Biomedical subjects

H Tsukada

Publications and source records attributed to H Tsukada.

At least 109 records · Page 6Linked to original sources

PubMed1998

Cerebral blood flow autoregulation following subarachnoid hemorrhage in rats: chronic vasospasm shifts the upper and lower limits of the autoregulatory range toward higher blood pressures.

We sought to determine whether chronic vasospasm following subarachnoid hemorrhage (SAH) would abolish the cerebral blood flow (CBF) autoregulation in anesthetized Sprague-Dawley rats. SAH was induced by intracisternal injection of autologous blood; in control animals saline was injected instead. CBF was measured 48 h after SAH, that is during chronic vasospasm, by laser-Doppler flowmetry over the frontal cortex under condition of hypertension (SAH, n = 6; control, n = 8) or hypotension (SAH, n = 6; control, n = 6). Hyper- and hypotension were induced by increasing mean arterial blood pressure (MABP) stepwise from 90 to 180 mmHg with phenylephrine (0.1-10 micrograms/min i.v.), or by decreasing it from 90 to 40 mmHg by controlled hemorrhage. An autoregulatory index (AI) expressed as delta CBF (%) per 10 mmHg increase or decrease in MABP was employed to analyze CBF response. CBF remained constant (-7 < AI < 7) at MABPs ranging from 60 to 130 mmHg in the control group and from 70 to 140 mmHg in the SAH group, showing CBF autoregulation. In the SAH group, that is, the upper and the lower limits of autoregulatory range were increased by 10 mmHg (p < 0.05). SAH did not increase intracranial pressure significantly (control 9.2 +/- 0.67 vs. SAH 10.0 +/- 1.05 mmHg, n = 5) 48 h after SAH was induced. These results indicate that, during chronic vasospasm, SAH does not abolish the autoregulation process but raises its lower and upper blood pressure limits. The capacity of spastic cerebral arteries to dilate in case of hypotension decreased, while their tolerance to hypertension increased.

Animals↗

PubMed1998

Application of a beta microprobe for quantification of regional cerebral blood flow with (15)O-water and PET in rhesus monkeys.

A beta microprobe was successfully applied to monitor arterial input function for quantification of regional cerebral blood flow (rCBF) in the monkey brain with (15)O-water and positron emission tomography (PET). The sensitivity of the probe was approximately 0.83 to 1.67 cps/kBq/ml depending on the studies. A preliminary study was performed to find a suitable use and to evaluate the performance of the system and data analysis procedure. The results showed that dispersion correction of measured input function was unnecessary if microprobes were connected directly to the arterial catheter. Then multiple CBF measurements were done in three monkeys under anesthesia. Identical regions of interest were placed with the aid of magnetic resonance imaging (MRI) of each monkey and rCBF values were estimated. Estimated rCBFs were reproducible for several measurements. The mean CBF value for a pentobarbital anesthetized monkey was 46.0 ml/min/100 g (PaCO2 = 46.3 mmHg). This shows that the use of the beta microprobe for quantification of rCBF with PET was validated. The lack of a need for dispersion correction of observed input function is an advantage with the beta microprobe system because the probes are small enough to be placed near the arterial sampling site.

Animals↗

PubMed1998

Lipomatosis of the ileum with volvulus: report of a case.

We herein present a patient with lipomatosis of the ileum including diverticulosis and volvulus. The patient presented with abdominal pain and vomiting. Preoperatively, we diagnosed lipomatosis with volvulus of the ileum based on the findings of abdominal ultrasonography (US) and computed tomography (CT). During surgery, the dilated ileum had rotated 720 degrees counterclockwise, and was found to contain lipomatosis and multiple diverticula. Although lipomatosis of the small bowel is extremely rare, it does show characteristic US and CT findings, thus making a preoperative diagnosis possible if this disease is included in the differential diagnosis.

Adult↗

PubMed1998

In vitro and in vivo characterization of (+)-3-[11C]cyano-dizocilpine.

