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Calcitonin (CT) and calcitonin gene related peptide (CGRP) are derived from preprohormones encoded by three mRNAs (CT, alpha-CGRP and beta-CGRP) from two genes (CALC1 and CALC2) on chromosome 11. Among 16 small cell lung cancer cell lines examined by RNase protection assay, 9 (56%) had detectable CT mRNA, 8 (50%) had alpha-CGRP mRNA, and 13 (81%) had beta-CGRP mRNA. At least one CALC1 transcript (CT or alpha-CGRP) was found in 11 (69%) cell lines with three having only CT mRNA, two having only alpha-CGRP mRNA, and six having both. beta-CGRP mRNA was detected in all of these 11 cell lines expressing a CALC1 transcript. Immunoreactive CT was detected by radioimmunoassay in eight of nine SCLC cell lines expressing CT mRNA, and immunoreactive CGRP was detected in 12 of 13 cell lines expressing a CGRP mRNA. The variety of expression of these three peptides in different cell lines of the same cell type should provide a useful system for further study of the control of expression of these peptides.

The study of the genetic alterations of tumor suppressor genes and protooncogenes in solid tumors has greatly increased our understanding of cancer biology. These findings have extended epidemiologic associations of carcinogens with certain tumors. Further analysis of patterns of genetic changes may implicate carcinogenic substances in cases where epidemiology has not been able to do so. Identification of germline mutations in p53, APC, and NF1 has provided improved diagnosis and presymptomatic screening in cancer kindreds. The identification of additional alterations in tumor suppressor genes may further improve the ability to predict inherent cancer risk. Screening strategies based on detection of genetic abnormalities of preinvasive cancerous lesions, such as mutant ras in colonic polyps, may improve early diagnosis. Finally, strategies to replace lost tumor suppressor function may provide a future therapeutic modality.

To determine the relative contribution of ectopic calcitonin (CT) production versus nonectopic secretion of CT in patients with small cell lung cancer (SCLC), serum and urine immunoreactive CT (iCT) levels of 86 different subjects were measured by radioimmunoassay (RIA) using two polyclonal antisera (Ab3b and Ab4). The subjects included 49 previously untreated patients with SCLC, 17 smokers, and 20 nonsmokers. Serum and urine iCT values were highest in the patients with SCLC, intermediate in the smokers, and lowest in the nonsmokers (p < 0.0003). Sixteen of the 49 patients with SCLC had tumor cell lines available for determination of CT mRNA expression by RNase protection assay (RPA) and iCT production by RIA. CT mRNA was detected in nine of 16 subjects and iCT in eight of 16. The tumor cell lines of seven patients had undetectable CT by both RPA and RIA, and of these, five had elevated urine or serum iCT values compared with those of nonsmokers, and two had levels above all values in the smoker group. Immunohistochemical staining of formalin-fixed, paraffin-embedded tumor samples detected iCT in two of four tumors from patients whose tumor cell lines had CT mRNA by RPA and iCT by RIA, but in none of six whose tumor cell lines had undetectable CT mRNA. Thus, increased iCT values in some patients with SCLC are likely due to sources other than CT production by tumor cells.

This study reports the first demonstration of a marked reduction in alpha-crystallin chaperone activity in an experimental model of cataract, and the study implicates activation of the cysteine protease calpain II (EC 3.4.22.17) as the in vivo protease responsible for decreased chaperone activity. Chaperone activity of normal alpha-crystallin from lenses of young rats was assayed by measuring attenuation of heat-induced aggregation and scattering of beta L-crystallin. alpha-Crystallin from the nucleus of lenses with selenite cataract showed specific selective proteolysis, and chaperone activity was diminished. Proteolysis of alpha-crystallin from selenite cataract lenses was mimicked by incubating normal alpha-crystallin with calpain II, and this also resulted in loss of chaperone activity. Two-dimensional gel electrophoresis and peptide mapping were used to identify four partially degraded alpha A- and alpha B-crystallin polypeptides following incubation of normal alpha-crystallin with calpain. Similar partially degraded alpha A and alpha B polypeptides were found in selenite cataract. Previous experiments indicated that alpha-crystallin chaperone activity decreases because of removal of the COOH terminus. Our experiments support this observation and suggest that calpain proteolysis of alpha-crystallin at the COOH terminus may result in a loss of chaperone activity in selenite cataract.

