Chromosome aberrations induced by benzo(a)pyrene in a feeder cell-mediated assay

Studies were made on chromosome aberrations induced by benzo(a)pyrene (Bp) in V79 cells in the presence or absence of feeder cells. In the presence of feeder cells, chromosome aberrations at Bp concentrations of 1.0–20.0 μg/ml depended on feeder cell density. The highest incidences of chromosome aberrations (aberrant cells) and of aberrant chromosomes per 100 metaphase cells were 24.0% and 38.0%, respectively, and were obtained at 20.0 μg/ml Bp in the presence of 2.0 · 10⁶ feeder cells/60-mm plastic dish. In the absence of feeder cells, chromosome aberrations were not induced; the incidences of aberrant cells and chromosomes on treatment with Bp in the absence of a feeder layer were 3.0–5.0 and 3.0–6.0%, respectively, while the spontaneous rates (of both) were 5.0%.     

Plasma insulin and free fatty acids in young people with postprandial glycosuria: Plasma insulin response in the cases with borderline glucose tolerance test

Summary Plasma immunoreactive insulin and free fatty acid (F.F.A.) responses to an oral glucose load were observed in young students with glycosuria and with glucose intolerance of a slight degree. — The groups with a diabetic or a borderline glucose tolerance test (G.T.T.) had a delayed and protracted plasma insulin and F.F.A. response. Both responses were significantly greater than in the control group. The result indicates that a sluggish but high rise and a delayed fall of plasma insulin during the glucose load is characteristic of chemical diabetics and this tendency is seen in the cases with a borderline G.T.T. — The subjects with oxyhyperglycemic G.T.T. also had an initial delay in the insulin response and the peak was distinctly higher than in the control, but the fall was sharp. This suggests that oxyhyperglycemia is one of the preceding states of diabetes. — The subjects with renal glycosuria, in the definition of Lawrence, had a high-normal G.T.T., but their insulin and F.F.A. responses showed no difference from those of the normal.     

Comparison of neuropathic pain induced by the application of normal and mechanically compressed nucleus pulposus to lumbar nerve roots in the rat.

We studied whether applying nucleus pulposus tissue, obtained from tail intervertebral discs that had been subjected to chronic mechanical compression, to the lumbar nerve roots produces hyperalgesia, which is thought to be a pain-related behavior in the rat. An Ilizarov-type apparatus was used for immobilization and chronically applied compression of the rat tail for eight weeks. Three weeks after application of extracted nucleus pulposus tissue on the lumbar nerve roots, motor function, sensitivity to noxious mechanical stimuli was measured. Eight weeks after application of the apparatus, the instrumented vertebrae were resected and sections were stained with hematoxylin and eosin to evaluate degeneration of the intervertebral disc. Mechanical hyperalgesia observed in rats treated with the compressed nucleus pulposus tissue was greater and of longer duration than in the rats treated with normal and non-compressed discs. The nucleus pulposus in the instrumented vertebrae showed some histological degeneration. In conclusion, chronic mechanical compression of nucleus pulposus, which resulted in degeneration to some extent, enhanced mechanical hyperalgesia, which was induced by application of nucleus pulposus on the nerve root in the rat. Degenerative intervertebral discs might induce more significant pain than normal intervertebral discs.     

Stimulation of growth by both androgen and estrogen of the EMP-K1 transplantable tumor with androgen and estrogen receptors from human extramammary Paget's disease in nude mice.

BACKGROUND: Experimental approaches using transplantable human tumors in nude mice have greatly improved studies on their pathogenesis and treatment. PURPOSE: We studied the establishment of a transplantable tumor, EMP-K1, derived from extramammary Paget's disease and the morphology and unique hormone dependence of this tumor. METHODS: Tissue fragments from a metastatic skin tumor of an 80-year-old man with primary genital extramammary Paget's disease were implanted into male nude BALB/c mice. Tissue fragments of the established tumor were implanted into 50 castrated male 8-week-old nude mice, which were given injections of 100 micrograms testosterone propionate (TP), 100 micrograms 5 alpha-dihydrotestosterone (DHT), 10 micrograms diethylstilbestrol (DES), or 1, 10, or 100 micrograms 17 beta-estradiol (E2). All injections were administered intramuscularly once daily, starting from the day of transplantation. The established tumors were examined immunohistochemically and biochemically. RESULTS: A transplantable tumor (EMP-K1) was established in the nude mouse. EMP-K1 tumor cells expressed antigens such as carcinoembryonic antigen and epithelial membrane antigen, cytokeratin, and c-erbB-2 protein and contained androgen, estrogen, and progesterone receptors. The growth of the EMP-K1 tumor was stimulated by TP, DHT, DES, and E2. CONCLUSIONS: These results suggest that both androgen and estrogen may stimulate the growth of the same tumor by both androgen receptor and estrogen receptor pathways. IMPLICATIONS: The EMP-K1 tumor is a useful tool for studies on the biology of extramammary Paget's disease, and further studies using these tumors will provide useful information concerning proper hormone therapy.     

