Changes in peripheral anti-Müllerian hormone concentration and their relationship with testicular structure in beef bull calves.

The aim of this study was to clarify the time-course of changes in anti-Müllerian hormone (AMH) and testosterone (T) concentrations in peripheral blood and to determine the relationships between blood AMH concentration and testicular development during the early postnatal and prepubertal periods in beef bull calves. A total of 17 Japanese Black bull calves were enrolled in this study. The wk in which the calf was born (within 6 d after birth) was defined as M 0. Blood samples were taken once in every mo from M 0 to M 6 from each bull calf, and plasma AMH and T concentrations were determined. Of the 17 calves, 10 were castrated at 6 mo of age (prepuberty) and the right testis was histologically examined. Plasma AMH concentration (means ± SE) at M 0, 1, and 2 were 123.5 ± 9.8, 189.6 ± 18.7, and 254.6 ± 14.1 ng/mL, respectively. From M 0 through M 2, plasma AMH concentration was significantly greater each mo than in the previous mo (P < 0.05); however, plasma AMH concentration significantly decreased over the last 3 mo of the study (P < 0.05). The average age at which plasma AMH concentration was the highest was 2.3 ± 0.1 mo of age. Plasma T concentration significantly increased from M 0 (0.18 ± 0.02 ng/mL) until M 6 (6.52 ± 1.41 ng/mL). Plasma AMH and T concentrations at M 4, 5, and 6 were significantly negatively correlated (P < 0.05). Linear regression did not reveal a significant relationship between Sertoli or Leydig cell numbers and plasma AMH or T concentrations, respectively. In conclusion, blood AMH concentration peaks at 2 mo of age and is negatively correlated with blood T concentration from 4 to 6 mo of age. Although prepubertal blood AMH or T concentrations did not reflect Sertoli or Leydig cell numbers at the end of the prepubertal period, blood AMH concentration may be indicative of abnormal Sertoli cells function.

ARAP3 inhibits peritoneal dissemination of scirrhous gastric carcinoma cells by regulating cell adhesion and invasion.

During the analysis of phosphotyrosine-containing proteins in scirrhous gastric carcinoma cell lines, we observed an unusual expression of Arf-GAP with Rho-GAP domain, ankyrin repeat and PH domain 3 (ARAP3), a multimodular signaling protein that is a substrate of Src family kinases. Unlike other phosphotyrosine proteins, such as CUB domain-containing protein 1 (CDCP1) and Homo sapiens chromosome 9 open reading frame 10/oxidative stress-associated Src activator (C9orf10/Ossa), which are overexpressed and hyperphosphorylated in scirrhous gastric carcinoma cell lines, ARAP3 was underexpressed in cancerous human gastric tissues. In this study, we found that overexpression of ARAP3 in the scirrhous gastric carcinoma cell lines significantly reduced peritoneal dissemination. In vitro studies also showed that ARAP3 regulated cell attachment to the extracellular matrix, as well as invasive activities. These effects were suppressed by mutations in the Rho-GTPase-activating protein (GAP) domain or in the C-terminal two tyrosine residues that are phosphorylated by Src. Thus, the expression and phosphorylation state of ARAP3 may affect the invasiveness of cancer by modulating cell adhesion and motility. Our results suggest that ARAP3 is a unique Src substrate that suppresses peritoneal dissemination of scirrhous gastric carcinoma cells.

Estrogenic activity of 37 components of commercial sunscreen lotions evaluated by in vitro assays.

