Search PubMed⌕ Search

Biomedical subjects

K Kawabata

Publications and source records attributed to K Kawabata.

At least 199 records · Page 11Linked to original sources
PubMed1995

Changes in soluble ICAM-1 level during hemodialysis.

Intercellular adhesion molecule-1 (ICAM-1) is expressed on the surface of various types of cells, including lymphocytes, monocytes and vascular endothelial cells. Recently, ICAM-1 was reported to be shed from the cell membranes and released into circulation. The soluble ICAM-1 (sICAM-1) level has been reported to be increased in patients with certain inflammatory diseases. It is well known that the functions of leukocytes including neutrophils, lymphocytes and monocytes are impaired in patients with chronic hemodialysis. In this study, we evaluated the effect of hemodialysis (HD) on the lymphocytes and monocytes by periodically measuring the serum concentration of sICAM-1 during HD. Pre-HD sICAM-1 levels in chronic hemodialysis patients were significantly increased as compared with healthy subjects. Two hundred and forty minutes after the start of HD, sICAM-1 levels were significantly higher than the pre-HD levels. The sICAM-1 levels at the venous side of the dialyzer were significantly increased compared with the levels at the arterial side. There was no significant difference between the sICAM-1 levels of the patients under hemodialysis with the regenerated cellulose membrane and those with the polymethylmethacrylate membrane. These results suggest that ICAM-1 is shed from the surface of mononuclear cells (lymphocytes and monocytes) and released into circulation stimulated by hemodialysis membranes. Chronic hemodialysis may impair the function of mononuclear cells by inducing the shedding of ICAM-1.

Aged↗
PubMed1994

Simultaneous multielemental analysis of daily food samples by inductively coupled plasma mass spectrometry.

Several toxic elements in total composite food samples of hospital diets were determined simultaneously by inductively coupled plasma mass spectrometry (ICP-MS). Trace element concentrations of Be, Cr, As, Cd, Sn, Sb, Ce, Hg and Pb changed widely ranging from a few ng.g-1 to less than 3 micrograms.g-1 in all 24 samples collected through a year. Be, Sn, and Hg were not detected in rice sample alone, and other trace elements, with the exception of Cr and As, were less than approximately 50% levels, as compared with mixed diet samples. The daily intakes of these toxic elements were in the ranges of a few to several hundreds of micrograms.

Food Analysis↗
PubMed1994

Differential expression patterns of mRNAs for members of the fibroblast growth factor receptor family, FGFR-1-FGFR-4, in rat brain.

We have examined the region-specific expression of mRNAs for four members of rat FGF receptor family, FGFR-1, FGFR-2 FGFR-3, and FGFR-4, in rat brain by in situ hybridization. The FGFR-1, FGFR-2, and FGFR-3 mRNAs were expressed widely but differentially in the brain. However, the FGFR-4 mRNA was not expressed in the brain. The FGFR-1 mRNA was strongly expressed in several regions including the hippocampus, cerebellum, and pedunculopotine tegmental nucleus. The FGFR-2 mRNA expression was high in the choroid plexus, and moderate in the fiber-rich regions (the corpus callosum, external capsule, and internal capsule) and the olfactory bulb. The FGFR-3 mRNA was expressed diffusely in the brain. We have also examined the cellular localization of these mRNAs in the brain. Although the FGFR-1 mRNA was expressed preferentially in neurons, the FGFR-2 and FGFR-3 mRNAs were expressed preferentially in glial cells. The present findings that the FGFR-1, FGFR-2, and FGFR-3 mRNAs were expressed widely but with region- and cell-specificity in the brain indicate that these receptors have different roles in the brain.

Amino Acid Sequence↗
PubMed1994

Anticancer chemosensitivity profile of freshly separated human pancreatic cancer cells assessed by DNA synthesis inhibition assay.

The chemosensitivity of 49 freshly separated human pancreatic cancers to seven kinds of anticancer agents were assessed by a DNA synthesis (3H-thymidine incorporation) inhibition assay. DNA synthesis is higher in involved lymph nodes (n = 7), malignant effusion (n = 15), liver metastasis (n = 7), primary cancer (n = 15), and skin metastasis (n = 5). Chemosensitivity assay demonstrates that etoposide, 4-epirubicin, carboquone, and 5-fluorouracil are more effective than cisplatin, mitomycin-C, and Adriamycin. In general, metastatic lesions of pancreatic cancer tend to show higher chemosensitivity than primary lesions. Pathological analysis demonstrates that small primary pancreatic cancers tend to be more responsive than large primary cancers, and primary pancreatic cancers with no regional lymph node involvement also tend to be more responsive than those with nodal involvement. No significant differences are seen in terms of tumor spread, vascular involvement, sex of patient, and histological type. When chemosensitivity assay is not available, the results of the present study may be beneficial to choose the regimens.

