Biomedical subjects

N Kawazoe

Publications and source records attributed to N Kawazoe.

At least 37 records · Page 2Linked to original sources

PubMed1997

Bcl-2 protein inhibits bufalin-induced apoptosis through inhibition of mitogen-activated protein kinase activation in human leukemia U937 cells.

In a previous study, we demonstrated that bufalin, which is an active principle of Chinese medicine, chan'su, caused apoptosis in human leukemia U937 cells by anomalous activation of mitogen-activated protein kinase (MAPK) via the signaling pathway of Ras, Raf-1, and MAPK kinase-1. Here, we report the effect of overexpression of bcl-2 in U937 cells on the signaling pathway of apoptosis that is induced by bufalin. The results indicated that the apoptosis induced by bufalin in U937 cells was significantly inhibited by overexpression of the Bcl-2 protein. No significant difference was detected in the activation of MAPK kinase-1 that is induced by bufalin in wild-type or Bcl-2-overexpressed U937 cells; however, the activation of MAPK by bufalin was significantly attenuated in the cells overexpressing Bcl-2. Bufalin treatment activated activator protein-1 transcriptional activity; however, this activation was decreased to 40% in bcl-2-overexpressed U937 cells. These results indicate that Bcl-2 acts downstream of MAPK kinase-1 but upstream of MAPK and suggest that, in the signaling pathway of the apoptotic process induced by bufalin, the transcriptional activity of activator protein-1 may be down-regulated through the inhibition of MAPK activity by Bcl-2.

Antineoplastic Agents↗

PubMed1997

Bufalin reduces the level of topoisomerase II in human leukemia cells and affects the cytotoxicity of anticancer drugs.

When human leukemia HL-60 cells were treated with 10(-7) M bufalin, the amounts of both topoisomerase (topo) II alpha and II beta and the activity of topo II decreased markedly and were almost undetectable 18 h after the start of treatment. The level of topo II mRNA started to decrease immediately after the start of treatment with bufalin, with a subsequent decrease in the amount of topo II alpha protein. These changes preceded the fragmentation of DNA, a typical feature of apoptosis. The results suggest that bufalin caused a marked decrease in the steady-state level of topo II alpha mRNA, which led to a decrease in the amount and activity of the enzyme and to the induction of apoptosis. A reduction in the level of topo II alpha by bufalin was also observed in other lines of human leukemia cells such as ML1 and U937. The results were exploited to potentiate the effects of cisplatin and retinoic acid (RA) on HL-60 cells: pretreatment of HL-60 cells with 10(-7) M bufalin for 6 h increased the inhibitory effects of cisplatin and RA on cell growth and enhanced the induction of cell death.

Antineoplastic Agents↗

PubMed1996

Patterned staining by fluorescein-labeled oligonucleotides obtained by in vitro selection.

We describe a new means of surface staining using a fluorescent oligonucleotide. A folic acid-specific, fluorescent-labeled oligonucleotide was selected from a group of randomly sequenced oligonucleotides by repeated elution through a folic acid-immobilized column and amplified by the polymerase chain reaction. We then examined the oligonucleotide scattered on a polyester film with folic acid immobilized in a defined pattern, by means of laser fluorescence microscopy. The results showed that the selected oligonucleotide fluoresced exactly following the pattern of immobilized folic acid.

Fluorescein↗

PubMed1996

Blood pressure and its regulation in spontaneously hypertensive rats bred on the lowest sodium diet for normal growth.

