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Biomedical subjects

R Kikuchi

Publications and source records attributed to R Kikuchi.

At least 37 records · Page 2Linked to original sources
PubMed1999

New metabolic pathway of (24R)-24,25-dihydroxyvitamin D3: epimerization of the 3-hydroxy group.

A new metabolic pathway of (24R)-24,25-dihydroxyvitamin D3 [24,25(OH)2D3] was clarified in the in vivo experiments. After the administration of 24,25(OH)2D3 to rats, a new monoglucuronide of a vitamin D metabolite was obtained from the bile together with 24,25(OH)2D3 3- and 24-glucuronides. The genin of the metabolite was identified as 3-epi-24,25(OH)2D3 in comparison with the synthetic sample based on the data from 1H-NMR, GC/MS, and LC/atmospheric pressure chemical ionization-MS. The conjugation position was determined to be the 24-hydroxy group by the LC/electrospray ionization-MS and -MS/MS/MS combined with derivatization. To our knowledge, this is the first reported instance of the epimerization of the 3-hydroxy group of vitamin D compound with no hydroxy group at the 1alpha-position.

24,25-Dihydroxyvitamin D 3↗
PubMed1999

Phagocytosis of Candida albicans by concanavalin-A activated peritoneal macrophages.

We evaluated the effect of treatment of mice with concanavalin-A (Con-A) on the phagocytosis of glutaraldehyde-fixed Candida albicans by peritoneal macrophages. The mean number of unopsonized C. albicans blastoconidia phagocytosed in vitro by peritoneal macrophages was doubled (from 1.3+/-0.1 to 2.7+/-0.14) by pre-treatment of the donor mice with Con-A. The percent of peritoneal cells phagocytosing the blastoconidia in vitro was increased about four times (from 22.3+/-8.6 to 80.3+/-3.2) by Con-A. This increase in phagocytosis was about 50% inhibited by addition of mannan (50 microg) plus mannose (50 mM) to the assay medium, suggesting that it was mediated by mannose receptors (MR). Phagocytosis in vitro in the presence of fresh non-immune serum (5%) was also increased, from 84.3+/-5.0 for untreated macrophages to 100% for Con-A activated peritoneal macrophages and the mean number of opsonized C. albicans blastoconidia increased from 2.3+/-0.1 to 4. 6+/-0.1. These results suggest that treatment of mice with Con-A increased both the phagocytosis of C. albicans blastoconidia mediated by mannose receptors and by complement receptors.

Animals↗
PubMed1998

Serum soluble interleukin-6 receptor and biochemical markers of bone metabolism show significant variations during the menstrual cycle.

We examined sequential changes of bone-resorbing cytokines and bone metabolic markers and the effect of ovarian hormones on bone metabolism during the menstrual cycle in 10 healthy Japanese women, aged 22-43 yr, with normal ovarian function. Serum soluble interleukin-6 receptor (sIL-6R) showed a significant variation; a rise during the early and late follicular periods followed by a fall during the early luteal period (P = 0.0423, P = 0.0334) and an increase during the mid and late luteal periods. There were significant changes in the levels of markers of bone formation: a rise in serum bone-specific alkaline phosphatase (ALP) during the mid and late follicular (P = 0.0265) periods and a fall in serum carboxyl-terminal propeptide of type I procollagen (PICP) during the midluteal period (P = 0.0161). As for the levels of bone resorption markers, urinary type I collagen C-telopeptide breakdown products (CTx) and free deoxypyridinoline (D-Pyr) decreased significantly during the early and midfollicular periods, urinary free D-Pyr and serum pyridinoline cross-linked carboxyl-terminal telopeptide of type I collagen (ICTP) (P = 0.0440) increased significantly during the early luteal period, and urinary CTx, free D-Pyr, and serum ICTP decreased significantly during the late luteal period (P = 0.0170-0.0008). The serum PTH level was significantly higher during the follicular than the luteal period (P = 0.0132). Serum sIL-6R significantly correlated with urinary CTx (r = 0.190, P < 0.05) and serum ALP (r = 0.209, P < 0.05) and serum estradiol with intact osteocalcin (r = 0.309, P < 0.0005) and serum ALP (r = 0.181, P < 0.05). These observations strongly suggest that cyclic variations in the levels of bone formation and resorption markers and of a bone-resorbing cytokine may be modulated by cyclic changes in serum steroid hormones during the menstrual period. In addition, the specific days of biochemical events in the menstrual cycle are crucial for evaluating osteoclastic and osteoblastic activities in pre- and perimenopausal women or in women starting GnRH agonist therapy.

Adult↗
PubMed1997

High incidence of pneumonia in elderly patients with basal ganglia infarction.

