What does Halobacterium tell us about photoreception? A photosensory mechanism is proposed for Halobacterium halobium based on the observation of light-induced motor responses. Possible mechanisms of signal transduction in Halobacterium are discussed. Bacteriorhodopsin and the visual pigment rhodopsin are compared with respect to their structural and functional properties. The conclusion is drawn that Halobacterium may help to understand primary photochemical events of rhodopsin rather than the transduction mechanism of visual photoreceptors.


Mechanism of disintegration of biological cells in ultrasonic cavitation. On the basis of elastic waves released by imploding cavitation bubbles, a mechanism for biological cell disintegration in high intensity ultrasound has been proposed. Comparison of this mechanism with the published results on yeast cells shows many points of agreement suggesting that yeast cell disintegration in ultrasonic cavitation occurs by shear stresses developed by viscous dissipative eddies arising from shock waves.


Ferrous iron oxidation and uranium extraction by Thiobacillus ferrooxidans. The microbiological oxidation of ferrous iron in batch and continuous systems has been investigated in relation to uranium extraction from a low-grade ore by Thiobacillus ferrooxidans. The influence of the parameters, agitation, and aeration on oxygen saturation concentration, rate of oxygen mass transfer, and rate of ferrous iron oxidation was demonstrated. The kinetic values, Vmax and K were determined using an adapted Monod equation for different dilution rates and initial concentrations of ferrous iron. The power requirements for initial leaching conditions were also calculated. Uranium extraction as high as 68% has been realized during nine days of treatment. Regrinding the leach residue and its subsequent leaching yielded 87% uranium solubilization.


[Effect of antidromic impulses on the afferent flow in A-delta fibers of a cutaneous nerve]. Analysis of the afferent activity in the myelinated Adetla-fibers was carried out using the modified colliding impulses method. Frequency characteristics of the orthodromic impulses pattern without any preliminary electrical stimulation of Adelta-fibers and after its application to the nerve were compared. It was found that the antidromic impulses appearing under the electrical stimulation of the nerve caused an increase in the frequency of impulses in the afferent pattern in adequate stimulation of the cutaneous receptors.


[Intravascular pressure and spontaneous lymph node contractions]. Interrelations between the spontaneous contractile activity and the level of intravascular pressure were studied on the isolated sections of lymphatic vessels. Spontaneous contraction proved to appear when the intravascular pressure was 1.5 cm H2O and decreased when it reached 10 cm H2O. The latent period of the origination of spontaneous contractile activity in rapid rise of pressure was shorter than such in its gradual rise. The amplitude and frequency of spontaneous contractions changed not only depending on the intravascular pressure value, but also on the rate of their change.


[Role of the kallikrein-kinin system of the kidneys in sodium and water transport and changes in it under the influence of indomethacin]. A direct relationship between the level of the kallikrein activity in the urine, and diuresis, natriuresis and the capacity of the kidneys to concentrate the urine in healthy rats was revealed. Low doses of indometacin (2 mg/kg, for 5 days) increased the kallikrein activity in the urine four-fold, with a simultaneous rise of diuresis; high doses (5 mg/kg, for 5 days) cut the kallikrein activity in the urine by half and decreased natriuresis three-fold. At the same time there was also a decreased capacity to concentrate the urine. Thus, indometacin changed not only the prostaglandine synthesis, but also that of kallikrein, this influencing the functional state of the kidney.


[Distribution of labeled cortisol in the tissues and media of the eye]. Incorporation of cortizol-3H and its uptake by the tissues and media of the eye was studied to expose the target tissue for the given hormone. Cortizol distribution was investigated in the sclera, ciliary body, cornea, iris, the lens capsule, aqeous humour, and the vitreous body. It was shown that the eye tissues and media had different intensity of cortizol incorporation, as well as different character of its elimination. The sclera, cornea, ciliary body and the lens capsule proved to be the target tissues for cortizol.


[Plasma renin and erythropoietic activity following a decrease in extracellular volume]. A reduction of the extracellular volume of the peritoneal dialysis in rats induced modifications in plasma renin activity, plasma erythropoietic activity, and in renin activity in the renal cortex. A significant increase in the renin and erythropoietic activity was revealed in the experimental animals. It is assumed that renin and erythropoietin could be regarded as two links of the same broad control system, responsible for optimum tissue oxygen supply.


[Lipid peroxidation and degeneration of the retinal photoreceptors in rats with avitaminosis E]. Alimentary E-avitaminosis in rats was accompanied (in vivo) by a sharply intensified formation of the lipid peroxidation products (hydroperoxides, dialkylperosides, "intermolecular links") in the retina and by degeneration of photoreceptors (chiefly of the external rod segment layer). Discussion of the experimental data obtained is based upon the views on the antioxidant alpha-tocopherol action mechanism in vivo.


[Effect of chronic administration of carbon tetrachloride on turnover of individual RNA fractions in rat liver tissue]. During the carbon tetrachloride treatment of rats (for 24 weeks) the 5-H3-uridine content and incorporation into different rat liver RNA fractions after a short-term exposure of labeled precursor were studied. These fractions were obtained by preparative 2.5% polyacrylamide gel electrophoresis from the nuclear and cytoplasmic RNA extracted by thermal phenol fractionation. CCl4 administration resulted in a decrease in the level of transfer and ribosomal RNAs in the rat liver. Chronic CCl4 treatment led to disturbances of the turnover simultaneousness of different components of rapidly labled RNA.


[Effect of UV-irradiation on human serum under normal and pathologic conditions]. The influence of the wide UV-spectrum on the level of dien conjugations in the blood serum of donors and patients with various pathological processes was studied. The level of dien conjugations increased statistically significantly in the lipid sera of donors after UV-irradiation; but it proved to decrease in the patients with inflammatory diseases. As to the patients with benign and malignant tumours, UV-irradiation showed practically no influence on the dien conjugation level in the blood serum lipids. This method can be used to elaborate the differential-diagnostic criteria of diseases of tumour and inflammatory nature.


[Mechanism of the effect of aspirin on the functional properties of thrombocytes]. As shown the inhibitory effect of aspirin administered in vivo on platelet aggregation and factor 3 release in vitro was due to the action of aspirin on the blood platelets and plasma cofactors: plasma from aspirinized rats dimished aggregability of platelets from untreated animals; plasma from untreated rats increased the aggregability and factor 3 availability of platelets from aspirinized animals.


[Adrenergic and cholinergic structures of guinea pig lungs under normal conditions and in experimental bronchial asthma]. Fluorescent and histochemical methods were applied to the study of the morpho-functional condition of the adrenergic and cholinergic nervous system of the bronchopumonary apparatus in guinea pigs under normal conditions and during sensitization (subcutaneous and inhalant) with tick Dermatophagoides pteronyssinus ticks. There was revealed a marked excitation of the adrenergic nervous system, and a reduction of the acetylcholine esterase activity in the bronchopulmonary tissue during the animal sensitization.


[Sensitivity of the lymphocyte RNA-synthesizing system of patients with different malignant neoplasms to phytohemagglutinin and dexamethasone]. RNA biosynthesis catalyzed with DNA-dependent RNA polymerase was demonstrated in the reconstructed system containing isolated lymphocyte nuclei, Mg2+ or Mn2+ salts, ammonium sulphate, in the presence of four nucleosidetriphosphates. Both the Mg2+ and Mn2+-dependent forms of this enzyme were revealed in the nuclei of normal lymphocytes and those of patients suffering from melanoma, carcinoma of the lung and sarcoma. The activities of both forms of RNA-polymerase were greater in the nuclei of the lymphocytes from sick individuals than in the normal analogues. DNA-dependent RNA-polymerase sensitivity to dexamethasone and PHA of the nuclei of lymphocytes obtained from patients with carcinoma of the lung, melanoma, and sarcoma was decreased in comparison with the normal.


[Hormontal treatment of pre-tumorous diseases of the testis in rats]. Tumours and proliferates of the testes from spermatogenic epithelium were treated with estrogens, and those from the interstitial cells-with androgens and 17-hydrosyprogesterone caproate. Depression of the folliculo-stimulating function of the pituitary body with a simultaneous stimulation of the luteinizing hormones (LH) production under the effect of estrogen led to cessation of teratoma and seminoma growth, and to the resolution of the proliferates. When androgens or 17-hydroxyprogesterone caproate were used, depression of the LH led to cessation of the tumour growth, and to the resolution of proliferion of proliferates from the interstitial cells.


[Hematopoiesis in an organ culture of embryonal human liver]. It was shown by the method of multiple organ cultures on millipore filters that hemopoiesis preferably of erythroid type remained for more than one and a half months in the human embryo liver culture. General morphology of 7--50-day cultures was studied and described. Myeloid population of the cells (CFU conut) was exhausted practically by the 14--16th days of cultivation.


[Study of a trophoblast cell culture in vitro]. The authors obtained trophoblast culture from an early chorion of human embryo. Trophoblastic cells of the main 4 types described were: giant cells, with processes, fibro-blast-like, and round. All the cells were rich in RNA, glycoproteins, had a set of enzymes of the Krebs pentose cycle, but low activity of succinic dehydrogenase. A marked cytooxic effect of lymphocytes from healthy pregnant woman on the allogenous cells of the trophoblast culature and the absence of any interaction between the neoatal lymphocytes with the latter was revealed.


[Influence of cultivation temperature on blast-transformation of lymphocytes from humans of different ages]. Studies on the effect of temperature in tissue culture upon the phytohemagglutinin blast-transformation of lymphocytes obtained from persons aged 20 to 35 and 90 to 102 years were carried out. The tissue culture temperature of 39 degrees C increased the blast-transformation index as compared with control (37 degrees C), whereas the temperature of 41 degrees C sharply decreased it. The effect of temperature upon the blast-transformation process in tissue culture had some peculiarities depending on donor's age.


[Circadian rhythm of the number of DNA-syns and following adrenalectomy]. The diurnal changes of mitosis and DNA-synthesizing cells count in the tongue epithelium of intact and adrenalectomized mice were studied. A partial desynchronization of mitotic division, as well as diminution of mitotic index variation amplitude and prolongation of high mitotic activity were observed in the operated animals in the course of 24 hours. The average 24-hour mitotic index in the basal layer of the tongue epithelium was the same in the intact and the operated animals. The rhythm of the DNA synthesis failed to differe from control. Thus, adrenalectomy in mice led to distrubances of the diurnal mitotic rhythm in the tongue epithelium, but had no effect on the rhythm of the DNA synthesis and the level of the proliferative activity.


