Search PubMed⌕ Search

Biomedical subjects

K Wei

Publications and source records attributed to K Wei.

At least 73 records · Page 4Linked to original sources
PubMed1998

Identification of a quantitative trait locus influencing plasma insulin levels after 70% pancreatectomy using the OLETF rat.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type non-insulin-dependent diabetes mellitus (NIDDM) in humans. The OLETF rat has poor capacity for proliferation of pancreatic beta-cells after partial pancreatectomy, which may be the critical pathogenetic event in NIDDM development. The poor pancreatic beta-cell proliferation in this model is characterized by reduction in beta-cell mass and decrease in insulin content in the remnant pancreas. Our investigation was designed to identify quantitative trait loci (QTLs) responsible for beta-cell mass and plasma insulin levels after partial pancreatectomy by performing a genome-wide scan in an F2 intercross obtained by mating the OLETF and the Fischer-344 (F344) rats. We have identified a suggestive QTL for the plasma insulin levels, near D20Mgh5 on rat chromosome 20, with a maximum lod score of 3.75 which accounts for 20% of the total variance, while no QTLs were detected for beta-cell mass. This chromosome 20 QTL, whose OLETF allele is associated with low plasma insulin levels through acting in an incompletely recessive manner, may affect insulin secretion itself rather than beta-cell proliferation.

Animals↗
PubMed1998

X-linked locus is responsible for non-insulin-dependent diabetes mellitus in the OLETF rat.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat has been recently established as the best model of non-insulin-dependent diabetes mellitus (NIDDM) with mild obesity. In this study, we found that the F1 progeny produced from the crosses of OLETF and F344 rats exhibit a reciprocal cross effect on NIDDM-relevant phenotypes, fasting and postprandial glucose levels and body weight, suggesting the existence of X-linked locus affecting susceptibility to NIDDM. We thus examined the linkage between 7 X-linked microsatellite markers and NIDDM-relevant phenotypes, using 160 (OLETF x F344)F2 progeny. Suggestive evidence for a X-linked locus affecting glucose levels at 120 min after glucose administration was found in a region near X-linked marker, DXMgh4. The identified locus also showed significant effects on fasting glucose levels and body weight.

Animals↗
PubMed1997

Myocardial perfusion imaging in the setting of coronary artery stenosis and acute myocardial infarction using venous injection of a second-generation echocardiographic contrast agent.

BACKGROUND: We hypothesized that by producing excellent myocardial opacification, venous injection of FS-069 coupled with intermittent harmonic imaging (IHI) can be used to determine the presence and severity of coronary stenoses during hyperemia, the size of the risk area during coronary occlusion, and the extent of myocardial salvage after reperfusion. METHODS AND RESULTS: Twelve dogs were imaged both continuously and intermittently (every end systole) in the fundamental (2 MHz) and harmonic (transmit at 2 and receive at 4 MHz) modes. FS-069 (1 mL) was injected intravenously for all stages and modes of imaging. Myocardial video intensity was severalfold (P<.01) higher during IHI than all other modes of imaging. Perfusion defects were difficult to measure during continuous and intermittent fundamental imaging and during continuous harmonic imaging. In comparison, the defects were clearly demarcated during IHI. When this mode was used, the magnitude of perfusion mismatch during hyperemia in the presence of a coronary stenosis correlated closely with the magnitude of flow mismatch when radiolabeled microspheres were used (r=.94). The perfusion defect sizes during coronary occlusion and reperfusion also correlated closely with postmortem risk area (r=.89) and infarct size (r=.96), respectively. CONCLUSIONS: Venous injection of FS-069 coupled with IHI produces excellent myocardial opacification. This approach can be used to determine the severity of coronary stenoses during hyperemia, the size of the risk area during coronary occlusion, and the extent of myocardial salvage after reperfusion. This approach, therefore, holds promise in the clinical setting.

Animals↗
PubMed1997

Myocardial contrast echocardiography in acute myocardial infarction using aortic root injections of microbubbles in conjunction with harmonic imaging: potential application in the cardiac catheterization laboratory.