(+)-3-[11C]Cyano-5-methyl-10,11 -dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine ([11C]MKC) was successfully synthesized as a potential radiotracer for PET studies on the NMDA receptor channel complex. In vitro binding properties of [11C]MKC were investigated with newly developed techniques for efficient evaluation of 11C-labeled compounds. The association curve of [11C]MKC binding in rat forebrain membranes showed that the specific binding reached an equilibrium within 30 min. Specific binding was saturable with affinity constant KD=8.2+/-0.4nM and Bmax=1.62+/-0.04 pmol/mg protein with glutamate and glycine included in the incubation medium. The binding of [11C]MKC was decreased by extensive washing of the membrane preparation. (+)- and (-)-Dizocilpine, 3-cyano-dizocilpine, and ketamine inhibited the specific binding of [11C]MKC with IC50 values of 37.3, 445.0, 65.8nM and 3.91 microM, respectively. High specific binding in in vitro autoradiography was distributed predominantly in telencephalic regions (the hippocampus, cerebral cortex, and striatum) followed by thalamus. PET studies using rhesus monkeys under anesthesia showed high uptake of [11C]MKC in the temporoparietal and frontal cerebral cortices, striatum, and thalamic regions, although it is problematic to verify the specific binding in vivo by PET.

Animals↗

PubMed1998

Dietary carbohydrate intake plays an important role in preventing alcoholic fatty liver in the rat.

BACKGROUND/AIMS: Dietary carbohydrate intake during ethanol ingestion augments the induction of hepatic cytochrome P450 2E1 (CYP2E1) by ethanol. This study addresses the role of carbohydrate intake in the development of alcoholic fatty liver in the rat. METHODS: Male Sprague-Dawley rats were pair-fed on liquid diets containing ethanol (3.5 g/day, 36% of total calories) with different amounts of carbohydrate and fat for 4 weeks, and the development of fatty liver was observed biochemically and morphologically. RESULTS: An ethanol-containing low-carbohydrate diet (protein 17%; fat 36%; carbohydrate 11%; ethanol 36%) had more markedly adverse effects on the liver of rats than did an isocaloric ethanol-containing high-carbohydrate diet (protein 17%; fat 5%; carbohydrate 42%; ethanol 36%). The hepatic triglyceride level in the rats that consumed the low-carbohydrate diet was higher than that in the rats kept on the high-carbohydrate diet, a finding that was confirmed histologically. The ethanol-containing low-carbohydrate diet caused a marked increase in the activity of hepatic CYP2E1. The CYP2E1 protein level, as measured by Western blot analysis, matched the activity of CYP2E1, as measured by the rates of dimethylnitrosamine, p-nitrophenol and ethanol metabolism. The severity of the fatty liver was well correlated with the increased CYP2E1 activity. CONCLUSIONS: Dietary carbohydrate intake plays an important role in the development of alcoholic fatty liver by affecting CYP2E1 activity in the liver. A liquid diet containing ethanol in which the ethanol is included at the expense of fat is more acceptable to rats than a diet in which the ethanol replaces carbohydrate.

Animals↗

PubMed1998

Effect of adrenomedullin on ion transport and muscle contraction in rat distal colon.

We have investigated the effects of adrenomedullin (AM) on mucosal ion transport using the Ussing method and smooth muscle contraction using the Magnus method in rat. Our results indicate that AM increases Isc (short-circuit current) for Cl- secretion (100 nM:170.0 +/- 41.2%, 1 microM:193.8 +/- 45.5%, 100% Isc:28.2 +/- 3.1 microA/cm2) with an initial small decrease of Isc, inhibiting Na+ absorption. Tetrodotoxin (TTX) inhibits the Isc response elicited by AM (86%). In addition, AM relaxes potassium-induced contraction (10 nM:11.1 +/- 8.51%, 100 nM:33.4 +/- 12.7%, 100% contraction: 1.8 +/- 0.22 g), and TTX inhibits the response elicited by AM (90%). We conclude that AM modulates water and ion transport as well as bowel movement, mainly through the colonic nervous system.

