PubMed Health⌕ Search

Biomedical subjects

K Kanda

Publications and source records attributed to K Kanda.

At least 73 records · Page 4Linked to original sources

[Results of clinical study with epirubicin hydrochloride injectable solution and cyclophosphamide in breast cancer].

A 10-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with breast cancer. One course of treatment consisted of one intravenous administration of Epirubicin-RTU at the dose of 60 mg/m2 followed by a 3-week drug-free interval and concomitant daily administration of oral cyclophosphamide at 100 mg/day during the period between Days 1 through 14. At least, two courses of treatment were given. Among 20 registered cases, all 20 cases were eligible and 16 cases completed the whole course of the study. In 16 completers, PR was observed in 5 cases, indicating the efficacy rate of 31.3% (5/16).. No local irritation was observed at the injection sites. Adverse reactions frequently observed were leukopenia, neutropenia, anorexia, alopecia, and nausea/vomiting, which were all reversible and tolerable. From the above results, Adverse reactions both locally and systemically were tolerable. Intravenous administration of Epirubicin-RTU was considered to be useful for the treatment of breast cancer.

Administration, Oral↗

A phase II study of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) with G-CSF for breast cancer patients with visceral metastases or hormone-independent tumors: a trial of the Japan Clinical Oncology Group.

To evaluate the efficacy and toxicity of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) therapy, a phase II study of EPI, 130 mg/m2, plus CPA, 1000 mg/m2, with G-CSF every 3 weeks was carried out for 51 advanced or recurrent breast cancer patients by the Japan Clinical Oncology Group (JCOG). Fifty out of the 51 patients who were eligible for our criteria were treated with this regimen as first-line chemotherapy for visceral metastases or hormone-independent tumors. In this trial, 203 cycles were administered with an average of four cycles per patients. In 50 patients who were evaluable for response, there were 7 complete (CR) and 25 partial responses (PR) with an overall response rate of 64% (95% confidence interval, 50.1-75.9%). Symptomatic and hematological acute toxicity more than grade 3 occurred frequently; however, no treatment-related death occurred. The incidence of toxicities (> or = grade 3) was as follows: leukopenia 98%, thrombocytopenia 42%, nausea/vomiting 56% and hair loss 12%. In each cycle, daily administration of 2 micrograms/kg G-CSF (granulocyte-colony stimulating factor) was given on days 2-15 subcutaneously. The incidence of cardiotoxicity was low. Arrhythmia (< or = grade 2) was observed in 8% and a slight decrease of ejection fraction index (< or = grade 2) was observed in 2% in this trial. The median follow-up period for patients was 37.2 (24.6-51.5) months and the median survival period was 17.4 months. These data indicate that high-dose EPI + CPA combination chemotherapy was effective and well tolerated for breast cancer patients with visceral metastases or hormone-independent tumors. A randomized trial of high-dose EPI vs conventional chemotherapy is required to ascertain the usefulness of this regimen.

Adult↗

[Effects of intermittent wakening on sleep pattern of nighttime caregiver: an EEG study with a single subject].

In order to investigate the effects of night wakening on sleep pattern of caregiver, a woman aged 45 years was studied using electroencephalogram (EEG). After two adaptation nights, her all-night EEG readings were recorded for six nights. During the first three consecutive nights, the subject slept by the side of a patient at a private ward of hospital and wakened by herself several times a night to provide care for the patient (care nights). Of the later three nights, her sleep EEGs were recorded at her home (free nights). The first free night was following three care nights and the other two free nights were after 2 weeks. The results were summarized as follows; 1) Sleep period time (SPT) of care nights differed in different nights. In contrast to the SPT range of 356-367 min during free nights, it was 271-391 min during the care nights. 2) The rhythm of sleep cycles of care nights was not stable, though the subject wakened by herself, not using an alarm clock. 3) Although there were few changes occurring in sleep efficiency (SE) and percent each stage for SPT (%SPT) between the first and second care night, SE of the third care night was more similar to SE of free nights than SE of the first two care nights, and so was %SPT of the third care night. 4) Sleep latency (SL) decreased during the four consecutive nights, i.e. the three care nights and the first free night, and SL of the third care night and the first free night were shorter than SL of the last two free nights. The accumulation of fatigue and stress of nighttime care was suggested.

