Biomedical subjects

A Iguchi

Publications and source records attributed to A Iguchi.

At least 19 recordsLinked to original sources

PubMed1996

Protective effect of interleukin-6 against the death of PC12 cells caused by serum deprivation or by the addition of a calcium ionophore.

Interleukin-6 (IL-6) is known to differentiate the rat pheochromocytoma cell line PC12 to neuron-like cells. We examined the effect of IL-6 on the death of PC12 cells. IL-6 significantly blocked the death of PC12 cells by serum deprivation. The protective effect of IL-6 was increased by preincubation of PC12 with IL-6 for 20 hr before serum deprivation. The inhibition of protein synthesis by cycloheximide had no effect on the protective effect of IL-6 on the serum deprivation-induced cell death. IL-6 also inhibited the death of PC12 cells induced by addition of the calcium ionophore A23187 to the culture medium. Specific in situ labeling of DNA cleavage was observed in PC12 cells subjected to both serum deprivation and A23187 for 24 hr. IL-6 inhibited DNA fragmentation in PC12 cells following serum deprivation. These results suggest that the death of PC12 cells induced by serum deprivation or by the addition of calcium ionophore is apoptosis, and that IL-6 blocks apoptosis of PC12 cells.

Animals↗

PubMed1996

Immobilization stress-induced increase of hippocampal acetylcholine and of plasma epinephrine, norepinephrine and glucose in rats.

We investigated the role of the hippocampal cholinergic neurons during immobilization stress in rats using a microdialysis technique. Blood levels of glucose, epinephrine and norepinephrine during immobilization stress were also determined. Acetylcholine release was initially increased by immobilization stress, then gradually decreased. Plasma level of epinephrine increased gradually and reached significance at 30 min after the start of immobilization and remained at the elevated level during immobilization. Plasma level of norepinephrine initially increased and reached significance at 30 min after the start of immobilization and remained at the elevated level during immobilization. Plasma level of glucose increased gradually and reached maximum and significance 45 min after the start of immobilization, then decreased. Fifteen min after immobilization, acetylcholine release increased again, while concentrations of epinephrine and norepinephrine were still elevated. Thus the response of acetylcholine and the other responses to immobilization stress were not parallel.

Acetylcholine↗

PubMed1996

Central administration of a nitric oxide synthase inhibitor impairs spatial memory in spontaneous hypertensive rats.

Nitric oxide is widely recognized as a putative retrograde messenger in the brain. We infused NG-monomethyl-L-arginine (L-NMMA; 25 mg/kg), an inhibitor of nitric oxide synthase (NOS), continuously for a week into the dorsal third ventricle (D3V) of spontaneous hypertensive rate (SHR) by an osmotic infusion pump. Rats administered with L-NMMA showed impaired performance of a radial arm maze task compared with control rats administered with saline. We observed significant reductions of the NOx level in the cerebrospinal fluid (CSF) of the rats administered with L-NMMA, but not in the control rats. Both groups showed no change in systolic blood pressure or serum NOx level. The results provide evidence of a more specific effect of NOS inhibition to the brain independent of alterations in the systemic hemodynamics.

Animals↗

PubMed1996

Increase in insulin release from rat pancreatic islets by quinolone antibiotics.

1. The present study was undertaken to elucidate the mechanism(s) of hypoglycaemia caused by quinolone antibiotics. We investigated the effects of various quinolone antibiotics on insulin release in rat pancreatic islets. 2. At a non-stimulatory concentration of 3 mM glucose, lomefloxacin (LFLX) or sparfloxacin at 1 mM and pipemidic acid (0.1-1 mM) induced slight insulin release but tosufloxacin or enoxacin up to 100 microM did not. 3. At the stimulatory concentration of 10 mM glucose, all quinolones augmented insulin release in a dose-dependent manner. LFLX (100 microM) shifted the dose-response curve of glucose-induced insulin release to the left without altering the maximal response. 4. At 10 mM glucose, LFLX (100 microM) increased insulin release augmented by forskolin (5 microM) or 12-O-tetradecanoyl phorbol-13-acetate (100 nM) but not by raising the K+ concentration from 6 to 25 mM. 5. Verapamil (50 microM) or diazoxide (50-400 microM) antagonized the insulinotropic effect of LFLX. 6. These data suggest that quinolone antibiotics may cause hypoglycaemia by increasing insulin release via blockade of ATP-sensitive K+ channels.