Adult↗
PubMed1994

Three-dimensional surface display of brain perfusion with 123I-IMP in Parkinson's disease.

We reconstructed three-dimensional (3D) surface images from single-photon emission computed tomography (SPECT) data using N-isopropyl-p[123I]-iodoamphetamine (123I-IMP) in 27 patients with Parkinson's disease and 11 normal control subjects. The 3D reconstruction was performed using distance-shaded methods at threshold levels with an interval of 5% from 45-80%. Any area of decreased perfusion at each threshold level was visualised as a defect area by the algorithm. In nondemented patients with Parkinson's disease, perfusion defects were frequently found in the parietal cortex at a threshold value of 65%. In demented patients, perfusion defects were frequently seen at thresholds of 45-65%, and were more marked in the temporal and parietal cortex bilaterally. This suggests that dementia in Parkinson's disease is related to a reduction of perfusion in the temporoparietal cortex.

Aged↗
PubMed1994

Cerebral blood flow in subcortical global aphasia. Perisylvian cortical hypoperfusion as a crucial role.

BACKGROUND AND PURPOSE: Global aphasia after subcortical stroke is very rare, and its pathophysiology remains unsolved. To clarify the mechanism underlying subcortical global aphasia, we investigated lesion sites and cerebral blood flow in patients with subcortical global aphasia and nonaphasic patients with subcortical stroke. METHODS: We examined four patients with global aphasia and four nonaphasic patients. Language testing was performed more than 4 weeks after the onset. Measurement of cerebral blood flow was done between 35 and 75 days after stroke by using single-photon emission computed tomography (SPECT) with N-isopropyl-p[123I]iodoamphetamine as a tracer and three-dimensional surface display generated from SPECT. RESULTS: All aphasic patients had subcortical lesions in the putamen, posterior internal capsule, temporal isthmus, and periventricular white matter in the left hemisphere. No cortical lesions were found on either magnetic resonance imaging or computed tomographic scanning. The nonaphasic patients had smaller periventricular white matter lesions and no temporal isthmus lesions. All aphasic patients showed cortical hypoperfusion mainly in the perisylvian areas, including Broca's and Wernicke's areas. In contrast, cortical cerebral blood flow of the nonaphasic patients was decreased in smaller areas and spared the perisylvian language areas. CONCLUSIONS: These results suggest that cortical hypoperfusion in the perisylvian language areas, presumably due to undercutting of the white matter, is crucial for the development of subcortical global aphasia.

Aged↗
PubMed1994

Decrease in vecuronium infusion dose requirements by nicardipine in humans.

This study was designed to analyze quantitatively the interaction of nicardipine with vecuronium using a constant infusion technique. Forty-seven patients undergoing elective otolaryngeal surgery were anesthetized with isoflurane (1% end-tidal) and nitrous oxide (67%). Patients were randomly assigned to receive one of four doses of nicardipine (0, 1, 2, and 3 micrograms.kg-1.min-1). Vecuronium infusion dose requirement was determined as a constant infusion rate which maintained 90% depression of control twitch tension. Nicardipine significantly decreased the vecuronium requirement in a dose-dependent manner, i.e., the vecuronium doses were 0.70 +/- 0.03, 0.55 +/- 0.04, 0.42 +/- 0.04, and 0.37 +/- 0.05 micrograms.kg-1.min-1 at nicardipine doses of 0, 1, 2, and 3 micrograms.kg-1.min-1, respectively. Nicardipine also reduced both the plasma concentration of vecuronium to maintain the 90% depression and the total plasma clearance of vecuronium. The reversal of the vecuronium effect with neostigmine was not influenced by nicardipine. The results indicate that the vecuronium infusion dose requirements are reduced as much as 53% by a clinical dose of nicardipine.

Adult↗
PubMed1994

[Undifferentiated carcinoma of cervical node metastases in patients with an unknown primary lesion: an immunohistochemical study].