Research on dominant oncogenes and tumor suppressor genes has characterized differences in genetic lesions between small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) and identified associations with clinical parameters. More than one half of all lung cancers contain a mutation of the p53 tumor suppressor gene. There does not appear to be an association between the presence of this mutation and survival. A ras family oncogene was found to be mutated in approximately 20 percent of tumors and tumor cell lines from patients with NSCLC in contrast to none of 45 tumors and tumor cell lines from patients with SCLC. The presence of a K-ras mutation was determined to be an adverse prognostic factor for survival in retrospective studies of patients with NSCLC. Mutations of K-ras are more common in tumors from smokers than nonsmokers and have not been detected in lung cancers resulting from occupational exposure to radon. Mutations in both the p53 gene and K-ras oncogene are most commonly G to T transversions in lung cancer vs G to A transitions in other cancers. Prospective studies of these mutations in resected tumor specimens taken from patients with accurate follow-up may continue to provide important clues about their potential clinical and biologic significance.

The structural gene for human keratinocyte growth factor (KGF), a member of the fibroblast growth factor family, consists of three coding exons and two introns typical of other fibroblast growth factor loci. A portion of the KGF gene, located on chromosome 15, is amplified to approximately 16 copies in the human genome, and these highly related copies (which consist of exon 2, exon 3, the intron between them, and a 3' noncoding segment of the KGF transcript) are dispersed to multiple human chromosomes. The KGF-like sequences are transcriptionally active, differentially regulated in various tissues, and composed of three distinct classes of coding sequences that are 5% divergent from each other and from the authentic KGF sequence. Multiple copies of KGF-like genes were also discovered in the genomic DNAs of chimpanzee and gorilla but were not found in lesser apes (gibbon), Old World monkeys (African green monkey and macaques), mice, or chickens. The pattern of evolutionary occurrence suggests that a primordial KGF gene was amplified and chromosomally dispersed subsequent to the divergence of orangutan from African apes but before the trichotomous divergence of human, chimpanzee, and gorilla 5-8 million years ago. The appearance of a transcriptionally active and chromosomally dispersed multigene KGF family may have implications in the evolution of the great apes and humans.

Virulent, wild-type equine infectious anemia virus (EIAV) is restricted in one or more early steps in replication in equine skin fibroblast cells compared with cell culture-adapted virus, which is fully competent for replication in this cell type. We compared the sequences of wild-type EIAV and a full-length infectious proviral clone of the cell culture-adapted EIAV and found that the genomes were relatively well conserved with the exception of the envelope gene region, which showed extensive sequence differences. We therefore constructed several wild-type and cell culture-adapted virus chimeras to examine the role of the envelope gene in replication in different cell types in vitro. Unlike wild-type virus, which is restricted by an early event(s) for replication in equine dermis cells, the wild-type outer envelope gene chimeras are replication competent in this cell type. We conclude that even though there are extensive sequence differences between wild-type and cell culture-adapted viruses in the surface envelope gene region, this domain is not a determinant of the differing in vitro cell tropisms.

Cobra venom (Naja naja naja) phospholipase A2 (PLA2) contains 14 cysteines in the form of 7 disulfide bonds amongst its 119 amino acids. A gene encoding the PLA2 was synthesized and inserted into a bacterial expression vector containing the phage lambda pL promoter. In order to obtain protein without the initiating methionine at the N-terminus, a Factor Xa site was engineered upstream from the PLA2 gene. Upon heat-induction of the cells transformed with the expression plasmid, the protein is produced as insoluble inclusion bodies. The enzyme was partially purified by washing the inclusion bodies with Triton X-100 and urea. The expressed protein was first denatured with 8 M guanidine-HCl and 10 mM DTT. After digestion with Factor Xa, formation of disulfide bonds and refolding into the fully active form was carried out in the presence of cysteine and Ca2+. The renatured recombinant protein was purified by Affi-gel blue column chromatography. The purified recombinant enzyme had the same specific activity as the native enzyme when assayed on a variety of substrates and cross-reacted with antisera prepared against the native enzyme. This is the first report of the expression of a recombinant PLA2 from any venom.

