulin treatment. Hyperglycemia (241 +/- 22 mg/dl, M +/- SE less than or equal to 1 year) progressed to 376 +/- 34 mg/dl (greater than 2 years) and ketosis to 3.5 mM (greater than 2 years) during the course of diabetes; this was roughly inversely proportional to hypoinsulinemia (3.4 microU/ml, 2 years). Serum cholesterol increased from 184 +/- 11 (less than or equal to 1 year) to 328 +/- 66 mg/dl (greater than 2 years) with the major increase in LDL-cholesterol (2.7-fold over control, greater than 2 years). HDL-cholesterol did not change at all throughout the experimental period. TG increased from 144 +/- 25 (less than or equal to 1 year) to 676 +/- 116 (greater than 2 years) with a major increase in the VLDL fraction (15-fold over control, greater than 2 years). Serum levels of apo B increased to 141 +/- 16 (less than or equal to 2 years) and 223 +/- 8 mg/dl (greater than 2 years) in contrast to control, 73 +/- 2. Morphologically, lipid deposition in the intima and fatty streaks have been observed in the abdominal aorta of all the diabetic monkeys with duration of more than 2 years. In six of the diabetic monkeys atheromatous changes such as intimal and medial thickening with smooth muscle cell proliferation were observed with foam cell formation. Similar atherosclerotic lesions were observed in renal and coronary arteries in at least six of these monkeys. In diabetic monkeys with duration of less than 2 years, mild atherosclerotic lesions were observed in two out of five. The results indicate that long standing insulinopenia leads to metabolic derangements characterized by hyperglycemia, ketonemia and hyperlipidemia. Elevation of LDL-cholesterol and VLDL TG with an increase of apo B is a characteristic of lipoprotein disorder. Morphologically, early to moderately advanced lesions of atherosclerosis were observed in aorta, renal and coronary arteries as a result of metabolic derangement due to insulin deficiency.
Animals↗
Increased ketogenesis related to insulin deficiency in isolated hepatocytes from NIDDM model rats.
To investigate the hepatic ketone body metabolism in NIDDM, we studied the ketone body production rates in hepatocytes from newly developed non-obese NIDDM model rats. NIDDM model rats were prepared by intraperitoneal injection of streptozotocin at 2 or 5 days of age (STZ2, STZ5 respectively). After 10-15 weeks, ketone body production rates in hepatocytes isolated from these rats were compared with those from control rats as well as ketotic rats made by intravenous injection of streptozotocin into adult rats. Basal ketone body production rates from 0.3 mM [U-14C] palmitate in hepatocytes from control, STZ 2, STZ 5 and ketotic rats were 11.7 +/- 0.98, 14.9 +/- 0.72, 16.0 +/- 0.45, 22.8 +/- 2.32 nmole.palmitate/mg.prot/hr, respectively. These rates were stimulated by 1 microgram/ml of glucagon in control, STZ 2 and STZ 5 rats (14.1 +/- 0.99, 18.6 +/- 1.36, 18.7 +/- 0.69 nmole.palmitate/mg.prot/hr, respectively), but not in ketotic rats (22.8 +/- 2.07 nmole.palmitate/mg.prot/hr). The similar effects were observed by 1 microgram/ml of epinephrine. The basal ketone body production rates were negatively correlated to both hepatic glycogen contents and plasma IRI levels. Considering these parameters together, the extent of metabolic derangement in STZ 2 and STZ 5 rats was between that in control and ketotic rats. These results indicate that the derangements of hepatic ketone body production are related to the severity of insulin deficiency and suggest that the enhanced hepatic ketogenesis contributes in part to the elevated plasma ketone body levels in non-obese NIDDM.
Animals↗
[Retroperitoneal giant malignant fibrous histiocytoma: report of a case].