To investigate the effects of dietary sodium restriction from conception to adulthood on blood pressure and its regulatory mechanisms, male offspring were derived from inbreeding in spontaneously hypertensive rats fed a diet containing sodium of 175 mumol/g food (control) or 22 mumol/g (low sodium), which is the least sodium content for normal growth. While urinary sodium excretion was markedly less, the low sodium diet did not inhibit body growth and failed to blunt the development of hypertension. Neither plasma catecholamine concentration nor depressor response to hexamethonium was different between the two groups at any age examined (8, 12, and 20 weeks). Plasma renin concentration was not elevated, whereas urinary excretion of aldosterone was increased at any age in the low sodium group compared with that in the control group. Other sets of rats were fed a diet containing sodium of 175 mumol/g plus mefruside (a diuretic) of 0.001% in the same manner as in the other two groups. Urinary sodium excretion per creatinine was higher than in the other groups. The diuretic treatment inhibited body growth and suppressed adult blood pressure. While the sympathetic function was not affected, both plasma renin concentration and urinary excretion of aldosterone were elevated. These results indicate that dietary sodium restriction with the least sodium for normal growth from conception cannot blunt either the sympathetic nervous function or the development of hypertension in spontaneously hypertensive rats. Aldosterone appears to play an important role in maintaining sodium homeostasis under the dietary sodium restriction.

Aldosterone↗

PubMed1996

Headache as a manifestation of myocardial infarction.

We report a 64-year-old man who complained of headache without chest pain at the onset of acute myocardial infarction (AMI). He had no history of chest pain or headache. Severe headache in this case was the first symptom of AMI. The headache was reproduced during stress test. During the angioplasty procedure, he also complained of headache without vasospastic change in the coronary artery. These findings suggest that the headache which accompanied AMI or myocardial ischemia in this case was due to referred pain rather than a generalized vasospastic disorder.

Angioplasty, Balloon, Coronary↗

PubMed1995

Modulation of baroreflex function by angiotensin II endogenous to the caudal ventrolateral medulla.

Neurons in the ventrolateral medulla (VLM) mainly determine the tonic sympathetic activity. The caudal VLM (CVLM) relays baroreflex signals to the rostral VLM. We have reported that endogenous angiotensin II (ANG II) contributes to the ongoing activity of the VLM neurons. In the present study, we examined if ANG II endogenous to the CVLM modulates the baroreflex function in anesthetized normotensive Sprague-Dawley rats. Changes in renal sympathetic nerve activity (RSNA) in response to changes in mean arterial pressure (MAP) induced by i.v. infusion of phenylephrine and nitroglycerin were recorded before and after bilateral microinjection of [Sar1, Thr8]-ANG II, an ANG II antagonist, into the CVLM. The ANG II antagonist injection into the CVLM significantly increased MAP and RSNA by 17.6 +/- 8.0 mmHg (mean +/- S.D.) and 36.3 +/- 18.1%, respectively. It also significantly increased the baroreflex sensitivity (BS) from -0.49 +/- 0.38 to -0.74 +/- 0.37%/mmHg during nitroglycerin infusion. In contrast, the BS examined by phenylephrine infusion was not altered by the pretreatment with ANG II antagonist. Injection of artificial CSF affected neither the baseline values of MAP and RSNA nor the BS. These results suggest that ANG II endogenous to the CVLM exert a modulating role in baroreflex control of RSNA.

Adrenergic Fibers↗

PubMed1995

Bufalin induces apoptosis and influences the expression of apoptosis-related genes in human leukemia cells.

A low concentration of bufalin, a component of bufadienoides in the traditional Chinese medicine chan'su, was shown previously to induce differentiation of a broad range of human leukemia cell lines. In the present study, we found that bufalin at concentrations of 10(-7) M and higher induced apoptosis in human leukemia cells, such as HL60, ML1, but not in mouse leukemia M1 cells. A mere 15 min pretreatment of HL60 cells with 10(-6) M bufalin, followed by incubation for 15 h without bufalin, caused fragmentation of DNA and a decrease in cell viability, indicating that the signal for induction of apoptosis is triggered rapidly upon treatment with bufalin. Bufalin-induced apoptosis in HL60 cells was inhibited by ZnCl2, an inhibitor of endonuclease, but not by cycloheximide, an inhibitor of protein synthesis. Northern blot analysis revealed that the levels of expression of the c-myc and bcl-2 genes in HL60 cells decreased with time after treatment with bufalin. These results suggest that bufalin induces apoptosis specifically in human leukemia cells by altering the expression of these genes involved in apoptosis.