BACKGROUND: Pneumonia is a major cause of death in patients with cerebral infarction. We assessed morbidity associated with pneumonia in 276 patients 65 years of age or older who were admitted to a long-term care facility. Furthermore, we studied the swallowing reflex during the day and at night and monitored the occurrence of silent aspiration during sleep. OBJECTIVES: To examine the possible relationship between the location of cerebral hemispheric infarctions and the incidence of pneumonia and to evaluate the role of silent aspiration in the development of pneumonia. METHODS: The incidence of pneumonia was analyzed in 4 groups of patients who were assigned to a group on the basis of the following computed tomographic findings: no infarct (group A); 1 or more unilateral basal ganglia infarcts (group B); bilateral basal ganglia infarcts (group C); and 1 or more cerebral hemispheric infarcts outside the basal ganglia (group D). Criteria for diagnosis of pneumonia were (1) a new pulmonary infiltrate seen on a chest radiograph and (2) 1 or more of the following features: cough, temperature greater than 37.8 degrees C, or subjective dyspnea. Before the study, the patients with stroke were followed up for more than 1 year after their ictus and were monitored to determine if they sustained affecting cerebral hemispheric structures. The average duration of observation for incidence of pneumonia was 22 months. To study the swallowing reflex and to monitor for the occurrence of silent aspiration during sleep, 15 of the patients who were confined to bed or chair were randomly selected from each of groups A through C. The swallowing reflex was examined at both 1 PM and 1 AM and was evaluated according to latency of response, which was timed from the injection of 1 mL of distilled water into the pharynx through a nasal catheter to the onset of swallowing. The incidence of silent aspiration during sleep was examined using indium-111 chloride as a radioactive tracer attached to the teeth, and scanning of the thorax was performed the next morning. RESULTS: The incidence of pneumonia was 2.12 times higher in the patients of group B (27.4%; P < .01) and 3.64 times higher in the patients of group C (47.0%; P < .001) than in the patients of group A (12.9%). The latency of response was longer in the patients of groups B (P < .05) and C (P < .001) than in those of group A at 1 AM. The percentage of positive scans was also higher in the patients of groups B (P < .01) and C (P < .001) than in those of group A. CONCLUSION: Basal ganglia strokes might predispose these patients to develop pneumonia owing to frequent aspiration during sleep.

Activities of Daily Living↗
PubMed1996

Pharmacodynamics and pharmacokinetics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) after administration of a rectal dosage vehicle.

The pharmacodynamic activities (leukopoietic effect) and pharmacokinetics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administered rectally in various doses as hollow-type suppositories were investigated in rabbits. Three kinds of rhG-CSF hollow-type suppositories were employed: suppository I containing rhG-CSF (100-1000 micrograms/kg) in 10 mM acetate buffer solution (ABS) at pH 4.0, suppository II containing rhG-CSF in ABS with alpha-cyclodextrin (alpha-CyD) as an absorption-enhancing agent, and suppository III containing lyophilized rhG-CSF powder. We found that the total count of leukocytes in peripheral blood (total blood leukocyte count) and serum granulocyte colony-stimulating factor (G-CSF) concentration showed a dose-dependent increase. Consequently, the area under the increased total blood leukocyte count-time curve (AUI), an index of pharmacodynamic activity, and the area under the serum G-CSF concentration-time curve (AUC), a pharmacokinetic parameter, increased with an increase in the rhG-CSF dose administered rectally. Good correlation was found between AUL and AUC; thus, it is concluded that an increase in AUC leads to an increase in the effect of rhG-CSF in inducing leukopoiesis in rabbits following rectal administration. We report for the first time the rectal absorption of rhG-CSF using a new rectal dosage vehicle (rhG-CSF hollow-type suppository) and its leukopoietic effect. The rhG-CSF hollow-type suppository is found to be a promising drug delivery system.

Administration, Rectal↗
PubMed1996

Pharmacodynamic activity (leukopoietic effect) of recombinant human granulocyte colony-stimulating factor (rhG-CSF) after rectal administration in rabbits with leukopenia induced by cyclophosphamide.

The pharmacodynamic activity (leukopoietic effect) and pharmacokinetics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administered in various doses as hollow-type suppositories were investigated in rabbits with leukopenia induced by cyclophosphamide (CPA-treated rabbits). We found that serum granulocyte colony-stimulating factor (G-CSF) concentration was increased following the rectal administration of rhG-CSF. Therefore, rhG-CSF could be absorbed from the rectal mucosa in leukopenic rabbits who received CPA at a dose of 30 mg/kg/d. When rhG-CSF of at least 300 micrograms/kg was administered rectally once a day for 3 d in CPA-treated rabbits 1 d after the induction of leukopenia (the total count of leukocytes in peripheral blood [total blood leukocyte count] was below 5000/microliter), decreased total blood leukocyte count returned to the normal physiological level and a maximum (7000-16000/microliter) was obtained 3 d after the start of the rhG-CSF multiple-dosing regimen. We report for the first time that rhG-CSF administered rectally induces leukopoiesis in CPA-treated rabbits and reduces the period of leukopenia induced by CPA. Thus, the rhG-CSF hollow-type suppository offers a promising means of reducing the risk of leukopenia, an adverse side effect of CPA therapy.