Caregivers↗

Effect of estrogen on the development of disuse atrophy of bone and muscle induced by tail-supension in rats.

Rat tail-suspension induces disuse atrophy of muscles and bones in hindlimbs. In the present investigation we studied how ovariectomy and estrogen substitution affect the development of the disuse atrophy induced by suspension. Five-week old female Wistar rats were ovariectomized and divided into two groups. One group received intramuscular injection of estradiol dipropionate once a week (OVX-E2 group), and the other received a vehicle injection (OVX group). After the third injection, each group was further divided into two groups, tail-suspended and non-suspended. After 7 days of tail-suspension, a significant decrease in the wet weight of femurs and their Ca and Pi content was observed in the OVX group. However, no significant change in those parameters was observed in the E2 group. In both E2 and OVX groups, a significant decrease in the wet weight of soleus and gastrocnemius muscles was demonstrated after the suspension. This demonstrated that estrogen administration to ovariectomized rats prevents the development of disuse bone atrophy but not that of muscle atrophy, suggesting that estrogen plays important roles in bone remodeling.

Animals↗

Effect of bisphosphonate administration on the excretion of stress hormones in tail-suspended rats.

We demonstrated that administration of a bisphosphonate, YH529, prevents the development of disuse atrophy of the hind limbs induced by tail-suspension in rats. Since tail suspension is accompanied by an increase in the secretion of stress hormones, we studied whether administration of bisphosphonate affects the secretion of stress hormones during that procedure. Tail suspension was carried out in a metabolic cage by connecting a wire inserted through tail bone to the ceiling of the cage. The control rat received the same treatment but was not suspended. YH529 or a vehicle (PBS=phosphate buffered saline) was administered daily starting 3 days before the commencement of tail suspension. Urine samples were collected before the wire was inserted (day 0), on the day of insertion (day 1) and 3, 5 and 7 days after. In the control rats receiving PBS, urinary excretion of corticosterone and epinephrine did not change throughout the 7-day experimental period. In the control rats receiving YH529, urinary excretion of corticosterone increased significantly on the day of tail-piercing and wiring but then returned to the prior level. This increase was not observed in the control group receiving PBS. In the tail suspended rats, excretion of corticosterone and epinephrine increased significantly in both PBS and YH529 groups, the highest level being observed on the first day of tail suspension. Although statistically not significant, corticosterone excretion on day 1 of tail suspension was higher in the YH529 groups than that in the PBS group. It is thus suggested that administration of YH529 causes an augmented response to stress load.

Animals↗

Administration of bisphosphonate prevents disuse bone atrophy induced by tail suspension.

We recently demonstrated that osteopenia induced by rat tail-suspension was associated with an initial increase in bone resorption. To study the significance of the increase in early bone resorption for osteopenia, we investigated whether administration of YH529, a third-generation bisphosphonate, prevents the development of osteopenia as evidenced by increased wet weight of the femur, together with its calcium and phosphorus contents, when compared with those of tail-suspended rats treated with the vehicle alone. These results suggested that the initial increase in bone resorption plays an important role in the development of osteopenia induced by tail suspension.

Animals↗

[A study of nursing systems in transition in developed countries].

