Search PubMed⌕ Search

Biomedical subjects

K Fujimoto

Publications and source records attributed to K Fujimoto.

At least 613 records · Page 34Linked to original sources
PubMed1991

Regional differences in extracellular choline dependency of acetylcholine synthesis in the rat brain.

Acetylcholine (ACh) synthesis under conditions of restricted extracellular choline uptake was investigated in order to clarify the procurement of choline for ACh synthesis using slices of several regions of the rat brain. Extracellular choline-independent ACh synthesis was observed in the hippocampus, frontal cortex and caudate putamen, which contain cholinergic nerve terminals, whereas little or no synthesis was observed in the medial septum or basal nucleus of Meynert, which contain cholinergic cell bodies. These results indicate that cholinergic nerve terminals, but not the cell bodies, may be able to synthesize choline for ACh biosynthesis. Extracellular choline-dependent ACh synthesis was observed in all regions examined. In the presence of 10 microM choline, the highest content of newly synthesized ACh and the proportionate increase in ACh compared with the unreleasable fraction (basal level) were observed in the caudate putamen. In the frontal cortex, although the level of synthesized ACh was low, the proportionate increase in ACh was high. In contrast, in the medial septum and basal nucleus of Meynert, high levels of ACh with a low proportionate increase compared with basal levels were observed. In the presence of hemicholinium-3, extracellular choline was also taken up for ACh synthesis in all regions examined, the level being especially high in the frontal cortex and medial septum. The present results indicate that the manner of choline procurement for ACh synthesis is heterogeneous among the various regions of the rat brain.

Acetylcholine↗
PubMed1991

Antihypertensive effect of synthetic tetrandrine derivatives in SHR rats.

1. Effects of oral administration of synthetic tetrandrine (TD) derivatives (20 mg/kg per day) for 9 weeks on blood pressure, heart rate, plasma renin concentration (PRC) and vascular reactivities to pressor substances were studied in spontaneously hypertensive (SHR) rats. 2. 7-O-Ethyl fangchinolin (7-O-EFC) and 7-O-isopropyl fangchinolin (7-O-IFC) produced a significant and sustained reduction in blood pressure from the first week of administration. 7-O-EFC reduced heart rate when determined under restraint conditions, but not under unanesthetized, freely moving conditions. 3. TD derivatives produced no effect on PRC. 4. Pressor response to phenylephrine was reduced significantly whereas the response to angiotensin II was enhanced after prolonged administration of 7-O-EFC and 7-O-IFC. 5. These results demonstrate that TD derivatives are potential antihypertensive drugs, and that attenuation of the pressor response to phenylephrine may contribute at least in part to its antihypertensive effect.

Alkaloids↗
PubMed1991

Antihypertensive and diuretic effects of YM-09730-5, a new calcium antagonist, in stroke-prone spontaneously hypertensive rats.

1. Effects of consecutive administration of YM-09730-5, (3S)-1-benzyl-3-pyrrolidinyl-methyl (4S)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxy lat e hydrochloride, a new calcium antagonist, for 9 wk on blood pressure and urinary excretion of electrolytes were studied in stroke-prone spontaneously hypertensive (SHRSP) rats. 2. YM-09730-5 (1 and 3 mg/kg per day, p.o.) prevented development of hypertension and produced a significant reduction in blood pressure from the first week of the experiment. Nicardipine (15 mg/kg per day, p.o.) produced almost the same degree of antihypertensive effect as YM-09730-5 at a dose of 3 mg/kg. 3. YM-09730-5 produced significant diuresis and increased urinary excretion of electrolytes throughout the experiment. 4. Chronic administration of YM-09730-5 (3 mg/kg) reduced the severity of glomerular lesions in the kidney and vasculitis in the mesenteric artery. 5. These results demonstrate that YM-09730-5 is a potential antihypertensive drug with a potency about 5 times higher than that of nicardipine.

Animals↗
PubMed1991

Angioscopy of the inferior vena cava: preliminary observations in cases with involvement by neoplasm. Work in progress.

Angioscopy of the inferior vena cava (IVC) was performed in 10 patients. Tumor thrombus extending into the IVC was suspected in six patients, and direct invasion of the IVC wall was suspected in four, based on computed tomographic and venographic findings. In each case, a fiberscope was directed to the area of interest in the IVC via a transfemoral 5-F catheter. Blood displacement by means of a saline infusion enabled angioscopic observation of the IVC wall. The neoplasms were seen clearly in all patients but one. The color and texture of the tumor thrombi surface made it easy to distinguish from the healthy IVC wall. In the four patients believed to have direct invasion of the wall, there were no angioscopic differences between the suggestive areas and adjacent areas of normal IVC wall. In these four cases, the absence of direct invasion was confirmed at surgery. Thus, angioscopy helps make an accurate nonoperative or preoperative diagnosis of tumor thrombi possible and may aid in the exclusion of direct invasion.