OBJECTIVES: The aim of this study was to evaluate myocardial contrast echocardiography using aortic root injections with harmonic imaging in experimental acute myocardial infarction to determine the potential of this approach in the cardiac catheterization laboratory. BACKGROUND: It would be desirable to have an adjunctive procedure that could evaluate myocardial perfusion at the time of cardiac catheterization in patients with acute myocardial infarction. A single injection of contrast medium in the aortic root would provide complete information on myocardial perfusion in a cross section of the heart. High quality images would provide on-line assessment of myocardial perfusion without recourse to image processing. These data could be very valuable for determining patient management. METHODS: Perfusion defects on myocardial contrast echocardiography were measured during coronary occlusion and reflow, using fundamental and harmonic imaging in both continuous and intermittent modes in nine open chest dogs. These defects were compared with risk area on technetium-99m autoradiography and infarct size on tissue staining. RESULTS: Whereas harmonic imaging increased myocardial video intensity by more than twofold (p < 0.001) compared with fundamental imaging after aortic root injection of contrast medium, intermittent imaging was not superior to continuous imaging. The improved signal to noise ratio of harmonic imaging allowed on-line definition of risk area (r = 0.98) and infarct size (r = 0.93) without recourse to off-line processing. Similar results could be obtained with fundamental imaging only after off-line processing. CONCLUSIONS: Aortic root injection of contrast medium coupled with harmonic imaging can be used to provide accurate on-line assessment of risk area and infarct size during acute myocardial infarction. These results have important implications for the catheterization laboratory.

Adenosine↗
PubMed1997

Interactions between microbubbles and ultrasound: in vitro and in vivo observations.

OBJECTIVES: We attempted to examine the interactions between ultrasound and microbubbles. BACKGROUND: The interactions between microbubbles and ultrasound are poorly understood. We hypothesized that 1) ultrasound destroys microbubbles, and 2) this destruction can be minimized by limiting the exposure of microbubbles to ultrasound. METHODS: We performed in vitro and in vivo experiments in which microbubbles were insonated at different frequencies, transmission powers and pulsing intervals. Video intensity decay was measured in vitro and confirmed by measurements of microbubble size and concentrations. Peak video intensity and mean microbubble myocardial transit rates were measured in vivo. RESULTS: Imaging at lower frequencies and higher transmission powers resulted in more rapid video intensity decay (p = 0.01), and decreasing exposure of microbubbles to ultrasound minimized their destruction in vitro. Although these effects were also noted in vivo with venous injections of microbubbles, they were not seen with aortic root or direct coronary artery injections. CONCLUSIONS: Ultrasound results in microbubble destruction that is more evident at lower frequencies and higher acoustic powers. Reducing the exposure of microbubbles to ultrasound minimizes their destruction. This effect is most marked in vivo with venous rather than aortic or direct coronary injections of microbubbles. These findings could lead to effective strategies for myocardial perfusion imaging with venous injections of microbubbles.

Albumins↗
PubMed1997

Three-dimensional myocardial contrast echocardiography: validation of in vivo risk and infarct volumes.

OBJECTIVES: The aim of this study was to determine whether three-dimensional (3D) myocardial contrast echocardiography (MCE) could provide an accurate in vivo assessment of risk and infarct volumes. BACKGROUND: MCE has been shown to accurately define risk area and infarct size in single tomographic slices. The ability of this technique to measure risk and infarct volumes by using three-dimensional echocardiography (3DE) has not been determined. METHODS: Fifteen open chest dogs underwent variable durations of coronary artery occlusion followed by reperfusion. At each stage, MCE was performed by using left atrial injection of AIP201, a deposit microbubble with a mean diameter of 10 +/- 4 microm and a mean concentration of 1.5 x 10(7) x ml(-1). Images were obtained over a 180 degree arc with use of an automated rotational device and were stored in computer as a 3D data set. Postmortem risk area and infarct size were measured in six to eight left ventricular short-axis slices of equal thickness using technetium-99m autoradiography and tissue staining, respectively. MCE images corresponding to these planes were reconstructed off-line. RESULTS: A close linear relation was noted between the volume of myocardium not showing contrast enhancement on 3D MCE during coronary occlusion and postmortem risk volume (y = 1.2x - 3.0, r = 0.83, SEE = 5.1, n = 15). The volume of myocardium not showing contrast enhancement on 3D MCE after reperfusion also closely correlated with postmortem infarct volume (y = 1.1x - 3.9, r = 0.88, SEE = 4.8, n = 11). No changes in systemic hemodynamic variables were noted with injections of AIP201. CONCLUSIONS: When combined with AIP201, a deposit microbubble, 3D MCE can be used to accurately determine both risk and infarct volumes in vivo. This method could be used to assess the effects of interventions that attempt to alter the infarct/risk volume ratio.

Animals↗
PubMed1997

Recent advances in myocardial contrast echocardiography.

