One-carbon metabolism in Neurospora crassa wild-type and in mutants partially deficient in serine hydroxymethyltransferase.

1. The concentrations of folate-dependent enzymes in Neurospora crassa Lindegren A wild type (FGSC no. 853), Ser-l mutant, strain H605a (FGSC no. 118), and for mutant, strain C-24 (FGSC no. 9), were compared during exponential growth on defined minimal media. Both mutants were partially lacking in serine hydroxymethyltransferase, but contained higher concentrations of 10-formyltetrahydrofolate synthetase than did the wild type. Mycelia of the mutants contained higher concentrations of these enzymes when growth media were supplemented with 1mM-glycine. In the wild-type, this glycine supplement also increased the specific activities of 5,10-methylenetetrahydrofolate dehydrogenase and 5,10-methylenetetrahydrofolate reductase. 5. During growth, total folate and polyglutamyl folate concentrations were greatest in the wild-type. Methylfolates were not detected in mutant Ser-l, and were only present in the for mutant after growth in glycine-supplemented media. Exogenous glycine increased folate concentration threefold in the wild type, mainly owing to increases in unsubstituted polyglutamyl derivatives. 3. Feeding experiments using 14C-labelled substrates showed that C1 units were generated from formate, glycine and serine in the wild type. Greater incorporation of 14C occurred when mycelia were cultured in glycine-supplemented media. Formate and serine were precursors of C1 units in the mutants, but the ability to cleave glycine was slight or lacking.


Location of an oligomycin-insensitive and magnesium ion-stimulated adenosine triphosphatase in rat spleen mitochondria.

1. When rat spleen mitochondria are incubated with oxidizable substrates, added MgCl2 (greater than 150 muM free concentration) markedly stimulates state-4 respiration and lowers both the respiratory control and ADP/O ratios; this effect is reversible on addition of excess of EDTA. 2. With [gamma-32P]ATP as substrate, an Mg2+-stimulated ATPase (adenosine triphosphate) was identified in the atractyloside-insensitive and EDTA-accessible space of intact rat spleen mitochondria. 3. Oligomycin has no effect on the activity of the Mg2+-stimulated ATPase at a concentration (2.0mug/mg of protein) that completely inhibits the atractyloside-sensitive reaction. Of the two ATPase activities, only the atracytoloside sensitive reaction is stimulated (approx. 40%) by dinitrophenol. 4. On digitonin fractionation the atractyloside-insensitive Mg2+-stimulated ATPase co-purifies with the outer membrane-fraction of rat spleen mitochondria, whereas (as expected) the atractylosidesensitive activity co-purifies with the inner-membrane plus matrix fraction. 5. Stoicheiometric amounts of ADP and Pi are produced as the end products of ATP hydrolysis by purified outer-membrane fragments; no significant AMP production is detected during the time-course of the reaction. 6. The outer-membrane ATPase is present in rat kidney cortex and heart mitochondria as well as in spleen, but is absent from rat liver, thymus, brain, lung, diaphragm and skeletal muscle.


Effect of p-chlorophenylalanine (PCPA) on pituitary hormones and testosterone in the human.

L-p-Chlorophenylalanine (L-PCPA) was given in a dosage of 1.5 g daily, to 6 healthy male subjects over a period of 12 days. No effect on plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), growth hormone (GH), thyroid stimulating hormone (TSH), testosterone and other steroid hormones could be observed. These results are discussed in respect to the sexually stimulating effect of PCPA.


Test of reliability of echocardiographic estimation of left ventricular dimensions and volumes.

This test is based on the incompressibility of myocardium, which dictates that left ventricular wall volume remains constant throughout the cardiac cycle. The volumes occupied by the left ventricular cavity, by ventricular wall plus cavity, and hence by ventricular wall alone were estimated, both at end-systole and at end-diastole, from ecocardiographic measurements of cavity transverse dimension and wall thickness. Wall volumes were determined by assuming an ellipsoid shape (the major axis being predicted from aggression equations relating angiocardiographic and echocardiographic cavity dimensions) and also by the cube method. A discrepancy between systolic and diastolic wall volume estimates indicates either that the measurements of ventricular dimensions were unreliable or that the assumptions of ventricular geometry involved in the volume calculations were incorrect. Studies were made on 60 subjects. Using the ellipsoid formula, values for wall volume ranged from 66 to 719 ml; systolic and diastolic wall volumes correlated closely (r = 0-96, mean difference = 6-8 +/- 0-9 (SEM) %) supporting the reliability of the echocardiographic dimensions and estimates of cavity and wall volume. In the 12 patients with very large end-diastolic cavity transverse dimensions (6-5 to 8-6 cm) however, correlation was less good (r - 0-81, mean difference = 14-3 +/- 2-3 (SEM) 5). Using the cube method, which does not allow for the changing relation between minor and major cavity axes with increasing cavity size, wall volumes were greater (76 to 986 ml) but correlation was similar (r = 0-94, mean difference = 7-1 +/- 0-9 (SEM)%). Having established that it is possible to obtain close agreement between wall volumes determined at different points in the cardiac cycle, this test can be used to assess the reliability of echocardiographic left ventricular dimensions and volume estimates in individual subjects.


Surgical treatment of postinfarction left ventricular aneurysm in 32 patients.

Thirty-two patients with large postinfarction left ventricular aneurysms shown at operation to consist of fibrous tissue are reported. All had angina and/or breathlessness, and none had a history of embolism. Thirty were correctly diagnosed by left ventricular cineangiography. Two of the 3 patients with inferior and 1 with an anterior aneurysm had associated ventricular septal defects, and 3 patients with an anterior aneurysm had mitral regurgitation. All had major coronary arterial lesions and 68 per cent had double or triple vessel disease. The aneurysm was excised in all patients; in 15 this was combined with saphenous vein bypass grafting of coronary arteries supplying surviving myocardium, in 3 with closure of a ventricular septal defect, and in 3 with mitral annuloplasty or replacement. Operative mortality was 6-2 per cent, and 79 per cent of the survivors are asymptomatic with average follow-up period of 18 months after operation.


Diagnostic criteria for computer-aided electrocardiographic 15-lead system. Evaluation using 12 leads and Frank orthogonal leads with vector display.

The criteria for the diagnosis of myocardial infarction and ischaemic heart disease by an automated 15-lead computer-aided electrocardiographic system were examined using electrocardiograms of 543 patients. Errors in the electrocardiographic diagnosis were evaluated for each lead system (Frank orthogonal 3-lead, 12-lead, and hybrid 15-lead) using clinical and catheterization data for definitive diagnosis before review of the electrocardiograms and their reports. The effects of combinations of these diagnoses and additional ventricular conduction defects were also studied. Myocardial infarction and left ventricular hypertrophy were more reliably diagnosed using 3-lead and 12-lead systems together than with either system alone. The most sensitive criteria for anterior infarction were a Q/R ratio in Z less than 0-1 and loss of the first 20 ms of anterior forces in the horizontal and sagittal planes of the vectorcardiogram. However, false positive results were frequent, particularly in association with left ventricular hypertrophy, non-specific intraventricular conduction defects, and left bundle branch system block. Our V lead criteria were more specific whether or not these associated conditions were present. No single criterion with an acceptable false positive rate could be found to be sensitive for inferior infarction in all situations. Our most sensitive criteria were those based on the limb leads, and the presence of superior forces for the first 30 ms in the frontal plane of the vectorcardiogram, but these were better in combination. Limb lead criteria were the most specific. False positive results for inferior infarction were more frequent in the presence of left ventricular hypertrophy or ventricular conduction defects other than left anterior hemiblock. ST and T wave abnormalities were more apparent in the 12 leads than in the orthogonal leads. Specificity and sensitivity of criteria were poor, and specificity was decreased and sensitivity was not significantly improved by combining 3-lead with 12-lead criteria. Because of frequent measurement errors of ST, T, and also Q waves by the computer programme, in practice we have achieved increased sensitivity in the diagnosis of ischaemia and infarction with the combination of 3-lead and 12-lead systems. It is concluded that errors of diagnosis by a computer-aided system can be reduced by using multiple leads and that both 12-lead and orthogonal 3-lead systems are necessary for optimal computer diagnosis of left ventricular hypertrophy, myocardial infarction, and ischaemia.


Mitral regurgitation in coronary heart disease.

Mitral reguritation is a relatively common finding in coronary heart disease. In this series of 127 patients, selected with a view to coronary or left ventricular surgery on the basis of severity of symptoms, the incidence was 39 (31%). Mitral regurgitation is significantly more common in patients with a history or electrocardiographic evidence of previous myocardial infarction. Clinically it may present as a pan- or late systolic or even a mid-systolic, ejection type murmur at the apex or at the left sternal edge; but in 39 per cent of the patients with angiographic mitral regurgitation no murmur was present. Angiographically important mitral regurgitation (grades 2-4/4) was usually associated with a systolic murmur; this finding was independent of ejection fractions. Left ventricular enlargement clinically or radiographically is likely to accompany mitral regurgitation but left atrial enlargement (electrocardiographically or on chest x-ray) is a more reliable pointer to mitral regurgitation and pulmonary venous hypertension is even more strongly suggestive of its presence. The electrocardiographic signs of papillary muscle infarction were rare in this series (15%) and were not related to angiographic mitral regurgitation. There was no difference in the incidence of mitral regurgitation in association with anterior or inferior myocardial infarction or in distribution of coronary artery disease. There is, however, a higher incidence of mitral regurgitation in more severe coronary arterial disease (P less than 0-05). The incidence of mitral regurgitation is significantly higher with reduction in left ventricular ejection fraction (P less than 0-001), with rise in the left ventricular end-diastolic pressure (P less than 0-02), and with abnormal contraction patterns, but the severity of mitral regurgitation is not significantly related to these findings.


Effect of myocardial infarction on components of fibrinolytic system.

A systematic investigation of the fibrinolytic system during the period after acute myocardial infarction in 42 patients showed a progressive reduction of fibrinolytic activity, with the longest lysis times on days 4 to 5 after the event. There is a concomitant rise in the levels of fibrinogen, plasminogen, and antiplasmin; only the latter parallels the delay in lysis. After 12 to 15 months, normal lysis times and fibrinogen levels were found in 24 patients re-examined. It is concluded that the reduced fibrinolytic activity in these patients was a transient phenomenon after myocardial infarction.


Structural study of pulmonary circulation and of heart in total anomalous pulmonary venous return in early infancy.

