Ustiloxins, antimitotic cyclic peptides from false smut balls on rice panicles caused by Ustilaginoidea virens.

Ustiloxins A (1a), B (1b), C (1c), D (1d) and E (1e), antimitotic peptides, have been isolated from the water extract of false smut balls caused on the panicles of rice plant by a fungus Ustilaginoidea virens. The structure of 1b was assigned from its spectral property and its amino acid analysis in relation to 1a whose structure was determined previously by a combination of X-ray crystallographic and amino acid analyses. Structures of 1c and 1d were elucidated by their spectroscopic data, specially based on their 1H and 13C NMR spectra. Bioactivities of these compounds against microtubule assembly as well as mammal, plant and fungal cells have been studied.

"Lupinosis"-like lesions in mice caused by ustiloxin, produced by Ustilaginoieda virens: a morphological study.

A crude toxin, obtained by methanol-extraction of a water extract of false smut balls (INA-KOUJI in Japanese) caused by Ustilaginoidea virens on rice panicles, was injected into mice intraperitoneally. Single injection of 100 or 200 mg/kg body weight of the extract was not lethal but caused acute, occasional necrosis of hepatocytes and renal tubular cells, followed by increased number of mitotic figures with occasional multinuclear giant cells. Erosions and ulceration of the forestomach and atrophy of the thymus were observed a week later. Repeated intraperitoneal injection of the crude toxin at the levels of 12 and 25 mg/kg body weight induced more severe necrosis of the liver and kidneys, with delayed occurrence of mitosis. Forestomach erosion also occurred. Serial injection for 10-12 days of either 3 or 6 mg/kg of the crude extract or 400 micrograms/kg of ustiloxin A, using the purified crystals, caused relatively mild but definite liver and kidney lesions similar to those described above. The lesions in the liver and kidney were quite similar to those observed in lupinosis caused by phomopsin A, a mycotoxin produced by Phomopsis leptostromiformis. Isolation of the toxic substance indicates that the contaminated rice panicles may cause toxicosis of cattle, although no field outbreaks have occurred yet.

Differences in growth of transplantable ascites hepatoma among various lines of Donryu rat.

A total of 48 Donryu rats from 8 colonies of 5 lines were inoculated intravenously with 10(7) cells of the ascites hepatoma strain AH 66. All the conventional rats of the lines D-1 and D-2 died between 9 and 15 days after inoculation with a good growth of implanted tumor cells. On the other hand, SPF rats of the lines A-1, B-1, C and E survived for 60 days showing complete rejection of the implanted tumor cells. A 50% of conventionalized ex-SPF rats of the lines A-2 and B-2, which had been once established as SPF colonies, and thereafter had been "re-conventionalized", rejected the tumor cells. The present observations indicate that the microbial conditions of the animal, e.g. whether the animal is SPF or not, might play an important role in the growth of the implanted ascites hepatoma.

Clinical characteristics of prostatic cancer detected by mass screening.

Since 1981 we have been studying prostate cancer (Pca) by mass screening in three cities, eight towns and seven villages in Gunma prefecture, Japan. From 1981 to 1985, 5,770 subjects were examined. The clinical character of Pca detected by mass screening is compared with control (i.e., Pca detected in the outpatient clinic in Gunma University). Of the 54 Pca patients detected by mass screening (Stage B: 28, C: 8, D: 18), approximately 50% had early-stage Pca. The ratio of early-stage Pca is significantly higher than in the control. An extended survival rate in high-stage Pca detected by mass screening also was observed through comparison with control. We determined two types of Pca in advanced stage: (1) asymptomatic or less symptomatic and better prognostic Pca found in mass screening and (2) symptomatic and worse prognostic Pca found in control.

[Study of voiding disturbances in elderly males. III. Analysis of flow rates and patterns in uroflowmetric studies: comparison between children, young adults and elderly men].

We performed uroflowmetric study in 8 boys (7 approximately 14 years old), 20 young adults (19 approximately 39 years old) and 552 elderly men (40 approximately 93 years old) with a DISA 21C10 mictiometer, and obtained 753 studies. Uroflowmetric studies were classified into 6 patterns: N type (normal), NB type (neurogenic bladder: wave-like curve), OB type (obstructive diseases: flat curve), AP type (anterior peak), PP type (posterior peak) and OT type (others). We studied the relationship between age and uroflowmetry with patterns and flow rates (maximum flow rate = MFR, average flow rate = AFR). In men over 19 years old, flow rates (MFR, AFR) decreased proportionally with age (MFR: 2.9 ml/s/10 years old, AFR: 1.6 ml/s/10 years old). In elderly men (over 40 years old), the N type flow curve decreased and OB type flow curves increased gradually with age.

Studies on macrocyclic lactone antibiotics. VIII. Absolute structures of rhizoxin and a related compound.