Thirty-seven chemical components of commercial sunscreen lotions were evaluated for estrogen agonistic and/or antagonistic activity using two in vitro assays, (1) an ELISA-based estrogen receptor competitive binding assay (ER-ELISA) and (2) a modified yeast two-hybrid estrogen assay, with and without addition of a rat liver preparation, S9 mix. Eleven compounds, most of which were benzophenone derivatives and parabens, showed binding affinity to ER by ER-ELISA without S9 mix. Although the activities of almost all of the compounds were attenuated by addition of S9 mix, 4-octylphenylsalicylate and 2,2'-dihydroxy-4,4'-dimethoxybenzophenone acquired estrogenic activity, suggesting metabolic activation of these compounds. Two benzophenones showed agonistic activity in the yeast two-hybrid assay without S9 mix. The activity of one of these was reduced by S9 treatment and a further two benzophenones was activated. Eight parabens were active in this assay without S9 exposure, but their activities were eliminated by S9 treatment. Benzophenones with para-phenolic hydroxyl groups and parabens with branched and/or longer linear chains were generally more potent in both bioassays. In addition, weak antagonistic activity of 4-t-butylphenyl-salicylate, 2-ethylhexyl 4-dimethylaminobenzoate and (+/-)-alpha-tocopherolacetate was observed with S9 treatment. In vivo testing of the compounds reported here to have estrogen agonistic and antagonistic activities is required to confirm their effects at an organismal level.

A comparative study of binding sites for diisopropyl phosphorofluoridate in membrane and cytosol preparations from spinal cord and brain of hens.

Biochemical events in the initiation of organophosphorus induced delayed neurotoxicity (OPIDN) are not well understood. To find new putative target(s) for OPIDN, we investigated the biochemical and pharmacological characteristics of [3H] diisopropyl phosphorofluoridate (DFP) binding to membrane and cytosol preparations from the brain and spinal cord of hens in vitro. [3H]DFP binding to both preparations was determined by the specific binding obtained by subtracting non-specific binding from total binding. The specific binding sites of [3H]DFP were found not only on membrane but also in cytosol. Kd values were higher and Bmax values were lower in cytosol than in membrane. Moreover, the Kd values in both membrane and cytosol preparations from spinal cord were lower than those of brain. The Bmax values in membrane and cytosol were similar between brain and spinal cord. The specific binding to both preparations was markedly displaced by unlabeled DFP. The specific binding of DFP to the membrane was highly or partly displaced by organophosphorus compounds (OPs) or a carbamate, respectively. However, both the OPs and the carbamate had considerably weaker blocking effects on the specific binding of DFP to cytosol. None of the compounds known to interact with neuropathy target esterase (NTE) had a strong blocking effect on the specific binding of DFP to either membrane or cytosol. These results show that the specific binding of DFP to the membrane may be binding with cholinesterase (ChE). However, cytosol, especially in spinal cord, may have DFP binding sites other than ChE and NTE.

Correlation of binding sites for diisopropyl phosphorofluoridate with cholinesterase and neuropathy target esterase in membrane and cytosol preparations from hen.

To find new putative target(s) for organophosphorus induced delayed neurotoxicity (OPIDN), we investigated the biochemical and pharmacological characteristics of [3H] diisopropyl phosphorofluoridate (DFP) binding to membrane and cytosol preparations from the brain and spinal cord of hens. Specific [3H]DFP binding was determined by subtracting non-specific binding from total binding. The binding sites of [3H]DFP, an organophosphate that induces OPIDN, were found not only on membrane but also in cytosol. Reduction of subsequent ex vivo specific [3H]DFP binding by in vivo pretreatment with unlabeled DFP was found in cytosol, not membrane. The reduced binding lasted to the onset of OPIDN, especially in spinal cord. These results suggest that the specific DFP binding sites in cytosol, rather than on membrane, are the most important with regard to the initiation of OPIDN. Inhibitors of cholinesterase (ChE) and neuropathy target esterase (NTE) other than DFP did not affect specific [3H]DFP binding to either membranes or cytosol in vivo. Additionally, inhibition of the activities of these esterases by these compounds was not consistent with either the degree of inhibition of the [3H]DFP binding or a time-dependent manner of OPIDN. These results suggest that DFP binding site(s) involved in the initiation of OPIDN may be different from the active sites of ChE and NTE.

Recent progress in the neurotoxicology of natural drugs associated with dependence or addiction, their endogenous agonists and receptors.

