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Biomedical subjects

H Satoh

Publications and source records attributed to H Satoh.

At least 271 records · Page 15Linked to original sources

Synthesis of L-enantiomers of 4'-thioarabinofuranosyl pyrimidine nucleosides.

L-Enantiomers of 4'-thioarabinofuranosyl pyrimidine nucleosides were synthesized from D-xylose. Methyl 2,3,5-tri-O-benzyl-D-xylofuranoside 6 was converted to the corresponding xylitol 7, which was treated with MsCl and then Na2S to give 1,4-anhydro-L-4-thioarabitol 8. As previously reported, Pummerer rearrangement of 8 followed by glycosylation with a silylated thymine and N4-acetylcytosine derivative and deprotection gave the corresponding alpha- and beta-L-4'-thioarabinofuranosyl pyrimidine nucleosides.

Antimetabolites, Antineoplastic↗

Inhibition by taurine of the inwardly rectifying K+ current in guinea pig ventricular cardiomyocytes.

Effects of taurine on the inwardly rectifying K+ current (IK1) in isolated guinea pig ventricular cardiomyocytes were examined using patch voltage-clamp methods. All experiments were performed at 36 degrees C. Taurine (10-20 mM) increased the action potential duration, but failed to affect the resting potential. Holding potential was maintained at -30 mV. The current was activated with an inwardly going rectification, and was completely blocked by Ba2+ (2 mM). Taurine inhibited IK1 at - 120 mV by 28.3+/-1.1% (n=6, P < 0.05) at 10 mM and by 36.0+/-2.1% (n=6, P < 0.01) at 20 mM. The reversal potential was shifted in the hyperpolarizing direction by 3.7+/-0.6 mV (n=6) at 20 mM. In inside-out patch-clamp experiments, the amplitude of unitary channels was -2.7+/-0.3 pA (n=21) at -90 mV. Symmetrical high-K+ (150 mM) solutions in both bath and pipette were used. The channel conductance was 32+/-2 pS (n=9). Taurine did not affect channel conductance, but markedly decreased the open probability at - 120 mV of channel by 21.5+/-2.4% (n=8, P < 0.01) at 10 mM, and by 56.7+/-3.8% (n=8, P < 0.001) at 20 mM. These responses were almost reversible. These results suggest that taurine directly modulates the open probability of the inwardly rectifying K+ current, resulting in regulation of the functions of heart cells.

Action Potentials↗

Cardiac actions of taurine as a modulator of the ion channels.

During ischemia, hypoxia and cardiac failure, the heart undergoes several adverse changes, including a reduction in taurine (2-aminoethanesulfonic acid). Oral administration of taurine under these disease conditions would be expected to act like a mild cardiac glycoside. Taurine would exert improvement in the accumulation of [Na]i and the loss of alpha-amino acids. Nonetheless, when intracellular taurine content is raised, there would be the benefit of increased Ca2+ release from the sarcoplasmic reticulum and increased Ca2+ sensitivity of the contractile proteins, as well as possible changes in the action potential associated with the actions of taurine on ion channels. In fact, intracellular application of taurine produces the opposite actions to extracellularly administration of the amino acid. From our previous experiments, the electrophysiological actions of taurine on cardiac muscle cells include the following. (a) Prolongation of action potential duration (APD) at high [Ca]i and shortening of APD at low [Ca]i. In multicellular preparations, however, taurine did not always prevent [Ca]o-induced effects. (b) Stimulation of spontaneous activity at low intracellular and extracellular Ca2+ concentrations ([Ca]i and [Ca]o), and vice versa. (c) Inhibition of the L-type Ca2+ current (ICa(L)) at high [Ca]i, and vice versa. (d) Enhancement of the T-type Ca2+ current (ICa(T)). (e) Inhibition of fast Na+ current (INa). (f) Enhancement of TTX-insensitive slow Na+ current. (g) Inhibition of delayed rectifier K+ current (IKrec) at high [Ca]i, and vice versa. (h) Enhancement of the transient outward current (Ito). (i) Inhibition of the ATP-sensitive K+ current (IK(ATP)). Since taurine acts on so many ion channels and transporters, it is clearly non-specific. Although it is very difficult to understand the diversity of taurine's actions, it is possible that taurine can exert its potent cardioprotective actions under the conditions of low [Ca]i, as well as Ca2+ overload. Thus, although taurine-induced modulation of ion channels located on the cardiac cell membrane is complex, the multiple effects may combine to yield useful therapeutic results.