Adrenomedullin↗

PubMed1998

Sustained withdrawal allows normalization of in vivo [11C]N-methylspiperone dopamine D2 receptor binding after chronic binge cocaine: a positron emission tomography study in rats.

In our previous positron emission tomography studies striatal binding for both [11C]SCH23390 and [11C]N-methylspiperone (NMSP) were decreased in the rat brain on the last day of chronic (14 days) binge cocaine administration. We have found that [11C]SCH23390 binding to dopamine D1 receptors returns to saline control levels within ten days withdrawal from chronic binge cocaine and remains at control levels after 21 days withdrawal. An 18% decrease in [11C]NMSP binding to dopamine D2 receptors was observed after ten days withdrawal. However, importantly, after 21 days withdrawal [11C]NMSP binding was at saline control levels. Changes of in vivo [11C]NMSP binding required a longer abstinence period for normalization than [11C]SCH23390 binding. The apparent recovery of dopamine D2 receptors after prolonged abstinence from chronic cocaine and the different rates of normalization for dopamine D1 versus D2 receptors may be critical information for development of pharmacotherapies for cocaine dependent patients.

Analysis of Variance↗

PubMed1998

Monitoring of Echinococcus multilocularis infection in red foxes in Shiretoko, Japan, by coproantigen detection.

The study was conducted to evaluate a mAb-based coproantigen detection assay for monitoring fox prevalence of Echinococcus multilocularis infections in the Shiretoko National Park in Hokkaido, Japan. Eight fox families, each consisting of 2-4 adults and their pups, were selected because their territories have been determined. Faeces of each family (total n = 537) were collected monthly from April to October, 1994. Detection of coproantigen and taeniid eggs was recognized in 58 and 27 faeces, respectively, but mostly restricted in 1 family, in which coproantigen ELISA OD values had dual peaks, one in June and the other in October, whereas taeniid eggs were detected only from April to July. Fox pup faeces (n = 51) collected around the dens used by the positive family were all coproantigen and taeniid egg negative except for 1 faeces. These results suggest that the prevalence and infection pressure in the study area were low and the infected family terminated the infection in the summer and acquired a new one in the early autumn, 1994. This monitoring method for fox infection will be a practical management tool for E. multilocularis infection, especially at the tourist spots in Hokkaido where close contact of fox with humans is frequently observed.

Animals↗

PubMed1998

Effects of okadaic acid on rat colon.

Effects of okadaic acid (OA) on mucosal damage were examined in rat colon. OA was sprinkled on rat colon mucosa under observation with an electronic-endoscopic system, and OA was also applied to the in vivo microscopic field. The OA-induced changes in transepithelial conductance (Gt) were measured by the Ussing voltage clamp technique. By endoscopic observation, the luminal sprinkling of OA (60 nmol/kg) evoked transient microthrombi in the submucosal venule, which was followed by mucosal edema. Histological study after endoscopic observation showed submucosal fluid retention, suggesting an increase of vascular permeability. The microthrombi were also detected by in vivo microscopy. By electrophysiological study after endoscopic observation with and without OA addition, the basal Gt values were 54+/-6.2 and 36.2+/-4.2 mS/cm2, respectively (P < 0.01). Furthermore in control rats, the serosal addition of OA evoked an increase in Gt in a concentration-dependent manner without increasing lactate dehydrogenase release. 2,4,6-Triaminopyrimidinium inhibited OA-induced Gt change by 60%. These results indicate that OA evokes an increase in paracellular permeability of epithelium. We conclude that the developed microthrombi are the first key event of OA-induced mucosal damage, followed by an increase in permeability in the submucosal venule and in the paracellular pathway of the epithelium.

Animals↗

PubMed1998

Role of sialylglycoconjugate(s) in the initial phase of metastasis of liver-metastatic RAW117 lymphoma cells.

