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Biomedical subjects

K Sakuma

Publications and source records attributed to K Sakuma.

At least 73 records · Page 4Linked to original sources
PubMed1996

Dietary control of lactase expression in the weaning rat.

The decline in lactase activity during weaning has been well established. However, its molecular mechanism remains to be explored. We studied changes in the expression of lactase in terms of the transcription and translation processes in rat microvillus membrane by Northern blot and Western blot analysis, respectively. To examine the effect of dietary change from a milk to a non-milk diet on the developmental pattern of lactase expression, weaning was prevented by keeping the rats under suckling conditions for 27 days after birth. This treatment only suppressed the extent of decline: while the weanlings showed 17 percent activity compared to that of 4-day-old rats, the prolonged suckling rats showed only 42 percent. The changes in the expression of lactase mRNA and protein were parallel with the change of lactase activity. In other words, the fundamental pattern of significant depression of lactase expression occurred relatively independent of dietary modification. This observation indicates that the regulation of lactase expression is firmly determined at the transcriptional level, and that dietary factor such as the termination of lactose ingestion has only a relatively minor effect.

Animals↗
PubMed1995

Are region-specific changes in fibre types attributable to nonuniform muscle hypertrophy by overloading?

Muscle fibre composition was compared among the proximal (25%), middle (50%) and distal (75%) regions of the muscle length to investigate whether compensatory overload by removal of synergists induces region-specific changes of fibre types in rat soleus and plantaris muscles. In addition, we evaluated fibre cross-sectional area in each region to examine whether fibre recruitment pattern against functional overload is nonuniform in different regions. Increases in muscle mass and fibre area confirmed a significant hypertrophic response in the overloaded soleus and plantaris muscles. Overloading increased the percentage of type I fibres in both muscles and that of type IIA fibres in the plantaris muscle, with the greater changes being found in the middle and distal regions. The percentage of type I fibres in the proximal region was higher than that of the other regions in the control soleus muscle. In the control plantaris muscle, the percentage of type I and IIA fibres in the middle region were higher than that of the proximal and distal regions. With regard to fibre size, type IIB fibre area of the middle and distal regions in the plantaris increased by 51% and 57%, respectively, with the greater changes than that of the proximal region (37%) after overloading. These findings suggest that compensatory overload promoted transformation of type II fibres into type I fibres in rat soleus and plantaris muscles, with the greater changes being found in the middle and distal regions of the plantaris muscle.

Adaptation, Physiological↗
PubMed1995

Nonuniform changes in fibre types in the soleus muscle of the developing rat.

Muscle fibre composition among the proximal (25%), middle (50%) and distal (75%) regions of the rat soleus muscle at various ages were compared to investigate whether the region-specific changes in fibre types known to occur under nonphysiological conditions (i.e. electrical stimulation along with immobilization in a lengthened position) also occur in the developing muscle. In addition, we attempted to detect fibres with nonuniform histochemical properties in the different segments, processing with myofibrillar actomyosin adenosine triphosphatase after pre-incubation at pH 10.3 against successive cryosections (200 microns apart). Samples were obtained from 66 Wistar rats of both sexes ranging in age from 13 to 85 days and subdivided into age groups of 2, 3, 4, 5 and 12 weeks. The mass and length of the soleus muscle increased most significantly at age 3-4 and 2-4 weeks, respectively. The distal region had a significantly lower percentage of type I fibres than the middle region at age 3 weeks, than the proximal and middle regions at age 4 weeks. In addition, some fibres [0.7 (SD 0.5)% n = 19 +/- 13] possessing nonuniform histochemical properties in different segments were observed from the middle and distal region at age 4 weeks. These findings would suggest that transformations from type II to type I fibres in the soleus muscle of the developing rat occur from the proximal or middle segments.

Aging↗
PubMed1995

Shortened silent period produced by magnetic cortical stimulation in patients with Parkinson's disease.