Adenosine Triphosphate↗

Inhibitory effects of prostaglandin D2 against the proliferation of human colon cancer cell lines and hepatic metastasis from colorectal cancer.

The inhibitory action of prostaglandin D2 (PGD2) and its effect on the cell cycle were examined in cell lines SW480 and LS174T of human colon cancer. The growth of the cell lines were assessed 24 h and 48 h after the addition of 1.0 microgram/ml and 10.0 micrograms/ml PGD2. The growth of SW480 cells was inhibited 48 h, but not 24 h, after the addition of 1.0 microgram/ml, and 24 h and 48 h after the addition of 10.0 micrograms/ml, while that of LS174T was inhibited by both doses after 24 h and 48 h. S-Phase DNA synthesis in the SW480 cells was significantly blocked 24 h after the addition of 10.0 micrograms/ml PGD2. The cell cycle of LS174T cells was arrested at the G0 + G1 phase 24 h after the addition of 1.0 microgram/ml and 10.0 micrograms/ml PGD2. The correlation between hepatic metastasis and PGD2 concentration in human cancer tissue was examined. The mean value of PGD2 concentrations in the primary cancer tissue was significantly lower in the hepatic metastasis group than that in the group without hepatic metastasis. These findings suggest that measuring the PGD2 in cancer tissue may be useful for detecting and predicting the hepatic metastasis from human colorectal cancer.

Biomarkers, Tumor↗

Systemic lupus erythematosus associated with primary large cell carcinoma of the lung.

The association between systemic lupus erythematosus (SLE) and malignancy has been controversial in the literature. We report a case of lung cancer in a 50-year-old woman with a 4-year history of SLE. She underwent surgery at a pathological stage of T2N2M0, but she eventually died of rapid recurrence of the cancer in the abdomen resulting in massive haemorrhage from the inferior vena cava (IVC). Immunological disorders related to SLE are thought to contribute to rapid progression of the malignancy.

Abdominal Neoplasms↗

Metastatic small cell lung cancer causing biliary obstruction.

We report a case with metastatic small cell lung cancer which first manifested with biliary obstruction due to metastasis. Prognosis of patients presenting with jaundice due to hepatic parenchyma involvement is thought to be poor. However, the patient was successfully treated with percutaneous transhepatic biliary drainage and combination chemotherapy with reduced dosage. We believe this to be the first such case report, despite the frequency of metastasis to the liver from small cell lung cancer.

Aged↗

[A case of coronary artery bypass grafting for effort angina in a patient with post skin grafting for an extramammary Paget's disease].

The extramammary Paget's disease of anogenital area is rare, and is seen as a precancerous lesion or carcinoma in situ. In most cases, surgical treatment including dissection of regional lymph nodes, skin resection and grafting should be considered first. A 74-year-old male suffered from effort angina and underwent triple coronary artery bypass grafting (CABG) including saphenous vein graft (SVG) harvested from right lower leg. Five years previously he underwent skin grafting for extramammary Paget's disease of both inguinal areas and the perineal area. The postoperative course was uneventful and he was discharged 23 days after the CABG operation. Extramammary Paget's disease is localized in epidermis for years and there has been no report of direct invasion into vessels. Therefore, there appears to be no reason not to use an SVG if there is no luminal thrombus or occlusion.

Aged↗

[Repair of complete atrioventricular septal defect with severe pulmonary hypertension--effect of re-pulmonary artery banding and analysis of lung biopsy: a case report].

We report a case complete atrioventricular defect with severe pulmonary hypertension. The patient was a girl aged 2 years and 6 months with Down's syndrome who had undergone pulmonary artery banding (PAB) 2 years previously. Postoperative catheterization after PAB showed severe pulmonary hypertension. Pulmonary resistance values were 9.3 and 7.3 units at 1 year and 5 months and 1 year and 9 months respectively. We performed re-PAB and lung biopsy when the patient was 2 years and 6 months old. The biopsy specimen at re-PAB classified as Heath-Edwards grade 3 and had an IPVD score of 1.7, indicating tolerance to radical operation. Six months after re-PAB, pulmonary vascular resistance decreased a level at which radical operation could be performed safely. Radical operation was performed 1 year and 4 months after re-PAB. The post operative course was uneventful, and pulmonary hypertensive crisis did not occur. The lung biopsy at the final operation was classified as Heath-Edwards grade 3, had an IPVD score of 1.1, and showed improvement when compared with the pathological findings at re-PAB.

Biopsy↗

Cloning and mapping of cat (Felis catus) immunoglobulin and T-cell receptor genes.