Sixteen patients with lymphatic metastases to the neck and a histological diagnosis of undifferentiated carcinoma from an unknown primary lesion were assessed using immunohistochemical staining. The results revealed a non-epithelial tumor in 11 cases (malignant lymphoma in 5 cases) and an epithelial tumor in 3 cases. The patients with malignant lymphoma had a good outcome, but those with other non-epithelial tumors did not. Treatment of patients with an unknown primary tumor, especially undifferentiated carcinoma, should be carefully evaluated based on immunohistological examinations to identify malignant lymphoma.

Adenocarcinoma↗
PubMed1994

[Control of in vivo characteristics of gene and antisense DNA disposition].

In order to construct a strategy for control of in vivo disposition characteristics of gene and antisense DNA, in vivo stability and basic pharmacokinetic properties of DNA were investigated. A model gene, plasmid DNA (pCAT), and model oligonucleotide (thymidine 10-mer; T10) derivatives with phosphoroamidate substitution at the 3' and/or 5'-terminal internucleotide linkage, were rapidly degraded in vivo after intravenous injection into mice. The degradation rates were much faster than those observed in in vitro experiments using plasma and whole blood, suggesting that they underwent enzymatic degradation in other compartments than the blood pool. More than 70% of injected pCAT was taken up by the liver within 5 minutes, and the uptake clearance was almost identical to the plasma flow rate in the liver. On the other hand, T10 derivatives were rapidly excreted in the urine and taken up by the kidney and liver. The urinary excretion clearance was close to the glomerular filtration rate. In an attempt to control T10 disposition characteristics, the oligonucleotide was conjugated to a macromolecular carrier, carboxymethyl dextran (CMD). The T10-CMD conjugate exhibited increased in vivo stability and prolonged plasma circulation time. Thus, the present study has shown that macromolecular conjugation is a useful approach to improve in vivo disposition of antisense oligonucleotides.

Animals↗
PubMed1994

[A case of scleroderma renal crisis with acute interstitial pneumonia, microangiopathic hemolytic anemia and refractory thrombocytopenia].

A 46-year-old woman who noticed tightness of the skin in September, 1993, was admitted to a local hospital due to hypertension, congestive heart failure and renal dysfunction on the 2nd of November. After admission, renal function deteriorated progressively. A diagnosis of scleroderma renal crisis (SRC) was suspected from her skin biopsy and clinical course. She was referred to our hospital for further evaluation and maintenance of hemodialysis. Her blood pressure was kept normal by anti-hypertensive drugs including cilazapril. Acute interstitial pneumonia, microangiopathic hemolytic anemia and thrombocytopenia appeared during her clinical course. Corticosteroid therapy was effective for acute interstitial pneumonia, but in-effective for thrombocytopenia. Plasma exchange was not effective for thrombocytopenia, which was successfully treated with intravenous gamma-globulin therapy. She died of cytomegaloviral encephalitis, which might have resulted from immunodeficiency caused by prolonged corticosteroid therapy and uremia. Complications other than SRC might have appeared during the clinical course based on the immune disorder of progressive systemic sclerosis itself. In order to improve the prognosis of patients with SRC such complications should be detected promptly and treated correctly.

Acute Disease↗
PubMed1993

Endometrial assessment by transabdominal ultrasonography in postmenopausal women.

We evaluated the usefulness of transabdominal ultrasonography (TAS) for endometrial abnormalities in postmenopausal women. A total of 232 postmenopausal women were examined by TAS and endometrial sampling. Abnormal findings, including endometrial hyperplasia, atypical hyperplasia and endometrial cancer, were noted in 0.7% (1/41) of sonographically measured endometrium < 2 mm and in 15.4% (14/91) of measurements > or = 2 mm. Endometrial cancer was found in 5.9% in the postmenopausal bleeding group (n = 85) and in 1.4% in the symptom-free group (n = 147). With one exception, all endometrial abnormalities were in endometrial thickness > or = 2 mm. We conclude that TAS has limitations as a technique but is useful in deciding which postmenopausal women require endometrial biopsy.

Adult↗
PubMed1993

Loxiglumide (CR1505), a cholecystokinin antagonist, specifically inhibits the growth of human pancreatic cancer lines xenografted into nude mice.

