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Biomedical subjects

Y Oka

Publications and source records attributed to Y Oka.

At least 397 records · Page 22Linked to original sources

Overexpression of glucose transporter modulates insulin biosynthesis in insulin producing cell line.

Glucose transporter (GT) has been suggested to be involved in the insulin biosynthesis. However, the functional relationship between GT and insulin biosynthesis is not well understood. In this report, we have generated rat pancreatic B cell lines (RINr) that stably overexpress a cDNA encoding the brain type GT. These cell lines showed 3- to 4-fold increase in insulin mRNA and protein. These results suggest that GT might have some relationship to the insulin biosynthesis in the pancreatic B cells.

Animals↗

Immature B cells can pass through a VHDJH/germ line state in the Ig H chain gene rearrangements.

SPL2-1-2, an Ig- murine immature B cell line, was established by the infection of immature B cells with tsOS-59, a temperature-sensitive mutant of Abelson murine leukemia virus. Southern blot and DNA cloning and sequencing analysis showed that SPL2-1-2 had a nonproductive VHQ52.DSP2.JH3 and a germ line (G) allele (VHDJH-/G), and that D to JH joinings followed by VH to DJH joinings progressed on the G allele during culture. These results indicated the existence of novel pathway of IgH gene rearrangements: G/G----DJH/G----VHDJH/G----VHDJH/DJH----VHDJH /VHDJH. This also implied that whether DJH/G state progressed to DJH/DJH or VHDJH/G state was stochastically determined, but not strictly controlled in an ordered fashion, although DJH/G state progressed more preferentially to DJH/DJH state than to VHDJH/G state.

Alleles↗

C-terminal truncated glucose transporter is locked into an inward-facing form without transport activity.

The facilitated glucose transporters comprise a structurally related family of proteins predicted to have 12 membrane-spanning domains, with the amino terminus, a relatively large middle loop and the carboxy-terminus all oriented towards the cytoplasm. An alternating conformation model has been proposed to explain the mechanism of facilitated glucose transport. To understand the structure-function relationships, especially the role of the intracellular C-terminal domain, we have modified the rabbit equivalent of the erythroid-type transporter, GLUT1 (ref. 18), using complementary DNA to code for a deletion mutant that lacks most (37 out of 42 amino acids) of the intracellular C-terminal domain. This deletion mutant is expressed at the cell surface of Chinese hamster ovary (CHO) cells, but is functionally inactive, probably because it has lost its capacity to alternate in conformation and so is locked into an inward-facing form.

Animals↗

Estimation of D segment usage in initial D to JH joinings in a murine immature B cell line. Preferential usage of DFL16.1, the most 5' D segment and DQ52, the most JH-proximal D segment.

We established SPL2-1-2, a murine immature B cell line transformed by tsOS-59, a temperature-sensitive mutant of Abelson murine leukemia virus. SPL2-1-2 has a VHDJH-/G (germ-line) configuration, and can continuously generate D to JH joinings from the germ-line allele during culture. The D to JH joinings are strongly promoted by the shift of the culture temperature from permissive (35 degrees C) to non-permissive temperature (39 degrees C). Using this H chain gene rearrangement system, we succeeded in the estimation of the frequencies of D segment usage in initial D to JH joinings by deletion-mapping analysis. The results demonstrated the preferential utilization of DFL16.1, the most 5' D segment and DQ52, the most JH-proximal D segment in initial D to JH joinings.

Alleles↗

[Combination chemotherapy with methotrexate, vincristine, cis-platinum, cyclophosphamide, adriamycin, and bleomycin: MVP-CAB for disseminated urological cancer].

