Sudden infant death syndrome (SIDS): cardiac pathologic observations in infants with SIDS.

To determine the relation between the sudden infant death syndrome (SIDS) and asymmetric septal hypertrophy (ASH), pathologic obervations weree made in 45 infants who died with SIDS. Ventricular septal to left ventricular free wall ratios were normal (less than 1.3) in 42 infants and increased in three others (ratios of 1.4, 1.4, and 1.6). However, in none of these three infants with abnormal septal-free wall ratios was the ventricular septum markedly thickened. Small foci of disorganized cardiac muscle cells, similar to those observed in patients with ASH (but less marked in severity), were present in the ventricular septum of 22 per cent of controls. Thus, we have found little pathologic evidence to suggest that SIDS and ASH are commonly associated, although a rare coexistence of these two conditions is possible.


Acute aortic arch dissection: reevaluation of the indications for medical and surgical therapy.

Of 42 patients with dissection of the aorta, 4 had important arch involvement. Results were good in 2 patients treated medically. In two other patients wrapping the arch with a Dacron graft successfully prevented fatal hemorrhage. This technique avoids the need for arch replacement in selected cases. From this experience and a review of others a flow sheet was developed to guide decision-making in the surgical and medical management of patients with aortic dissection.


Pathophysiologic assessment of hypertensive heart disease with echocardiography.

Assessment of the pathophysiologic changes associated with systemic hypertension has been limited by difficulty in justifying invasive studies of the left ventricle. Echocardiography, because it is notinvasive, offers an attractive method of assessing cardiac dimensions and function in hypertensive heart disease. Fourteen age-matched normotensive subjects and 31 patients with hypertension (but without clinical evidence of coronary artery disease) were studied before receiving any antihypertensive therapy. The patients with hypertension were classified into three groups on the basis of previously established electrocardiographic and chest X-ray criteria: group I, normal electrocardiogram and chest roentgenogram (13 patients); group II, left atrial abnormality by electrocardiogram and a normal chest roentgenogram (8 patients); and group III, left ventricular hypertrophy by electrocardiogram or chest roentgenogram, or both (10 patients). Mean arterial pressure increased significantly from group I to group II and from group II to group III (P is less than 0.01), and this increase was associated with a similar progressive increase in left ventricular mass assessed with echocardiogram (P is less than 0.01). A significant increase was also found in both posterior wall and septal thickness in groups II (P is less than 0.05) and III (P is less than 0.01). In association with this increased mass a significant decrease in ejection fraction and fractional fiber shortening was demonstrated in groups II (P is less than 0.05) and III (P is less than 0.01) although cardiac index was reduced only in group III (P is less than 0.05). Thus, increased ventricular mass can be identified with echocardiography at an early stage of hypertensive heart disease when only left atrial abnormality is identifiable with electrocardiographic criteria and decreased left ventricular performance occurs with increasing arterial pressure and left ventricular hypertrophy.


Histochemistry of intrafusal muscle fibers outside the spindle capsule.

Regional differences in histochemical properties along the length of rat intrafusal muscle fibers were examined. Outside the muscle spindle capsule the nuclear bagfibers lose their hitherto characteristic ATPase activity and stain in a manner similar to that of extrafusal type I muscle fibers, perhaps in relationship to spindle skeletofusimotor innervation.


Down syndrome with trisomy in one triplet.

The case presented here may be the first identified report of Down syndrome with 21 trisomy in one child of triplets. One triplet died at 1 month of age; his facial appearance was not typical of Down syndrome. Detailed testing of blood groups suggested identical origin in the remaining two children. However, the fluorescent banding technique of chromosome, one-way mixed lymphocyte culture test, and HLA typing were suggestive of dizygotic orgin. Skin transplant studies supported this contention.


Immune-complex glomerulonephritis in a patient with mixed connective tissue disease.

Renal involvement and hypocomplementemia in mixed connective tissue disease are reported to be rare. A patient is described here with mixed connective tissue disease and persistently low serum C'3 levels in whom renal insufficiency and nephrotic syndrome developed secondary to immune-complex glomerulonephritis. Light microscopy of the renal biopsy specimen showed predominantly a membranous lesion. Immunofluorescent staining showed granular deposition along the basement membrane of immunoglobulin G, immunoglobulin M, fibrinogen and C3. Electron microscopy showed numerous electron-dense deposits along the glomerular capillary membrane and in the mesangium.


The response of C3H mice to streptozotocin. I. Thymic depression and leukocyte toxicity.

Streptozotocin, an antibiotic with reported antileukemic activity, was administered to C3H mice to evaluate the response of peripheral blood leukocytes and thymic lymphocytes. The hematologic effects of a single diabetogenic dose of streptozotocin include an absolute neutropenia and a depression of tritiated thymidine incorporation into thymic lymphocytes.


Sampling the fetoplacental circulation. II. Combined laparoscopy-fetoscopy in the pregnant ovine.

Induction of pneumoperitoneum, laparoscopy, and intrauterine endoscopy (fetoscopy) were successfully accompished in 23 pregnant sheep at 45 to 60 days' gestational age. The fetoscope, a conventional 2.7 mm. Hopkins straightforward wide-angle telescope (Stortz 27018A) encased in a prototype 3.1 mm. eccentric cannula, incorporates a 25 gauge needle channel. Multiple pregnancy was encountered in 11 animals. Forty-two separate fetoscopic trials were accomplished; a fetoplacental blood sample was obtained in 52 per cent of the trials. A mean interval of 19 +/- 9 days (+/- S.D., range 6 to 37 days) was allowed between fetoscopy trials. Fetal deaths occurred in nine animals (39 per cent). We believe that laparoscopy permits preselection of the proposed fetoscopy puncture site and will permit the operator to thereby avoid the placenta and/or uterine vessels.


Characteristics of thyroid-stimulated Na+-K+-ATPase of rat heart.

The possibility that augmentation of cardiac Na+-K+-dependent adenosine triphosphatase (Na-K-ATPase) by L-3,5,3'-triiodothyronine (T3) was mediated by early changes in intracellular ion concentrations ([Na+]1, [K+]1) was explored by time-course analysis after a single injection of T3 in thyroid-ablated (131I) rats. At 6 and 16 h after injection, T3 had no significant effect on cardiac [Na+]1, [K+]1, or microsomal Na-K-ATPase activity. At 24 and 48 h, however, T3 elicited proportionate increases in [K+]1 and Na-K-ATPase activity. Thus, no evidence was adduced that the T3-dependent increase in ventricular Na-K-ATPase activity is an adaptive response to prior changes in intracellular ion concentrations. The increase in [K+]1 is attributable to an increase in Na+ pump activity. Administration of T3 to hypothyroid rats had no effect on the transition temperature or the activation energy of ventricular microsomal Na-K-ATPase, as analyzed by an Arrhenius plot. Thus, the lipid microenvironment and the properties of the enzyme may be independent of thyroid status. The latter inference was supported by kinetic analysis, in that T3 had no effect on the Km for ATP or the K1/2's for Na+ and K+. Injection of T3 of the hypothyroid rat, however, significantly increased the Vmax's for ATP, Na+, and K+ of ventricular microsomal Na-K-ATPase. These results are in accord with the inference of thyroidal induction of Na-K-ATPase indistinguishable from those present in the athyroid state.


A signal-processing system for real-time ultrasonic measurement of urine flow parameters.

An application of a signal-processing system to the urethra is described which allows for real-time measurement of the average velocity of the urine at a particular location along the urethra during voiding through measurement of the average frequency in ultrasonic return from scatterers in the flowing urine. In addition, this comparatively simple system provides, without additional instrumentation, the relative urethral cross-sectional area at this location and the relative urine flow rate as functions of time throughout the voiding period. Tests indicate its potential as a valuable transcutaneous diagnostic aid in the detection, study, and treatment of various disorders and diseases of the lower urinary system. The key element of the system is a circuit having a voltage transfer function magnitude proportional to the square root frequency.


Myocardial mechanics and energetics in experimental iron-deficiency anemia.

The effect of iron-deficiency anemia on myocardial mechanics and energetics was studied in 10 anesthetized bealge puppies. Nine littermates served as controls. Left ventricular/body weight ratio was increased 14.2% (P less than 0.05) and cardiac index 36.5% (P less than 0.02) in the anemic puppies. Heart rate, mean systolic pressure, myocardial lactate extraction coefficient, and lactic dehydrogenase isozymes were similar in both groups. Contractile state measured in vivo (pressure-velocity curves) and in isolated muscles (isotonic force-velocity curves) was virtually identical in the littermate groups. Despite markedly increased coronary blood flow in the anemia animals, oxygen consumption per unit weight of myocardium was the same in both groups. Contractile element efficiency averaged 18.3% in 10 adult mongrel dogs studied in a similar fashion and was 27.1% and 39.8% in the normal puppies and anemic puppies, respectively. The oxygen cost of internal or force-generating work was similar among the three groups of dogs. It is concluded that the volume load produced by iron-deficiency anemia was associated with a normal contractile state, normal unit myocardial oxygen consumption, no evidence of chronic anaerobiosis, and a high contractile element efficiency, perhaps as a consequence of increased diastolic fiber stretch.


Circuit for automatically zeroing aortic flow base line from electromagnetic flowmeter.

We describe an inexpensive circuit designed to correct base-line drift of electromagnetic flowmeters automatically when cardiac output is being measured. The circuit measures the flowmeter output voltage during a portion of each diastole when blood flow in the aorta is assumed to be zero. Any deviation of the flowmeter output voltage from zero during this time represents either base-line offset or drift. The output voltage obtained during zero flow conditions is stored throughout the next cardiac cycle and subtracted continuously from the flowmeter output during each beat, thus giving a beat-by-beat correction of any base-line drift.


Direct calibration of a totally implantable pulsed Doppler ultrasonic blood flowmeter.

A totally implantable pulsed Doppler ultrasonic blood flowmeter has recently been developed to provide information on the velocity-flow profile in a vessel as well as its diameter. Volume flow can be indirectly obtained according to the formula: Q = (phi/4)(diam)2-v. In order to determine the accuracy of this estimate, in vivo direct bleedout measurements were performed on the abdominal aorta of six dogs with an overall accuracy in 77 trials of +2.0 +/- 8.7% (mean +/- 1 SD). The best-fit mean linear regression line was found to be: flowmeter output = 1.013-true flow + 5.1 ml/min. The scatter in the flowmeter's accuracy is thought to be due to small variations in the angle of the transducer. The source of the 2% overestimation in the mean accuracy could not be directly attributed to any one condition; the error is sufficiently small that in many cases it can be neglected.