BACKGROUND: Cholecystokinin is thought to be an important factor regulating the growth of human pancreatic cancers. The study was designed to evaluate the effects of the cholecystokinin antagonist loxiglumide (CR1505) on the growth of human pancreatic cancer. METHODS: Human gastrointestinal cancer xenografted tumors (one esophageal, one gastric, two colorectal, two biliary tract, and two pancreatic cancers) were transplanted into nude mice. The mice were given CR1505 at 250 mg/kg daily for 14 days, either subcutaneously or intragastrically, and the tumor volumes before and after treatment were compared. In vitro effects of CR1505 were assessed by measuring the DNA synthesis (3H-thymidine incorporation). RESULTS: CR1505 inhibited the growth of the two pancreatic cancer lines but did not inhibit the growth of the other lines. CR1505 also inhibited in vitro DNA synthesis in the two pancreatic cancer lines at lower concentrations than in the other lines. This pancreatic cancer-specific inhibitory effect of CR1505 was retarded by exogenously administered cholecystokinin in one pancreatic cancer line but was augmented in the other line. The effect of CR1505 was inhibited by oral administration of the trypsin-inhibitor camostate (FOY-305) in both pancreatic cancer lines. CONCLUSIONS: These results suggest that CR1505 may specifically inhibit the growth of human pancreatic cancers and may be suitable for clinical study. However, its antiproliferative effect may not necessarily be dependent on its cholecystokinin-antagonism but may be mediated through the proteolytic enzymes found in the lysosomes of the pancreatic cancer cells.

Animals↗
PubMed1993

Stereoselective determination of the active metabolites of a new anti-inflammatory agent (CS-670) in human and rat plasma using antibody-mediated extraction and high-performance liquid chromatography.

The main metabolites of (+-)-2-[4-(2-oxocyclohexylidenemethyl)phenyl]propionic acid (CS-670), a new pro-drug anti-inflammatory agent of the 2-arylpropionic acid type, have one or two chiral centres arising from reduction of the oxocyclohexylidene moiety in addition to an original chiral centre in the propionic acid moiety. To determine these metabolites stereoselectively, antibody-mediated extraction was investigated as a stereoselective clean-up method prior to chiral HPLC. Immunoglobulin G, which recognizes each stereoisomeric cyclohexanol moiety, was coupled to cyanogen bromide-activated Sepharose 4B to prepare re-usable immobilized antibody, and its specificity was improved by examination of a washing process after charging of samples. Plasma extracted with the immobilized antibody column was derivatized with a chiral reagent to separate the enantiomers of the propionic acid moiety by HPLC. This newly developed analytical method clarified the stereoselective biotransformation of the pro-drug to pharmacologically active forms in humans and rats related to reduction of the oxocyclohexylidene moiety and chiral inversion in the propionic acid moiety.

Animals↗
PubMed1993

Inhibitory effects of a cholecystokinin antagonist, loxiglumide (CR-1505), on the growth of freshly separated and xenografted human pancreatic cancer.

The effects of cholecystokinin (CCK) and a CCK antagonist, loxiglumide (CR-1505), on four freshly separated and six xenografted human pancreatic cancers, were investigated. The level of DNA synthesis in only one of five tested pancreatic cancers was enhanced by CCK at concentrations of 0.01-10 nM, while in the other four cancers DNA synthesis was not affected. The levels of DNA, RNA, and protein synthesis (by 3H-thymidine, 3H-uridine, and 3H-leucine incorporation tests, respectively) in all the tested cancers were dose-dependently inhibited by loxiglumide at concentrations of 20-2000 microM, and the IC50 of loxiglumide for DNA synthesis in pancreatic cancers was 156 +/- 80 microM (means +/- SD). The in vivo effect of loxiglumide was assessed using a xenografted line (PC-HN) transplanted in nude mice. The in vivo 50% lethal dose of loxiglumide for nude mice was about 500 mg/kg. Death was caused by respiratory failure due to severe congestion of the lung after the administration of a large dose of loxiglumide. The growth of a PC-HN transplanted in the nude mice was significantly inhibited by subcutaneous loxiglumide at 250 mg/kg, twice a day for 28 days, which did not cause death. It is suggested that loxiglumide inhibits the in vivo and in vitro growth of human pancreatic cancer, perhaps independently of its action as a CCK antagonist, and this study also suggests that loxiglumide may be a new type of therapeutic agent to be used for the treatment of human pancreatic cancer.

