[Correlation between the brain serotonin and the hypothalamic neuro-secretion in rat (author's transl)]. Parenteral administration of PCPA (200 mg/kg) induces changes in the quantitiy and the distribution of hypothalamic neurosecretion. This action appears very quickly and increases during the 48 hours following the injection. The histologic observations disclose a large accumulation of neurosecretory material in the supraoptic nuclei and in the accessory magnocellular groups of the anterior hypothalamus. In the median eminence large Herring bodies are seen. These results are to be compared to those obtained after mesencephalic raphes lesioning. The histologic alterations observed in the anterior hypothalamic level, may be due to complex disturbances involving the monoaminergic neuromediation.


The kidney in streptozotocin diabetic rats. Morphologic, ultrastructural, and function studies. In order to study the nephropathy associated with experimental streptozotocin diabetes, serila morphologic, ultrastructural, immunohistologic, and functional studies were done in diabetic Lewis rats to study the course of the nephropathy. Early in the course of diabetes, these animals developed an increase in mesangial matrix, with electron-dense material, IgG, and C3 in the mesangium. These alterations were progressive. Mesangial bars, proximal tubular vacuolization, and myeloid bodies were also present. Progressive increase in protein excretion and increase in creatinine clearance were observed. Hyperglycemia was accompanied by weight loss, persistent glycosuris, hyperphosphaturia, and hypercalcuria. Urinary glomerular basement membrane-like protein and major urinary protein were decreased. Normal age-matched controls showed no abnormalities. Some of the changes observed in diabetic rats are present in human diabetes.


Cystic fibrosis. A dilemma in the metabolic pathogenesis of genetic disease. The fundamental pathological observations in cystic fibrosis (CF) were made over three decades ago. More recently, physiological findings have directed investigation toward a plethora of humoral substances and their possible role in disturbances of the secretory processes in CF. The application of the techniques of molecular biology and of tissue culture is beginning to increase our knowledge about the so-called CF factors and their diverse effects on epithelial and ciliated surfaces. Emphasis in current research is on the chemical characterization of the CF factors, the metabolism of cells cultured from patients with CF, and the biochemical events controlling the processes of secretion. Some current theories as to the metabolic pathogenesis of CF are considered in the context of existing findings.


Asymmetric septal hypertrophy in autopsies in men. Asymmetric septal hypertrophy (ASH) was not identified in the 2,790 autopsies performed in a Veterans Administration hospital since 1958. Recent reports consider ASH to be a common cardiac disease in the diffuse form that has extensive myofiber disorientation. A retrospective study of 419 autopsies was undertaken to see if that diagnosis had been overlooked; but, in 100 autopsies with detailed photographic records of ventricular and septal size, ASH was not found. There were slight average increases in the posterior portions of the septum and right ventricle, and an average septal-left ventricular ratio of 1.1. Since neither staff pathologists nor consultants who reviewed entire hearts with cardiomyopathy noted features of ASH, we consider it to be a rare disease in elderly veterans.


Failure of ultralightweight knitted Dacron grafts in arterial reconstruction. We have observed 11 cases in which the use of the ultralightweight knitted Dacron arterial graft made by the United States Catheter and Instrument Co. (USCI) was complicated by Interstitial hemorrhage dilation, or both. Although the incidence and specific cause of failure of this graft are unknown, we have discontinued its use on the basis of this experience.


[Changes in the lymph nodes of rabbits following application of the breakdown products of fluoroplast]. Tracheobronchial, mesenterial and inguinal lymph nodes of 15 mature rabbits which were subjected to inhalation of valatile products of fluoroplast destruction were studied. The action of this drug for 1-40 days activated the reactive centers of follicles. The amount of blasts, plasmic cells, eosinophils, macrophages, lymphocytes increased in regional tracheobronchial and distant mesenterial lymph nodes. The prolonged action during 120 days resulted in decreased blasto- and lymphopoesis in the regional tracheobroncheal lymph nodes, depression of the reticular epithelium, suppression of the phagocytic and plasm cell reactions, decreased nucleic metabolism in the cells. Mesenterial lymph nodes retained their functions. The lymphopoesis in them and nucleic metabolism in the cells were intensified. The blastic, plasmic cell, eosinophilic and mast cell reactions were well pronounced.


[A method of isolating inhibitors of the proliferative activity of liver hepatocytes]. A fraction containing two tissue specific regulators of the mitotic activity (chalone) and having a definite capacity to inhibit the DNA synthesis (G1-inhibitor) and to enter into the mitosis (G2-inhibitor) of hepatocytes of the regenerating liver was isolated from an aqueous extract by ethanol saturation from 70 to 81%. The fraction contains up to 10 substances of protein nature, 7 of which, due to the data of immunological analysis, are also present in other tissues and blood serum of rats.


[Ultrastructural-cytochemical features of the plasma membrane of sodium-transporting cells]. Electron microscopic and biochemical studies of the ATP-ase activity in different regions of the nephron and in the kidney microsomal fraction of the rat have revealed a pronounced increase of the total and Na+-+K+-ATP-ase activity in the process of compensatory hypertrophy. A decrease of the enzymatic activity was noted predominantly in proximal tubules under loading the animals by isotonic NaCl solution and after adrenalectomy--mainly in distal tubules. This speaks of the inhibition of the sodium-reabsorbing system in them. The transport of isotonic fluid in collecting tubes is accompanied by widening intercellular lacunae together with an increase of the ATP-ase activity of the lateral plasmic membrane of neighbouring cells. The data obtained suggest a close correlation between the electron-microscopically revealed ATP-ase activity of the plasmic membrane of tubular cells and the functional activity of the sodium-transporting system. A morphological equivalent of the sodium pump is a plasmolemma--mitochondrial pump which is characterized by: a) well developed foldness of the basal plasmic membrane where the enzymatic system is disposed; b) the high total and Na++K+-ATP-ase activity cytochemically and biochemically revealed; c) numerous regularly disposed mitochondria, having close contacts with the folds of the basal plasmic membrane.


The corneal host-graft function. Physiopathology of the scar. The scar of penetrating homografts was studied in experimental grafts in rabbits and monkeys. The purpose of the study was to analyze the healing process in those grafts and correlate these findings to clinical situations of abnormal graft healing. Light, transmission and scanning electron microscopy were done for morphological studies. Radioautography with tritiated thymidine and S-35 sulfate was done to study cell repopulation and ground substance development in the scar. More than 50 p. 100 of cells present in the scar came from the host and lay down circular collagen fibers in the stroma and new Descemet's material at the endothelial level. Very tight (continuous) 10-0 nylon sutures produce necrosis of the edge of the wound and delay healing. From the morphological point of view it appears that very thin scars have less tensile strength than wider scars. These usually show circular and crisscrossing collagen fibers. Radial scars induced by silk sutures or through and through placed monofilament nylon add tensile strength to the wound.