To elucidate the early events of blood-borne metastasis under actual blood flow, real-time trafficking of RAW117 large cell lymphoma cells, namely parental RAW117-P and liver-metastatic RAW117-H10 cells, was investigated using positron emission tomography (PET). Both types of cells accumulated in the liver immediately after injection via the portal vein, and were eliminated from the liver time-dependently. The elimination rate of RAW117-H10 cells, however, was slower than that of RAW117-P cells, suggesting that RAW117-H10 cells interact more strongly with hepatic sinusoidal endothelium than the parental cells. This result correlated with the metastatic potential of these cells: RAW117-H10 cells metastasized in the liver to a greater extent than RAW117-P cells after injection via this route. To investigate the role of sialylglycoconjugates in the interaction of RAW117-H10 cells with the hepatic endothelium after injection via the portal vein, the trafficking of RAW117-H10 cells was examined after the cells had been treated with sialidase. The elimination rate of RAW117-H10 cells from liver was observed to be greatly accelerated by sialidase treatment. To elucidate what kind of sialylglycoconjugates is related to this phenomenon, we analyzed the distribution of sialyl Lewis A and sialyl Lewis X antigens of both sublines of RAW117 by using flow cytometry. RAW117-H10 cells were found to express a much higher level of sialyl Lewis A than RAW117-P cells, whereas the amount of sialyl Lewis X did not differ significantly. These findings suggest that some sialylglycoconjugates, perhaps sialyl Lewis A in particular, play an important role in the initial interaction of RAW117-H10 cells with the hepatic endothelium, leading to metastasis.

Animals↗

PubMed1998

Effects of the anti-ICAM-1 monoclonal antibody on dextran sodium sulphate-induced colitis in rats.

Increased expression of intercellular adhesion molecule-1 (ICAM-1) in the colon of inflammatory bowel disease (IBD) has been reported. We evaluated the effects of monoclonal antibodies to ICAM-1 on acute colitis induced by dextran sodium sulphate (DSS) in rats. Colitis was induced by feeding rats 3% DSS for 7 days. Anti-ICAM-1 antibody or vehicle alone was injected intraperitoneally in rats daily from day 0 to day 6. On day 7 the rats were killed and colitis was evaluated histologically. Prophylactic treatment with anti-ICAM-1 significantly attenuated colonic damage, neutrophil infiltration and the shortening of the colon in DSS colitis. Our findings demonstrate that ICAM-1 plays an important role in this model of inflammatory bowel disease. Although this study does not directly address the effect of anti-ICAM-1 therapy in IBD, our findings encourage experiments using therapies that target ICAM-1 in rats with already developed disease.

Animals↗

PubMed1998

Antitumor activity of 5'-O-dipalmitoylphosphatidyl 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine is enhanced by long-circulating liposomalization.

We previously synthesized the 5'-O-diacylphosphatidyl derivative of 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine (CNDAC), a novel antitumor nucleoside, and observed it to have a high antitumor activity. Since this compound is readily incorporated into liposomal membranes, we liposomalized the compound using a formulation for conventional and long-circulating liposomes, and investigated the antitumor activity of liposomal 5'-O-dipalmitoylphosphatidyl CNDAC (DPP-CNDAC). Long-circulating liposomes composed of DPP-CNDAC, dipalmitoylphosphatidylcholine, cholesterol and palmityl-D-glucuronide (PGlcUA) (2:2:2:1 as a molar ratio), as well as liposomes containing dipalmitoylphosphatidylglycerol (DPPG) instead of palmityl-D-glucuronide and those composed of only DPP-CNDAC, were injected intravenously into Meth A sarcoma-bearing mice. DPP-CNDAC showed suppression of tumor growth, whereas CNDAC did not at the same concentration, suggesting that 5'-phosphatidylation is useful to enhance therapeutic efficacy. Furthermore, liposomal DPP-CNDAC reduced the acute toxicity, and liposomes containing PGlcUA showed more enhanced activities of reducing tumor growth and increasing the lifetime of the mice than liposomes containing DPPG. To obtain a higher therapeutic efficacy, we injected long-circulating liposomal DPP-CNDAC 5 times. The tumor growth was suppressed to 13.2% (86.8% inhibition), and the survival time of the tumor-bearing mice increased to 128.5% with one completely cured mouse out of five. Next, the effect of DPP-CNDAC incorporation on the in vivo behavior of PGlcUA and DPPG liposomes was examined by a non-invasive method using positron emission tomography (PET). Liposomes were labeled with [2-(18)F]-2-fluoro-2-deoxy-D-glucose, and administered to tumor-bearing mice. PET images and time-activity curves indicated that DPP-CNDAC/PGlcUA-liposomes tended to accumulate in tumor tissues a little bit more than DPP-CNDAC/DPPG-liposomes, although the difference between the two kinds of liposomal distribution was not as marked as between PGlcUA and DPPG liposomes, suggesting that DPP-CNDAC incorporation partly affected the liposomal behavior in vivo but that the long-circulating character of PGlcUA-liposomes might not be fully abolished. Thus, the enhanced therapeutic efficacy of long circulating liposomalized DPP-CNDAC observed here may be due to passive targeting of DPP-CNDAC to the tumor tissue, making this formulation of DPP-CNDAC useful for cancer chemotherapy.