Animals↗
PubMed1993

A phase II study of 5-fluorouracil, cisplatin, and 4'-epirubicin in the treatment of advanced solid cancers.

This phase II study was designed to assess the therapeutic potential of intensive course treatment with three anticancer agents: 50 mg of cisplatin on day 1, 40 mg/m2 of epirubicin on day 2, and 250 mg of 5-fluorouracil on days 2 through 5. Drug courses were repeated every 2 weeks and most patients received between 4 and 6 courses. Thirty-five patients with measurable advanced solid cancers entered the study. They consisted of 16 gastric, 5 colorectal, 4 gallbladder, 3 pancreatic, 3 lung, 2 esophageal, 1 uterine, and 1 ovarian cancers. Of the 35 patients, 29 were evaluated for therapeutic effect of the regimen, and the overall response rate was 31.0% (5 CR + 4 PR/29). A 33.3% rate of tumor regression, consisting of 2 complete responses (CR) and 3 partial responses (PR) out of 15 patients (2 CR + 3 PR/15), was seen for gastric cancers. For the other types of tumors the responses were achieved in 2 lung cancers (1 CR + 1 PR/3). 1 uterine cancer (1 CR/1), and 1 ovarian cancer (1 CR/1). The esophageal, colorectal, pancreatic, and gallbladder cancers were unresponsive to this regimen. Toxicities of the drug treatment were clinically tolerable and consisted of general malaise, nausea, vomiting, stomatitis, alopecia, and leucopenia. However, two patients died of uncontrollable metabolic acidosis after 1 and 2 courses, respectively. This intensive course treatment appears to promote the regression of gastric, lung, and gynecologic cancers.

Adult↗
PubMed1993

Comparative efficacy of antiarrhythmic agents in preventing halothane-epinephrine arrhythmias in rats.

BACKGROUND: Because the relative efficacy of antiarrhythmic agents on halothane-epinephrine arrhythmias has not been well characterized, this study was undertaken to comparatively evaluate the antiarrhythmic action of Na(+)-, K(+)- and Ca(2+)-channel blockers on epinephrine-induced ventricular arrhythmias during halothane anesthesia in rats. METHODS: Rats were anesthetized at random with either halothane (1.5%), isoflurane (2.0%), or pentobarbital (50 mg/kg intraperitoneally), and the lungs were mechanically ventilated with oxygen. The rats were studied in three consecutive protocols. Protocol I determined the arrhythmogenic thresholds of epinephrine during the three types of anesthesia in 33 rats. Protocol II determined the arrhythmogenic thresholds of epinephrine during halothane anesthesia in 64 rats receiving saline (control) or one of five antiarrhythmic agents. Protocol III measured the duration of epinephrine-induced arrhythmias during halothane anesthesia in 42 rats receiving saline (control) or one of five antiarrhythmic agents. RESULTS: In protocol I, the arrhythmogenic doses of epinephrine during halothane, isoflurane, or pentobarbital anesthesia were 1.7 +/- 3.2, 11.1 +/- 0.6, and 39.0 +/- 3.9 micrograms/kg, respectively, and the corresponding plasma concentrations were 4.3 +/- 0.8, 103.7 +/- 9.2, and 246.7 +/- 28.9 ng/ml, respectively. In protocol II, the arrhythmogenic doses were similar in rats receiving saline and in those receiving lidocaine. The arrhythmogenic doses in rats receiving verapamil, flecainide (Na(+)- and K(+)-channel blocker), E-4031 (K(+)-channel blocker), or amiodarone(K(+)-channel blocker with Na(+)-, Ca(2+)-, and beta-blocking activity) increased significantly, i.e., 4.2, 4.2, 5.5, and 31.7 times control (P < 0.01). In protocol III, lidocaine had no effect on the duration of arrhythmias. Flecainide, E-4031, and verapamil markedly reduced the duration of arrhythmias induced by epinephrine, 8 micrograms/kg intravenously (P < 0.01), whereas only amiodarone markedly reduced the duration of arrhythmias induced by epinephrine, 16 micrograms/kg intravenously (P < 0.01). CONCLUSIONS: It was concluded that agents with K(+)-channel blocking properties were the most effective in preventing halothane-epinephrine arrhythmias in rats.

Amiodarone↗