The present study was designed to investigate nursing systems in other countries in comparison with the current system in Japan, and thereby assess how nursing personnel should be in order to improve the quality of nursing. The study focused on the actual situation of the nursing system and licensed practical nurses (LPNs) or second-level nurses similar to LPNs in other countries. The survey was conducted in regard to six countries considered to be advanced in the development of nursing activities and likely to provide useful suggestions for the future direction of nursing in Japan: Australia, Canada, France, Sweden, the United Kingdom and the United States. Questionnaires were sent to the heads or staff of a total of 29 organizations, including WHO Collaborating Centers and professional organizations for nursing, in these countries. Nineteen organizations responded (response rate: 65.5%), and an effective response with completed questionnaire forms was obtained from 15 organizations. In addition, an interview survey was conducted on three nursing administration and education experts in the United States in order to acquire clear understanding of the actual state of nursing in health care practice. The results were as follows: 1. Six countries (Japan included) excluding France had LPNs. Educational preparation for LPNs has been discontinued in the United Kingdom. 2. The number of nurses per 1,000 population was lowest in Japan: the total number of registered nurses (RNs) and LPNs in Japan was less than the number of RNs in the United Kingdom. Only in Japan the proportions of LPNs and RNs were similar, while in other countries of number of LPNs was one-third to one-fourth of the number of RNs. 3. In the five other countries having LPNs, the nurse's competency or scope of practice was clearly defined for both LPNs and RNs. In contrast, no clear line was drawn between the two in Japan. 4. The length of education required for LPNs ranged from 11 to 14 years (including the period of compulsory education) and was shortest in Japan (11 years). The educational requirement for admission to LPN school in Japan was 9 years of compulsory education (graduation from junior high school), whereas in other countries it was at the level of senior high school graduation. 5. Four countries had conversion programs for LPNs to become RNs, and the conversion courses were positioned within the framework of higher education comparable to the university level. 6. In the United Kingdom, where the educational preparation for LPNs has been discontinued, nurses are included in a single higher level profession. At the same time there was found to be a need to train and educate auxiliary personnel in order to maintain multi-level care services. Because of the increasing tendency toward advanced medical technology and highly specialized medical care associated with the rapidly increasing care needs in the community, the current educational preparation for LPNs in Japan in unsatisfactory as a training and educational system for nursing manpower to cope with the current situation. The above findings suggest that the education system for LPNs be reviewed with a view to discontinuing it and consolidating nursing education in Japan.

Australia↗

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↗

Effects of bisphosphonate on bone metabolism in tail-suspended rats.

Our previous studies demonstrated that tail suspension causes early, transient increases in osteoclastic activity, followed by a decrease in osteoblastic activity in the hind limbs of rats. To assess whether this early increase in bone resorption is important in the development of disuse atrophy, the effect of YH529, a third generation bisphosphonate, was studied on hind limb atrophy in rats subjected to tail suspension. YH529 (YH group) or PBS (control group) were administered subcutaneously in 5-week-old male Wistar rats suspended for 7 days. In the control group, wet weight, calcium and phosphorus contents decreased significantly in the femur but they did not change in the humerus. In the YH group, however, these parameters did not change significantly in the femur, but both calcium and phosphorus increased significantly in the humerus. These results indicate that the inhibition of bone resorption by YH529 prevents the development of disuse atrophy induced by tail suspension. It is thus suggested that early increases in bone resorption are important for the development of disuse bone atrophy.

Animals↗

Changes in serum concentrations of calcium and its regulating hormones during tail suspension in rats.

To study the effects of mechanical unloading on systemic calcium homeostasis, we determined the changes in serum concentration of calcium, 1,25-dihydroxyvitamin D3 and parathyroid hormone (PTH) during tail-suspension experiments in rats. The serum concentration of ionized calcium significantly increased during the 14 days of the suspension, reflecting increased bone resorption in the hind limbs. This hypercalcemic condition should cause suppression in PTH secretion. Indeed, serum PTH levels decreased on Day 3 of the suspension. This decrease was associated with lower serum levels of 1,25-dihydroxyvitamin [correction of dihyroxyvitamin] D3 probably due to a decrease in the activity of 1 alpha-hydroxylase in the kidneys resulting from a decrease in PTH secretion. Since it is known that 1,25-dihydroxyvitamin D3 stimulates osteoblastic function, it is suggested that endocrine responses evoked by tail suspension aggravate disuse atrophy of the hind limbs.

Amino Acids↗

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↗