Magnetic cortical stimulation can produce silent periods (SP) following excitatory motor responses. In patients with Parkinson's disease (PD), a shorter SP was observed. The shortened SP in PD patients improved after levodopa administration. This shortened SP in PD patients may be related to the hyperactivity of the motor cortex, and to the dopaminergic system. In control subjects, sound stimulation produced prolongation of the SP at a time interval of 100 ms between sound and magnetic cortical stimulation-increase in the inhibitory function. However, the prolongation of the SP after sound stimulation was not observed in PD patients lack of an increase in the inhibitory function. Even after levodopa administration, sound did not prolong the SP in PD patients. The change of the auditory effects on the SP may be due to the abnormal function of the reticular formation in PD. This change might be independent of the dopaminergic system.

Acoustic Stimulation↗
PubMed1995

Oxidative enzyme activity in the rat soleus muscle and its motoneurons during postnatal maturation.

The effect of postnatal maturation on changes in the oxidative enzyme (succinate dehydrogenase) activity in the rat soleus muscle and its motoneurons was examined at 3, 6, and 12 weeks of age. The motoneurons innervating the soleus muscle were identified using the fluorescent retrograde neuronal tracer Nuclear Yellow. An inverse relationship between soma size and oxidative enzyme activity of soleus motoneurons was observed at 3 and 6 weeks of age, whereas there was no correlation between them at 12 weeks. Although the oxidative enzyme activity in the soleus muscle increased during postnatal maturation, it showed a decrease in the soleus motoneurons. These data demonstrate that the inverse relationship between soma size and oxidative enzyme activity of rat soleus motoneurons can only be detected in the early postnatal period and that the oxidative enzyme activity in the rat soleus muscle and its motoneurons can change independently during postnatal maturation.

Age Factors↗
PubMed1995

Relationship between tissue ischemia and venous endothelin-1 during abdominal aortic aneurysm surgery.

OBJECTIVES: Several substances may be released from ischemic tissues with the declamping shock that occurs during abdominal aortic aneurysm surgery. To clarify the relationship between tissue ischemia and venous endothelin-1 (ET-1) level in humans, plasma ET-1 and oxygen content in the iliac vein were measured before anesthesia, after the induction of anesthesia, after the release of the proximal and first distal clamps, after the release of the second distal clamp, and 1 hour after the second clamping. DESIGN: Prospective study. SETTING: A University hospital. PARTICIPANTS: Seven patients who underwent abdominal aneurysmectomy and replacement with bifurcated graft. INTERVENTIONS: A 20G catheter was inserted into the radial artery for the direct measurement of blood pressure and for collecting arterial blood. An 18G, 20-cm catheter was inserted into the femoral vein for collecting venous blood from the lower extremities. MEASUREMENTS AND MAIN RESULTS: The arterial and venous ET-1 levels did not change after the induction of anesthesia. Immediately after the initial release of the proximal and distal clamps, venous oxygen content dramatically decreased from 11.3 to 3.6 mL/dL (vol%) with significant increases in venous ET-1 concentration from 2.3 to 4.9 pg/mL. Concomitant with the decrease in venous oxygen content, venous plasma pH and base excess decreased with increase in PCO2, suggesting that ischemic changes in tissues distal to the cross-clamp may occur during aortic clamping. Venous ET-1 levels were significantly correlated with venous oxygen content, pH, PO2, oxygen saturation, base excess, blood sodium concentration, and potassium concentration. One hour after the second declamping, the venous ET-1 level remained high in comparison with the preanesthetic level, whereas the venous oxygen content returned to the preanesthetic level. There was no correlation between venous plasma ET-1 and venous plasma norepinephrine or epinephrine concentration. CONCLUSIONS: Tissue ischemia may increase venous ET-1 levels in humans. Factor(s) other than tissue ischemia may provoke the increase in venous ET-1 that occurs after the release of the second distal clamp.

Aged↗
PubMed1995

Prolonged silent periods produced by magnetic cortical stimulation in patients with cerebellar ataxia.

Magnetic cortical stimulation can produce silent periods (SP) following excitatory motor responses. The SP in eight patients with cerebellar ataxia was examined. The onset latency of the SP in hand muscles after magnetic cortical stimulation was not different from that in control subjects. The duration of the SP was longer than that in control subjects, but the difference was not significant statistically. The end latency of the SP in patients with cerebellar ataxia was more prolonged than that in control subjects. Therefore, the inhibitory function may be enhanced in patients with cerebellar ataxia.