Quantitative morphometric techniques have been applied to the injected and inflated lung and to the heart in 9 infants with total anomalous pulmonary venous return dying with obstruction to pulmonary venous return. In 5 (mean age at death 55 days) pge 20 days) to an infradiaphragmatic site. Structural changes were present in the pulmonary circulation in all patients, even in the youngest, an 8-day-old child. In both types of total anomalous pulmonary venous return increased arterial muscularity was severe, as shown by increase in wall thickness and by extension of muscle into smaller and more peripheral arteries than normal; these changes tended to increase with age. Where the pulmonary venous blood drained to a supradiaphragmatic site, the severity of arterial medial hypertrophy correlated inversely with the magnitude of the pulmonary: systemic flow ratio, increasing as the pulmonary blood flow fell. Vein wall thickness was increased and in all but the youngest child the veins were 'arterialised'. At the lung periphery the arteries and alveoli appeared to have multiplied normally. Arterial size varied according to whether pulmonary venous blood drained above or below the diaphragm; the diameter of pre- and intra-acinar arteries was increased only in cases where the pulmonary venous return drained to a supradiaphragmatic site, being normal when it drained to an infradiaphragmatic site. In the heart the left ventricle was of normal size in all but one case. Dilation and severe hypertrophy of the right ventricle and septum were present only in cases of drainage to a supradiaphragmatic site. In the older patients with the latter anomaly dilation of the pulmonary arteries and right ventricle suggested that a large left-to-right shunt had preceded the onset of obstruction to pulmonary venous return and that the more severe right ventricular and septal hypertrophy in these cases might be the result of a longer duration of pulmonary hypertension. In contrast, in total anomalous pulmonary venous return to an infradiaphragmatic site it appears that obstruction to pulmonary venous return develops soon after birth and prevents a large increase in pulmonary blood flow, and thus neither the pulmonary arteries nor the right ventricle become dilated. In infants with total anomalous pulmonary venous return and obstruction to pulmonary venous return, it is striking how rapidly the pulmonary circulation develops new muscle.


Innate and drug-induced resistance to acute lung damage caused in rats by alpha-naphthyl thiourea (ANTU) and related compounds.

During the 3rd and 4th weeks of life rats were highly resistant to the toxic effects of alpha-naphthyl thiourea (ANTU) and of thiourea and its derivatives but toxicity developed rapidly during the following 2 weeks. Marked resistance to lung damage by toxic thioureas could be induced in older, mature rats by pretreatment with the toxic agent itself (tachyphylaxis), with other toxic and non-toxic antithyroid drugs or with iodine or iodide--even if the rats were pretreated at an early age before susceptibility to the agent developed. ANTU-tachyphylaxis was dose-dependent. Total thyroidectomy did not affect either lung damage induced by ANTU or the resistance due to tachyphylaxis or to pretreatment with iodide or the antithyroid drugs thiourea, 1-ethyl-1-phenyl thiourea or propyl thiouracil. Neither total nor medullary adrenalectomy affected ANTU toxicity. Marked resistance to ANTU-induced lung damage was induced in rats by pretreatment with either an activator (3-4 benzypyrene) or an inhibitor (SKF 525-A) of drug-metabolizine mixed-function microsomal enzyme systems; the inhibitor, sodium phenobarbitone, had no significant effect on toxicity. The sulphydryl compound, AET, induced marked resistance to ANTU; cysteine was less effective. Neither autonomic blockade with nicotine and atropine nor actinomycin D had significant effects on toxicity to ANTU. The acute pulmonary oedema induced in rats by high pressure oxygen, chemical convulsants, pressor agents and ammonium sulphate differed in many respects from that induced by toxic thioureas; it was typically haemorrhagic in nature, did not result in significant pleural effusion, did not exhibit tachyphylaxis, and was not influenced by pretreatment with iodide or derivatives of thiourea.


Production of intestinal and other tumours by 1,2-dimethylhydrazine dihydrochloride in mice. II. Scanning electron microscopic and cytochemical study of colonic neoplasms.

Thum of colon induced by repeated subcutaneous injections of 1,2-dimethyl-hydrazine dihydrochloride in mice were studied by scanning electron microscopy. In addition, the surface composition of normal and malignant colonic epithelial cells were investigated by ultrastructural cytochemistry. The neoplastic, nodular tumour masses which protruded into the lumen of colon displayed an asymmetrical, irregular growth pattern and surface contour. In contrast to the normal surface structure, the shape of crypt openings in malignant areas was distorted and they were irregularly spaced. Cells varying in size and shape in the intercrypt regions often formed random patterns of elevations and depressions. Microvilli on neoplastic cells were larger, more club-shaped and showed more disorderly arrangement than their normal counterparts. The distribution and quantity of surface acid mucopolysaccharide content and adenosine triphosphatase activity varied considerably from cell to cell in the neoplastic epithelium while they were more uniform in the normal colonic surface cells.


Banked blood microfiltration. II. Dacron-wool microfilter.

It is well established that debris tends to accumulate in banked blood, the amount of debris increasing with storage time. If such a blood is transfused to a patient, it will be filtered by the capillary network of the lungs and could cause various intensities of microemboli. These can be prevented by microfiltration--the Swank IL200 transfusion filter made of Dacron wool is perfectly suitable. It removes more than 70% of the debris 29-100 mum size from four blood units and its  efficiency for particle removal is greatly increased by lactate priming.


Treatment of peripheral corneal ulcers by limlial conjunctivectomy.

We report the rapid healing of several cases of marginal corneal ulceration of various aetiologies after the excision of a 4 to 7 mm strip of adjacent limbal conjunctiva. After conjunctivectomy the remaining conjunctiva was loosely recessed (without sutures). In one case with coexisting scleromalacia, we excised strips of adjacent bulbar conjunctiva with equally good results. Some of the cases had failed to respond to other modes of treatment including topical collagenase inhibitors. One case responded to peritomy and cryotherapy to the ulcer edges, but we have abandoned this treatment in favour of conjunctival excision. Limbal conjunctivectomy with recession is presumed to act by eliminating conjunctival sources of collagenase and proteoglycanase.


Further studies on the interaction of actin with heavy meromyosin and subfragment 1 in the presence of ATP.

It has been postulated that, during the hydrolysis of ATP, both normal and SH1-blocked heavy meromyosin undergo a rate-limiting transition from a refractory state which cannot bind to actin to a nonrefractory state which can bind to actin. This model leads to several predictions which were studied in the present work. First, the fraction of heavy meromysin or subfragment 1 which remains unbound to actin when the ATPase equals Vmax should have the same properties as the original protein. In the present study it was determined that the unbound protein has normal ATPase activity which suggests that it is unbound to actin for a kinetic reason rather than because it is a permanently altered form of the myosin. Second, if the heavy meromyosin heads act independently half as much subfragment 1 as heavy meromyosin should bind to actin. Experiments in the ultracentrifuge demonstrate that about half as much subfragment 1 as heavy meromyosin sediments with the actin at Vmax. Third, the ATP turnover rate per actin monomer at infinite heavy meromyosin concentration should be much higher than the ATP turnover rate per heavy meromyosin head at infinite actin concentration. This was found to be the case for SH1-blocked heavy meromyosin since, even at very high concentrations of SH1-blocked heavy meromyosin, in the presence of a fixed actin concentration, the actin-activated ATPase rate remained proportional to the SH1-blocked heavy meromyosin concentration. All of these results tend to confirm the refractory state model for both SH1-blocked heavy meromyosin and unmodified heavy meromyosin and subfragment 1. However, the nature of the small amount of heavy meromyosin which does bind to actin in the presence of ATP at high actin concentration remains unclear.


Properties of deoxycholate solubilized sarcoplasmic reticulum Ca2+-ATPase.

The Ca2+-dependent ATPase of sarcoplasmic reticulum after solubilization with deoxycholate and removal of lipid by gel chromatography exists as a mixture of monomer, dimer, and smaller amounts of higher molecular weight aggregates. The binding capcity of deoxycholate by monomeric and oligomeric forms of the ATPase is 0.3 g/g of protein at pH 8 and ionic strength 0.11. Examination in the analytical ultracentrifuge results in estimates of protein molecular weight of monomer of 115 000 +/- 7000 and of Stokes radius of 50-55 A. The results indicate an asymmetric shape of both delipidated monomer and dimer. Solubilization of ATPase vesicles by deoxycholate at high protein dilutions leads to almost instantaneous loss of ATPase activity. However, ATPase may be solubilized by deoxycholate in presence of phospholipid and sucrose in a temporarily active state. Inactivation appears to be accompanied by delipidation and conformational changes of the protein as evidenced by circular dichroism measurements. Sedimentation velocity examination of enzymatically active preparations of soluble ATPase in presence of phospholipid and sucrose strongly suggests that the major part of enzymatic activity is derived from a monomer with an asymmetric shape. The extent of formation of soluble oligomers by column chromatography was dependent on the exact conditions used for initial solubilization of ATPase. No evidence for differences among monomer and dimer fractions was obtained by isoelectric focusing and amino acid analysis. The results of these studies are compatible with electron-microscopic studies by other authors which suggest that the ATPase has an elongated shape with limited hydrophobic contact with the membrane lipid. A resemblance of delipidated oligomers with the form in which ATPase occurs in the membrane is conjectural at present.


Mechanism of oxygen exchange in actin-activated hydrolysis of adenosine triphosphate by myosin subfragment 1.

The gamma-phosphoryl groups of two intermediates (M-ATP and M-ADP-P1) in the pathway of MgATP hydrolysis by myosin undergo extensive oxygen exchange with water. Actin activates the overall rate of hydrolysis at a rate-limiting step which follows these exchange reactions. Thus, actin, by decreasing the turnover time of hydrolysis, would be expected to proportionately decrease the time available for oxygen exchange. Using subfragment 1 of myosin, the turnover time of hydrolysis can be varied over a wide range by changing the concentration of actin. An estimate for the rate constant of exchange can then be obtained by relating these turnover times to measured values for oxygen exchange (incorporation of 18O from H218O into the inorganic phosphate (Pi) released by hydrolysis). The results of such an experiment, with turnover times between 0.2 and 25 s, indicate that, for each gamma-phosphoryl group, one oxygen from the medium is added rapidly (to cleave the phosphoryl group or form a pentacoordinate phosphroyl complex); two more oxygens exchange with a rate constant, kc, of about 1 s-1; and a fourth oxygen exchanges slowly with ke about 0.2 s-1. The higher value is about 18 times smaller than the rate constant, 5-3, for the reverse cleavage step of the myosin pathway, which is postulated to be responsible for oxygen exchange. The data, then, indicate that the rate-limiting step for oxygen exchange is not k-3, but may be the rate of rotation of oxygens around the phosphorus atom, with one oxygen severely restricted by its binding to the active site. The finding that kc differs for the four oxygens in each phosphate group is related to past observations on myosin-catalyzed oxygen exchange.