[Morhologic study of the hearts of rats exposed aboard biosatellites]. The hearts of rats exposed for 22.5 and 19.5 days aboard the biosatellites Cosmos-605 and Cosmos-782 were examined histologically and histochemically. Prolonged space flight induced no essential structural or metabolic changes in the myocardium of rats. The absolute weight of the heart remained unchanged. A short-term increase in the phosphorylase activity of the myocardium recorded 10 to 11 hours after the flight can be attributed to the complex of stress effects accompanying the recovery of the biosatellites.


[Electron microscopic study of the myocardium of mice with experimental infection caused by Coxsackie virus A13]. Diffuse myocarditis with alteation and proliferation was described in adult BALB/c mice infected with Coxsacke A13 virus. A marked tendency to sclerotic processes 30 to 60 days after the infection was noted; this can underly the reduction of the functional activity of the myocardium and lead to the development of cardiomyopathy.


[Electron microscopic study of the seminiferous tubules of white rats exposed to boric acid]. Boric acid in a dose of 1 g/kg was given orally to albino rats for a period of 2 weeks, daily. Changes in the nucleus and the cytoplasm of both the spermatozoids and spermatides were revealed at the early stages of their formation. The appearance of numerous multinuclear cells with an even and odd number of nuclei (from 2 to 10 and over) was noted. The formation of multinuclear cells can be apparently attributed to the action of boric acid on the prolonged processes of meiotic division of the spermatogenic epithelium cells (spermatocytes, spermatides).


Cranio-tubular dysplasia.

Cranio-tubular dysplasia. A general description of the different syndromes of cranio-tubular dysplasia is given and 3 cases are described. Surgery can be difficult because of the marble hard bone. The possibility of complications such as recurrence, profuse bleeding and medullary compression with fatal results is stressed. The results of treatment remain poor.


Cardiovascular effects of delta9-tetrahydrocannabinol in conscious and anaesthetized dogs. 1. Temporal effects of delta9-tetrahydrocannabinol (THC) on heart rate and blood pressure in conscious dogs were compared to those in anaesthetized dogs. 2. In conscious dogs, THC in doses of 0.25 and 0.1 mg/kg resulted in maximal heart rate reductions of 48 and 41%, respectively, and in no significant change in blood pressure. 3. In anaesthetized animals THC in doses of 0.5 and 0.25 mg/kg caused a peak reduction in heart rate of 38 and 34%, and of blood pressure of 24 and 8%, respectively. 4. The results demonstrate that the bradycardia in response to THC in dogs is independent of the concomitant anaesthesia. 5. We conclude that the discrepancy between heart rate response to THC in dogs and in man is due to a species difference.


Time course of lithium-induced alterations in renal and endocrine function in normal and Brattleboro rats with hypothalamic diabetes insipidus. 1. A lithium chloride (1.1 g/kg) supplemented diet was given to Long Evans (LE) and Brattleboro (DI) rats to investigate its actions in the presence (LE) and absence (DI) of vasopressin. 2. During the first 24 h, Li-supplemented LE rats displayed an initial water deficit (drinking less than renal output), increased plasma antidiuretic (ADH) titres and slightly increased plasma renin activities (PRA) and plasma osmolarities. Such changes were qualitatively similar to those seen in rats fed a normal diet, but deprived of water for 24 hours. After 12 days, the Li-supplemented rats had elevated plasma ADH titres, but reduced pituitary oxytocic and antidiuretic activities. 3. The urinary losses of Na, K and Cl exceeded dietary intakes in LE rats on the introduction of the Li-supplement, and the urinary osmolarity fell by 50%. Electrolyte balances were gradually re-established, although drinking and urine production increased in parallel to reach twice the control values by day 12 of the supplement. 4. Aldosterone and corticosterone secretory rates and their peripheral plasma concentrations were unchanged both after 24 h and 28 days of the Li-supplement. 5. Li elicited no water deficit or saluresis in DI rats, and although the polyuria and polydipsia were exacerbated, urinary osmolarity did not change over the 12 day observation period. 6. Li increased Ca excretion in both rat types; after 12 days the PRA of DI but not LE animals were increased. 7. It is concluded that the overall renal actions of Li are tempered by vasopressin rather than adrenocorticosteroids.


Aspirin at therapeutic concentrations does not affect 5-hydroxytryptamine uptake by platelets. Aspirin at therapeutic concentrations does not inhibit the uptake of 5-hydroxytryptamine (5-HT) by blood platelets nor induce release of 5-HT from platelets, although platelet aggregation responses to collagen and arachidonic acid (which are dependent on platelet prostaglandin synthesis) are abolished. This does not support an earlier claim that aspirin's effects on platelet function include inhibition of 5-HT transport.


Community psychiatry in a London borough. An eleven-year analysis of a socio-medical service for psychiatric illness. A study, covering the years 1964-67, of an integrated psychiatric service for a population of 92,000 was described in this Journal in 1969. This paper describes the continuation of this study to cover the further period 1967-75 and comments on data relating to the whole 11-year period. In this comment, the needs of this psychiatric service have been compared with data from other workers and with current Guidelines from the Department of Health and Social Security.


Psychiatric Decision Making.

Psychiatric Decision Making. Questionnaire replies from 43 experienced psychiatrists showed wide variation in the ways they would manage a common type of neurotic problem. There were considerable differences in the nature and duration of treatment and in the use of other members of the psychiatric team. The conclusions have implications for training and for the use of health care resources.


The course and outcome in depressive illness. A follow-up study of 122 cases in Madurai, India. One hundred and nine out of one hundred and twenty-two cases of endogenous depression were followed-up after their index diagnosis 3-13 years earlier. No recurrence occurred in 28 cases. Forty-two cases turned out to be bipolar and 21 remained unipolar. Manic episodes outnumbered the depressive ones. The change of polarity from depression to mania occurred within three years after the initial depression, though in others the shift occurred between three years and twelve years. The number of episodes of depression before the onset of mania varied from 1 to 3. While the onset of depression before the age of 40 years predisposed to recurrences, there was risk of chronicity in those patients who developed the illness after 40.


The use of Prostaglandin F2 Alpha in selective visceral angiography. Prostaglandin F2 Alpha has been used in 33 superior mesenteric and ten splenic  angiographic studies. In each instance, improved anatomic detail was obtained after injection of the Prostaglandin. Unlike other vasodilating drugs, the use of Prostaglandin F2 Alpha improved the arterial as well as the venous phase of each study. No systemic haemodynamic changes or significant side effects were observed after injecting the drug, and it appears that Prostaglandin F2 Alpha is an ideal choice as a pharmacologic aid in angiography.


Xeroradiography of the hand in patients with renal osteodystrophy. The hands of 40 patients with chronic renal failure and varying degrees of renal osteodystrophy were studied. The xerograph and radiograph of each patient were compared, assessing the degree of subperiosteal erosion, and of vascular, capsular and ectopic calcification. While the changes of osteodystrophy were clearly demonstrated on the xeroradiographs, they were also seen on the radiographs, even when only minor changes were present. The authors prefer the xeroradiograph for the measurement of the metacarpal cortical thickness, because of the sharp medial border of the cortex afforded by the "edge enhancement" of this technique.


Eye dose measurements using conventional and rare-earth screens during tomography of the para-nasal sinuses. Eye dose measurements have been performed when using medium speed conventional and rare-earth screen-film combinations during tomography of the para-nasal sinuses. The measurements show that using conventional intensifying screens with the A.P. view a total eye dose of about 20 rad may be given during an examination. This eye dose can be reduced by 98% using the P.A. position. If rare-earth screen/film combinations are employed the eye dose measured in the A.P. view was reduced by 75% of that obtained with conventional screens without detectable loss of image quality. A total eye dose reduction of about 99.5% was measured in the P.A. view with the rare-earth systems.


Bladder trauma in the long-distance runner: "10,000 metres haematuria". Profuse, short-lived haematuria occurring as an occasional event in a number of long-distance runners has been found to originate from lesions in the bladder. These lesions are either ecchymosis or frank contusions which have a typical distribution. They are sited on the inter-ureteric bar, the posterior half of the rim of the internal meatus and on the posterior bladder wall in which position there is "mirroring" of the trigonal lesions. The possible mode of injury is discussed.


Cinoxacin concentrations in plasma, urine and prostatic tissue after oral administration to man. Cinoxacin, a synthetic antibacterial compound, was given orally in a dose of 500 mg to 8 patients undergoing transurethral prostatectomy. The drug was well absorbed and the peak plasma level (mean 13.9 mcg/ml) occurred 1 or 2 hours after administration. Concentrations of cinoxacin in the urine reached a peak (mean 236.5 mcg/ml) 4 to 6 hours after dosing, and remained higher than the mean MIC for most common urinary pathogens for 12 hours after administration. The concentration of cinoxacin in prostatic tissue 2.5-4 hours after administration varied between 0.6 and 6.3 mcg/g. The individual variations were unrelated to the concurrent plasma level and appeared to be influenced more by inter-subject variation than by the physicochemical properties of the drug. In 1 patient the cinoxacin level was estimated in renal tissue (70.1 mcg/g), in muscle (12.6 mcg/g), and in perirenal fat (4.7 mcg/g).


A small cluster of Hodgkin's disease.

A small cluster of Hodgkin's disease. Nine cases of Hodgkin's disease and one of acute lymphoblastic leukaemia occurred in 1972-5 in an area of less than 1 km. Clinical, social, and drug histories provided no relevant information, and definite patient-to-patient contacts before the onset of disease were not established. There was a higher incidence of malignant neoplasms in first-degree relatives of the patients than in those of a small control group living in the same area. There was no apparent reason for this cluster of cases, but geographical, climatic, and entomological studies are being carried out.


Congenital heart disease and prenatal exposure to exogenous sex hormones. One-hundred and four infants with congenital heart disease were identified from their birth certificates and matched with normal controls. Their gestational histories were examined to see whether they had been exposed to exogenous sex hormones. Exposure was 8-5 times more common among the infants with malformations than among controls. A history of hormone exposure was more common among those patients with multiple malformations, and the exposed infants were also more likely to have died (and to have died earlier) than those who had not been exposed, which suggests that hormone exposure causes severe types of malformations. The commonest type of exposure was to hormone pregnancy tests, which was needless exposure. Only two of the mothers of malformed infants had inadvertently used oral contraceptives in the first trimester.