Animals↗

PubMed1995

Alpha 2-adrenoceptors in brain and kidney during development of hypertension in Dahl-Iwai salt-sensitive rats.

BACKGROUND: Both renal and extrarenal factors have been considered to contribute to the development of hypertension in Dahl salt-sensitive rats, but contents of both factors have not been established precisely. AIM: To clarify the role of those factors in the sympathetic nervous system, we examined the regulation of alpha2-adrenoceptors in the lower brainstem and the renal tubular basolateral membranes simultaneously during the development of salt-induced hypertension in Dahl-Iwai salt-sensitive rats. METHODS: Dahl-Iwai salt-sensitive or resistant rats were fed a high (8.0% NaCl)- or low (0.3%)- salt diet from 4 to 6 or 10 weeks of age. At 4, 6 and 10 weeks of age, the plasma membranes of the lower brainstem and the renal tubular basolateral membranes were obtained simultaneously and alpha 2-adrenoceptors were quantified by a radioligand binding assay using 3H-rauwolscine. RESULTS: In the salt-sensitive rats, systolic blood pressure was significantly higher in those fed a high-salt diet than in those fed a low-salt diet. In the salt-resistant rats, both the high- and the low-salt groups showed similar blood pressure levels. At 6 weeks of age, alpha 2-receptor densities of the salt-sensitive rats fed a high-salt diet were lower in the lower brainstem and higher in the renal basolateral membranes than those fed a low-salt diet. In contrast, in the salt-resistant rats, both the high- and the low-salt groups had similar densities. At 10 weeks of age, the difference between the high- and the low-salt groups in the salt-sensitive rats disappeared in both the brainstem and the renal basolateral membranes. CONCLUSIONS: Alpha 2-adrenoceptor regulation in the brainstem and the renal basolateral membranes differs between Dahl-Iwai salt-sensitive and salt-resistant rats. The modulation of alpha 2-adrenoceptors by a high salt intake may be essential particularly in the early phase of the development of salt-induced hypertension.

Animals↗

PubMed1995

[Two siblings with adult-onset sialidosis type I (cherry-red spot-myoclonus syndrome)].

Cases of two Japanese siblings with adult-onset sialidosis type I are reported. A 38-year-old man had gradually developed involuntary movement of the extremities from the age of 31. On admission, he had no skeletal abnormalities and hepatosplenomegaly, but showed myoclonus of the extremities and dyskinesia in the perioral region. We found cherry-red spots and a giant potential in a somatosensory evoked potential (SEP) study. Then, the diagnosis of sialidosis type I was confirmed by low activity of white blood cell sialidase. MRI (SE, TR 2,000/TE 100, 40) of the brain revealed a small high intensity are in the cerebral white matter adjacent to the posterior horn of the right cerebral ventricle. To our knowledge, no report on MRI findings of the brain in sialidosis type I has been reported. So far, it is uncertain whether or not such a lesion is caused by sialidosis. He was treated with clonazepam, sodium valproate, diphenylhydantoin, or haloperidol. The former two improved the symptoms, but SEP findings did not change. The subject's 43-year-old brother had also myoclonus and epilepsy since the age of 31, and low activity of sialidase. Their mother had no symptoms, but her sialidase activity level was as low as that of a carrier. These two are the eighth and ninth cases of sialidosis type I in Japan to be confirmed by enzyme activity.

Adult↗

PubMed1994

Selective inhibitory effect of bufalin on growth of human tumor cells in vitro: association with the induction of apoptosis in leukemia HL-60 cells.

