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Biomedical subjects

K Kawabata

Publications and source records attributed to K Kawabata.

At least 181 records · Page 10Linked to original sources
PubMed1995

Physicochemical and pharmacokinetic characteristics of plasmid DNA/cationic liposome complexes.

The objectives of this study were (i) to characterize the plasmid DNA encoding the chloramphenicol acetyltransferase reporter gene (pCAT) complexed with cationic liposomes (Lipofectin and LipofectACE) in terms of particle size and zeta potential, (ii) to compare pharmacokinetic characteristics, and (iii) to study the hepatic uptake mechanisms. DNA/LipofectACE complexes showed a negative zeta potential of -36 mV at 1:5 w/w ratio, but a positive zeta potential of (19 mV at 1:10 w/w ratio. Lipofectin samples showed a positive zeta potential) of 21-28 mV at these ratios. These preparations showed a wide particle size distribution ranging from 600 to 1200 nm. Following intravenous injection of 1:10 w/w ratio [32P]pCAT/liposome complexes at a dose of 0.1 mg DNA/kg into the tail vein of mice, radioactivity was rapidly eliminated from the plasma and almost 50-60% of the dose was taken up by the liver within 5 min after administration. Plasmid DNA/liposome complexes were predominantly taken up by the liver nonparenchymal cells. The hepatic uptake was inhibited by preceding administration of dextran sulfate (DS), but not by polycytidic acid (poly[C]) and polyinosinic acid (poly[I]), suggesting the involvement of a phagocytic process. We suggest that these complexes are preferentially taken up by the liver nonparenchymal cells mainly via Kupffer cell phagocytosis.

Animals↗
PubMed1995

The role of the left somatosensory cortex in human hand movement.

Hemispheric dominance for motor control in the human brain is still unclear. Here we propose asymmetric sensorimotor integration during human hand movements. We investigated the dexterity of hand movements and related sensory functions in four right-handed patients with cerebrovascular lesions in the postcentral gyrus. To clarify the distributions of cortical damage, semiquantitative analysis of regional cerebral blood flow (rCBF) was performed using single photon emission computed tomography (SPECT), and a three-dimensional surface display was generated from SPECT. Scores on motor and sensory tasks and rCBF values in the patients were compared with those in control subjects. All patients presented with asymmetric clumsiness of complex finger movements, in association with impairments of combined sensations such as stereognosis. These findings were indicative of a disorder of sensory information processing necessary to guide the movements. Two patients with left hemispheric damage showed bilateral clumsy hands, predominating on the right side, while the other two patients with right hemispheric damage showed only a left clumsy hand. In agreement with asymmetric clumsiness, measurement of rCBF along with a three-dimensional surface display revealed cortical hypoperfused areas, mainly in the perirolandic cortices, comprising the primary motor and somatosensory cortices. Perirolandic cortical hypoperfusion was bilateral in the two patients with bilateral clumsy hands, but only on the right side in the other two patients with left clumsy hands. These results suggest a dominant role of the left somatosensory cortex in sensorimotor integration for complex finger movements of humans.

Aged↗
PubMed1995

Focal cortical hypoperfusion in corticobasal degeneration demonstrated by three-dimensional surface display with 123I-IMP: a possible cause of apraxia.

To clarify cortical lesions responsible for apraxia in cortico-basal degeneration (CBD), we reconstructed three-dimensional surface images from single-photon emission computed tomography (SPECT) data with N-isopropyl-p[I-123]-iodoamphetamine in two patients with CBD. Both had limb-kinetic apraxia (LKA) and one also had constructional apraxia (CA). Both showed asymmetrical cortical hypoperfusion in the perirolandic area. The patient with CA had unilateral hypoperfusion in the posterior parietal area. Thus, cortical hypoperfusion in the perirolandic area corresponded to LKA, and that in the posterior parietal area to CA.

Aged↗
PubMed1995

The fate of plasmid DNA after intravenous injection in mice: involvement of scavenger receptors in its hepatic uptake.

PURPOSE: We examined the stability and disposition characteristics of a naked plasmid DNA pCAT as a model gene after intravenous injection in mice to construct the strategy of in vivo gene delivery systems. METHODS: After the injection of pCAT to the mice, stability, tissue distribution, hepatic cellular localization, and effect of some polyanions on the hepatic uptake were studied. RESULTS: The in vitro study demonstrated that the pCAT was rapidly degraded in mouse whole blood with a half-life of approximately 10 min at a concentration of 100 micrograms/ml. After intravenous injection, pCAT was degraded at a significantly faster rate than that observed in the whole blood, suggesting that pCAT in vivo was also degraded in other compartments. Following intravenous injection of [32P] pCAT, radioactivity was rapidly eliminated from the plasma due to extensive uptake by the liver. Hepatic accumulation occurred preferentially in the non-parenchymal cells. The hepatic uptake of radioactivity derived from [32P] pCAT was inhibited by preceding administration of polyanions such as polyinosinic acid, dextran sulfate, maleylated and succinylated bovine serum albumin but not by polycytidylic acid. These findings indicate that pCAT is taken up by the liver via scavenger receptors on the non-parenchymal cells. Pharmacokinetic analysis revealed that the apparent hepatic uptake clearance was fairly close to the liver plasma flow. CONCLUSIONS: These findings provide useful information for the development of delivery systems for in vivo gene therapy.