On the brain monoaminergic systems relatint to ejaculation. II. Brain serotonin and ejaculation.

The effects of 5-HTP and pCPA on manually induced ejaculation in dogs and on brain monoamines in dogs and rats were investigated. From the results obtained in this study it was concluded that the serotonergic system in the brain is the mechanism which inhibits the occurrence of ejaculation. Considered together with the results obtained in our previous paper, it is though that ejaculation occurs with the reconciliation of the dopaminergic and serotonergic systems.


Paget's disease of bone.

Paget's disease affects approximately 3% of the population over age forty. It may be genetically transmitted (autosomal-dominant), but recent evidence suggests a viral etiology. Effective agents for control of the disorder have been developed over the past decade, but all have significant drawbacks. Calcitonin tends to lose its effectiveness in significant numbers of patients over a few months, mithramycin has significant toxicity, and diphosphonates tend to cause osteomalacia.


IgA-associated glomerulonephritis.

In summary, IgA-associated glomerulonephritis is an interesting clinical problem. The immunohistochemical identification of renal IgA deposits is the sine qua non of its diagnosis, although most of the patients reported have had hematuric syndromes, particularly recurrent gross hematuria. The importance of this immunopathologic entity devolves from the crucial use of special stains to identify IgA, the enigmatic role of IgA, the usual mesangioapthic expression of histologic response, and the ill-defined relationship of this clinical problem to nephropathies associated with systemic diseases that also have glomerular IgA deposits. Although still unproven, it is likely that the usual instance of IgA-associated glomerulonephritis is due to deposition of circulating immune complexes containing IgA. The nature of the exciting antigen(s), quantitative measures and characteristics of such complexes, and the role of mediating systems, including coagulation, have not yet been elucidated.


Changing patterns of plasmid-mediated drug resistance during tetracycline therapy.

The patterns of drug resistance and the frequency of conjugative R plasmids in intestinal Escherichia coli from 88 patients treated for a skin disease (acne vulgaris) with low oral doses of tetracycline are reported. The proportion of patients with resistant bacteria was progressively greater in patients who received tetracycline for 1 week, 4 weeks, or longer (from 50 to 88%). No multiply drug-resistant bacteria were detected before treatment or after 1 week of treatment. After more than 4 weeks of treatment, multiply drug-resistant E. coli were isolated from about 50% of the patients. The origin and selection of R plasmid-determined multiple drug resistance are discussed.


Chloracne from manufacture of a new herbicide.

Forty-one chemical company workers had chloracne as a result of exposure to 3,4,3',4'-tetrachloroazoxybenzene (TCAB), an extraneous intermediate produced during the manufacture of a new herbicide. There was no laboratory evidence of significant hepatotoxicity or porphyria during the short time the herbicide was produced. An acnegenic when applied to the rabbit ear, TCAB is also a potent inducer of the microsomal enzyme aryl hydrocarbon hydroxylase. Prevention of chlorance is a difficult industrial engineering task and treatment of the disease is even more perplexing.


Cytochemical variation of mast cells in the skin of the rat.

The mast cells of the skin of the external ear of the rat have been examined, with a view to the possible identification of different cell-types. It was not possible to discern more than one type of cell using criteria of size, shape, nuclear chromophilia or sizes of granules. The cytoplasmic granules of all of the cutaneous mast cells were tingible with Alcian blue (pH. 1.0 and 2.5) and, metachromatically, with toluidine blue 0. These properties were attributable to the heparin contained in the granules. The cells all gave positive reactions with the diazosafranine method, possibly by virtue of their content of serotonin. About two thirds of the mast cells in the dermis contained granules which were stainable by the periodic acid-Schiff (PAS) method and which could bind concanavalin A. It is suggested that these latter cells contain, in addition to heparin, a neutral mucosubstance characterized by a high content of alpha-d-glucosyl and/or alpha-d-mannosyl monosaccharide residues. The PAS-positive cells were relatively more abundant in vascular adventitiae and nerves and less so in the general connective tissue of the dermis than were the mast cells which did not contain the second mucosubstance.


Zollinger-Ellison syndrome: special considerations.

Twelve patients with Zollinger-Ellison syndrome and one patient with WDHA syndrome are reviewed. Three of the Z-E patients exhibited MEA, two having hyperinsulinism and one hyperparathyroidism. Ages ranged from nine to 71 years. Diagnosis of Z-E syndrome was established from history, gastric acid secretion, radiologic studies, serum gastrin measurements and from actual tissue biopsy in 10 of the 12 patients. Total gastrectomy was performed in 8 of the 12 Z-E patients, with abolition of the ulcer diathesis in all. However, in none of our patients was there objective evidence of subsequent tumor regression. Three patients remain alive. Four died of tumor, one from post-total gastrectomy complications, one from post-subtotal gastrectomy in another hospital, two from ulcer hemorrhage, and one from electrolyte imbalance with autopsy diagnosis of Z-E tumor. A patient is recorded in detail who exhibited both hyperinsulinemia and hypergastrinemia from a malignant islet cell tumor, had the tumor "debulked" four times over a 14 year period and whose hepatic metastases were temporarily abolished by streptozotocin infusion. The question is raised regarding relationships between chronic organic hyperinsulinism and subsequent hypergastrinemia.


The human platelet. A diagnostic and research tool for the study of biogenic amines in psychiatric and neurologic disorders.

Comparison of the properties of blood platelets and serotonergic synaptosomes suggests that the human platelet can serve as an appropriate model for the transport, metabolism, and release of serotonin (5-HT) by CNS serotonergic neurons. The study of blood 5-HT levels and platelet 5-HT pharmacodynamics in patients with a variety of psychiatric and neurologic disorders has generated interesting leads into possible abnormalities of CNS 5-HT neurons in these patients. This article reviews the experimental evidence, which uses the human platelet model to investigate neurotransmitter-related abnormalities in Down syndrome, mental retardation, infantile autism, hyperactivity syndromes (minimal brain dysfunction), schizophrenia, affective disorders, Duchenne muscular dystrophy, Parkinson disease, Huntington chorea, and migraine headaches.


[The effect of various substances on the time of survival of rabbits under conditiones of oxygen-delay (author's transl)].

In 30 rabbits, which had accidentally been divided into five groups of different treatment the effect of the substance Persantin, Actihaemyl and Noleptan was investigated in view of the time of survival of the animals and the behaviour of the acid-base-balance and the blood-gases under conditions of oxygen-delay. There were two control-groups. One collective was treated with Haemaccel, the other with Glucose. In those groups treated with Persantin, Actihaemyl and Noleptan the time of survival of the animals is significantly higher in comparison with the animals of the control-groups. The behaviour of the acid-base-balance and the blood-gases in the collective treated with Persantin points to a reduction of the dimension of the metabolic acidosis. This effect cannot be assumed for Actihaemyl because of this investigation. The effect of Noleptan seems to depend on an improvement of the gas exchange in the lungs of the rabbits. The results of this investigation show that the application of Persantin and Actihaemyl might be an interesting enrichment of the medicamental treatment of the intrauterine acidoses.


[Several morphologic and histochemical aspects of the formation of the placenta in sheep].

Histological and histochemical methods were used to study morpho-functional properties in the development of the sheep placenta. General regularities of developmental changes in the structure of the placenta and its carbohydrate and protein metabolism have been found which speaks of the regular change of periods of the intrauterine development, related with changing the periods of the intrauterine feeding. The giant cells of the chorion were shown to participate in metabolic processes, in addition to the histolytic activity which was shown by presence of carbohydrate (glycogen, glyco- and mucoproteins, acid mucopolysaccharides) and protein compounds.


[Immunologic and electrophoretic detection of an epidermal chalone-containing complex in tissues of different origin].

The rabbit antiserum to one of the components of the tissue-specific protein complex isolated from the back skin of rats and containing G1- and G2-chalones was obtained. By means of this antiserum an antigen identical to the cutaneous one was found in the mucous membrane of the tongue, oesophagus, prestomach and vagina, in the epidermis of the tail and sole. The cornea, mucous membranes of the urinary bladder and intestine, liver, kidney and blood serum do not contain this antigen. According to data of disc-electrophoresis in 5%-polyacrilamide gel, the 55--81% alcohol extracts of the investigated tissues of the epidermal type, including the cornea and mucous membrane of the urinary bladder, are of similar quantitative and qualitative composition, different from that of tissues of other origin.


[Vaccine therapy of a case of onychomycosis caused by Candida albicans].

A case of onychomycosis due to Candida Albicans in an otherwise healthy girl is reported. A vaccine was prepared with the same strain as the Candida Albicans isolated from the nail culture, broken down into 12 ampoules containing progressive concentrations. An improvement was achieved up to complete cure and this persists many months later. The results of the therapy are commented on.


Fatty acid composition of lipids in cerebral myelin and synaptosomes in phenylketonuria and Down syndrome.

Lipid and fatty acid composition of myelin and synaptosomes isolated from brains of phenylketonuric (PKU) and Down syndrome (DS) patients and patients with neither of these disorders was determined. No differences were observed in the proportions of cholesterol to phospholipids in synaptosomes and cholesterol to galactolipids to phospholipids in myelin or in the fatty acid composition of phospholipids in synaptosomes. However, the myelin from PKU brains contained reduced proportions of unsaturated and long-chain fatty acids. We conclude that genetic PKU and its experimental model have in common a defect in cerebral fatty acid metabolism, and that cerebral lipid abnormalities in this condition, rather than being generalized, may be confined to the glial cell population that synthesizes myelin. We further conclude that DS is not associated with an abnormality of cerebral lipid metabolism.


Valproate sodium in Huntington chorea.

An open trial of valproate sodium in 14 patients suffering from Huntington chorea showed that the drug was ineffective in the two treatment schedules employed.


Spinal myoclonus with dermal and retinal changes affected by myelitis.

Intermittent, rhythmical myoclonus that had been present in the lower limbs of a 68-year-old man for more than 50 years was obviously increased in frequency during the period when the patients suffered from acute transverse myelitis. The same type of movements were readily induced by irrigation of the urinary bladder during the period of paraparesis. Removal of some possible inhibitory influences from a myoclonic focus in the lower spinal cord with resulting heightened excitability was thought to be the mechanism of these phenomena, although direct irritation of the myoclonic focus by the inflammatory process was also conceivable. The patient had keratosis palmoplantaris hereditaria and retinal pigment degeneration, suggesting the possibility of a congenital neuroectodermal dysplasia.


