PubMed HealthSearch

Biomedical subjects

K Kanda

Publications and source records attributed to K Kanda.

At least 19 recordsLinked to original sources

Expression of neuronal nitric oxide synthase in spinal motoneurons in aged rats.

We investigated the expression of nitric oxide synthase (NOS) in motoneurons of aged rats by the nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (NADPH-d) reaction. The number of NADPH-d positive neurons (i.e. presumed motoneurons) in the motor nucleus at L4-L6 level of the spinal cord was 0.0 +/- 0.0 for 13- to 15-month-old rats, 2.2 +/- 0.8 for 24-month-old rats, and 7.9 +/- 5.4 for 29- to 32-month-old rats. These NADPH-d positive neurons were multipolar in shape and the soma cross-sectional area was 820 +/- 245 mu2 (n = 56; range, 359-1460 mu2) which was similar to the value for alpha-motoneurons. The results indicate that nitric oxide (NO) may be produced by a few motoneurons in the aged rat spinal cord and may lead these neurons to eventual death.

Aging

Developmental alterations in NMDA receptor-mediated currents in neonatal rat spinal motoneurons.

Postnatal development of N-methyl-D-aspartate (NMDA) receptors expressed in motoneurons was studied by tight-seal whole-cell recordings from identified motoneurons in slices of neonatal rat spinal cord. The magnitude of NMDA-induced currents was large during the early postnatal period, and then it decreased gradually through postnatal day (PND) 15. The pharmacological properties of NMDA-induced currents altered during this period, suggesting that the combination of NMDA receptor subunits changes during development. The magnitude of the NMDA receptor-mediated component of excitatory postsynaptic current evoked by electrical stimulation of an adjacent neuron also decreased from PNDs 1-5 through PNDs 11-15. NMDA receptors appear to underlie the mechanisms of activity-dependent development of spinal motoneurons during early postnatal life.

2-Amino-5-phosphonovalerate

A percutaneously accessible pulsatile left ventricular assist device: modified assist device type 5.

To provide percutaneous access, a new circulatory assist system was developed. We call this newly developed system the modified assist device (MAD). The system is composed of a sac-type blood pump and cannula. Inflow and outflow valves are mounted in the apex and at the side wall 10 cm from the apex of the cannula, respectively. During systole, the blood is sucked from the left ventricle through the inflow valve of the cannula connected to the blood pump, and during diastole, the blood is ejected to the root of the aorta through the outflow valve. In vitro and in vivo evaluations of the pump performance were performed. The maximum flow rate of 1.9 L/min was obtained in the mock circulatory system. In our animal experiment, effective systolic unloading and diastolic augmentation were observed by activation of this system during regular sinus rhythm. In conclusion, the MAD-5 is thought to be percutaneously accessible and increases systemic and coronary flow.

Animals

Purification and properties of tyrosinase isozymes from the gill of Lentinus edodes fruiting body.

Six tyrosinase isozymes were purified from the browned gill of the fruiting body of Lentinus edodes by ammonium sulfate fractionation, DEAE-Sephacel and Q-Sepharose column chromatography, and partially denaturing SDS-PAGE. At the step of Q-Sepharose column chromatography, two active fractions (A and B) were obtained. Each fraction was separated to three further fractions, A1, A2, and A3, and B1, B2, and B3, respectively, by partially denaturing SDS-PAGE. All these isozymes consisted of two types of polypeptides: alpha polypeptide (A alpha or B alpha) and either beta (A beta or B beta) or gamma polypeptide (A gamma or B gamma). The alpha polypeptide contained the consensus amino acid sequence of the active site of known tyrosinases, which is considered to act as a catalytic subunit. From the results of peptide mapping and the amino acid composition, A alpha and B alpha polypeptides were considered to be different proteins. The kinetic properties of the purified tyrosinase isozymes differed greatly according to whether they contained beta or gamma polypeptide, indicating these polypeptides to be a possible regulatory subunit.

Amino Acid Sequence

Effects of the thermal conditions of the dressing room and bathroom on physiological responses during bathing.

