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Biomedical subjects

K Kanda

Publications and source records attributed to K Kanda.

At least 91 records · Page 5Linked to original sources

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↗

Changes in the markers of bone metabolism following skeletal unloading.

To elucidate the mechanism in disuse bone atrophy induced by skeletal unloading, we studied the indices of bone resorption and bone formation in the femur of tail-suspended rats. The duration of the suspension ranged from 1 to 14 days. Tartrate-resistant acid phosphatase mRNA, an index used to evaluate bone resorption, increased significantly more than the controls for the first 3 days of the tail-suspension experiments, compared those in controls. Osteocalcin and alkaline phosphatase, two common markers for bone formation, were also monitored. Osteocalcin mRNA started to decrease after 3 days of suspension. Five days later, alkaline phosphatase mRNA showed a decrease. Levels of both of these mRNAs remained low for the remaining suspension period. Sequential changes in the markers for bone metabolism indicate that the transient increase in bone resorption preceded the decrease in bone formation in the development of disuse bone atrophy induced by skeletal unloading.

Acid Phosphatase↗

Catecholamine response to stress: age related modifications in tail-suspended rats.

The catecholamine response to acute stress has been shown to change with age. However, alterations under chronic stress conditions have not been established. This study attempted to determine whether aging modifies the catecholamine response to chronic stress load in rats subjected to tail suspension. Urinary excretions of epinephrine (E) and norepinephrine (NE) were monitored before and during the tail suspension experiments in rats at two different ages: 5 weeks old (young) and 18 months old (aged). Basal excretions of E and NE before the suspension were higher in the aged rats, indicating that sympathetic-adrenal medullary activities increase with age under resting conditions. The chronic stress load elicited E responses in the aged rats similar to those in the young rats. The NE responses, however, were completely different in that tail suspension caused a greater increase in NE excretion in the young rats than in the aged rats. This finding suggests that the sympathetic response to chronic stress load changes with age.

Adrenal Glands↗

Effects of stress on Kv1.5 K+ channel gene expression in the left ventricle of rat hearts.

Voltage-dependent K+ channels contribute to the repolarization phase of the cardiac action potential. An increase in Kv1.5 K+ channel gene expression by a pharmacological dose of glucocorticoid was reported recently in the heart of an adrenalectomized rat. In this study, we examined whether physiological elevations of glucocorticoid induced by tail suspension affects the K+ channel gene expression. Five-week-old male Wistar rats were subjected to tail suspension for three days. Total RNA was extracted from the ventricle, and the level of Kv1.5 mRNA was determined by Northern blot analysis. On the first day, the Kv1.5 mRNA had increased over the non-suspended rat. By the third day, mRNA had increased significantly by more than 3-fold. knowing that urinary excretions of glucocorticoid increase in tail-suspended rats, these findings suggest that physiologically elevated glucocorticoid may upregulate Kv1.5 K+ gene expression.

Action Potentials↗

[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↗

A fundamental study on hyper-thermal neutrons for neutron capture therapy.

The utilization of hyper-thermal neutrons, which have an energy spectrum with a Maxwellian distribution at a higher temperature than room temperature (300 K), was studied in order to improve the thermal neutron flux distribution at depth in a living body for neutron capture therapy. Simulation calculations were carried out using a Monte Carlo code 'MCNP-V3' in order to investigate the characteristics of hyper-thermal neutrons, i.e. (i) depth dependence of the neutron energy spectrum, and (ii) depth distribution of the reaction rate in a water phantom for materials with 1/v neutron absorption. It is confirmed that hyper-thermal neutron irradiation can improve the thermal neutron flux distribution in the deeper areas in a living body compared with thermal neutron irradiation. When hyper-thermal neutrons with a 3000 K Maxwellian distribution are incident on a body, the reaction rates of 1/v materials such as 14N, 10B etc are about twice that observed for incident thermal neutrons at 300 K, at a depth of 5 cm. The limit of the treatable depth for tumours having 30 ppm 10B is expected to be about 1.5 cm greater by utilizing hyper-thermal neutrons at 3000 K compared with the incidence of thermal neutrons at 300 K.

Brain↗

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↗

Adrenocortical response to tail-suspension in young and old rats.

