Biomedical subjects

S Nakayama

Publications and source records attributed to S Nakayama.

At least 73 records · Page 4Linked to original sources

PubMed2000

[A case of postoperative lung and pleural recurrence after 20 years in a breast cancer patient with marked response to orally administered UFT and cyclophosphamide].

A 62-year-old woman who underwent standard radical mastectomy for left breast cancer developed pleural and pulmonary metastases 16 years later. She complained of slight dyspnea, and computed tomography of the chest revealed a tumor with marked pleural effusion. Her serum level of carcinoembryonic antigen was also increased (49 ng/ml). Systemic chemotherapy with cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) was performed, but she did not show a marked response to CAF therapy. Therefore, she was orally administered UFT and CPA for 5 consecutive days followed by 2 drug-free days. Pleural disseminated foci and a lung tumor were reduced in size on chest CT and the CEA level was decreased within the normal limit. Recently, it was reported that UFT demonstrated significant antiangiogenic activity. This effect may play an important role in the efficacy seen in this patient.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

[A case of breast cancer with multiple metastases successfully treated by medroxyprogesterone acetate with intermittent intra-arterial infusion low-dose chemotherapy to hepatic metastasis].

A 48-year-old woman who underwent breast-conserving therapy for left breast cancer developed bone, pleural, and liver metastases with local recurrence. The result was an improvement in each image with a marked improvement as seen by elevated tumor marker levels, with treatment by MPA (800 mg/day p.o.) and intermittent low-dose chemotherapy with hepatic arterial infusion. The side effects were acceptable. Normalization of imagings and an improvement in tumor markers continued for two years. Thus, in spite of being a palliative treatment, hepatic arterial infusion chemotherapy for liver metastasis from breast cancer might lead to prolongation of survival because of the improvement of other metastases due to the increased passage effect with MPA.

Antineoplastic Agents, Hormonal↗

PubMed1999

Effect of cilostazol, a phosphodiesterase III inhibitor, on experimental thrombosis in the porcine carotid artery.

Thrombus formation in the carotid artery is one of the common causes of transient ischemic attacks and stroke. Platelet aggregation seems to be an essential component in these processes. The present study was conducted to determine the ability of cilostazol, a phosphodiesterase III inhibitor, to prevent formation of totally occlusive thrombus in a porcine carotid artery, in comparison with ticlopidine. Castrated male Yorkshire pigs were allocated to control (n=8), cilostazol (30 mg/kg, twice a day [b.i.d] for 2 days, n=8), and ticlopidine (50 mg/kg, b.i.d. for 3 days, n=7) groups. The endothelium of the right common carotid artery was injured with electrical stimulation (150 microA) without constriction and blood flow in this region was monitored by Doppler flow probe. Arterial blood was sampled during electrical stimulation for the measurement of platelet aggregation. Total occlusion rates within 240 minutes were 87.5% (7:8), 37.5% (3:8), and 85.7% (6:7) in the control, cilostazol, and ticlopidine groups, respectively. Compared with the control group, the time to total occlusion was significantly prolonged in the cilostazol group, but not in the ticlopidine group. Consistently, platelet aggregation was significantly inhibited only in the cilostazol group. Because ticlopidine increases blood flow in the intact carotid artery before injury to a greater extent than cilostazol, direct antiplatelet action is thought to be responsible for cilostazol's beneficial effect in preventing thrombotic occlusion. These results suggest that cilostazol may be useful for the inhibition of the thrombus formation in the carotid artery and for the prevention of cerebral ischemic events.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1999

Effects of phosphorylation-related drugs on slow Ca2+ tail current in guinea-pig detrusor cells.