Twenty-eight evaluable patients with disseminated measurable malignancies of the genitourinary organs except testicular cancer were treated with MVP-CAB, between May 1985 and June 1988. Chemotherapy was given at 3 to 4 week intervals, as follows. On day 1, methotrexate 20 mg/m2, vincristine 0.6 mg/m2, cyclophosphamide 500 mg/m2, adriamycin 20 mg/m2, and bleomycin 30 mg/body were administered. On day 2, cis-platinum 50 mg/m2, on day 1 to 3, prednisolone 20 mg/body were also administered. The administration of bleomycin and adriamycin were limited to 90 mg/body and 400 mg/m2. The median age was 59 years. The median follow-up duration was 11 months. The primary lesions were urothelial tract cancer (19 patients), malignant lymphoma (1 patient), renal cell adenocarcinoma, penile cancer, prostatic adenocarcinoma, and leiomyosarcoma (2 patients each). CR was observed in 2 patients, and PR in 11 patients with urothelial tract cancer. The overall response rate was 68% (13/19). The response rates in primary and metastatic lesions were 56% (5/9) in primary, 73% (8/11) in lymph node, 71% (5/7) in lung, 67% (2/3) in liver, and 20% (1/5) in bone. The median duration of survival in the responders was 13.5 months, and in the non-responders was 5 months. The 1 year survival rate by Kaplan-Meier method was 70% in responders. On the other hand, the longest survival time in non-responders was 9 months. Marked improvement of survival time was noted in the responders. PR was observed in 1 patient with malignant lymphoma, prostatic adenocarcinoma, and leiomyosarcoma in each. The main toxic effect of MVP-CAB was bone marrow suppression. Leucopenia (WBC less than 4,000/mm3) was noted in 24 patients (86%), and 16 patients (57%) had a WBC count nadir below 2,000/mm3. Thrombocytopenia (plt less than 10 x 10(4)/mm3) was noted in 10 patients (36%). However, there were no deaths due to the bone marrow suppression.

Adult↗

Hemodynamic effects of high-frequency jet ventilation in dogs with acute right coronary arterial ligation and pulmonary arterial banding.

The hemodynamic effects of high-frequency jet ventilation (HFJV), synchronized with diastole, and intermittent positive-pressure ventilation (IPPV) were studied in 10 dogs with acute right-sided myocardial ischemia and elevated right ventricular pressure. Myocardial ischemia was produced by ligation of the proximal right coronary artery (RCA), then the right ventricular pressure was elevated to facilitate the ischemia by banding the main pulmonary artery. Before and 1, 2, 3, and 5 hr after the RCA ligation, cardiorespiratory variables for each ventilatory mode and creatine phosphokinase MB isoenzyme (CPK-MB) were measured. During HFJV compared with IPPV: there were significant increases in stroke index and left ventricular stroke work index at all ischemic periods, and decreases in peak and mean airway pressures and pulmonary vascular resistance at all ischemic periods, and in the product of systolic right ventricular pressure and heart rate at 2 hr, 3 hr, and 5 hr. The difference in mean airway pressure between IPPV and HFJV correlated significantly with those in cardiac index and stroke index (r = 0.575 and 0.779, respectively). CPK-MB was significantly greater at 3 hr and 5 hr than that before RCA ligation. These findings suggest that HFJV synchronized with diastole offers hemodynamic advantages over IPPV to ischemic right ventricle with constricted pulmonary artery, mainly due to lowering the mean airway pressure.

Journal Article↗

Screening test of stimulants in human urine utilizing headspace gas chromatography for field test.

An accurate and simple screening method of stimulants in human urine using headspace gas chromatography utilizing heat of dissolution of potassium carbonate was developed. A 4.9-g portion of potassium carbonate was put into the vial prior to sending to the field, and a 5-ml aliquot of urine, suspected of containing stimulants and internal standard components was pipetted. After the vial was sealed and shaken by hand, 1 ml of its headspace gas was taken by disposable syringe and injected into the gas chromatograph. A compact gas chromatograph device with flame ionization detector and fused silica capillary column was developed for this experiment. Detection limits of methamphetamine and amphetamine were 1.0 micrograms/ml and 1.5 micrograms/ml, respectively.

Amphetamine↗

The anatomical location of the transesophageal echocardiographic transducer during a short-axis view of the left ventricle.

This study was performed to clarify the location of a transesophageal echocardiographic (TEE) transducer when obtaining the short-axis view of the left ventricle (S-LV). The depth of the probe tip from the incisors when obtaining a S-LV, the relationship to the diaphragm, and the location of the cardia of the stomach using a gastroscope attached to the TEE probe were measured in 24 patients undergoing coronary artery bypass grafting. The location of the transducer relative to the cardia and diaphragm was determined. The study demonstrated that when obtaining a S-LV, the transducer was in the stomach in 72.7%, at the cardia in 13.6%, and in the esophagus in 13.6% of the patients. The predominantly intragastric position of the transducer suggests that gastric diseases should be included as contraindications to TEE. When the probe was advanced about 40 cm from the incisors, some resistance was often encountered by the TEE operator at about the level of the diaphragm. Careful manipulation is mandatory to avoid tissue damage by the probe. Visualization of the S-LV can be disturbed by gas in the stomach. This is a specific problem in anesthetized patients because gas is often pushed into the stomach at the time of induction.

