Developmental toxicity potential of grayanotoxin I in mice and chicks

Developmental toxicity potential of grayanotoxin I (GTX I), a toxic diterpenoid contained in plants of the family Ericaceae, with sodium ionophore activity, was studied in mice and chicks. In mice, intraperitoneal injections of 1.5 mg GTX I/kg body weight of mouse for three consecutive days during the organogenetic period caused some dams to die, but neither embryotoxicity nor teratogenicity was detected. In chicks, a single injection of 0.1-1.0 microgram GTX I per egg into the extraembryonic coelom on day 1.5 or 2 of incubation, or into the amnionic cavity on day 3 or 4 of incubation induced neither embryotoxic nor teratogenic signs, but 10 micrograms GTX I per egg showed lethal effects when applied on each of those days.     

Anorexia nervosa with neutropenia--response of neutrophils to G-CSF]

A 50-year-old woman with anorexia nervosa was admitted for evaluation of neutropenia (WBC 1,600/microliters). Her bone marrow was gelatinous, and myeloid cells had decreased. Homogeneous substance deposited in the marrow, stained by alcian blue (pH 2.5), indicative of acid mucopolysaccharides. CFU-G and CFU-GM were decreased in number and myeloid pool in the bone marrow also decreased. Anti-neutrophilic antibody was negative. Neutropenia may be related to myeloid hypoplasia, due to increase of acid mucopolysaccharides replacing adipose cells in the bone marrow under long-term mal-nutritional state. Neutrophils markedly increased by administration of rhG-CSF 5.0 micrograms/kg/day for 14 days without the first peak. Serum G-CSF level did not increase (less than 60 pg/ml). It is effective to administer G-CSF to anorexia nervosa with neutropenia.     

Left ventricular fibroma in an aged patient: Report of a case

We report herein the case of a 77-year-old man with a left ventricular tumor originating from the papillary muscle of the left ventricular wall, in whom a successful tumor resection with mitral valve replacement was performed. The pathological diagnosis of the tumor was confirmed as cardiac fibroma. His postoperative course was uneventful and he is currently well with no signs of recurrence 2 years after surgery.     

-Hydroperoxy diethyl peroxide, an unusual natural compound isolated from an ascidian (Phallusia mammillata): acute toxicity in DDY mice

-Hydroperoxy diethyl peroxide, a novel compound found in the tunic of ascidians, has two peroxide moieties per molecule. Since ascidians are a widely served food item in Japan, human exposure to this compound potentially exists in the seafood preparation industries. No toxicological data have so far been published on this compound, and so we determined the intraperitoneal 6-day LD₅₀ in mice and conducted histopathological examinations. The 6-day LD₅₀, was found to be 199 mg/kg with 95% confidence limits of 126–314 mg/kg. Histopathological examination revealed necrosis induced in a variety of cells that had been directly exposed to the compound. These cells included hepatocytes, parenchymal pancreatic cells and fat cells. It is concluded that direct contact with this compound is likely to elicit cellular necrosis of various organs. The specific toxicological effects are probably dependent on the route of exposure.     

An Experimental Study on the Relationship Between Artificial Korotkoff Sounds and Self-Excited Oscillation Using a Circulatory Simulator

In the medical field, Korotkoff sounds have been explained as sounds generated by the disturbed blood flow in the artery. However, in the biomechanics field, Korotkoff sounds are considered to be produced and/or modified by the self-excited oscillation of a collapsed artery. The self-excited oscillation is an oscillation of the arterial wall. In addition, it is influenced by the nonlinear pressure–flow relationships in the artery and the arterial compliance. In this paper, we proposed an arterial-compliance-measuring method, using Korotkoff sounds. We constructed a circulatory simulator with a brachial model that mimics the physiological circulation, because in vivo resolution of nonlinear pressure–flow relationships is very difficult. The simulator was utilized to generate artificial Korotkoff sounds similar to those in auscultation in the brachial model. Additionally, we prepared latex tubes as artificial brachial arteries. In the experiment, we investigated the relationship between the self-excited oscillation and Korotkoff sounds by the distinguishing its frequency characteristics. The frequency of the sounds was changed by the variation of the tube compliance. As a result, we have found that the changes of the sounds largely depended on the difference of the tube compliance in this simulator. In conclusion, Korotkoff sounds contain useful information for predicting brachial arterial compliance. These experiments indicate the effectiveness of noninvasive measurement for brachial arterial compliance using Korotkoff sounds.     

Maturation of Pulmonary Metastases of Wilms' Tumor after Therapy: A Case Report

A case is reported of Wilms' tumor associated with multiple pulmonary metastases histologically showing maturation of the tumor cells at 9 years after the resection of the primary tumor and intensive therapy. A huge tumor of a 22-month-old patient's right kidney was resected. The tumor was diagnosed as Wilms' tumor of mesenchymal type (stage 1), which consisted of predominantly immature mesenchymal tissue including rhabdomyoblasts, smooth muscle and fibrous tissue, and few blastemal and epithelial components. Intensive preoperative and postoperative chemotherapy with actinomycin D and vincristine and postoperative irradiation therapy totaling 16 Gy were carried out. The patient was regularly followed up uneventfully until 9 years after the surgery. On routine chest x ray at the age of 10 years 11 months, multiple pulmonary nodules were found. The excised nodules from the bilateral lungs disclosed similar histology, exclusively composed of dense collagen bundles and fibrocytes intermingled with mature striated muscle bundles. No immature tumor components were detected. The possible effect of intensive therapy in this maturation was stressed, although spontaneous benign differentiation of tumor cells cannot be excluded.     