The effects of the thermal conditions of the dressing room and bathroom on the physiological responses during bathing were assessed. Six female students participated in this experiment. Three climate chambers were used as a living room, a dressing room and a bathroom. The living room was thermoneutral and maintained at 25 degrees C, while the thermal conditions of the dressing room and bathroom were as follows: (A) cold (10 degrees C), (B) cool (17.5 degrees C) thermoneutral (25 degrees C). The subjects wore standard clothing (0.65 clo). Heart rate (HR), blood pressure, rectal (Tre) and skin temperature, and subjective thermal sensation were recorded. 1) Marked increases in systolic blood pressure (SBP) after undressing and redressing in the dressing room and during washing were observed under the cold conditions. 2) A significant negative correlation was found between the dressing room temperature and increased SBP compared to before bathing (r = -0.684, p < 0.01, n = 18). 3) After exposure, mean skin temperature (Tsk) showed marked differences among the three conditions despite the rest taken under the same thermal conditions. 4) A significant negative correlation was found between Tsk and the increase in SBP of after undressing relative to that before bathing (r = -0.695 p < 0.01, n = 18). These findings suggested that 25 degrees C was the most appropriate temperature for the bathroom and dressing room, since the increase in blood pressure was minimum and subjective thermal sensation was neutral (neither cool nor warm) to warm under this thermal condition, and 17.5 degrees C at which the increase in blood pressure was within the physiological fluctuation range (+/- 10 mmHg) is the minimum tolerable temperature.

Adult

Constitutive STAT1 tyrosine phosphorylation in U937 monocytes overexpressing the TYK2 protein tyrosine kinase does not induce gene transcription.

Janus kinase (JAK) family protein tyrosine kinases are constituents of a signaling path leading to tyrosine phosphorylation and activation of signal transducer and activator of transcription (STAT) family transcription factors. IFN-alpha activates two JAK family protein tyrosine kinases (TYK2 and JAK1) and two STAT family proteins (STAT1 and STAT2). We have generated a line of U937 promonocytes expressing a tyk2 transgene. 12-O-Tetradecanoylphorbol-13-acetate-mediated differentiation into monocytes resulted in transgene induction and both overexpression and constitutive activation of the kinase. TYK2 protein in the transgenic line was found predominantly in a membrane fraction. Coprecipitation experiments demonstrated an association of constitutively tyrosine-phosphorylated TYK2 with the IFN-alpha receptor 1 chain. TYK2 activity led to an IFN-alpha-independent appearance of tyrosine-phosphorylated STAT1 but not STAT2 or JAK1 proteins. Consistent with this, TYK2 activity also caused constitutive activation of the IFN-alpha-responsive transcription factor IFN-alpha activation factor, a dimer of tyrosine-phosphorylated STAT1, but not of the IFN-alpha-responsive transcription factor IFN-stimulated gene factor 3, a heterotrimer of tyrosine-phosphorylated STAT1 and STAT2 in association with a M(r) 48,000 DNA-binding subunit. Expression of STAT1 target genes was not observed in TYK2-overexpressing cells. Our results suggest that in addition to activated TYK2, there is a requirement for additional, IFN-alpha-dependent signals for the phosphorylation of STAT2 and the generation of IFN-stimulated gene factor 3 as well as for the conversion of tyrosine-phosphorylated STAT1 into transcriptionally active IFN-alpha activation factor.

Cell Differentiation

Dynamic and static sensitivities of muscle spindle primary endings in aged rats to ramp stretch.

Responses of the presumed primary sensory endings of de-efferented muscle spindles to a ramp stretch were investigated in the medial gastrocnemius muscle of male Fischer 344 rats of two age groups (i.e. 10-14 and 28-30 months) anesthetized with urethane and chloralose. The static sensitivity was similar for both middle-aged and aged rats, although the discharge frequency was lower for aged rats when compared at the same muscle length. The value of the dynamic index was significantly lower in aged rats than in middle-aged rats, suggesting a decrease in the dynamic sensitivity of muscle spindle primary endings in aged rats.

Aging

Fos induction in the medullary dorsal horn and C1 segment of the spinal cord by acute inflammation in aged rats.