4-Quinolones↗

PubMed1996

Do human papillomaviruses have a role in the pathogenesis of bladder carcinoma?

PURPOSE: Since little is known of the associations between bladder carcinoma and human papillomaviruses (HPVs), data on the role of HPV in bladder carcinogenesis are controversial. We attempted to clarify whether HPVs are present in bladder carcinomas. MATERIALS AND METHODS: We examined 36 specimens of bladder carcinoma for HPV positivity by the polymerase chain reaction method. RESULTS: HPV-16 deoxyribonucleic acid was detected in 1 specimen (3%) of a transitional cell carcinoma from a 37-year-old woman who had concomitant squamous cell carcinoma of the uterine cervix with positive para-aortic lymph node metastasis. The cervical tumor, bladder tumor and para-aortic lymph node metastasis were all positive for the same type of HPV. CONCLUSIONS: On the basis of this low rate of HPV detection (3%), HPVs are not likely to have a prominent role in carcinogenesis of the bladder.

Adult↗

PubMed1996

Physiological concentration of 17 beta-estradiol inhibits chemotaxis of human monocytes in response to monocyte chemotactic protein 1.

While estrogen is known to retard the development of atherosclerosis, the exact mechanism is unknown. The migration of monocytes into the arterial intima is important in the pathogenesis of atherosclerosis. Monocyte chemotactic protein 1 (MCP-1) is suggested to be a real chemotactic factor that is released from monocytes, endothelial cells, and smooth muscle cells. We investigated the effect of 17 beta-estradiol on the migration of human monocytes in response to MCP-1, using a modified Boyden chamber. A physiological concentration of 17 beta-estradiol (10(12) - 10(4)M) inhibited the migration of monocytes exposed to MCP-1. Two estrogen receptor antagonists, tamoxifen and clomiphene, each restored monocyte chemotaxis to MCP-1 to control level, even in the presence of 17 beta-estradiol, suggesting that estrogen receptors are related to the effect of 17 beta-estradiol. Progesterone and testosterone had no measurable effect on monocyte migration. These findings suggest that inhibition of the chemotactic response of monocytes exposed to MCP-1 may be one mechanism for the anti-atherogenic effect of 17 beta-estradiol.

Arteriosclerosis↗

PubMed1995

Effects of imidazoline antagonists of alpha 2-adrenoceptors on endogenous adrenaline-induced inhibition of insulin release.

We studied the effects of adrenoceptor antagonists and imidazoline derivatives on endogenous adrenaline-induced inhibition of insulin release in anesthetized rats. The intracerebroventricular injection of neostigmine increased plasma levels of catecholamines and glucose but not insulin. Pretreatment with an i.p. injection with phentolamine caused a dose-dependent increase in insulin secretion. When atropine was coadministered with phentolamine, the phentolamine-induced increase in insulin secretion was inhibited. Neither phentolamine nor atropine affected plasma levels of catecholamine. Yohimbine and idazoxan, which are alpha 2-adrenoceptor antagonists, and tolazoline, a non-selective alpha-adrenoceptor antagonist, also reversed adrenaline-induced inhibition of insulin secretion. Phenoxybenzamine, prazosin, propranolol, and antazoline, an imidazoline without alpha 2-adrenoceptor activity, did not affect insulin levels. When agents were preinjected i.p. in rats that were given saline into the third cerebral ventricle, phentolamine and antazoline, but not yohimbine and idazoxan, increased plasma levels of insulin. The results suggest that the inhibition of insulin release induced by adrenaline was reversed by antagonism of alpha 2-adrenoceptors. Phentolamine and antazoline, both of which are imidazoline derivatives, induced insulin secretion independently of the adrenoceptors only under the resting conditions.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1995

Estrogen increases endothelial nitric oxide by a receptor-mediated system.