Dynamic reversal of enzyme carboxyl group phosphorylation as the basis of the oxygen exchange catalyzed by sarcoplasmic reticulum adenosine triphosphatase.

Millisecond mixing and quenching experiments demonstrate an apparent t1/2 for the labeling of phosphorylated sarcoplasmic reticulum ATPase by 32Pi at pH 6 and 30 degrees C of 30 to 40 ms. Under the same conditions, the rate of exchange of water oxygens with inorganic phosphate (Pi) is about 40 mol of H2O exchanged with Pi per 10(6) g of protein per s. Theoretical equations are developed for the expected 32P-labeling pattern given various comparative rates of flux between Pi and the Michaelis complex and between the Michaelis complex and phosphorylated enzyme. The results show that the rapid reversal of the formation of the phosphorylated enzyme is a major source of the oxygen exchange and are consistent with such reversal being the only source.


Reversible inhibition of (Na+, K+) ATPase by Mg2+, adenosine triphosphate, and K+.

Adenosine triphosphate (ATP) hydrolysis catalyzed by the plasma membrane (Na+,K+)ATPase isolated from several sources was inhibited by Mg+, provided that K+ and ATP were also present. Phosphorylation of the adenosine triphosphatase (ATPase) by ATP and by inorganic phosphate was also inhibited, as was p-nitrophenyl phosphatase activity. (Ethylenedinitrilo)tetraacetic acid (EDTA) and catecholamines protected from and reversed the inhibition of ATP hydrolysis by Mg2+, K+ and ATP. EDTA was protected by chelation of Mg2+ but catecholamines acted by some other mechanism. The specificities of various nucleotides as inhibitors (in conjunction with Mg2+ and K+) and as substrates for the (Na+, K+) ATPase were strikingly different. ATP, ADP, beta,gamma-CH2-ATP and alpha,beta-CH2-ADP were active as inhibitors, whereas inosine, cytidine, uridine, and guanosine triphosphates (ITP, CTP, UTP, and GTP) and adenosine monophosphate (AMP) were not. On the other hand, ATP and CTP were substrates and beta,gamma-NH-ATP was a competitive inhibitor of ATP hydrolysis, but not an inhibitor in conjunction with Mg2+ and K+. The Ca2+-ATPase from sarcoplasmic reticulum and F1, the Mg2+-ATPase from the inner mitochondrial membrane, were also inhibited by Mg2+. Catecholamines reversed inhibition of the Ca2+-ATPase, but not that of F1.


Further purification of bovine spleen inhibitors of lymphocyte DNA synthesis (chalones).

Partially purified lymphocytic factors were obtained from boving spleen; these factors are non-cytotoxic and biologically active in vitro and in vivo: [3H]Thymidine incorporation into DNA of mitogen-stimulated mouse spleen cells in culture is inhibited; similar results are obtained with phytohaemagglutinin-stimulated peripheral human lymphocytes, where blast cells transformation is blocked. [3H]Thymidine incorporation into DNA of mitogen stimulated lymphocytes withdrawn from in vivo treated mice, is also reduced. The two factors in vitro and in vivo seem to act preferentially on mouse spleen cells compared to their action on liver, kidney and testicle cells in cluture, as far as thymidine incorporation into DNA is concerned. The following techniques were applied for their purification: 1. Homogenization of the fresh tissue in water, centrifugation, dialysis of the supernatant, centrifugation, fractionation of the supernatant by alcoholic precipitation and finally concentration in vacuo and lyophilization of the material soluble at 75% of alcohol yielded fraction F. 2. Preparation of an acetone powder from the spleen, extraction of the dry powder with water, then high speed centrifugation, followed by lyophilization of the supernatant produced fraction F'. Both fractions F and F' were further fractionated by chromatography on a Sephadex G75 column: 7 peaks were obtained (F1--F7). Biological activity was found in fraction F1, corresponding to high molecular weight material, and in  fraction F6, corresponding to low molecular weight substances. By rechromatography on Sephadex G 75, it is easy to dissociate from F1 a small molecular weight fraction which might be similar to F6 as far as elution volume and biological properties are concerned.


The measurement of ouabain binding and some related properties of digitonin-treated (Na+,K+)-ATPase.

1. Digitonin treated membrane preparations purified from dog kidney lose their (Na+,K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) activity, but the K+-phosphatase and Na+-dependent ADP-ATP exchange activities survive and remain ouabain-sensitive. Because the enzyme preparations consist largely of pure (Na+,K+)-ATPase, these effects of digitonin must be intrinsic to the Na+ pump. 2. Concomitant with these enzymatic changes, digitonin treatment alters the sensitivity of the phosphatase and exchange activities to ouabain. 3. Attempts to measure ouabain binding by the usual centrifugation or filtration methods proved unsuccessful. A filtration method involving a double 0.01 mum filter and omitting water washes is necessary to demonstrate ouabain binding. Under these conditions, ouabain binding capacity appears to be unchanged in the presence of digitonin, but the apparent dissociation constant is doubled. 4. Ouabain binding is rendered more reversible by digitonin treatment, since washing filters with water removes a large fraction of bound ouabain without affecting the retention of exchange activity. 5. The double filter method traps essentially all of the ADP-ATP exchange activity on the filter. However, a large and somewhat variable proportion of the K+-phosphatase activity passes through the filter. Sodium dodecyl sulfate polyacrylamide gel analysis of the filtrate shows that a small amount of filtrable protein catalyzed this phosphatase activity at greatly increased turnover rates. Both subunits of the (Na+, K+)-ATPase are present in this latter protein fraction.


Sulphydryl groups in photosynthetic energy conservation. IV. Inhibition of the ATPase of chloroplast coupling factor 1 by sulphydryl reagents.

1. O-Iodosobenzoate and 2,2'-dithio bis-(5-nitropyridine) inhibited by about fifty per cent the ATPase activity of heat-activated chloroplast coupling factor 1 only when present during the heating but were without effect when added before or after the activation. Reversion of this inhibition was only obtained by a second heat treatment with 10 mM dithioerythritol. 2. The inhibition of the Ca2+-ATPase of coupling factor 1 by o-iodosobenzoate or 2,2'-dithio bis-(5-nitropyridine) was not additive with similar inhibitions obtained with the alkylating reagents iodoacetamide and N-ethylmaleimide. 3. The heat-activated ATPase of o-iodosobenzoate-treated coupling factor 1 had a higher Km for ATP, without modification of V. The modified enzyme was desensitized against the allosteric inhibitor ADP.


The lipid requirement of the (Ca2+ + Mg2+)-ATPase in the human erythrocyte membrane, as studied by various highly purified phospholipases.

1. When complete hydrolysis of glycerophosphlipids and sphingomyelin in the outer membrane leaflet is brought about by treatment of intact red blood cells with phospholipase A2 and sphingomyelinase C, the (Ca2+ + Mg2+)-ATPase activity is not affected. 2. Complete hydrolysis of sphingomyelin, by treatment of leaky ghosts with spingomyelinase C, does not lead to an inactivation of the (Ca2+ + Mg2+)-ATPase. 3. Treatment of ghosts with phospholipase A2 (from either procine pancreas of Naja naja venom), under conditions causing an essentially complete hydrolysis of the total glycerophospholipid fraction of the membrane, results in inactivation of the (Ca2+ + Mg2+)-ATPase by some 80--85%. The residual activity is lost when the produced lyso-compounds (and fatty acids) are removed by subsequent treatment of the ghosts with bovine serum albumin. 4. The degree of inactivation of the (Ca2+ + Mg2+)-ATPase, caused by treatment of ghosts with phospholipase C, is directly proportional to the percentage by which the glycerophospholipid fraction in the inner membrane layer is degraded. 5. After essentially complete inactivation of the (Ca2+ + Mg2+)-ATPase by treatment of ghosts with phospholipase C from Bacillus cereus, the enzyme is reactivated by the addition of any of the glycerophospholipids, phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine or lysophosphatidylcholine, but not by addition of sphingomyeline, free fatty acids or the detergent Triton X-100. 6. It is concluded that only the glycerophospholipids in the human erythrocyte membrane are involved in the maintenance of the (Ca2+ + Mg2+)-ATPase activity, and in particular that fraction of these phospholipids located in the inner half of the membrane.


Transport parameters and stoichiometry of active calcium ion extrusion in intact human red cells.

Ca2+-transport and its energy consumption were studied in intact human red cells loaded with Ca2+ by the aid of the ionophore A23187. After the complete elimination of the ionophore the passive Ca2+-permeability of the membrane returned to its normal low value, except when the intracellular Ca2+-concentration was higher than 3 mM or the ATP level fell below 100 muM. Within these limits the rate of Ca2+-extrusion was independent of the cellular ATP content but was greatly enhanced by increasing [Ca2+]i and reached a plateau at about 1 mM intracellular Ca2+-concentration. The maximum rate of Ca2+-efflux was about 85 mumol/l of cells per min at 37 degrees C, pH 7.4. The activation energy of active Ca2+-extrusion was found to be 15 200 cal/mol, and the optimum pH in the suspension was 7.7. Ca2+-efflux was not connected with the counter-transport of cations. The Ca2+-pump was not affected by ouabain or oligomycin and only partial inhibition could be achieved by the SH-reagents: ethacrynic acid, N-ethylmaleimide and p-chloromercuribenzoate or with propranolol and ruthenium red. An 80 to 95% inhibition of the active Ca2+-extrusion was brought about by 50-250 muM lanthanum, which in the above concentrations caused no aggregation or haemolysis. The inhibition of the Ca2+-pump by lanthanum was found to be reversible, the site of inhibition being at the external surface of the cell membrane. To examine the energy consumption of the Ca2+-extrusion, ATPase activity was assessed by measuring inorganic phosphate liberation in Ca2+-loaded red cells the metabolism of which was inhibited by iodoacetamide + Na+-tetrathionate. Ca2+-activated ATPase activity connected with the Ca2+-pump was distinguished from other Ca2+-ATPases by using the non-penetrating inhibitor, lanthanum. The molar ratio of Ca2+-transported per ATP split was found to be 2 : 1.


Control of the production and partial characterization of repressible extracellular 5'-nucleotidase and alkaline phosphatase in Neurospora crass.