In order to elucidate the effect of aging on nociceptive neurons in the central nervous system, c-fos was used as a marker of excitability of neurons in the medullary dorsal horn (MDH) and the first spinal segment (C1) following noxious stimulation of the lateral face of young and aged rats. The distribution of c-fos-positive cells was dense in the superficial laminae and sparse in the deep laminae of the MDH and C1 in both young and aged animals following subcutaneous injection of formalin into the lateral face, whereas few c-fos-positive cells were labeled after saline injection. The distribution of c-fos-positive cells in the superficial laminae of the aged rats was found to be denser and more rostro-caudally expanded compared to that in the young rats. C-fos-positive cells were distributed more rostro-caudally in aged than in young rats. There was no difference between young and aged rats in the distribution of c-fos-positive cells in the deep laminae. Substance P (SP), 5-HT and calcitonin gene-related peptide-like immunoreactive (CGRP-LI) fibers and varicosities showed similar distribution density in the MDH and C1. Furthermore, many 5-HT-LI aberrant fibers and varicosities were observed in the MDH and C1 of the aged rats. The SP-LI and CGRP-LI cells in the trigeminal ganglion of aged rats were larger than those of young rats. These findings suggest that a deficit of the descending 5-HT inhibitory system produces the increment of c-fos-positive cells in the MDH and C1 of aged rats, resulting in the recruitment of a larger number of neurons in the superficial laminae of the MDH and C1 for conveying nociceptive sensory information to the central nervous system.

Age Factors

Evolution of the response patterns to dietary carbohydrates and the developmental differentiation of gene expression of alpha-amylase in Drosophila.

Intraspecific variation of alpha-amylase activity in D. melanogaster and D. immigrans, which is distantly related to D. melanogaster, and interspecific variation of alpha-amylase activity in 18 Drosophila species were examined. The amount of intraspecific variation of alpha-amylase activities measured in terms of coefficient of variation in D. melanogaster and D. immigrans was one-half and one-tenth or less, respectively, of the interspecific variation in 18 Drosophila species. We also surveyed the response patterns of alpha-amylase activity to dietary carbohydrates at the larval and adult stages. The levels of alpha-amylase activity depended on both repression by dietary glucose (glucose repression) and induction by dietary starch (starch induction). In general, our data suggest that glucose repression was conserved among species at both stages while starch induction was mainly observed in larvae, although the degree of the response depended on species. In D. lebanonensis lebanonensis and D. serrata, larvae expressed electrophoretically different alpha-amylase variants (isozymes) from those of adult flies. These results may suggest that the regulatory systems responsible both for the response to environment and developmental expression are different among species in Drosophila.

Animals

Differential effects of aging on motoneurons and peripheral nerves innervating the hindlimb and forelimb muscles of rats.

We examined the number and size of ulnar (forelimb) and medial gastrocnemius (MG, hindlimb) motoneurons in middle-aged (9 months of age) and aged (27 months of age) male Fischer 344 rats. Morphological properties of the ulnar and the MG nerves were also studied. No significant difference was found in the mean number of the ulnar motoneurons between the two age groups, while that of MG motoneurons was significantly less in aged animals. A decrease in the number of myelinated fibers (including both afferent and efferent fibers) in the ulnar nerves was less than that in the MG nerves, although the age difference was not significant in either of the nerves. Soma atrophy of aged motoneurons was found in both MG and ulnar motor nuclei. The mean fascicular areas and myelinated fiber diameters were significantly increased in both the MG and the ulnar nerves in aged rats, but these were less pronounced for the ulnar nerve. The results indicate that most ulnar motoneurons, unlike MG motoneurons, survive at least to the age of 27 months. Morphological changes in the peripheral nerves were also less for the ulnar nerve than for the MG nerve. Thus, we conclude that the effects of aging on motoneurons and peripheral nerves innervating MG muscle of the hindlimb are greater than those innervating forelimb muscles.

Aging

Clinical use of low porosity woven ultrafine polyester fiber grafts.