Nicotine in tobacco, tetrahydrocannabinol (delta 9-THC) in marijuana and morphine in opium are well known as drugs associated with dependence or addiction. Endogenous active substances that mimic the effects of the natural drugs and their respective receptors have been found in the mammalian central nervous system (CNS). Such active substances and receptors include acetylcholine (ACh) and the nicotinic ACh receptor (nAChR) for nicotine, anandamide and CB1 for delta 9-THC, and endomorphins (1 and 2) and the mu (OP3) opioid receptor for morphine, respectively. Considerable progress has been made in studies on neurotoxicity, in terms of the habituation, dependence and withdrawal phenomena associated with these drugs and with respect to correlations with endogenous active substances and their receptors. In this article we shall review recent findings related to the neurotoxicity of tobacco, marijuana and opium, and their toxic ingredients, nicotine, delta 9-THC and morphine in relation to their respective endogenous agents and receptors in the CNS.

A possible role of nitric oxide formation in the vasodilatation of rabbit ear artery induced by a topically applied Capsaicin analogue.

Effects of topical application of a capsaicin analogue, nonylic acid vanillylamide (NVA, 0.032-10.0 mM) on the arterial diameter in the ear skin were examined in conscious rabbits using a precise dial caliper. In addition, the possibility of nitric oxide (NO) participating in a vasodilatation induced by low concentrations of NVA was tested by an NO synthase inhibitor. At the lowest concentration of NVA (0.032 mM), no significant change in the diameter was observed after external application of the NVA ointment. At concentrations of 0.32 mM or more, NVA produced a significant vasodilator response. However, at higher concentrations of 3.2 and 10.0 mM, -NVA induced substantial shrinkage in the arterial diameter and oedema formation, which was not affected by L-NAME (NG-nitro-L-arginine methyl ester, 3 mg/kg, i.v.), suggesting fluid leakage induced by oedema from the vessels might suppress the vasodilatation. Thus, the concentration-response curve for NVA was bell-shaped. NVA (0.32 mM)-induced vasodilatation was not significantly affected by atropine (1 mg/kg, i.v.) or propranolol (80 micrograms/kg, i.v.). However, the NVA-induced vasodilatation was completely suppressed by an NO synthase inhibitor, L-NAME (3 mg/kg, i.v.) which had no influence on the resting diameter, but not by an inactive stereoisomer, D-NAME (3 mg/kg, i.v.). These findings suggest that vanilloid receptor activation results in the release of sensory neuropeptides, which in turn stimulate the synthesis of endothelial NO which is responsible for the vasodilatation.

Inhibition of collagen-induced platelet aggregation in Japanese black cattle with inherited platelet disorder, Chediak-Higashi syndrome.

Aggregation properties of platelets were examined in Japanese Black cattle with Chediak-Higashi syndrome (CHS) and normal control cattle. Platelet aggregation induced by collagen was decreased in platelets of the cattle with CHS, but not ADP (10-20 microM), thrombin (0.5-1.0 U/ml) and phorbol-12-myristate 13-acetate (PMA, 3.2 microM). The aggregation response induced by collagen in CHS platelets lacks the change in shape which usually occurs in normal platelets. Simultaneous stimulation by collagen (10 micrograms/ml) + ADP (10 microM) is effective in restoring collagen-induced aggregating response in CHS platelet, although pretreatment of ADP (10 microM) could not restore the collagen (10 micrograms/ml)-induced aggregating response, suggesting that there is a certain threshold of stimulation intensity above which collagen-induced aggregation of CHS platelet can begin. Control normal platelets, previously exposed to ADP (10 microM) and collagen (10 micrograms/ml), showed no further response to exposure to a third aggregating agent (arachidonic acid, 5 mM). On the other hand, the final agent was able to elicit aggregating responses in CHS platelets, suggesting that the arachidonate aggregating system may be suppressed in CHS cattle, but fully activated in control animals. Furthermore, normal platelets showed a significant decrease in aggregating response to collagen when pretreated with a cyclooxygenase inhibitor, indomethacin (10(-5) M), whereas CHS platelet was insensitive to indomethacin. This indomethacin-treated normal platelet mimicked the CHS collagen-induced aggregation pattern. These data suggest that a signal transduction process from receptor-operated events to arachidonate metabolism is suppressed in collagen-induced CHS platelet aggregation.