A new species of orthophosphate repressible extracellular 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) was found to be released into mycelial culture media when a wild type strain of Neurospora crassa was grown on limiting amounts of phosphate. The production of 5'-nucleotidase and extracellular acid and alkaline phosphatase was inhibited by the addition of rifampicin when it was added at the later stage of mycelial growth, but not when it was added at a very early stage. The 5'-nucleotidase and extracellular alkaline phosphatase were partially purified and characterized. pH optimum of the former was 6.8 and that of the latter was higher than 10.0. The 5'-nucleotidase activity was inhibited by ethylenediaminetetraacetate (EDTA) and ZnCl2 at pH 6.8 and stimulated by MnCl2 and CoCl2 at pH 4.0. Alkaline phosphatase activity was stimulated by EDTA, MgCl2, CoCl2 and MnCl2. 5'-nucleotidase activity was stimulated by EDTA, MgCl2, CoCl2 and MnCl2. 5'-nucleotidase hydrolyzed various 5'-nucletides but not 3'-nucleotides or other various phosphomono- and diester compounds. Alkaline phosphatase hydrolyzed all the phosphomonoester compounds tested. Mutants, nuc-1 and nuc-2, which were originally isolated by the inability to utilize RNA or DNA as a sole source of phosphate, were unable to produce 5'-nucleotidase or six other repressible enzymes reported previously. These mutants showed no or significantly reduced growth on orthophosphate-free nucleotide media depending on the number of conidia inoculated, mainly because of loss of ability to produce these repressible extracellular phosphatases.


Kinetic studies of the urokinase catalysed conversion of NH2-terminal lysine plasminogen to plasmin.

A method for determining initial velocities of the urokinase (EC 3.4.99.26) catalysed converstion of NH2-terminal lysine plasminogen to plasmin (EC 3.4.21.7) is presented. This reaction has been coupled with the hydrolysis of alpha-N-benzyoly-L-arginine ethyl ester, which is catalysed by plasmin, and its rate has been determined from the time course of the overall reaction. The proenzyme-enzyme conversion was found to obey the Michaelis-Menten rate equation. The following values of the kinetic parameters were obtained: the apparent Michaelis constant, Km = 40.7 +/- 6.2 muM; the catalytic constant, kc = 2.59+/-0.31 s(-1), and kc/Km = 6.36-10(4) +/- 0.24-10(4) M(-1)-s(-1).


Effect of ADP on ATPASE from a strain of Bacillus stearothermophilus.

Bacillus stearothermophilus ATCC 12016 was unable to grow at temperatures below 40 degrees C. On incubating the bacteria at the temperatures, ATP in cells disappeared, ADP was accumulated and ATPase (EC 3.6.1.3) was inactivated. When the purified ATPase was incubated at the temperatures for 1 h with 0.17 mM ADP in the presence of MgCl2, the enzyme was completely inactivated. The inactivated enzyme was reactivated on dilution or dialysis or on warming at 65 degrees C. During the incubation of the enzyme sample, the absorbance spectrum of the enzyme changed. On further incubating the sample over 1.5 h, the second step of spectral change occurred together with the change of the circular dichrosim and the dissociation into a lower molecular weight species of the protein. When the enzyme was treated with ADP-MgCl2 at 65 degrees C, the inactivation and conformational change of the enzyme was not observed.


Observations on the kinetics, subunit composition, and sulfhydryl reactivity of myosin from Physarum polycephalum.

A highly purified preparation of myosin from Physarum polycephalum has been shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis to contain heavy chains and only one molecular weight class of light chains, of approx. 15 000 daltons. Kinetic investigations of the Ca2+-ATPase and Mg2+-ATPase (ATP phosphohydrolases, EC 3.6.1.3) at pH 8.0 gave Km and V values of 17.3 muM and 1.25 mumol Pi/min per mg, and 2.4 muM and 0.12 mumol Pi/min per mg, respectively. Adenylyl imidodiphosphate, a beta-gamma-imido ATP analog, inhibited the ATPase activity of Physarum myosin competitively with Ki values equal to 350 and 12 muM in the presence of Ca2+ and Mg2+, respectively. The ATPase activity of Physarum myosin was inhibited at a very low rate (t1/2 = 24 h) by the ATP analog, 6,6'-dithiobis(inosinyl imidodiphosphate), with concentrations of inhibitor previously shown to inactivate (t1/2 approximately 10 min) skeletal and cardiac myosins rapidly by reacting with key cysteines.


[Effect of the dielectric permeability of the non-aqueous phase on enzymatic charge transfer through an oil-water inferface].

Charge transfer across the interface between two immiscible liquids in functioning enzyme membrane systems and chlorophyll is studied. Phenomenological theory is developed describing the influence of the dielectric permeability of oil phase on the change of the potential difference at the interface during the charge transfer across oil/water. It is shown that change of the potential difference when varying dielectric permeability can be explained as a change of the activation energy of charge transfer and as change of the capacity of double electric layer. The theory is compared with experimental data based on the vibrating capacitance method in charge transfer during the action of soluble mitochondrial or bacterial ATPases and chlorophyll.


[IR-spectra of skeletal muscle mitochondria and endoplasmic reticulum].

The existance of alpha- and beta-protein conformation in human straight abdomen muscle mitochondria and microsomal fraction was established. The stability of beta-conformation was provided by hydrophobic and lipid protein interactions. The band at 1730 cm-1, C=O stretching of the carboxyl groups, was more intensive in mitochondria, presented in microsomal fraction and disappeared after its isooctane treatment. From the reducing of NH, OH stretching frequency in microsomes films, was made a conclusion that hydrogen bonds were stronger in that membrane.


[Membrane function of the kidney].

Brush border membranes (luminal) and basal-lateral plasma membranes (contraluminal) of rat kidney proximal tubules were isolated by freeflow electrophoresis and their role in transepithelial transport was investigated. Enzymatic analysis revealed that the brush border membranes contain a bicarbonate stimulated ATPase and that the basal-lateral plasma membranes contain a Na+-K+-ATPase and a calcium stimulated ATPase. These findings suggest that an active, ATPase-mediated step in transepithelial bicarbonate or proton transport is located in the luminal membrane, whereas an active, ATPase-mediated step in transepithelial sodium and calcium transport is located in the contraluminal membrane. Transport studies with membrane vesicles demonstrated that sodium-dependent stereospecific transport systems for sugars, amino acids and phosphate are located in the brush border membrane; the basal-lateral plasma membranes contain sodium-independent transport systems for sugars; amino acids, phosphate and p-aminohippurate. The sodium-dependent systems represent sodium-substrate contransport systems which in the course of transepithelial transport derive energy from the transmembranel electrochemical potential difference of sodium for the intracellular accumulation and active transepithelial transport of sugars, amino acids and phosphate. The brush border membrane contains in addition a Na+/H+ exchange system which might be involved in the proton secretion of the proximal tubule. In the presence of a sodium gradient the permeability of the luminal membrane vesicles for L-lactate is higher than the permeability of the contraluminal membrane vesicles. This indicates that L-lactate-which is metabolized by the tubular epithelium-enters the tubular cell mainly from the tubular lumen. The role of membranes in the uptake of proteins by the tubular cell was investigated by isolation and biochemical characterization of microvilli, pinocytic vesicles and lysosomes. Pinocytic vesicles were found to be rich in acid phospholipids and glycoproteins which show a more rapid turnover than the proteins of the microvilli. It is concluded that pinocytic vesicles are biochemically defined entities with unique functions which are synthetized during the pinocytic process.


Obstetric and neonatal care related to outcome. A comparison of two maternity hospitals.

Infants of birthweight up to 2500 g born in 1966 in two district hospitals were followed-up until their school medical examination at six years. Neonatal mortality rates differed in the two cohorts despite similar maternal age, parity, and social class distribution; differences in the management of labour and in neonatal care may have been responsible. Numbers were small but the prevalence of mild or more severe handicaps among the survivors did not differ significantly between the cohorts; an improved mortality was not achieved at the expense of an increased overall morbidity, although there was a suggestion of a difference in cerebral palsy prevalence. It is suggested that the neonatal mortality rate in conjunction with the prevalence of handicaps among the survivors of low birthweight infants be used as an indicator of the efficacy of perinatal care.


A reappraisal of the Pfannenstiel incision.

The postoperative morbidity of incisions used in retropublic prostatectomies was examined. 350 patients with vertical midline incisions were compared with 411 patients with transverse or Pfannenstiel incisions. There was a significantly increased incidence of postoperative inguinal hernias in the group of patients who had had transverse incisions. The possible reasons for this were discussed. It was concluded that the normal architecture of the inguinal canal was deformed and weakened by extra-wide transverse incisions.


The effect of anti-thrombotic drugs on prosthetic grafts in the canine inferios vena cava.

The effect of phenylbutazone, an anti-thrombotic agent, on the occlusion rate of knitted Dacron grafts placed in the infrarenal inferior vena cava of dogs was studied. Grafts places in dogs treated with phenylbutazone remained patent significantly longer than those in untreated animals. All the grafts in the untreated group occluded, but 2 remained patent in the treated animals.


Improvement in experimental vascular graft patency by controlled defibrinogenation.

A sensitive animal model was used to investigate treatment designed to improve vascular graft patency. A Dacron graft was inserted into the infrarenal vena cava of 30 rabbits. Half were treated with subcutaneous Arvin for 28 days after operation. This produced a significant lowering of the post operative plasma fibrinogen. The patency rate of the grafts in the treated rabbits was significantly greater than in the control rabbits.


Inhibiton of neurons in the amygdala by dorsal raphe stimulation: mediation through a direct serotonergic pathway.

This study presents data showing that the dorsal raphe nucleus (DRN) has a marked inhibitory influence upon neurons in the amygdala and that this inhibitory effect is mediated by a direct DRN-amygdala serotonergic pathway. The evidence may be briefly summarized as follows:(1) on the same amygdaloid cells, both iontophoresis of serotonin (5-HT) and electrical stimulation of the DRN markedly inhibited spontaneous single unit activities; (2) the latency of DRN-induced inhibition was relatively short and is compatible with the conduction velocities (which were determined by antidromic activation of the 5-HT pathway) of unmyelinated 5-HT fibers; (3) destruction of 5-HT projections by 5,7-dihydroxytryptamine (5,7-DHT) or pharmacological depletion of 5-HT by parachlorophenylalanine (PCPA) prevented the inhibitory responsed to DRN stimulation in the great majority of cells studied; (4) in PCPA-pretreated animals, injection of 5-hydroxytryptophan (5-HTP) reversed the PCPA effect, restoring the responses of amygdaloid cells to DRN stimulation. In the amygdala, the presumptive 5-HT antagonists which we tested did not block the inhibitory effects of 5-HT except that intravenously administered LSD blocked the inhibitory responses produced by submaximal DRN stimulation. The implications of these results for the possible functions of 5-HT in the amygdala is discussed.


Percutaneous radiofrequency lumbar rhizolysis (rhizotomy).

