Estradiol binding to nuclear receptors in human breast cancer tissue (MCF-7 cell line) and in dimethylbenz(a)anthracene-induced mammary carcinoma.

PIP: The presence or absence of estrogen receptors in the nuclei of human breast tumor may be a useful tool in determining whether the tumor will or will not respond to endocrine therapy. This paper describes an assay which measures both unoccupied and occupied nuclear receptors in human breast cancer tumors. The assay was predicated on the fact that at low salt concentration, the nuclear receptor is bound to chromatin particles and can be separated from the soluble components containing proteolytic acitivity. Nuclear estradiol receptors were measured in human breast cancer tissue (MCF-7 cell line) and in DMBA (dimethylbenz(a)anthracene-induced rat mammary carcinomas) tumors. Complete translocation of the cytoplasmic receptor in the MCF-7 cells was observed compared to only 35-50% of the cytoplasmic receptors seen in the nucleus of the DMBA tumor after estradiol injection. The study also showed 6 pmol/mg DNA for total unoccupied nuclei and cytoplasmic estrogen receptors, and 25% of it in the nucleus; this finding differed from Zava et al's finding of 2 pmol/mg DNA and 75% in the nucleus, probably because of differing methodology or use of a later passage of cell line. 29 out of the 34 tumors with cytoplasmic receptors were found to contain unoccupied nuclear receptors, indicating that free nuclear receptors are not exceptions. The assay used in this study is currently being used to determine the translocative ability of the cytoplasmic receptors in human breast carcinomas.^ieng

Midbrain stimulation in the anesthetized rat: direct locomotor effects and modulation of locomotion produced by hypothalamic stimulation.

The midbrain contains circuits that modulate locomotion. To delineate some of the involved regions, low-level stimulation (25 microA, 10 s train of 0.5 ms pulses at 50 Hz) was applied to the midbrain during locomotor stepping. Stepping was elicited in the anesthetized (pentobarbital, 40 mg/kg) rat by stimulating the hypothalamus with 0.5 ms pulses at 40 Hz at various currents. The rat was held in a stereotaxic apparatus such that locomotor stepping movements turned a wheel. Facilitation of locomotion was produced by stimulation in the anterior ventromedial midbrain and in the posterodorsal midbrain. When presented alone, such stimulation produced locomotion. Inhibition of locomotion was produced by stimulation of the superior colliculus (ventral layers) and the ventromedial midbrain. Additional inhibitory sites were found in the central gray and the lateral tegmentum. Inhibitory collicular stimulation, when presented alone, was characterized by the absence of any hindlimb response. Inhibitory ventromedial stimulation, when presented alone, frequently produced poststimulation locomotion and when presented with hypothalamic stimulation was characterized by postinhibitory increases in locomotion. These results indicate that: (1) the locomotor effects of stimulation in midbrain and hypothalamic sites can summate: (2) multiple locomotor suppressive systems are present in the midbrain and among them are a collicular system and a ventromedial system.

Unoccupied binding sites for oestradiol in nuclei from human breast carcinomatous tissue.

The binding of oestradiol to a nuclear fraction extracted from human breast carcinomatous tissue was demonstrated. The material, which was extracted with KCl, sedimented at 3--4S and bound oestradiol with high affinity (dissociation constant approximately 2 X 10(-10) mol/l). Oestriol, diethylstilboestrol and 5 alpha-dihydrotestosterone (100-fold excesses) competed with [3H]oestradiol for the binding sites (binding inhibited by 89 +/- 8 (S.D.), 92 +/- 6 and 57 +/- 8% respectively), whereas progesterone and cortisol (100-fold excesses) did not (binding suppressed by 5 +/- 5 and 2 +/- 3% respectively). Similar competition patterns were found for cytoplasmic material which bound oestradiol. The binding occurred at 4 degrees C and was therefore considered to be a measure of the amount of binding material unoccupied by endogenous oestrogen, Unoccupied binding sites for oestradiol in the nucleus and cytoplasm were measured in 35 samples of breast carcinomatous tissue using sucrose gradient centrifugation. In 17 out of 35 tumorus, unoccupied nuclear and cytoplasmic 8S and 4S binding sites could be detected. Three out of 35 tumours contained unoccupied nuclear binding sites and 4S cytoplasmic binding sites. Nuclear binding sites only were found in two out of 35 tumours. Unoccupied nuclear binding sites were not detected in 13 out of 35 tumours and ten of these tumours also did not contain unoccupied cytoplasmic binding sites.