Aged↗
PubMed1995

[The effects of prostaglandin E1 and epidural anesthesia on peripheral blood flow].

We compared the effects of prostaglandin E1 (PGE1) and epidural anesthesia on peripheral blood flow by laser Doppler tissue flowmetry during lower abdominal surgery. Epidural anesthesia increased the blood flow of the toe, where the sympathetic nerve supply is of the same spinal cord segments as that of pelvic organs. On the other hand, PGE1 could not prevent the decrease of the blood flow of the toe, but increased that of the index finger, which did not receive the nociceptive stimuli from operative site. Thus, the use of epidural anesthesia together with PGE1 is considered to be effective to increase peripheral blood flow.

Abdomen↗
PubMed1994

D-myo-inositol 1,4,5-trisphosphate binding domain of phospholipase C-delta 1.

D-myo-Inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) binding domain of phospholipase C-delta 1 (PLC-delta 1) was determined by examining binding activity of the synthetic peptide corresponding to residues 30-43 of PLC-delta 1. The peptide coupled with carrier proteins such as keyhole limpet hemocyanin or bovine serum albumin bound Ins(1,4,5)P3, whereas a scrambled peptide with the same amino acids did not do so. Polyclonal antibody against the peptide was examined to determine whether it would cause inhibition of the Ins(1,4,5)P3 binding to PLC-delta 1. Fab fragment of antibody to the peptide did inhibit binding to PLC-delta 1, in a dose-dependent manner. Thus it seems likely that the region of residues 30-43 of PLC-delta 1 is responsible for the binding of Ins(1,4,5)P3.

Amino Acid Sequence↗
PubMed1994

Expression and characterization of an inositol 1,4,5-trisphosphate binding domain of phosphatidylinositol-specific phospholipase C-delta 1.

It was previously found that the 85-kDa protein purified from rat brain using an inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-immobilized matrix was the delta 1 isoform of phosphatidylinositol-specific phospholipase C (PLC). We expressed rat PLC-delta 1 in Escherichia coli as a fusion protein with glutathione S-transferase, and found that the bacterial lysate shows a significant amount of Ins(1,4,5)P3 binding. The lysate was applied to Ins(1,4,5)P3-immobilized column chromatography and the eluate with 2 M NaCl solution containing only a 100-kDa protein showed high Ins(1,4,5)P3 binding. The lysate was also purified to near homogeneity using a glutathione-Sepharose 4B affinity system. Bacterially-expressed enzyme thus purified showed essentially the same inositol phosphate binding characteristics as the brain-derived enzyme. PLC-delta 1 consists of the amino-terminal nonconserved region and two well-conserved regions among isozymes, designated as X and Y, which are thought to constitute a catalytic core of the enzyme. Using a combination of deletion mutants and proteolytic products of the enzyme, we were able to locate an Ins(1,4,5)P3 binding domain in the molecule. Deletion of 223 residues from the amino terminus completely abolished the binding activity, while deletion of X region only partially inhibited the binding and deletion of Y region did not affect the binding. A 76-kDa proteolytic product of the expressed PLC-delta 1 which lacked 60 amino acids at the amino terminus showed a minimal Ins(1,4,5)P3 binding activity. A peptide consists of 14 amino acids corresponding to residues 30-43 of PLC-delta 1, which contains 6 basic amino acids, binds to an Ins(1,4,5)P3-immobilized matrix. Moreover, Ins(1,4,5)P3 binding was blocked by phospholipid vesicles containing phosphatidylinositol 4,5-bisphosphate. These results, taken together, indicate that the amino-terminal domain of PLC-delta 1 is important for the binding of both Ins(1,4,5)P3 and phosphatidylinositol 4,5-bisphosphate.

Amino Acid Sequence↗
PubMed1994

Hypoxia modifies the vasodilatory effects of nitroglycerin, prostaglandin E1, and hydralazine on isolated porcine coronary arteries.

