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Biomedical subjects

T Koizumi

Publications and source records attributed to T Koizumi.

At least 73 records · Page 4Linked to original sources
PubMed2000

Distribution, metabolism and excretion of butylidenephthalide of Ligustici chuanxiong rhizoma in hairless mouse after dermal application.

The absorption, distribution and excretion of butylidenephthalide after dermal application to hairless mouse have been examined with [8-14C]butylidenephthalide. By the investigation of the whole body autoradiogram and liquid scintillation analysis, it was indicated that the transdermally applied butylidenephthalide quickly permeate into peripheral circulation system without accumulation in the skin and then distribute into lung, liver, bile and kidney. The total radioactivity, however, was decreased due to excretion into urine, and in the case of i.v.-administration, 80% of the administered butylidenephthalide was excreted into urine within 24 h, while only 5% was excreted into feces within 24 h. Then, the metabolite in urine was determined to be a cysteine conjugate by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. Thus, it has been concluded that after dermal application butylidenephthalide quickly permeates through skin into peripheral circulation system; distributes to lung, liver, bile and kidney; and then excreted into urine as a cysteine adduct.

Administration, Cutaneous↗
PubMed2000

Lung lymph response to overinfusion with hydroxyethyl starch in sheep. Comparative studies of high and low molecular weight compounds.

BACKGROUND: Several hydroxyethyl starch (HES) solutions are available clinically. We performed comparative studies of low and high molecular weight HES to evaluate the effects on lung lymph flow in sheep, to see the difference in the types of HES. METHODS: We prepared awake sheep with vascular monitorings and lung lymph fistulas. We measured systemic artery pressure (Psa), pulmonary artery pressure (Ppa), and left atrial pressure (Pla) continuously. Cardiac output (CO) was measured every 30 min. Lung lymph flow (Qlym) was collected every 15 min. After baseline measurements, two HES solutions were infused over 2 h, respectively. Experiment 1 (n=6): low molecular weight HES (MW 70 000, substitution ratio 0.5-0.55), Experiment 2 (n=5): high molecular weight HES (MW 450 000, substitution ratio 0.7). RESULTS: Both low and high molecular HES behaved similarly as a volume expander, increasing Psa, CO, Pla and Ppa, and decreasing hematocrit. In addition, the actual oncotic pressure gradient (plasma - lymph) was widened after the start of either low or high molecular HES, but the value for high molecular HES was significantly higher than that for low molecular HES. Qlym of low molecular HES rose significantly from the baseline and the percent increase in Qlym for low molecular HES was significantly higher than that for high molecular HES. CONCLUSION: These data suggest that low molecular HES is as useful a plasma substitute as high molecular HES, but may increase lung fluid filtration in the overinfused state.

Animals↗
PubMed2000

Long-term molecular remission induced by donor lymphocyte infusions for recurrent acute myeloblastic leukemia after allogeneic bone marrow transplantation.

A case of acute myelogenous leukemia with a t(8;21) translocation relapsed 5 months after allogeneic bone marrow transplantation (allo-BMT). After chemotherapy-induced hematologic remission, the patient received donor lymphocyte infusions (DLI); 4.9 x 108/kg T cells were infused. After DLI, she achieved molecular CR for the first time after allo-BMT, which lasted for 40 months. However, she suffered from grade III acute GVHD of the skin and the liver. Hepatic GVHD was sustained and resulted in fatal outcome. The case demonstrates that DLI is a double-edged sword. Further study is necessary before DLI can be considered to be a beneficial therapy for acute leukemia. Bone Marrow Transplantation (2000) 26, 809-810.

Adult↗
PubMed2000

Case-control study of perinatal factors and hepatoblastoma in children with an extremely low birthweight.