Chlamydial infection of the urogenital tract in promiscuous and non-promiscuous women. Chlamydia trachomatis infection of the urogenital tract of women presumed to be non-promiscuous, and in presumably promiscuous women attending a Special Clinic in Manchester was studied. Two hundred female members of hospital staff, who formed the non-promiscuous group, were found to have a 1% incidence of chlamydial infection. This compared with an incidence of 26% among 200 women attending the clinic. Among the clinic patients, chlamydial infection was significantly linked with the presence of gonorrhoea, mixed infections, and other sexually transmissible diseases--such as, trichomoniasis. No correlation could be made be made between the incidence of chlamydial infection and the use of oral contraceptives.


Characterization of an activating factor required for hydrolysis of Gm2 ganglioside catalyzed by hexosaminidase A. Separation of the hexosaminidase A (EC 3.2.1.52) and B isozymes of human liver by ion-exchange chromatography results in recovery of greater than 80% of the activity in crude extracts when synthetic substrates are used to monitor enzyme activity. Only 15% of hexosaminidase activity toward the N-acetylgalactosaminyl (N-acetylneuraminyl) galactosyl glucosylceramide (Gm2 ganglioside) substrate is recovered and all of this activity is associated with the hexosaminidase A Fraction. The low level of Gm2 ganglioside hydrolase activity in the hexosaminidase A fraction could be enhanced by coincubation with column fractions which contain hexosaminidase B. The activating factor, which has been partially purified by gel filtration, is a heat-stable protein with a molecular weight of 36 000 and is without enzyme activity toward hexosaminidase substrates. Highly purified hexosaminidase A or crude hexosaminidase A recovered after gel filtration on Sephadex G-100 has no Gm2 ganglioside hydrolase activity. The Gm2 ganglioside hydrolase activity of these hexosaminidase. A preparations can be completely restored by addition of activating factor. The activating factor does not affect the rate of hydrolysis of synthetic substrate or asialo Gm2 ganglioside catalyzed by hexosaminidase A.


The thermal denaturation of bovine cardiac G-actin. The thermal denaturation of bovine cardiac G-actin has been studied by ultraviolet difference spectroscopy and circular dichroism between pH 7.5 and 10.5. As with proteins previously studied, thermal unfolding is incomplete compared with unfolding by urea or GuHCl. However, the same conformational change is observed over the pH range studied, and the available evidence indicates it is a two-state transition. Thermodynamic analysis of the data shows that deltaHo and deltaSo are strongly dependent on the temperature, that deltaCp is 1300 cal deg-1 mol-1, and that G-actin has a temperature of maximum stability near -5 degrees C.


Glutathione-insulin transhydrogenase activity in pregnant mouse mammary gland: hormonal influences studied in tissue culture. Glutathione-insulin trandhydrogenase (GIT) activity has been shown to be stimulated in culture of explants of pregnant mouse mammary gland by a mixture of insulin, cortisol, and prolactin. Since this hormone mixture stimulates lactogenesis in vitro it is possible that the increase in GIT activity is functionally related to one of the processes of milk secretion or ejection. Oxytocin is degraded by GIT and the interaction of this hormone with its mammary gland receptors may be influenced by the change in enzyme activity. The increase in GIT activity caused by insulin, cortisol, and prolactin in vitro can be prevented by the addition of progesterone or oxytocin to the culture medium.


Duplex formation of complementary oligoribonucleotides corresponding to the dihydrouridine loop neck region of several transfer ribonucleic acids. Formation of short, double-stranded RNA helices by the complementary oligoribonucleotides GpApGpC, GpCpUpC, and ApGpCpUpC was established by the temperature-dependent changes in uv hypochromicity and circular dichroism spectra. These studies provide additional thermodynamic data on duplex formation. Duplexes (formula: see text) are especially significant as they: (1) correspond to a natural sequence, the dihydrouridine loop neck region, common to several tRNA molecules; (2) correspond to a proposed, partial recognition site for yeast phenylalanyl-tRNA ligase (EC 6.1.1.20); and (3) represent the first demonstration of a duplex with four base pairs, one of which is an A--U pair. These duplexes should serve as models for studies on tRNA-ligase interaction.


Relationship of potassium ion transport and ATP synthesis in pea cotyledon mitochondria. Simultaneous monitoring of ATP synthesis and K+ movements across pea mitochondrial membranes revealed information about the competition of the two processes for mitochondrial energy. In the presence of valinomycin and at low extramitochondrial K+ concentration, ADP could be phosphorylated rapidly. This occurred with a decrease in net potassium ion uptake. At higher external K+ concentrations respiratory energy was unavailable for ATP synthesis and only a portion of added ADP could be phosphorylated within a reasonable time. Magnesium ions were shown to have an inhibitor effect on the K+ uptake, and stimulated a greater rate of ATP synthesis. When valinomycin and ADP were added simultaneously so that phosphorylation of the ADP and enhancement of K+ uptake could complete for mitochondrial energy, K+ uptake was preferred over ATP synthesis.


Stoichiometry and accessibility of histone 3 sulfhydryl groups in chromatin subunits. The accessibility of the sulfhydrl groups of histone 3(H3) in chromatin subunit particles has been investigated by reaction with p-hydroxymercuribenzoate. The resuls indicate that the carboxy-terminal regions of H3 are buried in the native particle, and suggest the presence of 2 mol of H3 per chromatin monomer.


In vivo incorporation of isotopically labelled amino acids into vertebrate proteins: L-[Me-3H]methionine incorporation into chicken egg white lysozyme. The in vivo incorporation of L-[Me-3H]methionine into egg white lysozyme of the laying hen has been examined. Using a versatile synthetic chicken diet which consisted of 75% free amino-acid ration and 25% normal laying ration, 5-8% incorporation of the [3H]methionine into lysozyme was demonstrated. The utility of this vertebrate in vivo incorporation technique is discussed in terms of its application to the incorporation of 13C-enriched amino acids into vertebrate proteins as a prelude to macromolecular 13C nuclear magnetic resonance studies.


Significance of unilateral diminished activity in renal scanning. Renal scanning is an important diagnostic aid in assessing kidney function; the authors have attempted to correlate the results of renal scanning with the findings from intravenous pyelography and the final diagnosis. In non-mass lesions of the kidney the renal scan correlated well with the intravenous pyelogram and the final diagnosis. In mass lesions, a diminished uptake of isotope corresponding to the site of the lesion seen on the intravenous pyelogram was suggestive of a cyst; diminished uptake of isotope in the whole kidney including the mass lesion on the renal scan was suggestive of renal carcinoma. Review of the literature showed only one previous reference to such an observation.


Facial fractures and snowmobile accidents. Snowmobile accidents are now common in winter; there is a local pattern of facial fractures associated with accidents involving these machines. Facial fractures connected with snowmobile accidents over a period of two successive winters were reviewed; 14 were found to be of special interest because of their severity and localized extent. Compared with motor vehicle accidents most of these fractures were isolated; the patients often had suffered only minimal trauma elsewhere. After reviewing the histories of these patients it was clear that alcohol, night driving, inadequate facial protection and the use of unknown terrain were common precipitating factors. Elimination of these hazards and the use of appropriate protective head-gear would probably reduced the number and severity of such injuries.


An approach to solving problems of growth retardation in the child and teenager. The physician who looks after children and teenagers is often confronted with the problem of short stature or growth failure. Common causes of growth failure include genetic background, intrauterine disease, malnutrition, chronic illness and hormonal disorders; some cases are attributed to mental retardation or primary central nervous system disease. A major concern in the evaluation of these patients is when, and how extensively, to investigate the problem.  From a practical standpoint assessment can be related to height percentiles. The aims of treatment are a) to identify and treat appropriately the patients in whom there is an organic cause and b) to provide psychologic counselling and support.


A simplified antepartum high-risk pregnancy scoring form: statistical analysis of 5459 cases. An antenatal high-risk assessment form has facilitated the identification of the fetus at risk, Although such a form in general has potential limitations its simplicity and demonstrated ability to assist in high-risk selection makes it worth including in an antenatal high-risk program.


Dose response evaluation of adriamycin in human neoplasia. Because patients treated with 60-90 mg/m2 every three to four weeks reach cardiotoxic doses of 550 mg/m2 within 36 weeks, prolonged treatment with Adriamycin is limited. The purpose of this study was to determine whether lower doses could be given over longer periods without loss of efficacy. Good risk patients treated with 75, 60, or 45 mg/m2 had remission rates of 25, 27, and 19%; poor risk patients treated with 50 and 25 mg/m2 had remission rates of 16 and 12% respectively. Although a dose response was identified, there were no statistically significant differences in remission rates, durations of remission, or toxicities in the dose schedules studied. Irreversible congestive heart failure occurred in five patients with cumulative doses of 240-390 mg/m2. Unless rapid remission induction is urgent, we recommend 60 mg/m2 X four doses and measurement of myocardial function if treatment is to continue.


Combination chemotherapy of metastatic malignant schwannoma with vincristine, adriamycin, cyclophosphamide, and imidazole carboxamide: a case report. This report describes a patient with a 15-year history of schwannoma (peripheral nerve sheath sarcoma) who developed extensive pulmonary metastases associated with hypoxemia. Treatment with chemotherapy consisting of cyclophosphamide, vincristine, Adriamycin, and imidazole carboxamide resulted in a complete remission lasting 17+ months. Malignant schwannoma should probably be regarded as a drug sensitive neoplasm.


Adriamycin therapy in advanced mycosis fungoides. Thirteen patients with advanced mycosis fungoides received induction therapy with Adriamycin, 60/m2 I.V. repeated at 21-day intervals. Ten patients had extensive skin tumors; all patients had lymph node enlargement with mycosis fungoides involvement in eight; four patients had biopsy-proven visceral involvement. Only two patients had received no prior therapy. The overall response rate with Adriamycin therapy was 85% with three patients (23%) achieving a biopsy-proven complete remission and five patients (39%) partial remissions. The median number of courses to maximum response was two (range two to four). The principle toxicity was myelosuppression, but this was not severe and the entire group received more than 90% of the intended doses of Adriamycin. One patient developed probable Adriamycin cariotoxicity. Maintenance therapy for patients achieving a remission was methotrexate 15 mg/m2 I.M. twice weekly and cyclophosphamide 750 mg/m2 I.V. every 21 days. The median duration of complete remission was 32+ weeks (range 16+-40+ weeks) while the median duration of partial remission was 18 weeks (range 8-111+ weeks). Adriamycin has proven to be an effective induction agent in the treatment of advanced mycosis fungoides and its incorporation into combination chemotherapy regimens is warranted.


Hormonal sensitivity of human breast tumors in vitro: pentose-shunt activity. Recent studies indicated that response to endocrine therapy might be predicted in human breast carcinomas using the sensitivity of the pentose-shunt pathway to hormones in organ culture. Thirty breast tumors were examined using this histochemical method, and three independent assessments were made. There was poor agreement between the observers, and we consider that this test is not reproducible in its present form.