Immunological comparison of normal, regenerating, and cultured corneal cells. Two types of corneal cell membrane receptors are described, one occurs on the surface of only regenerating or cultured cells, that is, actively metabolizing and/or proliferating ones. The other type of corneal membrane receptors occurs on the cell surface independent of the metabolic state, e.g. on excised resting cells. In contrast to the restricted ontogenic specificity of the metabolically dependent corneal cell membrane antigens, the metabolically independent cell surface antigens were found to be universally distributed across ontogenic or species barriers. Such metabolically independent corneal cell surface antigens include Forssman or blood group antigens. The immuno-cytotoxic reaction of corneal cells involving the metabolically independent cell surface antigens was enhanced by complement, whereas a similar immunocytotoxic reaction involving the metabolically dependent antigens was not.


Corneal cryo-preservation and its clinical application. Shortage of fresh corneal tissue for keratoplasty and expensive equipment needed for cryo-preservation has confined the field of corneal transplantation. The development of a simple medium for storage of corneal tissue which is inexpensive, which requires no technical assistance, and which provides the surgeon with excellent tissue would be very helpful. Forty-five of 55 human corneas stored for up to seven days in a simple tissue culture medium remained clear and thin after keratoplasty. Corneal deturgescence rates of tissue stored in this medium compared favorably with those rates for fresh and cryopreserved tissue.


[Exploration of the choriocapillaries by equidensity technic]. The author has studied the choriocapillaris using the equi-density technique on early fluorescein angiography pictures of normal human fundi. This new method of examination seems to prove that the circulation in the chorio-capillaris in man has a very particular form, similar to that demonstrated in the monkey.


[A case of leiomyoma of the iris].

[A case of leiomyoma of the iris]. A case of leiomyoma of the iris confirned to the nasal quadrant in a 64 year old man is presented. The clinical and histopathological characteristics of this observation confirms the classical data about this rare tumor : clinical silence, discovery through a complication, difficult diagnosis, therapeutical value of the surgical biopsy and good prognosis.


[Functional exploration of the perimacular and macular retinal region by means of flicker E.R.G. and the determination of perceptive fusion thresholds of an intermittent light (De Lange's curve)]. This study compares and verifies the efficiency of two functional tests based on intermittent light stimulation. One is the De Lange curve, the other flicker E.R.G. recorded in defined photopic conditions and analysed with different methods. The studied cases belong to a reference group and other groups including foveolar lesions, parifoveolar and diffuse retinopathy, ethambutol and quinoline derivative retinal intoxication. The results show that both objective and subjective methods are sensitive and show some parallelism : both methods aid in distinguishing between foveolar and perifoveolar involvements; a possible comparison between the two tests is also possible.


[Hypermetric refixation: objective sign of abnormal retinal correspondence]. In squinting patients with A.R.C. during the cover test, the keeping of fixation exhibits sometimes an hypermetric movement of the eye, which is accounted with a false localization of images.


[Regeneration of corneal endothelium in the rabbit: microscopic study and relation with corneal thickness]. The corneal cells are destroyed within a 10 mm diameter circular belt by liquid nitrogen application in vivo. The endothelial regeneration is followed from day to day using endothelial flat preparation technic, and is compared to the corneal thickness measurement and to the estimation of transparency. From the 5th day, Descemet's membrane is entirely covered by the regenerated endothelium; from this time, both thickness and transparency of the stroma become normal. Therefore, in spite of the persitence of morphologic abnormalities, the regenerating endothelial cells preserve or obtain again very rapidly their specific function of a barrier against hydration of the stroma.


The structure of keratan sulphates from various sources. Quantitative structural comparisons were made between keratan sulphates isolated from various sources, namely pig nucleus pulposus, bovine cornea, and the costal cartilages of children, a young adult with Marfan syndrome and of old human autopsies. In human costal cartilage the amount of keratan sulphate increases markedly with age, although total mucopolysaccharide decreases to some extent, concomitant with a decrease in chondroitin 4-sulphate and an increase in chondroitin 6-sulphate. Comparison of molecular weights estimated by gel chromatography with those calculated from the molar ratio of galactose to mannose indicates that keratan sulphates of human costal cartilages of children and of a young adult with Marfan syndrome, and of pig nucleus pulposus, contain one mannose residue per chain, whereas keratan sulphates of old human costal cartilage and of bovine cornea contain one to two, and two, per chain respectively. After mild acid-catalysed desulphation of pig nucleus pulposus keratan sulphate, approx. 12% of the mucopolysaccharide aggregates irreversibly once the water is removed from the polysaccharide. The following conclusions have been drawn from a methylation analysis of keratan sulphates of various sources, aided by g.l.c.-mass spectrometry. (1) Fucose and N-acetylneuraminic acid are non-reducing terminal residues and the sialic acid is linked to the 3-position of galactose residues. (2) Pig nucleus pulposus keratan sulphate has approximately 4 non-reducing terminal groups per molecule and appears to be slightly less branched than the costal-cartilage keratan sulphate of children. The branching in human costal-cartilage keratan sulphates decreases with age. Bovine corneal keratan sulphate appears to be unbranched. (3) Mannose residues are linked by 3 different substituents in human costal-cartilage and bovine corneal keratan sulphates, and by two different substituents in pig nucleus pulposus keratan sulphate. (4) The sulphate ester groups are all on the 6-position of N-acetyl-glucosamine and galactose residues. The degree of sulphation increases with age in costal keratan sulphates with the increase mainly of the galactose 6-sulphate residues.


Studies on the polydispersity and heterogeneity of cartilage proteoglycans. Identification of 3 proteoglycan structures in bovine nasal cartilage. 1. Three chondroitin sulphate components were isolated from adult bovine nasal cartilage after treatment with alkaline NaB3H. Average molecular weights of 13000, 18 600 and 28 000 were obtained for chondroitin sulphate species representing 10, 52 and 38% (w/w) of the total chondroitin sulphate respectively. Each chondroitin sulphate pool has a narrow molecular-weight distribution. 2. A proteoglycan subunit preparation, isolated from one nasal cartilage by extraction and density-gradient fractionation in dissociative solvents, partitioned on a CSCl density gradient according to size and composition. Variation of proteoglycan molecular weight across the gradient was directly related to the average chondrotin sulphate chain length, which in turn reflected the relative proportion of the three chondroitin sulphate pools in each proteoglycan fraction. Consideration of proteoglycan molecular parameters, compositions and behaviour on sedimentation leads to a proposal that nasal cartilage contains 3 distinct proteoglycan pools, each of which has a constant number of chondroitin sulphate side chains of different average molecular weight. 3. Molecular-weight distribution parameters for these proteoglycan preparations indicate that all serine residues on the protein core capable of initiating chondroitin sulphate biosynthesis are occupied and that proteoglycan polydispersity results directly from the polydispersity of the attached chondroitin sulphate component.