BACKGROUND: There is a significant association between hepatoblastoma and low birthweight. A case-control study was conducted to reveal risk factors for hepatoblastoma in children of extremely low birthweight (< 1,000 g). METHODS: Prenatal and postnatal histories, including parental histories, of 12 hepatoblastoma cases and 75 birthweight-matched controls were compared. RESULTS: The gestational age of the hepatoblastoma cases (23-32 weeks: median 25 weeks), tended to be lower than that of the controls (23-36 weeks; median, 27 weeks; P = 0.072). The time for an infant's bodyweight to return to the same level as the birthweight also tended to be longer in hepatoblastoma cases than in controls (P = 0.055). All hepatoblastoma cases received oxygen therapy for a period of 4-508 days (median 114 days), which was significantly longer than the 0-366 days (median 62 days) in the controls (P = 0.022). Furosemide was given to all hepatoblastoma cases and was used for a significantly longer period in these infants (6460 days; median 89 days) than in the controls (0-241 days; median 44 days P = 0.027). A univariate Cox regression demonstrated that the time taken to regain bodyweight at birth and the duration of both oxygen therapy and furosemide treatment were significantly associated with the development of hepatoblastoma (hazard ratio (HR)= 1.044, P= 0.013; HR = 1.006, P= 0.001; and HR = 1.007, P= 0.001, respectively). Although there were significant correlations between the factors, a multivariate Cox regression analysis identified the duration of oxygen therapy as a significant independent risk factor (HR = 1.006, P = 0.001). CONCLUSIONS: Oxygen therapy and furosemide treatment, along with the rate of growth, are risk factors for the development of hepatoblastoma in children of extremely low birthweight, and the duration of oxygen therapy is the most important factor in predicting the development of hepatoblastoma. Further studies are necessary to determine the real reasons for the development of hepatoblastoma and to protect children of low birthweight from the development of cancer.

Case-Control Studies↗
PubMed2000

The molar vesicle fluid contains the beta-core fragment of human chorionic gonadotropin.

The human chorionic gonadotropin (hCG) beta-core fragment (beta-CF) is a major molecular form of hCG beta subunit (hCGbeta) immunoreactivity in the urine of pregnant women and patients with trophoblastic disease. The majority of evidence supports the fact that the beta-CF is a degradative product of intact hCG and free hCGbeta in the kidneys. We found a beta-CF-like substance in the fluid of molar vesicles from a patient with complete hydatidiform mole. The molar fluid beta-CF (mbeta-CF) was indistinguishable from the beta-CF in the patient's urine (ubeta-CF) by immunoreactivity and by elution profile on gel chromatography. The binding study to lectins, however, showed that mbeta-CF contains a carbohydrate moiety that differs from that of ubeta-CF. Immunohistochemistry with anti-beta-CF antibody demonstrated a strong immunoreactivity in a large number of macrophages in the molar villous stroma. In vitro incubation of intact hCG with peritoneal macrophages showed a slow increase of intact hCG in the cell cytosol with the appearance of beta-CF-like substance in the cell supernatant. In conclusion, the source of beta-CF in molar fluid is likely to be macrophages existing in the villous stroma. Thus macrophages may ingest intact hCG and act as a local regulator of gonadotropic hormones.

Body Fluids↗
PubMed2000

Quantitation of Fas and Fas ligand gene expression in human ovarian, cervical and endometrial carcinomas using real-time quantitative RT-PCR.

Alterations in the expression of Fas (CD95/APO-1) and its ligand (FasL) have been demonstrated in various types of cancers as a mechanism for tumour cell to escape from the immune system. In the present study, we evaluated the expression of the Fas and FasL genes in a wide range of primary gynaecological carcinomas. These included 31 ovarian, 29 cervical and 25 endometrial carcinoma tissues as well as four ovarian and three cervical carcinoma cell lines. Our real-time quantitative reverse transcription polymerase chain reaction analysis revealed that down-regulation of Fas expression is more prominent than the up-regulation of FasL expression in all types of gynaecological cancer studied. This down-regulation of Fas expression was also true for the seven carcinoma cell lines. Only one cervical carcinoma cell line, DoT, exhibited a high level of FasL expression. These results indicated that down-regulation of Fas expression is a common abnormality in many types of cancers including gynaecological cancers, whereas an increase in FasL expression is not a common phenomenon in these cancers.

Cervix Uteri↗
PubMed2000

Peroxynitrite production by TNF-alpha and IL-1beta: implication for suppression of osteoblastic differentiation.