A woven fabric graft made of ultrafine polyester fibers (UFPF) (Toray Graft, water porosity: 100 ml/min/cm2:120 mm Hg H2O) was clinically applied in 81 cases (28 thoracic aortic aneurysms, 6 thoracoabdominal aortic aneurysms, 42 abdominal aortic aneurysms, and 5 atherosclerotic obstructions of the peripheral arteries). Eight patients died after surgery due to causes unrelated to the graft. The other 73 patients were in good condition after surgery. For operations requiring extracorporeal circulation, the graft was presealed with human albumin. For the abdominal aortic aneurysms, the graft was preclotted in situ with nonheparinized autoblood after the completion of the proximal anastomosis. It took about 2 min to complete the preclotting. A nonsealed graft was used for the reconstruction of peripheral arteries for the intraaortic balloon pumping procedure. The graft was easy to handle. There was no cut edge fraying problem with the graft in any direction of cutting. Even after presealing, the graft was soft and pliable enough to enable easy adaptation and anastomosis. Just after implantation, bleeding was minimal from the graft wall, anastomotic sites, and suture pores, and it stopped spontaneously. These clinical data showed that the woven UFPF graft exhibited both easy handling despite in spite of low porosity and safe application in the reconstruction of arterial systems even under totally heparinized conditions during extracorporeal circulation.

Aortic Aneurysm

Thermal conditions in the bathroom in winter and summer, and physiological responses of the elderly during bathing.

Thermal conditions in the bathroom and physiological responses were examined during winter and summer. The subjects were 22 male and 20 female elderly people, between 65 and 88 years old living in 25 houses in Gunma Prefecture, Japan. Heart rate, blood pressure, skin temperature and thermal sensation were measured during bathing. Changes in thermal sensation due to bathing were assessed in the living room and dressing room on a 9-point scale. Then they were asked about the purposes of bathing and the facilities of bathroom and dressing room. The results are summarized as follows: 1. The purpose of bathing in winter was to warm up for more than 80% of the subjects. In summer, all subjects felt refreshed by bathing. Eighty-five percent of the subjects took a bath every other day in both seasons. 2. Fifty-two percent of the bathrooms had no ventilating fans and 32% had no exclusive dressing rooms. 3. The average room temperature in the dressing rooms was 13-14 degrees C in winter. Thermal sensation was 'cool', 'slightly cold' or 'cold' for more than two-thirds of the subjects when they were partially nude, and there were no heaters in most dressing rooms. 4. The heart rate increased steadily, and reached a maximum value in a partially dressed condition in both seasons. 5. In winter, a marked increase of systolic blood pressure was observed in the partially nude condition. There was a significant difference between the before bathing condition and partially nude condition in winter.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Body movements of the elderly during sleep and thermal conditions in bedrooms in summer.

The frequency of body movement in the elderly and young people during sleep was measured in order to investigate the effect of hot thermal environments on sleep in summer. Simultaneously, room temperature and humidity were also measured. In the morning after measuring body movements, the subjects completed a questionnaire about their night's sleep. The results obtained were as follows: 1) The time of going to bed and rising in the elderly was significantly earlier than the young. 2) The elderly had a tendency to judge their sleep as "good", however, there were no significant differences between the two groups. 3) The room temperature for the elderly during sleep ranged from 25 to 28 degrees C (mean 26.5 degrees C). On the other hand, it was between 20 and 30 degrees C (mean 27.1 degrees C) in the young, which was significantly higher than that of the elderly. 4) Body movement in the elderly during sleep was significantly greater than those in the young. 5) A significant relation between body movement and room temperature was found within each group. Under conditions of less than 28 degrees C of room temperature, there were significantly higher rates of body movement in the elderly.

Adult

[Experimental study on organ perfusion by intraaortic balloon counterpulsation with double balloon catheter].