Administration, Rectal↗
PubMed1995

Management of early invasive colorectal cancer. Risk of recurrence and clinical guidelines.

PURPOSE: The purpose of this study was the evaluation of various factors in the formulation of guidelines for treatment of early invasive colorectal cancer, in which malignant cells extend through the muscularis mucosa into the submucosa but do not deeply invade the muscularis propria. METHOD: A total of 182 patients were followed for at least five years or until death, with early invasive cancer diagnosed between 1982 and 1989. Patients were grouped according to the level of invasion, as follows: 64 patients with slight carcinoma invasion of the muscularis mucosa (200-300 microns; sm1), 82 with intermediate invasion (sm2), and 36 with carcinoma invasion extending to the inner surface of the muscularis propria (sm3). RESULT: The configuration, diameter, and histologic grade of adenocarcinoma and lymphovascular invasion were correlated with level of invasion. After endoscopic polypectomy or local resection, 4 patients showed local recurrence and 13 patients showed lymph node metastasis. None of these 17 patients had sm1 disease. The level of invasion, configuration, and location were significant risk factors for development of lymph node metastasis or local recurrence (P < 0.05), but lymphovascular invasion, histologic grade, and diameter were not risk factors. CONCLUSIONS: Preoperative assessment of the level of invasion using this classification, in which the submucosa is divided into three depths, may decrease the incidence of unnecessary surgery for sessile polyps. Assessment according to the level of invasion is useful in the formulation of appropriate guidelines for the treatment of early invasive cancer.

Adenocarcinoma↗
PubMed1995

Dependence of collateral and small airway resistances of CO2 and volume in dog lobes.

We examined the hypothesis that collateral channels were identical within small airways and ducts, therefore both should respond similarly to chemical and mechanical stresses. A double lumen catheter was wedged into a segmental bronchus of the dog and humidified air or 10% CO2 in air (Vs) flowed at a segmental bronchial pressure (Pb) of 2 cm H2O. A small circular area about 1 cm diameter was peeled from the wedged segment and covered with a capsule glued to the surrounding pleura for measuring either a small airway flow (Vsaw) or capsule pressure (Pcap). Collateral resistance (Rcoll) and small airway resistance (Rsaw) were calculated as Rcoll = Pb/(Vs-Vsaw), Rsaw = (Pb-Pcap)/Vsaw, respectively. Hypocapnia (air) resulted in increases in Rcoll and Rsaw, while hypercapnia (10% CO2) generally had the opposite effect. Gcoll and Gsaw both increased linearly with lung volume (VL). The pattern of the responses of Rsaw closely paralleled those of Rcoll to local hypercapnia and hypocapnia, and to changing VL, implying that the major sites of resistance along collateral channels and along the airways are functionally and structurally similar.

Airway Obstruction↗
PubMed1995

Increase in total blood leukocyte count following intranasal administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rabbits with cyclophosphamide-induced leukopenia.

We investigated the effects of intranasal (i.n.) administration of recombinant human granulocyte colony-stimulating factors (rhG-CSF) on the total count of leukocytes in peripheral blood (total blood leukocyte count) of rabbits with leukopenia who received cyclophosphamide (CPA). When CPA (30 mg/kg per d) was administered intravenously, the total blood leukocyte count decreased to levels below 5000/microliters approximately 4 d after the initiation of CPA multiple dosing. The decreased level of the total blood leukocyte count was maintained throughout the period of CPA dosing. RhG-CSF was given once a day for 3 d in CPA-treated rabbits via i.n. administration of aqueous preparations containing rhG-CSF with or without alpha-cyclodextrin (alpha-CyD). The total blood leukocyte count increased from levels below 5000/microliters to the normal physiological level following i.n. administration of rhG-CSF preparation and reduced the period of leukopenia induced by CPA. The coadministration of rhG-CSF and alpha-CyD was more effective in increasing the total blood leukocyte count. It is suggested that i.n. administration of rhG-CSF is promising for reducing the risk of cytotoxic chemotherapy (CPA)-induced leukopenia as an adverse side effect.

Administration, Intranasal↗
PubMed1995

Pharmacokinetics and pharmacodynamics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) following intranasal administration in rabbits.