[On the multiple-dose kinetics of glibornuride in man (author's transl)]. The multiple-dose pharmacokinetics of 1-(2-endo-hydroxy-3-endo-bornyl)-3-(p-tolyl-sulfonyl)-urea (glibornuride, Glutril¿) was examined in 7 subjects with maturity-onset diabetes treated with the drug over a period of 4 weeks (25 mg every twelve hours). The steady-state levels of glibornuride (maximum and minimum concentrations) were determined experimentally and by calculation (using the pharmacokinetic parameters obtained following oral administration of 50 mg glibornuride on the 1st day of the treatment). There was good agreement between experimental and calculated values. The results afford evidence for the regular pharmacokinetic pattern of glibornuride. There was neither unexpected accumulation of the drug nor diminution of the steady-state levels as might occur as a consequence of induction of microsomal enzymes.


Therapeutic studies in NZB/W mice. IV. Effect of combination drug therapy on immune complex deposition. Azathioprine, cyclophosphamide, and methylprednisolone given individually to NZB/NZW mice retard the development of autoimmune nephritis and prolong survival in these mice. Administration of the combination of all three drugs is superior to one or two drug regimens. In the present study the kidneys of mice treated with all single, double, and triple drug regimens were compared for the degree of deposition of immunoglobulin and complement. The triple drug regimen significantly reduced overall deposition of immunoglobulin and complement compared with any other regimen. Complement and gamma2 were significantly reduced by triple drug therapy compared with any other regimen. The triple drug regimen reduced gamma1 compared with untreated and double drug treated mice. The single, double, and triple drug regimens significantly reduced gammaM deposition to about the same degree. Deposition of gammaA was not significantly reduced by any regimen. Circulating levels of these immunoglobulin classes were not reduced, a fact suggesting that the reduction in autoimmune nephritis resulting from triple drug therapy is associated with superior reduction in immune complex deposition rather than with generalized, non-specific immunodepression.


Cyclophosphamide protection in NZB/NZW disease. Mechanisms and therapeutic regimens. Regular administration of cyclophosphamide to NZB/NZW female mice effectively protects against the nephritis that is thought to be a model for human SLE nephritis. Reductions in serologic, histologic, and immunogluorescent parameters of the disease are correlated. Intermittent as well as continuous administration of the drug is effective without the development of leukopenia. Possible mechanisms of drug action and a modified approach to therapy of immune complex disease are discussed.


Separation, identification and mechanism of action of the granulocytic chalone. The preparation of highly purified granulocytic chalone from bone marrow conditioned medium is described. A sequence of gel-chromatographic steps on Sephadex G-25, G-15 and Biogel P-6 is applied. The end product has a sigmoid dose-response-curve with a plateau at 40-50% inhibition of thymidine incorporation. The inhibition is only observed with bone marrow cells as target cells whereas lymphoid cells are not affected. When bone marrow cells are treated for 1 min with 0.005% trypsin and subsequently used for assaying chalone activity in the presence of cycloheximide, no inhibition is found. These results may indicate that chalone specific receptor sites (of protein nature) are present on the surface of the target cells, which are destroyed by the trypsin treatment. Granulocytic chalone is soluble in aqueous solvents and in polar organic solvent mixtures. Its activity is destroyed by trypsin but only after prolonged treatment. The elution behaviour of chalone is discussed in detail. Chromatography on Sephadex G-75 and Ultrafiltration point to a molecular weight of several thousands, whereas chromatography on G-25 or G-15 or on Biogel P-6 would indicate a rather low molecular weight.


Modification of granulocytopoietic cell proliferation by granulocyte extracts. Saline extracts of mature granulocytes have been partially purified by an ultrafiltration technique. The fraction in the 500-2000 daltons molecular weight range was retained and tested in a variety of experimental systems. Comparable fractions of erythrocyte and lymphocyte extracts were used for control purposes. Measurement of the structuredness of the cytoplasmic matrix (SCM) of cells is shown to be a very sensitive measure of the effects of the extract. Specific and reversible increases in SCM of proliferating granulocytic cell populations indicate changes compatible with reduced proliferation and these are confirmed by autoradiographic observations following tritiated thymidine labelling. Repeated labelling experiments to obtain the rate of flow of cells through the cycle gave a mean cell cycle time of 15 hrs in the controls but in animals treated with the granulocyte extract this was increased to about 30 hrs. The duration of DNA synthesis was increased slightly but there was no effect on G2 as measured by the stathmokinetic index method. Cell production in developing spleen colonies was reduced by repeated doses of the extract over a period of 4 days. Approximately two cell doublings were lost during this period due to the prolonged cell cycle.


Biology of the granulocyte chalone.

Biology of the granulocyte chalone. Granulocyte chalone is a cell line-specific, species non-specific regulator substance, which inhibits cell proliferation in the granulocyte system in a reversible manner. The existence and specificity of action of this substance has been shown both in vitro and in vivo in widely different assay conditions and using a broad spectrum of assay techniques. Granulocyte chalone inhibits cell proliferation in the transit populations of the granulocyte system; it seems to act at the level of cell membrane and divert cells from the G1 phase to the "G0" phase with some direct or indirect effect on S phase cells as well. The substance is non-cytotoxic and it has no detectable effect on any other tissue than normal and leukaemic granulocytes even after long-lasting in vivo treatment. Granulocyte chalone offers an exciting potential for the treatment of myeloid leukaemia and, therefore, the substance is of more than academic interest.


Lymphocyte chalone concentrates and their effects upon leukemic cells in vitro. Lymphocyte chalone is a cell-specific but not species-specific noncytotoxic and endogenous inhibitor of the transformation and mitotic activity of normal lymphocytes stimulated in vitro by either lectins or antigens. However, human- and mouse-established lymphoblastic cell lines were killed and their uptake of thymidine was inhibited after incubation for almost one complete mitotic cell cycle. The chalone lymphocytotoxicity effect was also demonstrated, using primary cultures of EL-4 lymphoma cells. Lymphocyte chalone was highly cytotoxic to leukemic cells under crowded condition (cells in G1-G0) in contrast to S phase chemotherapeutic agents. Finally, thymus chalone lymphocytotoxicity appears to be specific for T versus B lymphoblastic cell lines.


