Quantitation and identification of human monocytic colony-stimulating factor in human serum by enzyme-linked immunosorbent assay

An enzyme-linked immunosorbent assay (ELISA) system for the quantitation of human monocytic colony-stimulating factor (hM-CSF) was established, which was based on the "dual antibody immunometric sandwich" principle using horse and rabbit polyvalent antibodies against human urinary colony-stimulating factor (CSF-HU). The minimal detectable level of hM-CSF was 10 U/mL, and the assays showed good reproducibility. As measured by this method, the average serum hM-CSF level of 20 normal adults was 540 +/- 110 U/mL (range, 300 to 800 U/mL). The peak of hM-CSF measured by ELISA was identical to that measured by bioassay when semipurified CSF-HU was fractionated by reversed-phase high performance liquid chromatography (HPLC). This method detected two types of hM-CSF, which had approximate molecular weights of 85 Kd (CSF-HU) and 45 Kd in human serum and urine; the ratio of 85:45 Kd was very high in serum and the amounts of the two types were nearly equal in urine. After anticancer chemotherapy, the serum hM- CSF level of one half of the patients with hematological malignancy was elevated according to the reduction in neutrophil number, while it was almost in the normal range in the other half of the patients, indicating the possibility that anticancer chemotherapy damaged the hM- CSF-producing cells. This ELISA method may be useful for monitoring the serum hM-CSF level after anticancer chemotherapy.     

MR imaging of dural arteriovenous malformations with ocular signs

Summary Four patients with dural arteriovenous malformation (AVMs) draining into the cavernous sinus, who presented ophthalmic manifestations, were studied by magnetic resonance (MR) imaging. In all patients signal decrease in the involved cavernous sinus was demonstrated in coronal spinecho (SE) imaging. It is attributable to rapid venous flow in the sinus, and this high velocity signal loss is a fairly pathognomonic finding in this condition. We stress the validity of MR imaging in the primary diagnosis of dural AVMs with ophthalmic symptoms.     

Use of a Paracorporeal Pneumatic Ventricular Assist Device for Postoperative Cardiogenic Shock in Two Children with Complex Cardiac Lesions

Pneumatic ventricular assist device (VAD) was utilized for cardiogenic shock after intracardiac operation in two children with complex cardiac anomalies based with single ventricle. In the first case (a 10-year-old), after a modified Fontan operation, VAD was placed between the functional left atrium and ascending aorta, serving as a "artificial single ventricle" with neither pumping chamber nor artificial support in the right side of the heart. The systemic circulation was maintained by keeping relatively high central venous pressure. In another child (a 3-year-old) who underwent repair of incompetent atrioventricular valve leaving intracardiac lesions, VAD was placed between the common atrium and ascending aorta, serving as a pump for both pulmonary and systemic circulation with regulation of pulmonary blood flow through an aortopulmonary Gore-Tex shunt. The circulatory assist with VAD was utilized for 5 and 6 days, respectively. Although weaning from the device was not feasible in both patients because of the pulmonary dysfunction, these experience showed the possible use of VAD for cardiogenic shock after surgery in patients with complex cardiac anomalies.     

Reduced Inhomogeneity of Angelica acutiloba Plants Propagated Clonally Through Somatic Embryoids

Clonal plants propagated from a single plant of a commercial variety of ANGELICA ACUTILOBA (Umbelliferae) through somatic embryoids induced in cell suspension cultures proved to be significantly more uniform with respect to the contents of medicinally important chemical constituents (ligustilide and choline) of the root when compared with seed-propagated plants.     

The future of 5-HT1A receptor agonists. (arylpiperazine derivatives)

Mitsukuni Murasaki and Sadanori Miura: The Future of 5-HT_1A Receptor Agonists. (Aryl-Piperazine Derivatives) Prog. Neuro- Psychopharmacol-& Biol Psychiat, 1992, 16(6): 833–845.

1. 1. At present the dominant position among anti-anxiety medications has changed from meprobamate to the benzodiazepine derivatives.

2. 2. In order to avoid benzodiazepine's (BZ) undesirable side effects such as impairment of psycho-motor function, memory impairment, low dose dependence and withdrawal symptoms, a third generation anxiolytic agent, buspirone, the focus of the aryl-piperazine group of anti-anxiety agents, has been introduced recently.

3. 3. Aryl-piperazine derivatives work as 5-HT_1A receptor partial agonists and are known as serotonin normalizers.

4. 4. Therefore, they are expected to have not only an anxiolytic function but also an anti-depressant effect as well.

5. 5. A characteristic of the aryl-piperazine derivatives is that they have no sedative and muscle relaxant effects, and they do not have BZ's undesirable side-effects, especially in regard to withdrawal symptoms. However they have a rather weak anxiolytic action and a slow onset of action.

6. 6. Aryl-piperazine derivatives will not take the place of BZ, but the use of BZ and buspirone as bridge medications, making the most of the strong points of both, can be proposed as a way to compensate for their respective disadvantages.

Long-term effect of urokinase therapy in IgA nephropathy

Effects of urokinase (UK) therapy in patients with moderate to advanced degrees of IgA nephropathy (IgAN) were examined. Twenty-seven patients were treated by "two weeks" UK administration, 14 patients were treated by "consecutive" UK administration and 16 patients were treated by antiplatelet drugs. There were marked improvements in urinary protein concentration, serum creatinine and blood urea nitrogen after UK therapy, especially in patients treated by "consecutive" UK administration which was performed by "single shot" UK injection. Clinical prognosis was favorable in patients treated by UK administration compared with those given antiplatelet treatment. It was concluded that "consecutive" UK administration might be useful for treatment of IgAN with moderate to advanced renal injuries.     

