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Biomedical subjects

T Naruse

Publications and source records attributed to T Naruse.

At least 235 records · Page 13Linked to original sources
PubMed1989

NB-355: a novel prodrug for L-DOPA with reduced risk for peak-dose dyskinesias in MPTP-treated squirrel monkeys.

Prodrugs may be used to improve the absorption and bioavailability of certain active compounds. We have examined the ability of a novel catechol monoester of L-DOPA, NB-355 [L-3-(3-hydroxy-4-pivaloxyloyphenyl)alanine], to stimulate locomotor activity and induce dyskinesias in MPTP-treated primates. In the presence of carbidopa, a dose-dependent increase in locomotor activity over 4 1/2 h was observed following administration of L-DOPA (10, 20 or 40 mg/kg p.o.) or NB-355 (20, 40 or 80 mg/kg p.o. dopa equivalent). The dose-response curve for NB-355 was shifted to the right such that approximately twice the dopa equivalent dose of NB-355 was required to stimulate locomotor activity to the same level observed for L-DOPA. At doses matched for total locomotor stimulation over the 4 1/2-h period (20 mg/kg L-DOPA and 40 mg/kg NB-355), there was a more gradual rise and increase in the duration of motor stimulation by approximately 40% using NB-355. At these doses, drug-induced dyskinesias were less severe following treatment with NB-355 than with L-DOPA. Our findings suggest that NB-355 may be a useful therapeutic agent for increasing the duration of action of L-DOPA and reducing the severity of peak-dose dyskinesia.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Hypoparathyroidism during alpha-INF therapy in a patient with multiple myeloma.

A 66 year-old woman with multiple myeloma developed hypoparathyroidism during combination chemotherapy with melphalan, prednisolone, and alpha-interferon (INF). Seven weeks after commencement of the therapy, the serum calcium (Ca) level decreased to 7.4 mg/dL, and the phosphorus (P) level increased to 7.2 mg/dL; parathyroid hormone (PTH) was at a critically low level. By 13 weeks after discontinuation of alpha-INF, the levels of Ca, P, and PTH had returned to normal values: 8.6 mg/dL, 4.5 mg/dL, and 310 pg/ml, respectively. These changes suggest a strong correlation between hypoparathyroidism and the administration of alpha-INF. Autoantibodies against the parathyroid gland cell were not present in the serum of this patient by indirect immunofluorescent techniques. The mechanism of hypoparathyroidism by alpha-INF could not be identified, but this is the first case of this condition during alpha-INF therapy.

Aged↗
PubMed1988

Effects of naloxone and picrotoxin on diazepam- or pentobarbital-induced hyperphagia in nondeprived rats.

Diazepam and pentobarbital administered intravenously increased food intake in a dose-dependent manner in nondeprived rats. Low doses of naloxone inhibited diazepam-induced feeding, but did not inhibit pentobarbital-induced feeding. On the other hand, picrotoxin inhibited feeding induced by both drugs. These findings suggest that diazepam-induced hyperphagia is related to endogenous opioid mechanisms, but pentobarbital-induced hyperphagia is not. Hyperphagia induced by both drugs may be related to GABAergic neurons.

Animals↗
PubMed1988

Effect of drug administration on experimental renal glomerular thrombosis.

Experimental thrombosis which developed exclusively in glomerular capillary walls was induced in rats by the combined injection of nephrotoxic antiserum (0.2 ml of pooled material) as a preparatory agent and 20 micrograms or more of lipopolysaccharide as a provoking agent. Effects of some antiplatelet and anticoagulant drugs on the glomerular lesions were tested in this experimental glomerular thrombosis. With administration of 2000 units/kg or more of heparin at the time of provoking injection, coagulation time was prolonged for over 5 hr, and the glomerular thrombosis was adequately prevented. Prolongation of prothrombin time (PT) for over 60 sec to prevent thrombosis required warfarin, but with this drug there was only a narrow margin between an effective dose and that which produced a fatal hemorrhage. Low levels of fibrinogen (less than 50 mg/dl) induced by batroxobin seemed to protect partially and high doses of urokinase did not seem to protect from glomerular thrombosis. OP-41483, a derivative of prostacyclin which is about five times more active than PGE1 in inhibiting platelet aggregation, and other anti-platelet drugs except for ticlopidine were not effective in preventing glomerular thrombosis. These findings were in accordance with the fact that thrombocytopenia induced by antiplatelet antiserum did not prevent glomerular thrombosis. Ticlopidine may have a unique and valuable therapeutic potential for the control of this condition.