In isolated guinea-pig detrusor cells, large conditioning depolarizations evoke slowly deactivating Ca2+ tail currents, considered to represent the second open state. The possible involvement of channel phosphorylation in this open state was examined. Application of isoprenaline caused a marginal increase in Ca2+ channel current evoked by simple depolarization, while forskolin did not. During application of either drug, slow-tail currents were never observed after simple depolarizations. The conditions necessary to induce slow-tail currents were not changed, even when cyclic AMP, ATP-gamma-S (adenosine 5'-O-(3-thiotriphosphate)), GDP-beta-S (guanosine 5'-O-(2-thiodiphosphate)) (in the pipette) or H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride) (to the bathing solution) was applied. The frequent depolarization protocol, known to facilitate Ca2+ current via Ca2+ and cyclic AMP-dependent phosphorylation mechanism(s) in cardiac myocytes, did not induce slow-tail currents. These results suggest that the transition of Ca2+ channels to the second open state during large depolarization is not a result of (voltage-operated) channel phosphorylation itself. Possible underlying mechanisms are discussed.

Adrenergic beta-Agonists↗

PubMed1999

Long-term use-dependent enhancement of impulse-induced exocytosis by adrenaline at frog motor nerve terminals.

Adrenaline (5-20 microM) use-dependently increased end-plate potentials (EPPs) in normal Ringer solution (containing d-tubocurarine to partially block acetylcholine receptors) and a low Ca2+, high Mg2+ solution for more than several hours and decreased the coefficient of variation of EPP amplitude in the latter solution in frog neuromuscular junctions. The amplitude and frequency of miniature EPPs and impulse-induced increases in intraterminal Ca2+ concentration were unaffected. Adrenaline thus causes sustained enhancement of impulse-induced exocytosis by acting at a mechanism of exocytosis downstream to Ca2+ entry.

Animals↗

PubMed1999

Effects of bisphosphonate on experimental jaw metastasis model in nude mice.

The mechanism of osteolysis associated with metastatic cancer of the jaws is essentially osteoclast-mediated. Therefore, it is likely that potent osteoclastic bone resorption inhibitors such as bisphosphonates would be efficacious for the treatment of jaw metastasis. We examined the effects of a third generation bisphosphonate, YM175, in a nude mice jaw metastasis model with intracardiac injection of a human breast cancer cell line, MDA-MB-231. The metastatic lesions in untreated mice were radiographically observed at the body and angle of the mandible. Histology of the mandible of untreated mice revealed that most of the bone marrow cavities had been occupied by the metastatic tumor with active osteoclasts along the trabecular bone. The experimental group showed that YM175 markedly reduced the size of tumor and the number of osteoclasts. These results suggest that YM175 may suppress metastasis formation and tumor growth in jaw through inhibition of osteoclastic bone resorption.

Animals↗

PubMed1999

Apolipoprotein E phenotypes in healthy normal controls and demented subjects with Alzheimer's disease and vascular dementia in Mie Prefecture of Japan.

In order to clarify the association between apolipoprotein E4 (ApoE4) and the pathogenesis of Alzheimer's disease (AD), we analyzed the distribution of the apolipoprotein E (ApoE) phenotypes and the frequency of the apo E alleles epsilon2, epsilon3, and epsilon4 in Japanese healthy controls (n = 1090, an average age of 51.2+/-12.6 years) and demented patients (n=103, mean age of 73.6+/-9.2 years). Demented subjects were divided into three subgroups: early-onset AD group (EOAD; n=25, mean age 63.0+/-6.2 years), late-onset AD group (LOAD; n=33, mean age 79.3+/-5.1 years), and vascular dementia group (VD; n=45, mean age 75.3+/-8.0 years). The apolipoprotein E phenotype was determined by isoelectric focusing and immunoblotting. There were no significant differences in the distribution of the apo E phenotypes by gender or age, and the estimated frequencies of epsilon2, epsilon3 and epsilon4 were 0.05, 0.86 and 0.09, respectively, in the normal controls. There was a significant difference in the distribution of the apo E phenotypes between LOAD and elderly controls aged more than 65 years (P<0.0001). The distribution of the apo E phenotypes in EOAD was the same as that in LOAD. The frequency of the epsilon4 allele was significantly higher in LOAD (0.35, P<0.0001) and EOAD (0.28, P<0.0001) than that in the control subjects (0.07), but not in VD (0.12, P=0.1630). The present findings suggest that ApoE4 is related with both EOAD and LOAD, but not with VD, and support the hypothesis that it is a genetic risk factor of AD.