Adult↗
PubMed1991

Synthesis and biological evaluation of quinocarcin derivatives: thioalkyl-substituted quinones and hydroquinones.

Varieties of thioalkyl-containing quinone and hydroquinone analogues of quinocarcin (1a) were prepared effectively, by addition of mercaptan to 3a-c, which were derived from 1a via DX-52-1 (1b). Antitumor activities of these analogues were preliminarily evaluated by growth inhibition of HeLa S3 cells (in vitro) and increased life span of P388 implanted mice (in vivo). Bis(alkylthio)quinones 4a-d and 5a-d, and corresponding hydroquinones 9b-d exhibited high activities both in vitro and in vivo. They were superior to 1a especially in single administration. Selected compounds 4a, 4d, 5a, 5d, and 9b were subjected to further evaluation, and bis(methylthio)quinone 5a was revealed to possess broad-spectrum activity toward human xenographted carcinomas MX-1, Co-3, St-4, and LC-06.

Animals↗
PubMed1991

Immunohistochemical localization of superoxide dismutase in the human ovary.

To elucidate the physiological function of superoxide dismutase (SOD) in the ovary, we examined the immunohistochemical distribution of CuZn-SOD in the human ovary. We also measured the CuZn-SOD concentration in human follicular fluid by enzyme-linked immunosorbent assay (ELISA). The germinal epithelium and tunica albuginea showed no or weak immunoreactivity. No or weak staining activity was also observed in the non-antral follicle. Once the follicle began to form the antral cavity, theca interna cells began to show intensive immunostaining of SOD, as compared with no staining in the granulosa and theca externa cells. In the gestational corpus luteum, theca and granulosa lutein cells showed intensive and moderate staining activity, respectively. The concentration of CuZn-SOD was 0.222 +/- 0.186 ng/mg protein (mean +/- SD) in the preovulatory follicular fluid. In the present study, the immunohistochemical distribution of SOD was confirmed in the human ovary for the first time. Taking into consideration the fact that SOD catalyses the dismutation reaction of superoxide anion radicals, the present results suggest that theca interna cells play an important role in the protection of the developing oocyte from oxygen radicals by acting as a blood-follicular barrier during follicle maturation.

Adult↗
PubMed1991

Kindling-induced neuronal plasticity in the dorsal hippocampus CA1 in acutely prepared rabbits: unit activity analysis.

To elucidate kindling-induced neuronal plasticity single cell discharge analysis, responses consisting of action potentials orthodromically elicited in the dorsal hippocampus CA1 by a single electric shock to the neighboring region were serially observed before, during and after kindling i.e. the repetition of stimulus trains applied to the same hippocampal region in acutely prepared rabbits. Eventually, the orthodromic unit response with identical amplitudes, which were regarded as a single cell origin, gradually increased in the firing rate at the interictal stages during and after the kindling. Further, an inhibitory period following the unit responses, during which no spontaneous unit activity appeared, was remarkably prolonged during and after the kindling. Both the increase of the unit responses and the prolongation of the inhibitory period irreversibly lasted for hours once they occurred. Such unit activity analysis confirms kindling-induced excitatory and inhibitory synaptic plasticity.

Action Potentials↗
PubMed1991

Determination of acetylcholine release in the striatum of anesthetized rats using in vivo microdialysis and a radioimmunoassay.

A vertical-type in vivo microdialysis probe and a sensitive, specific radioimmunoassay (RIA) were used to study the mechanism of acetylcholine (ACh) release in the striatum of anesthetized rats. Without the use of physostigmine, a cholinesterase inhibitor, our RIA could still detect the amount of ACh present in the perfusate (5.6 +/- 0.6 fmol/min, n = 16). Tetrodotoxin (1 microM) produced a significant decrease in the amount of ACh collected in the perfusate, suggesting that basal ACh determined under the present experimental conditions was related to cholinergic neural activity. Atropine (0.1-1 microM) applied topically via the dialysis probe did not affect the amount of ACh recovered in the perfusate in the absence of physostigmine. Addition of physostigmine (10 microM) to the perfusion fluid produced about a 100-fold increase in the amount of ACh collected. In the presence of physostigmine, topical administration of atropine and pirenzepine (0.01-1 microM) through a dialysis probe produced a further three- to fourfold increase in ACh output, whereas a slight increase was produced by AF-DX 116 at the highest concentration (1 microM). These results indicate that presynaptic modulation of ACh release in the striatum does not occur under basal conditions, and that presynaptic M1 muscarinic receptors are involved in the modulation of ACh release when the ACh concentration is raised under certain conditions.

