Assessment of autonomic reinnervation of cardiac grafts by analysis of heart rate variability.
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3-Iodobenzylguanidine↗
Biomedical subjects
Y Kobayashi
Publications and source records attributed to Y Kobayashi.
Effects of cryopreservation of aortic xenografts on graft patency and immunogenicity.
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Animals↗
Studies of the multiorgan procurement system from non-heart-beating donors.
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Adenosine↗
Induction of apoptosis of activated murine splenic T cells by cycloprodigiosin hydrochloride, a novel immunosuppressant.
Two types of immunosuppressants, cycloprodigiosin hydrochloride (cPrG) and L-leucyl-L-leucine methyl ester (LeuLeuOMe), both have the ability to selectively inhibit the lysosomal function, and a related compound to cPrG, prodigiosin 25-C, and LeuLeuOMe have been reported to selectively inhibit the T cell function in vitro. We therefore examined the cell-type specificity of cPrG and LeuLeuOMe using murine splenocytes. Concanavalin A (Con A)- and lentil lectin-induced proliferation was suppressed by cPrG more profoundly than lipopolysaccharide-induced proliferation. At the optimal concentration, Con A induced the proliferation of both CD4+ and CD8+ cells, whereas at a supra-optimal concentration Con A induced rather selective proliferation of CD8+ cells. Irrespective of the dose of Con A, CD4+ and CD8+ cells were equally affected by cPrG. In contrast, LeuLeuOMe induced the selective loss of CD8+ cells. cPrG enhanced the apoptosis of murine splenocytes and nylon fiber column-purified T cells cultured in the presence of Con A, as shown by the decrease in cell size and/or DNA fragmentation. Overall, this study revealed that the cell-type specificity of cPrG is different from that of LeuLeuOMe, and that the immunosuppression by cPrG is associated with apoptosis.
Animals↗
A mathematical analysis of the characteristics of the system connecting the cerebellar ventral paraflocculus and extraoculomotor nucleus of alert monkeys during upward ocular following responses.
Movements of the visual scene evoke short-latency ocular-following-responses (OFR). Many studies suggest that a neural pathway containing the cerebellar-ventral-paraflocculus (VPFL) mediates OFR. The relationship between eye movement and simple-spike firing in the VPFL during OFR has been studied in detail using an inverse dynamics approach. The relationship between eye movement and cell firing in the extraoculomotor nucleus (MN) has already been reported. However, no studies have examined the information transformation that occurs between the VPFL and the MN during OFR. In this paper, using an inverse dynamics approach, we derive a transfer function that represents the characteristics of the structure connecting the VPFL and the MN during upward OFR. This structure appears to contain a kind of neural integrator, which constructs eye-velocity-and-position information from eye-acceleration-and-velocity information. We propose a diagram for the neural integration commonly at work during all types of upward eye movement. This is a closed-loop circuit containing a low-pass filter. The low-pass filter can construct eye-velocity-and-position information from an eye-acceleration-velocity-position command similar to the final motor command used commonly for all upward eye movements. Anatomical and electrophysiological data suggest that the vestibular nuclei-interstitial nucleus of Cajal-vestibular nuclei loop might perform such neural integration.
Action Potentials↗
Expression of MAGE, GAGE and BAGE genes in human liver diseases: utility as molecular markers for hepatocellular carcinoma.
BACKGROUND/AIMS: The MAGE, GAGE and BAGE genes encode tumor antigens recognized by autologous cytotoxic T lymphocytes. The aim of this study was to evaluate the possibility of using these genes as molecular markers and as the targets of specific immunotherapy for human hepatocellular carcinoma (HCC). METHODS: The expressions of MAGE-1, MAGE-3, GAGE1-6, GAGE1-2 and BAGE mRNA in 33 surgically resected HCC samples and 26 of their corresponding non-cancerous samples (11 liver cirrhosis and 15 chronic hepatitis) were studied by a reverse-transcription polymerase chain reaction, and were compared with clinicopathological parameters. The expression of MAGE-1 was also examined in 16 biopsied HCC samples. RESULTS: MAGE-1, MAGE-3, GAGE1-6, GAGE1-2 and BAGE mRNA were expressed in 67%, 39%, 36%, 30%, and 21% of the HCC, respectively. At least one transcript was detected in 88% of the HCC, while no expression was observed in the non-cancerous livers. There was no significant correlation between the expression of any of the tumor antigens examined and the differentiation stage or size of the HCC. Especially, MAGE-1 was highly expressed in small HCC with a diameter of less than 2 cm and in well-differentiated HCC (81% and 70%, respectively), and was also expressed even in alpha-fetoprotein-negative and PIVKA-II-negative HCC (58% and 76%, respectively). The MAGE-1 expression was detected in 69% of biopsied HCC samples and the expression was high in both small and well-differentiated HCC. CONCLUSIONS: These tumor-specific antigens can be useful as molecular markers and as the possible target molecules for the specific immunotherapy of human HCC.