To determine the mechanism of the antiatherosclerotic effect of estrogen, we investigated the effect of estrogen on endothelial nitric oxide synthase (NOS-3). Preincubation with a physiologic concentration of 17 beta-estradiol (10(-12)-10(-8) M) over 8 hours significantly enhanced the activity of NOS-3 in endothelial cells of cultured human umblical vein (HUVEC) and of bovine aortas (BAEC). 17 beta-estradiol also enhanced the release of nitric oxide (NO) as measured by an NO selective meter and NO2-/NO3-, metabolites of NO, from endothelial cells. Western blot showed a similar effect of 17 beta-estradiol on NOS-3. The estrogen receptor antagonists, tamoxifen and ICI182780, each inhibited the effect of 17 beta-estradiol by 80%. The effect of 17 beta-estradiol gradually decreased in cells beyond the 10th passage and was not significant in cells beyond the 16th passage. Immunocytochemistry showed the existence of estrogen receptor in HUVEC and BAEC (less than 5 passages) and the sparseness of the existence in BAEC beyond the 16th passage. Estrogen increases NOS-3 via a receptor-mediated system, and estrogen receptor, which appeared to be altered by cell senescence, could be important in the release of NO from endothelium.

Animals↗

PubMed1995

Decreased interleukin-6 level in the cerebrospinal fluid of patients with Alzheimer-type dementia.

We examined IL-6 levels in the cerebrospinal fluid (CSF) of patients clinically diagnosed with Alzheimer-type dementia (ATD) and with vascular dementia (VD) and of age-matched normal subjects. The IL-6 levels in the CSF of ATD, but not VD patients, were significantly decreased. In the early onset ATD patients (disease onset < 65 years), IL-6 levels were reduced to 21% of the control level. The IL-6 levels in the CSF were not associated with the severity of the dementia or the duration of the disease since the identification of the first symptoms.

Acute-Phase Reaction↗

PubMed1995

Protective effects of probucol against glutamate-induced cytotoxicity in neuronal cell line PC12.

The sympathetic nerve cell line PC12 is reportedly destroyed by glutamate in a concentration-dependent manner. In this study, cytotoxicity induced by 10 mM glutamate was blocked in a dose-dependent manner by incubating or pre-incubating cells with the antioxidant probucol (1-50 microM). Probucol also inhibited the increase in cellular thiobarbituric acid-reacting substances induced by glutamate exposure. These results suggest that the propagation of cellular lipid peroxidation may be related to glutamate-induced toxicity in PC12 cells.

Animals↗

PubMed1995

Induction of angiogenesis by smooth muscle cell-derived factor: possible role in neovascularization in atherosclerotic plaque.

The development of atherosclerotic plaque is associated with neovascularization in the thickened intima and media of vascular walls. Neovascularization may have a role in the progression of atherosclerotic plaque as well as in the development of intraplaque hemorrhage. However, the mechanism and stimulus for neovascularization in atherosclerotic plaque are unknown. We postulated that smooth muscle cells (SMCs), a major cellular component in the vascular wall, might contribute to the induction of neovascularization in atherosclerotic plaque through the secretion of an angiogenic factor. We observed that endothelial cells (ECs) cultured on collagen gel with SMC-conditioned medium became spindle shaped, invaded the underlying collagen gel, and organized a capillary-like branching cord structure in the collagen gel. The conditioned medium also stimulated EC proliferation and increased the EC-associated plasminogen activator activity. The angiogenic factor in SMC-conditioned medium was retained in a heparin-Sepharose column and eluted with 0.9 M NaCl. Neutralizing anti-vascular endothelial growth factor (VEGF) antibody attenuated the angiogenic activity in the conditioned medium, including the induction of morphologic changes in ECs, mitogenic activity, and increased plasminogen activator activity associated with ECs. Immunoblotting analysis confirmed the secretion of VEGF from SMCs. These observations indicate that SMC may be responsible for the neovascularization in atherosclerotic plaque through the secretion of VEGF.