In the past few years, significant advances have been made in the production of microbubbles that are more stable in the circulation. Our understanding of the interactions between microbubbles and ultrasound has also led to the development of new ultrasound imaging techniques that result in excellent myocardial opacification after an intravenous administration of microbubbles. This review focuses on advances made with these technologies in the setting of acute coronary syndromes and chronic coronary artery disease.

Cardiomyopathies↗
PubMed1996

Cytosine deaminase gene as a positive selection marker.

Cytosine deaminase (EC 3.5.4.1), a non-mammalian enzyme, catalyzes the deamination of cytosine and 5-fluorocytosine to form uracil and 5-fluorouracil, respectively. Eukaryotic cells have been genetically modified with a bacterial cytosine deaminase gene to express a functional enzyme. When the genetically modified cells are combined with 5-fluorocytosine, it creates a potent negative selection system, which may have important applications in cancer gene therapy. In this paper, we introduce a novel positive selection method based upon the expression of the cytosine deaminase gene. This method utilizes inhibitors in the pyrimidine de novo synthesis pathway to create a condition in which cells are dependent on the conversion of pyrimidine supplements to uracil by cytosine deaminase. Thus, only cells expressing the cytosine deaminase gene can be rescued in a positive selection medium.

3T3 Cells↗
PubMed1996

Xenogeneic ICAM-1 gene transfer suppresses tumorigenicity and generates protective antitumor immunity.

Tumorigenicity in Fischer rats was not significantly reduced when the rat ICAM-1 gene was overexpressed in the rat tumor cell lines, JM-1 and SST-2. When these rat tumor cell lines were genetically modified with a gene encoding human ICAM-1, tumorigenicity was dramatically reduced. Expression of xenogeneic ICAM-1 did not alter the growth rate, expression of the major histocompatibility complex, nor morphological appearance of the cells. However, it did facilitate a tumor-specific immunological recognition and rejection of the genetically modified tumor cells. This effect resulted in a tumor-specific, long-term protective immunity directed against genetically unmodified tumor cells. Most importantly, administration of tumor cells genetically modified with genes encoding xenogeneic ICAM-1 can facilitate an immunological response to genetically unaltered pre-existing tumors. Transferring splenocytes from animals 'vaccinated' with the xenogeneic ICAM-1 gene altered tumor cells was able to transfer the antitumor response into recipient animals. Furthermore, transfer of CD8+ T lymphocytes produced the same result. These results suggested that tumors specific CD8+ T lymphocytes were activated by the xenogeneic altered tumor cells. THis activation generated the long-term, tumor-specific immunity.

Animals↗
PubMed1995

A mutant strain (LEC) of rat with low degree of zinc-induced hepatic metallothionein gene expression.

A mutant strain (LEC) of rats was found to possess the feature of low degree of the zinc-induced hepatic metallothionein (MT) gene expression due to an alteration of the transcription factor concerned in the gene expression. Northern blot analyses showed that the amount of MT-1 mRNA induced by intraperitoneal zinc injection is smaller in LEC mutant rat liver than in normal rat liver, while the amount of MT-1 mRNA induced by copper injection is indistinguishable between LEC and normal rat livers. Gel retardation assays showed that LEC and normal rat livers are different in the nuclear protein which binds to the metal-responsive element (MRE) of the MT gene in a zinc-dependent manner, and that the efficiency of the zinc-dependent binding of the nuclear protein to the MRE is lower in LEC rat liver than in normal rat liver. LEC rat should provide a useful model to understand the transcription factor concerned in the MT gene expression by zinc.

Animals↗
PubMed1995

Association between QT dispersion and autonomic dysfunction in patients with diabetes mellitus.