To evaluate the potency of vasodilatory drugs in hypoxia, we studied the effects of nitroglycerin (NTG), prostaglandin E1 (PGE1), and hydralazine on porcine coronary artery constricted with endothelin-1 (ET-1) in both oxygenated and hypoxic conditions. Removal of endothelium potentiated NTG-induced relaxation in oxygenated conditions. Hypoxia potentiated relaxation of endothelium-intact arteries induced by NTG, but not relaxation of endothelium-denuded arteries. These findings suggest that hypoxia may modify endothelial function in NTG-induced relaxation. The relaxation of endothelium-intact and -denuded arteries induced by PGE1 in hypoxia was significantly greater than that in the oxygenated condition. PGE1 significantly increased the content of cyclic AMP in the hypoxic condition; it was much greater than that in the oxygenated condition, suggesting that hypoxia may enhance PGE1-induced relaxation by increasing cyclic AMP levels. Hypoxia attenuated hydralazine-induced relaxation in both endothelium-intact and denuded arteries. Indomethacin and aspirin attenuated hydralazine-induced relaxation in the oxygenated condition, suggesting that cyclooxygenase-related eicosanoid(s) may be involved in hydralazine-induced relaxation. However, indomethacin did not alter relaxation of hypoxic arteries induced by hydralazine. These findings suggest that hypoxia may inactivate cyclooxygenase in hydralazine-induced relaxation. Hypoxia may greatly modify the action of vasodilators on porcine coronary smooth muscle.

Alprostadil↗
PubMed1994

Effects of tizanidine administration on exteroceptive suppression of the temporalis muscle in patients with chronic tension-type headache.

The aim of this study was to clarify the changes of inhibitory interneuronal activity in patients with chronic tension-type headache with disorder of pericranial muscle after treatment, and the pharmacological mechanisms of tizanidine--an alpha 2 adrenergic agonist. The effects of tizanidine on exteroceptive suppression (ES) of the temporalis muscle were examined in eighteen patients with chronic tension-type headache with disorder of pericranial muscles, before and two weeks after the administration of tizanidine. The left mental nerve was stimulated, under the maximal voluntary contraction of the temporalis muscles. Two types of stimulation were used: weak stimulation with four times the sensory threshold, and strong stimulation with 10 times the sensory threshold. The rectified electromyographic activity was recorded from the right temporalis muscle. ES2 produced by four times the sensory threshold was lengthened after tizanidine administration. This fact suggests that tizanidine improves the inhibitory function in the central nervous system, and then relieves headache. However, ES produced by 10 times the sensory threshold did not change. This suggests that the effect of tizanidine may be relatively mild. The interneurones mediating ES2 may be modified by the alpha 2 agonist.

Clonidine↗
PubMed1993

Modification by CO2 of endothelin-1-induced contraction of isolated guinea pig trachea.

To investigate the effect of changes in CO2 tension on airway smooth muscle tone induced by various agonists, contractile responses to acetylcholine, histamine and endothelin-1 (ET-1) were studied in isolated guinea pig tracheae at very low PCO2 (16 +/- 0 mmHg, n = 38), moderately low PCO2 (28 +/- 0 mmHg, n = 23), normal PCO2 (38 +/- 1 mmHg, n = 70) or high PCO2 (94 +/- 1 mmHg, n = 32). The minimum concentration of ET-1 (10(-10) M) needed to induce contractions was lower than that of acetylcholine (10(-7) M) and histamine (10(-7) M) at normal PCO2. Changes in PCO2 did not significantly affect acetylcholine- or histamine-induced contractions. In contrast, very low and moderately low PCO2 attenuated the contractions induced by ET-1, but high PCO2 potentiated those induced by a high concentration of ET-1. Very low PCO2 with normal pH and with high pH attenuated the contractions caused by ET-1, whereas normal PCO2 with high pH did not. These results suggest that ET-1-induced airway smooth muscle contraction can be modified by PCO2 per se. Aspirin and indomethacin potentiated the responses to ET-1 at very low PCO2 more than at normal PCO2, but attenuated the responses to low concentration of ET-1 at high PCO2. These results also suggest that cyclooxygenase-related eicosanoids are involved in the effects of PCO2 on ET-1-induced contractions.