In vitro production of lymphocyte and granulocyte proliferation inhibitors (chalones?) from living cells. Media conditioned with viable rat and calf spleen lymphocytes were seen to be able to inhibit 3H-thymidine uptake by rat thymocytes and the mitogenic response of human lymphocytes to PHA but not bone marrow cells proliferation. The inhibitor appeared to have a molecular weight greater than 50,000 daltons, as determined by Amicon Diaflo ultrafiltration. Media conditioned with rat granulocytes had a similar tissue specific but species non-specific inhibitory action. Also human leukemic cells appeared able to produce in vitro an inhibitor of cell proliferation when a certain degree of differentiation was present.


Further purification of the lymphocyte inhibiting extract from the thymus. A crude thymic extract, demonstrated to possess both immunosuppressive activity on T lymphocytes in vivo, and inhibitory action on DNA synthesis in T lymphocytes in vitro, has been purified by ultra-filtration and ion exchange chromatography procedures. The immunosuppressive activity was found to be associated with a high molecular weight fraction (greater than 50,000 daltons), devoid of immunosuppressive properties, a basic peptide has been isolated which retains the in vitro inhibitory activity on DNA synthesis.


[Aphrodisiac action of MAO inhibitors and of parachlorophenylalanine (PCPA) in sexual asthenias]. The sexual function in man can be modified decreasing brain serotonin by PCPA and increasing brain cathecolamines by monoamineoxidase inhibitors. In 5 volunteers, sexual deficient men, the combination of PCPA with phenelzine (IMAO) stressed an increase in sexual stimulation, measured by number of erections. In two subjects this effect lasted for 2 months. A clear improvement in mood has also been shown. This pharmacological combination opens new and interesting possibilities in sexual deficiency treatment.


Extradural analgesia in obstetrics: a controlled trial of carbonated lignocaine and bupivacaine hydrochloride with or without adrenaline. Four local anaesthetic solutions (2% carbonated lignocaine with or without adrenaline and 0.5% bupivacaine HCl with or without adrenaline) were used randomly for 335 continuous lumbar extradural blocks in labour. Carbonated lignocaine caused a more rapid onset of analgesia than bupivacaine HCl. The addition of adrenaline made little difference to the onset times, prolonged markedly the duration of analgesia with carbonated lignocaine and had little effect on the duration of analgesia with bupivacaine HCl. Tachyphylaxis was a feature with carbonated lignocaine and adrenaline, but not with the other solutions. The incidence of unblocked segments was 7-9% in the four groups. The incidence of unilateral analgesia was 6% with plain lignocaine and 13% in the other groups. Complete pain relief occurred more frequently with bupivacaine HCl than with carbonated lignocaine and the use of adrenaline had little effect on the degree of analgesia.


Effects on non-depolarizing neuromuscular blocking agents on peripheral autonomic mechanisms in cats. Intravenous dose-response relationships were used to correlate neuromuscular paralysis with effects on autonomic mechanisms in anaesthetized cats. Whereas autonomic blockade with tubocurarine occurred at parasympathetic and sympathetic ganglia, neuromuscular paralysing doses of gallamine, alcuronium, pancuronium and fazadinium caused blockade at vagal postganglionic sites in the heart. The vagolytic (atropinic) activity of these compounds in cats relative to their neuromuscular blocking activity appeared to correlate well with their known liability to cause undesirable hypertension and tachycardia in man. The absence of cardiovascular effects after the administration of neuromuscular blocking doses of dimethyl tubocurarine would support its more extensive clinical use, but the need remains for a short-acting muscle relaxant with properties similar to those of dimethyl tubocurarine.


Acquired pigmentation of skin folds with the histological picture of seborrhoeic wart. The case history is presented of a woman with acquired lesions in the axillary, submammary, intermammary, inguinal, genitocrural and perianal skin folds. These lesions were confluent pigmented macules, giving rise to extensive (en nappe) reticulate patches. History revealed changes typical of seborrhoeic wart. The name patchy (en nappe) seborrhoeic wart is suggested for this condition.


The lipid composition of sebaceous glands as a reflection of gland size. Following 4 h incubation in vitro, the patterns of incorporation of [I-14C] acetate into the lipid classes of human sebaceous glands which were dissected from small skin biopsies have been established for glands of different size. It has been shown that in the larger sebaceous glands proportionately more of the labelled acetate is incorporated into squalene at the expense of triglycerides. Experiments are presented as a result of which we conclude that this in vitro phenomenon, observed with [I-14C] acetate incorporation, does reflect parallel changes in the proportions of these lipids actually present in glands of different size. It is suggested that the larger sebaceous glands of the acne patient elaborate sebum which has an enhanced potential for inducing comedo formation by virtue of an increased concentration of squalene. This work also demonstrates that, in the interpretation of in vitro studies of sebaceous gland lipogenesis utilizing labelled precursors, the size of the sebaceous glands must be carefully considered whenever patterns of incorporation are being compared.


Necrotizing vasculitis: a circulating immune complex producing inflammatory skin lesions. A patient with acute necrotizing vasculitis is described in whom tests for circulating immune complexes were negative. The patient's serum injected intradermally produced lesions which closely resembled those occurring spontaneously. When the serum was fractionated, the skin-reactive fraction was found to be associated with IgG, but was of a higher molecular weight than normal IgG. Immunofluorescent studies showed that lesions induced by this active fraction contained IgG and complement in the epidermal basement membrane zone and within the small dermal vessels. We conclude that an immune complex of relatively low molecular weight is present in the active fractions, and capable of initiating the lesions of acute necrotizing vasculitis.


Skin surface lipid composition in rosacea. Skin surface lipid composition was measured in thirty-one patients with rosacea and their age-matched controls. Patients with rosacea had normal lipid composition, and there was no correlation between the lipid composition and the severity of the disease. Tetracycline therapy produced no measurable change in lipid composition.