Suppression of polymorphonuclear leucocyte chemotaxis by Pseudomonas aeruginosa elastase in vitro: a study of the mechanisms and the correlation with ring abscess in pseudomonal keratitis.

Bacteria, or the culture supernatants of an elastase non-producing strain of Pseudomonas aeruginosa, elicited a chemotactic response from polymorphonuclear leucocytes (PMN) in vitro. The chemoattractive capacity was diminished under the presence of Boc-Phe-Leu-Phe-Leu-Phe, a receptor antagonist of N-formyl-Met-Leu-Phe (fMLP) which is a bacterial chemotactic peptide to PMN. This indicated that the chemoattractant derived from Pseudomonas aeruginosa was a fMLP-like molecule(s). In contrast, culture supernatants of an elastase producing strain of Pseudomonas aeruginosa produced negligible chemotactic response from PMN. Indeed, an inhibitory effect of the culture supernatants or of purified Pseudomonas aeruginosa elastase (PAE) on PMN chemotaxis was observed when fMLP was used as a chemoattractant. Another fMLP-induced function of PMN, respiratory burst activation, was also diminished by pretreatment of PMN with PAE. PAE hydrolysed fMLP at the Met-Leu bond and diminished the chemoattractant capacity. In addition, a receptor analysis with fML-3H-P demonstrated a decrease in numbers of fMLP receptors on PMN without changing the dissociation constant values after the treatment of the cells with PAE. In the primary structure of the fMLP receptor previously reported, a preferential amino acid sequence for cleavage by PAE was identified in what was believed to be an extracellular portion of the receptor molecule. These results suggested that PAE could diminish PMN infiltration in response to Pseudomonas aeruginosa in vivo by cleavage of the fMLP-like pseudomonal chemotactic ligand and the receptors on PMN.

Therapeutic intervention with chicken egg white ovomacroglobulin and a new quinolone on experimental Pseudomonas keratitis.

BACKGROUND: Chicken egg white ovomacroglobulin (ovoM) is a potent protease inhibitor with broad-spectrum activity against various proteases. The combined effects of ovoM and the new quinolone, ofloxacin (OFLX) on experimental Pseudomonas aeruginosa keratitis were investigated. METHODS: The in vitro inhibitory effects of ovoM on protease activity in culture fluid of clinically isolated P. aeruginosa and on activity of human neutrophil elastase and cathepsin G were assayed using azo-casein as substrate. Albino rabbits received intrastromal injection of the isolated Pseudomonas strain (1 x 10(5) colony-forming units). At 16 h after inoculation, three treatment groups--0.1% ovoM alone, 0.3% OFLX alone, and a combination of both--and a non-treatment control group were tested. RESULTS: Protease activity in the culture solution and human neutrophil elastase was inhibited by ovoM, whereas cathepsin G was not inhibited effectively. In vivo additive therapeutic effects of ovoM and OFLX were observed at 96 h (P < 0.05 compared with OFLX alone). CONCLUSION: The results indicate that inhibition of proteolytic activity with ovoM is useful in preventing stromal degradation in P. aeruginosa keratitis.

The role of Pseudomonas aeruginosa elastase in corneal ring abscess formation in pseudomonal keratitis.

In order to identify the causative factors of ring abscess, which is the characteristic feature of pseudomonal keratitis, pseudomonal endotoxin, exotoxin A, and elastase were each separately injected into guinea pig cornea. There was no formation of ring abscess. Injection of living Pseudomonas aeruginosa strains IFO3455 and Takamatsu which produce all three molecules, clearly induced ring abscess. In contrast, when heat-killed bacteria strain IFO3455 or living bacteria of the non-elastase-producing strain PA103 were injected, ring abscess was not induced. Furthermore, when living bacteria strain IFO3455 were injected with anti-elastase antibody or a protease inhibitor, ovomacroglobulin, ring abscess formation was significantly inhibited. Histological examination demonstrated that the ring abscess was a dense accumulation and aggregation of polymorphonuclear leukocytes (PMN) with debris of cells and lamellae in the deep stroma at the corneal margins, suggesting prevention of PMN migration to the central lesion. The presence of anti-elastase antibody or a specific elastase inhibitor facilitated PMN migration towards living bacteria strain IFO3455 in an in vitro model. These results indicate that pseudomonal elastase is a necessary but not sufficient factor in the formation of ring abscess in pseudomonal keratitis.