A case of histiocytoma in a 63-year-old woman with general fatigue is described. Ultrasonography and radiological examination revealed a large mass at the retroperitoneum displacing the right kidney to medial anterior abdomen. Exploration of the tumor with right kidney was done via a transperitoneal approach because the tumor had invaded the hilar fat tissue of the right kidney. The total resected weight was 3,200 g. Histological study showed malignant fibrous histiocytoma, storiform-pleomorphic type. Post-operative chemotherapy consisting of cyclophosphamide, vincristine, adriamycin, dimethyl triazeno-imidazole carboxamide (CYVADIC) was performed and the patient is doing well without any evidence of recurrence or metastasis.
Antineoplastic Combined Chemotherapy Protocols↗
In vitro stimulation of glucose utilization by insulin in primary cultures of rat hepatocytes.
The effect of glucose concentration and insulin on glucose incorporation was studied in primary cultures of rat hepatocytes. The rate of glucose incorporation into hepatocytes was proportional to the medium glucose concentration from 100 to 800 mg/dl. At 800 mg/dl glucose the rate reached a plateau. Of the glucose taken up by hepatocytes, 16 and 18% was incorporated into glycogen and lipid, respectively, and 58% into the nucleotide fraction after incubation for 4 h. In the medium, lactate was the major product found. Insulin stimulates glucose incorporation by 20-112% into all the above pathways at glucose concentrations between 100 and 800 mg/dl. The insulin effect was noted as early as 2-4 h (early effect) and up to 24 h (delayed effect). This effect of insulin was observed to be dose dependent from 5 to 200 ng/ml insulin. While the delayed insulin effect was abolished by cycloheximide, the early effect of insulin was not affected. With respect to the key enzyme activities of glucose utilization, activation of glycogen synthase (increase of I-activity/total activity) and pyruvate kinase (activation at 0.2 mM phosphoenolpyruvate) was noted 4 h after insulin addition, and these effects were not abolished by cycloheximide. These two enzymes increased in total activity after 24 h. Both glucokinase and glucose-6-phosphate dehydrogenase activities increased by 30-35% and 65-93% at 4 and 24 h, respectively. The results indicate that hepatocytes directly utilize glucose in a dose-dependent manner with respect to glucose and insulin. A major early and delayed effect of insulin appeared due to the activation and induction of the key hepatic enzymes of glucose utilization, respectively.
Animals↗
M. cervico-humeralis--a case report.
An abnormal muscle, so-called M. cervico-humeralis, was found bilaterally in a 50-year-old Japanese male in a dissection practice at Jikei University in 1989. This is the third report of the cervico-humeral muscle in Japan, and the first case which occurred bilaterally. Both muscles were similar in shape, origin, course, and insertion. The flat and triangular-shaped muscle arose by tendinous slips from the transverse processes of the sixth and seventh cervical vertebrae (VC6 and VC7). These two tendons converged to form a single slip which passed through the brachial plexus. This single slip became a muscle running obliquely downward and laterally together with the brachial plexus and subclavian vessels to reach the medial surface of the humerus. The muscle inserted linearly by a thin flattened tendon into the lower end of the lesser tubercle and into the medial lip of the intertubercular sulcus of the humerus. The supplying nerve originated directly from the posterior cord of the brachial plexus in both muscles. The artery to the right cervico-humeral muscle arose from the axillary artery together with a branch to the subscapular muscle.
Cervical Vertebrae↗
Effect of long-term hindlimb suspension on blood components.
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Adaptation, Physiological↗
Development of stable film test for rapid estimation of blood or plasma 3-hydroxybutyrate.