Low back pain may arise from degenerative changes in the posterior joints of the lumbar spine. These joints are innervated by a branch of the posterior primary ramus, which follows an anatomically constant course. Pain impulses from these joints can be interrupted by coagulating this nerve with a radiofrequency wave, the probe having been placed in the area of the nerve percutaneously. Percutaneous lumbar rhizolysis was carried out under local anesthesia on an outpatient basis in 82 patients, most of whom had multiple level rhizolysis. Rhizolysis was successful in 67% of patients with mechanical low back pain without evidence of disc herniation and nerve-root compression or psychogenic pain, who had not previously undergone an operation for relief of the pain.


Comparative physiologic dispositions of 5-fluoro-2'-deoxyuridine and 5-fluorouracil in mice bearing solid L1210 lymphocytic leukemia.

The physiologic disposition of 5-fluoro-2'-deoxyuridine (FUdR) and its metabolites, in particular the postulated active metabolite, 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP), has been studied in BDF1 mice bearing 6-day solid L1210 lymphocytic leukemia between 2 and 72 hours after a single iv dose of 14C-2-FUdR at 380 or 760 mg/kg (400-1300 microcuries/kg). FUdR itself was rapidly eliminated from tissues by urinary excretion and metabolism. However, its metabolites, including 5-fluorouracil (FU), persisted for 72 hours in the acid-soluble and -insoluble fractions of tissues. In tumor and small intestine, 60% of the 0- and 72-hour exposure to FdUMP, based on the area under the concentration-time curve, occurred between 24 and 72 hours after dosing. The results are compared with the physiologic disposition of FU after administration at 200 mg/kg iv which is an equimolar dose to FUdR at 380 mg/kg and approximately equitoxic to FUdR at 760 mg/kg. The molar concentrations of total drug equivalents, and of FU itself, after FUdR at 760 mg/kg were comparable to those after FU. However, the concentrations of FdUMP were lower than after FU, whereas the concentrations of drug equivalents incorporated into the acid-insoluble fraction, which includes equivalents incorporated into RNA, were generally higher than after FU. These data are correlated with the comparative antitumor effects and toxicity in mice of the fluorinated pyrimidines and with their clinical effectiveness.


Ruthenium red staining of the neural lamella of the brain of Galleria mellonella.

The outer surface of the neural lamella, the connective tissue ensheathing the brain, shows the ability to bind ruthenium red in the wax moth larva. Ruthenium red-positive material is sensitive to neuraminidase, hyaluronidase and to some extent to phospholipase C, what suggests that the negative charge on the external surface of the neural lamella depends on the presence of the anionic groups of sialic and hyaluronic acids and phospholipids.


The ultrastructure and ultracytochemistry of the basement membrane of the Galleria mellonella fat body.

The fat body lobes of Galleria mellonella are surrounded by basement membrane - a fine granular layer of connective tissue. This membrane has an affinity for ruthernium red. The results obtained after treatment of the fat body with neuraminidase, hyaluronidase, phospholipase C and proteolytic enzymes suggest that glycoproteins and phospholipoproteins are constituents of this basement membrane. The basement membrane also has the ability to bind concanavalin A-peroxidase, which is associated with the presence of mannoside residues.


[Functional study of cultured bone cells].

Osseous cells in culture synthesize and excrete glycosaminoglycans, collagen and alkaline phosphatases, revealed by the classical histochemical reactions. Observation of the living cells iwth the polarizing microscope, after a five day-culture, reveals the presence of micro-crystals of mineral salts only at the level of cells and cellular groupings.


[Ultrastructure of the particles reconstituted by complementation of extracts from chl-r mutants of Escherichia coli K 12].

By freeze-fracturing it is shown that the vesicles reconstituted by complementation of the chlA and chlB mutants of E. coli K 12 extracts are characterized by an asymmetric membrane bilayer. In a feature quite similar to the original intact plasma membranes, the membrane splits in two halves and the intramembranous particles are asymmetrically distributed on the two facture faces. It is proposed that the process of membrane reconstitution, which is also associated with the restoration of nitrate-reductase activity, relies on a sequence of increasing complexity of the molecular organisation.


Six year review of the results of freehand aortic valve replacement using an antibiotic sterilized homograft valve.

The long-term behavior of an antibiotic-treated homograft aortic valve inserted in a freehand fashion was assessed in 121 patients operated upon for aortic valve disease and followed from four to six and one-half years. There were seven hospital deaths (5.7%) and 30 late deaths, only one of which was related to the homograft valve. The six year survival was 69% (77% for single valve and 52% for multiple valve surgery). At six years 9% had important homograft aortic valve incompetence (HAVI) and most of these required reoperation. Important HAVI occurred in only 5% of patients with an aortic root diameter less than 24 mm and in 38% of those with a markedly dilated or distorted proximal aorta (P less than 0.01). The freehand aortic homograft was considered superior to prosthetic devices because of the absence of chronic anticoagulation, thromboembolism, sudden death from valve failure and significant obstruction in a small aortic root. With slightly restricted patient selection the valve failure rate is expected to fall to less than 1% per year.


Cystic fibrosis: the effect of medium from cultured cystic fibrosis fibroblasts on ATPase activity.

Culture medium from fibroblasts of cystic fibrosis patients and controls was examined for the ability to inhibit (calcium plus magnesium)-activated ATPase and (sodium plus potassium)-activated ATPase. The ATPase systems used were both a solubilised preparation from dog-fish and a membrane associated preparation from human erythrocyes. Contrary to other reports the medium from cystic fibrosis fibroblasts did not inhibit ATPase activity.


Passive transfer of autoimmune aspermogenic orchiepididymitis (AIAO) by antispermatozoa sera. Influence of the type of autoantigen and of the class of antibody.

Three different autoantigens (S, P and T), extracted and separated from guinea-pig spermatozoa, give rise to an autoimmune aspermogenic orchitis (AIAO) when injected with Freund's complete adjuvant (FCA). They also induce specific antibodies, such as anaphylactic (with S and P), complement-fixing (with P and T), spermotoxic (only with T) and precipitating and Arthus-inducing antibodies (only with P). Passive transfer of AIAO was attempted by injections of high total doses (15-20 ml per animal) of immune sera directed against one of the three antigens. Successful passive transfers were evaluated by the intensity of the epididymal and testicular lesions which were comparable to the actively induced ones, and by the rapid appearance of these lesions in less than 1 week and their lasting for at least 2 weeks. The disease was passively transferred with anti-P immune sera in as many as 64% of these cases and up to 40% with anti-T immune sera. Anti-S sera did not transfer AIAO more than did control normal and anti-DNP-BGG guinea-pig sera. The incidence and intensity of lesions were greatly for anti-P or slightly for anti-T increased by pretreating the future recipients with FCA. Hyperimmune sera are considerably more effective than early sera even when the latter are used in a time sequence reproducing that of the active reaction. The orchitogenic acitvity of anti-T sera appears to be localized in IgG2 DEAE fractions while that of anti-P has been found only in Ig1-containing DEAE fractions.


Generation of activated lymphocytes. Analysis of giant SRBC rosettes.

Giant SRBC rosette-forming cells were detected in samples of mitogen-stimulated human peripheral blood lymphocytes. When the concentrations of mitogens were varied, the amount of [3H]TdR incorporated by the lymphocytes also varied. In general, the higher the amount of [3H]TdR incorporated, the higher were the percentages of giant rosettes. Hence the percentages of rosettes constituted a reliable index of mitogenic responses. Lymphocytes were stimulated by mitogens and cultured in the presence of cardiac glycosides or inhibitors of the synthesis of DNA, RNA or protein. The generation of giant SRBC rosette-forming cells was found to be dependent on RNA and protein synthesis and the integrity of membrane Na+ K+ ATPase, but not on DNA synthesis.


Lymphocyte tissue culture studies on human heart transplant recipients. III. Prediction of outcome of transplantation based on immunologic studies.

Using in vitro lymphocyte tissue culture screening tests human heart transplant recipients during the academic year 1973/1974 were evaluated and an attempt made to predict their post-operative rejection course. The tests involved screening for serum depressive factors and screening for the recipient's lymphocyte reactivity. A scoring system was devised whereby the laboratory results could be converted to a predicted rejection score. Of the nine patients studied, eight are still doing well. Three recipient's who had a high postoperative rejection score as determined by an independent clinical team, were correctly identified pre-operatively and one of them had to be retransplanted. These screening tests may be helpful in the future in the selection of recipients.


The haemodynamic effect of an intracranial arteriovenous anomaly. A Doppler-haematotachographic study.

Determination of the mean blood flow velocity by means of Doppler haematotachography is suggested as an aid in evaluating the haemodynamic changes associated with an intracranial arteriovenous anomaly. A Doppler haematotachogram (HTG) was obtained in 13 patients with a radiologically diagnosed arteriovenous anomaly, with marked interindividual variations in dimensions and blood supply; in 6 of these patients the Doppler HTG was obtained before and after total neurosurgical extirpation. The large majority of the patients showed a significant increase in diastolic, and to a lesser degree in systolic flow velocity at the level of the common carotid artery. In most cases the flow velocity curve of the ophthalmic artery showed a decrease in amplitude. These are the most useful parameters in evaluating the haemodynamic effect of an intracranial arteriovenous anomaly. After the surgical removal of the anomaly, the carotid flow velocity decreased significantly. In the internal and external jugular veins, Doppler-haematotachographic pulse waves were registered for the first time. These may have been conducted from the internal carotid artery to the jugular veins via the arteriovenous anomaly. The usefulness of this parameter is reduced because of the cumbersome calculations required to determine the time within which an arterial pulse wave conducted via the arteriovenous anomaly reaches the jugular vein. Registration of this unusual pulse wave is solely of theoretical value.


Sodium valproate in Huntington's chorea.

In a single-case study of Huntington's Chorea the effect of sodium valproate on motor behaviour was first compared with that of L-Dopa and than investigated further alone. Drug effect was assessed in terms of number of EMG-bursts with concurrent determinations of serum-levels of sodium valproate. The main result of this study was the development of a state of tolerance to sodium valproate.


Normal lymphocyte function in the presence of delta-9-tetrahydrocannabinol.

Delta-9-tetrahydrocannabinol (delta-9-THC), the psychoactive component of marijuana, in concentrations of 0.6 X 10(-4) M to 10.6 X 10(-4) M, has no effect on the deoxyribonucleic acid (DNA) synthesis of resting normal human lymphocytes or on their responses to phytohemagglutinin or to allogeneic lymphocytes.


Renal hypertrophy in streptozotocin-diabetic rats.