Acetylcholine↗
PubMed1991

Effect of ischemia-reperfusion on lipid digestion and absorption in rat intestine.

The purpose of this study was to assess intestinal function after ischemia-reperfusion (I/R). In two groups of intestinal lymph fistula rats (experimental), the superior mesenteric artery (SMA) was isolated and occluded for 10 min. In the remaining two groups (controls), the SMA was isolated but not occluded. Twenty-four or forty-eight hours after I/R, a lipid test meal containing radioactive triolein was infused at 3 ml/h for 8 h. Radioactive lipid in lymph, lumen, intestinal wall, portal and systemic blood, epididymal fat pads, and liver was determined. Lymph radioactive lipid output was markedly depressed in the 24-h experimental rats compared with the other three groups, and this deficiency was restored 48 h after I/R. This reduction in lipid output in lymph appeared to be the result of an increased portal transport of the infused radioactive lipid rather than a deficiency of digestion or absorption of infused triolein. We have further validated the markedly increased portal transport of radioactive lipid after I/R by using Triton WR-1339, which blocks peripheral metabolism of hepatic very low-density lipoproteins (VLDL). When Triton WR-1339 was introduced in 24 experimental and control animals, the experimental rats accumulated significantly more radioactive lipid (12-14% of infused lipid) than the control animals (2-3% of infused lipid), indicating a marked increase in portal transport of radioactive lipid, which was taken up by the liver and then resecreted into circulation as VLDL. Thus intestinal lipid absorption is sensitive to the deleterious effects of ischemia followed by reperfusion, and therefore it may be used as a functional assessment of the small intestine after I/R-induced injuries.

Adipose Tissue↗
PubMed1991

Effects of glycerol tripalmitate and glycerol trioleate on intestinal absorption of glycerol tristearate.

The goal of the present study was to determine 1) whether the poor digestion and absorption of glycerol tristearate (TS) that we observed previously is due to amount fed and 2) whether the digestion, absorption, and lymphatic transport of TS is affected by the presence of either a saturated fat [glycerol tripalmitate (TP)] or a monounsaturated fat [glycerol trioleate (TO)]. Three groups of intestinal lymph fistula rats were used. Group A was fed a lipid emulsion containing 12.5 mumol of TS (labeled as [glyceryl-1,3-14C]tristerate), 7.8 mumols of egg phosphatidylcholine, and 57 mumols of sodium taurocholate in 3 ml of phosphate-buffered saline per hour for 8 h. Group B rats were fed the same emulsion as group A, but with 12.5 mumols of TO added. Group C rats had 12.5 mumols of TP instead of TO added to the group A emulsion. The lymphatic radioactivity and triglyceride outputs were significantly lower in group A, with group C next and group B having the highest outputs. Significantly more TS remained in the lumen of the group A rats compared with groups B and C. The majority of the radioactivity in the lumen was still in the TS form in all three groups, indicating poor lipolysis. However, once the fatty acid and monoglyceride were absorbed, the reesterification process was similar in all three groups. When we studied the ability of the three groups of animals to transport the absorbed lipid into lymph (lymph transport index), both groups B and C were significantly better than group A rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Ischemia-reperfusion-induced mucosal dysfunction: role of neutrophils.

The ability of the small intestine to absorb and transport lipid into lymph is markedly reduced 24 h after a 10-min total occlusion of the superior mesenteric artery (SMA). The aim of this study was to define the role of neutrophils in the ischemia-reperfusion (I/R)-induced decrement in lipid absorption. A lipid test meal containing 40 mumol of radioactive triolein was infused intraduodenally at 3 ml/h for 8 h, and radioactive lipid output in lymph was monitored during lipid infusion in intestinal lymph fistula rats. Animals rendered neutropenic with antineutrophil serum (ANS) did not exhibit the reduction in lipid absorption and transport in lymph normally observed 24 h after I/R. This protective effect of ANS was specifically related to the reduction in the number of neutrophils in the intestinal mucosa. The amount of radioactive lipid detected in the liver of untreated rats was significantly higher than in control rats, suggesting an increased portal transport of infused radioactive lipid. Neutropenia reduced the liver lipid level toward the control value. The intestinal blood flow response to SMA occlusion was not altered by neutropenia. Our results suggest that neutrophils play an important role in the mucosal dysfunction associated with ischemia-reperfusion.

Animals↗
PubMed1991

Ornithine decarboxylase is involved in repair of small intestine after ischemia-reperfusion in rats.

