Biomedical subjects
Publications and source records attributed to S Cannon.
The management of a case of Ewing's sarcoma of the left proximal humerus in a 15-year-old girl is presented, and the radiological and pathological findings are described. The chemotherapeutic, radiotherapeutic and surgical management of Ewing's sarcoma are discussed with reference to the case.
In humans caffeine stimulates thermogenesis by unknown mechanisms and its effect on body weight has not been studies. The effect of placebo and 100, 200, and 400 mg oral caffeine on energy expenditure, plasma concentrations of substrates and hormones, blood pressure, and heart rate was investigated in a double-blind study in healthy subjects who had a moderate habitual caffeine consumption. Caffeine increased energy expenditure dose dependently and the thermogenic response was positively correlated with the response in plasma caffeine (r = 0.52; p less than 0.018), plasma lactate (r = 0.79; p less than 0.000001), and plasma triglyceride (r = 0.53; p less than 0.02). Stepwise regression analysis with the thermogenic response as the dependent variable excluded plasma caffeine and yielded the following equation: thermic effect (kcal/3 h) = -0.00459 X heart rate + 0.30315 X (triglyceride) + 0.53114 X (lactate) + 15.34 (r = 0.86; p = 0.0001). The results suggest that lactate and triglyceride production and increased vascular smooth muscle tone may be responsible for the major part of the thermogenic effect of caffeine.
Large subunits of ribulosebisphosphate carboxylase/oxygenase (Rubisco) (3-phospho-D-glycerate carboxy-lyase (dimerizing), EC 4.1.1.39) from prokaryotic sources can assemble into intact enzyme either in vitro or in Escherichia coli cells. Large subunits of higher plant Rubisco do not assemble into Rubisco in E. coli cells, nor is it possible to reconstitute higher plant Rubisco from its dissociated subunits in vitro. This behavior represents an obstacle to any practical attempts at engineering the higher plant enzyme, and it suggests that the in vivo assembly mechanism of higher plant Rubisco must be more complex than is commonly expected for oligomeric proteins of organelles. In pea chloroplasts, a binding protein interacts with newly synthesized large subunits, in quantities expected for an intermediate in the assembly process, as judged by Western blotting. Radiotracer-labeled large subunits which interact with this binding protein can be shown to assemble into Rubisco in reactions which lead to changes in the aggregation state of the binding protein. Antibody to this binding protein specifically inhibits the assembly of these subunits into Rubisco. Rubisco synthesis appears to be subject to many types of control: gene dosage, transcription rate, selective translation of message, post-translational degradation and threshold concentration effects have been observed in various organisms' synthesis of Rubisco. The biochemical mechanisms underlying most of these effects have not been elucidated. The post-translational assembly mechanism in particular appears to require further study.
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The incorporation of newly synthesized large subunits into ribulose bisphosphate carboxylase/oxygenase (RuBisCO) in pea chloroplast extracts occurs at the expense of intermediate forms of the large subunit which are complexed with a binding protein. Most subunits of this binding protein are found in dodecameric complexes in chloroplast extracts. Addition of small subunits to these extracts results in approximately 40 to 60% increased incorporation of newly made large subunits into RuBisCO at low or zero concentrations of ATP, but is without significant effect at high concentrations of ATP, a condition in which the dodecameric binding protein complex is dissociated into subunits. Overall, these data support the assumption that the incorporation of large subunits into RuBisCO in chloroplast extracts reflects de novo assembly rather than ;mere' exchange of subunits. The in vitro assembly of large subunits into RuBisCO is a function of the conditions under which the large subunits are synthesized in organello. When the large subunits are made in chloroplasts suspended in 188 millimolar sorbitol, they are approximately 2- to 3-fold better able to assemble into RuBisCO when subsequently incubated in vitro than when they are synthesized in chloroplasts suspended in 375 millimolar sorbitol. This observation indicates that mere synthesis of large subunits is not sufficient to confer maximal assembly competence on large subunits.
We are studying the stability of the binding protein which associates with newly synthesized large subunits of ribulose bisphosphate carboxylase. In chloroplast extracts, it has been shown that a dodecameric complex of the large subunit binding protein dissociates extensively into binding protein monomers and 7S (117 kilodaltons) large subunit-containing complexes in the presence of ATP. The concentrations of ATP which bring this about are quite low, prompting some investigators to suggest that the dodecameric complex might not exist in vivo. We have found, however, that in concentrated chloroplast extracts, at protein concentrations which are closer to those which occur in organello, the dissociation of the binding protein complex by ATP is much less extensive. For this reason, we have tested the stability of the binding protein in organello, by illuminating chloroplasts followed by lysis and polyacrylamide gel electrophoresis of the extracts. Radioactive large subunits associated with the dodecameric binding protein dissociated extensively in the light. The results are consistent with the idea that the high molecular weight form of the binding protein can function as a reservoir of large subunits which can be tapped in vivo, in a reaction dependent on light and ATP.