1. Kidney weight and content of protein, RNA and DNA were measured in rats with streptozotocin diabetes of varying duration. 2. Diabetic rats had larger  kidneys than control rats: after 3 days of diabetes the weight increase was 15 per cent and after 42 days of diabetes it was 90 per cent. The protein content rose in parallel to the weight. 3 RNA content was already increased after 36 h of glycosuria, whereas DNA content was unchanged for the first 3 days of diabetes, and increased thereafter. The protein/DNA ratio increased rapidly during the first 3 days but remained constant thereafter. 4. Insulin treatment decreased the renal weight gain by about 67 per cent during the first 8 days of diabetes, but did not prevent the increase in DNA. When insulin was started after 25 days of diabetes there was only a slight regression of kidney growth.


Estimation of protein-ligand binding parameters from contiuous ultrafiltration results.

A method of analyzing the result of continuous ultrafiltration experiments to obtain protein-ligand binding parameters is presented. This method employs a nonlinear least-squares regression algorithm coupled with a model of protein-ligand binding which alloww the computation of free ligand concentrations, and a second-order Runge-Kutta method to integrate free concentrations with respect to collected ultrafiltrate. The approach is general and effectively removes the constraints on maximum fraction size imposed by other methods.


The activity of four antimicrobial agents. Including three nitroimidazole compounds, against Bacteroides sp.

Forty strains of Bacteroides sp. were tested against three nitroimidazole compounds, metronidazole, tinidazole and nimorazole and the aminoglycosidic antibiotic spectinomycin. The effect of altering the inoculum and the presence of serum upon the minimum inhibitory concentration (MIC) was also noted. The three nitroimidazole compounds were all very active (average MIC = circa 0.25 mg/l). Tinidazole was twofold more active. The MIC of spectinomycin was 32 mg/l.


[Treatment of iliac artery stenosis with low dose streptokinase (author's transl)].

Ten patients with 13 stenoses in the pelvic area were treated with low doses of streptokinase (30 000 U/h) for 72 hours. A significant improvement in the degree of stenosis was obtained as shown by post-stenotic pressure values. Biochemically there was a marked plasminaemia with moderately low fibrinogen levels. Streptokinase treatment with low doses could form an alternative method of treatment in arterial stenoses.


Steroid hormone formation in human ovarian follicles in vitro.

Ovarian follicles of 5 to 15 mm in diameter were isolated from 45 ovaries of 34 patients in the follicular and luteal phases of the cycle. Three experiments were done. In the first, follicles were minced and incubated in Krebs-Ringer bicarbonate buffer containing 1 to 2muCi of testosterone-4-14C in the presence or absence of 100 IU human chorionic gonadotropan (hCG). In the second, minced follicles were incubated with 100 muCi of sodium acetate-I-14C under identical conditions. In the third, ten follicles from a single patient in the late proliferative stage of endometrial dating were cut in halves and incubated with 100 muCi of acetate-I-14C under identical conditions. The minced follicle preparation was capable of aromatizing testosterone-4-14C into radioactive estrone and estradiol in significant amounts. Incorporation of radioactive acetate into pregenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, estradiol and estrone was assessed by reverse dilution analysis with recrystallization to constant specific activity. The major radioactive products formed were androstenedione and 17-hydroxyprogesterone in the latter two experiments. Dehydroepiandrosterone was one of the major steroids in the second experiment. The minor products were testosterone, progesterone and pregnenolone. Smaller, but definite incorporations of radioactive acetate into estradiol and estrone occurred in the second experiment. On histological examination, the follicles were characterized by atretic changes. This distribution pattern of radioactive acetate among the steroids was considered to represent the steroidogenic profile of unstimulated or atretic follicles.


Inhibition of actomyosin ATPase by high concentrations of 5-hydroxytryptamine. Possible basis of lesion in 5HT-induced experimental myopathy.

The effect of 5-hydroxytryptamine (5HT) on the ATPase activity and sulphydryl group reactivity of mammalian skeletal muscle actomyosin has been studied. 5HT inhibited the Mg2+-activated but not the Ca2+-activated ATPase activity of actomyosin. It slightly activated myosin ATPase. The sulphydryl groups of actomyosin reacting with 5,5'-dithiobis-(2-nitrobenzoic acid) were blocked by concentrations of 5HT which inhibited the Mg2+-activated ATPase. The significance of the results are discussed in relation to the muscle lesions in the experimental myopathy induced by 5HT and imipramine.


Pyoderma gangrenosum in Crohn's disease: report of a case.

A case of pyoderma gangrenosum of the abdominal wall occurring in a patient with histologically proven Crohn's disease of the colon is described. An aggressive surgical approach (wide excision with delayed skin grafting) resulted in rapid healing of the abdominal wall. Subsequent colectomy through the previously involved abdominal site was accomplished without complication.


On the influence of age on immunity in Down's syndrome.

In 23 subjects of different ages with Down's syndrome a number of parameters of non-specific defense of humoral and cellular immunity were investigated. While in all age groups complement factors C3, C4 and C5 as well as phagocytosis and NBT indices were in the normal range, a dysgammaglobulinaemia increasing with age with a hyperglobulinaemia of the IgG, IgA and IgD types was found, sparing immunoglobulins IgM and IgE. In addition the transformation capacity of peripheral blood lymphocytes decreased with age. This is understood as the consequence of premature aging of the thymus-dependent immune system.


The influence of catecholamines and serotonin on histamine uptake and metabolism by guinea pig atrium.

The influence of serotonin and catecholamines on the uptake and metabolism of 14C-histamine by isolated guinea pig atrium has been investigated. Epinephrine, norepinephrine and serotonin were found to reduce the histamine uptake and the formation of methylhistamine, in a dose-dependent fashion. The order of potency was epinephrine greater than norepinephrine greater than serotonin. Aliphatic diamines, such as spermine, do not affect the accumulation and metabolism of histamine. It is suggested that serotonin and catecholamines, may enhance histamine responses by decreasing the uptake and metabolism of this amine.


The induction of mounting behavior in female rats by p-chlorophenylalanine.

The effect of p-chlorophenylalanine (pCPA) and testosterone propionate (TP) on mounting behavior of ovariectomized female rats towards receptive and non-receptive stimulus females was studied. Both pCPA and TP facilitated mounting and the effect was intensified when these compounds were administered together. pCPA increased mounting behavior in the non-receptive stimulus condition. The results are interpreted as further evidence that pCPA affects sexual behavior in two ways: at first by a direct influence on the neutral substrate underlying masculine sexual behavior, and secondly by changing information processing of the sensory input from the partner.


Regional training program of laparoscopy: impact on regional care.

In response to large numbers of requests for laparoscopic sterilization, the University of North Carolina began a training program to provide this service on a regional basis throughout the state. This report reviews the final distribution of centers providing these services: one within 50 miles of every person in the state. The clinical experience of 30 private physicians (excluding experience of residency training programs) was reviewed and found to parallel the national experience in provision of services, in complications, and in pregnancies. The brief but intense training program (2 days at the University of North Carolina and one morning at the physician's hospital) was found to result in rates of complications and failures similar to national levels of performance. Should the demand for laparoscopic sterilization increase in the coming years, the region has sufficient numbers of safely trained physicians to respond.


[Mechanical activity of the papillary muscles of the rat heart under high altitude conditions].

Mechanical activity of isolated papillary muscles in the left ventricle of rats was studied during permanent high altitude adaptation. The main computer parameters were: maximal developing tension, force of contraction, and capacity of papillary muscles at different periods of mountain adaptation (3, 15, 30 and 45 days). On the 15th day of mountain exposure, a statistically significant increase of maximal developing tension and papillary muscles activity was observed, which remained until the 45th day. Capacity was considerably increased on the 30th--45th day of adaptation. The data suggest positive effect of high altitude hypoxia on inotropic function of intact myocardium.


[Myocardial "bridges". A new pathogenetic problem in angina without coronary obstruction (author's transl)].

Six patients showing at coronary angiography normal coronary arteries during dyastole, but a segmental constriction of the left anterior descending artery during systole, were studied. Four of these patients in which the degree of systolic artery narrowing was more evident had typical angina and positive stress test. In two of these cases, a probable idiopathic cardiac hypertrophy was present. The pathogenetic significance of the angiographic findings are discussed, on the basis of common knowledge of coronary physiology and of pathophysiology of angina with normal coronary arteries.


[An evaluation of right ventricular compliance (author's transl)].

Right ventricular "compliance" and "stiffness" in a casuistry of 51 patients were studied with varied pressure loads, using the "specific compliance" (SC) index proposed by Smith and coll. (1974) for the left ventricle and the "stiffness" constant proposed by Gaasch and coll. (1972, 1975). The pateints were subdivided according to a hemodynamic criterion, on the basis of telediastolic volume values (RVEDV) and telediastolic pressure (RVEDP) of the right ventricle. The average "specific compliance" was 0.1203 +/- 0.0283 in patients with RVEDP below or equal to 7 mmHg and 0.0517 +/- 0.0269 in those with RVEDP greater than 7 mmHg. In these two groups, the respective average values of the "stiffness" constant were 0.0136 +/- 0.0007 and 0.0210 +/- 0.0016. Comparison of the groups showed a significant statistical difference among the indices. In the subdivision into groups with telediastolic volume, the average SC values were respectively 0.0832 +/- 0.0083 in the patients with RVEDV below 150 ml/m2; 0.1131 +/- 0.0375 in the patients with RVEDV between 150 and 200 ml/m2; 0.0650 +/- 0.0132 in the patients with RVEDV above 200 ml/m2. None of the three groups demonstrated statistically significant differences. In the telediastolic volume groups, the average values of the "stiffness constant" were respectively: 0.0235 +/- 0.0020; 0.149 +/- 0.0007; 0.0117 +/- 0.0006. A comparison of the three groups showed statistically significant differences for this index. The authors consider that in pressure overloading of the right ventricle with different etiopathogenesis of "stiffness" and "compliance" indices, based on the measuring of volume and pressure, are unable to give absolute measuring of the physical characteristics of the ventricular walls. Thus, recourse to methods that can evaluate wall "stress" are necessary. However, the parametres considered are quite useful for indicating the variations of ventricular distensibility in homogenous casuistries and are therefore comparable.


Na+ transport in jejunal crypt cells.

As enterocytes migrate from crypts to villi they differentiate and mature. To examine the effect of epithelial differentiation on ion transport we studied 22Na+ efflux and (Na+--K+)-adenosine triphosphatase activity in suspensions of epithelial cells selectively isolated from different regions of the villus to compare crypt cells with villous tip cells. Enterocytes were isolated from rat jejunum by a dilation-vibration technique. Thymidine kinase, sucrase, and alkaline phosphatase activities were measured as markers of specific cell populations. Compared to villous cells, cells from the crypt region demonstrated lower (Na"--K+)-adenosine triphosphatase activity, lower total and passive Na+ efflux rate constants, and failure of Na+ transport to respond to an actively transported nonelectrolyte.