Age of Onset↗

PubMed1999

[The booster phenomenon in two-step tuberculin testing of employees in a community hospital].

A study was made to clarify to what degree the booster phenomenon was present when the employees in a community hospital in Japan received two-step tuberculin testing (PPD). Of the seventy-five employees, most of all BCG-vaccinated subjects, twenty-three showed strongly positive of more than 30 mm of induration at the first test (PPD/T1), and the remaining fifty-two subjects received a second (PPD/T2) after 2 weeks. The second PPD showed a marked increase in reactivity, sixteen subjects newly became strongly positive and six of eight who were initially PPD negative (< 10 mm) were converted positive, and the mean reaction size changed from 14.7 +/- 5.6 mm (PPD/T1) to 31.5 +/- 15.5 mm (PPD/T2). The degree of boosting, measured by the change in millimeters induration size between PPD/T1 and PPD/T2 (PPD/T2-PPD/T1), was correlated with neither the size of PPD/T1 nor the age of the study participants, and was not associated with the difference of the position in the hospital. Thus, we could not explain the factor why such a marked boosting was observed in this study. However, these results indicated that the two-step tuberculin testing is an essential means of distinguishing new tuberculous infection from booster phenomenon. We agree with the current recommendation for routine two-step testing of new employees in the hospital.

Adult↗

PubMed1999

Voltage sensitivity of slow wave frequency in isolated circular muscle strips from guinea pig gastric antrum.

In circular muscle preparations isolated from the guinea pig gastric antrum, regular spontaneous electrical activity (slow waves) was recorded. Under normal conditions (6 mM K+), the frequency and shape of the slow waves were similar to those observed in ordinary stomach smooth muscle preparations. When the resting membrane potential was hyperpolarized and depolarized by changing the extracellular K+ concentration (2-18 mM), the frequency of slow waves decreased and increased, respectively. Application of cromakalim hyperpolarized the cell membrane and reduced the frequency of slow waves in a dose-dependent manner. Cromakalim (3 microM) hyperpolarized the membrane, and slow waves ceased in most preparations. In the presence of cromakalim, subsequent increases in the extracellular K+ concentration restored the frequency of slow waves accompanied by depolarization. Also, glibenclamide completely antagonized this effect of cromakalim. In smooth muscle strips containing both circular and longitudinal muscle layers, such changes in the slow wave frequency were not observed. It was concluded that the maneuver of isolating circular smooth muscle altered the voltage dependence of the slow wave frequency.

Animals↗

PubMed1999

Genetic analysis of HLA- and HPA-typing in idiopathic (autoimmune) thrombocytopenic purpura patients treated with cepharanthin.

We performed genetic analysis of human leukocyte antigen (HLA) and human platelet antigen (HPA) in 45 patients with cepharanthin-treated idiopathic thrombocytopenic purpura. HLA-typing was performed by the polymerase chain reaction-restriction fragment length polymorphism method, and HPA-typing by a polymerase chain reaction-sequence-specific primer method. There were 14 responders and 31 nonresponders. Responders included many patients who had already been treated with prednisolone. HLA-DRB1*0901 was significantly more common in responders than in nonresponders. In contrast, HLA-DRB1*0410 and DQB1*0401 were significantly more common in nonresponders. The a/b genotype of HPA-2a/2a (Ko(b)/Ko(b)) was significantly increased in responders. In contrast, HPA-2a/2b (Ko(b)/Ko(a)) and HPA-3a/3b (Bak(a)/Bak(b)) were significantly more common in nonresponders. These findings suggest that genetic studies of HLA and HPA can predict the response of idiopathic thrombocytopenic purpura to cepharanthin.

Adult↗

PubMed1999

[Medulloblastoma originating in the pons].