Animals↗
PubMed1987

Intravenous self-administration of diazepam in rats.

Diazepam 0.5-2.0 mg/kg per injection was self-administered intravenously by rats on a continuous reinforcement schedule in a dose-dependent manner over a 30 day period. The rates of diazepam self-administration were relatively stable after responding was established, in comparison with rats self-administering morphine 0.5 mg/kg per injection whose rates continued to increase. At a fixed ratio 4 or 8 schedule, higher maximum rates of responding were seen with diazepam than with morphine. During withdrawal, reductions in body weight tended to occur in a manner dependent on the preceding rates of diazepam self-administration and were possibly caused by physical dependence. These findings suggest that diazepam acts as an intravenous reinforcer in rats and that the procedure we describe is of use to predict the dependence liability of drugs considered to have only a weak potential for abuse.

Animals↗
PubMed1987

Local recurrence of breast cancer: treatment of nine patients with a recurrence in the skin flap of the chest wall.

From 1975 through 1985, nine patients with a local recurrent lesion (LRL) of breast cancer to the skin flap of the chest wall were treated. Four had undergone primary mastectomies in our clinic and the other five were referred from other surgeons, following signs of recurrence. Aggressive topical therapy, such as resection or irradiation, proved effective in eradicating the LRL in all cases, thereby indicating that topical therapy is useful for improving quality of life. Adjuvant systemic chemo-immuno-endocrine therapy is also required for patients with LRL, to increase longevity. Seven of the patients died of a distant metastasis within 66 months after the onset of LRL.

Adult↗
PubMed1986

Isolation and characterization of rat nephritogenic and non nephritogenic brush border antigens.

Two kinds of brush border antigens were isolated from pronase-treated rat tubular material by gel filtration, DEAE-chromatography and disc-electrophoresis, successively. One, a 0.05 M antigen which was eluted from DEAE-column with 0.05 mol of NaCl solution, has no nephritogenic ability when inoculated into homologous rats. The other, a 0.30 M antigen eluted with 0.30 mol of NaCl solution, induces membranous nephritis when injected into rats. Immunoprecipitation studies show no common factor between these two antigens. SDS-polyacrylamide electrophoresis shows the molecular size of 0.05 M and 0.30 M antigens to be respectively over 200 kD and about 90 kD. Rabbit antiserum against the 0.05 M antigen fixed to the GBM in a diffuse granular fashion as well as to the brush border by immunofluorescence when incubated in vitro with normal rat kidney section. Rabbit antiserum to the 0.30 M antigen, however, fixed exclusively in vitro to the brush border. Passive transfer of nephritis was studied with these rabbit antisera. When antiserum to 0.05 M antigen was injected into normal rat, diffuse granular deposition of rabbit IgG was observed in the GBM within 2 h of the injection, but the deposits became negative 1 week later. Rats injected with antiserum to the 0.30 M antigen showed no glomerular deposition within 2 days but diffuse granular deposits of rabbit IgG were observed within 1 week and increased until 2 weeks after the injection. These facts should be considered in the studies on passive Heymann nephritis and its pathogenesis.

Animals↗
PubMed1986

[Rapid establishment of nicotine intravenous self-administration behavior in rats].