[Embryonal rhabdomyosarcoma of the orbit. Apropos of 24 cases].

A composite review of 24 cases of embryonal rhabdomyosarcoma which is seen in fact to be the commonest orbital malignant tumour in children. In its evolution, most often very rapid, sometimes pseudo-inflammatory, this tumour presents many different histological appearances among which the alveolar form and the botryoidal form should be particularly distinguished. Although it was for a long time confused with reticulosarcoma the tumour is in fact derived from primitive undifferentiated mesenchymal cells and can therefore in this sense be considered as a blastoma. Since the prognosis is grave and its treatment often disappointing, it should in many cases combine surgery with radiotherapy and polychemotherapy.


[Tissue groups and ophthalmology].

By typing of 90 patients with ocular pathology (uveitis, diseases of optic nerve, Eale's disease, pseudo-tumor cerebri) the authors have found a constant and significant increase in the frequency of H.L.A. A2 especially in uveitis by streptococcus. However, a frequency of H.L.A. B27 as elevated as in previous publications was not found--but the parallelism: H.L.A. B27--ankylosing spondylitis was always found. Finally, the authors emphasized the haplotype H.L.A. A2 H.L.A. B5 in two cases of pseudo-tumor cerebri.


[Secondary glaucoma after cataract surgery].

The analysis of 900 operated cataract cases shows that for 16 cases the secondary glaucoma has appeared 1,77 p. 100. As pathogenesis, in 5 cases by being late for recover of the anterior chamber, in 2 cases by vitrean obstruction, in 2 cases by the anterior chamber epithelisation, and in one case the secondary glaucoma has been post-haemoragical. The medical treatment has been diversificated according to the cause which has generated it, with normalisation of the ocular pressure and sight ameliorations in 50 p. 100 of cases. It is shown that the prophylaxis measures which are imposed for the far diminuation of the frequency in the secondary glaucoma cases after the cataract operation.


[Study of the composition of aqueous humor in normal subjects by means of automatic analytical technics].

Five new constituents in the aqueous humour were measured as part of a study on the constitution of the aqueous in normal subjects; urea, glucose, phosphorus, calcium and the carbonates and bicarbonates representing the alkaline reserve. Each of these constituents were measured by an automatic method using the Technicon auto-analyser, a similar sample of aqueous humour serving in some cases for simultaneous measurement of several constituents. The principles of the reaction, the Manifold used and the results obtained are reported for each of these. The latter were studied more particularly as a function of age on the one part and also a function of the serum levels of the same constituent. This simultaneous study establishes a relationship between the aqueous humor and the plasma which is compared with preceding reports in the literature and with results obtained more often in animals. Several important physiological and physiopathological considerations arise from these findings.


[Experimental keratoplasty after sensitization by a bacterial antigen (Streptococcus A group)].

Experimental (rabbit) penetrating keratoplasties with donor tissue sensitized to a bacterial antigen (Streptococcus Group A) were placed in normal rabbits and animals sensitized to the same antigen. Severe graft reactions developed two months after grafting in sensitized rabbits while no reaction occurred in controls. It is possible that homograft reactions can be triggered and super-imposed to the immuno-allergice reaction to the foreign antigen present in host and donor.


Dermatoses in geriatric patients.

Geriatric patients, though they may present many of the dermatological problems occurring throughout adult life, show a greater incidence of the degenerative skin changes consequent on sun exposure in the form of collagen degeneration, solar keratoses, keratoacanthoma and skin cancer. The benign, precancerous and malignant skin tumours, the various types of eczema, senile pruritus and certain other conditions will be discussed.


Hypertension and headache.

The frequent association between headache and hypertension has been recognized since the introduction of the sphygmomanometer. A cause and effect relationship proposed by early writers and widely accepted in the medical and lay community has been proposed, questioned and re-examined. The purpose of this review is to scan the literature on the subject, to present some factual data obtained from a 20 year follow-up study carried out at the Cardio-Vascular Clinic, Sydney Hospital and to summarize some personal views currently held on the relationship of hypertension and headache.


Regulation of actin-myosin interaction.

In the presence of the regulatory protein complex tropomyosin-troponin ATPase activity of vertebrate skeletal muscle actomyosin is either higher or lower than in the absence of tropomyosin-troponin. The actual behavior depends on ionic strength, Ca2+ concentration, ATP concentration (determining the amount of rigor complexes present), and the ratio between actin and myosin. This effect of the myosin-actin ratio implies that under certain conditions cooperativity in actin-myosin interaction can be seen.


Ca++ activation of ATPase activity, ATP-Pi exchange, and tension in briefly glycerinated heart muscle.

In the course of MG-dependent ATP splitting by heart actomyosin, an "energy rich" actomyosin-ADP complex is formed, which promotes the incorporation of phosphate 32P into ATP in myofibrils. The rate of this ATP-phosphate exchange reaction depends on the extent of actin-myosin overlap which can be decreased by stretching glycerinated muscle fibres. In heart muscle, the calcium-ion dependence of this reaction is similar to that of the actomyosin ATPase, the tension, and "immediate fibre stiffness" (which is "hookean" and which is a measure for the number of myosin cross-bridges attached to and interacting with actin). These findings suggest that calcium increases the amount of "contractile" actomyosin-ADP complexes. The proportionality between tension and ATPase activity further suggests that the rate-limiting step of the cross-bridge cycle (which determines the molecular turnover number, the "Wechselzahl" of the ATPase) is only little affected by calcium ions. These ions act by recruiting more bridges rather than by accelerating their reactions. In addition, the depressing effect of inorganic phosphate on the contractile tension and its presumable role in energetic insuffciency will be discussed.


Elementary events in excitation-contraction coupling of the mammalian myocardium.

Excitation-contraction coupling of the mammalian myocardium is widely assumed to comprise the following chain of events: (1) Influx of Ca++ into the cell during the plateau phase of the action potential as well as Ca++ release from the subsarcolemmal cisternae of sarcoplasmic reticulum. (2) Activation of the contractile proteins by interaction of Ca++ with the troponin-tropomyosin system. (3) Relaxation due to reuptake of Ca++ by the sarcotubular system as well as by pumping of Ca++ out of the cell through the surface membrane and the transverse tubular system. (4) Movement of Ca++ in the longitudinal tubules back to the subsarcolemmal cisternae. A short comment is included about the effects of hypertrophy on the excitatory processes as well as on cellular structural constituents directly involved in excitation-contraction coupling.


The partitioning of altered mechanics in hypertrophied heart muscle between the sarcoplasmic reticulum and the contractile apparatus by means of myothermal measurements.

Cardiac hypertrophy in the rabbit, secondary to pulmonary artery stenosis, results in a decrease in unloaded shortening velocity (Vmax) and maximum rate of isometric force development (dP/dtmax), while the peak isometric twitch tension is unchanged and time to peak tension (TPT) is increased. The principle hypothesis used to explain these results involve 1) slowing of myosin cross bridge movement as reflected in depressed myosin ATPase activity and 2) changes in excitation contraction coupling phenomena resulting in changes in intracellular Ca++ movement. Ca++ and actin activated myosin ATPase from the hypertrophied (H) muscles is depressed by 30%. Total initial heat, tension dependent heat and tension independent heat are depressed in H muscles by 57, 56, and 61% respectively. The rate of tension independent heat production in H preparations is depressed by 66%. From these data it is concluded that 61% of the depression in Vmax could be accounted for by the alteration in myosin with the reminder attributable to changes in EC coupling. Increased TPT can be accounted for by the change in rate of Ca++ flux as indicated by the alterated rate of tension independent heat evolution.


The reversal of the calcium pump of cardiac sarcoplasmic reticulum.

The reversal of the calcium pump of cardiac sarcoplasmic reticulum (SR) prepared from dogs was investigated. Phosphorylation of the calcium transport ATPase by orthophosphate and ATP synthesis from ADP and orthophosphate by SR passively preloaded with calcium are demonstrated. The ADP-dependent calcium efflux from SR loaded with calcium in the presence of acetylphosphate is stoichiometrically coupled to ATP synthesis from ADP and orthophosphate.


Myocardial function in different models of cardiac hypertrophy. An attempt at correlating mechanical, biochemical, and morphological parameters.

Based on mechanical, biochemical and electron microscopic studies performed in the same stage of experimental cardiac hypertrophy, an attempt is made to define the significance of individual factors responsible for the alterations in myocardial function. Using swimming rats, it is demonstrated that a load-induced increase in cardiac mass is not necessarily connected with an impairment of contractile capability on a cellular level. Yet, also, the reduction of specific ATPase activity and unloaded shortening velocity in pressure-induced hypertrophy (goldblatt rats; aortic stenosis) seems to be the expression of adaptation rather than of cellular damage, at least in the earlier stages. Although there are distinct indications of alterations in Ca-dependent activation and deactivation, in the Goldblatt model electromechanical coupling does not seem to be the main cause of altered contraction parameters. The correlation between specific ATPase activity of actomyosin and unloaded shortening velocity as well as the persistance of decrease in shortening velocity, also under optimal electromechanical coupling conditions, point to an inner relationship between the two values. A discrepancy between unloaded shortening velocity on the one hand and developed tension on the other is mainly due to an increased content of contractile structures. In later stages, an increased connective tissue content influences both isometric and isotonic parameters.


Analytical approach to mathematical modelling of the isometric contraction of the hypertrophied myocardium.

It is attempted on the basis of the Hill two-element model to simulate mathematically the rising phase of the isometric mechanogram in the pressure-hypertrophied rat myocardium (Goldblatt II). The evaluation is based on the experimentally determined force-velocity relation as well as on the characteristic of the series-elastic stiffness. The changes in the isometric mechanogram of the hypertrophied heart muscle observed in the experiment can be mathematically predicted solely by means of the alterations in the force-velocity relationships induced by the hypertrophy, whereby the characteristic of the series-elastic stiffness is considered to be unchanged.


Cardiac function in the chronically volume-overloaded canine heart.

In the chronically volume-overloaded canine heart due to AV-block evaluations of cardiac function were performed during the development of hypertrophy and at stable hypertrophy. In an early stage (1 and 2 weeks of AV-block) when no or only a slight increase of cardiac muscle occurred, contractility measured from dP/dtmax at comparable load is elevated, while later (10 weeks of AV-block) when stable hypertrophy is present, contractility becomes again normal, In the hypertrophied heart a non-depressed cardiac performance and contractility and functional reserve was established from insitu experiments and from evaluations in the isolated heart.


