Biomedical subjects
Publications and source records attributed to D Hamilton.
Cimetidine significantly slowed metastatic development and prolonged survival in tumour-bearing mice, in association with inactivation of suppressor cells. Pharmacological blockade of the suppressor cell system may represent a new strategy for successful immunotherapy of human neoplasia.
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A 10-year-old boy with discrete subaortic stenosis had coexisting abnormal systolic anterior motion of the mitral valve, demonstrated by echocardiography, a sign normally taken as indicating the presence of idiopathic hypertrophic subaortic stenosis. Surgical removal of a fibromuscular diaphragm abolished the echocardiographic signs of discrete subaortic stenosis but abnormal systolic anterior motion of the mitral valve persisted. A severe low cardiac output state complicated immediate recovery after removal of the left ventricle outflow obstruction, and was overcome only with considerable difficulty. The presence of hypertrophied septal muscle, and the associated small left ventricular cavity size, was thought to be the immediate cause of these problems, so that recognition of marked septal hypertrophy, together with abnormal anterior systolic movement of the mitral valve, should serve as a warning that similar difficulties are likely to bae encountered by other patients, after removal of the obstruction in subaortic stenosis. In our experience other forms of left ventricle outflow tract obstruction have not been found to show such a marked degree of asymmetric septal hypertrophy, but this does not mean it may not occur.
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Confluent and reticulated papillomatosis (CRP) of Gougerot and Carteaud is the least common occurring of the papillomatoses. Its recognition as a distinct disease entity has long been questioned. Four new cases are presented, and the literature is reviewed. It is our conclusion that CRP is a definite disease entity.
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A 56-year-old man developed several deep cutaneous nodules in the pelvic area and on the upper extremities, trunk, and scalp. Biopsy revealed cutaneous metastases from a follicular carcinoma of the thyroid, for which the patient had been treated two and one-half years previously.
The acute airway response to smoking a single cigarette was assessed in eight symptom-free male smokers. The changes in airway function were determined using a computer analysis of maximal and partial expiratory flow volume curves together with measurement of airway resistance. The amount of smoke inhaled was assessed by measuring levels of nicotine in venous blood. When the results of all studies were analysed for the group as a whole only small and inconsistent changes in airway function were observed after smoking a cigarette, although all the subjects appeared to inhale the smoke. Although the group showed inconsistent changes, one subject exhibited a change on all four occasions in the studies using the maximal and partial expiratory flow volume curves. This was seen particularly for Vmax50 and Vmax40 obtained from the maximal and partial expiratory flow volume curves respectively. There appeared to be no difference between the two manoeuvres in their sensitivity to smoke-induced change. One subject showed a response to smoking when airways resistance was measured but this was on only one of two occasions. It is therefore possible that certain smokers are more susceptible to inhaled cigarette smoke and such individuals may be those who develop chronic airflow obstruction. The absence of a group effect was attributed to any smoking response being smaller than the other factors which affect measurements of airway function.
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We describe a simple technique for isolating deletion mutants of phage lambda and use it to dissect a cloned fragment of foreign DNA. The technique is based on our previous finding that the normally essential product of lambda head gene D is dispensible for phage growth if the DNA content of the phage is less than 82% that of lambda wild-type (Sternberg and Weisberg, 1977). A significant fraction of the few phage that form plaques when a D amber mutant is plated on a nonsuppressing host contains deletions that reduce the phage chromosome size to less than 82% that of wild-type. It is possible to isolate deletions ranging in size from less than 1.5 kb to 14 kb (3 to 27% of wild-type lambda), and the size range can be restricted by an appropriate choice of the DNA content of the starting phage. This method, unlike the older EDTA or heat resistance methods, permits the scoring of deletions because of the absence of phenotypic variants. We investigated the effect of several host and phage mutations on deletion frequency and type and have determined that a host polA mutation increases the frequency of deletions about 30-50-fold without changing the type of deletions. A host mutD mutation or thymine deprivation increases deletion frequency about 10-fold. In contrast, a host ligts mutation has no effect on the frequency of deletions. We have also determined that the size of the smallest lambda chromosome packageable in a plaque-forming phage particle is 72-73% that of lambda wild-type.
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Paraplegia is a common problem in developing countries. They are the most pitiable group of cases seen, but they can all be offered some help, however limited one's resources. The main causes are Potts Disease, arachnoiditis, tropical spastic paraplegia, trauma, lathyrism and cord compression. The usual trauma is falling from trees and the use of trained monkeys to gather leaves and nuts whilst humorous should not be dismissed. The author saw some 35 cases of paraplegia, of which four are described--two good results and two bad. The physician going to a developing country is advised to prepare himself for the care of these cases and to be prepared to motivate staff, patients and relatives. He will find local medical assistants are kind and enthusiastic and rapidly acquire the necessary skills. Nearly all cases should receive a simple and inexpensive anti-tuberculous regime, vitamins and a very generous diet. Necessary equipment required for the home should be locally made and nothing requiring more than simple maintenance should be used.
We describe the dissection and reconstruction of a complex control circuit, the P1 immunity system, by a method that involves inserting EcoRI-generated fragments of P1 DNA into lambda vectors that can then be sequentially inserted into a bacterial cell. Using these techniques we have isolated lambda-P1 hybrid phages that express the products of P1 genes c1, c4, ant, and ban and, in appropriately constructed lysogens, confirmed the roles played by the first three of these products in phage immunity. In addition we have localized to particular P1 fragments the sites requisite for expression and repression of these gene products. The analysis leads to the conclusion that gpant acts in trans to antagonize repression mediated by gpc1, in support of one of two proposed models for gpant action. Moreover, two features of the immunity system are revealed: (i) a hitherto unknown component that effects gpc1 repression; and (ii) an unexpected ability of gpc4 to channel a superinfecting c1+ phage into the lysogenic state, which suggests that gpc4 activity regulates the establishment phase of lysogeny.
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The degree of cyclic AMP-dependent protein kinase activation in response to dibutyryl cyclic AMP and norepinephrine was determined in samples of rat heart obtained from hyperthyroid and euthyroid animals. The data indicate that thyroid hormone-induced supersensitivity to the metabolic effects of the catecholamines cannot be explained on the basis of a change in activity of supernatant protein kinase.