Adult↗

Intraoperative assessment of pulmonary vein flow.

This study was undertaken to assess the suitability for intraoperative pulmonary vein flow measurements in 15 patients undergoing coronary artery bypass grafting. Using two-dimensional color Doppler transesophageal echocardiography, all four pulmonary veins--right upper and lower and left upper and lower pulmonary veins were easily visualized. Pulmonary vein flow was pulsatile. J wave occurred in the ventricular systole with relaxation of the left atrium and K wave in the ventricular diastole with relaxation of the left ventricle. There were differences in suitability for flow measurements among four pulmonary veins: (1) consistent visualization; (2) stable visualization throughout measurement; (3) minimal angle between ultrasonic beam and pulmonary vein course; and (4) minimal shift of sampling volume during measurement. The left pulmonary veins were suitable for flow velocity measurement by transesophageal echocardiography. The left lower pulmonary vein was stable for visualization once it was visualized although the angle was occasionally large. The left upper pulmonary vein was consistently visualized although the angle was occasionally large. On the other hand, the right pulmonary veins were unsuitable for flow measurement. Since sampling volume shifted in the direction of the long axis by the average of 5 to 6 mm during cardiac cycle, it should be positioned inside of the pulmonary vein at about 5 mm from the orifice of the left atrium.

Aged↗

Intraoperative monitoring of regional wall motion abnormalities for detecting myocardial ischemia by transesophageal echocardiography.

Transesophageal two-dimensional echocardiography has been used for intraoperative monitoring of regional wall motion of the left ventricle. Regional wall motion abnormality is a sensitive indicator of myocardial ischemia and the use of two-dimensional transesophageal echocardiography may have a substantial advantage for early detection of myocardial infarction and thus for initiating timely and appropriate therapy in preventing postoperative myocardial ischemia. With an expected increase in the use of intraoperative transesophageal echocardiography for monitoring regional wall motion, we described the practical aspects of transesophageal echocardiography: (1) insertion technique of transesophageal echocardiographic probe; (2) the technique for obtaining an optimal short-axis view of the left ventricle; and (3) the method for evaluating regional wall-motion abnormality and myocardial ischemia. Regional wall motion abnormality is best monitored at the mid-papillary muscle level where all three coronary arteries meet. In obtaining this view, the transesophageal echocardiographic probe was found to be predominantly located in the stomach. Failure in obtaining short-axis view of the left ventricle at this level occurred in patients with left ventricular dilatation or obesity. Because of the anatomical reason, the echocardiographic transducer cannot reach a proper plane. In anesthetized patients, air can be pushed into the stomach during induction and may disturb the visualization. The pitfalls in examining regional wall motion abnormalities include: (1) shifting of the center of left ventricular contraction; (2) inadequate direction of the scanning plane; and (3) paradoxical septal movement. Three cases are presented to demonstrate the usefulness of transesophageal echocardiography in managing coronary artery surgical patients.

Aged↗

Serum immunoreactive pancreatic phospholipase A2 in patients with various malignant tumors.

The high incidence (40.6%) of elevated serum pancreatic phospholipase A2 (PLA2) was demonstrated in patients with various malignancies. Serum PLA2 was significantly increased in cancer patients compared with healthy sex- and age-matched blood donors (358.4 +/- 168.0 vs. 241.7 +/- 69.0 ng/dl; p less than 0.01). No correlation was observed between serum PLA2 and carcinoembryonic antigen (CEA) in these patients. Although patients with advanced and distantly metastatic cancer of the liver, gallbladder and pancreas showed higher PLA2 levels in serum than those with early cancer, patients with other cancers showed no correlation between serum PLA2 and clinical stage. A combined assay of PLA2 and CEA increased the sensitivity of detection of cancers to 60.8%.