Molecular cloning and chromosomal mapping of the cat immunoglobulin (Ig) and T-cell receptor (TcR) genes were carried out to provide basic information for genetic analysis of immunologic diseases including leukemias and lymphomas in cats. We cloned two Ig constant genes, IGHM and IGHG and three TcR constant genes, TRAC, TRGC, and TRDC, by polymerase chain reaction (PCR) amplification of cDNA from cat peripheral blood mononuclear cells. For chromosomal mapping of the Ig and TcR loci including the IGK, IGL, and TRB on the cat genome, we performed PCR screening of DNAs from 37 cat x rodent somatic cell hybrids by using specific primers for the given genes. Consequently, three loci for IGH, TRA, and TRD, and two loci for TRB and TRG were found to be syntenic and assigned to cat chromosomes (FCA) B3 and A2, respectively. Further, IGK and IGL loci were mapped on FCA A3 and D3, respectively. These findings support the notion that the genetic linkages between the Ig and TcR genes are extensively conserved between humans and cats.

Amino Acid Sequence↗

Importance of type IV collagen, laminin, and heparan sulfate proteoglycan in the regulation of labyrinthine fluid in the rat cochlear duct.

The distribution of major components of the basement membrane, such as type IV collagen, laminin, and heparan sulfate proteoglycan (HSPG), was investigated in the rat cochlear duct. Immunofluorescence demonstrated that type IV collagen, laminin and HSPG were distributed along capillaries in the cochlear duct, including the stria vascularis, spiral ligament, spiral prominence and spiral limbus. Additionally, type IV collagen, laminin and HSPG were found to be distributed from the basement membrane of Reissner's membrane to that of the spiral prominence in a linear pattern. The scala media was surrounded by these basement membrane components, demarcating endolymph from perilymph, along epithelial cells except at the stria vascularis. These findings suggest that type IV collagen, laminin and HSPG create the anatomical separation between endolymph and perilymph, thus indicating that they may be involved in the regulation of fluid transport between the endolymph and perilymph.

Animals↗

Differences in stretch reflex responses of elbow flexor muscles during shortening, lengthening and isometric contractions.

Stretch reflexes were evoked in elbow flexor muscles undergoing three different muscle contractions, i.e. isotonic shortening (SHO) and lengthening (LEN), and isometric (ISO) contractions. The intermuscle relationships for the magnitude of the stretch reflex component in the eletromyographic (EMG) activities of two main elbow flexor muscles, i.e. the biceps brachii (BB) and the brachioradialis (BRD), were compared among the three types of contractions. The subjects were requested to move their forearms sinusoidally (0.1 Hz) against a constant pre-load between elbow joint angles of 10 degrees (0 degrees = full extension) and 80 degrees during SHO and LEN, and to keep an angle of 45 degrees during the ISO. The perturbations were applied at the elbow angle of 45 degrees in pseudo-random order. The EMG signals were rectified and averaged over a period of 100 ms before and 400 ms after the onset of the perturbation 40-50 times. From the ensemble averaged EMG waveform, the background activity (BGA), short (20-50 ms) and long latency (M2, 50-80, M3, 80-100 ms) reflex and voluntary activity (100-150 ms) components were measured. The results showed that both BGA and reflex EMG activity of the two elbow flexor muscles were markedly decreased during the lengthening contraction compared to the SHO and ISO contractions. Furthermore, the changes of reflex EMG components in the BRD muscle were more pronounced than those in the BB muscle, i.e. the ratios of M2 and M3 magnitudes between BRD and BB (BRD:BB) were significantly reduced during the LEN contractions. These results would suggest that the gain of long latency stretch reflex EMG activities in synergistic muscles might be modulated independently according to the model of muscle contraction.

Adult↗

Suppressive responses to calcium and catecholamines in immobilization stress-loaded rats.

1. Modulations of electrophysiological actions on the right atria of immobilization (restraint) stress-loaded rats by extracellular Ca2+ concentration, [Ca]0, catecholamines and some drugs were examined. 2. The serum concentration of corticosterone increased compared with native rats, and peptic ulcerization was observed. 3. The stress-loaded rats had a stronger contraction and a higher sinus rate. Increasing [Ca]0 (0.9-3.6 mM) enhanced the contractile force in native rats, whereas increasing [Ca]0 inhibited it in stress-loaded rats. The cycle length decreased with an increase in [Ca]0 in native rats more than in stress-loaded rats. 4. Enhancement induced by isoprenaline (0.1-10 microM) at normal [Ca]0 was more suppressive in stress-loaded hearts. At 0.1 to 10 microM, norepinephrine and phenylephrine significantly caused a negative inotropic effect in both native and stress-loaded hearts, and norepinephrine caused a positive chronotropic effect in native hearts but not in stress hearts. 5. Both taurine and nicotine had negative inotropic and chronotropic effects in native rats. However, the drugs enhanced the contractile force in stress rats. 6. These results indicate that immobilization stress decreases the sensitivities to [Ca]0, and increasing [Ca]0 easily elicits Ca2+ overload. Low sensitivities to sympathetic drugs also are produced by the stress loading, whereas taurine and nicotine may exhibit protective actions.