Preparation and Characterization of a Murine Monoclonal Antibody (MDR3M) Reactive with mdr3 Gene Product

A murine monoclonal antibody (MDR3M) (isotype: IgM) reactive with mdr3 gene product was generated by immunizing mice with mdr3 -specific peptide (H₂N-¹²WRPTSAEGDFELGISSKQKRKKTKTVKMI⁴¹G-COOH) and hybridizing the primed mouse splenic B cells with X63-Ag8,6.5.3 mouse plasmacytoma cells. MDR3M did not cross-react with mdr1 gene product. This monoclonal antibody may be useful for analyzing the role of mdr3 gene product in cells and tissues.     

Ventilatory effects of dexmedetomidine, atipamezole, and isoflurane in dogs.

Dexmedetomidine (DMED) is a novel alpha 2 adrenergic agonist that has been shown to have potent analgesic and anesthetic sparing effects. This study was designed to investigate the effects of DMED, both alone and combined with isoflurane, on resting ventilation, the hypercapnic response, and the hypoxic response in dogs. When given alone, 1 microgram/kg decreased resting ventilation by 22% but at larger doses (10, 20, and 100 micrograms/kg) resting ventilation increased, doubling at 100 micrograms/kg. Doses of 10 micrograms/kg and greater caused a maximum depression of 60% in the slope of the hypercapnic response, but no dose had a significant effect on the hypoxic ventilatory response. A dose of 3 micrograms/kg of DMED reduced isoflurane MAC from 1.3% to 0.37%, and the ventilatory effects of this 1 MAC combination were intermediate between the awake values and those of isoflurane-anesthetized (1.3%) dogs. Atipamezole is a specific centrally acting alpha 2 receptor antagonist and when given with DMED in isoflurane-anesthetized dogs prevented the ventilatory depression. However, atipamezole alone also ventilatory stimulating effects, which may indicate tonic alpha 2 adrenergic activity. The ventilatory depression caused by DMED, either alone or combined with isoflurane, at doses that significantly reduce anesthetic requirements are relatively mild.     

Cytosolic calcium concentration-force relation during contractions in the rabbit femoral artery: time-dependency and stimulus specificity.

1. By use of front-surface fluorometry with fura-2-loaded rabbit femoral arterial strips, both the cytosolic Ca2+ concentration ([Ca2+]i) and force were simultaneously monitored. By utilizing the [Ca2+]i-force curves, we were thus able to examine the temporal changes in the relationships between [Ca2+]i and force ([Ca2+]i-force relationship) during contractions induced by a high external K+ solution, noradrenaline (NA) and 5-hydroxytryptamine (5-HT). 2. The 'basic' [Ca2+]i-force relationship of the Ca(2+)-induced contractions was obtained by the cumulative applications of extracellular Ca2+ (0-10 mM) during 118 mM K(+)-depolarization (Ca(2+)-contractions). 3. When each vascular strip was exposed to high external K+ (30 mM K(+)-118 mM K+) solutions, the [Ca2+]i abruptly increased until it reached a peak, and then slightly decreased and eventually reached a steady-state level. The force also rapidly rose to reach a maximum plateau level. The changes in [Ca2+]i were more rapid than those in the force. Thus, the [Ca2+]i-force curves observed during the contractions induced by high+ (30 mM-118 mM) solutions showed a counter-clockwise rotation, over time. The entire curve shifted to the right, in a concentration-dependent manner, as compared with the line of the 'basic' [Ca2+]i-force relationship of the Ca(2+)-contraction. However, the [Ca2+]i-force relationship of the steady-state of contractions induced by the single dose applications of high K+ (30 mM-118 mM) overlapped with the line of the 'basic' [Ca2+]i-force relationship of Ca(2+)-contractions. 4. As references, the levels of [Ca2+]i and the force at rest (without stimulation) and at the steady-state of the contractions induced by a single dose application of 118 mM K+ solution were designated as 0% and 100%, respectively. When the vascular strips were exposed to NA (10(-5) M) and to 5-HT (10(-4) M), the [Ca2+]i abruptly rose, and reached a peak (107.1 +/- 5.8%) and 101.3 +/- 2.8%, respectively) after 1 min and 2 min, respectively (the [Ca2+]i-rising phase), and thereafter declined with a similar time course (the [Ca2+]i-declining phase) until reaching a low steady level (the steady-state phase). The force induced by 10(-5) M NA and 10(-4) M 5-HT reached a peak at 4 min (129%) and at 2 min (115%), respectively, and thereafter gradually declined. In contrast to the similarity in the [Ca2+]i transient between NA and 5-HT, the force induced by NA declined more slowly and reached higher steady levels than that seen with 5-HT.(ABSTRACT TRUNCATED AT 400 WORDS)