Adult↗
Insertion/deletion polymorphism in ACE gene is not associated with renal progression in Japanese patients with IgA nephropathy.
We determined the relationship between the gene polymorphism of angiotensin I-converting enzyme (ACE) and the progression of immunoglobulin A (IgA) nephropathy in a large cohort in a multicenter trial of ethnically homogeneous Japanese patients (n = 527). Patients with biopsy-proven IgA nephropathy were recruited from several clinics in Japan. The mean observation period was 8.4 +/- 4.7 years. ACE insertion/deletion (I/D) genotype was determined by polymerase chain reaction amplification using allele-specific primers. Clinical factors investigated in all patients were date of birth, sex, levels of urinary protein excretion, duration of observation, serum creatinine (sCr) level, and creatinine clearance (CCr). ACE genotype distribution did not differ between patients who maintained normal renal function (II, 41%; ID, 44.7%; DD, 14.3%) and those who progressed to renal impairment (II, 41.7%; ID, 40.4%; DD, 17.9%). Kaplan-Meier analysis did not show a significant difference in renal survival rate among the three groups of each genotype. In multivariate analysis, only two variables, proteinuria greater than 1.0 g/d of protein and impaired renal function (sCr >1.2 mg/dL or CCr <70 mL/min) at the time of renal biopsy, were found to be risk factors for disease progression leading to a poor outcome. No association was observed between these variables and ACE genotype. It appears that ACE I/D polymorphism may not affect the progressive deterioration of renal function in patients with IgA nephropathy from our multicenter trial.
Adult↗
Effect of the space environment on the induction of DNA-repair related proteins and recovery from radiation damage.
Recovery of bacterial cells from radiation damage and the effects of microgravity were examined in an STS-79 Shuttle/Mir Mission-4 experiment using the extremely radioresistant bacterium Deinococcus radiodurans. The cells were irradiated with gamma rays before the space flight and incubated on board the Space-Shuttle. The survival of the wild type cells incubated in space increased compared with the ground controls, suggesting that the recovery of this bacterium from radiation damage was enhanced under microgravity. No difference was observed for the survival of radiosensitive mutant rec30 cells whether incubated in space or on the ground. The amount of DNA-repair related RecA protein induced under microgravity was similar to those of ground controls, however, induction of PprA protein, the product of a newly found gene related to the DNA repair mechanism of D. radiodurans, was enhanced under microgravity compared with ground controls.
Bacterial Proteins↗
Successful control with bromide of two patients with malignant migrating partial seizures in infancy.
A 3-month-old male and a 4-month-old female infant with intractable seizures were diagnosed as having malignant migrating partial seizures in infancy (MMPSI) with developmental arrest on the basis of characteristics of symptoms, clinical courses and EEGs. We treated these two patients with potassium bromide (80 mg/kg) after conventional antiepileptic drugs failed to adequately control the seizures. The potassium bromide therapy resulted in complete control of seizures in one patient, and more than 95% reduction in seizure frequency in the other.
Bromides↗
Enhancement of hepatocarcinogenesis initiated with diethylnitrosamine or N-nitrosobis(2-hydroxypropyl)amine by a choline-deficient, L-amino acid-defined diet administered prior to the carcinogen exposure in rats.