Dynamics of the hypertrophied left ventricle in the rat. Effects of physical training and chronic pressure load.

Left ventricular hypertrophy of about 40% was produced in rats by narrowing one renal artery (Goldblatt II) and of about 6% by swimming-training for 2 hours a day for 14 weeks. The dynamics of the hypertrophied ventricles were investigated by means of the isovolumic systolic and diastolic pressure-volume relations, the stress development during afterloaded and isovolumic contractions, and the force-velocity relation. The following results were obtained: The performance of the whole hypertrophied ventricle is increased. The developed stress and the maximum rate of stress development are enhanced, probably as a consequence of the increased density of the contractile proteins. The maximum shortening velocity can be reduced at the same time.


Effects of hypertrophy on contractile function in man.

In patients with chronic pressure and volume overload matched with respect to elevated left ventricular muscle mass contractile function assessed by isovolumic as well as by ejection phase indexes is depressed to a similar extent. Pressure overload hypertrophy in aortic stenosis is associated with a reduced inotropic state of the individual contractile units. Despite this diminution of contractility hypertrophy may be effective in maintaining a normal ejection fraction as long as afterload does not become excessive. Aortic valve replacement leads to a significant reduction of the preoperatively elevated ventricular muscle mass and to a significant improvement of contractile function.


Dynamic geometry of the left ventricle in hypertrophy studied by quantitative angiocardiography.

An automated videoangiocardiographic system has been developed and used for the study of dynamic internal left ventricular geometry, in 53 patients (12 normals, 20 patients with different degrees of left ventricular [LV] pressure-, and 8 with LV volume overload. 9 patients had different types of cardiomyopathy and 4 atypical or failing LV). From the measurements of ejection phase parameters of contraction, the degree of endsystolic and enddiastolic excentricity of the LV, the ejection fraction, and the circumferential fiber shortening or shortening velocities it has been shown that there are no signs of impaired left ventricular function in mild and moderate left ventricular hypertrophy due to pressure or volume overload.


Cellular changes in mechanically overloaded heart.

From the ultrastructural aspects of the myocardial cell in different types of heart overloading, several points concerning the adaptation of the myocardial cell were briefly summarized: the respective role of hypertryphy and hyperplasia in heart enlargement, the nature of the myofibrillar changes; the changes in the volume, number and size of mitochondria, and the dependence of the cellular lesions on the severity of the load.


Myocardial hypertrophy. Light microscopic findings on the myocardium. Blood supply. Ventricular dilatation and heart failure.

The heart is an organ with an almost constant number of muscle cells under physiological conditions. But beyond the critical heart weight (500 g) there is an increase in the number of muscle fibers (hyperplasia) and a similar increase in the number of capillaries. The relation of 1 capillary to 1 muscle fiber remains constant. During physiological growth there is a rather close correlation between the growth of human coronary arteries and the growth of the myocardium. Under pathological conditions the growth of coronary arteries is slower than that of the myocardium. In many animal species investigated up to now there is a rather close correlation between the diameter of coronary arteries and the diameter of the heart. As a rule, hearts with chronic insufficiency are dilated. They work under unfavourable geometrical conditions. The post-mortem ventricular volume is influenced to a very great degree by rigor mortis.


Time course of electron microscopic alterations in the hypertrophied myocardium of Goldblatt rats.

In Goldblatt rats, electron microscopic investigations of morphological changes in heart tissue during the compensatroy stage of pressure induced cardiac hypertrophy were performed. Myocardial cellular size enlarged considerably within the first 4 weeks after renal artery coarctation. An enlargement of the T-tubular system is particularly striking. The ratio of myofibril volume to total cell volume is significantly increased from the 4th-24th week and can at least partially explain a rise in developed tension which occurs in spite of a frequent disarrangement of myofibrils. In later stages severe changes in the vessel walls take place and there is an augmentation of connective tissue which impairs a correlation between myocardial cell alterations and mechanical parameters.


Hypertrophy due to chronic volume overloading in the dog heart. A morphometric study.

Cardiac hypertrophy due to chronic volume overloading was produced in dogs by experimental complete AV-block. Ten weeks after operation a quantitative electron microscopic study was carried out for determination of the volume density of contractile material and mitochondria. The results were compared with a two-week group and normal dogs. The ratio of the volume density of contractile material and mitochondria is nearly constant during the course of developing hypertrophy.


The common mechanism of the heart's adaptation and deadaptation: hypertrophy and atrophy of the heart muscle.

The short-term adaptation of the heart cells to changing demands is controlled by the phosphorylation potential. By influencing protein synthesis, the same parameter also determines the long-term adaptation. Alterations in protein synthesis are not only of great significance for heart weight, but result in altered structural and enzymatic properties of cardiac cells which are decisive for mechanical performance. These alterations of myocardial tissue depend on the turnover rate of individual proteins. In the stage of adaptation, the proportion of short-living proteins increases whereas it decreases in the overadapted or deadapted (atrophic) organ. Thus, the variations in the ratio of cell structures in heart adaptation, overadaptation, and deadaptation can be explained by the quantitative difference in the control characteristics of transcriptiones encoding of short-living and long-living proteins.


Metabolism of myofibrillar proteins in the normal and hypertrophic heart.

The pathways of myofibrillar assembly and degradation were studied in normal heart and during developing hypertrophy by two independent methods: amino acid incorporation kinetics and the double isotope technique. The validity and sensitivity of both methods were evaluated by computer analysis of data for which leucyl-tRNA was used as a protein precursor. The data obtained indicate that the myofibrillar proteins turn over at nonuniform rates. The half-lives of the proteins studied increase as follows: myosin HC = alpha-actin = tropomyosin greater than LC1 = LC2 greater than actin. In the case of light chains, a macromolecular precursor pool was detected which contributes to the observed lower labeling with 3H-leucine. During developing hypertrophy, the rate of light-chain labeling is increased relative to that of heavy chains.


Changes of myocardial adenine nucleotide and protein synthesis during development of cardiac hypertrophy.

1. Studies on three models of cardiac hypertrophy (aortic constriction, application of isoproterenol, daily administrations of 3,3'5-triiodo-L-thyronine, respectively) reveal that the enhancement of de novo synthesis of adenine nucleotides occurs very early during the development of cardiac hypertorphy and always precedes the increase of protein synthesis. Therefore, it seems likely that the accelerated synthesis of adenine nucleotides is an important factor among those metabolic processes involved in the stimulation of protein synthesis in the hypertrophying heart. 2. As far as the mechanism for the observed enhancement of adenine nucleotide synthesis is concerned, it has been demonstrated that the available pool of 5-phosphoribosyl-l-pyrophosphate, an essential precursor substance of de novo synthesis, is increased in the hypertrophying heart due to isoproterenol and 3,3'5-triiodo-L-thyronine, respectively.


Cardiac myosin. Phylogenic and pathological changes.

Several proteins of the sarcomere differ from one muscle to the other, but it is also becoming evident that cardiac myosin, tropomyosin and troponin are species specific. Moreover, several properties of cardiac myosin could be modified under the influence of thyroxine, exercise, or overloading. These changes are closely related to the speed of shortening of the muscle and to the degree of stimulation of protein synthesis, but nobody is presently able to say if, in heart overloading, the modifications of myosin are a primary defect which is the origin of the failure or if they are only expressing a better adaptation of myocardial efficiency to the decrease of work.


Characteristics of the hypertrophied left ventricular myocardium in Goldblatt rats.

In Goldblatt rats (GV) 4-24 weeks after coarctation of one renal artery the following characteristics were registered as compared to controls (CV) of the same age: Arterial blood pressure increased to 190-200 mmHg in comparison to 105-110 mmHg in controls. This pressure overload induced an increase in ventricular weights (34%-54%). Noteworthy differences in myocardial water, total protein, and nonprotein substance contents were found. Hydroxyproline concentration in GV did not increase significantly until 24 weeks after onset of pressure overload. No significant alterations were detected in the relationship of myocardial, sarcoplasmic, and stromal protein fractions. However, greater changes could be registered in the concentration of the myofibrillar protein fraction and its single components. Furthermore, a correlative depression in specific actomyosin ATPase activity and in maximum shortening velocity of the unloaded cardiac muscle (2,3) was observed.


The role of Ca++ ions in the hypertrophied myocardium [proceedings].

Pressure-hypertrophied right ventricular myocardium (RVH) demonstrates paradoxically increased oxygen consumption (MVO2) related to increased in vitro energy-linked mitochondrial calcium flux. The present experiments were designed to measure mitochondrial Ca++ retention in intact RVH and relate changes in mitochondrial Ca++ metabolism to altered RVH contractile behavior and relaxation. Sixteen cats were pulmonary artery banded and their hearts plus paired controls were perfused with 45Ca Krebs-Henseleit at 30 degrees C, 120 beats/min for 10 min. At Lmax papillary muscles showed reduced active tension, a slower contraction rate, a reduced relaxation rate, a greater time to peak tension and a greater relaxation time. Retained 45Ca of mitochondria was increased from 16.75 + .96nM/mg protein in controls to 20.82 +/- .98 in RVH, (p less than 0.005). This increase in mitochondrial 45Ca retention correlated (r equal to 0.93), (P less than 0.001) with the decreased rate of papillary muscle relaxation. These data show an increased 45Ca retention of mitochondria in pressure-induced RVH and relate this biochemical abnormality to a decreased myocardial relaxation in this state.


Restriction of beta-adrenergic responsiveness in hypertrophied ventricular myocardium of rats.

A singel subcutaneous dose (1 mg/kg) of isoproterenol (ISO) increases the net calcium-45 uptake into the ventricular myocardium of normal rats by a factor of 4 within 6 hours. When the same dose of ISO was administered to rats with aortic constriction the rise in labelled Ca uptake by the hypertrophied myocardium of the left ventricle was greatly reduced. A decrease in ISO-induced Ca uptake also occurred in the non-hypertrophied right ventricular myocardium. Consequently, the stimulatory effect of ISO on the Ca-dependent high energy phosphate consumption was considerably diminished. A similar restriction of ISO-induced radiocalcium uptake and ATP utilization occurred in hypertrophied hearts of chronically ISO-treated rats or when the rats were exposed to other forms of experimental stress such as bleeding or cold. Although the ISO-induced cardiomegaly was reversed within 7 days, the insensitivity to beta-adrenergic stimulation persisted for more than 3 weeks. The results indicate that the decrease in responsiveness to beta-adrenergic agents is not due to the hypertrophy itself but must be considered to be an independent phenomenon - possibly resulting from adaptation to chronic beta-adrenergic overstimulation.