Detection of metastatic malignant melanoma by chest roentgenography. The latest premortem chest roentgenogram on 17 patients with known metastatic malignant melanoma was examined and the results were compared with the findings in the chest at autopsy. In nine of the 17, disease not visible on the roentgenogram was found at autopsy. Preliminary data would indicate that a significant number of these metastases could have been identified premortem by other radiographic modalities, e.g., tomography.


Seminoma in Klinefelter's syndrome with 47, XXY, 15s+ karyotype. A 32-year-old man was found to have seminoma of the right testis which had been subjected to orchiopexy for cryptorchism 14 years earlier. The left testis was small and firm, and the patient was further studied for hypogonadism. Chromosome analysis revealed a karyotype of 47, XXY, 15s+ with an extra X chromosome and enlarged and fluorescent satellites on chromosome 15. The satellites were also found in the mother as well as in two sisters and one brother out of his four siblings. Endocrine studies, histological pictures of the biopsied left testis and dermatoglyphic analysis were compatible with Klinefelter's syndrome. To our knowledge this is the first reported case of seminoma associated with the syndrome. Several implications are discussed for the rare occurrence of a germinal cell tumor in Klinefelter's syndrome.


Plasma immunoglobulin levels in patients with breast cancer. The plasma levels of the immunoglobulins IgA, IgG and IgM have been measured in 55 patients with benign breast disease, 28, 68 and 22 patients with early breast cancer one day before, 10-14 days after and three-six months after mastectomy, respectively, and 35 normal healthy control women. The mean levels of IgA, IgG and IgM were similar for all groups examined except for IgG levels in breast cancer patients 10-14 days after mastectomy. In this latter case there was a significant decrease in IgG level shortly after mastectomy but at three-six months after surgery the amounts of plasma IgG were within the normal range. There was no correlation between the amounts of immunoglobulin measured at 10-14 days after surgery, and time to recurrence of the disease.


Plasma prostaglandins across the tumor bed of patients with gynecologic malignancy. Prostaglandin E produced by tumors has recently been implicated as a mechanism by which tumors may subvert the immune system and grow despite their antigenicity. Arterial and venous determinations of prostaglandin E were performed in eleven patients with gynecologic malignancy. No significant difference was found when arterial and venous levels were compared and there was no difference in venous PGE levels when subjects with cancer were compared to patients with benign gynecologic disease.


The prediction of tumor regression in human squamous carcinoma by means of the potential tumor doubling time. Thirty-three patients with locally advanced epidermoid cancer of the mouth were investigated by means of the potential tumor doubling time prior to each of four weekly infusions of methotrexate. The agent used to induce metaphase arrest was vincristine sulphate 2 mg intravenous push and the methotrexate was given in a dose of 100 mg/M2 body surface. In twenty-one patients the investigation was completed. It was found that in those patients where the P.T.D.T. was maintained at its original level there was a greater than 50% reduction in the size of the lesion, whereas when the P.T.D.T. became greatly prolonged there was no such reduction. It is suggested that the P.T.D.T. provides a simple same day method of evaluating one parameter in the cell kinetics of accessible tumors and that this information can be used to individualize chemotherapy schedules.


Carcinoma of the breast: the prognostic significance of extranodal extension of axillary disease. A retrospective study to determine the effect of extranodal axillary disease on prognosis in invasive carcinoma of the breast was undertaken in a series of 152 cases. It was found that extranodal disease has an unfavorable effect on prognosis in those patients with three or less involved axillary nodes and no effect on prognosis in those patients with four or more involved axillary nodes. Extranodal axillary disease was found to have no influence on the interval between surgery and initial recurrence nor on the anatomic distribution of the recurrence, local or remote.


A new deoxyuridine-5'-triphosphatase in Yoshida sarcoma cells involved in deoxyuridine 5'-triphosphate metabolism. A magnesium-independent deoxyuridine-5'-triphosphatase was found in Yoshida sarcoma cells but not in normal rat liver. The phosphatase is specific for deoxyuridine 5'-diphosphate and deoxyuridine triphosphate, and its Km for deoxyuridine triphosphate is 2.7 X 10(-7) M. The enzyme was not inhibited by fluoride and required no divalent cations. Thus it differs from known nucleotide phosphatases. Deoxyuridine monophosphokinase, which is detectable in a crude extract of normal rat liver, could not be detected in an extract of Yoshida sarcoma cells. However, with hydroxylapatite column chromatography of the extract, a deoxyuridine 5'-monophosphate kinase activity as high as that in normal rat liver was found in fractions separated from the phosphatase activity. Thus the absence of detectable deoxyuridine 5'-monophosphate kinase activity in the crude extract of Yoshida sarcoma cells is due to the presence of this nucleotide phosphatase.


Development and characterization of established cell lines from primary and metastatic regions of human endometrial adenocarcinoma. Cell lines designated SNG-P and SNG-M were established from operation specimens of primary and metastatic regions of human endometrial adenocarcinoma. The cell lines grew well without interruption for over 13 months and were subcultivated more than 65 times. They continue to exhibit stable growth. The cultured cells appeared epithelial in shape, showing a pavement arrangement and multilayering without contact inhibition. The cytology revealed anaplastic and pleomorphic features. Upon electron microscopic observation, most of the cultured cells were characterized by highly indented nuclei with multiple large nucleoli and by desmosomal cell contact. The chromosomal number varied widely and showed aneuploidy, but the modal chromosomal number was stable at the diploid range. No marker chromosome could be identified. Both of these cell lines, SNG-P and SNG-M, were transplanted to an immune-depressed hamster cheek pouch and produced a tumor resembling the original.


Effect of prolonged administration of gastrin on experimental carcinogenesis in rat stomach induced by N-methyl-N' -nitro-N-nitrosoguanidine. The effects of gastrin on gastric acid secretion and on the incidence of gastric carcinoma induced by N-methyl-N'-nitro-N-nitrosoquanidine were investigated in rats. At Week 50 after the start of the experiment, it was found that prolonged administration of gastrin after treatment with N-methyl-N'-nitro-N-nitrosoquanidine resulted in a significant increase in gastric acid secretion and a significant reduction in the incidence of adenocarcinomas of the glandular stomach. The administration of gastrin did not influence the histological appearance of the few gastric adenocarcinomas that did develop.


Prenatal multicarcinogenesis by ethylnitrosourea in mice. The Role of prenatal age, sex, and the maternal background upon the incidence, multiplicity, and spectrum of tumors induced by ethylnitrosourea has been studied in the offspring of reciprocal hybrids of the same genotype. The first generation (F1) offspring of C57BL/6J X C3HeB/FeJ and the reciprocal hybrids were observed throughout their life-span for tumor development following single i.p. injections of ethylnitrosourea (60 microng/g) given to pregnant mothers at 12, 14, 16, or 18 days of gestation. Animals exposed to ethylnitrosourea survived on the average for only 90 weeks. They developed by that age tumors in lungs, livers, ovaries, nervous system, and forestomach. Control mice killed at 90 weeks were essentially free of tumors. The fetal age at the time of administration of the carcinogen was one of the most significant modulators of tumor development in lung, liver, ovaries, and nervous system. The sex of the animals influenced the rate of development of liver tumors, whereas maternal background affected the multiplicity of lung tumors.


Effects of 6-thioguanine on RNA biosynthesis in regenerating rat liver. 6-Thioguanine, at a dose of 40 mg/kg body weight, was administered to rats at 12 hr after partial hepatectomy; 6 hr later, liver polysomes and cell sap were isolated and utilized to measure the effects of this antimetabolite on protein synthesis in vitro. When radioactive leucine was used to label peptides synthesized in vitro, no difference was observed between polyacrylamide gradient gel scans of systems derived from control regenerating liver and those from 6-thioguanine-treated regenerating liver. However, when radioactive tyrosine was used as the tracer to monitor synthesized peptides, a depression in the 30,000-molecular weight region of scans of products synthesized in systems derived from 6-thioguanine-treated regenerating liver was observed. Recombination experiments showed this effect to be due to the polysome component of the system. When equal amounts of polyadenylic acid-containing RNA from 6-thioguanine-treated or control regenerating liver were added to a wheat germ in vitro protein-synthesizing system, polyacrylamide gel scans of the products synthesized in the presence of radioactive tyrosine showed that more peptides were synthesized from polyadenylic acid-containing RNA from 6-thioguanine-treated rats than from control polyadenylic acid-containing RNA. That this phenomenon might be the result of incorporation of the analog into RNA was shown by the finding that all types of RNA containing 6-thioguainine, with the greatest concentration occurring in polyadenylic acid-containing RNA.


The development of prostatic adenocarcinoma in Nb rats following prolonged sex hormone administration. The low spontaneous incidence of grossly recognizable adenocarcinomas of the dorsal lobe of the prostate in Nb rats over 13 months old (0.45%) was increased to 18.38% in 130 rats by prolonged treatment with pellets of suitable sex hormones. Although testosterone propionate alone was effective, if the testosterone propionate was combined with treatment by estrone carcinomas of the prostate occurred after a shorter interval. Tumors tended to metastasize and transplanted readily, and all were autonomous, with a single exception that exhibited the growth pattern of a typical estrogen-dependent tumor.


[Structure of chromogen I of the Morgan-Elson reaction]. Alkaline treatment of 2-acetamido-2-deoxy-3,4:5,6-di-O-isopropylidene-aldehydo-D-glucose, or of the analogous D-mannose derivative, gave the same crystalline material, unambiguously identified as 2-acetamido-2,3-dideoxy-alpha-D-erythro-hex-2-enofuranose (3) by n.m.r. and mass spectrometry, and crystallography. Treatment of 3 with methanol in acidic medium gave methyl 2-acetamido-2,3-dideoxy-alpha,beta-D-erythro-hex-2-enofuranoside (11). The identical compound was obtained from Chromogen I under identical conditions.


Preparation and antitumor activity of o-palmitoyldextran phosphates, o-palmitoyldextrans, and dextran phosphate. Dextran was modified by introduction of palmitoly and phosphate groups. The derivatives were analyzed by sequential periodate oxidation-sodium borohydride reduction. Only one of these derivatives showed a significant growth-inhibitory effect when administered alone, while a second derivative showed, in combination therapy with an ineffective dose of Mitomycin C, a marked synergistic effect.