Animals↗

PubMed1998

Clinical features of polymyositis/dermatomyositis with steroid-resistant interstitial lung disease.

Polymyositis and dermatomyositis (PM/DM) without creatine kinase (CK) elevation shows a poor prognosis. PM/DM is complicated with interstitial lung disease (ILD), some of which progress rapidly. To clarify the clinical features of PM/DM from the viewpoint of ILD progression, the clinical data of 25 PM/DM patients with ILD were reviewed. They were classified as responders or non-responders. The patients whose ILD responded to steroid therapy and elicited good clinical courses were termed as responders. On the other hand, the patients who had rapidly progressive ILD resistant to steroid therapy were considered as non-responders. The patients diagnosed to have DM were likely to be steroid-resistant. The non-responder group revealed significantly high aspartate aminotransferase (AST), low CK, low white blood cell (WBC), and low absolute lymphocyte counts in their peripheral blood. High CK/AST may be a favorable predictor of the disease. The percentages of lymphocytes in bronchoalveolar lavage fluid were increased in both groups. However, the percentages of two responders with low CK/AST were lower than those of three non-responders. A steroid-resistant ILD group with PM/DM may be clinically different from a steroid-responsive ILD group.

Aged↗

PubMed1998

Changes in cerebral blood flow and postsynaptic muscarinic cholinergic activity in rats with bilateral carotid artery ligation.

UNLABELLED: Changes in both regional cerebral blood flow (rCBF) and postsynaptic muscarinic cholinergic activity in the rat brain were investigated after ligation of the common carotid arteries (CCAs) bilaterally with (15)O-labeled water (H2(15)O) and [11C]N-methyl-4-piperidylbenzilate, a potent muscarinic receptor antagonist. METHODS: PET was performed in the same Wistar rat, 7 days and 1 mo after the CCA ligation. Regional cerebral blood flow and the transfer coefficient k3, the rate of binding of 11C-NMPB, were measured, based on the autoradiographic method and the graphical plotting analysis, respectively. RESULTS: The levels of rCBF in the frontal cortex of the ligated group were significantly lower than those in the cerebellum and those in sham group, after 7 days and 1 mo postoperation. Although the level of k3 in the frontal cortex 7 days after operation was not altered, it decreased significantly after 1 mo in the ligated group. Neither cortical infarct nor cortical neuronal loss was observed histologically. CONCLUSION: Common carotid artery ligation in Wistar rats caused a prolonged cerebral hypoperfusion without degeneration of the cortical neurons and a later decline of postsynaptic cholinergic receptor activity. These findings suggest that the decline in the postsynaptic cholinergic activity that is associated with the prolonged reduction in the cerebral blood supply may reflect pathophysiology that is equivalent to the deterioration of cognitive function in patients with chronic cerebrovascular insufficiency.

Animals↗

PubMed1998

[Left S1+2+3 segmentectomy by using the auscultatory triangle thoracotomy].