Acetylcholine↗
PubMed1993

Stress fracture of the proximal phalanx of the great toe.

Three cases of stress fracture of the proximal phalanx of the great toe occurring in a 12-year-old female volleyball player, a 17-year-old female long distance runner, and a 12-year-old male soccer player are reported. This condition probably develops after repeated forced dorsiflexion of the first metatarsophalangeal joint with changing steps. When athletes who repeatedly run and jump complain of pain in the first metatarsophalangeal joint, and there is no history of trauma, this condition should also be considered.

Adolescent↗
PubMed1993

Hereditary lipo-muscular atrophy with joint contracture, skin eruptions and hyper-gamma-globulinemia: a new syndrome.

We previously reported two siblings with decreased subcutaneous adipose tissue, muscular atrophy, joint contractures, recurrent skin eruptions, hyper-gamma-globulinemia, and reduced natural killer cell activity. Some of their clinical features are similar to those of partial lipodystrophy, but they are distinct in that muscular atrophy, joint contractures and recurrent skin eruptions are not found in patients with partial lipodystrophy. Thirteen other Japanese patients with similar clinical manifestations have been reported. We propose that such cases should be considered a distinct clinical entity.

Contracture↗
PubMed1993

[Effects of intravenous injection of ioversol, a nonionic contrast medium, on circulating blood volume: comparison among different combinations of its dose and volume injected].

Effects on circulating blood volume (CBV) of the intravenous injection of a nonionic contrast medium, ioversol, with various doses were assessed in order to find a way of injection with less effects on systemic circulation. Ioversol was injected as a bolus to 20 mongrel dogs at doses of A: 3.75 ml/kg (n = 8) or B: 2 ml/kg (n = 6) of a solution containing 320 mg iodine per ml, or C: 2 ml/kg (n = 6) of a 240 mgI/ml solution. Colloid oncotic pressure (COP) of the bloods drawn before and 1, 2, 3, 5 min after the injection of ioversol was measured by a needle type osmometer, and changes in CBV were calculated using the COP values. Upon injection of ioversol CBV increased rapidly and then gradually returned to the preinjection levels. The change in CBV induced by ioversol was significantly less than those reportedly induced by an ionic contrant medium, iothalamate, and a nonionic medium, iopamidol, and comparable to that by another nonionic medium, iohexol. The degree of increase in CBV and the blood concentration of ioversol were related to the amount, but not the volume, of ioversol injected. Thus, ioversol proved to be one of the low osmotic nonionic contrast media with less effects on CBV. Furthermore, it is suggested that the amount, rather than volume, of contrast medium should be taken into consideration when the angiography of the patients with reduced cardiac function, children or aged patients is performed in whom the contrast medium-induced CBV expansion needs to be as less as possible.

Animals↗
PubMed1993

Ultrastructural changes of collagen fibers in the anterior cruciate ligament of bipedal rats after enforced running.

The effect of enforced running on the morphological characteristics of the fibroblasts and on the distribution of the collagen fibril diameter in the anterior cruciate ligament of bipedal rats was examined by electron microscopy. Twelve bipedal rats were divided into two groups of equal numbers: (1) those without exercise, and (2) those with enforced exercise on a treadmill for four weeks. Ninety percent of the fibroblasts in the rats without exercise were ovoid-shaped with a round nucleus, whereas eighty-one percent of those in the rats with exercise were spindle-shaped with indented nucleus. There was a significant difference in the ratios of ovoid-shaped to spindle-shaped cells between the two groups (p < 0.05). There was an increased number of rough surfaced endoplasmic reticula and lysosomal vesicles in the fibroblasts of the rats with exercise. The collagen fibril diameters of the rats with exercise varied in size from 20 to 120 nm, while those of the rats without exercise were uniform in size, mostly between 50-80 nm. Mean collagen fibril diameter was 70.8 +/- 16.6 nm in the rats without exercise, and 66.6 +/- 21.9 nm in the exercised rats. This difference was significant (p < 0.05). These electron-microscopical findings indicate an increased collagen metabolism in the anterior cruciate ligament of rats with enforced running.

Animals↗