Arteriosclerosis↗

PubMed1995

Physiological concentration of estradiol inhibits polymorphonuclear leukocyte chemotaxis via a receptor mediated system.

Estrogen exhibits a variety of actions, including immuno-modulatory effects, in vivo and in vitro. The mechanism by which estrogen exerts its anti-inflammatory effect is not yet understood. We investigated the possible mechanisms of estradiol acting via the polymorphonuclear leukocytes (PMNs), which are important in the immune response. The agent, 17 beta-estradiol, but not 17 alpha-estradiol, significantly reduced PMNs chemotaxis to FMLP in a dose-dependent manner (control vs estrogen 10(-10)-(-6) M, P < 0.05). Physiological concentrations of estradiol significantly reduced the chemotaxis of PMNs (10(-10) mol). Pre-incubation with clomiphene or tamoxifen which are estrogen receptor antagonists, eliminated the inhibitory effect of 17 beta-estradiol on the chemotaxis of PMNs, restoring it to the control level. These observations suggest that 17 beta-estradiol suppressed the chemotaxis of PMNs by a receptor-dependent mechanism. In addition, the level of estradiol in human plasma, which PMNs were drawn, showed a close, inverse correlation with the PMNs chemotaxis to FMLP (r = -0.821 p < 0.001). Estrogen may modify the activity of neutrophils during the normal menstrual cycle, not only during pregnancy, and influence inflammation.

Adult↗

PubMed1995

Pressor response induced by the hippocampal administration of neostigmine is suppressed by M1 muscarinic antagonist.

We investigated the roles played by three muscarinic receptors (M1, M2, and M3) in the pressor response with bradycardia that followed the injection of neostigmine (5 x 10(-8) mol) into the hippocampus of anesthetized rats. These changes were blocked by the co-administration of methylatropine (5 x 10(-8) mol). The intrahippocampal injection of pirenzepine (M1 antagonist) (5 x 10(-9) - 5 x 10(-7) mol) suppressed the neostigmine-induced pressor response dose-dependently. However injection of gallamine (M2 antagonist) (5 x 10(-8) - 5 x 10(-7) mol) and of 4-DAMP (M1 and M3 antagonist) (5 x 10(-8) - 5 x 10(-7) mol) did not suppress this hypertensive response. These findings suggest that the neostigmine-induced pressor response with bradycardia is mediated through the M1 muscarinic receptor subtype.

Animals↗

PubMed1995

In situ perfusion by retrograde cannulation of a tumor artery for nephron-sparing surgery.

BACKGROUND: Although ice slush cooling or ex situ perfusion with bench surgery is most widely used for protecting ischemic renal damage which possibly accompanies complicated nephron-sparing surgery, each has its own disadvantages. The former does not allow excessively long ischemia and the latter requires complicated procedures as autotransplantation. In order to mitigate against these problems, we devised a novel method of in situ renal perfusion with intracellular hyperosmolar solution. METHODS: One renal segmental artery mainly supplying a tumor was isolated and cannulated with a small feeding tube. The tube was introduced through a small arteriotomy incision directed towards the proximal side, advanced until its tip remained in the main or first branch of the renal artery, and then it was anchored to that artery. After the main renal artery and vein were clamped, the kidney was perfused with cold Euro-Collins' solution through the tube, while the venous blood and perfusate were drained from the left gonadal vein or small venotomy incision of the right renal vein. RESULTS: In one case of renal cell carcinoma and three cases of angiomyolipoma, two of which ruptured, nephron-sparing surgery was carried out under in situ hyperosmolar perfusion. Ischemic time of these four cases was an average of 96 minutes, varying from 45 to 145 minutes. All the kidneys functioned well postoperatively. CONCLUSIONS: The method presented here is very simple, requires no unusual dexterity and safely allows for a long period of renal ischemia. This method is best indicated in cases where simple clamping of the renal pedicle with ice-slush cooling appears insufficient, yet ex situ surgery with autotransplantation seems excessive.