The objective of this study was to evaluate the pharmacokinetics and pharmacodynamics of G-CSF as well as their relationship following intranasal (i.n.) administration of aqueous rhG-CSF preparations with or without additives. In order to achieve a better understanding of the dosage regimen and the effectiveness of intranasally administered rhG-CSF in inducing leukopoiesis, we investigated rhG-CSF absorption and blood leukocyte dynamics with respect to dose in rabbits. RhG-CSF could be absorbed through the nasal cavity of rabbits when rhG-CSF aqueous preparations, especially those containing alpha-cyclodextrin (alpha-CyD) were intranasally administered. We found that serum G-CSF levels and the total count of leukocytes in peripheral blood (total blood leukocyte count) showed a dose-dependent increase with rhG-CSF. The area under the serum G-CSF concentration-time curve (AUC, a pharmacokinetic parameter) and the area under the increased total blood leukocyte count-time curve (AUL, a pharmacodynamic parameter) increased with increase of dose of rhG-CSF administered intranasally. Good agreement was observed between log AUC and AUL; thus, it is concluded that an increase of AUC leads to an increase in effectiveness of rhG-CSF in inducing leukopoiesis in rabbits. A novel rhG-CSF delivery system in the form of i.n. administration of rhG-CSF was thus achieved.

Administration, Intranasal↗
PubMed1994

Bronchomotor agents and hysteresis of collateral resistance in dog lobe.

The effect of smooth muscle tone on hysteresis of collateral channels was examined and compared with that of airways, in freshly excised dog lobes. A double lumen catheter was sealed into a branch off the main bronchus, and air (Vs) flowed through the outer lumen while the pressure in the segment (Ps) was measured by the inner lumen. Collateral conductance (Gcoll) was calculated as Gcoll = Vs/Ps. In another series of experiments a pleural capsule was used to measure either segmental airway flow (Vsaw) or capsule pressure (Pcap). Segmental airway conductance (Gsaw) was calculated as Gsaw = Vsaw/(Ps-Pcap). Hysteresis for Gcoll vs lung volume (VL) curves were almost absent in control and after isoproterenol inflation Gcoll was greater than deflation Gcoll at a given VL (clockwise history). Conversely, after histamine Gcoll vs VL curves showed a counterclockwise history. The behaviors of Gcoll and Gsaw against a bronchomotor agent were similar. We conclude that major collateral channels have muscular walls, and being that of an airway type.

Airway Resistance↗
PubMed1994

High incidence of silent aspiration in elderly patients with community-acquired pneumonia.

Pneumonia is a major cause of death in the elderly. To investigate the role of silent aspiration in community-acquired pneumonia, we examined the occurrence of silent aspiration during sleep in 14 elderly patients with acute episode of pneumonia and 10 age-matched control subjects by a new technique using indium111 chloride. Scanning of the thorax demonstrated that 71% of patients aspirated, whereas aspiration was observed in only 10% of control subjects. The percentage of positive scans was significantly higher in patients with acute episode of pneumonia than in control subjects (p < 0.02). The results may indicate an important role of silent aspiration in the development of community-acquired pneumonia in the elderly.

Acute Disease↗
PubMed1993

Absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and blood leukocyte dynamics following intranasal administration in rabbits.

Absorption of recombinant human granulocyte colony-stimulating factors (rhG-CSF) following intranasal administration of aqueous preparations containing rhG-CSF with or without dimethyl-beta-cyclodextrin was investigated. It was found that rhG-CSF was absorbed and the total leukocyte numbers in peripheral blood markedly increased after intranasal instillation of rhG-CSF solution (pH 4) without excipients. Simultaneously administered dimethyl-beta-cyclodextrin enhanced nasal absorption of rhG-CSF. Consequently, serum rhG-CSF concentrations and total leukocyte numbers were greatly increased.

Administration, Intranasal↗
PubMed1992

Influence of lung volume history and increased surface forces on collateral resistance.

In order to investigate the major route for collateral ventilation, the influences of lung volume history and increased surface forces on collateral resistance (Rcoll) were studied in excised canine lower lobes. Measurements were made during inflation and deflation in two states, i.e. before (control) and after stiffening by large tidal ventilation raising peak recoil pressure (Ptp) by 8-10 cmH2O. Air flowed into a wedged segment via a double lumen catheter (Vcoll) keeping segmental pressure (PS) constant at 2 cmH2O as monitored through the other lumen, giving Rcoll = Ps/Vcoll. Rcoll vs lung volume (VL) showed little hysteresis, in sharp contrast to Rcoll vs Ptp (Rcoll higher during inflation). Thus, in each state, Gcoll (= 1/Rcoll) depended primarily on VL, but the stiffed state appeared to have permanently enlarged channels or recruited new ones. The relations between Gcoll and VL or Ptp somewhat resemble reported bronchial diameter behaviour. The ventilation process itself, rather than higher surface forces per se, appeared to distend collateral channels in the stiff lung. The results are consistent with the major component of Gcoll being located at the bronchiole level.

Airway Resistance↗