[Results of electron beam irradiation for tongue cancer].

One hundred and eighty three patients with squamous-cell carcinoma of the tongue were treated with electron beam irradiation at the Dept. of Radiology, Nihon University School of Medicine, from 1967 to 1988. We analyzed the therapeutic results of the investigation to find out indications of squamous-cell carcinoma of the tongue to see if it could be treated by intra-oral cone irradiation with electron beam (IOC). The patients were restaged, as follows: stage I, 38 cases: stage II, 64 cases: stage III, 58 cases: stage IV, 23 cases. There were 113 males and 70 females, ranging in age from 18 to 87 years old. IOC was applied for T 1 or smaller T 2 cases. External neck irradiation and IOC were combined for larger T 2, T 3 or T 4 cases. The two-year local-control rates for primary lesions with the present method were 85% for T 1, 73% for T 2, and 58% for T 3. There were no two-year local-control cases for T 4. Clinical feature of the tumor were classified into tumourous type, small ulcerating type, and large ulcerating type. The two-year local-control rates were as follows: 80% for tumorous types, 68% for small ulcerating types and 53% for large ulcerating types. Uneven fractionated irradiation was performed on 144 cases and even fractionated irradiation was performed on 39 cases. The two-year local-control rates were as follows: 68% for uneven fractionated irradiation cases, 61% for even fractionated irradiation. In T 2 and T 3 cases, the two-year local-control rates were as follows: 77%, 63% for uneven fractionated irradiation cases, 56%, 40% for even fractionated irradiation cases. The two-year local-control rates were increased by uneven fractionated irradiation for T 2, T 3 cases (P < 0.05). We analyzed the therapeutic results in details for T 3 cases. T 3 patients were classified into two categories according to tumor size (category 1: long axis X short axis > 1000mm2: category 2: long axis X short axis < or = 1000mm2). The two-year local-control rates were 48% for category 1, and 72% for category 2. T 3 patients were classified into two categories according to clinical feature of the tumor (tumors with ulcers and tumors without ulcers). The two-year local-control rates were 43% with ulcers, and 74% without ulcers. The actuarial five-year survival rates were 92% for stage I, 72% for stage II, 67% for stage III, and 12% for stage IV.(ABSTRACT TRUNCATED AT 400 WORDS)

[Usefulness of electrocardiogram gated 99mTc-methoxy isobutyl isonitrile (MIBI) single photon emission computed tomography for detection of wall motion abnormality of left ventricle].

We evaluated whether the newly developed perfusion imaging agent "99mTc-methoxy isobutyl isonitrile (MIBI)" has a possibility to detect wall motion abnormality of left ventricle. Electrocardiogram (ECG) gated single photon emission computed tomography (SPECT) was performed in 6 patients with myocardial infarction (anterior: 3 and inferior: 3). Apical and basal short axis images were selected from each patient and circumferential analysis was performed on end-diastolic (ED) and end-systolic (ES) images respectively. Count in end-diastole (EDC) and count in end-systole (ESC) were obtained, then % (ESC-EDC) and (ESC-EDC)/EDC were calculated. Wall motion of left ventricle was evaluated by either ultrasonic cardiogram or left ventriculography. Left ventricle was divided into anterior, septal, posterior and lateral areas and then each area was divided into apical and basal segments (finally the heart was divided into 8 segments). Of 48 segments, 33 segments showed normal wall motion and 15 segments showed abnormal wall motion: hypokinesis, akinesis and dyskinesis. % (ESC-EDC) was 74.39 +/- 16.85% in segment of normal wall motion and 33.27 +/- 23.56% in segment of abnormal wall motion (p < 0.001). (ESC-EDC)/EDC was 48.67 +/- 13.35% in segment of normal wall motion and 23.33 +/- 18.83% in segment of abnormal wall motion (p < 0.001). From these data, lower limit of % (ESC-EDC) and (ESC-EDC)/EDC in normal wall motion was defined as 40 and 22 respectively: mean -2SD of normal wall motion. Sensitivity of diagnosis of abnormal wall motion was 73% in % (ESC-EDC) and 60% in (ESC-EDC)/EDC (n.s.). Specificity was 94% and 97% (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Chronological changes of MRI findings on striatal damage after acute cyanide intoxication: pathogenesis of the damage and its selectivity, and prevention for neurological sequelae: a case report.