Effects of pre-administration of a choline-deficient, L-amino acid-defined (CDAA) diet on hepatocarcinogenesis initiated with diethylnitrosamine (DEN) or N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats were investigated. A pre-administrating period was set as 1 week, because CDAA diet induces liver injuries by this time-point. In a time-course study, male Fischer 344 rats, 6 weeks old, received a 1-week pre-administration of choline-supplemented, L-amino acid-defined (CSAA) or CDAA diet, DEN at a dose of 100 mg/kg body weight by a single intraperitoneal injection, then CSAA or CDAA diet for up to 8 weeks, and were sacrificed 4, 6 and 8 weeks after DEN. CDAA diet administered only after DEN significantly increased the numbers of glutathione S-transferase placental form (GST-P)-positive lesions 4, 6 and 8 weeks after DEN and their sizes 6 and 8 weeks after DEN. CDAA diet administered both before and after DEN similarly increased the numbers and sizes of GST-P-positive lesions, but with a significantly greater degree than obtained by the diet administered only after DEN. In a dose response study, rats received vechicle or DEN, at a dose of 0.001, 0.01, 0.1, 1, 10, 20, 50, 100 or 200 mg/kg body weight, 1 week after the commencement of CSAA or CDAA diet, and sacrificed 8 weeks after vehicle or DEN. The significant increases of the numbers of GST-P-positive lesions were obtained after 50-200 mg/kg body weight of DEN under the CSAA diet administration, whereas those were detected after 10-200 mg/kg under CDAA diet administration. Sizes became significantly larger with only 200 mg/kg body weight of DEN in the CSAA case but with 50-200 mg/kg in the CDAA case. Male Wistar rats received a 1-week pre-administration of CSAA or CDAA diet, vehicle or BHP, at a dose of 600 or 1200 mg/kg body weight, by a single intraperitoneal injection, then CSAA or CDAA diet for 8 weeks, and were then sacrificed. The numbers of GST-P-positive lesions demonstrated significant increment with 1200 mg/kg body weight of BHP by CDAA diet administered only after BHP and, to a significantly greater degree, by the diet administered both before and after BHP. While CDAA diet administered only after BHP did not alter the sizes of GST-P-positive lesions, the diet administered both before and after 600 and 1200 mg/kg body weight of BHP significantly increased the sizes of the lesions. These results indicate that the pre- plus post-administration of CDAA diet enhances hepatocarcinogenesis initiated with DEN or BHP, more than the post-administration only, thus providing a sensitive model to detect weak liver carcinogenic potency of environmental chemicals.
Amino Acids↗
Stress responses during laparoscopy with CO2 insufflation and with mechanical elevation of the abdominal wall.
STUDY OBJECTIVE: To compare the intensity of stress responses caused by laparoscopy combined with CO2 insufflation (CI) with those caused by mechanical elevation of the abdominal wall (MEA). DESIGN: Prospective study (Canadian Task Force classification I). SETTING: Tertiary care university hospital. PATIENTS: Thirty-one women. Intervention. Laparoscopy, 16 with CI and 15 with MEA. MEASUREMENTS AND MAIN RESULTS: Circulating levels of norepinephrine, epinephrine, cortisol, and interleukin (IL)-6 were compared in the two groups. Arterial partial pressure of CO2 (PaCO2) did not increase during laparoscopy by either method. Plasma norepinephrine and epinephrine levels increased after extubation in the MEA group but not in the CI group. Circulating cortisol levels in both groups increased during laparoscopy; mean intraoperative levels were higher in the CI group. Serum IL-6 levels increased after extubation in the MEA but not the CI group. Mean heart rate increased during laparoscopy in both groups, whereas blood pressure increased only in the CI group. More patients in the MEA group required postoperative analgesia. CONCLUSION: Laparoscopy with MEA caused more pronounced adrenosympathetic and cytokine responses than that with CI when PaCO2 was maintained within the range of normocapnia.
Carbon Dioxide↗
Green tea polyphenols inhibit the sodium-dependent glucose transporter of intestinal epithelial cells by a competitive mechanism.