Elasticity of frozen aortic valve homografts. Homograft aortic valves were treated and stored in different ways and then tested for elastic qualities. It appears from the findings that the most satisfactory long-term storage technique is to flash-freeze the valves in the presence of dimethyl sulphoxide immediately after dissection.


Praecordial mapping of Q waves and RS ratio changes in acute myocardial infarction. The theory related to the loss of R waves and appearance of Q waves in acute myocardial infarction is discussed. A method of praecordial mapping of RS ratio changes and the appearance of Q waves that occur in acute myocardial infarction is described. The serial changes in these electrocardiographic signs in 17 patients during acute infarction are recorded. The potential value of these serial measurements in delineating the extent of myocardial injury in patients with acute infarction, and evaluating the effects of any treatment aimed at limiting infarct size is discussed.


Muscular reflex and baroreflex influences on heart rate during isometric contractions. Isometric hindlimb contractions were induced in anaesthetised dogs by stimulation of appropriate spinal ventral roots. During such contractions there were appreciable reflex systemic pressor responses accompanied by small increases in heart rate. The heart rate responses during contractions were small because the primary cardioacceleratory reflexes from muscle were partly masked during contractions by opposing baroreceptor-cardiodepressor reflexes.


Postnatal development of the suprachiasmatic hypothalamic nucleus of the rat. Light and electron microscopy of newborn, four day, one, two, three and five week old rats revealed principally a progressive increase in the diversity and number of synaptic contacts in the suprachiasmatic nucleus (SCN). The major increase in synaptic diversity occurred between four days and one week of age. Correlation between this finding and the adult synaptic morphology of SCN (Gülder, 1976) on the one hand, and the ontogeny of circadian rhythms on the other were made. This suggested that the retinal afferents arriving on day four form asymmetrical contacts with dendrites. While increase in synaptic number was progressive, it was most marked between three and five weeks of age. By five weeks, most features of the adult SCN were present. No significant morphological effects were evident as a result of neonatal retinal lesions.


The organisation of the lamina ganglionaris of the crabs Scylla serrata and Leptograpsus variegatus. The gross structure and neuronal elements of the first optic ganglion of two crabs, Scylla serrata and Leptograpsus variegatus, are described on the basis of Golgi (selective silver) and reduced silver preparations. Of the eight retinula cells of each ommatidium, seven end within the lamina, while the eighth cell sends a long fibre to the external medulla. Five types on monopolar neurons are described, three types of large tangential fibres, and one fibre which may be centrifugal. The marked stratification of the lamina is produced by several features. The main synaptic region, the plexiform layer, is divided by a band of tangential fibres; the short retinula fibres end at two levels in the plexiform layer; and two types of monopolar cells have arboriasations confined to the distal or proximal parts of the plexiform layer. The information presently available concerning the retina-lamina projection in Crustacea is examined. Some of the implications of retina and lamina structure are discussed in conjunction with what is known about their electrophysiology.


The autonomic innervation of rabbit salivary glands studied electron microscopically after 5-hydroxydopamine administration. In submandibular glands of rabbits both adrenergic and cholinergic axons are intimately associated with parenchymal cells of the intercalary ducts and the granular tubules, lying beneath the basement membrane and often in the space between the parenchymal cell and an associated myoepithelial cell. The submandibular acini receive a less intimate and less plentiful innervation by adrenergic and cholinergic axons which remain outside the basement membrane and are still associated with Schwann cells. Occasional axons of both adrenergic and cholinergic type occur beneath the basement membrane of submandibular striated ducts in intimate association with basal parts of the cells. In the parotid glands numerous adrenergic and cholinergic axons are found beneath the basement membrane of acini and intercalary ducts in intimate association with the cells.


Cell membrane structure of vascular smooth muscle of circle of Willis. Cell membranes of vascular smooth muscles of the circle of Willis were studied in thin sections and freeze-replicas. The cell membranes were differentiated into a caveolae intracellulares zone and caveolae-free zone, both of which were generally arranged in an alternate manner and parallel to the major axis of the smooth muscle cell. In the former zone, the caveolae intracellulares, about 600 A in diameter, were neatly oriented in one to several rows running parallel to the longitudinal axis of the muscle cell with a center-to center distance of about 800 A. The latter zone was of variable width and smooth, apart from membrane particles or scattered caveolae, and corresponded mainly to the dense area and partially to the myofibril area beneath the cell membrane. Membrane particles were generally more numerous on face A than on face B, and their average number per micronm2 was about twice as many inside the rows of the caveolae as outside. Rosette formations of membrane particles were often evident at the stomal rims of the caveolae. Adherentes and gap junctins were occasionally found on the caveolae-free areas which often protruded externally. Tight junctions appeared as a collection of scattered strands, which frequently showed free ends and were parallel to each other and also to the major axis of the smooth muscle cell.


The nervous system of the early echinopluteus. An ectodermal network of nerve cells has been observed in the echinopluteus. It seems to connect the ectodermal cell bodies with each other and with deeper parts of the nerve system. Together with the neurohumour containing parts of the ventral and oral ciliated bands, the nerve cells probably provide the larva with the capacity of coordinating muscular and ciliary responses to mechanical, chemical and electrical stimulation.


Fine structure of the gap junction in the tunicate heart. The plasma membranes of the tunicate heart exhibit an abundance of macular gap junctions distributed widely over the membrane surface. A study of these junctions by the freeze-etch technique was undertaken in an effort to elucidate the fine structure of this important membrane modification in a primitive heart. In cross or near-cross fractured junctions the junctional particles in contiguous membranes appear to be paired in register and to meet in the midline. In favorable face views, the junctional particles are seen to be disposed in hexagonal array. The individual particles display a distinct rosette-like substructure consistent with a six-membered ring of globular protein molecules clustered around a central channel. Similar junctional-type particles can be found in nonjunctional areas of membrane suggesting that the transport mechanism which they may represent is not restricted to the gap junction.


Effect of partial hepatectomy on the interrenal tissues of Xenopus laevis (Daudin). Partial hepatectomy was carried out on Xenopus laevis to investigate its influence on the endocrine system. In addition to other endocrine effects, a marked hypertrophy and stimulation of the interrenal gland was observed. Activated cells contain mitochondria with extended and irregularly coiled tubules embedded in a low electron dense matrix. Hepatectomy induces two phases of proliferation [3 and 35 days postoperative (p.o.)]. After 106 days p.o. giant mitochondria possessing narrow and closely packed, parallel tubules surrounded by an electron dense matrix indicate a phase of inactivation. The smooth endoplasmic reticulum and the Golgi apparatus proliferate after hepatectomy. During activation the high lipid content seen in controls in decreased significantly.


Sterol synthesis. A novel reductive rearrangement of an alpha,beta-unsaturated steroidal epoxide; a new chemical synthesis of 5alpha-cholest-8(14)-en-3beta, 15alpha-diol. Reduction of 3beta-benzoyloxy-14alpha,15alpha-epoxy-5alpha-cholest-7-ene with either lithium triethylboro-hydride or lithium aluminum hydride (4 molar excess) gave 5-alpha-cholest-8(14)-en-3beta,15alpha-diol in high yield. Reduction of the epoxy ester with lithium triethylborodeuteride or lithium aluminum deuteride (4 molar excess) gave [7alpha-2-H]-5alpha-cholest-8(14)-en-3beta,15alpha-diol. Reduction of 2beta-benzoyloxy-14alpha,15alpha-epoxy-5alpha-cholest-7-ene with a large excess (24 molar excess) of lithium aluminum hydride gave, in addition to the expected 5alpha-cholest-8(14)-en-3beta,15alpha-diol, a significant yield (33%) of 5alpha-cholest-8(14)-en-3beta-o1. Reduction of the epoxy ester with a large excess (24 molar excess) of lithium aluminum deuteride gave [7alpha-2H]-5alpha-cholest-8(14)-en-3beta,15alpha-diol and 5alpha-cholest-8(14)-en-3beta-o1 which contained two atoms of stably bound deuterium.


A method for 13C enrichment of phospholipid acyl chains using Tetrahymena. A method has been devised for obtaining highly 13C enriched (20-25%) phospholipids and membranes from the ciliate Tetrahymena, the enrichment occurring in the acyl chains. This method provides both phosphatidylcholine and phosphatidylethanolamine with enriched chains. The central feature of the method is the monoaxenic growth of Tetrahymena on an E. coli mutant which has a high incorporation of exogenous acetate into fatty acid chains. The 13C NMR spectra of the phospholipids are sufficiently enriched to permit NMR relaxation studies.


Prevention of the development of renal hypertension by anteroventral third ventricular tissue lesions. Several reports have suggested that a central action of the renin-angiotensin system plays a role in the development of renal hypertension. Based on the identification of the anteroventral thrid ventricle (AV3V) as a site of central angiotensin dipsogenic and pressor mechanisms, the present study examined the effect of electrolytic lesions in the AV3V region on the development of renal hypertension in rats. Lesioning alone produced a temporary but profound adipsia and, in one-half of the rats, a substantial transient elevation in arterial pressure. After lesioned rats had recovered normal drinking and blood pressure, unilateral nephrectomy with figure-of-eight wrapping of the remaining kidney failed to produce the hypertension and increased drinking observed after renal wrapping in shamlesioned rats. The possibility that the failure of lesioned rats to increase water intake after wrapping prevents hypertension development was ruled out by experiments demonstrating that normal rats exhibited identical rises in arterial pressure after wrapping regardless of whether or not they were allowed to increase water intake. The fact that unanesthetized lesioned rats exhibit attenuated drinking and pressor responses to systemically administered angiotensin suggests this mechanism as a possible explanation for the failure of AVV-lesioned rats to increase drinking and blood pressure after renal wrapping.


Influence of thiazide on salt hypertension. This study was undertaken to evaluate the effect of chronic diuretic therapy with chlorothiazide on the course of salt hypertension in hypertension-resistant (R) and hypertension-sensitive (S) strains of rats. Investigation of the effects of chlorothiazide on blood pressure, 24-hour urinary 24Na and aldosterone excretion, and plasma renin activity (PRA) produced the following observations: (1) Chlorothiazide failed to prevent the development of salt hypertension in S rats. (2) After 12 weeks, S rats on high salt puls chlorothiazide exhibited a rapid fall in blood pressure to levels indistinguishable from those of S rats on low salt. (3) Chlorothiazide significantly increased urinary 24Na excretion only in S rats on high salt (P less than 0.01). (4) Chlorothiazide significantly increased PRA and urinary aldosterone excretion in both strains on low or high salt diets (P less than 0.001). (5) Morbidity and mortality of salt hypertension were alleviated by chlorothiazide treatment. The unique aspect of this study is the finding that chlorothiazide did not abolish the hypertensiogenic action of salt in S rats.