Medulloblastoma usually originates in the cerebellum. We report here a case of medulloblastoma originating in the pons. Pontine medulloblastoma is extremely rare, with only one report in the literature. An 11-year-old girl was admitted to our hospital with vertigo. Magnetic resonance imaging (MRI) revealed a tumor originating in the pons. On the 4th day after admission, the tumor bled. Because the patient's life was in danger from brain herniation, hematoma removal and tumor resection were carried out. The diagnosis was medulloblastoma. After surgery, the patient received radiation therapy and chemotherapy. Unlike tumors originating in the cerebellum, this tumor did not seem to be effectively reduced by these therapies. Radiation therapy and chemotherapy may not be effective for medulloblastoma originating in the pons. We considered it necessary to make a histological diagnosis even though the tumor originated in the pons and resection was difficult technically.

Brain Neoplasms↗

PubMed1999

Implication of expression of GDNF/Ret signalling components in differentiation of bone marrow haemopoietic cells.

Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) mediate their actions through a unique multicomponent receptor system composed of Ret receptor tyrosine kinase and glycosyl-phosphatidylinositol-linked cell surface proteins (designated GFRalpha-1 and GFRalpha-2). In the present study, expression of these signalling components in the process of differentiation of haemopoietic cells was investigated. Ret was expressed at variable levels in normal and malignant cells of the myelomonocyte lineage. Immunohistochemical analysis of human and mouse tissues revealed that Ret expression was increased in intermediate mature myeloid cells such as promyelocytes and myelocytes and decreased in mature granulocytes and monocytes. Consistent with this observation, when THP-1 monocytic and HL-60 promyelocytic leukaemia cells expressing Ret were differentiated toward macrophages or granulocytes by treatment of 12-O-tetradecanoylphorbol-13-acetate (TPA) or all-trans retinoic acid (RA), Ret expression strikingly decreased during differentiation. Expression of GDNF, NTN, GFRalpha-1 and GFRalpha-2 was undetectable in THP-1 and HL-60 cells as well as in bone marrow haemopoietic cells. In contrast, bone marrow stromal cells appeared to express GDNF, GFRalpha-1 and GFRalpha-2 but not Ret. These findings suggested that the interaction between stromal cells and Ret-expressing haemopoietic cells in the bone marrow microenvironment may play a role in the differentiation of myelomonocyte-lineage cells through activation of the GDNF/Ret signalling pathway.

Animals↗

PubMed1999

[A case of breast cancer patient of CAF (cyclophosphamide, adriamycin, 5-fluorouracil) resistant lung metastasis with remarkable response to reverse drug-resistance by toremifene].

A 43-year-old female underwent muscle preserving mastectomy with 6 cycles of adjuvant CMF chemotherapy for breast cancer. She developed multiple lung metastases 16 months later. The metastases were refractory to 3 cycles of CAF administration, and worsened (PD). We therefore added high-dose toremifene to her treatment. This combination therapy brought a marked decrease in the lung metastases. After 9 cycles of CAF with high-dose toremifene therapy, lung metastatic findings had almost disappeared from her chest X-ray. Following this treatment, UFT and toremifene were orally administered for maintenance therapy. Thirty-two months later at present, no increase in these lesions has been observed. High-dose antiestrogen drugs have the potential to inhibit P-glycoprotein. The combination of high-dose toremifene with CAF is potentially effective against ADM-resistant breast cancer.

Adult↗

PubMed1999

[A breast cancer patient with docetaxel-resistant pleural recurrence with remarkable response to doxifluridine and cyclophosphamide].

A 47-year-old female underwent mastectomy after neo-adjuvant chemotherapy including an anthracycline agent for advanced breast cancer. She developed a pleural metastasis on 16 months later, which was refractory to intrathoracic cisplatinum administration and intravenous Docetaxel therapy. Brain metastases were also found. We therefore treated her with whole brain radiation therapy and oral chemotherapy with 5'-DFUR and cyclophosphamide. This combination therapy produced a marked decrease in each metastasis. The adverse effects were not remarkable. This regimen may play an important role not only from the standpoint of its effectiveness against tumor growth but also the quality of life of the patient.