Sebaceous lipogenesis in human skin. Variability with age and with severity of acne. Lipogenesis from [14C] glucose was measured in skin biopsies from the shoulder-blade region of forty-two male subjects. In the acne age range, dermal lipogenesis showed an upward trend with increasing severity of acne; a similar trend was found in forehead sebum excretion rate, but no correlation was obvious between dermal lipogenesis (back) and sebum secretion rate (forehead) in the same subject. In older subjects, dermal lipogenesis was significantly increased in those with a past history of severe acne. At high rates of dermal lipogenesis there was a small but significant increase in wax ester labelling relative to triglyceride and squalene. No increase was found in squalene labelling relative to other lipids, either with increasing lipogenic rate or in severe acne. Dermal and epidermal lipogenesis rates showed no correlation with age. In dermis, however, there was a decrease in wax ester labelling relative to triglyceride, and a marked decrease in squalene labelling relative to both triglyceride and wax esters, with increasing age.


Contact dermatitis from antioxidants.

Contact dermatitis from antioxidants. In a search for contact sensitivity to antioxidants we patch tested consecutive patients referred with eczematous dermatitis. Six cases of allergic contact sensitivity to nordihydroguairetic acid (NDGA) were observed. Three had been sensitized by one brand of cream containing 0.1% NDGA, in three patients the source of sensitization could not be traced. In four patients we found positive patch tests to butylated hydroxyanisole and/or to butylated hydroxytoluene. In two cases the positive patch tests were relevant, since both patients remained asymptomatic when antioxidants were avoided in food. They both had acute flares of vesicular eczema on the fingers after oral administration of small amounts. Gallate esters and Vitamin E (d,l-alpha-tocopherol) each gave one unexplained positive patch test. The present data suggest that further search for hidden sensitizers in topical medicaments and cosmetics is warranted. A declaration of all ingredients in industrial products should be placed on the label.


The unwanted effects of clindamycin in acne. A review of seventy matched acne patients on clindamycin and seventy-two on tetracycline shows that nine patients on clindamycin had diarrhoea whereas no patients on tetracycline had any side effect; no frank pseudomembranous colitis was seen. Although we heed the side effects of clindamycin, it should not be withheld from patients with severe and resistant acne.


Lipid molecular motion and enzyme activity in sarcoplasmic reticulum membrane. In biochemically active sarcoplasmic reticulum vesicles (SR) the physical state of the membrane lipids was studied by high angle x-ray diffraction and proton nuclear magnetic resonance (NMR) at 220 MHz, and related to thermal effects observed in SR functional parameters. It is shown by high angle x-ray diffraction that even at temperatures as low as 1 degree C nearly all the SR lipid hydrocarbon chains are in a disordered conformation and only a very small part (less than 3%) are in rigid crystalline order. Consistent with this observation, the NMR data indicate that the majority of SR phospholipid molecules are in a state of restricted anisotropic motion having no apparent crystalline order at temperatures as low as 5 degrees C. At this temperature most of the resonance signal is contained in a broad feature-less line of 700-Hz half-width. On the other hand, as the temperature is raised, high-resolution NMR signals, representing groups with highly isotropic motion, begin to grow in intensity. It is estimated that by 35 degrees C 90-100% of the phosphatidylcholine N-methyl protons and 35% of the hydrocarbon-chain protons give high-resolution signals. Concurrent studies on functional parameters reveal thermal effects giving rise to nonlinear Arrhenius plots for the rates of calcium transport and calcium activated ATPase. The thermal effects observed on functional parameters and on the character of phospholipid molecular motion exhibit a parallel behavior, suggesting a relationship between enzyme activity and the physical state of the membrane lipids.


Specificity of thrombin: evidence for selectivity in acylation rather than binding for p-nitrophenyl alpha-amino-p-toluate. The lysyl ester analogue p-nitrophenyl alpha-amino-p-toluate hydrobromide was synthesized, and its reactions with thrombin, trypsin, and plasmin were studied by stopped-flow and conventional methods. Kinetic parameters were compared with those determined for the arginyl ester analogue, p-nitrophenyl p-guanidinobenzoate hydrochloride, with these enzymes. By following nitrophenol release or proflavin absorption changes in the stopped-flow spectrophotometer, the constants Ks (enzyme-substrate binding), k2 (acylation), and k3 (deacylation) were determined. The major findings were: (1) Ks values were similar regardless of the substrate or the enzyme; (2) k3 was approximately the same for the reaction of the lysyl ester analogue with any enzyme; (3) k2 for the lysyl ester analogue was 1100 times greater with trypsin than with thrombin; and (4) k2 with thrombin was 60 times greater for the arginyl than for the lysyl ester analogue. The results suggest that the limited cleavage of lysyl bonds by thrombin is due in part to restricted acylation rather than substrate binding. The active site of thrombin, compared with that of trypsin, appears to have a more stringent requirement for the spatial relationship between the cationic group and the bond cleaved in substrates.


Interaction of a new fluorescent reagent with sulfhydryl groups of the (Na+ + K+)-stimulate ATPase. The (Na+ + K+)-ATPase enzyme of rat brain microsomes can be reversibly inhibited by a new fluorescent sulfhydryl (SH) probe, dimethylaminoaphthalenecysteine-Hg+ (Dn-cys-Hg+). This reagent is more reactive than N-ethylamaleimide (MalNEt) toward membrane sulfhydryl groups. A procedure using the two SH reagents sequentially seems to permit a more selective labelling of the SH groups involved in the (Na+ + K+)-ATPase than is possible by using MalNEt alone. Brain microsomes treated by this method incorporate the fluorescent label within or near the active site of the enzyme. When the probe was bound a blue shift of its fluorescence emission maximum (from 540 to 495 nm) and a 20-fold increase in relative fluorescence occurred. This indicates that the Dn moiety is within a very non-polar region of the membrane.


Changes in some marker enzyme activities of liver plasma membranes during regeneration after partial hepatectomy in rats. Liver plasma membranes were isolated from regenerating rat livers between 20 h and 10 days after partial hepatectomy in order to study the effect of partial hepatectomy on some membrane enzyme activities. Mg2+-ATPase (EC 3.6.1.4) activity, but not (Na+ + K+)-ATPase activity, decreased slightly at 2 days, whereas leucyl beta-naphthylamidase (EC3.4.1.1) and 5'-nucleotidase (EC3.1.3.5) activities increased considerably at 1-2 and 3-5 days, respectively. These changes were not parallel to a sharp increase in mitotic activity of liver cells which occurred at 36 h.


[The state of the "glycocalyx" of rat lung cells following left-sided pneumonectomy]. Edema in the tissue of the right lung developed 24 hours after the leftsided pneumonectomy. It was found that: 1) the layer of acid mucopolysaccharide on the surface of the alveolar and endothelial cells became thicker; 2) accumulation of the product of reaction with the RR on the surface of the alveolar cells of type 1 and of the endothelial cells took place; 3) "blisters" coated with the product of reaction with the RR (Red Ruthenium) appeared. These "blisters" were connected with the plasmolemma of the alveolar and endothelial cells. All these findings suggest that acid mucopolysaccharides of the lung surfactant system participated in the accumulation and elimination of the water from the tissues of the air-blood barrier.