Volume-pressure relationships during development of mineralocorticoid hypertension in man. Serial measurements of urinary sodium excretion, sodium space, plasma volume, and plasma renin concentration were made during the development of hypertension in patients who were exposed to an excess of endogenous or exogenous mineralocorticoid activity. Five patients with primary aldosteronism due to adenoma were followed during spironolactone treatment, for 35-55 days after the drug had been stopped, and finally, after surgery. Blood pressure rose continuously after stopping spironolactone. Sodium balance, however, showed an initial phase of sodium gain, followed by a phase of gradual sodium loss. Sodium space and exchangeable sodium rose by 5.0 +/- 0.48 liters/1.73 m2 of body surface area (BSA) (P less than 0.005) and by 865 +/- 97 mEq/1.73 m2 BSA (P less than 0.005), respectively; the values were maximal after 10-15 days, declined afterward, but remained higher than during spironolactone treatment. Plasma and blood volumes rose by 624 +/- 90 ml/1.73 m2 BSA (P less than 0.005) and by 327 +/- 74 ml/1.73 m2 BSA (P less than 0.01), respectively; they were maximal after 20-25 days, and then returned to their initial values. Exchangeable sodium, during the phase of sodium loss, was inversely correlated with the rise in blood pressure (P less than 0.01). Renin fell during the phase of sodium gain, and remained low afterwards. Blood pressure and sodium space declined after surgery, but plasma volume showed no change. The postsurgery values of these parameters were not significantly different from those measured during spironolactone treatment. Two subjects with adrenocortical insufficiency, who were followed for 45-60 days during treatment with dexamethasone and 9alpha-fluorocortisol acetate, also showed a transient rise in sodium space and plasma volume. The results suggest a redistribution of body fluids during development of hypertension. They also suggest that the tendency of body fluid volumes to return to normal is pressure-dependent. The long-term effects of mineralocorticoid excess on the interrelations between pressure, volume, and renin bear some resemblance to the pattern observed in patients with established essential hypertension, i.e., pressure remains elevated despite a decrease of volume, and renin is "inappropriately" suppressed in relation to the sodium and volume status.


Isolation of a hypertension-producing compound from normal human urine. A protein fraction has been isolated from normal human urine which, when injected over a period of 10-15 days in normal rats, produced sustained hypertension. On cessation of injection, the blood pressure fell to normal level within 7-10 days. The hypertension was accompanied by expansion of plasma volume, retention of sodium, and alteration in urinary Na/K ratio. Further, it led to hypertrophy of the adrenal cortex and increased circulating aldosterone without a change in plasma corticosterone values. These results suggest that the protein fraction increased arterial pressure in rats through direct stimulation of aldosterone production resulting in sodium retention and volume expansion.


Pressor and stereoidogenic actions of [des-Asp1]angiotensin I dependency on conversion to angiotensin III. In the conscious rat, angiotensin III, [des-Asp1]angiotensin II, stimulates aldosterone biosynthesis and exhibits 30-50% of the pressor potency of angiotensin II. A potential precursor of the biologically active heptapeptide is [des-Asp1]angiotensin I, the C-terminal nonapeptide of angiotensin I. The in vivo pressor and the in vivo and in vitro steroidogenic actions of [des-Asp1]angiotensin I were investigated in the presence and absence of an inhibitor of converting enzyme. The pressor responses to [des-Asp1]angiotensin I and [des-Asp1]angiotensin II were similar and showed comparable changes in responsiveness when the rats were maintained on diets with different sodium content. The pressor activity of [des-Asp1]angiotensin I was attenuated progressively by pretreatment with increasing doses of converting enzyme inhibitor and was totally abolished in five of seven rats at an inhibitor dose of 1,200 microng/kg. In isolated zona glomerulosa cells from rats on normal sodium diets, angiotensin I and [des-Asp1]angiotensin I had only weak steroidogenic effects relative to angiotensin III. The administration of [des-Asp1]angiotensin I, 1 nmol/kg, subcutaneously to six rats on normal sodium diets resulted in a rise in the 6-hour urinary aldosterone excretion from 46.5 +/- 6.6 to 99.5 +/- 11.8 ng (P less than 0.01). Treatment with converting enzyme inhibitor (2 mg/kg) prevented this steroidogenic response to [des-Asp1]angiotensin I. These in vivo studies in the conscious rat show that the administration of [des-Asp1]angiotensin I results in increases in both blood pressure and urinary aldosterone excretion which are dependent on the hydrolysis of the nonapeptide by converting enzymes to angiotensin III. If [des-Asp1]angiotensin I is formed in this species, then it will be an immediate precursor of angiotensin III.


Socially handicapped children.

Socially handicapped children. There is general agreement that adverse environmental circumstances have a stunting effect on child development, even if account is taken of a possible genetic component in the variation of intelligence. A short account of relevant investigations is followed by a summary of some aspects of an interdisciplinary study recently completed by the authors which included interviews with parents as well as psychological tests and ratings on their children in school.


Histamine receptors in the coronary circulation of the dog. Effects of mepyramine and metiamide on responses to histamine infusions. The effect of histamine on coronary blood flow  (CBF) was studied in anaesthetized grayhounds. CBF and systemic blood pressure were measured using electromagnetic flow transducers and catheters in the aorta during infusions of drugs into the left circumflex coronary artery. Histamine infusions (5, 10, and 20 microng/min) produced dose-related increases in CBF without changing heart rate or blood pressure. Metiamide (100 microng/min) given simultaneously produced a parallel displacement of the histamine dose-response curve to the right (P less than 0.05) with a dose ratio of 2. Mepyramine (100 microng/min) produced a larger parallel displacement of the dose-response curve (dose ratio = 4). Together, metiamide and mepyramine greatly reduced the histamine response (dose ratio = 16), showing that the metiamide blockade is augmented in the presence of mepyramine. Similarly, mepyramine blockade is augmented in the presence of metiamide. The increase in CBF produced by histamine infusion (20 microng/min) was similar to the peak flow response of reactive hyperemia following 8-second occlusions. However, mepyramine and metiamide together had no effect on the peak flow response, duration, or total repayment of flow debt in reactive hyperemia. These results show that histamine-induced coronary vasodilation is mediated by both H1 and H2 receptors. However, the vasodilation of reactive hyperemia after brief coronary artery occlusions does not appear to involve histamine.


Renal responses of the fetal lamb to fetal or maternal volume expansion. Fetal and maternal glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume, sodium excretion, and fractional sodium reabsorption were measured in a chronically instrumented sheep preparation. Fetal GFR was essentially stable between 110 and 135 days of gestation (term = 147 days). There was a significant increase in GFR after 135 days. After the infusion of 50 ml of normal saline over a 30-minute period, fetal GFR and sodium excretion increased significantly. Fractional sodium reabsorption was significantly decreased. Thus, the fetus is capable of responding to volume expansion with saline with an increase in GFR and a decrease in fractional sodium reabsorption. After the infusion of 1000 ml of normal saline into the ewe in 1 hour, maternal GFR and RPF rose significantly. Sodium excretion rose 6-fold and fractional sodium reabsorption fell significantly. After the infusion of saline into the ewe, there was no change in fetal GFR, RPF, sodium excretion, urine volume, or fractional sodium reabsorption. Since there were no changes in fetal renal function after maternal volume expansion with saline there was no evidence for the transplacental passage of a natriuretic factor from ewe to fetus.


Reflex regulation of sympathetic activity in the spontaneously hypertensive rat. The influence that the pressure-sensitive receptors in the cardiovascular system have on renal nerve activity and on heart rate was compared in normotensive rats (NTR) and spontaneously hypertensive rats (SHR). The cardiovascular receptors were stimulated by raising the blood pressure (BP) with intravenous phenylephrine. The duration of silence in the record of renal sympathetic nerve activity produced by a number of different rises in BP was measured. We found that the pressure that was just able to produce a silence in the nerve activity (threshold pressure) was higher in the SHR (170 mm Hg) than in the NTR (130 mm Hg). Also, comparable rises in BP above the threshold  pressure in the SHR and NTR were less effective in the SHR in producing a complete inhibition of sympathetic nerve activity as judged by the short duration of inhibition. In contrast, we found that the changes in heart rate produced by rises in BP above threshold pressure were similar in NTR and SHR although the threshold pressure was somewhat higher in the latter. It was, therefore, concluded that the cardiovascular pressure receptors, apart from being reset to operate at a higher pressure level in the SHR, are less able to inhibit ongoing sympathetic activity than in the NTR. It is suggested that this is most likely due to a high sympathetic activity in the SHR.


Relationship between epicardial ST-segment elevation, regional myocardial blood flow, and extent of myocardial infarction in awake dogs. This study was designed to examine the relationship between epicardial ST change (EpST) and regional myocardial blood flow (RMBF) following coronary occlusion and extent of myocardial infarction (MI) in awake dogs. Fifteen min and two hr after coronary occlusion simultaneous measurements of EpST and RMBF were made. Six days later histologic MI and RMBF were determined in transmural myocardial samples from each electrode site. Greatest ST elevation occurred at sites of greatest ischemia and MI. However, 15 min after occlusion 29% of sites with greater than 50% MI and 39% of sites with greater than 50% reduction in RMBF did not demonstrate ST elevation greater than 2 mV. There were poor correlations between EpST and MI (r = 0.59) and RMBF (r = 0.57). Comparable relationships were observed two hr after occlusion. In the present study, there were not close quantitative or qualitative relationships between EpST and MI or RMBF. A good correlation was observed between RMBF at two hr and MI (r = 0.89).


The origin of ventricular arrhythmias 24 hours following experimental anterior septal coronary artery occlusion. The anterior septal coronary artery was acutely ligated in 16 open-chest anesthetized dogs to produce an infarct of the septal myocardium. Twenty-four hours following occlusion complete epicardial mapping and extensive plunge electrode recording techniques were used to localize the sites of origin and patterns of activation of the ventricular tachyarrhythmias that developed during recovery. The earliest electrical activity for 13 individual rhythms was recorded from surviving septal subendocardial Purkinje fibers at the margins of the infarct, in the right or left ventricle, directly underlying the sites of earliest epicardial breakthrough. The sites of origin were verified by demonstrating unchanged activation sequences during pacing through the electrode sites which recorded the earliest activity. None of the arrhythmias arose from the His bundle or bundle branches despite the fact that these tissues course directly through the necrotic septum. The data presented supports the hypothesis that ventricular arrhythmias occuring in the 24-36 hour post acute infarction period may originate in the surviving subendocardial Purkinje system. Our experimental model shows that in cases in which a malignant rhythm arises from a focus, whether it is due to enhanced automaticity or local re-entry, epicardial mapping alone may not identify the source of the arrhythmias. Extensive endocardial mapping may provide a more rational basis for surgical interventions designed to abolish these arrhythmias.