OBJECTIVES: We hypothesized that QT dispersion would be increased in patients with diabetes mellitus and autonomic dysfunction and that QT dispersion would be related to abnormal iodine-123 (I-123) metaiodobenzylguanidine (MIBG) uptake. BACKGROUND: Patients with diabetes mellitus and autonomic dysfunction have an increased incidence of sudden death. This event may be due to a sympathetic imbalance causing disturbances of repolarization. QT dispersion has recently been demonstrated to reflect dispersion of ventricular refractoriness and is a marker of arrhythmogenic potential. Uptake of I-123 MIBG is a reliable measure of whether the tissue examined receives sympathetic neuronal innervation. METHODS: Fifty-one diabetic patients and 11 normal subjects were studied. All patients had clinical evaluation for autonomic dysfunction (defined as at least two abnormal heart rate and blood pressure responses to five validated tests). Rest 12-lead electrocardiograms were recorded for measurement of QT dispersion, defined as the longest QT interval minus the shortest QT interval, and corrected for heart rate using Bazett's formula. Visual and quantitative measurements of I-123 MIBG uptake were performed using I-123 MIBG, and technetium-99m sestamibi uptake was used to assess perfusion. RESULTS: Thirty-five diabetic patients had autonomic dysfunction. Corrected QT dispersion was significantly greater in the patients than in the normal subjects (p = 0.02). The I-123 MIBG scores were also significantly greater in patients with than without autonomic dysfunction (p = 0.0004) and in normal subjects (p = 0.008). There was no correlation between QT dispersion and I-123 MIBG uptake score (r = 0.006, p = 0.97). CONCLUSIONS: Diabetic patients with autonomic dysfunction have increased QT dispersion and larger I-123 MIBG uptake defects. This finding suggests that such patients have a greater inhomogeneity of repolarization. The lack of correlation between QT dispersion and I-123 MIBG uptake suggests that these abnormalities are mediated by different mechanisms.

3-Iodobenzylguanidine↗
PubMed1994

Adaptive response to mutagenesis and its molecular basis in a human T-cell leukemia line primed with a low dose of gamma-rays.

The effect was studied of a low dose of gamma-ray preexposure on the frequency and molecular spectrum of radiation-induced mutations at the hprt locus in a human T-cell leukemia line. When the cells were preexposed to 0.01 Gy of gamma-rays, the yield of mutations induced by a subsequent 2-Gy challenge dose was reduced by 60%, compared with the 2 Gy of irradiation alone. The data of Southern blot analysis showed that 47% of the mutants induced by 2 Gy in the cells without low-dose preexposure were of the deletion or rearranged mutations type. In contrast, in the low-dose radioadapted cells the proportion of this type of 2-Gy-induced mutations decreased to 28%. This is close to the control level (22%) of spontaneous mutations. Our results confirm that a low dose of gamma-ray preexposure leads to a decreased susceptibility to gene deletions and rearrangements after high-dose irradiation.

Dose-Response Relationship, Drug↗
PubMed1993

Cultured mouse SR-1 cells exposed to low dose of gamma-rays become less susceptible to the induction of mutagenesis by radiation as well as bleomycin.

The effect of pre-exposure of cultured mouse SR-1 cells to a low dose of gamma-rays on the induction of mutations at the hprt locus by subsequent high dose radiation or bleomycin was studied. When cells were pre-exposed to 0.01 Gy gamma-rays, the induction of mutations by a 3 Gy gamma-ray dose given 18 or 24 h later was significantly reduced as compared with those which did not receive the low dose pre-exposure. When cells were challenged with 5 or 10 micrograms/ml bleomycin for 12 h, which can produce double-strand breaks in DNA, instead of 3 Gy gamma-rays, a similar mutagenetic adaptive response was observed. We conclude that this resistance to radiation- or bleomycin-induced mutation is attributed to the induction of a DNA double-strand break repair mechanism.

Animals↗
PubMed1993

X-ray induced DNA double-strand breakage and rejoining in a radiosensitive human renal carcinoma cell line estimated by CHEF electrophoresis.

Cell intrinsic radiosensitivity is of great importance in radiation therapy, but its molecular basis is still uncertain. Since DNA double strand breakage is considered to be the most important lesion related to cell death induced by ionizing radiation, the relationship between DNA double-strand breakage, repair and cell survival was investigated in three cell lines: Chinese hamster cell (CHO-K1), human fibroblast and human renal carcinoma (Tu 25). The D0 values after X-irradiation were 1.73, 1.23, and 0.89 Gy, respectively, showing that Tu 25 was the most sensitive among them. DNA double-strand breaks were measured by CHEF electrophoresis, the initial yield of double-strand break per dose in the three cell lines was almost the same, and no correlation to cell survival was found. However, the rejoining capacity for DNA double-strand break differed. After a dose of 20 Gy, the repair rate was markedly lower in Tu 25, with a half repair time of 40 min, as compared with the other two cell lines with half repair times of 15 min. The results strongly supported the correlation between the repair capacity for DNA double-strand break and cell survival. It was concluded that DNA repair capacity is one of the determinants of cell radiosensitivity. Estimation of DNA double-strand break rejoining by CHEF was suggested as a predictive assay for radiosensitivity of human tumor cells.

Animals↗