Newly-developed catheter for the intraaortic balloon counterpulsation with cardio-renal assist was examined on animal model. The catheter consists of two balloon segments between which the celiac trunk, the superior mesenteric artery and the renal artery are to be placed. Statistical comparison on each hemodynamic element was carried out between the catheter (DBC), conventional single balloon catheter (SBC) of the same balloon volume as DBC and no assist (None) groups. There were no significant changes between SBC and DBC in cardiac output, femoral arterial flow and central venous pressure. Renal arterial flow and urinary output were significantly increased in DBC (None 14.4 +/- 3.9, SBC 22.6 +/- 5.6, DBC 31.0 +/- 6.9 ml/min in renal arterial flow, None 33 +/- 9, SBC 64 +/- 14, DBC 78 +/- 20 ml/h in urinary output, p < or = 0.05). After the remodeling adjust to the human stature, a clinical application would be considered.

Animals

Developmental alterations in NMDA receptor-mediated [Ca2+]i elevation in substantia gelatinosa neurons of neonatal rat spinal cord.

Using spinal cord slices prepared from neonatal rats, the intracellular free Ca2+ concentration ([Ca2+]i) in neurons located in the dorsal horn substantia gelatinosa (SG) was measured with microscopic fluorometry by loading fura 2-AM into neurons. Developmental alterations in the elevation of [Ca2+]i elicited by the glutamate analogs, NMDA and AMPA, were investigated from postnatal day (PNDs) 1 to 17. During the 1st week of postnatal life, when neuronal maturation of the SG is known to take place, the NMDA response remained large or even slightly increased. It subsequently showed a gradual decline. This pattern of postnatal changes is consistent with previously reported autoradiographic studies on NMDA-binding sites. The affinity of receptors for NMDA was found to decrease constantly during the period examined. The AMPA response and resting [Ca2+]i showed no significant developmental changes. Neonatal treatment with capsaicin, which has been shown to degenerate fine primary afferent fibers terminating in the SG, delayed the developmental decline in the NMDA-induced [Ca2+]i response. It is suggested that the number and the molecular properties of NMDA receptors expressed in the SG change during early postnatal neuronal maturation. The temporal coincidence between postnatal alteration in NMDA-induced [Ca2+]i elevation and neuronal maturation of the SG may indicate that intracellular Ca2+ regulated by NMDA receptor activation is related to postnatal neuronal maturation. Activation of fine primary afferent fibers may contribute to the observed developmental alterations in the NMDA response of SG neurons.

Animals

A targeting model of boron neutron-capture therapy to hepatoma cells in vivo with a boronated anti-(alpha-fetoprotein) monoclonal antibody.

We described previously that 10B atoms delivered by monoclonal antibody (mAb) exerted a cytotoxic effect on AH66 cells in a dose-dependent manner upon thermal neutron irradiation in vitro. In the present study, the delivering capacity of boronated anti-(alpha-fetoprotein) (AFP) mAb to carry 10B atoms to AFP-producing tumor xenografts in nude mice was determined. Boronated mAb was prepared by conjugating 50 mM 10B compound to an anti-AFP mAb (2 mg/ml) using N-succinimidyl-3-) (2-pyridyldithio) propionate. The number of 10B atoms conjugated directly to the mAb was estimated to be 459/antibody by prompt gamma-ray spectrometry. Boron concentrations in tumor tissue obtained 12, 24, 72, and 120 h after injection of 3.0 mg 10B-conjugated anti-AFP mAb were 11.10 +/- 3.12 (SD, n = 6). 29.30 +/- 5.11, 33.02 +/- 11.8, and 12.91 +/- 5.62 ppm respectively. For control 10B-conjugated anti-dinitrophenol (DNP) mAb, the values were 9.59 +/- 0.99, 10.37 +/- 2.86, 10.00 +/- 2.95, and 8.83 +/- 4.71 ppm respectively. The concentrations in blood were less than 0.40 +/- 0.10 ppm with anti-AFP mAb and less than 0.51 +/- 0.15 ppm with anti-DNP mAb at each sampling time (12, 24, 72, and 120 h). The number of 10B atoms delivered to the tumor cells was calculated to be 0.62 x 10(9), 1.63 x 10(9), 1.84 x 10(9) and 0.72 x 10(9) at each sampling time after injection of 10B-anti-AFP mAb. The amount of 10B atoms necessary for effective boron neutron-capture therapy was estimated to be 10(9)/tumor cell. We were able to carry 1.84 x 10(9) 10B atoms to AH66 tumor cells by using 10B-anti-AFP mAb. The accumulation reached its peak 72 h after injection. These data indicated that the 10B-conjugated antitumor mAb could deliver a sufficient amount of 10B atoms to the tumor cells to induce cytotoxic effects 72 h after injection upon thermal neutron irradiation.