We recently showed that increased glucocorticoid secretion aggravates disuse atrophy when induced by skeletal unloading. Disuse atrophy in the elderly is becoming a serious problem in many developed countries. In this study we attempted to examine how aging affects the glucocorticoid response to skeletal unloading. Three groups of rats (aged 5 weeks, 12 months and 18 months) were subjected to 7 days of hind limb unloading by tail-suspension. Urinary excretion of corticosterone over a 24-hr period were monitored every other day. Corticosterone excretion in the control group of 5-week-old rats was initially 87.4 +/- 12.8 ng/day and did not change throughout the experiment. Tail-suspension experiments yielded a significant increase (more than 3 fold) in excretion on days 1 and 3 of the suspension before returning to control levels. In the 12-month-old rats, a marked increase in the basal corticosterone level was observed in the control rats throughout the experiment, while the increase by tail-suspension was attenuated with a transient, significant increase on day 5. In 18-month-old rats, a further increase in the basal level was observed in the control group, although excretions tended to increase steadily from day 1 to day 3 and remained high until day 7. Urinary excretion of corticosterone among the 18-month-old suspension group was similar to those observed in the control group. These results indicate that the younger (5-week-old) rats adapted the stress load caused either by tail-suspension or manipulation alone faster than the older rats did (12 or 18 months old). The observation that basal corticosterone excretion increases with age suggests, alterations in the hypothalamic-pituitary-adrenal axis among the aged rats which might aggravates disuse atrophy induced by skeletal unloading.

Adaptation, Physiological↗

Changes in serum 1,25-dihydroxyvitamin D3 and mRNAs for osteocalcin and alkaline phosphatase in femur unloaded by tail suspension in rats.

To elucidate the mechanism involved in the development of disuse atrophy of bone by skeletal unloading, changes in osteocalcin and alkaline phosphatase mRNAs, markers for bone formation, were studied in the hind limb bones of tail-suspended rats. Tail suspension for 8 and 14 days resulted in a significant decrease in osteocalcin mRNA in the femur when compared with age-matched non-suspended controls. Serum 1,25-dihydroxyvitamin D3 decreased to 60% of the control level after 8 days of skeletal unloading but regained almost normal levels over the next 7 days. Since it is known that vitamin D3 up regulates and glucocorticoid down regulates transcription of the osteocalcin gene, the endocrine response evoked by tail suspension may have aggravated the disuse atrophy caused by skeletal unloading in this study.

Alkaline Phosphatase↗

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↗

[Manometric study of the biliary sphincter zone: a comparison between the length of phasic activity and the narrow distal segment].

Motor activity of the sphincter of Oddi has been evaluated in 26 patients who underwent ERCP examination. Manometric recordings from the common bile duct and the sphincter of Oddi were performed with a single end-lumen perfused catheter. The number of successive 3 mm spaced black marks, observed during the pull-through from the first appearance of the proximal sphincter activity to that of duodenal pressure, was used to measure the length of the sphincter zone. In 14 of 26 patients, the length of phasic activity zone of the sphincter of Oddi was 9 mm. However, the narrow distal segment of the common bile duct was 15.1 +/- 3.6 mm in length. In same patients, the length of phasic activity zone was shorter than the anatomical one. The mean sphincter of Oddi pressure (SOP) at the distance of 6 mm from the papillary pore (77.8 +/- 22.1 mmHg) was greater than that of 9 mm (58.4 +/- 27.0 mmHg) and 12 mm (51.0 +/- 16.9 mmHg). These results suggest that the location of the orifice of catheter should be taken into consideration when comparing the SOP.

Adult↗

Suppression of rabbit VX-2 subcutaneous tumor growth by gadolinium neutron capture therapy.

VX-2 tumors growing in hind legs of New Zealand White rabbits (n = 4) were exposed to thermal neutrons for 40 min (2.1 x 10(12) neutrons cm-2) while one of two hind leg tumors of each rabbit was infused continuously with meglumine gadopentetate through a branch of the left femoral artery. The contralateral (uninfused) tumors served as controls. Although no differential distribution of gadolinium was achieved between the tumor and its adjacent normal tissue, the gadolinium concentration in the infused tumor was approximately 5-6 fold higher than that in the contralateral tumor. Growth of gadolinium-infused tumors was significantly inhibited compared to that of control tumors (P < 0.05) between the 16th and 23rd days after treatment.

Animals↗

Effects of isosorbide in patients with Menière's disease.

The effects of isosorbide on vertigo, disability, hearing loss and tinnitus in 32 patients with Menière's disease were evaluated after a 24-month observation period. Vestibular symptoms in 80% of patients were assessed as improved according to the 1985 AAO-HNS post-treatment reporting criteria. In contrast, the effect of this osmotic diuretic on cochlear symptoms was limited.

Administration, Oral↗