PIP: This study examines unoccupied binding sites for estradiol by using carcinomatous tissues of human breast. Estradiol, estriol, diethylstilbestrol and dihydrotestosterone demonstrated a higher affinity for binding sites, while progesterone and cortisol did not. Similar patterns were found for cytoplasmic material, and the binding occurred at 40C. In addition the quantities of unoccupied binding sites for estradiol in nuclei and in cytoplasm from 35 samples of human breast carcinomatous tissue were measured. Nuclear binding sites only were found in 2 out of 35 tumors, while unoccupied nuclear binding sites were not detected in 13 out of 35 tumors; 10 of these 13 did not contain unoccupied cytoplasmatic binding sites.

Subarachnoid spinal cord transplantation of adrenal medulla suppresses chronic neuropathic pain behavior in rats.

Several weeks after transection of the sciatic and saphenous nerves, rats respond by self-injury of the denervated limb ('autotomy'). This behavior serves as a model of neuropathic pain. In this study we allografted fragments of rat adrenal medulla into the subarachnoid space of other rats, at lumbar spinal cord level, in an attempt to suppress autotomy behavior. The results show that autotomy was reduced by an average of 63% throughout the 8 week observation period. Catecholamine (CA) histofluorescent staining performed up to 120 days postoperatively (P0) revealed viable transplants in 75% of the rats. Transplant viability correlated with suppression of autotomy. This suggests that medullary chromaffin cells function as a local, long-lasting source of anti-nociceptive agents at the spinal segments which process input from the injured nerves.

Neuropathic pain behavior in rats depends on the afferent input from nerve-end neuroma including histamine-sensitive C-fibers.

Sciatic and saphenous neurectomy in rats produces nerve-end neuromas, known to be a source of afferent input. Concurrently rats self-injure the denervated hindpaw ('autotomy'), a behavior related to neuropathic pain in humans. Here we show that surgical resection of the neuromas in various groups of rats, each at a different postoperative time (days 22, 33, 48) suppress autotomy. This recalls the pain relief in humans following resection of painful neuromas. We also show that daily injections of astemizole, a peripheral anti-histamine which blocks histamine H1-receptors, suppress autotomy. Since mostly C-fibers in rat neuroma are sensitive to histamine, these results corroborate the suggestion that autotomy is driven by afferent neuroma input, mainly in histamine-sensitive C-fibers.

[Current parameters of the epidemiological process in campylobacteriosis]. / Nekotorye sovremennye parametry épidemiologicheskogo protsessa kampilobakterioza.

Data on some parameters of the epidemic process of campylobacteriosis in the Ukraine are presented. Campylobacteriosis patients were found to constitute 1.9 +/- 0.095% of all examined patients with acute enteric infections (AEI). No statistically significant difference in the proportion of campylobacteriosis among child and adult AEI patients was established. The proportion of sick persons at the period of the spring-summer rise in morbidity was 71.5%. A definite relationship between the epizootic and epidemic processes in campylobacteriosis was noted. In the Ukraine the predominant infective agent was Campylobacter jejuni belonging mainly to serotype Lio and biotype 1. Quite frequently campylobacteriosis was found to be accompanied by mixed infections.

[The diagnosis of campylobacteriosis]. / Diagnostika kampilobakteroza.

Results of assays for Campylobacter in patients with intestinal dysfunction are presented for the period from 1984 to 1991. 4147 cases were analyzed in 144 of which (3%) Campylobacter was detected in feces. Children constituted 12% of this group. They were distributed by age in the following way: 1 year and younger--1%, from 1 to 2 years--4.2%, from 3 to 6 years--3.8%, from 7 to 16 years--2.3%. 15 Campylobacter-positive patients were established to discharge other enteropathogenic microorganisms. 4% of children suffered from severe form of campylobacteriosis associated with exsicosis, 80% had moderate form of the disease. In order to study reservoirs of the infection 102 samples of intestinal content in livestock were analyzed for Campylobacter 57.1% of which proved to be positive.