Postpoliomyelitis syndrome is characterized by new neuromuscular symptoms, including weakness, developing years after recovery from acute polio. Bilateral vocal cord paralysis is presented as a new manifestation of this syndrome. Other clinical features of post-poliomyelitis syndrome in this report are discussed. The etiology of this syndrome is unknown, though attrition or immune-mediated destruction of collateral muscular innervation appears likely. The pathologic findings include scattered individual muscle fiber atrophy as well as evidence of chronic denervation and reinnervation. This form of motor deterioration is not life-threatening, but potentially may cause increasing disability in a large number of polio survivors. Proper supportive care of facial, laryngeal, and pharyngeal weakness is crucial in the management of these patients.
We have developed an assay to monitor in vitro the posttranslational assembly of the chloroplast protein, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO). Most of the newly synthesized 55-kD catalytic ("large") subunits of this enzyme occur in a 29S complex together with 60- and 61-kD "binding" proteins. When the 29S complex is incubated with ATP and MgCl2 it dissociates into subunits, and the formerly bound large subunits now sediment at 7S (still faster than expected for a monomer). Upon incubation at 24 degrees C, these large subunits assemble into RuBisCO. The minority of newly made large subunits which are not bound to the 29S complex also sediment at 7S. When endogenous ATP was removed by addition of hexokinase and glucose, the dissociation of the 29S complex was inhibited. Nevertheless, the 7S large subunits assembled into RuBisCO, and did so to a greater extent than in controls retaining endogenous ATP. Thus the 7S large subunits are also assembly competent, at least when ATP is removed. Apparently, in chloroplast extracts, ATP can have a dual effect on the assembly of RuBisCO: on the one hand, even at low concentrations it can inhibit incorporation of 7S large subunits RuBisCO; on the other hand, at higher concentrations it can lead to substantial buildup of the 7S large subunit pool by causing dissociation of the 29S complex, and stimulate overall assembly. At both high and zero concentrations of ATP, however, antibody to the binding protein inhibited the assembly of endogenous large subunits into RuBisCO. Thus it appears that all assembly-competent large subunits are associated with the binding protein, either in the 7S complex or in the 29S complex. The involvement of the binding protein in RuBisCO assembly may represent the first example of non-autonomous protein assembly in higher plants and may pose problems for the genetic engineering of RuBisCO from these organisms.
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Recent animal and human studies suggest that prenatal exposure to carcinogens may increase the risk of childhood malignancy. The Texas Childhood Cancer Study (1976-1977) was designed to test the hypothesis that parental exposure to hydrocarbon-related occupations or industries increases this risk. The study subjects, parents of children with and without cancer, were questioned about their job histories. Parents of 296 children with cancer were not exposed to hydrocarbon-related occupations or industries more often than the uncles and aunts of these children, the parents of neighborhood children, or the parents of 283 children without cancer. During the year before birth, odds ratios for fathers of children seen at a hematology clinic with cancer relative to the uncles of these children (0.93), the fathers of neighborhood children (1.33), and the fathers of children seen at the clinic without cancer (0.50) were not statistically significantly different from 1.00 (p greater than 0.05). This lack of association persisted for the year after birth, the year before diagnosis, and the interval from the year before birth to the year of diagnosis; for different diagnoses; for different ages at diagnosis; and for the industries and occupations of female as well as male parents.
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Hyponatremia (HN) is the commonest electrolyte abnormality in elderly patients. Its etiology in this setting is poorly understood. In this study, the authors aim to compare the hemodynamic and hormonal responses of a group of older patients with a predisposition to HN with a group of age-matched controls. We assessed hemodynamic and hormonal responses to postural challenge in 15 patients over age 65 with serum sodium concentrations of less than 130 mM (mean 128.7 mM) and 15 age-matched controls with normal sodium concentrations. Patients remained recumbent for 1 h and stood for the second. Blood was drawn at baseline and at 15 min intervals. Blood pressure (BP) and pulse rates (PR) were monitored electronically. Plasma arginine vasopressin (AVP), atrial natriuretic peptide (ANP), renin and aldosterone were determined periodically during the study period. No difference in BP between groups was noted. PR increased significantly in the HN group only within 3 min of standing (from 71 +/- 4 to 86 +/- 5, P<0.01) and remained significantly higher than controls until 90 min (87 +/- 5 vs. 69 +/- 4, P<0.01). While plasma AVP levels increased significantly following 30 min standing and remained elevated for both HN and control groups, it did not differ significantly between the two. Baseline plasma ANP levels were significantly higher in HN patients compared with controls and remained significantly higher (P<0.05) throughout the study. There was no significant difference in plasma renin or aldosterone levels between groups during the study period. We have demonstrated differing autonomic and hormonal responses to orthostatic challenge between HN patients and age-matched controls. Water retention due to the syndrome of inappropriate anti-diuretic hormone secretion (with reset osmostat) may lead to raised ANP levels in this older cohort of patients. Further physiological studies are required to clarify the precise mechanism of these varying responses.