We found that bufalin, an active principle of the Chinese medicine chan'su, has selective inhibitory effects on the growth of various human cancer cells. In order to examine whether the growth-inhibitory effect of bufalin on human cancer cells is associated with apoptosis, human leukemia cells were treated with bufalin. HL-60, ML1, and U937 leukemia cells treated with bufalin at 10(-8) M and above had condensed and fragmented nuclei. Flow cytometric analysis of these cells treated with bufalin showed fragmented DNA smaller than that of the G1 phase. DNA of HL-60 cells treated with bufalin showed a ladder pattern characteristic of apoptosis, as analyzed by agarose gel electrophoretic analysis. DNA synthesis and topoisomerase II activity of HL-60 cells were markedly inhibited as the concentration of bufalin was increased. The concentration needed for inducing apoptosis of HL-60 cells was 10(-8) M, which is comparable to that of camptothecin, but lower than those of other antitumor drugs such as cisplatin, VP16 and all-trans retinoic acid. Apoptosis was not observed when human mononuclear and polymorphonuclear cells were treated with 10(-6) M bufalin for 24 h. These results indicate the association of the growth-inhibitory effect of bufalin with the induction of apoptosis, at least in HL-60 cells, and suggest the usefulness of bufalin for differentiation-apoptosis-inducing therapy for cancer.

Antineoplastic Agents↗

PubMed1994

Neural effects on renal blood flow during acute hypotension vary with antihypertensive drugs.

To examine the neural effects of antihypertensive drugs on renal blood flow, we measured blood flow and renal sympathetic nerve activity simultaneously in conscious spontaneously hypertensive rats aged 13 to 15 weeks. One to two days after surgery, intravenous administration of manidipine (calcium antagonist, n = 10), doxazosin (alpha 1-adrenergic receptor antagonist, n = 9), and clonidine (n = 7) lowered mean arterial pressure by at least 20% from baseline levels. Manidipine initiated a reduction of renal blood flow when mean pressure decreased by 20 +/- 2 mm Hg. At the maximal decrease in renal blood flow (mean pressure, -33 +/- 2 mm Hg), percent decrease in flow (-27 +/- 2%) significantly correlated with percent increase in renal nerve activity (+205 +/- 40%, r = -.878). Doxazosin began to decrease renal blood flow at a level of arterial pressure similar to that in manidipine treatment, whereas the maximal decrease in flow (-19 +/- 2%; mean pressure, -33 +/- 2 mm Hg; nerve activity, +225 +/- 44%) was significantly less than that in manidipine treatment. Although clonidine decreased arterial pressure and renal nerve activity, renal blood flow did not decrease even at the maximal decrease in mean pressure of 29 +/- 1 mm Hg. The addition of clonidine to manidipine treatment suppressed reflexly enhanced renal nerve activity and restored blood flow to the pretreatment level despite pronounced hypotension. These results clearly demonstrate that antihypertensive drugs with blocking action on renal nerve activity are capable of maintaining renal blood flow and that those associated with reflex-induced enhancement of nerve activity exert deteriorating effects on renal blood flow. Furthermore, a decrease in renal blood flow induced by calcium antagonists is mainly attributed to reflexly enhanced renal nerve activity.

Animals↗

PubMed1994

Infected right atrial thrombus and pulmonary emboli associated with a perforated jejunal diverticulitis.

We describe a patient with an infected right atrial thrombus and pulmonary embolism who died suddenly. Jejunal diverticulitis, which was found at autopsy, was suspected to be the source of the bacterial thrombus. The 41-year-old female patient was admitted because of dyspnea and syncopal attacks. Physical examination on admission revealed an obese woman with a body temperature of 36.5 degrees C, systolic heart murmur and abnormal diastolic heart sound. Two-dimensional echocardiography revealed a strand-shaped mass in the right atrium. Lung blood perfusion scintigraphy revealed multiple perfusion defects in both lung fields. She suddenly developed severe dyspnea leading to death on the 6th hospital day. At autopsy, a strand-shaped organized thrombus was found in the right cardiac chambers. Microscopically, the thrombus was found to be infiltrated with numerous gram-positive cocci, leukocytes and a small number of gram-negative cocci. Most of the major pulmonary arterial branches were occluded by bacterial thromboemboli, and multiple pulmonary infarctions were found in both lungs. A perforating diverticulum with microabscess was found in the jejunal mucosa which was assumed to be the source of the bacterial thromboembolism.

