Glucocorticoid-induced exacerbation of metastatic human melanoma.
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Biomedical subjects
Publications and source records attributed to M J Walker.
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Receptors for all classes of steroid hormones were identified in cytosols of adenocarcinoma of the lung. In contrast, the incidence of receptor in squamous cell carcinoma was limited and small cell carcinomas appeared devoid of receptor. Receptor binding was of high affinity, saturable and localized to the 8, 6-7 and 4s regions of sucrose density gradients. Demonstration of high affinity cytosol receptors for steroids in adenocarcinoma and squamous cell carcinoma of the lung provides suggestive initial evidence that steroids may influence the natural history of a subset of human lung carcinomas.
Field observations at breeding kennels in eastern England support the view that perinatal transmission is of minor importance in the epidemiology of Uncinaria stenocephala infections in greyhounds. Patent infections became established soon after weaned pups were put onto gas paddocks. Egg-counts rose to high levels, tending to peak in dogs 25-35 weeks old and to decline thereafter. This pattern was related to the age of the host and was not seasonal. The consequent deposition of large numbers of eggs onto the paddocks at irregular intervals distorted the seasonal fluctuations in herbage larval counts previously found to be a consistent feature of grass paddocks used for exercising adult racing greyhounds.
The effect of continuous exposure to proprietary rubefacients (Tiger Balm Red and Tiger Balm White), which contain menthol and camphor as well as clove, cajuput and cassia oils, was tested in rabbits. Dermal irritancy was determined by a 21-day continuous-application patch test (0.5 g/patch) and was assessed according to the Draize method of scoring. At the end of the 21-day test period, the skin was also examined histopathologically. In these tests, Tiger Balm Red (which contained 5% cassia oil plus 5% clove oil) caused irritation consisting of erythema, eschar formation and some oedema, to which a degree of tolerance developed. This irritation resulted in hyperkeratosis and sometimes inflammatory changes but no major damage to the skin. Tiger Balm White (no cassia oil and 2% clove oil) was better tolerated and produced less irritation and histological change than either TIger Balm Red or a mixture of commercial waxes similar in composition to the wax base for Tiger Balm Red. None of the treatments produced any signs of systemic toxicity.
Herpesvirus hominis type 1 (HSV-1) was isolated from fallopian-tube biopsies of two women who were using an intra-uterine contraceptive device; the strains were isolated on different dates and at different hospitals. Both the isolates were shown to be HSV-1 by restriction-enzyme analysis, polypeptide profiles and indirect immuno fluorescence; the two isolates could not be distinguished by these tests, but the tests distinguished them from HSV-1 strain 71-15 and HSV-2 strain 333. The viruses were again isolated from samples of fallopian-tube tissue stored in liquid nitrogen, and their polypeptide and restriction-enzyme profiles were the same as those in the initial isolates. Virus was not isolated from fallopian-tube samples obtained from other IUD patients undergoing surgery at the same two hospitals at the same time.
The effect of prostacyclin (PGI2) on blood pressure and heart rate (in vivo) and on isolated heart tissue has been investigated in different species. Isolated cardiac tissue had limited responses to PGI2 tested at 10(-13) to 10(-5) M. Cultured neonatal rat heart cells did not respond to PGI2, neither did intact rat hearts or rabbit cardiac tissue. Guinea pig and rat atria showed limited dose-dependent responses to PGI2 at concentrations greater than 10(7) M. In rat atria, 10(-5) M PGI2 produced a limited elevation of tissue cAMP content. When given by intravenous injection or infusion, PGI2 produced hypotension in anaesthetized primates (three species), rat, rabbit, pig, and dog. As a vasodepressor in all species, PGI2 (on a weight basis) was more active than prostaglandins of the B or E type and, in most species tested, it was approximately five times more active than PGE2. Heart responses in intact animals were often paradoxical in that decreases in heart rate often accompanied blood pressure falls.
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A retrospective analysis of 72 cases of primary malignant tumors of the parotid gland treated at the University of Illinois Hospital, Chicago, from 1950 through 1978 revealed that six of these had developed from two to 24 years after irradiation of the head or neck for various benign and malignant neoplastic conditions. At the time of irradiation, ages ranged from 7 to 73 years; the sex distribution was equal. From our findings and those in 26 cases reported by various other authors, the following criteria are proposed for the designation of a parotid tumor as being radiation induced: (1) well-documented radiation exposure; (20 port of irradiation must incorporate the gland in which the cancer subsequently arises; (3) exposure to a minimum of 300 rads; and (4) minimum latent period of two years. In view of the widespread use in the past of head and neck irradiation of benign neoplastic disease, the surgeon should be aware of this possible link with parotid gland tumor.