A 31-year-old male technician in an electroplating factory, who had been suffering from the temporal lobe epilepsy for 24 years and from hypertension for 2 years, took an unknown amount of potassium cyanide apparently over the lethal dose, in an attempt to commit suicide. He was treated successfully and survived without any neurological sequelae. The electroencephalograms and the nature of the seizures were not different before and after the poisoning. The T2-weighted magnetic resonance images at 9 and 51 days after the poisoning showed bilateral elevation of signals in the caudate nuclei and the putamina. At the 143th and 286th days. T2-weighted high-resonance areas were restricted to the lateral portion of the putamina. The T1-weighted images at the 51st day showed abnormal signal elevations in both putamina, while those of 9th, 143th and 286th days were mainly normal. Selective vulnerability of the putamen and the caudate nucleus may be due to their specific structural properties of high oxygen and glucose utilization, and enzyme distribution. Both chronological changes of striatal damage and the absence of neurological sequelae in this patient suggest the possibility that anti-epileptics and a calcium antagonist played a neuroprotective role in the acute cyanide intoxication.

[Effects of contrast media under systemic heparinization on blood coagulation and fibrinolytic system during angiocardiography--comparison of ionic and nonionic contrast media].

Nonionic contrast media are suggested to cause increased thromboembolism (in vivo), because of less inhibitory action on blood coagulation and platelet aggregation (in vitro) as compared with ionic contrast media. Therefore, to prevent thrombotic complication, we examined whether differences in blood coagulation and fibrinolytic system between the two groups received nonionic (iopamidol) and ionic (ioxaglate) contrast media are seen in vivo when 2,500 unit heparin is administered during angiocardiography. 20 patients undergoing routine angiocardiography were randomized to two groups of 10 patients each. Blood heparin concentration, activated partial thromboplastin time, prothrombin time, thrombin-antithrombin III complex (TAT), antithrombin III, fibrinogen, alpha 2-plasmin inhibitor plasmin complex, fibrinogen and fibrin degradation product were measured at four stages during the procedure: before and 5 min after 2,500 unit bolus heparin administration, 5 min after left ventriculography, and at the end of procedure. Systemic heparinization inhibited clot formation in the presence of nonionic contrast media. TAT generations were elevated before heparinization, after heparinization, however these generations were remarkably inhibited in both groups. No remarkable differences were noted at 40 +/- 14 min duration of procedure when these parameters were compared between the two groups. Since nonionic contrast media did not activate blood coagulation and fibrinolytic system with 2,500 unit heparin administration as compared with ionic contrast media, systemic heparinization was demonstrated to be effective in the prevention of thrombotic complication.

[Property of electrocardiogram gated single photon emission tomography by 99mTc-methoxy isobutyl isonitrile].

99mTc-methoxy isobutyl isonitrile (MIBI) is a new developed myocardial perfusion imaging agent. Because this compound has higher photon energy than thallium (Tl), electrocardiogram gated single photon emission tomography (SPECT): end-diastolic (ED) and end-systolic (ES) short axis (SA) images could be taken. To investigate property of gated MIBI SPECT, MIBI myocardial scintigraphy, Tl scintigraphy (TMS) and analysis of left ventricular wall motion were performed in 6 patients with myocardial infarction. Left ventricle was divided into 8 segments. Perfusion defect (PD) was scored: "0" (normal), "1" (hypo-perfusion), "2" (defect). Wall motion abnormality (WMA) was also scored: "0" (normokinesis), "1" (hypo-kinesis), "2" (a-, dys-kinesis). Severity and extent of PD and WMA were calculated. Severity of WMA was 3.0 +/- 2.0 (M +/- SD), severity of PD was 3.3 +/- 1.7 in TMS, 3.7 +/- 1.3 in no-gated MIBI, 5.0 +/- 0.6 in ES-MIBI, 7.3 +/- 2.0 in ED-MIBI. Extent of WMA was 2.3 +/- 1.0. Extent of PD was 2.5 +/- 1.3 in TMS, 3.0 +/- 1.6 in no-gated MIBI, 3.5 +/- 0.8 in ES-MIBI, 4.8 +/- 1.0 in ED-MIBI. Compared with wall motion abnormality, severity and extent of PD in ED-MIBI was larger. From our data, it is concluded that perfusion defect in ED-MIBI was overestimated significantly. When we evaluate gated MIBI image, we must consider this property.