To determine the roles of nitric oxide (NO) and its metabolite, peroxynitrite (ONOO(-)), on osteoblastic activation, we investigated the effects of a NO donor [ethanamine, 2, 2'-(hydroxynitrosohydrazono)bis- (dNO)], an O(-2) donor (pyrogallol), and an ONOO(-) scavenger (urate) on alkaline phosphatase (ALPase) activity and osteocalcin gene expression, which are indexes of osteoblastic differentiation. dNO elevated ALPase activity in the osteogenic MC3T3-E1 cell line. The combination of dNO and pyrogallol reduced both ALPase activity and osteocalcin gene expression. Because both indexes were recovered by urate, ONOO(-), unlike NO itself, inhibited the osteoblastic differentiation. Furthermore, treatment with a combination of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) was found to yield ONOO(-) as well as NO and O(-2). The reductions in ALPase activity and osteocalcin gene expression were also restored by urate. We conclude that ONOO(-) produced by TNF-alpha and IL-1beta, but not NO per se, would overcome the stimulatory effect of NO on osteoblastic activity and inhibit osteoblastic differentiation.

Alkaline Phosphatase↗
PubMed2000

Spontaneous pneumomediastinum in 33 patients: yield of chest computed tomography for the diagnosis of the mild type.

BACKGROUND: Spontaneous pneumomediastinum (SPM) usually occurs in young people without an apparent precipitating factor or disease. Although there have been many studies focused on the clinical features and standard chest X-ray (CXR) findings of SPM, few have reviewed the chest computed-tomographic (CT) findings. OBJECTIVES: We assessed SPM using CXR and CT, and the relation between them. METHODS: We evaluated 33 patients (26 males) diagnosed with SPM on the basis of symptoms and chest radiological findings. RESULTS: Three patients showed normal CXR but a diagnostic CT scan. Seven showed mild pneumomediastinum on CXR. In these 10 patients, pneumomediastinum was easily detected by chest CT. Moderate and severe SPM were easily detected by both CXR and CT. CONCLUSIONS: These findings suggested that CXR alone poorly detected approximately 30% of SPM and that chest CT scan was needed to make the diagnosis in these cases. It seems likely that SPM is underdiagnosed by 30% or more in clinical practice.

Adolescent↗
PubMed2000

Pharmacokinetics of propranolol and its metabolites in horses after intravenous or oral administration.

The pharmacokinetics characteristics of propranolol (PPL) in horses was studied by administering the drug intravenously or orally to the animals. The predominant primary pathway was ring oxidation, and 4-hydroxypropranolol glucuronide (4-OHPG) was the major metabolite in both plasma and urine. Side-chain glucuronidation and oxidation were not significant. A two-compartment model was employed for PPL followed by a one-compartment model for 4-OHPG. After oral administration, one-step absorption and two-step first pass metabolism were employed. The fraction absorbed of PPL was approximately 70% after oral administration, and the bioavailability varied among individual horses from 1 to 79% depending on the first pass metabolism. The biologic half-life (T1/2) of PPL obeys the allometric equation in some animal species including rats and horses, except for human. T 1/2 of PPL in horses was approximately 2 h.

Administration, Oral↗
PubMed2000

Drug targeting efficacy to underlying muscle following topical application. I. Evaluation based on a physiological pharmacokinetic model.

A physiological pharmacokinetic model describing the absorption and disposition of topically applied drugs was proposed, and the effect of various pharmacokinetic and physiological parameters on the drug delivery into the targeted muscle was simulated. The proposed model consists of vehicle, and stratum corneum, viable epidermis and muscle below the application and reference sites, and plasma, each joined with transfer clearance and plasma flow. Indomethacin concentrations in tissues and plasma after topical application to rats could be explained by the model. Most indomethacin delivered into the underlying muscle was via direct penetration. The model simulation showed that the increase in plasma clearance and clearance between viable skin and muscle, and the decrease in application area and plasma flow rate into viable skin and muscle would promote the targeting efficacy of topically applied drugs to the underlying muscle.