To assess whether ornithine decarboxylase (ODC) is involved in mucosal repair after ischemia-reperfusion (I/R), two approaches were used: 1) measurement of mucosal ODC activity at different intervals after I/R, and 2) inhibition of ODC activity with alpha-difluoromethylornithine (DFMO, an irreversible inhibitor). In the first series of experiments, rats were allowed to recover after superior mesenteric arterial occlusion (10 min) before harvesting the intestinal mucosa for measurement of ODC activity. ODC activity increased markedly 6 h after I/R, and greater than 72 h were required for enzyme activity to return to normal. DFMO treatment completely abolished the I/R-induced increase in ODC activity. In another series of experiments, rats with an intestinal lymph fistula were infused intraduodenally at 3 ml/h with vehicle or 2% DFMO in vehicle immediately after I/R. Lipid absorption was measured at 24 and 48 h after I/R. In the DFMO group, lymph radioactive lipid output at 24 h after I/R was significantly lower compared with time-matched sham-operated controls. Lymph lipid output in rats receiving the vehicle was restored to a normal level at 48 h after I/R. However, this restoration of normal lymphatic lipid transport at 48 h I/R was not observed in the DFMO group. These observations indicate that ODC activity plays an important role in the repair process that results in complete restoration of mucosal function 2 days after I/R.

Animals↗
PubMed1991

Regional relationships between focal hypofixation images in 123I-IMP single photon emission computed tomography and epileptic EEG foci in interictal periods in patients with partial epilepsy.

Single photon emission computed tomographic (SPECT) brain scans with N-isopropyl-(iodine-123)-p-iodoamphetamine were performed in interictal periods in 40 patients with partial epilepsies and normal X-ray CT findings, and the regional relationships between the SPECT abnormalities and interictal epileptic EEG foci were studied. Twenty-six patients (65%) had abnormal SPECT images consisting of one or more focal hypofixation images, i.e., zones of decreased regional cerebral blood flow, while the remaining 14 patients showed normal images. Nineteen (73%) of the 26 patients showed complete or partial regional agreement between the abnormal SPECT findings and the interictal epileptic EEG foci determined from EEGs recorded repeatedly during their clinical course, while the regional relationships with the EEG foci determined from the single EEG recorded just after the SPECT scans or a short interval after the scans showed a lower rate of agreement (13 of 21 patients, 61.9%). These results confirm the utility of SPECT scans in the regional diagnosis of epileptic foci.

Adolescent↗
PubMed1991

Human recombinant granulocyte colony-stimulating factor for the treatment of autoimmune neutropenia.

We have recently treated a case of autoimmune neutropenia in a 57-year-old male. Because neutropenia persisted despite the administration of prednisolone for 30 days, daily subcutaneous injection of human recombinant granulocyte colony-stimulating factor (rhG-CSF) at a dosage of 100 micrograms was started. Neutrophil count increased gradually and reached a plateau of 5,000/microliters by day 25 after administration of rhG-CSF. This observation suggests that rhG-CSF is effective for the treatment of autoimmune neutropenia.

Autoimmune Diseases↗
PubMed1991

Neoadjuvant therapy for locally invasive bladder cancer: results of randomized trials in 40 patients.

The present investigation was conducted to examine the effect of a neoadjuvant cyclophosphamide, doxorubicin and cisplatin (CAP) regimen with radiotherapy for locally invasive bladder cancer as a well-controlled randomized trial. Since 1986, a total of 40 patients with primary transitional cell carcinoma of the urinary bladder have been randomized into two groups: neoadjuvant CAP plus radiation-treated group and control group. Of 18 patients who received neoadjuvant chemotherapy, complete and partial responses were observed in 52.9% of 17 measurable and evaluable patients and downstaging was observed in 92.9% of 14 evaluable patients. The 3-year survival rates of the neoadjuvant-treated and control group were 93.8 and 83.6%, respectively. No statistical significance was achieved in the survival rates. These results indicated that neoadjuvant CAP would be useful in the management of invasive bladder cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Morphometrical changes in the apical surface of the colonic absorptive cells in perinatal rats with special reference to the effect of fetal oral administration of milk in utero.

Perinatal changes in the apical surface of the colonic absorptive cells in the rat were studied morphometrically. Cell microvilli length increased from day 20 through neonatal day 3, during which a maximum incremental growth rate was noted between fetal day 22 and neonatal day 1. Microvilli width remained almost constant throughout the period. Enlargement of the apical surface of the microvilli showed a similar developmental pattern as was seen from the measurement of length and surface area of any one of the microvilli. Fetal oral administration of milk in utero caused incremental growth in length and surface area, as well as an associated apical surface enlargement. The present study indicates that the function of the colonic absorptive cells, which is acquired later on in utero, is activated by ingestion of maternal milk after birth.

Administration, Oral↗