The reinforcing effect of nicotine was investigated using the intravenous self-administration method in rats. After forced iv injection of nicotine (3, 10 and 30 micrograms/kg/inj) at 1-hr intervals for 3 days in 3 dose-level groups, self-administration sessions under the continuous reinforcement schedule were carried out for 15 days. Rats initiated self-administration of nicotine rapidly in 10 and 30 micrograms/kg/inj groups. Daily self-administration responses by nicotine (30 micrograms/kg/inj) were 3-10 times the control levels. Total self-administration responses for 15 days increased in a dose dependent manner. When the fixed ratio was increased from 1 to 4 and 8 after the 15 days self-administration session in the nicotine (10 and 30 micrograms/kg/inj) groups, lever press responses increased only about 2 times, and self-administration responses decreased in the both groups. These findings suggest that nicotine becomes a reinforcer rapidly, but the magnitude of reinforcing effect is relatively week after the acquisition of nicotine for a short period.

Animals↗
PubMed1985

Osteopathia striata with cranial sclerosis affecting three family members.

Skeletal surveys were performed on a 38-year-old Japanese mother, her son and daughter. The radiographs of both children showed characteristic features of osteopathia striata. However, in the mother, the skull, mandible, and lower extremities were homogeneously sclerotic with no evidence of a striated pattern of sclerosis in her skeleton. Additional features of striated sclerosis of the mandible in patients with osteopathia striata are discussed.

Adult↗
PubMed1985

[Effects of single and repeated oral administration of MK-421 and captopril on blood pressures in normotensive and experimental hypertensive rats].

In the single dose study, the aortic blood pressure in conscious normotensive rats, 2-kidney, 1-clip renal hypertensive rats (2K-RHR), 1-kidney, 1-clip renal hypertensive rats (1K-RHR) or DOCA hypertensive rats was measured for 24 hr after the oral administration of angiotensin converting enzyme (ACE) inhibitors such as MK-421 or captopril. MK-421 at 3 mg/kg and captopril at 10 mg/kg markedly lowered the blood pressure of 2K-RHR. MK-421 at 10 mg/kg and captopril at 30 mg/kg only modestly lowered the blood pressure of 1K-RHR. In contrast, both ACE inhibitors failed to reduce blood pressure in DOCA and normotensive rats. In the repeated dose study, the systolic blood pressures in normotensive rats, 2K-RHR or spontaneously hypertensive rats (SHR) were measured twice a week for 3 weeks treatment of either MK-421 at 3 mg/kg or captopril at 10 mg/kg. Both ACE inhibitors produced significant antihypertensive effects in these model rats, and the effects were sustained throughout the treatment period. The antihypertensive effects in 2K-RHR were greater than those in SHR and normotensive rats. These results indicate that MK-421 and captopril cause the most significant antihypertensive effect in 2K-RHR in which the renin-angiotensin system played a dominant role in blood pressure regulation. The antihypertensive effect of MK-421 was approximately 3 times as potent as that of captopril in these hypertensive models.

Animals↗
PubMed1985

[Correlation between the inhibition of renin-angiotensin system and antihypertensive effect of MK-421 and captopril in 2-kidney, 1-clip renal hypertensive rats after single and repeated oral administration of MK-421 or captopril].

The angiotensin converting enzyme (ACE) activity in tissues and plasma renin activity (PRA) were measured in 2-kidney, 1-clip renal hypertensive rats (2K-RHR) and normotensive rats after a single and 3-weeks oral administrations of ACE inhibitors such as MK-421 and captopril. In the single dose study, MK-421 (1 and 3 mg/kg) and captopril (3 and 10 mg/kg) inhibited the ACE activities in kidney, aorta and plasma in a dose-dependent fashion. The inhibition of ACE activity in kidney or aorta was observed for a longer time than that in plasma. PRA took a time course reversal to that of plasma ACE activity. In the 3-weeks repeated dose study, the ACE activity in kidney and aorta was strongly inhibited after the administration of each ACE inhibitor, while there was no significant change in lung ACE activity at any time point examined. The plasma ACE activity markedly elevated after the administration of each agent. PRA significantly increased after the administration of either agent, while the plasma angiotensin II level was significantly inhibited. These results indicate that the inhibition of the ACE activity in blood vessel or kidney correlate well with the antihypertensive activity in 2K-RHR after a single and repeated administration of both ACE inhibitors, but not well with the inhibition of plasma ACE activity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

Selective glomerular thrombosis in rats induced by combined injections of nephrotoxic antiserum and lipopolysaccharide.