Development of two inbred strains of rats and characteristics of their skin reactions.

Two inbred strains of rat (Donryu and Sprague-Dawley strains) were developed. The skin reactions of these strains immunized with M. tuberculosis, hen egg albumin (OVA) or hen egg lysozyme and challenged with the purified protein derivative (PPD) or each antigen were even and uniform. The Donryu strain showed a typical Arthus reaction with petechiae and edema and a negligible delayed skin reaction, whereas the Sprague-Dawley strain showed a poor Arthus reaction and a typical delayed skin reaction with central necrosis and induration. The Arthus reaction or delayed skin reaction could be passively transferred to recipient rats of each strain by immune sera or sensitized peritoneal exudate cells (PEC), respectively.


Transmural distribution of myocardial blood flow and of coronary reserve in canine left ventricular hypertrophy.

Left ventricular hypertrophy was induced by banding of the ascending aorta in pupies at the age of 6 weeks. At the age of one year left ventricular weight per body weight was increased by 87% compared to control litter mates. While myocardial perfusion and myocardial oxygen consumption per 100 g were identical in the hypertrophy and control group, there was a significantly diminshed ratio of subendocardial/subepicardial flow in the hypertrophy group during moderate exercise. With maximal coronary dilation subendocardial diastolic resistance (mm Hg/ml-min-1 per 100 g) was 0.16 +/- 0.03 in the control group and 0.26 +/- 0.03 in the hypertrophy group. This diminished coronary reserve indicates an insufficient growth of the vascular bed in these hypertrophied hearts.


Myocardial oxygen consumption and substrate uptake in man during physiological and pathological volume load.

It is shown in trained and untrained healthy individuals that the energy requirement of the physiologically hypertrophied heart is lower at rest and even more pronounced during submaximal heavy exercise compared to the non-hypertrophied state. This difference exceeds the changes which could have been anticipated by deviations in hemodynamics and total heart weight. In patients with mild or moderate aortic insufficiency the energy expenditure of the pathologically hypertrophied heart per unit tissue mass is comparable to the non-hypertrophied state at rest or during exercise. It is increased in severe aortic regurgitation or additional myocarditis. The transition from compensation to failure may be associated with a steep decreased of the metabolic and flow reserve of the whole heart.


Left ventricular systolic wall stress as a primary determinant of myocardial oxygen consumption: comparative studies in patients with normal left ventricular function, with pressure and volume overload and with coronary heart disease.

Left ventricular dynamics, coronary blood flow (Vcor), and myocardial oxygen consumption (MVO2) were determined in normal patients (N), in chronic pressure overload (aortic stenosis, AS), in chronic volume overload (aortic incompetence, AI), and in coronary heart disease (CHD). Peak systolic and enddiastolic wall stress were increased in AS and AI by 26-52 per cent, the systolic stress being preferably increased in AS, whereas enddiastolic stress was markedly greater in AI. Vcor and MVO2 were elevated in both groups by 45-55 per cent (p less than 0.001). Sufficient correlation was present between peak systolic wall stress and the MVO2 (r equal to 0.82). Since at a given wall stress the MVO2 was somewhat increased in AI and AS when compared with N and CHD, the considerable inhancement of the rate of pressure development (AS) was well as of the external cardiac work (AI) may contribute to the increase in overall oxygen consumption. It is concluded that systolic wall stress represents a primary determinant of MVO2 in pressure and volume overload and that the MVO2 increases in these diseases when hypertrophy becomes inappropriate with regard to the pressure and volume demands imposed to the left ventricle.


Industrial rheumatology. Clinical investigations into the influence of the pattern of usage of the pattern of regional musculoskeletal disease.

Regional musculoskeletal diseases are exceedingly common in all segments of society, and dramatically so in industry. For generations, medicine has assumed that many such entities are use-associated. A critical review of several examples of back and upper extremity disease demonstrates that the literature supporting these assumptions is almost entirely anecdotal. It is argued that if defined patterns of usage were associated with defined clinical syndromes, such knowledge would have considerable therapeutic and prophylactic potential. Industrial rheumatology is proposed as an investigative discipline for the study of such relationships. The prerequisites in terms of assumptions and methods as well as potential fallacies and pitfalls are discussed.


Immune complexes and complement catabolism in ankylosing spondylitis.

In serum samples from 37 patients with ankylosing spondylitis (AS), immune complexes were quantitated by the 125I-Clq binding test; in paired plasma samples the C3 breakdown product C3d was measured by an immunochemical method. Compared to results in 30 blood donors, the Clq binding activity was significantly (greater than 2 SD), although discretely, increased in 5 of 8 patients with seropositive AS, but not in other AS patients. All C3d levels were within the normal range. In a parallel investigation, increased Clq binding activity and C3d levels were found in 87% and 90%, respectively, of patients with seropositive rheumatoid arthritis.


Heparitin sulfates (heparan sulfates) of atherosclerosis-susceptible and atherosclerosis-resistant pigeon aortas.

Electrophoretic mobilities of heparitin sulfates (HS) from the thoracic aorta and the celiac bifurcation of atherosclerosis-susceptible White Carneau and atherosclerosis-resistant Show Racer pigeons at four ages were examined. Atherosclerosis-susceptible White Carneau aortas contain, in addition to their normal HS component, a variant type of HS (HS') in pre, early- and moderately-atherosclerotic celiac foci which is not found in the thoracic regions of either breed or in Show Racer celiac foci at any age. These findings are interpreted to suggest a role of HS' in the pathogenesis of atherosclerosis and to propose an explanation for atherosclerotic susceptibility and resistance in pigeons.


[Correlation between seizure susceptibility and brain catecholamine levels. An experimental study using a kindling preparation].

Correlation between the kindled seizure susceptibility and brain monoamine levels was investigated in the hippocampal and amygdaloid kindled cats. Increase of interictal discharge (IID) frequency and morphological change of IID into self-sustained discharge appeared following reserpine administration. alpha-MPT also increased the IID frequency. These changes in reserpine- and alpha-MPT-treated cats were suppressed completely by the administration of L-DOPA, suggesting that depletion of norepinephrine and dopamine exacerbate the kindled seizure susceptibility. In a second experiment, the assay study of brain catecholamine showed significant and parallel depletion of both norepinephrine and dopamine in the hippocampal kindled cat brain. It is concluded that catecholamine may play an inhibitory role in the establishment and neurohumoral control of the kindled seizure susceptibility.


Inhibitory effect of YC8 leukaemia cell line on in vitro lymphocyte reactivity.

Mitomycin-treated transplantable Moloney virus-induced lymphatic leukaemia cells (YC8) not only failed to stimulate normal allogeneic lymphocytes in one-way mixed leucocyte culture (MLC) but also exerted a strong inhibitory effect on the proliferative response of normal lymphocytes, in MLC and after stimulation by mitogens. Potentially inhibitory factors which could be released in the culture fluids by the YC8 cells were not found, but a YC8-derived adherent cell subpopulation was identified as being responsible for the in vitro suppression.


A comparison of ipratropium bromide, deptropine citrate and placebo in asthma and chronic bronchitis.

A new anticholinergic aerosol, ipratropium bromide, was compared in a double-blind cross-over trial with an established preparation, deptropine citrate, and placebo in 16 patients with defined asthma or chronic bronchitis. Ipratropium bromide produced a significantly greater and more rapid bronchodilation than did deptropine citrate or placebo in the doses used, and its effect was slightly greater in the asthmatic than in the chronic bronchitic group. No unwanted effects on secretion were seen with ipratropium bromide.


The release of beta glucuronidase from leukocytes in the presence of immune complexes.

The lysosomal enzyme beta glucuronidase was selectively released from leukocytes when these were incubated with insoluble immnue complexes and also from the leukocytes of patients with immune complex disease when these were incubated with their own plasma.


Structural characteristics of heparan sulfates with varying sulfate contents.

Structural properties of heparan sulfate preparations from hog mucosa and beef lung sources were obtained by application of Smith degradation and nitrous acid reactions. Products formed by these reactions indicated that most of the iduronic acid present in these mucopolysaccharides is ester sulfated, whereas N-sulfated glucosamine residues are ester sulfated much less frequently. Repeating units with sulfated iduronic acid found to occur almost entirely in single sequences. Futhermore, the iduronic acid moieties may be bound to either N-acetylated or N-sulfated glucosamine units, with these occuring at either end of the uronic acid unit.


Purification and characteristics of (Na+, K+)-ATPase from canine kidney by zonal centrifugation in sucrose density gradient.

Microsomes were prepared from the outer medulla of canine kidney. Partially purified preparation of (Na+, K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) was obtained by solubilization of microsomes with sodium deoxycholate, and by precipitation with dilution. The deoxycholate-enzyme thus obtained was further purified by incubation with sodium dodecyl sulphate in the presence of ATP followed by a single zonal centrifugation in a sucrose density gradient by the method of Jørgensen [(1974) Biochim. Biophys. Acta 356, 36-52]. The (Na+, K+)-ATPase was purified to a specific activity of 1600--1800 micronmol Pi - h-1 - mg-1 protein. The yield was 20 mg per single centrifugation with a zonal rotor. Electron microscopy showed that the sectioned pellet of the purified enzyme contained exclusively membranous fragments in contrast with membranous vesicles of starting microsomes. Sodium dodecyl sulphate polyacrylamide gel electrophoresis showed that almost all proteins were accounted for by two polypeptides with molecular weights of 105 000 and 58 000, and that the mass ratio of the large to the small polypeptide was 82 : 18.


Purification and characterization of an extracellular ATPase from oviductal secretions.

Oviductal secretions include an ATPase (EC 3.6.1.3) that is transferred from the outer surface of the secretory cells to the surface of the ovulated oocyte. The enzyme has been purified and is a highly labile, very high molecular weight lipoprotein complex (greater than 4-10(6)). It consists of 47% protein and 53% lipid. Lipid composition is limited to phosphatidylcholine, phosphatidylethanolamine and sphingomyelin. The basic protein subunit has a molecular weight of 170 000. The enzyme exhibits many of the characteristics of ectoenzyme ATPase. The enzyme is Mg2+ or Ca2+ dependent; the Mg2+-ATPase has pH optima at 6.0 and 7.8 and the Ca2+-ATPase at 9.0. Substrate specificity is limited to ATP with lesser activity towards GTP, CTP, UPT and ADP. Km for ATP is 0.88 mM and the enzyme is inhibited at substrate concentrations greater than 3 mM ATP.