Animals↗
PubMed1995

Anticancer chemosensitivity changes between the original and recurrent tumors after successful chemotherapy selected according to the sensitivity assay.

OBJECTIVE: The authors compare and characterize the changes in chemosensitivity between the original tumors before chemotherapy and recurrent tumors after responses. SUMMARY BACKGROUND DATA: The drug resistance in clinical chemotherapy appears to be different from that in experimental chemotherapy, and the profile and mechanisms of clinical drug resistance in recurrent tumors, especially after successful chemotherapy has scarcely been studied. METHODS: Applied chemotherapies were selected out of four agents, cisplatin (CDDP), adriamycin (ADR), mitomycin-C (MMC) and 5-fluorouracil (5-FU), singly or in combinations by a DNA synthesis inhibition assay, by which the sensitivity of recurrent tumors was assessed. Responses were defined according to the standard criteria, and successful chemotherapy indicates complete response (CR) or partial response (PR) for solid tumors and complete disappearance for malignant effusion. RESULTS: In 37 patients, the effectiveness of four agents were compared between before chemotherapy and after recurrence, and the response lasted between 2 and 26 months (mean +/- SD, 7.7 +/- 5.5). The results suggest that locally recurred tumors may become resistant to the agents previously administered; by contrast, distantly recurred tumors may not necessarily become resistant to the agents administered. The recurrent tumors are suggested to be sensitive to the agents as follows: locally recurrent solid tumors, 5-FU; distantly recurrent solid tumors, 5-FU and CDDP; locally recurrent effusion, CDDP; distantly recurrent effusion, ADR. Twenty-three of 37 recurrent tumors were re-treated with chemotherapies selected according to the sensitivity assay, singly or in combination with a biologic response modifier (BRM)--a streptococcal preparation, OK-432, or interferon-alpha. Responses were seen in 1 of 13 solid recurrent tumors and in 6 of 10 recurrent effusions. Responses were seen only when the patients were treated with a combination of chemotherapy and BRM. CONCLUSION: There may be a notable differences in the basic biologic characteristics of tumor cells with respect to local versus distant recurrences, and between effusion versus solid recurrences. Various approaches, including a combination of chemotherapy and BRM, therefore, may have to be applied to overcome these drug resistances in practical chemotherapies for recurrent tumors.

Antineoplastic Agents↗
PubMed1995

Visual evoked potentials (VEPs) in Parkinson's disease: correlation of pattern VEPs abnormality with dementia.

There has been some debate about abnormalities in visual evoked potentials (VEP) in Parkinson's disease (PD). To elucidate the mechanism underlying abnormal VEPs, we investigated the relationship between pattern-reversal VEPs elicited by large checks and mental functions in PD patients (n = 32), as compared with VEPs of age-matched control subjects (n = 22). The PD patients were divided into two groups: PD without dementia (nD-PD; n = 21) and PD with dementia (D-PD; n = 11). All patients but five of the nD-PD patients were being treated with anti-parkinsonian drugs. The D-PD patients showed significantly prolonged P100 latencies compared with both the nD-PD patients and controls (p < 0.01 and p < 0.01, respectively). The PD patients treated with levodopa had significantly longer P100 latencies than the other PD patients. In PD patients, the P100 latency correlated significantly with illness duration (p < 0.05). There was also a significant negative correlation with P100 latency and Mini-Mental State Examination (MMSE) score (p < 0.05). The MMSE score did not correlate with illness duration in PD patients. These findings suggest that the VEPs abnormality elicited by large checks is related to dementia independent of progression of the illness, and that a nondopaminergic neurotransmitter system may play a role in the development of VEPs delay elicited by large checks.

Aged↗
PubMed1995

Comparison between transabdominal and transvaginal ultrasonography for identifying endometrial malignancies.

Transvaginal ultrasound (TVS) is generally considered superior to transabdominal ultrasound (TAS) in the estimation of endometrial abnormalities. A disadvantage of TVS is the limited field of view. The purpose of this study is a comparison between TAS and TVS for endometrial cancer screening. Ninety-one postmenopausal women were included. They were evaluated by TAS, TVS, and endometrial tissue sampling. The mean endometrial thickness estimated by TVS was larger than that obtained by TAS (p < 0.0001). Sensitivity and specificity of TAS were 83.3 and 58.8% and of TVS 100 and 54.1%, respectively. We conclude that TVS might be superior to TAS, especially in patients with a retroflexed uterus.

Abdomen↗
PubMed1995

[Experimental study on effects of a high-sugar diet and physical exercise on serum phospholipids in young adults].

The life style of young adults has been receiving attention with a view to its improvement to prevent coronary heart diseases (CHD) later in life. In this study, to determining the influence of different life styles on the serum phospholipids level, we carried out experimental studies on the effects a high sugar diet and physical exercise on serum phospholipid levels. Considering the trend for young people to consume large quantities of carbonated drinks, in which most of the sugar is sucrose, we tested the effect of a high carbohydrate diet on one group of six healthy male subjects and did not find that it caused a significant increase in the serum phospholipids level. In another group of 108 healthy young female subjects, a mild exercise regimen results in a slight, but significant decrease in the serum phospholipid level (p < 0.01). The serum total cholesterol level of the group did not exhibit a significant change.