Experimental glomerular thrombosis was induced in rats by combined injections of nephrotoxic antiserum and lipopolysaccharide. For the development of glomerular thrombosis, administration of nephrotoxic antiserum (greater than or equal to 0.1 ml pooled material) was required as a preparatory agent and greater than or equal to 100 ng lipopolysaccharide as a provoking agent. The severity of renal lesions was not parallel with the amounts of nephrotoxic antiserum and lipopolysaccharide injected. Transient clamping of a unilateral renal artery for 10 to 20 minutes at the time of the nephrotoxic antiserum injection partially prevented the development of glomerular thrombosis in the clamped side. Intervals between the preparatory and provoking injections were found to be -4 to 72 hours for the development of renal lesions. With the preparatory injection of 0.1 to 0.3 ml nephrotoxic antiserum a thrombotic lesion developed exclusively in glomerular capillary walls greater than or equal to 2 hours after the lipopolysaccharide injection. No thrombotic lesion was observed in other tissues such as lung, liver, or intestine, but a generalized Shwartz-manlike phenomenon was observed with the preparatory injection of 0.5 ml nephrotoxic antiserum. When rats were pretreated with nephrotoxic antiserum and 3 hours thereafter transfused with 1 to 3 X 10(8) polymorphonuclear leukocytes, which had been incubated with lipopolysaccharide for 30 minutes in vitro and washed three times with buffered physiologic saline solution, a marked glomerular thrombosis was also induced. The result indicates that lipopolysaccharide plays a role in the development of thrombosis by a direct effect on leukocytes. The development of glomerular thrombosis was prevented in a leukocytopenic state when leukocyte count was less than 600/microliter, but not in thrombocytopenic rats with a platelet count 8.7 to 30 X 10(3)/microliter. Leukocyte count and plasma fibrinogen level decreased, and prothrombin time and activated partial thromboplastin time were prolonged significantly during the pathologic course. Platelet count and FDP did not change significantly. This experimental model has a basic similarity to the generalized Shwartzman reaction, but the lesions develop exclusively in glomeruli.

Animals↗
PubMed1984

Pheochromocytoma without specific symptoms.

A 72-year-old Japanese woman with pheochromocytoma, who had had no characteristic symptoms was treated. A large retroperitoneal tumor was discovered incidentally by sonographic examination for mild upper abdominal pain and, with CT-scan and abdominal angiography confirmed that the tumor originated in the right adrenal gland. The tumor was suspected of being a pheochromocytoma because preoperative laboratory examinations revealed only a mild elevation of daily urinary excretions of adrenaline and noradrenaline. Provocation tests for pheochromocytoma and even angiographic examination revealed no diagnostic change in serum levels of catecholamines and distinctive clinical signs were nil. Thus, surgery was performed without preoperative prescription of any catecholamine blockade. During the surgery, the blood pressure and pulse rate fluctuated considerably. A non-functioning pheochromocytoma detected incidentally must be preoperatively managed as a functioning one, even in the absence of specific symptoms of pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1984

Minimal thyroid carcinoma: a report of nine cases discovered by cervical lymph node metastases.

From 1962 to 1983, nine patients with minimal carcinoma of the thyroid were referred to Aichi Cancer Center Hospital and to Aichi Medical University Hospital for evaluation of enlarged lymph nodes in the neck. The radiographic study and scintigraphy of the thyroid were useful in detection of small thyroid lesions. In two cases, a lymph node biopsy was required for confirmation of the diagnosis. The thyroid lesions were histologically papillary carcinoma, in all the cases. A modified neck dissection with total thyroidectomy was carried out in five patients and modified neck dissection with thyroid lobectomy was done in four cases. Nine patients were followed for 6 months to 20 years and all the patients except one are alive.

Adult↗