We performed a left S1+2+3 segmentectomy by preserving latissimus dorsi muscle on 3 patients with primary lung cancer and measured pre-operative and post-operative respiratory function. During the 3 post-operative months, VC, FEV1.0, Peak flow and MVV recovered almost to the same level of pre-operative values, while DLCO did not recover sufficiently. Seroma should be ignored for the first 4 post-operative weeks unless infection appears, because seroma will be absorbed naturally.

Aged↗

PubMed1998

Bronchial wall schwannoma removed by sleeve resection of the right stem bronchus without lung resection.

A 28-year-old man presented with a bronchial wall schwannoma occurring in the right main to the intermediate bronchus. The tumor was resected en-bloc with the stem bronchi without pulmonary resection. Airway reconstruction consisted of an end-to-end anastomosis of the intermedius bronchus to the right main bronchus, and an end-to-side anastomosis of the right upper lobe bronchus to the lateral wall of the trachea. Postoperative course was uneventful. Bronchoplastic procedure with preservation of the lung parenchyma seems to be the technique of choice for benign tumors occurring intramurally in the stem bronchus.

Adult↗

PubMed1997

Use of positron emission tomography to measure the effects of nalmefene on D1 and D2 dopamine receptors in rat brain.

Positron emission tomography (PET) has been used in humans and in non-human primates to image and measure radioligand binding to neuroreceptors. The present study evaluated the feasibility of performing high-resolution PET experiments in a rodent model to measure receptor kinetics. The effects of acute and chronic administration of the opioid antagonist, nalmefene, on the binding activity of [11C]SCH23390 and [11C]N-methylspiperone at D1 and D2 dopamine receptors, respectively, was investigated in the rat. The interaction between central opioid and dopaminergic systems has been the focus of much attention due to their interactive role in mediating reinforcement and locomotor activity. In the present study, adult male Sprague-Dawley rats received either a single injection of 10 (mg/kg of nalmefene or control vehicle solution 1 h prior to the PET scan or were chronically administered 10 mg/kg/day of nalmefene or vehicle for 7 days by an osmotic minipump. Following acute administration of nalmefene, the binding potential of [11C]SCH23390 in the striatum was significantly increased. No changes in [11C]N-methylspiperone binding were found. Following chronic nalmefene administration, no significant change in either [11C]SCH23390 binding potential or [11C]N-methylspiperone binding was detected. These results suggest that nalmefene administration produces transient changes in the binding potential of D1-receptors in the striatum that are normalized after 1 week of steady-state administration.

Animals↗

PubMed1997

Tumor cells with organ-specific metastatic ability show distinctive trafficking in vivo: analyses by positron emission tomography and bioimaging.

To elucidate the behavior of various metastatic tumor cells with different characteristics in the blood flow, we have developed a system to investigate real-time trafficking using positron emission tomography. In this study, positron-labeled cells, i.e., lung-metastatic B16BL6 melanoma and two sublines of liver-metastatic RAW117 large cell lymphoma, were injected i.v., and the trafficking of these cells was noninvasively determined. All sublines tested accumulated in the lungs immediately after injection, presumably because the lungs were the first organ passed through after i.v. injection. The elimination of RAW117 cells from the lungs, however, was fast compared with that of B16BL6 cells. The latter showed a release rate from the lungs of less than 1%/min, whereas that of RAW117 cells was greater than 2%/min. Reflecting the elimination from lungs, RAW117 cells accumulated in the liver in a time-dependent manner. Biodistribution of metastatic cells was also analyzed by whole-body autoradiography after injection of 5-[125I]iodo-2'-deoxyuridine-labeled cells, using a bioimaging analyzer system. The method is invasive; however, it enables a precise determination of the biodistribution of metastatic cells. Bioimaging analyzer system analysis also showed the organ-specific accumulation of these metastatic cells. Furthermore, colonized distribution of B16BL6 cells in the lungs and that of RAW117 cells in the liver were observed. The present data suggest that the trafficking of metastatic tumor cells greatly influences the organ specificity of cancer metastasis.

Animals↗