Amylases↗

Establishment of a pancreatic beta cell line that retains glucose-inducible insulin secretion: special reference to expression of glucose transporter isoforms.

Two cell lines have been established from insulinomas obtained by targeted expression of the simian virus 40 T antigen gene in transgenic mice. These cell lines, designated MIN6 and MIN7, produce insulin and T antigen and have morphological characteristics of pancreatic beta cells. MIN6 cells exhibit glucose-inducible insulin secretion comparable with cultured normal mouse islet cells, whereas MIN7 cells do not. Both cell lines produce liver-type glucose transporter (GT) mRNA at high level. Brain-type GT mRNA is also present at considerable level in MIN7 cells, but is barely detectable in MIN6 cells, suggesting that exclusive expression of the liver-type GT is related to glucose-inducible insulin secretion. MIN6 cells do not express either major histocompatibility (MHC) class I or class II antigens on the cell surface. However, treatment with interferon-gamma induces high levels of MHC class I antigens, and a combination of interferon-gamma and tumor necrosis factor-alpha induces a MHC class II antigen on the cell surface. These results emphasize that the MIN6 cell line retains physiological characteristics of normal beta cells. The MIN6 cell line will be especially useful to analyze the molecular mechanisms by which beta cells regulate insulin secretion in response to extracellular glucose concentrations. We discuss a possible role of GT isoforms in glucose sensing by beta cells.

Animals↗

Increased liver glucose-transporter protein and mRNA in streptozocin-induced diabetic rats.

The effect of insulin-deficient diabetic states on the rat liver glucose-transporter (L-transporter isoform) protein and mRNA levels were studied. Rats were injected with 65 mg/kg streptozocin to induce diabetes and were maintained for 10 days and then treated with or without insulin for the next 5 days. The L-transporter isoform with apparent Mr of 55,000 was observed to be increased approximately twofold in the membranes from liver homogenates of diabetic rats compared with control rats when assessed by Western blot analysis with an anti-peptide antibody directed against rat L-transporter isoform. Insulin treatment of diabetic rats decreased the amount of L-transporter isoform protein toward levels observed in nondiabetic rats. Northern blot analysis demonstrated similar alterations in the rat L-transporter isoform mRNA that paralleled the changes observed in the L-transporter isoform protein. The increased levels of the L-transporter isoform protein and mRNA in diabetic rats are in marked contrast to the effects of insulin deficiency in rat adipocytes, which specifically decrease the amount of the adipocyte glucose-transporter isoform protein and mRNA. These results suggest that glucose-transporter isoforms in rat liver and adipocytes are regulated by different mechanisms and that an increased synthesis of the L-transporter isoform may contribute to the increased glucose output that occurs from the liver during insulin deficiency.

Amino Acid Sequence↗

Serum interleukin 6, C-reactive protein and pancreatic secretory trypsin inhibitor (PSTI) as acute phase reactants after major thoraco-abdominal surgery.

We measured serum immunoreactive interleukin 6 (IL-6) levels in patients after major thoraco-abdominal surgery and compared them with changes in serum C-reactive protein (CRP) and pancreatic secretory trypsin inhibitor (PSTI) levels. Serum IL-6 levels were elevated earlier than serum CRP or PSTI. There were significant relationships between the peak levels of serum IL-6 and the operation time (p less than 0.05) or the volume of blood loss during surgery (p less than 0.05), showing that serum IL-6 can be a useful laboratory test for the evaluation of tissue injuries due to surgical intervention. Though there was a significant relationship between the peak levels of IL-6 and CRP (p less than 0.01), there was no relationship between the peak levels of IL-6 and PSTI.

Acute-Phase Reaction↗

Response to IL-6 stimulation of human hepatoblastoma cells: production of pancreatic secretory trypsin inhibitor.

LPS-stimulated macrophage conditioned medium and IL-6 markedly stimulated the secretion of PSTI by cultured hepatoblastoma cells. The mechanism underlying the cellular response of IL-6-induced secretion of PSTI was investigated. Among the agents affecting the signal transduction pathways, forskolin significantly induced PSTI secretion whereas PMA or A23187 did not, suggesting that IL-6 induced PSTI secretion is mediated by cAMP dependent protein kinase A.

Animals↗