Through extensive reviews of literature, the semi-lunar cartilaginous discs (located within the tibiofemoral joint) will be examined with regard to their make-up, function, and response to trauma. Methods of diagnosing meniscal injury will be explored, as will past and present surgical procedures. An outlook into future methods of treating meniscal lesions will be touched upon.

Injuries sustained during competitive sport activities are accepted as an inherent part of the game. While it may be true that the associated risk of participating in certain sports increases the chance of becoming hurt, it is safe to assume many injuries can be avoided if preventive medicine is practiced. Conditioning and strength training go a long way in protecting the athlete from possible harm, but in some cases this is not enough. The accumulated effect of psychological stressors (in and outside the athletic world) may cloud the mental functioning of the athlete and override physical conditioning enough to precipitate injury or prolong it. After extensive reviews of literature, it has been determined that a collective researched list of psychological risk factors can be recognized which may predispose an athlete (especially in a contact sport) to injury (real or imagined).

The addition of cyclic AMP (cAMP) to Saccharomyces cerevisiae cyr1 mutant cells resulted in an increase in the rate of phosphatidylinositol synthesis at the expense of phosphatidylserine synthesis. The decrease in phosphatidylserine synthesis correlated with the down regulation of phosphatidylserine synthase activity by cAMP-dependent protein kinase phosphorylation. The increase in phosphatidylinositol synthesis was not due to the regulation of phosphatidylinositol synthase by cAMP-dependent protein kinase.

Recent studies suggest a new and important role for the chest film and cardiac fluoroscopy in the assessment of coronary artery disease. The detection of coronary artery calcification and the radiographic appearance of myocardial infarction are just two of the topics thoroughly described in this article.

Concern for side effects of contrast materials limits the volume that can be used for angiocardiography in infants; many of these effects are related to hyperosmolality. The effects of intracardiac injections of ionic (meglumine sodium diatrizoate) and nonionic (metrizamide) contrast agents on the left ventricle and body fluids were compared in an infant model. Immediately after injection, meglumine sodium diatrizoate (MSD) caused increases in left ventricular peak systolic pressure (LVPSP) (+26 +/- 5%) (control (C) = 92 mmHg), LV dp/dt (+21 +/- 6%) (C = 2610 mmHg/sec), left ventricular end-diastolic dimension (LVEDD) (+31 +/- 5%) (C = 10.5 mm), and left ventricular end-systolic dimension (LVESD) (+28 +/- 6%) (C = 7mm). Subsequently, LVPSP and dp/dt decreased to -16 +/- 6% and -23 4 +/- 6% of control, while LVEDD and LVESD rose. Dimension changes resolved by 15 minutes. Metrizamide caused immediate increases in LVPSP (+27 +/- 4%) (C = 86 mmHg) and LV dp/dt(+25 +/- 4%) (C = 2640 mmHg/sec). These parameters never declined significantly below control levels and were at control level at 15 seconds. Initial increases in LVEDD (+17 +/- 3%) (C = 10 mm) and LVESD (+6 less than 4%) (C = 6.5 mm) with metrizamide were significantly less than with MSD (P less than 0.008). MSD caused greater and more persistent elevations of serum osmolalities than metrizamide. Differences between the two agents were accentuated during systemic hypoxemia. Thus, ionic contrast agents appear to have a greater propensity for inducing toxic cardiovascular effects in infants than nonionic agents.

The plain chest radiograph and the M-mode echocardiogram provide the radiologist with means of diagnosing and assessing the severity of most forms of acquired heart disease. The salient diagnostic features of the important acquired heart diseases are summarized in Table 3.

Experience with four children undergoing apicalaortic shunts for relief of aortic valvular disease is reported. All children tolerated the procedure uneventfully, and postoperative cardiac catheterization in three revealed restoration of normal hemodynamics. In one unique case severe aortic regurgitation in a two year old boy was managed by suture closure of the aortic valve producing total left ventricular output through the apical-aortic conduit.