Animals

Glucocorticoids potentiate the action of atrial natriuretic polypeptide in adrenalectomized rats.

Adrenal insufficiency in human and rat is associated with an impairment of the diuretic response to water load, and only glucorticoids (GCs) restore this deficit. Our observation that GCs potentiate atrial natriuretic polypeptide (ANP)-stimulated cGMP production in cultured renal cells prompted us to examine the possibility that GCs may restore the diuretic response through the potentiation of ANP action. Initially, changes in urine volume and ANP levels were studied in adrenalectomized (Adx) and sham-operated intact rats after an oral water load of 5 ml/100 g BW. Urine volume after water load was 4.5 +/- 0.5 ml/30 min in the intact rats, whereas it was 0.8 +/- 0.2 ml/30 min in the Adx rats. In the intact rats, a significant increase in plasma ANP level was observed 30 min after the water load, whereas no increase was observed in Adx rats. This defective ANP response may be involved in the impairment of the diuretic response in Adx rats. Indeed, pretreatment of Adx rats with dexamethasone (Dex, 20 micrograms/100 g BW) increased plasma ANP levels even before water load and improved diuretic response. Subsequently, effect of iv administration of human or rat ANP at a pharmacological dose (2.5 micrograms/100 g BW) on urine volume, osmolarity, and urinary excretion of cGMP, and sodium was studied in Adx rats that received an oral water load 30 min before ANP. Dex treatment was achieved by per os administration 3 h before the ANP injection. In Adx rats, the urine volume after ANP administration was 1.2 +/- 0.1 ml/30 min, and pretreatment with Dex markedly increased the urine volume to 6.3 +/- 0.4 ml/30 min. Dex also increased ANP-induced osmolar and sodium excretion by 2.6- and 2.9-fold, respectively. Although urinary excretion of cGMP was increased in Adx rats by ANP administration, a further significant increase was observed by the pretreatment with Dex. Injection of (Bu)2cGMP to Adx rats pretreated with Dex resulted in a significant increase in urine volume and osmolar and sodium excretion. However, no significant increase in urine volume was observed in Adx rats not pretreated with Dex. The present study suggests that GCs restore the diuretic response to acute water load not only by increasing the secretion of ANP but also by potentiating ANP-stimulated cGMP production. Furthermore, GCs may augment ANP action at one or more steps other than cGMP formation because administration of (Bu)2cGMP to Adx rats did not correct the diuretic response to water load.

Adrenalectomy

Boron neutron capture therapy of malignant melanoma using 10B-paraboronophenylalanine with special reference to evaluation of radiation dose and damage to the normal skin.

A treatment regimen for boron neutron capture therapy of malignant melanomas is described using 10B-paraboronophenylalanine as the tumor-targeting compound. As a therapeutic dose, we adopted the maximum tolerable dose for the skin regardless of tumor 10B concentration. In practice, the maximum neutron fluence should be decided prior to starting irradiation. For this purpose, the kinetics of the concentration of 10B in the blood and skin and the skin-to-blood ratios were analyzed in the six patients who received 170 mg/kg of the compound intravenously, and skin concentrations during irradiation were predicted using a standard skin factor curve. This yields a skin concentration at time T based on the blood concentration at time 0. We calculated the maximum tolerable fluence yielding but not exceeding 18 RBE-Gy by assuming that the RBE of 14N(n,p)14C and 10B(n, alpha)7Li reaction for skin damage is 2.5. Actual skin reactions in three of five patients treated with the therapy were, as predicted, within tolerable limits, and we were able to obtain complete tumor regression in four cases. The results indicate that application of our logical approach will be useful for subsequent cases and further development of this therapy.

Aged