Administration, Oral↗

PubMed1999

[A case of successful palliative operation of asplenia syndrome with total anomalous pulmonary venous return in young infant].

We reported a successful palliative operation for asplenia syndrome with total anomalous pulmonary venous return (TAPVR Ia) in an infant. The boy was suffering from cyanosis and tachypnea. He was diagnosed as asplenia syndrome with TAPVR and hiatus hernia. After he was admitted to our hospital, pulmonary congestion gradually progressed in a month. At 58 days of age, a palliative operation (repair of TAPVR and pulmonary artery banding with band of 20 mm in length) was performed. The postoperative course was uneventful. At 114 days of age, he underwent curative operation for hiatus hernia without cardiac failure. Postoperative cardiac catheterization at 179 days of age showed appropriate pulmonary artery pressure. We emphasize that pulmonary artery banding which is tighter than usual well controls pulmonary blood flow, although the length of the band in each case should be considered individually.

Cardiac Surgical Procedures↗

PubMed1999

[Epidural anesthesia for cesarean section in a patient with dilated cardiomyopathy (DCM)].

A 23-year-old patient with dilated cardio myopathy (DCM) was scheduled for a cesarean section. We inserted an epidural catheter at the L 2/3 interspace and injected 1.5% lidocaine 6 ml with epinephrine 30 micro g and fentanyl 50 micro g. The analgesic level 15 minutes after injection was achieved up to the eighth thoracic dermatome. Dopamin 5 micro g.kg-1.min-1 was infused simultaneously. Analgesia was sufficient for the surgery, and heart rate and blood pressure were stable throughout the operation. The infant's apgar scores were 9 and 10. Epidural anesthesia is one of the options for cesarean section in pregnant women with DCM.

Adult↗

PubMed1998

Fulminant hepatic failure secondary to herpes simplex virus infection in a neonate: A case report of successful treatment with liver transplantation and perioperative acyclovir.

Neonatal disseminated herpes simplex virus (HSV) infection, including fulminant hepatic failure (FHF), is lethal, and the patients rarely have a chance for liver transplantation because of the rapid development of the disease. We describe of a case of FHF secondary to HSV infection in a neonate successfully treated by aggressive intensive care followed by liver transplantation.

Acyclovir↗

PubMed1998

Regulation of intracellular free Mg2+ concentration in isolated rat hearts via beta-adrenergic and muscarinic receptors.

Regulation of the intracellular free magnesium concentration ([Mg2+]i) was investigated in isolated rat hearts, using 31P-nuclear magnetic resonance (31P-NMR). [Mg2+]i was found to be slowly and significantly decreased during prolonged application of isoproterenol (ISO) through beta-adrenergic receptor stimulation, and restored by subsequent washouts. The ISO-induced decrease in [Mg2+]i was antagonized by addition of a muscarinic receptor agonist, carbachol (CCh). In the presence of atropine, CCh did not exert this effect. A water-soluble forskolin derivative, NKH477, which directly activates adenylate cyclase, also caused a decrease in [Mg2+]i, which could be antagonized by CCh, but a greater concentration was required as compared to the ISO case. The manner of [Mg2+]i regulation mimicked those noted for the action potential duration and the Ca2+ channel current, in which cAMP is known to act as a second messenger. Even in the presence of a Ca2+ channel blocker, verapamil, [Mg2+]i was reversibly decreased by ISO. Changes in the intracellular ATP concentration demonstrated any clear correlation with changes in [Mg2+]i. These results suggest that [Mg2+]i can be controlled by a balance of sympathetic and parasympathetic activities. cAMP may play a key role in the [Mg2+]i regulation via beta-adrenergic and muscarinic receptors, although some other metabolic pathways also appear to be involved. Hormonally induced changes in [Mg2+]i have possible clinical significance.

Animals↗