The absolute structure of rhizoxin, a potent antifungal and antitumor antibiotic, was determined by interrelation with compound 2 whose structure was established by X-ray analysis. Since a 18OH group was introduced at C-3 on a hydrolytic cleavage of C-2, C-3 epoxy group with alkaline H2(18)O, the original epoxy oxygen should be retained at C-2. The stereo-chemistry at C-2 and C-3 positions in rhizoxin was, therefore, determined as 2R,3S.

Rhizoxin, a macrocyclic lactone antibiotic, as a new antitumor agent against human and murine tumor cells and their vincristine-resistant sublines.

Rhizoxin, isolated from a plant pathogenic fungus which causes rice seedling blight, inhibits the mitosis of the tumor cells in a manner similar to that of Vinca alkaloids as revealed by morphological study and flow cytometry analysis. This new 16-membered macrocyclic lactone showed similar chemotherapeutic effects to those of vincristine against L1210 and P388 leukemia-bearing mice. The drug is also effective against B16 melanoma inoculated i.p. or s.c. Rhizoxin, in contrast to the ansamacrolide, maytansine, was effective against human and murine tumor cells resistant to vincristine and Adriamycin in vitro and in vivo. A maximum 60% increase in life span was obtained in mice inoculated with P388 leukemia resistant to vincristine. Rhizoxin showed greater cytotoxicity in cultured tumor cells than did vincristine. Rhizoxin seems to bear consideration for further development as a new chemotherapeutic agent.

[Study on voiding disturbance in elderly males. II. Analysis of the patterns in uroflowmetric studies in patients with obstructive diseases in lower urinary tract and neurogenic bladder].

Uroflowmetry was examined in 192 patients with obstructive urinary symptoms. They were 173 males with obstructive diseases in lower urinary tract (302 uroflowmetric studies) and 19 males with neurogenic bladder (29 uroflowmetric studies). We classified the patterns of uroflowmetric curve into 6 types: N type (normal), NB type (neurogenic bladder: wave like curve), OB type (obstructive diseases: flat curve), AP type (anterior peak), PP type (posterior peak) and OT type (others). The 331 uroflowmetric curves were classified into the above 6 types, and the relationship between each type of flow curve and other uroflowmetric parameters (voided volume = VV, residual urine volume = RU, maximum flow rate = MFR, average flow rate = AFR) was analyzed. The types of 229 flow studies (140 patients) in benign prostatic hypertrophy were OB (77.7%), AP (16.6%), OT (3.9%), N (0.9%) and PP (0.9%). The types of 39 flow studies (25 patients) in prostatic cancer and 13 studies (8 patients) in urethral stricture were similar; 92.3% of the flow studies being classified into OB type. The types of 21 flow studies (10 patients) in so-called bladder neck contraction were OB (42.9%), AP (33.3%), OT (14.3%) and NB (9.5%). AP type flow curves were more frequent than other in obstructive diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on macrocyclic lactone antibiotics. VII. Structure of a phytotoxin "rhizoxin" produced by Rhizopus chinensis.

A new 16-membered macrolide designated as rhizoxin was isolated as a toxin produced by Rhizopus chinensis, the causal agent of rice seedling blight . The skeletal structure was determined by detailed NMR spectroscopic investigation of this compound and of its derivatives. Rhizoxin induced at a concentration of 10 ng/ml abnormal swelling of rice seedling roots, which is one of the characteristic symptoms of this disease. This compound also exhibited potent antifungal activity but little effect against bacteria.

A case of juxtaglomerular cell tumor diagnosed preoperatively.

A case of juxtaglomerular cell tumor, the fourth case in the world diagnosed preoperatively, was reported. Neither strict sodium restriction nor loading of upright position increased a grade of hyperreninemia observed at recumbant position on ordinary diet, but Pald elevated in response to them. Abnormal glucose tolerance was considered to be due to hypopotassemia. Selective renal arteriography revealed a small number of tumor vessels, a lucent area on the nephrogram and early appearance of the renal vein of the diseased side. Histologically, the tumor contained some canalicular structures among the polygonal nonepithelial tumor cells with rhomboid bodies. These findings suggested that this tumor was a hamartoma originated from the juxtaglomerular apparatus.

[A new method of autotomography in cerebral angiography (author's transl)].

Acompanied with the recent advances of various techniques of cerebral angiography, the angio-tomography is now going to be recognized as one the significant techniques. But, this angio-tomography requires a special work place with tomographic equipment. Thus the applicability of the method is now limited as far as the routine use is concerned. So, the technique of autotomography is often tried as a convenient substitute for the angiotomography, because this technique is very simple and does not need any special facilities. But, as the autotomography is only possible to take the midline tomogram, it's application is strictly limited. So, we have invented a new method of the autotomography using a simple device. This device is constituted of two portions; one is a plate of rotation, and the other is a box to fasten a patient's head. By sliding the box on the plate, it is possible to move the rotatory axis to the aimed portion of the head. In this way, it is possible to take an arbitrary tomographic plane. As our device is simple and it's use is very easy, this method of the autotomography is possible to apply in a routine examination. This report describes the principle and the method of the use of our new device and demonstrates several films taken by this method.