Differentiation of a hemodynamically significant cardiovascular abnormality from lung disease in the newborn infant may remain problematic after clinical, radiographic, and echocardiographic evaluation. Single-view aortography was performed in 38 preterm and one full term infant in the neonatal special care nursery. Special lateral views were obtained consisting of either a horizontal x-ray beam with oblique angulation of the supine patient or a vertical bean with 30 degree head-up angulation of the patient. These views projected the ductus caudal to the aortic arch and enabled visualization of the entire length of the ductus and focal constrictions of the ductus. The severity of patent ductus arteriosus was judged by anatomic (diameter of the ductus compared to the descending aorta) and physiologic (preferential opacification of the aortic arch or pulmonary circulation) criteria.

The effects of LV dynamics of the intracoronary administration of three new contrast materials with reduced osmolality were compared with those of a monomeric ionic material, sodium iothalamate, and the nonionic material, metrizamide. In eight anesthetized dogs, the monacid dimer, P286, caused increases in LV dimensions and decreases in LV systolic pressure and parameters of the contractile state. The changes were less than those caused by sodium iothalamte. The alterations in LV function tended to be greater, but not significantly so, during systemic hypoxemia compared to the normal state. The nonionic materials, P297 and iopamidol, like metrizamide, caused no deleterious effects on LV dynamics in either the normal or hypoxemic state. Nonionic materials actually caused a slight increase in parameters of the LV contractile state.

Rapid administration of protamine sulfate after arteriography or cardiopulmonary bypass has occasionally been associated with marked hypotension. Since it is unclear whether this is due entirely to vasodilatation or to myocardial depression in addition to vasodilatation, the authors assessed the direct myocardial and systemic circulatory effects of this drug in seven anesthetized dogs. Direct effects of protamine sulfate on global and regional myocardial function and peripheral arterial resistance were determined in the presence and absence of segmental myocardial ischemia. Effects on the myocardium were determined by intracoronary administration of protamine; effects on the systemic circulation were determined after intravenous administration. Intracoronary administration of protamine caused no significant change in left ventricular contractility in either the normal or ischemic state. Intravenous administration produced hypotension due to peripheral vasodilation.

The radiographic features of five patients with arteriohepatic dysplasia are presented. These patients had congenital intrahepatic cholestasis with elevated serum bile acids, vertebral body abnormalities of shape and/or segmentation, shortened digits, and congenital heart disease, particularly peripheral pulmonic stenosis. They also had dysmorphic facies, eye abnormalities, hypercholesterolemia, and mild fat malabsorption. Some of the patients had neurologic, endocrine, and/or renal abnormalities as well, and they may have had hoarse voices due to vocal cord nodules. Variability in expression of the syndrome and vertical transmission suggest an autosomal dominant pattern of inheritance.

Fifty-one patients were divided into two groups: 20 patients with proven rheumatic mitral valve disease (RMVD) and 31 patients with left atrial enlargement (LAE) of a nonrheumatic etiology. The latter group included patients with ischemic papillary muscle dysfunction, mitral valve prolapse, and congestive cardiomyopathy. Radiographic studies showed that enlargement of the left atrial appendage (LAAE) was present in 18 of 20 rheumatics but in only one of 31 non-rheumatics. There was no direct relationship between enlargement of the LAA and radiographic or echocardiographic left atrial size, degree of pulmonary venous hypertension (PVH), or presence of atrial fibrillation. It is postulated that rheumatic inflammation of the LAA allows it to dilate out of proportion to the body of the left atrium. In the adult patient with radiographic findings of PVH, LAAE is a valuable and specific radiographic sign of rheumatic mitral valve disease.