Administration, Topical↗
PubMed2000

[Kinetic analysis of drug disposition and biological response].

This review deals with pharmacokinetic/pharmacodynamic analysis of drugs. For the analysis of antipyretics, it was assumed that: (1) The rat body is divided into two compartments, core and skin. (2) Metabolic heat (M) is generated in the core compartment. (3) Heat loss by vaporization (V) is mainly originated from a respiratory effect and occurs in the core compartment. (4) At the skin compartment, heat is gained from the core compartment by conduction (K) and is transferred to the ambient air by radiation and convection. (5) Central nervous system commands efferent signals for M, K and V to change their values according to changes in afferent signals from core and skin temperatures. (6) The effect of antipyretics is shown as afferent signals to the controller. For loop diuretics, it was assumed that: (1) The diuretic rate can be correlated with the urinary excretion rate of diuretics. (2) If there is no intervention in a body fluid regulation system, the relationship between the diuretic rate and the corresponding urinary excretion rate can be described by a Hill equation. (3) Intensity of the body fluid regulation is also described by the Hill equation, in which the intensity is correlated with cumulative amount of drugs excreted in the urine. For neuromuscular blockade, assumptions were: (1) There exists an acetylcholine (ACh) compartment at a motor nerve terminal. (2) ACh in the compartment is eliminated by a first-order rate process. (3) All of the ACh in the compartment is released by one electrical stimulus. (4) The compartment is replenished by two kinds of ACh mobilization. One is a slow mobilization with a constant rate and the other is a momentary mobilization which takes place just after the release of ACh. (5) The released ACh is metabolized immediately after binding to receptors and causing a twitch response. For centrally acting drugs, the quantitative electroencephalographic (EEG) method was used as a surrogate measure of a pharmacological response. Signals from two electrodes fitted on the skull of rats were continuously measured, recorded and subjected to off-line analysis. Total amplitude from aperiodic analysis was taken as an EEG parameter.

Analgesics, Non-Narcotic↗
PubMed2000

Assessment of aortic atherosclerosis and carotid atherosclerosis in coronary artery disease.

The present study investigated the relationship between aortic atherosclerosis and carotid atherosclerosis, and studied the effects of coronary risk factors for these arteries. The subjects consisted of 78 patients with coronary artery disease (CAD) and 69 patients without CAD. All subjects underwent enhanced computed tomography and B-mode ultrasonography within a short time period to determine the extent of aorta and carotid atherosclerosis. Significant correlations between maximal aortic wall thickness (MAWT) and aortic wall volume (AWV) with carotid intima-media thickness (IMT) were demonstrated. MAWT, AWV and IMT were significantly higher in patients with CAD compared with controls (p=0.009, p=0.024, p=0.001, respectively). Furthermore, there were significant differences in MAWT, AWV and IMT among groups classified by the number of coronary artery stenoses, and no significant differences among groups classified by risk factors, but it was shown that MAWT, AWV and IMT increased gradually as the risk factors increased in number. MAWT, AWV and IMT had positive correlations with age, systolic blood pressure and triglyceride, and a negative correlation with high density lipoprotein-cholesterol. This study demonstrated that both aortic atherosclerosis and carotid atherosclerosis are closely correlated with coronary atherosclerosis, and that the atherosclerosis indices are independently associated with age and hyperlipidemia.

Aortic Diseases↗
PubMed2000

Successful resection of intracardiac invasive thymoma with right ventricular inflow tract occlusion.

A 72-year-old man presenting with the superior vena cava syndrome and intracardiac mass was admitted to our hospital. The mass was resected and confirmed to be invasive thymoma. Three years later, he was re-admitted with recurrence into the intracardiac space without any changes in the anterior mediastinum mass. The mass occupied the right atrial cavity and protruded into the right ventricle, causing right ventricular inflow tract obstruction. He underwent re-operation and irradiation. His postoperative course was uneventful, and he has remained alive. Invasive thymoma with intracardiac extension is extremely rare.

Aged↗
PubMed2000

Transarterial embolization with HEMA-MMA of variant convexity-superior sagittal sinus dural arteriovenous fistula--case report.