[The relationship between systolic time intervals and the electrocardiographic pattern in essential hypertension (author's transl)].

Systolic time intervals at rest and after exercise were studied in 56 patients with essential hypertension. The patients were divided into groups according to the presence or absence at rest of electrocardiographic patterns of left atrial hypertrophy, and left ventricular strain. An impaired left ventricular function was shown, at rest and after exercise, in patients who had an electrocardiographic pattern of "left ventricular strain".


[Hereditary polymorphism in the haptoglobin system of schizophrenic patients and healthy subjects].

Hereditary polymorphism of haptoglobin is studied by means of starch gel electrophoresis in schizophrenic patients (200 persons) and in healthy people (154 persons), in habitants of Minsk. It is concluded that Minsk inhabitants do not differ considerably from the rest European population in their frequencies of haptoglobin alleles. No reliable differences in the distribution of haptoglobin genotypes were found between patients and healthy persons. However, hereditary types of haptoglobins turned to be markers of the course and the prognosis of schizophrenia.


Fourier analysis of the cranium in trisomy 21.

A comparative study of individuals exhibiting the trisomy 21 syndrome (Down's) and a normal group has shown statistically significant differences in cranial shape (norma lateralis). These differences illustrate the departure from normal growth seen in individuals displaying the trisomy 21 syndrome. Fourier analysis is a preferred method since it is more efficient than conventional techniques in the analysis of complex shapes. Fourier analysis is also attractive because the series terms are orthogonal, hence independent; further, the Fourier approach allows for the control of size differences. A three-way analysis of variance was used to test for significant differences between mean Fourier coefficients. The results showed significant difference between individuals with trisomy 21 and controls. Age differences were also significant, only sex differences tended to be non-significant. Finally, the trisomy 21 sample is twice as variable as the controls.


Surface features of cells in human lymphoproliferative disorders. An immunoelectron microscopy study.

Peroxidase conjugated antibodies were applied to cell suspensions in order to detect surface associated immunoglobulins. Cell suspensions were fixed prior to incubation with reagents, a procedure avoiding membrane alterations induced by antibodies to surface component. By immunoelectron microscopy an identification of B lymphocytes could be made with simultaneous observation of their surface architecture. Basic findings were that normal circulating human B lymphocytes had a villous surface. This relationship was not confirmed however by examinating samples from various B and T cell proliferations establishing that surface morphology is not sufficient to categorize cells in disease. Specimens from hairy cell leukemia were also examined. Despite salient surface characteristics as revealed by the present method, the categorization of cells remains unclear.


Leucocyte migration in presence of leukaemia-associated antigens in children with Down's syndrome.

The effect of leukaemia-associated antigens prepared from leukaemic lymphoblasts and myeloblasts has been studied on the migration of peripheral leucocytes obtained from children with Down's syndrome. Membrane extract from leukaemic lymphoblasts had no effect, while that from leukaemic myeloblasts was slightly inhibitory, i.e. it was "recognized" as antigen by the lymphocytes of children with Downs syndrome.


[The supposed cancer risk from mammography. Opposition to the assertions (author's transl)].

The view that exposure to diagnostic radiation presents a cancer risk to the female breast should be considered together with the fact that the major factor is ageing of the patient. This risk factor is hidden in experimental and statistical studies on cancer production by exongenous agents; for instance, in studies of radiation effects, it is inherent in the time taken. The assumption that mammography presents a cancer risk is unjustifiable and is denied.


[An improved method of examining the stomach by thincoating double-contrast technique (author's transl)].

Double contrast techniques represent a considerable advance in improving diagnostic accuracy during examinations of the stomach. This technique was developed primarily by Japanese workers (H. Shirakabe and others) for the diagnosis of early carcinoma of the stomach and has reached a high degree of excellence. A particular technique of this method is the use of thin coating of the gastric mucosa. This paper deals with the principal of this examination and its use and is illustrated by a number of examples.


[The radiological findings in oesophagitis due to Crohn's disease (author's transl)].

The radiological changes in oesophagitis due to Crohn's disease are described in five patients. Like the pathological and anatomical findings, the appearances proved very variable. Neither in our own observations, nor in the literature, are there any radiological findings which are diagnostic. The diagnosis can only be made on the basis of radiological, endoscopic and histological findings.


[The manifestations of regional enteritis (Crohn's disease) in the stomach and duodenum (author's transl)].

Involvement of the stomach and duodenum is relatively rare, but produces distrinct radiological changes. In the stomach the antrum and pyloric portion are affected most frequently. Simultaneous involvement of the duodenum is common. Typical radiological changes consist of funnelshaped narrowing of the antrum, decreased motility of the wall of the stomach, cobblestone mucosa with flat ulcers, deformity of the pylorus and first part of the duodenum and stenosing lesions of the duodenum. If the gastro-duodenal changes occur together with the typical appearances in the jejunum, ileum and colon, then the diagnosis can be made by radiology alone.


[The radiological diagnosis of Crohn's disease with special reference to involvement of the stomach (double-contrast method (author's transl)].

The manifestations of Crohn's disease in the stomach can be demonstrated by a doublecontrast technique. Recognition of detailed mucosal changes, together with certain other typical findings, makes a diagnosis possible, as has been demonstrated by one case.


[Is there a connection between infection with Yersinia enterocolitica and regional enteritis? (Preliminary communication) (author's transl)].

After a brief description of the micro-biological, pathological, anatomical and clinical picture of infections with Yersinia enteroclitica, attention is drawn to the striking radiological similarity between three patients with Yersinia infection and regional enteritis (Crohn's disease). Whilst the radiological findings due to Yersinia infection usually resemble the group of so-called non-sclerosing ileitis (Golden) they occasionally differ from this group and resemble the findings in Crohn's disease. In each case the infection was confirmed bacteriologically. The underlying pathology has not been elucidated and it is doubtful whether there is any connection with Crohn's disease.


[The radiological appearances of caustic burns in the upper intestinal tract (author's transl)].

Seventy-three caustic burns of the upper gastrointestinal tract were divided into early and late effects; the radiological findings were analysed and, as far as possible, compared with the endoscopic results. The central role of radiology proved to be indisputable, particularly for the demonstration of a perforation, for the control of treatment by drugs or dilatation and before surgery. Endoscopy is of particular value in the diagnosis of caustic burns if the radiological findings are negative, for following treatment and for clarifying atypical late changes in order to exclude malignant degeneration.


[Epi- and sub-dural haematomas on computer tomograms (author's transl)].

The computer tomographic investigation of two epidural and 26 subdural haematomas is described. Various computer tomographic signs are discussed and illustrated by some examples. Measurements of absorption values of subdural haematomas were related to in-vitro experiments.


[Radiological determination of skull thickness and skull thickness increase in patients with severe blood dyscrasias and hyperplasia of the red marrow (author's transl)].

A method is described for measuring the thickness of the cranial bones in x-ray pictures of the skull, which in a reliable way can only be done in the frontal and the parietal bones. From the results, representative and comparable values have been obtained consisting of the mean and maximum thickness of the bones and of the mean deviation of the thickness in the bone. By using these values, the thickness has been determined in normal persons and the increase of thickness established in different patients suffering from a number of blood disorders. A scale of increasing degrees of thickening could be set up ranging form normal conditions to extraordinary enlargement. As the thickening of the bones is due to the hyperactivity of the red marrow contained in the bones, and the increase of thickness depends on the intensity of the overgrowth of the marrow and of the time of its action on the osseous substance, from the thickness of the bones a conclusion can be drawn regarding the presence, the severity and the duration of the existing blood disorder. Since, moreover, the enlargement of the bones is irreversible, an increased thickness of the cranial bones may, in patients without alterations in the blood, point to a former blood disorder.


[Salivary gland scintigraphy after radio-iodine therapy. Functional scintigraphy of the salivary gland after high dose radio-iodine therapy (author's transl)].

Following high dose radio-iodine therapy, some radiation damage to the salivary glands is to be expected since iodine is taken up by these glands. The great individual variation in the uptake makes it impossible to predict the severity of the damage. T max and maximal excretion capacity after stimulation were therefore estimated by a camera functional scintigram with digital read out in patients following radioiodine therapy (0.1-3.2 Ci); the excretion index was used as an indirect measure of salivary flow. After a dose up to 0.3 Ci there is a change of T max and maximal excretion capacity in 30% of patients; after a dose of 0.5 to 1 Ci it is found in 60 and 80% and after very high doses of 1.1 to 3.2 Ci an abnormal Tmax was found in two-thirds of all patients and reduced or absent excretion capacity in all nine patients in this group. The excretion index also depended significantly on the cumulative dose. All patients who had received very high doses showed marked hyposialia or asialia. The early results of interim examinations suggest, similar to radio-iodine induced hypothyroidism, a cumulative risk of reduced function. In view of the long survival period of patients with differentiated thyroid carcinomas attention should be drawn to this side effect.


[Clinical experience with a 30 cm. image intensifier with special reference to a 100 mm. film technique (author's transl)].

The report deals with one year's experience of two new 30 cm. image intensifiers with special reference to a 100 mm. film technique. Attention was paid to its applicability to routine work and the usefulness of this format when demonstrated to a large audience. Comparative dose measurements using the image intensifier and a direct film technique are given. The running costs have been analysed. Suggestions for further improving the technique using this format are given.


[Pharmaco-kinetic investigations of a new gall bladder contrast medium--iodoxaminic acid (author's transl)].

Pharmaco-kinetic studies of the cholecystographic contrast medium iodoxaminic acid (Diglumin-Iodaxamate) which is characterised by low toxicity, revealed a half-value period of 93 minutes in the serum and a urinary excretion rate of 12.5% in 24 hours. This indicated the probability that this medium would be suitable for the radiological demonstration of the biliary tract when compared with known and tried contrast media.


[Modulation transfer function of the radiograph (author's transl)].

Individual modulation transfer functions of the recording system were related to total modulation transfer function; examples derived from radiographs of the lungs, stomach and gall bladder were used to show that proper evaluation of the radiograph requires consideration of the relationship between original contrast and detailed size. The total transfer function shows a rapid decline of the contrast factor with increasing point frequency. It has been shown that the pseudo record which could be expected from the usual transfer functions of the recording system does not, in fact, appear.


The diagnostic accuracy of lymphography in Hodgkin's disease (author's transl).