Combined dopamine and nitroprusside therapy in congestive heart failure. Greater augmentation of cardiac performance by addition of inotropic stimulation to afterload reduction. The hemodynamic benefits of combining administration of dopamine with nitroprusside (NP) were evaluated in nine patients with chronic congestive heart failure due to ischemic, idiopathic myocardial or valvular cardiac disease. NP alone (68 microng/min) produced decline in left ventricular end-diastolic pressure (LVEDP) from 25.4 to 14.1 mm Hg (p less than 0.01) but modest increase in cardiac index (CI) from 2.41 to 3.02 L/min/m2 (P less than 0.05). Dopamine alone (6 microng/kg/min) caused an elevation of CI to 3.36 (P less than 0.01) but without decrease of LVEDP. Simultaneous infusion of the two agents resulted in favorable alterations in both hemodynamic variables: LVEDP decreased to 15.7 (P less than 0.01) and CI increased to 3.52 (P less than 0.01). It is concluded that dopamine substantially enhances the effectiveness of nitroprusside therapy in congestive heart failure by providing concomitantly the principal beneficial actions of the vasodilator and dopamine used separately. Thus combined dopamine with NP treatment considerably raises low CI while markedly reducing elevated LVEDP and provides a potentially efficacious pharmacologic modality for the treatment of severe congestive heart failure due to left ventricular dysfunction.


Electrophysiologic delineation of the specialized atrioventricular conduction system in two patients with corrected transposition of the great arteries in situs inversus (I,D,D). Electrophysiologic delineation of the atrioventricular conduction system at surgery is described in two patients with corrected transpostion of the great arteries in situs inversus. Intra-atrial electrograms were recorded in one patient from sites immediately adjacent to the coronary sinus located in the left-sided right atrium. The intraventricular portion of the atrioventricular conduction system was identified in both patients along the posterior and inferior margin of the ventricular septal defect, in contrast to the superior and anterior location found in corrected transposition of the great arteries in situs solitus. In contrast to the superior and anterior location found in corrected transposition of the great arteries in situs solitus. The course of the conduction system in the hearts of these two patients and a possible relationship to the cardiac loop and dual origin of the atrioventricular node is discussed. These cases illustrate the usefulness of segmental diagnosis of congenital heart disease and of electrophysiologic identification of the specialized atrioventricular conduction system at surgery.


Natural history of ventricular septal defect. A study involving 790 cases. The development of 790 untreated patients affected by ventricular septal defect (VSD) has been the object of a 25-year study. Of these patients, 72% had had at least one catheterization; 13% had several. The mean observation interval is six years, and the average age at the latest data is 19.5 years. This study covers 4717 patient-years. For the entire population, the incidence rate or aortic regurgitation is 6.3% (4.3 for 1000 patient-years) and that of bacterial endocarditis is 3.7% (2.4 for 1000 patient-years). Twenty-five patients died, 15 of them between the ages of one and 39. Of the 499 cases with several clinical examinations, 71% remained stable. In 21%, changes suggesting some level of closure developed; in 7%, infundibular stenosis began to evolve and in 1% pulmonary vascular disease began to appear or became accentuated. These different rates are studied and discussed in relation to patients' age, VSD type, and various follow-up characteristics.


Coronary spasm, variant angina, and recurrent myocardial infarctions. A 24-year-old male student had three myocardial infarctions, one prior to and two following the angiographic documentation of normal coronary arteries. A spontaneous episode of variant angina prompted repeat coronary angiography, during which intravenous ergonovine caused spasm of the left anterior descending coronary artery, transient ST-segment elevation, and ischemic chest pain; the previously normal right coronary artery was found to be occluded proximally. This constellation of clinical and angiographic findings suggests that coronary spasm can cause acute myocardial infarction as well as variant angina.


Simultaneous measurement of secondary and tertiary tricyclic antidepressants by GC/MS chemical ionization mass fragmentography. We present a method for measuring seven commonly used tricyclic antidepressants in plasma. This method is suitable for monitoring therapeutic concentrations and for screening drug overdoses in cases where the identity of the abused tricyclic antidepressant may not be known. Drugs from alkalinized plasma are extracted into hexane in one step; two injections into the gas chromatograph/mass spectrometer follow. The tertiary amines (amitriptyline, doxepin, and imipramine) are analyzed by direct injection; the secondary amines (nortriptyline, desmethyldoxepin, desipramine, and protriptyline) are analyzed after derivitization with trifluoroacetic anhydride. Clomipramine and desmethyltrimipramine are suitable internal standards. Chemical ionization mass fragmentography, with methane as the reactant gas, is used. While maintaining specificity for these drugs, concentrations in human plasma ranging from 5 to 500 microng/liter can be measured. The coefficients of variation are about 4 to 11%.


A stopped-flow clinical analyzer in which immobilized-enzyme reaction loops are used. A stopped-flow clinical analyzer is described that makes use of a reaction loop containing immobilized enzyme(s) for the determination of the analyte/substrate. The analyzer has been evaluated by determining glucose with immobilized glucose oxidase. The stopped-flow mixing system was constructed at a current cost of less than  $500. The analyzer separates the enzymatic reaction from a followup, spectrophotometric indicator reaction. This separation allows the enzymatic reaction to be used in either a fixed-time, kinetic mode or in an equilibrium mode. Likewise, the indicator reaction can be used in either mode. Results for glucose in blood serum indicate that good precision and accuracy can be obtained.


Choice of monitoring isotope in double label radioimmunoassays with nonimmunological separation techniques. We discuss the suitability of some radioactive isotopes as volume markers in radioimmunoassays, from a radiochemical point of view. For three eligible isotopes (22Na, 60Co, and 75Se) we studied the concentration of the marker in the precipitate formed in the separation phase of radioimmunoassays. For all those kinds of separations tested (charcoal, ammonium sulfate, polyethylene glycol, and ethanol), binding or coprecipitation was virtually absent or negligible with 22Na but 75Se was strongly concentrated in the precipitate. Concentration of 60Co occurred only with charcoal and ethanol precipitation. Because heavy metals tend to bind to serum proteins, we conclude that of all radioactive isotopes commercially available only 22Na should be used in radioimmunoassays with nonimmunological separation methods.


Plasma lactate dehydrogenase activity will be increased if detergent and platelets are present. Plasma lactate dehydrogenase activity is artifactually increased when analyzed on the SMAC (Technicon) continuous-flow analyzer. The factors responsible are incomplete centrifugation and the presence of detergent in the dilution buffer. The contribution of platelet lactate dehydrogenase in the plasma is demonstrated with a case of thrombocytosis.


Furildioxime method for nickel analysis in serum and urine by electrothermal atomic absorption spectrometry. We describe a method of analysis for nickel in serum and urine. After the sample (1 ml) has been subjected to acid digestion, Ni(II) is extracted into methylisobutylketone as a furildioximate complex, and is measured by electrothermal atomic absorption spectrometry. The method is more sensitive and more convenient than previous methods, and is less subject to nickel contamination because the digestion and extraction steps are performed in a single tube. Analytical recovery of Ni(II) (10 or 20 microng/liter) added to 20 specimens of serum or urine averaged 101% (range, 94 to 107). The following values (mean +/- SD) were obtained for nickel concentrations in specimens of serum and urine from 19 healthy adults living in central Connecticut: serum = 3.1 +/- 1.6 microng/liter; urine = 2.7 +/- 1.6 microng/liter. The method provides a practical means for monitoring occupational exposures of workers to nickel compounds.


Binding of dye to albumin, as studied by ultrafiltration. We describe a procedure for measuring the binding of small molecules to proteins by means of a dynamic ultrafiltration system. A continuous binding curve is obtained by continuously monitoring the absorbance of ultrafiltrate as a function of ultrafiltrate volume, and corrections are made for the retention of the small molecule by the membrane and the leakage of the protein through the membrane. The method is applied to the binding of bromcresol green to human albumin. Some major sources of uncertainties in the method are discussed.


Deficiency of propionyl-Co A carboxylase and methylcrotonyl-Co A carboxylase in a patient with methylcrotonylglycinuria. The enzymes 3-methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase were studied in fibroblasts derived from a patient with 3-methylcrotonylglycinuria and from control individuals. There was a parallel defect in the activities of both enzymes in extracts of the cells of the patient. Supplementation with biotin of the medium in which the cells were grown restored the activity of both carboxylases to the normal range. Kinetic analysis of the activities of the carboxylases obtained from cells grown in biotin revealed KM values for each enzyme that approximated normal. These data indicate that the primary defect in this patient is in the enzyme holocarboxylase synthetase which is responsible for activating biotin and transferring it to the apocarboxylase proteins.


A new sulfur amino acid, named hawkinsin, identified in a baby with transient tyrosinemia and her mother. An unknown compound present in the urine of a girl with prolonged transient tyrosinemia and her mother was isolated and identified as (2-L-cystein-S-yl-1,4-dihydroxycyclohex-5-en-1-yl)-acetic acid (IVa). The new amino acid was named hawkinsin (Haw) and characterized by gas  chromatography-mass spectrometry (GC-MS) of its penta-trimethylsilyl (TMS) derivative and of its desulfuration components. Haw was compared with the synthetic reference compound using GC-MS, IR, TLC, PC, ion-exchange chromatogrpahy and high-voltage electrophoresis. IVa and (2,6-bis-L-cystein-S-yl-1,4-dihydroxycyclohexyl-1)-acetic acid were synthesized from 4-quinolacetic acid, the latter was prepared in two different ways. It is postulated that Haw originates from an intermediate in the 4-hydroxy-phenylpuruvate hydroxylase reaction (EC 1.14.2.2), and that mother and child are heterozygous for an inborn error of metabolism characterized by a defect in this hydroxylase system, which is unable to rearrange the intermediate to homogentisic acid.


Hypomagnesemia and hypermagnesemia.

Hypomagnesemia and hypermagnesemia. With the availability of reliable methods for measurement of magnesium in body fluids, a great deal of information has accumulated on magnesium homeostasis. We reviewed the pertinent data on various aspects of magnesium metabolism. The conditions associated with hypo- and hypermagnesemia and the clinical and laboratory findings as well as the management of these disorders are discussed. Finally, the effects of renal failure on magnesium homeostasis are presented.