The crystallization of beef heart mitochondrial adenosine triphosphatase.

Conditions are described under which crystals are formed with the ATPase enzyme from beef heart mitochondria. Enzyme activity is retained during the crystallization process. Some unit cell parameters have been determined by electron microscopy of negatively stained crystals; comparison with the unit cell crystalline matris inclusions indicates that such inclusions could be ATPase crystals.


Tryptic fragmentation of 30-S dynein from Tetrahymena cilia.

30-S dynein ATPase from Tetrahymena cilia was digested with trypsin (dynein: trypsin = 20:1, by weight) at 25 degrees C for 20 min, resulting in the release of a 12-S fragment possessing ATPase activity. The 12-S ATPase fraction obtained by sucrose gradient centrifugation contained several polypeptide chains as indicated by SDS gel electrophoresis. The largest chain was smaller than the subunit of 30-S dynein and almost the same size as 14-S dynein. On the other hand, when 14-S dynein was digested in a similar manner, its sedimentation value changed from 14 to 12 S, but the peak of ATPase activity was retained at 14 S, suggesting differences in amino acid sequences between the 30 and 14-S dyneins. When the time course of tryptic digestion of 30-S dynein was investigated in a trypsin:dynein ratio of 1:200, discrete fragmentation took place, producing an intermediate fragment of 24 S and the 12-S fragment. The 24-S fragment recombined with outer fibers to some extent, while the 12-S fragment lacked this ability. However, the 12-S fragment was somewhat stimulated to recombine with outer fibers in the presence of other components involved in the trypsin digest. The enzymatic characteristics of the 12-S fraction were different from those of 30-S dynein, especially the activity dependence on pH showing a typical bell-shaped curve.


[Allosteric effect of substrate on sarcoplasmic reticulum Ca-ATPase].

High concentration of ATP is found to activate Ca-dependent ATPase from sarcoplasmic reticulum both in membrane fraction and in purified enzyme preparation. The treatment of Ca-ATPase preparation with tripsin results in the elimination of the activating effect of ATP, which is accompanied by the disappearance of 100.000 molecular weight protein and by the appearance of fragments with molecular weight of 45.000 and 55.000. Repeated freezing of the enzyme preparation eliminates activating effect of ATP. ATP action is analysed from the viewpoint of allosteric kinetics, which postulates the existence of two Ca-ATPase conformers, their mutual conversion being induced by ATP binding at allosteric center. Kinetic parameters of the conformers studied are calculated.


[Interaction of a membrane preparation of Na+, K+-ATPase with a spin-labeled analog of ATP].

Interaction of membrane Na+, K+-ATPase preparation from brain gray matter with spin-labelled ATP analogue, in which free iminoxyl radical is joined as a result of 2'(3')-OH ribose groups acylation, is studied. The rotatory mobility of spin-labelled ATP analogue in Na+,K+-ATPase preparation is found to change in non-linear manner during temperature variation (the break-point on the curve being at 20-23degrees C). It correlates with temperature dependence of Na+,K+-ATPase and temperature dependence of lipid viscosity in the membranes, determined by means of hydrophobic spin probes. Substitution of Mg2+ ions with paramagnetic Mn2+ ions resulted in an intense magnetic dipole-dipole interaction between a spin label and Mn2+ ion, which indicated the formation of triple complex enzyme--spin-labelled ATP--Mn2+.


The development of glycolytic and pentose phosphate shunt enzymes in human brain.

A quantitative enzyme analysis of 32 fetal human brains of 6--42 weeks gestational age range was carried out for the major glycolytic and pentose phosphate shunt enzymes. A critical period of raised enzyme levels was observed at 14 weeks. The glycolytic rate was probably controlled by the activities of hexokinase and phosphofructokinase which appear from the development patterns to have independent genetic sites. A rise in most enzyme activities was experienced in the final weeks of gestation towards levels consistent with those of adult tissues. Pentose phosphate shunt enzyme levels remained virtually unchanged during gestation after 14 weeks.


Study of blood aminoacids in experimental hyperphenylalaninemia.

Hyperphenylalaninemia was induced in rats treated with p. chlorophenylalanine and cotrimoxazole, without administration of excess phenylalanine. Enhancement of phenylalaninemia and abnormalities in other serum amino acids were similar to those found in phenylketonuric patients, out of the restricted diet.


A quantitative model of actin-myosin interaction in skeletal muscle.

Biochemical schemes for the actomyosin ATPase cycle as well as the cooperative regulation of ATPase activity are incorporated into a model of the contractile process of intact muscle. This model is shown to describe accurately the tension developed by skinned muscle fibers in the absence of Ca. This work adds to the evidence that the extrapolation of results from purified protein systems to intact muscle may be valid. Extensions to the case of Ca-activated tensions are discussed.


Dependence of energy transduction in intact skeletal muscles on the time in tension.

In intact single crayfish muscle fibers and frog semitendinosus muscles we have studied the tension response to sinusoidal length changes in the frequency range of 0.25-133 Hz. By this method we have resolved three processes in the interaction of myosin cross-bridges with actin in fully activated preparations. They are (A) a low-frequency phase advance, (B) a middle-frequency delay, and (C) a high-frequency advance. These processes can be used as probes to study the chemomechanical coupling of contractility. Process (B) represents net power output from the muscle preparation (oscillatory work). With maximal K or caffeine activation of crayfish muscle at 20 degrees C, it decreases to zero in the initial 45 s of maintained tension. Similar results were obtained with frog semitendinosus whole muscles. We interpret this decrease of (B) with time as a gradual decrease in actomyosin ATP-hydrolysis rate.


Flow cytometric measurement of the polarization of fluorescence from intracellular fluorescein in mammalian cells.

Based on the description of a laboratory-built flow cytometer, the necessary modifications of this instrument for the measurement of fluorescence polarization are described. At a maximum rate exceeding 1,000 cells/s, the instrument is capable of measuring simultaneously the horizontally and vertically polarized component of the fluorescence emitted from stained cells excited with vertically polarized light. By mathematical analysis of the accumulated data, the distribution of polarization values in the population is obtained. Various sources of instrumental error have been investigated. The large aperture of the detector optics leads to systematic underestimation of the polarization values. Other errors are negligible, and the instrument is shown to give results consistent with the theory of fluorescence polarization. Application of the instrument is illustrated by experiments with mammalian cells exposed to the fluorogenic substrate fluorescein diacetate (FDA). The polarization of the fluorescence from intracellular fluorescein produced by hydrolysis of FDA is measured, giving information on the cytoplasmic microviscosity. It appears that this microviscosity is constant over the cell cycle. On the other hand, it is significantly affected by the osmolarity of the medium.


[Effect of hydrocortisone on the fractional makeup of acid mucopolysaccharides in the aorta].

Five components of the acid mucopolysaccharides were isolated from rabbit aorta; these were hyaluronic acid, heparitin sulphate, chondroitin sulphate A, C and B. Prolonged administration of hydrocortisone increased the hyaluronic acid concentrations and decreased the level of heparitin sulphate. Fifteen days after the cessation of the hormone administration the aortic tissue proved to contain a lower percentage of chondroitin sulphate A, C anc B.


A trial of the comparability of peak expiratory flow meters in schoolchildren.

In many circumstances it may not be possible to measure peak expiratory flow rate on all subjects using the same meter. A small trial was carried out to assess the variability of such meters. Five newly calibrated adult Wright peak expiratory flow meters, which gave comparable readings when rechecked on another rotameter, were compared in a trial on 160 schoolchildren. Each child blew once into each meter, and the design was balanced so that the effect of order of blow was eliminated. Statistically significant differences were found between the meters, although the difference between any  pair of meters was less than 5% of the average peak flow rats. Since the meters were chosen because they were very similar it is likely that larger differences would be found in other circumstances. This could be an important source of error in multicentre studies where several meters have to be used.


[Cytotoxicity of cadmium : study on root meristems of Allium sativum L].

Cadmium nitrate, acetate and sulphate cause death of root meristems of Allium sativum at 5.10(-7) Mol/ml concentration for the two first ones and 10(-7) Mol/ml for the last one. Lower concentrations do not induce chromosomal aberrations. As to the cellular toxicity, cadmium salts are between phenyl-mercuric-hydroxid and lead nitrate, the first one being the most active.


[In vivo activation of blood and arterial prophospholipase by an activator of blood platelet origin].

When partially purified platelet-rat lysate is injected in the rat aorta, transformation of prophospholipase into phospholipase is observed. Blood prophospholipases are activated almost entirely during about 15 minutes; aortic phospholipase are entirely activated for a longer time.


[Action of vestibular receptors pn the spontaneous afferent activity of an ipsilateral semicircular canal in the frog].

In the frog, the influence of both the part of the efferent system which depends on ipsilateral vestibular inputs and the receptor-receptor fibre system on the afferent activity of semicircular canals is either null or facilitatory. The receptor-receptor fibre system being inhibitory, it seems that the part of the efferent vestibular activity which depends on ipsilateral vestibular inputs is facilitatory, which agrees with previous results.


[Tonic conjugated action of receptor-receptor fibers and of the efferent vestibular system on the spontaneous afferene activity of a semicircular canal in the frog].

In the frog, the joint action of non-afferent vestibular systems [i.e. the efferent vestibular system and the receptor-receptor fibre system] on the afferent vestibular activity is null or very small. The receptor-receptor fibre system being inhibitory, it seems that the efferent vestibular system as a whole is facilitatory, which agrees with previous results.


[Action of 9-aminoacridine on the axonal membrane of the cockroach [Periplaneta americane L].

When applied externally to the cockroach giant axon, the substance 9-aminoacridine diminishes both sodium and potassium conductane increases. The K+ CURRENT DIMINUTION SHOULD BE DONE TO A 9AA-induced potassium inactivation or to an accumulation of K+ ions in the periaxonal space.


[The properties, especially antispamodic, of total alkaloids of the roots of Xylopia quintasii Engl. and Diels. Annomacea].

DL50 of the total alkaloids of Xylopia quintasii is 850 mg/kg per os in the mice. Papaverine like properties are described.


[Ultrastructure of impuberal vaginas cultivated under various hormonal conditions].

Differentiation of rat vaginal epithelium has been studied in organotypic culture in vitro under different hormonal conditions [evolution in association with ovary or testis, and after injection to rats of progesterone 5 mg. and estradiol 0.1 lambda). Whatever the hormonal preconditioning before the vaginal culture the same, complet cornification occurs.