A film test for the rapid detection of plasma/serum 3-hydroxybutyrate (3-OHB) has been developed. The film contains NAD, nitro blue tetrazolium, 3-OHB dehydrogenase, and diaphorase, and the surface is coated with modified biomembrane and can detect 50-1500 microM 3-OHB within 2-3 min. One drop or 50 microliters of plasma/serum or blood is applied to the film, and the violet color is read via reflectance meter after 2 min. Plasma/serum samples greater than 1500 microM 3-OHB can be measured by dilution with saline. In blood with 40% hematocrit, the color developed is 50% less than with plasma/serum, and this was adjusted in the reflectance meter. A good correlation (r = 0.99) was observed between results with automated and film methods and between visual methods and reflectance meter. In insulin-dependent diabetes mellitus, all 3 subjects with positive ketonuria (+ +), 8 of 12 subjects with mild ketonuria (+), and 7 of 25 subjects without ketonuria exhibited elevation of 3-OHB in blood greater than 200 microM. The results indicate that 3-OHB film is valuable not only in the emergency room for the differential diagnosis between ketoacidotic and nonketotic hypersomolar coma but also as a marker for insulin dependency, energy dependency on fatty acid compared with glucose, and metabolic control of diabetes.
3-Hydroxybutyric Acid↗
[Clinical significance of blood ketone body analysis in the diagnosis of diabetic diseases and analytical methods].
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Aged↗
Sex differences in blood constituents of rats following tail suspension.
Tail suspension was utilized to study sex differences in the effects of hypokinesia on blood constituents of rats. Twelve male and twelve female rats were used. After four weeks of exposure to tail suspension or non-treatment, the rats were laparotomized under ether anesthesia and blood samples were obtained. Biochemical tests on the blood samples were then performed immediately. Hematocrit and serum iron were also estimated. The results were as follows: 1) The same tendencies were noted in blood constituents between male and female rats in the control group and the tail suspension group. 2) The average levels of blood albumin, creatinine, uric acid, glucose, triglyceride, serum iron and hemoglobin in the tail suspension group were lower than those in the control group, especially in male rats.
Animals↗
Increased plasma plant sterol levels in heterozygotes with sitosterolemia and xanthomatosis.
Plasma sterol levels in a family of sitosterolemia and xanthomatosis were determined by a high performance liquid chromatography. Three affected siblings manifested marked xanthomatosis including subcutaneous soft tissues and generalized atherosclerosis. Two other siblings as well as children of the patients did not show such clinical symptoms and signs. Plasma levels of cholesterol, sitosterol, campesterol, and cholestanol in three affected subjects were 190 +/- 18.5, 25.9 +/- 11.6, 16.1 +/- 7.8, 1.84 +/- 0.92 mg/dl (mean +/- SD), respectively. Four daughters of the affected subjects, who should be considered as obligatory heterozygotes, showed moderately increased levels of these sterols (195 +/- 41.7, 1.33 +/- 0.44, 1.56 +/- 0.69, 0.80 +/- 0.28 mg/dl), which were significantly higher than those of normal subjects. Treatment with cholestyramine had little effect on the increased plasma plant sterol levels, but markedly decreased plasma cholestanol concentrations in two affected siblings. This report presents the clinical features of the patients with sitosterolemia and xanthomatosis and also demonstrates that heterozygotes with this disorder have increased plasma levels of plant sterols as well as cholestanol, and suggests that this rare disease might be inherited as an autosomal co-dominant trait in certain cases. The data also indicate that cholestyramine administration was not effective in this family for treatment of sitosterolemia.
Adult↗
Chronically streptozocin-diabetic monkey does not closely mimic human diabetic neuropathy.
In order to evaluate the value of diabetic Japanese monkeys (Macaca fuscatus) as an animal model for studying the pathogenesis of diabetic neuropathy, morphological examinations were performed on myelinated nerve fibers and endoneurial microvessels at three levels of the lower limb nerve in eight streptozocin (STZ)-diabetic monkeys with the duration of diabetes up to 36 months and in four roughly age-matched control monkeys using a computer-assisted image analyzer. Nerve fiber loss was not found, although a tendency for nerve fiber atrophy was found in diabetic monkeys. Endoneurial microvessels did not show either endothelial or pericyte proliferation or basement membrane thickening. The results suggest that chronically STZ-diabetic Japanese monkeys with the duration of diabetes up to 36 months might be useful for studying diabetic axonopathy, but do not closely mimic the nerve pathology found in human diabetic neuropathy.