Adult↗
PubMed1995

Evaluation of the effects of various factors on the serum alpha hydroxybutyrate dehydrogenase activity in young females.

In this study, for determining the influence of different life style on the serum alpha hydroxybutyrate dehydrogenase activity (alpha HBD), we carried out surveys and laboratory studies on the relationships of the nutritional intake, physical activity, cigarette smoking and alcohol consumption of young females with their serum alpha HBD activity. There are significant positive correlation between alpha HBD and GOT, GPT, LDH, CPK, phospholipids, total cholesterol, and HDL-cholesterol, and significant negative correlation between alpha HBD/LDH and GOT, GPT, and gamma GTP. There are significant positive or negative correlation between alpha HBD and systolic pressure, diastolic pressure, cardiac index, stoke volume and total periperal resistance, and significant negative correlation between alpha HBD/LDH and vital capacity in young females. The serum alpha HBD activity levels of nonsmokers was significant higher than those of smokers (p < 0.05). There are significant positive correlations between serum alpha HBD activity and beverage consumption, and between alpha HBD/LDH and protein, calcium, vitamin A, B1, B2, C, pulses, vegetables and milk in young females. The finding shows that the group of serum alpha HBD activity level of 240 or more units exhibited higher level of rate of those who exercised sometimes+usually than the other group in young females. However, the serum alpha HBD activity level did not show significant correlation with energy expenditures per day. Exercise at 50 and 70% VO2 max may produce a significant increase in their serum alpha HBD activity. There is a possibility that serum alpha HBD activity may serve as an indicator for ones health condition. It is undeniable that observation of variation of serum alpha HBD activity is highly significant in health maintenance.

Activities of Daily Living↗
PubMed1995

[Activation of complement during hemodialysis].

In hemodialysis using 3 types of dialysis membrane materials [regenerated cellulose (RC), cellulose triacetate (CTA), and polysulfone (PS)], activation of the complement, reduction of white blood cells, and variation of vitronectin (VN) were observed. RC membrane caused a significant reduction of white blood cells and elevations of Bb and soluble membrane attack complex (S-MAC), indicating a strong activation of the alternative complement pathway. Especially, the increase of S-MAC persisted for a long time during hemodialysis. Because reduction of VN was transient, it was assumed that the S-MAC escaping removal by VN receptors might have persisted in the circulation. These findings suggested that S-MAC would become useful as an index for evaluating biocompatibility of various artificial organs including dialysis membranes.

Aged↗
PubMed1995

In vivo disposition characteristics of plasmid DNA complexed with cationic liposomes.

To control disposition and hence gene expression, we investigated the disposition characteristics of plasmid DNA complexed with the cationic liposomes Lipofectin and LipofectACE after intravenous injection in mice via the tail vein. The optimum ratios of DNA and liposome complexes were selected through in vitro cytotoxicity and transfection studies. The highest transfection was found at the DNA:liposome ratio of 1:5 w/w. Hence, this ratio was used for in vivo disposition studies, and the distribution patterns were compared with that of naked pCAT. Following intravenous injection of [32P] pCAT, radioactivity was rapidly eliminated from plasma and approximately 60% of the dose was taken up by the liver within 1.5 min. In the case of LipofectACE samples, radioactivity elimination from plasma was equally rapid, but its accumulation was observed in both the liver (35%) and the lung (45%). For Lipofectin samples, radioactivity was initially accumulated in both the liver (55%) and the lung (25%), but lung accumulation was not sustained beyond 5 min after administration. Both liposomal samples showed in vivo gene expression in the lung, heart, kidney and spleen, but not in the liver. Thus, the present study demonstrated that disposition and gene expression of pCAT can be controlled by complex formation with liposomes.

Animals↗
PubMed1995

[A study on immunohistochemical detection of estrogen receptor in the breast cancer tissue--a comparison between routinely paraffin-embedded and frozen sections].

On immunohistochemical detection of estrogen receptor in the breast cancer tissue, we examined whether ER1D5 [Anti-estrogen receptor monoclonal antibody, clone ER1D5(MBL)] using routinely fixed paraffin-embedded section may take the place of ERICA [Estrogen receptor immunocytochemical assay kit (DAINABOT)] using frozen one or not. With 63 breast cancer cases, estrogen receptor was positive in 63.4% of the cases by ERICA, while in 25.4% and 28.6% by ER1D5 in which enhancement of the antigen with microwave heating (high frequency power 500W 5 minutes) and autoclave heating (121 degrees C, 20 minutes) had been carried out. At present, it is unreasonable for ER1D5 to take the place of ERICA. However, it is noteworthy that estrogen receptor is detectable with paraffin-embedded section although the rate of positivity is low. It is desirable that further development of the antibody for estrogen receptor in the breast cancer tissue with paraffin-embedded section will be continued.

Breast Neoplasms↗