[Diuretic action of calcitonin: demonstration of an inhibiting effect on sodium reabsorption in the ascending limb of Henlé's loop].

It was found that calcitonin (porcine) at the dose: 4 I.U. MRC./kg/hr (i.v.), in the rabbit, increased the diuresis and oxmolal excretion, and simultaneously decreased free-water reabsorption and urinary osmolality. The results suggest that calcitonin acts by inhibiting sodium reabsorption in the ascending limb of Henl's loop. This hypothesis was confirmed by renal autoradiography study with 22Na.


[Influence of feeding rhythm on blood insulin in growing rats].

Plasma insulin in ad libitum fed growing rats increases during dark hours and decreases during light hours. In contrast, meal fed growing rats [6 equal meals at regular interval during the day] exhibit a constant plasma insulin level. It may be inferred that improvement of nitrogen retention in meal fed rats is not related to an increase in insulin secretion.


[Application of a truncated Poisson distribution for the counting of virus plaques by micromethod. Variation of its relative inaccuracy].

The microculture plaque titration of virus shows an important disadvantage : the reduction of the areas observation brings out plaque convergence and prevents from their exact enumeration. Nevertheless, a method, proposed by Moore, enables the estimation of virus title. The influence of the dilution and repetition factors on the title precision has been investigated. Two examples are treated.


[Demonstration by immunofluorescence of somatotropic cells and prolactin cells in the monkeys Erythrocebus patas, Cercopithecus aethiops and Papio hamadryas].

Using antibodies against human STH and ovine prolactine, it is possible to identify somatotropic and prolactin cells in the pituitary anterior lobe of three species of monkeys: Erythrocebus patas, Cercopithecus aethiops and Papio hamadryas. The somatotropic cells are numerous in both adult and infant male or female monkeys, especially in the lateral lobes of the pituitary gland. The prolactin cells can be distinguished in all pituitaries studied, regardless age or sex; indeed there are more numerous in adult females. The immunofluorescent technique reveals a more great number of cells of somatotropic and prolactin type than the classical tetrachrome technique.


[Influence of temperature on the motility of human spermatozoa].

The mean swimming speed of a suspension of human sperms has been estimated by applying a kinetic theory and using an image analysing computer. This technique allowed the study of the evolution of motility in terms of temperature: the global swimming speed significantly increases from 22 degree C to 31 degrees C, and then remains rather constant. However the percentage increases are very varying according to samples.


[Microassay by nondispersive spectroscopy of human spermatozoa in electron microscopy. Preparation of samples and determination trials].

The proposed choice of a stardised fixation for human spermatozoa constitutes an important step for microanalysis. Zinc determination on the spermatozoa was done. A comparison with extracellular control analysis cannot lead to a significant interpretation in the absence of a quantitative approach.


[Cholinesterases (acetyl and pseudocholinesterase) in human amniotic fluid].

Study on 41 cases. The cholinesterasic activity of human amniotic fluid, free from blood, is very weak, in average 0,10 microkatal, approximatively 300 times weaker than mother's serum. In this "total cholinesterase", we find a large amount (about 40%) of acetylcholinesterase. Amniotic cholinesterases have an prominent placentary origin, with, in addition, a likely activity proceeding from cellular elements.


[Experimental stomach cancerization in the rat].

Simulated gastric cancers in rats have been realised by implantation of walker tumour with three different methods. The best results are obtained with the injection of 0,1 ml of tumour cells suspension in the antral wall. With this method, no important trauma is done to the antral wall, and percentage of tumour implantation in antral wall is high (84%).


[Spatio-temporal development of Walker tumor implanted in the stomach wall of the Wistar rat].

Simulated gastric cancers have been realised in rats with injection of 0,1 ml of tumour cells suspension in the antral wall. A macroscopic and a microscopic study have been done. The antral tumour showed a constant growth pattern and rats died between 12th to 16th days after tumour implantation. During the first days (1 to 9) the tumour growth is relatively slow, the tumour does not extend out of the antral wall and remains in the submucous part of the gastric wall. After this time, the tumour growth is faster and the anatomicals structures of the wall are destroyed. It is possible with our method, to induce gastric cancer in large series of rats, which can be examined at different stage of Walker tumour growth.


[In vitro effect of serotonin on the enzyme activities of glutamate decarbosylase and GABA transaminase at the level of acellular preparations of rat mesencephalon synaptosomes].

The effect of serotonin on glutamate decarboxylase and GABA-transaminase was studied, in vitro, in synaptosome homogenates from rat mesencephalon. Serotonin dissolved in the incubation medium inhibits glutamate decarboxylase activity and stimulates GABA-transaminase activity.


[Study of a placental protein binding AMPc. Its subcellular distribution. Hypothesis of a relationship with chorionic somatommamotropin hormone].

The authors have shown the presence in the human placenta of a binding activity for cAMP. This activity is protein like substances bound and is principaly located in cytosol and in nucleus. The authors have tried to purified this protein by gel filtration and chromatography on DEAE cellulose. Whatever the method employed, there is always in the protein a mixed activity: cAMP binding activity and HCS immunological activity. Purified HCS by classical method shows no binding activity. However when cAMP is added in immunological system HCS-immun-serum anti-HCS, the reaction is modified in an inhibitory way. This behaviour seem to be specific since never HGH nor TSH have the same. This behaviour has been confirmed several times as well during competition curves which shift toward left in presence of cAMP, as for assays of individual serums or amniotic fluids. In this last cases, the results are twice as eleveted depending if the lecture is done on a curve done without cAMP or with cAMP.


[Induction of N-acetyllactosamine synthetase activity in the mouse mammary gland by prolactin and placental lactogen hormone].

The authors show that the ovine prolactine promote induction of N. acetyl lactosamine synthetase in tissue culture of mammary glands of pregnant mice. A crude extract of human placenta has also a lactogenic activity as tested by the same method, but in this case the blank values are very high for large concentration of crude extract. The molecular forms of HCS are tested: the slow band has a lactogenic activity, the intermediate band has no activity and the rapid band seems to be inhibitory.


[Molecular forms of human growth hormone (HGH) secreted by cultured fetal pituitary cells].

Cultures of foetal human pituitary cells excrete and synthetize different molecular forms of proteins with HGH immunological activity. These cells incorporate tritiated-leucine in these proteins. Gel chromatography on sephadex using different length of column allow us to separate: One form excluded in front of the dead volume and which has a high molecular weight. This form is not dissociated by treatment with urea 8 M, guanidine 6 M and dithiothreitol. Nor this form is modified by treatment by ribonuclease. One form excluded within the dead volume and which is probably a dimere. This form is no more modified by the different treatments. One form which is excluded like a monomere--it is the more important form--. This form is dissociated in fragments of lower molecular weight by urea 8 M. This dissociation is partially reversible by dialysis.


[Heterogeneity of ovine prolactin after labeling with iodine 125: value of labeling with lactoperoxidase].

The authors have shown an heterogeneity of the ovine prolactine molecule after labelling with iodine 125. As well with chloramine T as with lactoperoxydase, it appears three molecular species which react with the immune serum antiprolactine (I.S.). The first species is of high molecular weight and is probably constituted of aggregates. Their combination with the I.S. is non specific and give blanks of high value. The second species is a dimere and the third one is the monomere. The two last species react with the I.S. and can give competition curves when they are choosen as tracer. However, if one uses as tracer a product obtained by labelling with chloramine T, the competition appears for high concentrations of native hormone. As if the I.S. recognizes much more the labelled protein than the native one. But if one uses the same species but labelled with lactoperoxydase, the competition appears for concentrations lower than five nanogrammes. In the same time one can see that the specificity toward different I.S. is modified. The authors think that the labelling with lactoperoxydase better preserves the tertiary structure of the native protein than do the labelling with chloramine T.


[Incidence of ligation of terminal vessels of the uterine artery on nidation and fetal growth].

We have ligatured uterine terminal vessels in the rabbit fifteen days befor coitus. This uterine vasculature alteration product first one decrease of the number of implantations and then product one foetal growth retardation and perhaps one teratogenic effect.


[Presence of monogalactosyl diglyceride in the rat nerve sciatic].

We present a pattern of fractionation of total lipids, leading to the isolation of individual glycolipids, MGDG contains as sugars, a high quantity of galactose and a low level of glucose. The study of the fatty acids distribution shows: a) a high level of saturated short chains fatty acids, b) a high level of palmitic acid (C 16:0, 68% of the total).


[Effects of sodium n-dipropylacetate on the GABA level in various areas of the mouse brain].

Regional brain GABA distribution studies show that after administration of sodium n dipropylacetate, a competitive inhibitor of GABA transaminase, the concentration of GABA increases in some regions i.e. Olfactory Bulbs, Hypothalamus, Cortex, Cerebellum. The GABA level remains unchanged in Caudate Nucleus, Pons Medulla, Hippocampus in our experimental conditions. These variations do not correlate with the initial GABA level.


[Effect of short-term cyclophosphamide administration on rabbit sperm].

Daily injection in the rabbit of 60 mg cyclophosphamide, during four days, product during 8 to 9 weeks one importance decrease of the number and the mobility of the ejaculated spermatozoa. This interval correspond with the spermatogenesis and epididymal transit period. Low doses injections product only one mobility decrease.


[Further experiments on the conditioning and pseudoconditioning of the tarsal reflex in the drosophila (Drosophila melanogaster): effect of low intensity electric shocks].

In a recently described procedure of negative instrumental conditioning, applied to the tarsal reflex of Drosophila (Médioni and Vaysse, 1975), it was attempted to eliminate some "noise" sources superimposed on the associative conditioning effect. 1) By increasing the preliminary reiteration of the sugar stimulus (US for the tarsal reflex), the suppressive influence of "desensitization" (i.e. sensory adaptation and/or central habituation) could be minimized, at least in the first 20 trials of the training phase. 2) By lowering the intensity of the electrical shock used as an aversive reinforcer, the pseudo-conditioning rate could be substantially reduced too. However the relative weight of the pseudoconditioninq effects could not be decreased by these means: for the effectiveness of the mild shock became weaker for the "true" conditioning as well.


[Influence of various physical factors on the developmental capacities of the ovum of Artemia salina].