Angiography↗

PubMed1995

New approaches to the prevention of atherosclerosis.

In recent years, remarkable progress has been made in the prevention and treatment of atherosclerosis. However, much of the research has been devoted to the investigation of lipid metabolism and lipid-lowering drugs. This review highlights some recent topics in both experimental and clinical investigations, with emphasis on studies other than those on lipid-lowering drugs. These topics include oxidative modification of lipoproteins, hyperfibrinogenaemia, hyperhomocysteinaemia, female sex hormones and endothelium-derived relaxing factor (or nitric oxide). Some of these approaches have already been applied in the clinic.

Animals↗

PubMed1995

[Treatment of advanced renal cell carcinoma with a combination of interferon alpha and gamma].

A total of 29 patients with advanced renal cell carcinoma entered a pilot study of combination therapy with interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma). IFN-alpha (HLBI: 3 x 10(6) IU, BALL 1:5 x 10(6) IU, IFN-alpha-2a: 9 x 10(6) IU or IFN-alpha-2b: 6 x 10(6) IU) was given intramuscularly every day and IFN-gamma (IFN-gamma-1a: 3 x 10(6) JRU) was given intravenously by drip infusion 3 times a week (every 2-3 days). The treatment was continued for 3 months as the induction therapy, and then the tumor response was evaluated. Of the 22 evaluable patients, 4 achieved a partial response (PR), 10 showed no change (NC), and in 8 the disease had progressed (PD) during the therapy. Thus, the overall response rate was 18.2% [95% confidence interval (CI) 2.1-34.3%]. A favorable response tended to be obtained in patients with good performance status or small pulmonary metastases, or in those who had no prior therapy with IFN-alpha, who received this treatment immediately subsequent to radical nephrectomy, or who received IFN-gamma as much as possible according to this regimen. Toxicity was evaluated in 28 patients: fever, general fatigue, anorexia, leukocytopenia and impaired liver function were frequently noted, and 3 patients were withdrawn from the study because of such adverse effects. In patients who had a PR or NC, the same dosage of IFN-alpha was continued to be given intramuscularly 2-3 times a week (every 2-4 days) as the maintenance therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

[Megaureter in adults].

In comparison with megaureters in children, their reports in adult are not common. We had an opportunity to treat seven adults with megaureters during the last six years. They were all female and ages ranged from 46 to 67 years. Five patients with grade II and one with grade III (Pfister-Hendren's classification) were treated by reconstructive surgery, excision of the narrow segment, tapering of the dilated lower ureter and reimplantation through a submucosal tunnel. The outcome of all the grade II patients was excellent and the case with grade III showed mild improvement. The results suggested that surgical reconstruction could be equally effective for megaureters in adults compared to those in children.

Aged↗

PubMed1995

[Concomitant replacement of the complete aortic arch with coronary artery bypass grafting and ilio-femoral bypass grafting by means of selective cerebral and coronary perfusion technique].

A seventy-two-year-old male patient was diagnosed to have major three kinds of atherosclerotic disease including transverse aortic arch aneurysm, ischemic heart disease and stenosis of left external iliac artery. Complete graft replacement of aortic arch was performed concomitantly with the coronary arterial bypass grafting and iliofemoral bypass grafting under selective cerebral and coronary perfusion technique. In addition, the graft used for iliofemoral arterial reconstruction was tailored to have two branches, which facilitate the insertion of the inflow cannula for a bypass and the occlusion balloon catheter. His postoperative course was uneventful and was discharged under a satisfactory condition.

Aged↗