[Dynamics of changes in the cerebral and erythrocyte ATPase activity of rats with hypoxic hypoxia]. A long-term (for 3 hours) hypoxic hypoxia was accompanied in rats by wave changes of the brain tissue Na++K+-ATPase activity. This activity decreased after a 15-minute exposure; it increased after 2 hours and fell again after a 3-hour hypoxia (decompensation period). The membrane transport enzymes of erythrocytes proved to be more resistant to hypoxia than the brain cell enzymes.


Explanation for the apparent lack of ouabain inhibition of pyruvate production in hemolysates: the "backward" PGK reaction. The concept that ouabain-sensitive membrane (Na+ + K+)-ATPase-generated adenosine diphosphate (ADP) preferentially serves as the substrate for the phosphoglycerate kinase (PGK) step of erythrocyte glycolysis has been reexamined. Membrane ATPase readily provides ADP for and utilizes ATP generated in the pyruvate kinase (PK) step and is ouabain sensitive. Earlier reports in the literature, which have suggested that in hemolysates the ATPase reaction facilitating the PK reaction is ouabain-insensitive, are reinterpreted: in crude hemolysates ADP generated in the "backward" PGK reaction can account for these data. We conclude that there is no convincing evidence of selective linkage of (Na+ + K+)-ATPase with the PGK reaction.


Effects of anticonvulsant and convulsant drugs on the ATPase activities of synaptosomes and their components. 1. The effects of anticonvulsants, and other drugs on the Na+, K+-adenosine triphosphatase (ATPase) (ouabain-sensitive) and Mg++-ATPase activities of synaptosomes and their components have been determined. 2. The Mg++-ATPase activity of synaptosomes was not affected by the drugs but the Na+, K+-ATPase activity was inhibited by phenytoin (diphenylhydantoin), ethosuximide and diazepam. 3. Fractions containing mainly membranes, mitochondria or synaptic vesicles, were prepared from synaptosomes by osmotic shock and subsequent density gradient centrifugation. Inhibition of Na+, K+-ATPase activity by phenytoin, ethosuximide and diazepam was apparent only in the membrane fraction. 4. The fraction containing synaptic vesicles exhibited pronounced Md++-ATPase but no Na+, K+-ATPase activity. In contrast to the enzymes of the membranes and mitochondria, the Mg++-ATPase of the vesicles was inhibited by diazepam and all of the anticonvulsants tested.


Prolonged effects of p-chlorophenylalanine on the blood pressure of conscious normotensive and DOCA/saline hypertensive rats. 1. In deoxycorticosterone acetate (DOCA) saline hypertensive rats a single dose of p-chlorophenylalanine methylester (PCPAME) (400 mg/kg i.p.) produced a significant fall in blood pressure (20-43 mmHg) which lasted for at least 8 days and was accompanied by a parallel depletion of brain stem 5-hydroxytryptamine (5-ht) but not of noradrenaline (NA). 2. In normotensive rats single doses of PCPAME (200 and 400 mg/kg i.p.) produced a significant hypotension (15-20 mmHg) after a latent period of 5 days. An initial pressor response (12 mmHg) was observed at the higher dose level only on day 3. 3. The hypotensive response to PCPAME (200 mg/kg i.p.) in normotensive rats was not modified by pretreatment with 5,6-dihydroxytryptamine (5,6-DHT; 50 mug i.c.v.) or 6-hydroxydopa (6-ohda; 3 X 250 mug intracerebroventricularly). 4. It is concluded that the hypotensive response to PCPAME in normotensive rats in independent of brain stem depletion of 5-HT and is probably not mediated by the formation of a false transmitter substance acting via central noradrenergic inhibitory pathways. The mechanism involved in the antihypertensive response to PCPAME in DOVA/saline hypertensive rats has yet to be defined.


Effects of drugs acting on cerebral 5-hydroxytryptamine mechanisms on dopamine-dependent turning behaviour in mice. 1. The effects of drugs acting on cerebral 5-hydroxytryptaminergic mechanisms on drug-induced turning behaviour in mice with unilateral destruction of nigro-striatal dopaminergic nerve terminals have been studied. 2. Administration of L-tryptophan (400 mg/kg) or 5-hydroxytryptophan (200 mg/kg) increased brain 5-hydroxytryptamine and decreased the turning induced by both apomorphine (2 mg/kg) and amphetamine (5 mg/kg). 3. Parachlorophenylalanine (3 X 500 mg/kg) decreased brain 5-hydroxytryptamine and increased both apomorphine and amphetamine-induced circling behaviour. 4. Varying the protein content of dietary intake significantly altered brain 5-hydroxytryptamine and tryptophan levels, spontaneous locomotor activity and amphetamine-induced circling behaviour in these mice. 5. Systemic administration of methysergide (0.5-4 mg/kg), lysergic acid diethylamide (0.025-0.2 mg/kg), cyproheptadine (2.5-20 mg/kg) or clomipramine (0.6-20 mg/kg) produced no consistent effect on drug-induced turning behaviour. 6. The results suggest that circling behaviour due to striatal dopamine receptor stimulation is depressed by an elevation of brain 5-hydroxytryptamine and enhanced by a reduction in brain 5-hydroxytryptamine. 7. The possible physiological relationship between dopamine and 5-hydroxytryptamine neurones in the basal ganglia is discussed.


Some pharmacological effects of p-chlorophenylalanine unrelated to tryptophan hydroxylase inhibition. 1 Experiments were performed on a variety of tissues from different species to establish whether or not the properties of p-chlorophenylalanine methyl ester (PCPA) included a 5-hydroxytryptamine (5-HT)-like action which might explain the soporific action of PCPA in chicks. 2 PCPA, like 5-HT, contracted the rat fundal preparation (as did PCPA base), and in cats enhanced twitch tension of a lower limb flexor reflex, evoked adrenal medullary secretion and attenuated histamine-induced gastric secretion; the effects on the rat fundal strip and the adrenal medulla were prevented by methysergide. 3 Like 5-HT, PCPA elicited bronchoconstriction of guinea-pig lungs, isolated or in vivo; this was not prevented by methysergide but reduced by polyphloretin and by indomethacin. Perfusate collected from the lungs during PCPA-induced bronchoconstriction and applied to superfused isolated tissues contained a substance with prostaglandin-like activity. 4 In contrast, the effect of PCPA on the guinea-pig isolated ileum differed from that of 5-HT, since it relaxed the ileum when contracted by transmural excitation, by acetylcholine, histamine of 5-HT and contracted the ileum on wash-out.