Artemia salina dry eggs exhibit a great resistance to different physical factors: acceleration and vibration, low temperature, high vacuum and magnetic fields. Vibration test, alone or combined with acceleration test decreases the Artemia salina egg developmental capacity. Nevertheless, the differences are small and much lower than those observed in previous space experiments. The viability of Artemia eggs is not impaired by low temperature, high vacuum exposure and by high magnetic fields (15, 25 and 150 Koersted) or by earth magnetic field shielding.


[Measurement of the blood flow in various areas of the rat brain by means of microspheres].

A method is described to measure regional blood flow in different structures of the rat brain. Microspheres (15 micron) are injected, the brain is sectioned, stained for myeline, radioautographs are prepared and the microspheres in the different structures are counted. The values obtained for different brain structures are counted. The values obtained for different brain regions (cortex, corpus callosum, thalamus hipocampus, hypothalamic region, colliculi, cerebellum, pons, medulla) compare well with those published by others on larger animals. In rats fed 1% of lead from birth, higher blood flow is found in the cortex and a lower one in the interior part of the brain compared to controls.


[Effect of intravenous infusion of (+/-)-noradrenaline on the urinary clearance of H3 (+/-)-noradrenaline].

In anesthetized dog, intravenous infusion of NA does not modify the relationship between [3H]-(+/-)-NA urinary clearance/GFR. Urinary excretion of NA is directly related to glomerular ultrafiltration.


[Effects of lead administered during pregnancy to C57B1 mice].

Treatment of female mice with high doses of lead from different times of the gestation, induces abortion or retardation of growth of the embryos. When it is given from birth, it provokes important mortality in the youngs and a retardation of the postnatal growth. In most cases, lead administered from the first day of gestation delays slightly the development of the embryo and inhibits its implantation. It seems that a deficiency in the plasmatic progesterone levels is directly implied in this inhibition.


Nuclear suppressors of the (poky) cytoplasmic mutant in Neurospora crassa. II. Mitochondrial cytochrome systems.

The mitochondrial cytochrome aa3 and b deficiencies of the [poky] cytoplasmic mutant of Neurospora crassa are partially suppressed by mutant alleles of any one of six nuclear genes, namely sup-1, sup-3, sup-4, sup-5, sup-10 and sup-14. The suppressor-induced increases in the concentration of both cytochromes are detected in the mitochondria from exponentially growing [poky] cultures, and, thus, are clearly distinguishable from the age-dependent changes in the cytochrome system that occur in cultures that approach, or have reached, the stationary phase of growth. The relative amounts of mitochondrial cytochromes aa3 and b show a direct correlation with the relative efficiency of the various sup genes as suppressors of the slow-growth phenotype of [poky]. Since [poky] is defective in mitochondrial protein synthesis due to a lack of 30 S mitochondrial ribosomal subunits, it is proposed that the six suppressors promote the assembly of functional mitochondrial ribosomes.


Reversible dysfunction of T-lymphocytes in common variable immunodeficiency.

A 30-year-old man with recurrent sinopulmonary infections, eventually fatal, was found to have common variable immunodeficiency. In addition to low serum immunoglobulin concentrations he also had lymphopenia and cell-mediated immunodeficiency as shown by cutaneous anergy and a poor lymphocyte response to phytohemagglutinin (PHA) in vitro. However, intradermal injection of PHA produced a vigorous cutaneous response, showing that some cell-mediated responsiveness remained. The responsiveness of his lymphocytes to PHA was restored towards normal (confirmed by chromosome studies) by the addition of a small number of normal leukocytes to cultures; thus a reversible functional defect in his T-lymphocytes was revealed. Experiments indicated that the defect was cellular and not due to serum factors and it was concluded that normal leukocytes restored a missing factor to the patient's T-lymphocytes. Although counts of macrophage precursor cells in the bloodstream were low, thus contributing to the immunodeficiency, this could not have caused the reduced PHA response. Several relatives of this patient had lymphoma; two cousins had common variable immunodeficiency.


Nuclear and nucleolar ultrastructure of Sézary cells.

Sézary cells were studied in the peripheral blood and characteristic skin lesions of the Sézary syndrome and mycosis fungoides by transmission electron microscopy to obtain more information on their nuclear and nucleolar ultrastructure. Sézary cells contain nucleoli with nucleolonemas or ring-shaped nucleoli similar to those of lymphoblasts and mature lymphocytes. "Maturation asynchrony" of the nucleolus and cytoplasm was evident in some cells that contain large numbers of ribosomes and ring-shaped nucleoli and in other cells that contain nucleoi with nucleolonemas and few ribosomes. The maturation asynchrony of the nucleolus and the cytoplasm, the presence of mitochondrion-like inclusion bodies in the nucleus, and fusion of mitochondria with the nucleus in Sézary cells are ultrastructural abnormalities of this neoplastic lymphocytic variant. The presence of the intranuclear "mitochondrion-like" inclusion body and nuclear rodlets in Sézary cells were exceptional findings.


Myosin and paramyosin of Caenorhabditis elegans: biochemical and structural properties of wild-type and mutant proteins.

Myosin and paramyosin have been purified from the nematode, Caenorhabditis elegans. The properties of the myosin in general resemble those of other myosins. The native molecule is a dimer of heavy (210,000 dalton) polypeptide chains and contains 18,000 and 16,000 dalton light chains. When rapidly precipitated from solution, it forms small, bipolar aggregates, about 150 nm long, consistent with the expected molecular structure of a rigid rod with a globular head region at one end. Its ATPase activity is stimulated by Ca2+ and EDTA. The myosin binds to F actin in a polar and ATP-sensitive manner, and the Mg2+-ATPase is activated by either F actin or nematode thin filaments. Dialysis of myosin to low ionic strength produces very long filaments. When a myosin-paramyosin mixture is dialyzed under the same condtions, co-filaments form which consist of a myosin cortex, surrounding a paramyosin core. Some properties of myosin from the mutants E675 and E190, which have functionally and structurally altered body wall muscles, are compared with those of wild-type myosin. These myosins of these results are discussed in terms of the myosin heavy chain composition.


[Solubilization and purification of Na+-K+ ATPase of human erythrocyte mambranes using sodium deoxycholate].

The (Na+-K+)-dependant ATPase prepared from human erythrocyte ghosts has been purified with sodium deoxycholate in a high ionic medium. After the purification, 60% of the native activity bound to the membranes was recovered.


Congenitally complete heart block. Developmental aspects.

Three cases of congenitally complete heart block are described of hearts in which other minor congenital malformations were not in themselves severe enough to disrupt the atrioventricular conduction system. The cases fitted well into the categorization of complete heart block suggested by Lev. Two exhibited lack of communication between the atrial and conducting tissues, the other had discontinuity of the penetrating atrioventricular bundle. In an attempt to explain why this discontinuity between different segments of the conducting tissues occurs, we re-examined several series of graded human embryos. This investigation suggested that the anulus fibrosus in the normal heart is derived from sulcus tissue of the atrioventricular junction, the endocardial atrioventricular cushions playing a minor role in the separation of atria from ventricles. The relationships between the sulcus tissues and the different components of the atrioventricular junctional area are discussed in terms of an explanation both for the existence of different types of congenitally complete heart block and for persistence of Mahaim (nodo-ventricular and nodo-fascicular) fibers.


Mild and severe Hunter syndrome (MPS II) within the same sibships.

X-linked Hunter syndrome (MPS II) is presently thought to exist in two clinically and genetically distinct forms, mild and severe, which are biochemically indistinguishable. However, two sibships have been studied in which both mildy and severely affected children are present. Therefore, genetic counseling for families with MPS II should be reconsidered to take into account the possibility of heterogeneity within a family in terms of the degree of psychomotor retardation and potential longevity.


Post-transplant monitoring of renal allograft recipients for T, B and null lymphocyte subpopulations.

Time-course studies in ten allograft recipients showed a significant reduction in the percentage of T cells in the immediate post-transplantation period. This was accompanied by an increase in the percentage of both B and 'null' cells. T, B and 'null' cell percentages reverted to normal by the 6th month after transplantation at a time when patients had achieved stable renal function and were receiving only maintenance immunosuppressive therapy. Similar trends were observed with regard to absolute number of T, B and null cells. Both pre- and post-transplant plasma samples failed to inhibit T-rosette formation. Transient B rosette inhibitory activity was, however, observed in the plasma samples of two patients but did not appear to correlate with the mixed leucocyte culture blocking factor activity (MLC-BFA) of these plasma samples. In the group of patients studied there was no apparent association between percent or absoulte T, B and 'null' cell determinations and the onset of rejection crises.


Early and late complications following surgical correction of renovascular hypertension.

In surgery for renovascular hypertension one should try to avoid prothetic material. In general, it seems preferable to use methods without transplanted tissue at all, for instance the direct desobliteration in atherosclerosis or resection and end-to-end anastomosis in fibromuscular disease. General complications should be avoided in a carefully postoperative observation of the patients with exact equilibration of blood vulume and electrolytes.


Clinical significance of skin lesions in the diagnosis of gastrointestinal malignancies.

Distinctive syndromes correlating skin manifestations and gastrointestinal malignancies are described. The skin lesions may precede, accompany, or follow the primary disease in the gastrointestinal tract and can be important diagnostic clues. They should alert the physician to the possibility that his patient may have an associated internal cancer.


Acne vulgaris: treatment with topical benzoyl peroxide acetone gel.

The topical effect on acne of a benzoyl peroxide acetone gel was studied over an eight week period and simultaneously compared with the effect of a benzoyl peroxide lotion and a vitamin A acid cream. The three formulations produced a significant reduction in the number of comedones. The two benzoyl peroxide formulations substantially reduced the number of papules, but this effect was not observed to a significant degree with the vitamin A acid. Burning sensation following application, a common problem with the benzoyl peroxide alcohol gels, was not reported by patients using the benzoyl peroxide acetone gel.


Incidence and significance of the low-voltage electrocardiogram in acute myocardial infarction.

In a retrospective study of 304 patients with acute transmural myocardial infarction admitted to the coronary care unit, 22 percent (67 patients) exhibited low voltage on their electrocardiograms within 72 hours of admission. The course of hospitalization of these patients was compared with an equal number of consecutive patients with transmural infarctions and normal electrocardiographic voltages. Among the patients with low voltage, there was a significantly higher incidence of previous infarction or present extensive infarction, congestive heart failure, and cardiogenic shock. This group of patients also demonstrated a markedly higher mortality. This study substantiates the clinical impression that acute myocardial infarction complicated by a low-voltage ECG implies a poor prognosis. It is speculated that this electrocardiographic pattern may reflect decreased ventricular performance as a result of widespread myocardial damage.