[Multi-institutional trials of radiation and Furtulon combination therapy for malignant tumors].

The efficacy of the response and safety in combination therapy of radiation and furtulon, a derivative of fluoropyrimidine, for malignant tumors were tested on a multi-institutional basis. Patients in this study were given daily 800 mg of oral furtulon and also irradiations. Twenty-three out of 30 evaluable cases showed CR or PR response (response rate was 77%). The response rates of the cases classified into regions of primary sites were 67% of stomach (4/6), 57% of colorectum (4/7), 100% of breast (9/9), 67% of esophagus (4/6), 100% of ovary (1/1) and 100% of lung (1/1). Four out of 36 cases were not given the full scheduled treatments due to grade 3 side effects, consisting of one diarrhea case suspected due to furtulon side effect, 2 impaired general condition cases according to the progression of diseases, and one case showing radiation dermatitis, dysphagia due to radiation mucositis and leukocytopenia. These results show that the combination therapy of radiation and furtulon is an efficacious and safe modality for primary and metastatic tumors.

[Effects of uro-angiographic contrast media on blood coagulation--a scanning electron microscopic study on time dependent changes of blood clot and a clinical study].

Anticoagulant activity of ionic and nonionic contrast media (CM) was investigated in vitro and in vivo. Based on the time course of FPA and TAT generations and gross examinations of the blood clots on the catheters placed in CM-blood mixtures [an 2 to 8 ratio (20% v/v)]. It was demonstrated that blood coagulation was activated during the period of 20 to 30 minutes when nonionic CM (iopamidol, iohexol) was employed, but no activation of blood coagulation was noted with ionic CM (diatrizoate, ioxaglate). Scanning electron microscopic examinations of the clots on the catheters revealed that fine fibrin meshwork fibers, in which many red blood cells were trapped in bound, were observed with nonionic CM. In contrast, no fibrin mesh was formed with ionic CM after 30 minutes. In vivo, antithrombin III and fibrinogen significantly decreased in the patients who underwent infusion of nonionic CM. Our studies confirmed that nonionic CM show weaker anticoagulant activity than do ionic CM. And these findings account for previous reported thromboembolic complications with the use of nonionic CM. Extreme caution should be therefore exercised when nonionic CM are employed during prolonged angiographic and interventional procedures.

[Experience of multimodal therapy for advanced neuroblastoma].

The prognosis of advanced neuroblastoma is extremely poor. We treated 5 patients with advanced neuroblastoma, older than 3 years, with multimodal therapy including intraoperative irradiation and autologous bone marrow transplantation. Elevated serum NSE and ferritin level and unfavorable histology according to the Shimadas histological classification, all of which are indicators of poor prognosis, were found in all of them. N-myc oncogene was amplified in 3 cases. After preoperative intensive induction chemotherapy, delayed primary operation and intraoperative irradiation (10-15 Gy) were performed. The postoperative lethal dose chemotherapy and total body irradiation (33 Gy x 3 days) were followed by autologous bone marrow transplantation. Tumor cells were purged using immunomagnetic beads method. Two cases showed recurrence (brain; 1, bone and bone marrow; 1) and a metastatic brain tumor was extirpated completely. All of them are alive during the follow up period from 6mo. to 4y8mo. (mean; 2y5mo.) with no evidence of disease except one. It may be concluded that our multimodal therapy is effective in achieving better results for advanced neuroblastoma.