Male, Wistar rats (50-74 g) were given a semi-purified diet containing cholesterol (10 g/kg diet) for 4 weeks, groups of control and experimental animals killed, and the remainder of the cholesterol-fed animals given either a semi-purified cholesterol-free diet without a fibre source or a similar diet with pectin (50 g/kg diet) for 8 weeks. Animals were killed at 2-week intervals and serum and liver cholesterol and triglycerides, faecal neutral steroids and acidic steroids measured. Animals given pectin had significantly lower serum cholesterol levels than animals given the basal diet after 4 and 6 weeks. Both experimental groups efficiently decreased their liver cholesterol levels during regression. Bile acid excretion was elevated in both groups, especially in rats receiving pectin, but neutral steroid excretion was unchanged. The increase in bile acid excretion was primarily in the form of chenodeoxycholic acid and its metabolites. This increased bile acid excretion is postulated to result from stimulation of the normal mechanism for increased steroid excretion in the rat, i.e. a change in the value of cholic: chenodeoxycholic acid or from a mechanism not yet elucidated.

Attack of dominant colony males of an albino rat (Rattus norvegicus) strain, on introduced strangers, produced a non-random distribution of bites, with ventral trunk virtually never bitten. Also, vibrissae-contact of attacker and defender interfered with bites to the defender's head and upper back. The specific agonistic reactions of attacking and defending rats appeared to involve strategies based on these limitation on attack: defenders utilized 'boxing' and lying 'on-the-back' behaviour, which interposed ventral trunk and vibrissae between attacker and defender. In turn, the 'lateral display' permitted attackers to circumvent the defender's behaviour. Limitations on attack therefore appeared to underlie the specific agonistic behaviour of both attacking and defending rats.

The radiologist plays an important role in the examination of nontraumatized patients with chest pain presenting in the emergency room. In some instances, a diagnosis can be made on the basis of the initial radiograph. In others, consultation with the referring physician may either make the diagnosis or indicate a need for additional view or other imaging procedures. In this discussion, medical conditions associated with various radiographic appearances of the chest have been considered. We have not attempted to be encyclopedic, but have confined ourselves to the more common or distinctiive radiographic findings. Obviously, chest pain can occur from many other causes including primary disease in the neck, abdomen, and skeletal system.

5-Thio-D-glucose ( 5TG ) elicits a time-dependent effect on net D-glucose transport and metabolism in the mouse small intestine. When incubation periods were less than 45 min, 5TG inhibited net D-glucose transport. As incubation periods were lengthened to 60 min or greater, net D-glucose transport was potentiated by 5TG , with a concomitant inhibition of lactate production from exogenous D-glucose. Furthermore, D-glucose inhibited 5TG transport at every time point studied. Initial velocity profiles done with 5TG and D-glucose, respectively, resulted in a KT of 6.3 mM and a Tmax of 18.5 mumole/g/30 min for 5TG ; while for D-glucose the KT was 11.7 mM and the Tmax was 43.4 mumole/g/30 min. Competitive inhibition between 5TG and D-glucose was demonstrated. The apparent KI's for 5TG and D-glucose were 3.0 mM and 9.3 mM, respectively. These findings indicated that 5TG has a lower affinity for the hexose-transport carrier than D-glucose. 5TG was also found to inhibit 3-O-methyl-D-glucose (3MG) and D-galactose transport in a dose-dependent manner. Basal levels of lactate production were not affected by 5TG nor did 5TG affect lactate levels in the presence of 3MG. These results suggest that 5TG decreases intestinal utilization of D-glucose via glycolysis to partially account for the observed increase in net transmural transport of D-glucose.

The echocardiographic findings in a case of cor triatriatum are described. The diagnosis was suggested by a normal anterior mitral valve echo and a dense band of echoes posterior to the aortic root and within the body of the left atrium; it was documented at cardiac catheterization and proved surgically. Echocardiography is an important diagnostic aid in assessing pulmonary venous obstruction in children.

The clinical, roentgenographic, hemodynamic, and angiographic features of a patient with a right cervical aortic arch and retroesophageal aortic obstruction associated with a ventricular septal defect are presented. Surgical relief of the aortic obstruction was successfully achieved by placement of a bypass graft between the left common carotid artery and the descending thoracic aorta.