Between 1972 and 1975, exploratory laparotomies were carried out on 52 otherwise untreated patients with histologically verified Hodgkin's disease in stages I, II and III following lymphography. 84% of patients with negative lymphograms had histologically normal lymph nodes. 16% of negative lymphograms were shown to have to have histologically positive lymph nodes. Two out of eight patients diagnosed as positive on lymphography (25%) proved to be false positives caused by extensive lymph node involution. The diagnostic accuracy lymphography was therefore 83%. Surgical exploration was of value only in histologically positive cases. Post-operative control by means of lymphanigiography is essential for the evaluation of the course of Hodgkin's disease.


[Echinococcus of the heart. Infundibular pulmonary stenosis due to a large solitary cyst of the ventricular septum (author's transl)].

An echinococcus cyst in the ventricular septum is described, which produced an infundibular pulmonary stenosis. Following angiography, surgical intervention could be accurately planned and proved successful. The incidence, course, radiological features and diagnosis of cardiac echinococcus are reviewed.


[An investigation into the problem of streaming in the femoral artery by means of high speed serial angiography and synchronous pulse recording (author's transl)].

A method is described which allows one to correlate pulsephase dependant streaming and movement of the vessel wall by means of synchronous registration of pulse volume curves and the appearance of streaming as shown by serial angiograms. The results  of this investigation in the femoral artery confirm the accepted view that the appearance of streaming depends on the movements of the vessel wall. The prognostic value for vessel reconstruction is discussed.


[Calcification in mass lesions in the kidney (author's transl)].

In 80 mass lesions of the kidney, we found 11 cases with calcification; six of these occurred amongst 48 tumours and five amongst 32 solitary cysts. In particular, the following were found: 1. The frequency of calcification of 12 to 14% corresponds with that given in the literature. If other radiological signs fail  indicate the nature of the space-occupying lesion, then calcification may be of diagnostic value. 2. Calcified cyst walls appear as fine, even, curvi-linear lines, Dense, irregular and extensive calcification indicates a solid tumour. 3. Ring or curvi-linear calcification in not a reliable sign of a cyst. Tumours may also show this type of calcification indicates a solid tumour. 3. Ring or curvi-linear calcification is not a reliable sign of cyst. Tumours may also show this type of calcification. Calcification occurs in solitary cyst with about the same frequency as in tumours. 4. Histologically all calcified tumours were clear cell carcinomas, mostly hypervascular. Only one case showed central necrosis.


[Reconstruction of the spacial configuration of the spine from stereoradiographs (author's transl)].

The value of stereo-radiographs was demonstrated by its application to scoliotic spines. Individual vertebrae were measured with a stereo-comparator. The spacial co-ordinates of standard points on the body were evaluated by a computer. Subsequently the position and size of the vertebral bodies were obtained by reconstructing a model. In this manner a spine could be built up which spacially resembled the original spine. The model spine was demonstrated on a display. The computer was able to produce any required view of the spine. An impression of depth is produced by simulated rotation of the display. By this means an excellent visual impression of the spine in three dimensions is produced. The measurements obtained can be used as the basis for further calculation.


[The radiological diagnosis of recurrent subluxations of the shoulder (author's transl)].

Contrast arrhrography has shown that this is a neccessary investigation in all cases of recurrent dislocation of the shoulder, in order to show the changes in the shoulder joint. The examination can be carried out in the early or late stages after trauma. The method is also indicated before carrying out reconstructive operations on the joint.


Stages and roentgenological picture of diabetic osteoarthropathy.

The course and roentgenographic signs of diabetic osteoarthropathy are discribed on the basis of literary data and of 23 cases of the author. Three stages are distinguished: in stage I dislocation, circumscribed porosis and cortical defect are observed. The characteristic sign of stage II is osteolysis, accompained by fragmentation, fracture, periosteal reaction. In stage III the healing takes place according to five radiologically distinguishable patterns. The good healing tendency is typical. Regarding the differential diagnosis of the disease, the possibility of inflammatory and tumourous changes and neurothropic osteoarthropathies of other origin must be considered.


[Difficulties in the differential diagnosis of a non-traumatic, active myositis ossificans during pregnancy (author's transl)].

A 28 year old patient complained of sensory disturbances and pain in the right upper arm during pregnancy. During the 32nd week of her pregnancy, a large painful mass developed in the flexor muscles which, radiographically, showed some calcification. A diagnosis of a parosseous sarcoma was made; biopsy, however, indicated a diagnosis of non-traumatic myositis ossificans. Since the histological appearances of active myositis may be vary difficult to distinguish from a juxtacortical sarcoma, a right brachial angiogram and scintiscan were obtained. The angiographic and scintigraphic findings were erroneously considered to suggest malignancy. Following delivery, the tumour was removed. Futher histology confirmed the diagnosis of localised, non-traumatic myositis ossificans. The value of radiology, biopsy, angiography and scintigraphy are discussed with reference to our experience.


[Sequential hepato-splenic scintigraphy for measurement of hepatic blood flow (author's transl)].

The arterial and portal components of total liver blood flow were determined quantitatively in 31 patients by means of a new, non-invasive method. Sequential hepato-splenic scintigraphy has been employed, using a scintillation camera linked to a computer system. In normals, the proportion of portal flow was 71%, whereas in patients with portal hypertension it averaged 21%. Our experience indicates that the procedure can be of considerable value in the pre-operative diagnosis and postoperative follow-up of portal hypertension.


[Estimation of regional cerebral blood flow with the gamma-camera (author's transl)].

Using a computerized gamma camera regional cerebral blood flow and regional cerebral blood transit time are measured after injection of Xenon 133 and Technetium 99m respectively into the internal carotid artery. Equipment, technical procedures and methodology are described. Typical cases are presented to describe the usefullness of this procedure.


[Percutaneous, transhepatic thrombosis of the coronary vein in the treatment of bleeding oesophageal varices (author's transl)].

Percutaneous, transhepatic catheterisation of the portal vein in order to occlude the gastric coronary vein was carried out in six patients with bleeding oesophageal varices. Bleeding stopped in three patients, but in the other three ceased only temporarily. Complications were one pleural effusion and one haemothorax. At autopsy, marginal portal vein thrombosis was found in two cases. The indication for this procedure is the presence of bleeding from oesophageal varices which cannot be controlled by conservative means in a patient unfit for operation. It provides an opportunity for carrying out a decompression shunt operation in the interva between the bleeds.


[The effect of oral anti-diabetic agents (suphonyle ureas) on the excretion of intravenous biliary contrast media (author's transl)].

Sulphonyle ureas used in the oral treatment of diabetes occupy albumen-binding capacity. Hepatotropic contrast media therefore have difficulty with protein binding and renal excretion is increased. The proportion excreted through the kidneys has been determined in 50 diabetic patients on oral treatment. Demonstration of contrast in the urine was done radiologically, qualitative measurements by a subtraction method. As a control, the same group of patients were examined, having been taken off suphonyle ureas, as well as a group of 50 diabetic patients treated with insulin. While under medication, heteroptropic excretion rose on average to 55% and in some cases to 80%. This results in definite reduction of contrast filling of the biliary tree, occasionally to the extent of preventing a diagnosis. Displacement of sulphonyle urea by contrast was not observed.


[RI angiocardiography of idiopathic cardiomyopathy (author's transl)].

This study was aimed to evaluate the noninvasive method of radioisotopic angiocardiography for detecting a disproportionate thickning of the interventricular septum relative to the left ventricular free wall in the patient with idiopathic hypertrophic cardiomyopathy. The experimental study was performed to compare the imaged size of myocardial wall obtained my filling up with technetium 99 m labeled sponge in biventricular cavities, with the actually measured thickness of the heart specimen. The resultant  correlation between actual and imaged size of the left ventricular wall was excellent (r = 0.95). In the clinical application of this method, a gated cardiac blood pool scan was performed after the intravenous administration of technetium 99 m labeled human serum albumin in a dose of 10 mCi. The cardiac images were obtained in anterior, 30, 35, 40 and 45 degree left anterior oblique projection, and evaluated by visual inspection and semi-quantitatively by tracing the myocardial borders. As a result, the imaged asymmetric septal hypertrophy was evident in all four patients with PMD, with a ratio of septum to left ventricular free wall of 1.35 compared to 0.76 in five patients with left ventricular hypertrophy of known heart disease, and 0.88 in twenty-one miscellaneous cardiac patients without left ventricular hypertrophy. Thus, RI angiocardiography provides a safe, repeatable method for detection and evaluation of Primary Myocardial Disease.


Sequential examination of lymphocyte proliferative capacity in patients with malignant melanoma receiving BCG immunotherapy.

A series of 42 patients with malignant melanoma treated with BCG adjuvant immunotherapy were studied for sequential changes in cellular immune reactivity to non-specific mitogens. Lymphocyte preparations were made monthly and stored in a viable condition in liquid nitrogen. After 6 months of treatment, all lymphocyte samples from an individual were recovered and tested for DNA synthesis after stimulation with PHA, PWM, Con A, PPD and MLC. The responses to the mitogens in the blastogenesis test were stable during the course of therapy. The MLC response did not increase significantly in patients treated with tumor-cell vaccines, and declined sharply in the six patients who subsequently relapsed and died. The in vitro PPD response increased 1 to 3 months after initiation of BCG in patients who were initially unresponsive to PPD in vitro. However, PPD-positive patients did not show any significant alteration of the PPD response. The PPD response did increase less sharply in patients whose disease eventually recurred than in those who remained without evidence of clinical disease. BCG therapy does not appear to correct lymphocyte proliferative defects in melanoma patients. Of the assays employed, the MLC and PPD tests appear to be the most useful as monitors of clinical status and response to therapy.


Why work kills. A brief history of occupational safety and health in the United States.

In the early 20th century, U.S. monopoly corporations responded to the movement against work accidents by setting up a business-controlled "compensation-safety establishment," which kept down compensation costs but did little to improve working conditions. The "establishment" was able to keep the issue of occupational safety and health out of public debate until the late 1960's through its control of research, education, compensation, and government appointments in the area, and by creating the public impression that the problems of occupational disease were almost nonexistent. Despite the occurrence of sporadic rank-and-file uprisings, unions have been seriously involved in health and safety only since the late 1960's, when they mobilized in an effort to pass the Occupational Safety and Health Act of 1970. The passage of the OSHA law was made possible by the help of progressive professionals, worker dissatisfaction, the new environmental consciousness, and a general climate of social unrest. Although the corporate elite, through the "compensation-safety establishment," has been able to dominate the operation of the federal institutions created by the new law, the question of occupational health and safety is now on the permanent agenda of workers, unions, and the public.