The development of health risk appraisal for Japanese as a new health educational tool

Health risk appraisal (HRA) is a new health educational tool widely-used in the United States, which informs clients about how their health habits and lifestyles affect their probability of dying from potentially preventable causes and helps to motivate them to reduce their personal health risks. It personalizes mortality statistics and epidemiologic data by combining these data with a person's risk factors. We have got started the development of HRA for Japanese with reference to a new version of HRA named "Healthier People" revised by the Carter Center of Emory University and the Centers for Disease Control in the United States.     

Reversal of multidrug resistance by new dihydropyridines with lower calcium antagonistic activity

Summary BS compounds, a series of new dihydropyridines, successfully overcame multidrug resistance in P388/ADR cells in vitro. These agents synergistically potentiated the cytotoxicity of Adriamycin to P388/ADR cells at a concentration of 1–2 M, whereas they showed hardly any synergistic effect in the parental cell line (P388/S) at the same concentration. They inhibited the active drug efflux in P388/ADR cells as well as the binding of [G-³H]-vinblastine to membrane vesicles from P388/ADR, which was increased in resistant P388 cells as compared with parental cells. Besides, unlike the activity of clinically used calcium antagonists, the calcium antagonistic activity associated with BS compounds was very weak: their arterial relaxation activity was <21% of that of verapamil. These data suggest that BS compounds specifically overcome multidrug resistance without the serious hypotensive side effects that accompany the use of verapamil orother calcium antagonists.     

Pharmacokinetic study of iminodibenzyl antipsychotic drugs,clocapramine and Y-516 in dog and man

The pharmacokinetic properties of the iminodibenzyl antipsychotic drugs clocapramine (CCP, 3-chloro-5-[3-(4-carbamoyl-4-piperidino piperidino) propyl]-10, 11-dihydro-5H-dibenzo[b, f]azepine) and Y-516 (3-chloro-5-[3-(2-oxo-1, 2, 3, 5, 6, 7, 8, 8a-octahydroimidazo [1,2-a] pyridine-3-spiro-4-piperidino) propyl]-10, 11-dihydro-5H-dibenzo[b, f]azepine) were investigated in dog and man. Dogs were administered CCP and Y-516 intravenously, intraperitoneally, and orally, and the concentrations of the parent drugs and their metabolites in the plasma and urine were determined. Half-life (t1/2) was approximately the same by all three administration routes, being approximately 5 h for CCP and 3 h for Y-516. Bioavailability following oral administration was 0.16±0.01 (mean ± SD, n=3) for CCP and 0.29±0.07 for Y-516. The fractions of dose absorbed following oral administration were 0.43±0.07 and 0.79±0.24, and the fractions of dose metabolized in the liver due to the first-pass effect were 0.63±0.05 and 0.63±0.04 for CCP and Y-516, respectively. Y-516 was detected in the plasma after intraperitoneal and oral administration of CCP. The ratio of the AUC of Y-516 to that of CCP was 0.06 following intraperitoneal administration and 0.40 following oral administration. This indicated that while the metabolism of CCP into Y-516 may occur partly in the liver due to the first-pass effect, it occurs mostly within the gastrointestinal tract itself or its mucosa. When CCP and Y-516 were given orally to man, the plasma concentrations of both parent drugs increased in a dose-dependent manner. The t1/2 of CCP at a dose of 50 mg was 46±6 h (n=3) while that of Y-516 at a dose of 25 mg was 15±2 h (n=5), so that elimination from the circulation was slower than in the dog in both cases. As in the dog, Y-516 was detected in the plasma following administration of CCP, but its concentration was approximately one fifth that of CCP and lower than that found in the dog. From the ratios of Y-516 produced upon oral administration of CCP in dog and man, we concluded that Y-516 is involved to a considerable degree in the pharmacological action of CCP in the dog and, though to a lesser degree, in man as well.     

Recent Trends in the Treatment and Prognosis of Adult Leukemia with Characteristics of Patients in Japan: Transition during the Fifteen Years from 1971 to 1985

Patients with acute (2,569) and chronic (957) leukemia diagnosedat 19 institutes took part in the study on the "MultidisciplinaryTreatment of Leukemia" between 1971 and 1985 and were investigatedretrospectively. By dividing the 15 years into three five-yearperiods, we were able to compare patient ratios in the differentperiods. The proportions of acute to chronic leukemia casesshowed no obvious change; however, the proportions of casesdiagnosed as acute lymphocytic leukemia in acute leukemia showeda significant increase. The main chemotherapeutic drugs usedduring the three time periods were cytarabine or its analogues,the anthracyclines, 6-mercaputopurine and prednisolone, againstacute myelogenous leukemia, and the vinca alkaloids, prednisoloneand the anthracyclines against acute lymphocytic leukemia. Therate of complete remission from acute myelogenous leukemia mademarked progress, from 45.1% during 1971–1975 to 62.3%during 1981–1985, but that of acute lymphocytic leukemiashowed no significant progress, being 65% during 1971–1975and 69.7% during 1981–1985. The durations of remission,however, and the survival times for patients with acute lymphocyticleukemia, as well as for those with acute myelogenous leukemia,became significantly longer over the three periods. Median survivaltimes from chronic myelocytic leukemia were 37–40 mo inall three periods, showing no progress. There was a better prognosisin cases of chronic myelocytic leukemia with, than without,Philadelphia chromosome. Except for a low incidence of chroniclymphocytic leukemia in Japan, adult leukemia patients' characteristicsand prognoses seem to be almost the same in Japan as in theU.S.A. and Europe.