Adult↗

PubMed1993

Serum albumin is a strong predictor of death in chronic dialysis patients.

We examined the predictive value of various clinical variables in assessing survival in chronic hemodialysis patients (N = 1,243, 524 females, 719 males) who were under treatment with hemodialysis as of January 1991 in Okinawa, Japan and who were followed up until April 1992. Basal clinical data such as sex, starting date of dialysis, primary renal disease, blood pressure, blood chemistry values, and dialysis prescription data obtained just prior to dialysis were registered at the start of the study. As of the end of April 1992, 104 had died, 16 were transplant recipients, and five had been transferred. Those who died had significantly lower levels of total protein, serum albumin, total cholesterol, triglyceride, BUN, serum creatinine, body weight, body height, diastolic blood pressure, and duration of hemodialysis than those who survived. Older patients and those with diabetes mellitus had a poorer prognosis. A forward stepwise logistic procedure by SAS was used to determine the predictive value of the above clinical variables. With the addition of laboratory variables, the predictive value of diabetes was lost, as the diabetic patients had low serum levels of albumin and creatinine. The standardized coefficient was -0.380 (P = 0.0001) at age of entry, 0.316 (P = 0.0001) for serum albumin, 0.280 (P = 0.0001) for serum creatinine, 0.138 (P = 0.043) for body mass index (BMI), and -0.139 (P = 0.016) for male sex. The prescribed dialysis dose (M2 hr per week) was significantly correlated with serum creatinine (r = 0.48, P = 0.0001), serum albumin (r = 0.135, P = 0.0001) and BMI (r = 0.275, P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Survival analysis of dialysis patients in Okinawa, Japan (1971-1990).

We analyzed longitudinal data obtained from the initiation of chronic dialysis in Okinawa, Japan. A total of 1,982 patients (824 females and 1,158 males) were registered in the Okinawa Dialysis Study (OKIDS) up to the end of 1990. The number of patients dying, undergoing renal transplantation, or being transferred was 605 (30.5%), 75 (3.8%), and 23 (1.2%), respectively. The mean acceptance rate per million population increased from 19.7 in 1971 to 1975 to 157.4 in 1986 to 1990. The percentage of diabetic patients and the annual gross mortality rate were, respectively 0% and 0.52 (1971 to 1975), 7.3% and 0.12 (1976 to 1980), 14.4% and 0.06 (1981 to 1985), and 24.6% and 0.07 (1986 to 1990). Cox proportional hazard analysis was used to determine the relative risk (RR) for sex, primary renal disease, age at entry, and the year of starting dialysis. The RR for males was 1.09 (1.00 for females) and the 95% confidence interval (CI) was 0.93 to 1.28. The RR for diabetics was 1.88 (95% CI; 1.55 to 2.28) when that for nondiabetics was set at 1.00. The RR (95% CI) for starting dialysis in 1976 to 1980, 1981 to 1985, and 1986 to 1990 was 0.65 (0.59 to 0.72), 0.43 (0.35 to 0.52), and 0.28 (0.20 to 0.38), respectively, when the RR in 1971 to 1975 was taken as 1.00. During the last two decades, the survival of chronic dialysis patients in Okinawa has continued to improve despite the large increase in acceptance rate, the older age of the new patients, and the increase in diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Carbamazepine-induced hyponatremia in a patient with partial central diabetes insipidus.

A 51-year-old Japanese man was referred for the evaluation of persistent hyponatremia. The serum sodium level remained around 120 mmol/l despite mild water restriction. His past history included chronic alcoholism, myocardial infarction and lumbar disc herniation. Carbamazepine (200 mg, b.i.d.) has been used for more than 8 years for low back pain. Serum sodium returned to normal after carbamazepine was stopped, and rechallenge produced acute symptomatic hyponatremia (117 mmol/l) on day 2 after a total dose of 600 mg. Hepatic, renal and endocrine function were within normal limits, and the response to a water load (20 ml/kg) was also normal. Partial central diabetes insipidus was diagnosed by his response to water restriction and nasal desmopressin administration. Polyuria and hypernatremia were not evident in this case, probably due to a combination of low solute intake and low, but not deficient, levels of plasma ADH. This case demonstrates that carbamazepine may cause acute hyponatremia even in central diabetes insipidus, probably by sensitizing the distal renal tubules.