The effect of drugs on the beating rate of cultured heart cells can be monitored in a number of ways. The simultaneous automated measurement of beating rates of a number of cells allows drug effects to be rapidly quantified. A photoresistive detector placed on a television image of a cell, when coupled to operational amplifiers, gives binary signals that can be processed by a microprocessor. On this basis, we have devised a system that is capable of simultaneously monitoring the individual beating of six single cultured heart cells. A microprocessor automatically processes data obtained under different experimental conditions and records it in suitable descriptive formats such as dose-response curves and double reciprocal plots.
Sixty-six human soft-tissue sarcoma specimens were assayed for incidence and distribution of steroid hormone receptors. Liposarcomas (43%) and leiomyosarcomas (60%) had a high incidence of estrogen receptor. In contrast, sarcomas of fibrous and synovial tissue origin lacked any detectable receptor for estrogen. Malignant fibrous histiocytoma had the highest incidence of glucocorticoid (66%) and androgen (66%) receptors. The incidence of receptors for estrogen and glucocorticoid was higher in female than in male patients (62% and 38%, respectively). Sucrose density gradients demonstrated 8s-type receptors for both estrogen and glucocorticoid. Data from this study suggest that specific high-affinity cytosolic receptors for steroid hormones are present in human soft tissue sarcoma and that their distribution may depend on the histogenetic origin and the sex of patients.
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Massive diffuse subcutaneous emphysema resulting from perforation of the proximal jejunum is presented. Seventy-nine reported instances of subcutaneous emphysema of gastrointestinal origin were reviewed. Emphysema originating from the jejunum has not been previously reported. The colon (26 patients) and rectum (16 patients) were the more common sites of perforation. Perforations of the stomach and duodenum were found in 14 patients. The most common site for presentation of the subcutaneous air was the lower abdominal wall and thigh, and the more common causes were carcinoma of the colon and rectum and diverticulitis. The pathogenesis of emphysema in the patient described, as well as in the great majority of other patients, is from intraluminal gas rather than from gas-forming organisms. The air spreads along neurovascular bundles and other anatomic planes and may rapidly reach areas distant from the perforation. The recognition of these phenomena in the diagnosis of gastrointestinal perforation is important.
As an initial step in investigating the role of steroid hormones in skeletal tumors, the incidence of cytosol receptors for steroid hormones was determined. Four osteosarcoma (two primary, two metastatic), two chondrosarcomas, one Ewing's sarcoma, and one malignant giant cell tumor were assayed for receptor. Six of eight tumors (75%) had receptors for at least one steroid, and four of eight (50%) tumors had more than one receptor. Receptor for glucocorticoid was found in four of seven tumors cytosols (57%). Receptor for androgen and progesterone was present in three of seven cytosols (43%), while estrogen bound to two of eight (25%). Characterization of steroid binding in a subset of skeletal tumors revealed specific, high affinity, saturable receptors for all steroid classes with Kd's similar to those found in other tumors. These data suggest a rationale for a prospective, randomized, double blind study of endocrine therapy in advanced metastatic disease of primary bone sarcomas.
Malignant neoplasm after immunosuppressive therapy is a well-known entity. Though a considerable number of such lesions are cutaneous in origin, melanoma has rarely been reported. In this communication, six such melanoma cases are reported.
1 (-)-Adrenaline sensitivity in 1 to 20 day-old rat heart tissue was investigated as rate, force and cyclic adenosine 3',5'-monophosphate (cyclic AMP) production responses together with sensitivity to (+/-)-propranolol blockade.2 Resting performances were measured and responsiveness to (-)-adrenaline then determined as ED(50) values and maximal responses together with sensitivity to propranolol (pA(2) values).3 Resting force, corrected for sample size, did not change with age, whereas resting atrial rate doubled between 1 and 20 days.4 ED(50) concentrations in atria were constant with age, but decreased in ventricles. Cocaine (10(-5) M) and other drugs did not consistently affect ED(50) values.5 Maximal responses were not age-dependent in right atria, but increased in left atria. In 2 to 5 day-old hearts there was no inotropic response to adrenaline and the very small maximal response in ventricles rose 5 to 7 fold by 20 days.6 Propranolol sensitivity increased slightly (2 to 4 times) with age in all tissue from a pA(2) value of 7.5 at 2 days to 8.2 at 20 days.7 Control cyclic AMP was higher in 2 day than in 20 day-old tissue and in atria than ventricular strips or hearts. In 2 and 20 day-old atria, hearts and ventricles, force increases with different adrenaline concentrations correlated linearly with the log of the increase in cyclic AMP. Such a correlation was not seen in 2 day hearts and ventricles for cyclic AMP rose without corresponding force increases.8 Results suggest slight maturational changes in atrial beta-receptors. In 1 to 5 day-old ventricles, normal ED(50) concentrations and good cyclic AMP response in the presence of a much reduced force response may indicate receptor-response transduction inefficiency, assuming a beta(1)-receptor occupation and cyclic AMP production response mechanism for inotropism with adrenaline.
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