Intestinal glucose uptake is mainly performed by the sodium-dependent glucose transporter, SGLT1. The transport activity of SGLT1 was markedly inhibited by green tea polyphenols, this inhibitory activity being most pronounced in polyphenols having galloyl residues such as epicatechin gallate (ECg) and epigallocatechin gallate (EGCg). Experiments using brush-border membrane vesicles obtained from the rabbit small intestine demonstrated that ECg inhibited SGLT1 in a competitive manner, although ECg itself was not transported via SGLT1. The present results suggest that tea polyphenols such as ECg interact with SGLT1 as antagonist-like molecules, possibly playing a role in controlling the dietary glucose uptake in the intestinal tract.
Animals↗
Analysis of posterior mitral annular activation during entrainment and catheter ablation of mitral isthmus ventricular tachycardia using a coronary sinus catheter.
A detailed analysis of the ventricular activation along the posterior aspect of the mitral annulus was made using a multipolar catheter positioned in the coronary sinus in a patient with mitral isthmus ventricular tachycardia (VT) associated with a remote inferior myocardial infarction and prior cryosurgical ablation for the elimination of a different preexisting VT. A change in the timing and sequence of the ventricular activation along the isthmus could be observed during induction of the VT and entrainment pacing. A radiofrequency (RF) current application directed at the posterolateral region of the isthmus successfully eliminated this tachycardia. During the RF delivery, complete conduction block was confirmed by a sudden change in the activation sequence during sinus rhythm.
Aged↗
Three-dimensional solution structure of a disulfide bond isomer of the human insulin-like growth factor-I.
The solution structure of a disulfide bond isomer of human insulin-like growth factor-I (IGF-I) was determined using homonuclear NMR methods. A total of 292 interatomic distance constraints, including 12 related to the disulfide bridges, was used in the distance geometry calculations. The determined structures contain two helical rods corresponding to the sequence regions, Ala8-Cys18 and Leu54-Cys61. Comparison with the previously determined structure of native human IGF-I revealed partial correspondence of the secondary structure (helices I: Ala8-Cys18 and helices III: Leu54-Cys61) and internal packing. Helix II in native human IGF-I (residues Gly42-Cys48) is disrupted in the isomer. A similar relationship has been described between the structure of native insulin and a homologous disulfide isomer, suggesting that these alternative folds represent general features of insulin-like sequences. In each case the precision of the distance geometry ensemble is low due in part to resonance broadening and a paucity of NOEs relative to other globular proteins of this size. These observations suggest that tertiary structure of the isomer is not highly ordered. Comparison of the biological activities of native and the disulfide bond isomer of human IGF-I highlight the importance of Tyr24, Phe25, Phe49-Cys52 and Phe16 in binding to the IGF-I receptor or specific IGFBPs. The relationship of this proposed receptor-binding surface of human IGF-I to those of insulin is discussed.
Amino Acid Sequence↗
Differential growth inhibitory effect of melatonin on two endometrial cancer cell lines.
The effect of melatonin on endometrial cancer cell growth was investigated using two cell lines, SNG-II and Ishikawa, which are different in their estrogen receptor status. A physiological concentration of melatonin (10(-9) M) showed no growth inhibitory effect on SNG-II cells, which are estrogen receptor-negative at all cell densities and incubation times. In contrast, melatonin significantly inhibited Ishikawa cells, which are estrogen receptor-positive at all cell densities tested after 96 hr incubation. The greatest inhibition of Ishikawa cell growth was observed at 10(-9) M melatonin, compared with other supra (10(-6), 10(-8) M) or subphysiological concentrations (10(-10), 10(-12) M). This growth inhibitory effect of melatonin on Ishikawa cells was completely blocked by 10(-10) to 10(-8) M concentrations of 17-beta estradiol administration. Pretreatment with luzindole, which is a selective melatonin receptor antagonist, prior to the addition of melatonin also blocked the inhibitory effect of melatonin on Ishikawa cells. This is the first study to demonstrate an anti-proliferative effect of physiological melatonin on endometrial cancer cells in vitro. The present study revealed that melatonin also inhibits the growth of estrogen receptor positive endometrial cancer cells and that this effect of the pineal indole may be mediated by both steroid and melatonin receptors.
Adenocarcinoma↗
Participation of mitogen-activated protein kinase in thapsigargin- and TPA-induced histamine production in murine macrophage RAW 264.7 cells.