Carbamazepine↗

PubMed1993

[Relationship between the Ki-67 nuclear antigen content and cell-cycle perturbation on WiDr cells treated with 5-FU].

The profile of Ki-67 nuclear antigen content according to the change in the cell-cycle of WiDr cells affected by 5-fluorouracil (5-FU) was studied by flow cytometry. The cases who received 10 micrograms/ml for 1 hr and showed reproliferation in the growth curve presented significant accumulation at G2M phases. However, significant increase of Ki-67 antigen content was not observed in G2M phases. Meanwhile, the cases who continuously received 10 micrograms/ml for 72 hr and showed the suppression of cellular proliferation without reproliferation presented gradual accumulation into S phase and Ki-67 antigen content was found to be significantly increased. This increase occurred in G1 phase, and the cells with Ki-67 antigen content of the largest increase in G1 phase shifted to S phase. It indicates a possibility that Ki-67 nuclear antigen content is destined to be controlled specifically in G1 phase of the cell-cycle. 5-FU seems to damage this regulation system and, as a result, increase Ki-67 nuclear antigen.

Cell Cycle↗

PubMed1993

Arterial pressure and its regulation in rats bred successively on low sodium diet.

To investigate the effects of long-term sodium restriction on mechanisms regulating cardiovascular function, Wistar rats at weaning (F0) were placed on a normal (0.4%) or low (0.05%) sodium diet. The first (F1) and second (F2) generations were derived from inbreeding within each group. The resting mean arterial pressure did not differ between the diet groups of F0 or F1 rats, but it was significantly lower in F2 rats on the low sodium diet. Plasma renin concentration was similar in the two groups in each generation, and the F2 rats on both diets responded to [Sar1, Ala8] angiotensin II with the same degree of decrease in arterial pressure. Plasma norepinephrine was not influenced by sodium intake in the F0 or F1 rats, but was significantly lower in F2 rats on the low sodium diet. The depressor response to hexamethonium was similar in the two F1 groups, while low sodium F2 rats exhibited a lesser response. These results suggest that rats bred successively on a low sodium diet have a suppressed sympathetic nerve function with no enhancement of the renin-angiotensin system, which in turn results in a lower arterial pressure.

Animals↗

PubMed1993

Renin responses in patients with orthostatic hypotension: case reports.

In orthostatic hypotensive patients renin is reported to increase in response to head-up tilt unless the lesion involves postganglionic sympathetic efferent nerves. The authors examined responses of plasma renin activity (PRA) to acute blood pressure reduction in 4 patients with orthostatic hypotension. When the coexistence of normal plasma norepinephrine (PNE) and normal or high-normal pressor response to alpha stimulant is considered to be a sign of preserved function of postganglionic fibers, 2 of the patients had sympathetic lesions mainly confined to central and/or preganglionic fibers. They were diagnosed as having multiple system atrophy (MSA). The other 2 were diagnosed as having idiopathic orthostatic hypotension with possible postganglionic lesions. Although 1 MSA patient showed an increase in PRA from 2.0 to 4.7 ng/mL/hr in response to the tilt, the other MSA patient showed no PRA response to the tilt. The head-up tilt did not provoke an apparent PRA response in patients with idiopathic orthostatic hypotension. The authors infused sodium nitroprusside (SNP) in the 3 patients whose PRA did not respond to the head-up tilt. The infusion decreased blood pressure by 40 mmHg or more, but PRA responses were inappropriately small or suppressed. In all cases, PNE did not respond at all to the head-up tilt and to the infusion of SNP. These findings suggest that possible preservation of postganglionic fibers does not necessarily indicate an intact responsiveness of PRA. The PRA profiling may not be an accurate predictor for the site of the fiber degeneration in orthostatic hypotension.

Aged↗