An updated, systematic approach to the diagnosis of cyanosis in the infant or child has been presented. It involves the use of clinical data (to establish the presence of cyanosis), radiographic information (to assess lung parenchyma, pulmonary vascularity, and certain key, border-forming, cardiac structures), and M-mode and cross-sectional echocardiographic data (the source of detailed intracardiac anatomic information). Specific radiographic and echocardiographic features of the 10 most common cyanotic congenital heart lesions have been presented. Using this approach, one should be able to diagnose accurately the cyanotic infant or child. Further planning for cardiac catheterization and angiocardiography can then be accomplished with an informed and rational point of view.

A metastatic tumor in the right ventricle was clearly visualized using two-dimensional echocardiography. The location, size, and mobility of the tumor were easily demonstrated. Two-dimensional echocardiography is superior to M-mode echocardiography in such cases.

The effects of intracoronary administration of contrast materials on regional and global left ventricular (LV) function were assessed in anesthetized dogs with segmental myocardial ischemia produced by critical stenosis of the circumflex coronary artery. Effects caused by sodium meglumine diatrizoate (R76), sodium meglumine calcium metrizoate (ISO), and metrizamide were evaluated. In the nonischemic state R76 produced an early (0-10 seconds) decrease in LV contractility followed by a late (10-20 seconds) positive inotropic effect. In the presence of regional ischemia there was prolongation of the negative inotropic effect. ISO produced only positive inotropic effects without significant differences between responses in the nonischemic and ischemic states. Metrizamide produced almost no alterations in LV function.

The addition of inositol to the growth medium of Saccharomyces cerevisiae resulted in rapid changes in the rates of phospholipid biosynthesis. The partitioning of the phospholipid intermediate CDP-diacylglycerol was shifted to phosphatidylinositol at the expense of phosphatidylserine and its derivatives phosphatidylethanolamine and phosphatidylcholine. Serine at 133-fold greater concentrations than that of inositol shifted the partitioning of CDP-diacylglycerol to phosphatidylserine at the expense of phosphatidylinositol but to a much lesser degree. Kinetic experiments with pure phosphatidylserine synthase and phosphatidylinositol synthase indicated that the partitioning of CDP-diacylglycerol between phosphatidylserine and phosphatidylinositol was not governed by the affinities both enzymes have for their common substrate CDP-diacylglycerol. Instead, the main regulation of phosphatidylinositol and phosphatidylserine synthesis was through the exogenous supply of inositol. The Km of inositol (0.21 mM) for phosphatidylinositol synthase was 9-fold higher than cytosolic concentration of inositol (24 microM). The Km of serine (0.83 mM) for phosphatidylserine synthase was 3-fold below the cytosolic concentration of serine (2.6 mM). Therefore, inositol supplementation resulted in a dramatic increase in the rate of phosphatidylinositol synthesis, whereas serine supplementation resulted in little affect on the rate of phosphatidylserine synthesis. Inositol also contributed to the regulation of phosphatidylinositol and phosphatidylserine synthesis by having a direct affect on phosphatidylserine synthase activity. Kinetic experiments with pure phosphatidylserine synthase showed that inositol was a noncompetitive inhibitor of the enzyme with a Ki of 65 microM.

We have discussed several diseases that diffusely affect the pulmonary parenchyma. The diagnostic problem is to separate cardiac pulmonary edema from noncardiac pulmonary edema, diffuse interstitial fibrosis, and lymphangitic spread of carcinoma. Frequently, this may not be possible by radiographic means alone, and additional historic and physiologic information must be obtained. It is also important to know that cardiac pulmonary edema may present in a focal or regional distribution in patients with chronic obstructive pulmonary disease. Several additional radiographic tests may be used to evaluate abnormal pulmonary parenchymal densities seen on the portable chest radiograph, when the differential diagnosis includes increased extravascular water, pneumonia, and pulmonary fibrosis. The easiest of these tests to perform is the gravitational shift test.