Animals↗
[Significance of ketone body analysis in clinical tests].
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Chromatography, Gas↗
Toxicity of oxidized low-density lipoprotein to cultured fibroblasts is selective for S phase of the cell cycle.
Oxidized LDL (o-LDL) is toxic to a variety of cultured cells. Preliminary results suggested that susceptibility is enhanced by cell proliferation. As a step toward determining the mechanism of cytotoxicity, we chose to identify the cell cycle phase(s) during which exposure of cultured human fibroblasts to o-LDL leads to death. Cytochalasin B, which blocks cell migration and proliferation, and irradiation, which prevents mitosis but not migration, both blocked cytotoxicity. Colchicine, which arrests cells in mitosis but does not inhibit DNA synthesis, did not block cytotoxicity. Treatment of cells with hydroxyurea, which blocks cells prior to S phase, prevented cell death. Addition of o-LDL to cells immediately after S phase allowed mitosis without death. The above results coupled with results using cells synchronized by three different means indicate that cell death is selective for proliferating cells and occurs after exposure to o-LDL during S phase. Understanding the mechanism of o-LDL-induced death may have implications for tissue damage in vivo in the numerous instances of pathology in which oxidized lipoproteins or lipids are present.
Cell Cycle↗
Study of insulin response to oral glucose load after acute and chronic glycemic control in type 2 diabetic subjects.
To investigate whether correction of fasting hyperglycemia per se improves the insulin secretion in type 2 diabetic subjects, plasma insulin response to 75 g oral glucose load has been studied after acute and chronic normalization of fasting plasma glucose levels in 7 overt type 2 diabetic subjects. For the acute normalization of elevated fasting plasma glucose levels, an artificial endocrine pancreas was employed. Although fasting plasma glucose concentrations were normalized before the oral glucose challenge, insulin response to oral glucose was not improved compared to those without normalization of fasting plasma glucose levels. After 1-3 month control of hyperglycemia, the insulin response to glucose in the subjects was significantly improved compared to those without treatments. Results indicate that chronic metabolic control is essential for the improvement of insulin response to glucose in type 2 diabetic subjects, and also suggest that the impaired insulin secretion in type 2 diabetes is not due to hyperglycemia per se, but due to the metabolic derangements which lead to chronic hyperglycemia.
Adult↗
Determinants in the pathways followed by the carbons of acetone in their conversion to glucose.
[2-14C]Acetone was infused into rats that were fed or fasted. Each was infused with either a trace quantity of acetone or a large quantity that resulted in a blood concentration of acetone of at least 4 mM. The distribution of 14C in the carbons of glucose from each rat was determined. Two of the rats were given acetone in their drinking water and one was diabetic. Whether a rat was chronically exposed to acetone, fed or fasted, normal or diabetic, if given the trace dose, over 80% of the 14C in the glucose it formed was in carbons 1, 2, 5, and 6 of the glucose. If a rat was given the large dose, about 50% was in carbons 3 and 4. Thus, the major determinant of the pathways followed by acetone when it is metabolized is its concentration and not the prior dietary state of the animal or its previous exposure to acetone. Incorporation into carbons 1, 2, 5, and 6 occurs in the conversion of the carbons of [2-14C]lactate into glucose, whereas incorporation into carbons 3 and 4 occurs in the conversion of the carbons of [1-14C]acetate into glucose. Therefore, at high acetone concentration, the pathway that has been proposed for acetone's metabolism via acetate predominates, and via acetate there can be no net synthesis of glucose from acetone. When rats were given cyanamide and then the large dose of acetone, 74% of the 14C in the glucose they formed was in carbons 3 and 4 of the glucoses. Thus, the relative contribution of the pathway to lactate, or its metabolic equivalent, that has been proposed appears to be lessened by the administration of an aldehyde dehydrogenase inhibitor.
Acetates↗