A 62-year-old male presented with a variant dural arteriovenous fistula (DAVF) within the wall of the convexity-superior sagittal sinus, fed by branches of the bilateral external carotid arteries and only cortical venous drainage despite the presence of a patent sinus. Transarterial embolization with poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (HEMA-MMA) was performed, resulting in complete obliteration of the DAVF. Embolization with HEMA-MMA is an effective and safe procedure for the treatment of DAVF.

Biocompatible Materials↗
PubMed2000

[Evaluation of Tl-20 lung uptake and impairment of pulmonary perfusion on scintigraphies in pulmonary tuberculosis].

Tl-201 lung uptake in 74 patients (85 lesions) and pulmonary perfusion in 105 patients were studied to evaluate clinical usefulness of Tl-201 lung uptake and perfusion lung scintigraphy in pulmonary tuberculosis, using a scintillation camera with a mini-computer system. As indices of Tl-201 lung uptake, lung (lesion) to upper mediastinum uptake ratio (L/M) and visual grading were used. L/M in pulmonary tuberculosis was 1.96 +/- 0.66, which was significantly larger than 1.04 +/- 0.24 in healthy controls and lower than that in heart diseases with left heart failure and idiopathic interstitial pneumonia, and showed no significant differences with that in acute pneumonia, pyothorax, primary lung cancer and malignant mediastinal tumor. L/M in pulmonary tuberculosis did not correlate with CRP, erythrocyte sedimentation rate, Gaffky number of sputum and body temperature. It correlated with the type of pulmonary tuberculosis according to the Gakken Classification reflecting the disease activity. It was larger in the exudative type, caseo-infiltrative one, disseminated one, one with cavity in infiltrative lesion than the fibro-caseous one. On perfusion lung scintigram, impairment of pulmonary perfusion larger than area of the entire unilateral lung was observed in 68 cases (64.8%). Area of hypoperfused lung field, which correlated with % vital capacity (r = 0.60, p = 0.0002) and PaO2 (r = 0.39, p = 0.0024), was significantly larger in patients with silicosis and those with bilateral pleural involvements such as pleural callosity than in those with type III according to the Gakkai Classification. Most of the patients showed decreased pulmonary perfusion and Tl-201 accumulation of which grade reflects the disease activity in active tuberculous lesion. Patients with miliary tuberculosis and those with silicotuberculosis showed diffuse Tl-201, accumulation in the both lungs. Tl-201 lung scintigraphy seems to be useful for visualizing active tuberculous lesions, particularly the ones that could not be detected by the chest radiograph in patients with destroyed lung and with pleural callosity. Joint use of Tl-201 and perfusion lung scintigraphies provides useful informations about the pathophysiology and disease process in pulmonary tuberculosis.

Aged↗
PubMed2000

Kinetics of serum cytokines after allogeneic bone marrow transplantation: interleukin-5 as a potential marker of acute graft-versus-host disease.

Cytokine levels in sera from 14 patients undergoing allogeneic bone marrow transplantation (alloBMT) or donor lymphocyte infusion (DLI) were sequentially measured to evaluate the roles of cytokines in clinical graft-versus-host disease (GVHD). In clinical courses, interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were measured by enzyme-linked immunosorbent assay. Among the evaluable cases, 6 patients developed acute GVHD. Serum IL-5 levels increased to more than 100 pg/mL in 5 of the 6 patients before, or simultaneously with, the clinical manifestation of acute GVHD. Elevation of IL-5 was transient in 3 patients. In the other 2 patients who showed regimen-related toxicity and/or thrombotic microangiopathy as well as acute GVHD, remarkable and sustained elevation of the serum IL-5 level was observed. In 7 patients without acute GVHD, IL-5 levels remained below 100 pg/mL. An association of acute GVHD was less prominent with TNF-alpha than with IL-5 in our study. Elevation of IL-6 was associated with infections. In 2 patients with severe extensive chronic GVHD, serum IL-10 was elevated in parallel with exacerbation of clinical symptoms. Our findings suggest that an elevated serum IL-5 level may be a marker of acute GVHD.

Acute Disease↗