The treatment of ischemic heart disease is dependent upon defining the physiologic significance of coronary arterial stenoses demonstrated on coronary arteriograms. Accordingly, physiologic--angiographic correlates were studied in 12 anesthetized dogs prepared with an electromagnetic flowmeter and micrometer-controlled occluder on the circumflex coronary artery, a pair of sonic crystals in the myocardium within the distribution of the circumflex artery, and a catheter in the thoracic aorta. Measurement of arterial diameters on coronary arteriograms was made to define the minimum percent stenosis that caused: (1) decrease in resting coronary blood flow (CBFr); decline in the peak level of coronary blood flow (CBF) produced by intense vasodilatation induced by intracoronary infusion of ATP (CBFATP); and (3) segmental left ventricular (LV) dysfunction. CBFR decreased at an average stenosis of 80.45 +/- 9.13% (SD) (percent reduction in luminal diameter), while CBFATP declined at a stenosis of 31.83 +/- 5.64%. Segmental LV dysfunction was observed at a stenosis of 85.92 +/- 9.83%. In all dogs, the initial stenosis causing decline in CBFATP was a less than or equal to 40% reduction in luminal diameter. The results of this study indicate that coronary arterial stenoses of 40% or less may be hemodynamically significant under situations of augmented CBF. On the other hand, regional contractile function at rest is preserved up to stenosis in excess of 80%.

The development of lung metastases from subcutaneously implanted tumors or the development of lung nodules from intravenously injected tumor cells are model systems for metastases formation. Animals bearing subcutaneous Lewis lung tumors (50-100 mm3) were treated with a single dose of Fluosol-DA followed by 1 h of breathing carbogen or maintenance in air. Their lungs were examined for metastases 25 or 40 days after tumor cell implantation. Treatment with Fluosol-DA and carbogen or air breathing reduced by almost 4-fold the number of lung metastases seen. The addition of Fluosol-DA with air or carbogen breathing to treatment of the tumor-bearing limb with 20 Gy reduced the number of lung metastases by 2-fold compared to radiation treatment alone. If Fluosol-DA was administered immediately before or up to 3 days prior to an intravenous challenge with Lewis lung tumor cells, there was a 2- to 3-fold reduction in the number of lung nodules formed. Fluosol-DA administered immediately before or up to 4 days prior to B16 melanoma cells caused a 2- to 3-fold reduction in the number of lung nodules observed. The vascular endothelial cell monolayer adhesion assay was used to test the effects of prior exposure to Fluosol-DA on the attachment of radiolabelled B16 melanoma cells in vitro. There was a trend toward increasing attachment of B16 cells to the endothelial monolayer with prior exposure to increasing concentrations of Fluosol-DA; however, this difference did not reach statistical significance.

A case of single coronary artery from the right sinus of Valsalva with a connecting branch passing between the aorta and right ventricular infundibulum is described. The anomaly was demonstrated at coronary arteriography and verified at surgery. This type of single coronary artery has been associated with sudden exertional death in young persons. The case prompted a review of the classification of single coronary artery with emphasis on clinical significance of the various subtypes and angiographic findings.

The membrane-associated phospholipid biosynthetic enzyme CDP-diacylglycerol synthase (CTP:phosphatidate cytidylyltransferase, EC 2.7.7.41) was purified 2,300-fold from Saccharomyces cerevisiae. The purification procedure included Triton X-100 solubilization of mitochondrial membranes, CDP-diacylglycerol-Sepharose affinity chromatography, and hydroxylapatite chromatography. The procedure resulted in a nearly homogeneous enzyme preparation as determined by native and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Radiation inactivation of mitochondrial associated and purified CDP-diacylglycerol synthase suggested that the molecular weight of the native enzyme was 114,000. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme preparation yielded two subunits with molecular weights of 56,000 and 54,000. Antibodies prepared against the purified enzyme immunoprecipitated CDP-diacylglycerol synthase activity and subunits. CDP-diacylglycerol synthase activity was dependent on magnesium ions and Triton X-100 at pH 6.5. Thio-reactive agents inhibited activity. The activation energy for the reaction was 9 kcal/mol, and the enzyme was thermally labile above 30 degrees C. The Km values for CTP and phosphatidate were 1 and 0.5 mM, respectively, and the Vmax was 4,700 nmol/min/mg. Results of kinetic and isotopic exchange reactions suggested that the enzyme catalyzes a sequential Bi Bi reaction mechanism.