Depression in patients with Parkinsonism. Forty-five patients with parkinsonism were carefully matched for age and sex with 45 chronically disabled control patients with a significantly more severe grade of physical handicap. Depression was measured by the Hamilton Rating Scale, and it was found that the parkinsonian group was very significantly more depressed than the control group (p less than 0-0001). Depression scores in both groups were unaffected by the patients's sex or by the severity of the disability. Analysis of the individual ratings of the Hamilton Scale showed that parkinsonian patients had significantly higher scores on items relating to suicide, work and interests, retardation, psychic anxiety, general somatic symptoms, and loss of insight. It was concluded that patients with parkinsonism suffer a degree of depression which cannot be solely a reaction to the stress of physical disability. This finding is discussed with reference to the monoamine hypothesis of depressive illness.


A biochemical study of short-cycle manic-depressive psychosis in mental defectives. Four mentally defective patients who were suffering from short-cycle manic-depressive psychosis were each studied under metabolic ward conditions for about six months. Weekly estimations of erythrocyte Na-K ATPase activity, ouabain sensitive potassium influx, sodium concentration, whole blood cell ATP concentration and blood haematocrit were made. The findings in each patient differed, but the erythrocyte Na-K ATPase activity, sodium and ATP concentration appeared to show cyclic changes related to, though out of phase with, the clinical state.


Group B streptococci in venereal disease clinic patients. The isolation rates of group B streptococci for 457 men and 300 women attending a venereal disease clinic were 16-4 and 20-6% respectively. The frequencies were significantly increased by using a selective medium and by taking specimens from the female urethra as well as the cervix. In contrast to gonorrhoea the presence of group B streptococci could not be related to promiscuity. In addition, the isolation of group B streptococci was found to be independent of a concomitant gonococcal infection. This study indicates that group B streptococci have little relation to the clinical signs and symptoms of genital infection, such as dysuria, discharge and inflammatory mucosal reaction.


The functional role of the muscle spindles--facts and hypotheses. A review is given of recent work on the functional role of muscle spindles in the control of movement. The fusimotor neurons (gamma motoneurons) maintain the spindles in a state of responsiveness to length and to rate of change of length of muscle. Centrifugal control of muscle spindles takes two forms: first, a steady or slowly fluctuating tonic firing of fusimotor neurons, as a part of general states of arousal or readiness-to-move, independent of the firing of skeletomotor neurons (alpha motoneurons), and not related in time to specific movements; secondly, a precise coactivation of skeletomotor and fusimotor neurons (alpha-gamma linkage) which is related to the time-course of specific movements. Both types are likely to be important in man. Recent work on the connexions at the segmental level between spindle inputs, descending pathways, interneurons, gamma motoneurons and alpha motoneurons is reviewed and discussed, with special attention to work on man. These segmental circuits, rather than their individual components, are the units which are operated by reflexes and by central programmes for movemenst.


Responses of snake muscle spindles to mechanical and electrical stimulation. Responses of the sensory ending of snake muscle spindle to mechanical and electrical stimulation were examined. In the short-capsule spindle the dynamic index increases more rapidly with increase in initial muscle length. The threshold muscle length for initiating a long sustained discharge from the short-capsule spindle is significantly higher than that for the long-capsule spindle while the position sensitivity is similar in the two types of spindle. The relation between rate of discharge of the ending and current applied to the impulse initiating site was found to be similar in both types of spindle.


[Radiobiological studies on the behavior of normal and tumorous plant tissues cultivated in vitro]. Vegetable tumoral tissue are more radiosensitive than the homologous normal tissue. Tumoral tissue are more stimulated by yeast extract and yeast s-ARN than normal tissue. Yeast extracts and s-RNA extracts from yeast also restore more the growth of tumorous tissue than normal tissue, which were subjected to gamma radiation from 60Co. A mixture of mononucleotides obtained from fractionated s-RNA has the same stimulatory effect. It is suggested that the active principle from yeast and s-RNA is a cytokinin like substance, which have been detected in yeast extract and in soluble ribonucleic acid from yeast.


[Nucleic acids during tumorous transformation in plants]. Crown-gall, one of the "plant cancer" is induced in the presence of a soil bacterium Agrobacterium tumefaciens which elaborates a Tumor inducing principle (T.I.P.), the nature of which is unknown. Several informations suggest that some DNA sequences of bacterial origin are included in tumorous cells of tissue cultures. A ribonuclease inhibits induction. An RNA extracted from Agrobacterium induces some hyperplasia transplantable by graft.


[Process of cecidogenesis].

[Process of cecidogenesis]. Among mechanisms of cecidogenesis, an initiation by a mechanical action of the insect can be observed. More generally, a chemico-induction produced by material buccal spittle, at the laying, on by excrements is at the origin of these mechanisms. The active factor could be vegetal substances with hormonal effect on enzymatic systems resulting of metabolism. The classical cancers of animals resulting from a multiplication of daughter cells genetically differentiated and totally different from zoocecidies formed neighbour cells exposed to an exceptional morphogene field.


[Tumorous nature of hyperplasia obtained experimentally]. The determination of the tumorous nature of an overgrowth provides one of the most essential information for all research concerning animal and plant cancerisation. The experimental procedure which will be described here answers to this imperative: it allows to prove the tumorous characteristics of proliferations obtained by inoculation of Agrobacterium tumefaciens RNA fractions to Datura stems.


[Tumor formations and cell proliferation in invertebrates]. Critical analysis of the present status of invertebrate oncology through an appreciation of data relative to the various origins of tumors : spontaneous formations, cell proliferations induced by viruses, so-called hereditary tumors, effects of injuries induced by carcinogenic agents, irradiations or hormones on the formation of neoplasms in invertebrates. Attempts are made to interpret these data as compared with those obtained in medical and veterinary oncology. The possible direction of studies on invertebrates towards comparative oncology is considered, emphasizing the great usefulness for the medical research to study the phylogenetic development of oncogenesis.


[Tumors in insects].

[Tumors in insects]. The spontaneous tumors in insects are the result of an aggregation of hemocytes. The tumors appearing in Locusta migratoria and Leucophaea after severing the gastric nerves originate from abnormal proliferation of the epithelial cells, particularly in the regenerative nidi in the midgut wall. These tumors can be transmitted by an injection of hemolymph from tumorous animals, of crushed tumor homogenates and cell-free extracts and of ribonucleic acid extracted from tumorous organs.