Experimental minute gastric cancer induced by N-ethyl-N'-nitro-N-nitrosoguanidine in dogs

150 micrograms/day of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) was administered to a total of 8 dogs, (4 mongrels at age of 4 months and 4 beagles at age of 6 months) over a period of 8 months by Kurihara 's method. As a result of the administration, we found development of minute cancer as follows: In 3 animals, male beagle killed at 575th day, male mongrel at 1, 105th days and male mongrel at 1, 245th days, a total of 20 neoplasms of the stomach was found (18 early cancers and 2 advanced cancers). 13 of which being the minute cancer measuring less than 0.5 cm. There were 11 mucosal cancers and 2 submucosal cancers. When classified by the macroscopic pathological type, none was classified as the elevated type (I, IIa types), 5 lesions as the flat type (IIb type), and 8 lesions as the depression type (IIc type). Two lesions of submucosal cancer belonged to IIc type. When classified by the histological type, 2 were classified as papillary adenocarcinoma, 2 as well differentiated tubular adenocarcinoma, 1 as moderately differentiated tubular adenocarcinoma, 5 as poorly differentiated adenocarcinoma and 3 as signet-ring cell carcinoma.     

Accelerating effects of pentobarbitone on the inactivation process of the calcium current in Helix neurones.

The effect of pentobarbitone on Ca2+ current (ICa), separated from other ionic currents was studied under voltage clamp using a suction pipette technique in Helix neurones. Pentobarbitone depressed the maximal peak amplitude (MPA) of ICa in a concentration-dependent manner without shifting the current-voltage (I-V) relationships along the voltage axis. Increases in external Ca2+-concentration [( Ca2+]o) overcame the inhibitory action of the agent on MPA. Pentobarbitone markedly accelerated the decay phase of ICa which took a distinctly different time course from that of the control. The accelerating action of the agent on the decay phase of ICa was not overcome by increases in [Ca2+]o. In the presence of internal EGTA (20 mM), pentobarbitone also accelerated the decay of ICa. Changes in pH of the external perfusing solution altered the potency of pentobarbitone in depressing MPA; in the presence of pentobarbitone (3 X 10(-4) M) at pH of 7.0, 8.0 and 9.0, fractional inhibition was approx. 46%, 21% and 4%, respectively. Internal application of pentobarbitone (10(-4)-10(-3) M) inhibited MPA, but exerted no effect on the decay phase of ICa. Pentobarbitone (10(-4) M) markedly accelerated the decrease of MPA of ICa induced by repetitive stimuli applied at an interval of 150 ms, indicating a use-dependent depression of MPA. Results provide evidence that pentobarbitone has a dual action on ICa, inhibiting MPA and accelerating the decay phase of ICa.     

Zinc metabolism in thyroid disease.

This study was designed to evaluate the zinc metabolism in adults of both sexes with thyroid disease. Plasma and erythrocyte zinc concentration and urinary zinc excretion were investigated. The mean concentration of plasma zinc in hypothyroid patients and in euthyroid patients, previously either hyperthyroid or hypothyroid, was lower than that of control subjects, whereas no statistically significant differences were observed in plasma zinc values between hyperthyroid patients and control subjects. The average erythrocyte zinc level in patients with thyroid disease was significantly lower than that in control subjects. Erythrocyte zinc concentration was significantly decreased in hyperthyroidism compared with hypothyroidism, or patients previously either hyperthyroid or hypothyroid but now euthyroid. Increased urinary zinc excretion in hyperthyroidism was noticed compared to euthyroid and hypothyroid patients and to control subjects. Increased urinary zinc concentrations may result from increased tissue catabolism such as muscle. The results of this study suggest that abnormal zinc metabolism occurs commonly in patients with thyroid disease.