Hypercalcemia and hypocalcemia.

Hypercalcemia and hypocalcemia. This report discusses the various aspects of the hypercalcemic and hypocalcemic disorders. We first describe the physicochemical state of serum calcium and the interpretation of a rise or a fall in total serum calcium. The various diseases associated with alterations in the concentration of serum calcium are presented. The clinical manifestations of the hypercalcemic and hypocalcemic disorders and their management are described.


Studies on digitalis. XI. Digitoxin metabolism in patients with impaired renal function. The metabolic pattern of cardioactive and conjugated digitoxin metabolites was studied in 10 uremic patients on maintenance treatment with digitoxin 24 hr after the last dose (mean dose, 0.060 mg/day). Urine was collected over 24 hr. The mean serum digitoxin level was 9.4 ng/ml, and urine level was 6.8 ng/ml. The metabolic pattern of cardioactive metabolites was studied in 5 patients on hemodialysis. Their mean serum digitoxin level was 6.3 ng/ml and urine level was 7.3 ng/ml, on a digitoxin dose of 0.072 mg/day. Unchanged digitoxin was the main cardioactive substance present in both serum and urine of uremic patients. Uremic patients had significantly less unchanged digitoxin and had more hydroxylated (DG-3) and hydroxylated and hydrolyzed (DG-2, DG-1, and DG-0) metabolites than control patients. The extent of conjugation was the same in the two groups. Our data suggest that uremic patients produce more digitoxose than control patients and that digitoxin elimination is more rapid in uremic patients. The altered pattern of digitoxin metabolites is most consistent with uremia-induced changes in hydroxylation and hydrolysis. The hemodialysis group had a pattern of digitoxin and cardioactive metabolites similar to control patients, indicating that patients on hemodialysis differ from other uremic patients with respect to digitoxin metabolism.


Spironolactone and canrenoate-K: relative potency at steady state. Relative dose ratios of the mineralocorticoid antagonists spironolactone (100 mg and 200 mg daily) and canrenoate-K (200 mg daily) at steady state were defined in six healthy subjects with fludrecortisone as the mineralocorticoid agonist. The urine log 10 Na/K responses during spironolactone treatments were consistent with the law of mass action. The potency of canrenoate-K was 0.68 (95% C.L. 0.53 to 0.89) that of spironolactone on a weight basis. Approximately 72% of the renal antimineralocorticoid activity of spironolactone could attributed to the metabolite canrenone. The results at steady state are contrasted with those of a previously study comparing single doses of spironolactone and canrenoate-K.


Investigation of the non-jaundiced patient by percutaneous transhepatic cholangiography. The investigation of the non-jaundiced patient by percutaneous transhepatic cholangiography (PTC) and the indications for this examination are presented. Diagnostic examinations were obtained in all 15 patients studied despite the absence of jaundice at the time of examination. Complications were minimal. The value of this method particularly after previous biliary surgery is emphasized. It is suggested that PTC may be of great value, and safely used in non-jaundiced patients.


Radiology of the Eustachian fossa.

Radiology of the Eustachian fossa. The Eustachian fossa, when visualised in contrast radiography and cinefluorography, shows a wide variety of shapes and sizes. Moreover, the fossa also exhibits varying degrees of changes during swallowing. Brief accounts of the technique of contrast radiography and the appearance of the normal nasopharyngograms are given to facilitate the understanding of the radiological features of the fossa.


The accuracy of bolus ascending phlebography in demonstrating the ilio-femoral segment. The phlebograms of the ilio-femoral segment obtained by a bolus technique in 100 patients were reviewed. The technique of bolus phlebography from bipedal injections is described in detail. In 92% of the phlebograms the ilio-femoral segment was considered to be sufficiently well opacified to exclude thrombus. Follow-up of the patients confirmed the accuracy of the method.


Useful radiological signs in acute appendicitis in children. Straight X-rays of 92 control patients with acute appendicitis and 92 control subjects were studied for radiographic abnormalities. Disturbance in intestinal gas pattern was the most common abnormality. Presence of a faecolith, free peritoneal fluid, scoliosis and a soft tissue mass were useful supporting signs. Loss of the properitoneal fat line and the right psoas outline were not reliable signs as they occurred with equal frequency in both groups.


The radiological approach to leiomyoma of the oesophagus with a long-term follow-up. Long-term follow-up of leiomyomas in the oesophagus is discussed from the radiological point of view. It is the authors' impression that surgical intervention is not a matter of urgency in the treatment of these tumours as their tendency to undergo malignant change is very rare. Nine cases of leiomyoma of the oesophagus were followed for periods ranging from 1 to 15 years. None showed malignant degeneration.


Coronary angiography in complicated acute myocardial infarcts. Left ventriculography with selective coronary angiography was performed on 13 patients with acute myocardial infarcts complicated by cardiogenic shock of left ventricular failure and hypotension. Twelve patients (92-3%) tolerated the procedure well. Irreversible ventricular fibrillation resulting in death occurred in one patient 7-7%) during the opacification of the left coronary artery. Seven (87-5%) of the eight patients treated surgically and two (50%) of the four patients treated medically died. This study shows that although acute myocardial infarction increases the risk of coronary angiography, it is justifiable if surgical therapy is contemplated.


Calcification of the intrarenal branches of the renal arteries. Mild to extensive calcification of the intrarenal branches of the renal arteries seen in 13 patients over a period of 12 months is described. This type of renal vascular calcification appeared to be associated with generalised atherosclerosis in patients of advancing age. The association of diabetes mellitus and intrarenal arterial calcification could not be supported by the cases presented here.


Pseudocysts: diagnosis in the adult by total body opacification. Recent use of higher doses of contrast material for excretory urography in adults has made differentiation between cystic and solid masses feasible in adults just as it has been in children. The first two adults to have the cystic nature of their pseudocysts ascertained by total body opacification are presented. In one case, the mass was not palpable because the abdomen was markedly tender, suggesting that total body opacification may be helpful in the examination of the acute abdomen. The second case suggests the importance of the prone position.


Necropsy of animals for scientific research. Techniques for the necropsying of animals and the trimming of tissues for histologic sections have been described for scientific research. It has been helpful to refer to the description, records, fixatives, and to other special procedures. The comment explains the reasons for using some of the procedures.


XAD-2 resin drug extraction methods for biologic samples. The XAD-2 resin extraction procedure is rapidly becoming an important tool for both the clinical and forensic toxicology laboratory. Although different investigators use different elution solvents and techniques, the basic procedure is to adsorb drugs onto the XAD-2 resin and then elute these drugs with an appropriate organic solvent. A number of parameters have been shown to be involved in obtaining good results. These include pH of sample, flow rate, type and volume of eluting solvent. These parameters can be adjusted so that maximum overall drug recoveries are obtained. Since XAD-2 extraction of urine by Fujimoto and Wang [2] was introduced, the procedure has been extended to all types of biologic specimens. Various elution techniques have been reported [12, 13], namely, the differential elution of drugs from the resin into acid and neutral, and basic drug fractions. Overall, the techniques vary from rapid simple procedures for drugs of abuse in urine to more elaborate methods of extraction of autopsy material. The extraction procedure itself is flexible enough so as to suit the needs of almost any toxicology laboratory.


A congenital pulmonary anomaly (hamartoma) in a seven-month-old bovine fetus. A case of an unusually large congenital pulmonary malformation (hamartoma) in a seven-month-old aborted Holstein fetus is reported. This was the dam's sixth gestation; the previous five had terminated in November or early December with delivery of a normal, live calf. Abortion was spontaneous without prior clinical signs noted by the herdsman. The condition of the aborted fetus indicated abortion followed closely intrauterine fetal death, which probably resulted from vascular insufficiency owing to crowding in the fetal thorax by the massive pulmonary malformation.


Intracutaneous cornifying epithelioma ("keratoacanthoma") of dogs and keratoacanthoma of man. The intracutaneous cornifying epithelioma ("keratoacanthoma") of dogs was compared with keratoacanthoma of man based on findings in the literature and in house studies. The two tumors differ at the following points: epithelium of origin, rate of growth, infiltration, spontaneous involution, breed predisposition (Norwegian Elkhound, generalized form), occurrence in dogs at a younger or middle age. The development of this tumor in dogs seems to be comparable with the development of so-called keratoacanthoma in Mastomys natalensis, which is virus-induced. Further investigations have been initiated to uncover the possible virus nature of the intracutaneous cornifying epthelioma (so-called keratoacanthoma) in dogs.


Experimentally induced pine needle abortion in range cattle. Pine needle-induced abortion in cattle is a serious problem in many areas of western United States and Canada. Field observations on pine needle abortion indicate that this condition is stress related. The results of this research indicate that the pine needle-induced abortion occurs much more readily if cows are under stress.


B-chromosome systems in the pocket mouse, Perognathus baileyi: meiosis and C-band studies. The heterochromatin characteristics and meiotic behavior of the B-chromosome system of the pocket mouse, Perognathus baileyi, and described. B-chromosomes are associated both with a meiotic accumulation mechanism and with an increase in average chiasma frequency in the A-chromosome set in males. Three morphological classes of B-chromosomes are recognizable, and the mechanisms of origin of each are discussed.


Comparative study of human chromosome replication in primary cultures of embryonic fibroblasts and in cultures of peripheral blood leucocytes. III. Distribution of AT- and GC-nucleotide pairs along the length of chromosomes 1, 2, 3, and 16 in the two types of human cells. Distributions of AT- and GC-base pairs along the length of chromosomes 1, 2, 3 and 16 in primary cultures of embryonic fibroblasts and of peripheral blood leucocytes were studied by autoradiography with: 1. 3H-thymidine and 3H-deoxycytidine; 2. 3H-deoxyadenosine and 3H-deoxyguanosine. It has been shown that the two types of cells differ in the DNA content and proportion of AT- and GC-nucleotide pairs in the centromeric heterochromatin of chromosome I: this region contains more DNA in fibroblasts than in leucocytes mainly due to AT-pairs. In both types of cells the telomeric region of the short arm of this chromosome contains more GC- than AT-pairs. Similar results were obtained for C-heterochromatin of chromosome 16: the frequencies of labelling of this region by 3H-deoxyadenosine and 3H-thymidine in fibroblast cultures were higher than in case of 3H-deoxycytidine and 3H-deoxygyanosine, and in leucocyte cultures these frequencies were almost equal. No differences in the distributions of base pairs along the length of chromosome 2 and 3 were established in the two types of cells. -- The nature of the established phenomenon may be connected with under-replication or loss in another way of part of the genetic material in the process of development and differentiation of cell systems.