Adrenergic Agonists↗

Review of some actions of taurine on ion channels of cardiac muscle cells and others.

1. Taurine has recently been known to protect against ischemia and heart failure. Taurine possesses plenty of actions on the ion channels and transports, but is very non-specific. 2. Taurine may directly and indirectly help to regulate the [Ca]i level by modulating the activity of the voltage-dependent Ca2+ channels (also dependent on [Ca]i/[Ca]o), by regulation of Na+ channels, and secondly via Na-Ca exchange and Na(+)-taurine cotransport. 3. Taurine can prevent the Ca2+ ([Ca]o or [Ca]i)-induced cardiac functions. 4. Therefore, it seems possible that taurine could exert the potent cardioprotective actions even under the condition of low [Ca]i levels as well as under the Ca2+ overload condition. 5. The electrophysiological actions of taurine on cardiomyocytes, smooth muscle cells, and neurons from recent studies are summarized.

Animals↗

Inhibition of the fast Na+ current by taurine in guinea pig ventricular myocytes.

1. Effects of taurine on the fast Na+ current (INa) in isolated guinea pig ventricular cardiomyocytes were examined by using the whole-cell voltage-clamp method. Experiments were performed at room temperature (22 degrees C). 2. Test pulses were applied from -60 to +40 mV from a holding potential of -90 mV. Addition of taurine to the bath solution markedly inhibited the INa in a concentration-dependent manner; at -30 mV, by 39.0 +/- 4.1% (n = 8, P < 0.01) at 10 mM and by 56.1 +/- 4.7% (n = 9, P < 0.001) at 20 mM. 3. Simultaneously, the time constant of inactivation phase for INa decreased to 0.95 +/- 0.4 ms (n = 8, P < 0.05) at 10 mM and to 1.02 +/- 0.3 ms (n = 9, P < 0.05) at 20 mM, from 1.29 +/- 0.3 ms in normal Tyrode solution. 4. These results indicate that taurine inhibits the INa current, which would play an important role in the cell functions.

Animals↗

Modulations by taurine of the spontaneous action potentials in right atrial muscles of rats.

1. Effects of taurine on the spontaneous action potentials in right atrial muscles of rats were examined using a conventional microelectrode method at 36 degrees C, and at different extracellular Ca2+ concentrations ([Ca]o). 2. When [Ca]o was 1.8 mM, taurine (10 and 20 mM) increased the sinus rate in a concentration-dependent manner. On the other hand, in 5.4 mM [Ca]o solution, 10 mM taurine also increased the sinus rate, but at 20 mM decreased it. 3. Taurine (20 mM) at 1.8 mM [Ca]o decreased the action potential duration, but at 5.4 mM [Ca]o increased it. Other action potential parameters were not altered to a significant extent. 4. In addition, at 5.4 mM [Ca]o, taurine at 10 mM elicited dysrhythmias such as bigeminy, and at 20 mM depressed the spontaneous action potentials and prolonged cycle length. 5. These results indicate that taurine caused a positive chronotropic effect at both [Ca]o levels; however, at 5.4 mM [Ca]o, taurine (20 mM) reversed the positive to a negative chronotropic effect, presumably resulting in the development of cellular calcium overload.

Action Potentials↗

Curved chest tube for drainage of malignant pleural effusion.

Thoracentesis with a chest tube insertion and drainage of large pleural effusion is widely performed in patients with malignant lung diseases. One potential problem with a conventional chest tube placement is occasional incomplete evacuation of effusion owing to inappropriate position of the tip where the drainage holes opened. We have developed a curved chest tube and evaluated the position of tip placement just after the placement and before removal on plain chest X-ray in 20 patients with massive pleural effusions due to lung cancer. In 15 of the 20 patients, the tip of the tube was successfully positioned at the paravertebral gutter in posterobasal with higher drainage efficacy compared with other patients whose tube tips happened to be positioned at other sites. There were no significant complications. This study suggested that the curved chest tube would be safe and useful in completing drainage of pleural effusion.

Adult↗