Extreme variations of heart rate caused clinical and radiographic findings of heart failure in six neonates in the absence of structural heart disease. Two infants had heart block with heart rates below 50/min and four had paroxysmal atrial tachycardia with rates approaching 300/min. Each infant had interstitial or alveolar pulmonary edema and most had cardiomegaly. After restoration of a normal heart rate, there was rapid and dramatic resolution of pulmonary edema and reduction in cardiac size.

The effect of patient positioning on thallium-201 images in the left lateral projection was evaluated in 28 patients. The left lateral image was performed with the patient on his right side (LLrs) and also supine (LLsup). False-positive inferoposterior defects were reported in five patients (18%) in the LLsup view, but not in the LLrs view. Image quality was better in the LLrs view. The false-positive results in the LLsup view may result from two factors: a) overlap of the left hemidiaphragm and myocardium; or b) changes in orientation of the heart in the two lateral positions. Therefore, thallium-201 images in the LL position should be performed with the patient lying on his right side.

Cardiac fluoroscopy followed by a submaximal exercise electrocardiogram was used to evaluate 129 healthy men (average age 49 p 6) for assessment of possible latent ischemic heart disease in an asymptomatic population. Of 108 subjects who completed the exercise protocol, 37 (34%) had at least one fluoroscopically detected calcified coronary artery. Of the 16 subjects with a positive exercise stress test, 13 (81%) had calcification of at least one coronary artery, Thirteen of 37 (35%) with calcification had a positive exercise test. Those with calcification of at least one coronary artery had a ninefold increased risk of a positive exercise stress test (p less than 0.0001). The location of a calcific deposit conferred greater risk of exercise-induced ischemic changes than did multivessel involvement. Forty-seven per cent of men with calcification in the left anterior descending coronary artery had an abnormal exercise electrocardiogram vs. 33% and 16% of persons with left circumflex and right coronary artery calcifications, respectively.

A Saccharomyces cerevisiae mutant (cdg1 mutation) was isolated on the basis of an inositol excretion phenotype and exhibited pleiotropic deficiencies in phospholipid biosynthesis. Genetic analysis of the mutant confirmed that the cdg1 mutation represents a new genetic locus and that a defect in a single gene was responsible for the Cdg1 phenotype. CDP-diacylglycerol synthase activity in mutant haploid cells was 25% of the wild-type derepressed level. Biochemical and immunoblot analyses revealed that the defect in CDP-diacylglycerol synthase activity in the cdg1 mutant was due to a reduced level of the CDP-diacylglycerol synthase Mr-56,000 subunit rather than to an alteration in the enzymological properties of the enzyme. This defect resulted in a reduced rate of CDP-diacylglycerol synthesis, an elevated phosphatidate content, and alterations in overall phospholipid synthesis. Unlike wild-type cells, CDP-diacylglycerol synthase was not regulated in response to water-soluble phospholipid precursors. The cdg1 lesion also caused constitutive expression of inositol-1-phosphate synthase and elevated phosphatidylserine synthase. Phosphatidylinositol synthase was not affected in the cdg1 mutant.

Left ventricular angiograms of six children were reviewed, and it was found that those obtained in axial (long axial oblique and hepatoclavicular) projections enhanced precision in the diagnosis of subvalvular aortic stenosis. The methods for obtaining these views are described, and the results presented. Axial views are never inferior to standard (posteroanterior, lateral, and right anterior oblique) projections, and are usually superior to them, especially when there are associated lesions, such as ventricular septal defects, left-sided obstructive lesions, and patent ductus arteriosus.

Chest radiographs of 100 patients with suspected pericardial effusion who underwent echocardiography were reviewed. Fifty were echo-positive and 50 were negative. The differential density sign was present in 34 patients (68%) who were echo-positive and 2 patients (4%) who were negative; on frontal (62%) and lateral (41%) projections; and in patients with small, moderate, and large effusions. Computed tomographic findings in 1 patient correlated closely with those obtained radiographically. Experimental models suggest this sign is related to different tissue attenuation coefficients for blood and saline, different tissue thicknesses of the spherically shaped heart, the presence of epicardial fat around the heart, and chest film exposure factors. "Trapping" of the middle lobe or anterior lingula may also contribute. When pericardial effusion is not suspected, the presence of this sign should be an indication for echocardiography.