1. Stimulation of the murine macrophage cell line RAW 264.7 with thapsigargin, an endomembrane Ca(2+)-ATPase inhibitor, induced histamine production in a time- and concentration-dependent manner. 2. The protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA), also enhanced histamine production. 3. alpha-Fluoromethylhistidine, a suicide substrate of L-histidine decarboxylase (HDC), suppressed the thapsigargin (30 nM)- and TPA (30 nM)-induced histamine production. 4. Both thapsigargin (30 nM) and TPA (30 nM) induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase. 5. PD98059, a specific inhibitor of MEK-1 which phosphorylates p44/p42 MAP kinase, strongly suppressed both the thapsigargin (30 nM)- and TPA (30 nM)-induced histamine production, whereas SB203580, a specific inhibitor of p38 MAP kinase, inhibited them only partially. 6. The other MEK-1 inhibitor, U-0126, also inhibited both the thapsigargin- and TPA-induced histamine production in a concentration-dependent manner. 7. Thapsigargin (30 nM) and TPA (30 nM) increased the levels of HDC mRNA at 4 h, but PD98059 suppressed both the thapsigargin- and TPA-induced increases in the HDC mRNA level. 8. These findings indicate that thapsigargin and TPA induce histamine production in RAW 264.7 cells by increasing the level of HDC mRNA, and that both the thapsigargin- and TPA-induced histamine production are regulated largely by p44/p42 MAP kinase and partially by p38 MAP kinase.
Animals↗
Cardiac conduction abnormalities in patients with breast cancer undergoing high-dose chemotherapy and stem cell transplantation.
Cardiac toxicities in 39 consecutive patients with breast cancer receiving high-dose chemotherapy (HDC) with stem cell transplantation were reviewed. All 39 patients received various anthracycline-containing regimens in adjuvant settings and/or for metastatic disease before HDC. As a cytoreductive regimen, all received cyclophosphamide 2000 mg/m2 and thiotepa 200 mg/m2 for 3 consecutive days. No immediate fatal toxicities were observed, but one patient developed chronic congestive heart failure and two had transient left ventricular dysfunction. Pericardial effusion was observed in another three patients. ST-T abnormalities during HDC were observed in two patients and arrhythmias were observed in nine, four of which occurred during stem cell infusion (SCI). There were three atrial arrhythmias, two ventricular arrhythmias, and four atrioventricular (AV)-block episodes. Two patients developed advanced and complete AV-block with an asystolic pause. Notably, three patients experienced AV-block with uncontrolled vomiting. No relationship was observed between the cumulative dose of anthracycline and cardiac toxicities during HDC. These results suggest that abnormalities in the conduction system during HDC may be more frequent than previously reported. Vagal reflex secondary to emesis may play an important role in the development of AV-block. Bone Marrow Transplantation (2000) 25, 185-189.
Adult↗
Prognostic significance of the cell cycle inhibitor p27Kip1 in acute myeloid leukemia.
There are few molecular biologic determinants that are prognostic for patients with acute myeloid leukemia (AML). Hence, we examined whether cellular levels of the cyclin-dependent kinase inhibitor p27Kip1 in acute myeloid leukemia could be used to predict clinical outcome in AML. Using immunoblot analysis, levels of p27 were assessed in blast cells from 72 AML patients who were registered and treated by the identical chemotherapy protocol. AML cases were classified into three groups on the basis of the percentage of the expression level of p27 compared to a control cell line. AML cases exhibiting p27 expression at low, moderate, and high levels were 43, 9, and 20 cases, respectively. No significant differences in the rates of complete remission (CR) were observed among the three groups. Although the level of p27 expression was not correlated with any other possible prognostic markers, such as age, white blood cell count, chromosome abnormalities, and FAB subclasses, patients with high p27 expression had a significantly increased disease-free survival (DFS) (78% vs 19%, P = 0.004). We further examined the expression of cyclin E at the protein level in all 72 AML cases. We observed a statistically significant correlation between a high cyclin E level and a high p27 level (P < 0.005). However, we failed to find any correlation between the rates of CR or DFS and cyclin E expression. The present study reveals that levels of p27 expression can be one of the useful prognostic molecular markers for AML. Leukemia (2000) 14, 28-33.
Acute Disease↗