[Hereditary melanotic tumors of Drosophila. Determination of the tumorous transformation of larva hemocytes]. Two different phenomena contribute to the histogenesis of melanotic formations in tumoral strains of drosophila : an abnormal multiplication of certain blood cells and their encapsulation by normal hemocytes. The statistical distribution of melanotic tumors in populations of individuals submitted during precise periods of their life to the action of agents such as supraoptimal temperature or ionizing radiations, permits to suggest for the tumoral transformation of larval hemocytes in drosophila, the following mechanism : this transformation is caused by an event occuring in the cytoplasm and determined by the activity of a nuclear gene.


[Study of the dependancy of an ovarian portal graft in the rat on gonadotropins for durations of 1-to-6 months]. Gonadotrophins influence in ovarian portal graft growth is studied. Grafts are made or in immature female rats and let to growth for one month, either in adult female rats and let to growth for six months. FSH and LH production is stopped with methallibure. In the two cases the graft, tumourous or not, is under the gonadotrophins dependancy, but others, gonadal or hypophysal, factors have a part in its growth.


[Study of the distribution of haptoglobin groups in Marseilles, in normal and in cancer subjects]. Authors have studied 758 sera from normal subjects in Marseille area. The genotype frequencie Hp 1 is 0,39, similar that of France in general. The phenotype repartition is 16% for Hp 1-1, 45% for Hp 2-1 and 39% for Hp 2-2. People with carcinoma have shown a increase of the frequencie of the phenotype Hp 2-2 and a decrease of the frequencie of genotype Hp 1, mostly in lung carcinoma (Hp 1 = 0,29) and in carcinoma of digestive track (Hp 1 = 0,19). However, a control group, which is constituted by people hospitalized in the Anti-Cancerous Center, has a Hp 1 frequencie of 0,29 a well as lung carcinoma, no explication was found.


Some characteristics of neuromuscular block in the respiratory musculature in anaesthetized man. The ability to breathe against a mild expiratory obstruction was examined in 64 adult patients under halothane-nitrous oxide-oxygen anaesthesia. The trachea of all patients were incubated. It was found that d-tubocurarine 0.11 mg/kg blocked the respiratory musculature by 50 per cent. The onset of block was immediate, with the peak effect reached within one minute. The duration of block was either very short (1 to 2 minutes) or long (paralleling the blockade in the thumb twitch), depending upon the dose of d-tubocurarine. Following injection of a small dose (up to 0.1 mg/kg) the respiratory musculature might be blocked by 30 per cent but for only one minute, disproportionately short as compared with the thumb twitch. Following injection of a large dose (0.1-0.3 mg/kg) the duration was long, but the recovery was only slightly ahead of the thumb. Following an intermediate dose, a biaphasic pattern was observed. An initial partial recovery was observed during the first 1 to 2 minutes. Comparison of the respiratory musculature and the thumb twitch revealed that the respiratory musculature was highly sensitive to block and has a different time course. Succinylcholine 0.08 mg/kg blocked the respiratory force by 50 per cent with a time course similar to the block in the thumb twitch. The clinical significance of these observations are discussed.


The effects of substrate concentration on the Mg-adenosine triphosphatase activity of myosin. Using myosin, heavy meromyosin, and subfragment-1 the steady state rate of Mg-modified adenosine triphosphatase (Mg-ATPase) was determined over a range of substrate concentrations between 10(-8) M and 5 X 10(-3)M, at 0.5 M and 0.05 M KC1 (pH 7.4 at 20 degrees C). At the substrate concentrations below 10(-5) M, myosin Mg-ATPase was observed to show that two active sites interact, as suggested by the analysis of transient kinetic studies (Walz, F. G., Jr.: J. Theor. Biol. 41, 357-373 (1973)). The increase in the activity at Mg-ATP concentrations higher than 10(-4) M corresponds to the binding of Mg-ATP to myosin sites not responsible for the catalytic action. With heavy meromyosin and subfragment-1, the activity was best expressed by the Michaelis equation. With heavy meromyonsin, the activation at high ATP concentrations is detectable, though not as pronounced as with myosin, but not with subfragment-1.


A high molecular weight dihydro-orotate dehydrogenase of Neurospora crassa. Purification and properties of the enzyme. Some of the unusual molecular and catalytic properties of a high molecular weight dihydro-orotate dehydrogenase (DHOD) from Neurospora crassa have been determined. Comparison of the properties of this enzyme with the properties of the soluble biosynthetic enzyme of prokaryotes has revealed several important differences. The fungal enzyme is located in a mitochondrial membrane in a position consistent with linkage with the respiratory chain through ubiquinone (Miller, R. W.: Arch. Biochem, Biophys. 146, 256-270 (1971)). Release of the enzyme from the membrane results in a solubilized protein complex containing bound lipids and inactive hydrophobic proteins. Non-specific protein aggregation is minimized during purification by Triton-X-100 and phospholipase treatments. The catalytically active enzyme has an apparent molecular weight of 210 000. In contrast to soluble DHOD preparations the high molecular weight enzyme has no endogenous dihydro-orotate oxidase (EC 1.3.3.1) activity and is relatively insensitive to inactivation by sulfhydryl-reactive reagents in the presence of dihydro-orotate (DHO). The enzyme activity is highly sensitive to conditions causing oxidation of flavin mononucleotide (FMN). The activity cannot be restored by cysteine or other means. FMN is present in all purified preparations in a bound, non-fluorescent (reduced) form until dihydro-orotic acid is removed or oxidized. Catalytic efficiency of the purified enzyme was 12 000 mol DHO oxidized per minute per mole FMN. This high turnover rate is due in part to the small flavin content of the purified enzyme, equivalent to 1 mol FMN per 120 000 g of catalytically active protein. Iron was detected in the purified enzyme by atomic absorption spectroscopy but labile sulfide was absent. Thenoyltrifluoroacetone, an iron chelator, only partially inhibited DHO oxidation regardless of electron acceptor. Fatty acids interact with a hydrophobic site of the enzyme in non-competitive fashion but under certain conditions appear to significantly alter the Km for ubiquinone. Orotate, by comparison, is a purely competitive inhibitor. Both types of inhibitor may function to regulate the biosynthesis of orotate in vivo. Superoxide anion is not produced in significant quantities by the DHO-reduced enzyme unless both ubiquinone and a suitable single electron carrier such as phenazine methosulfate are present. DHOD has been proposed as a source of superoxide anion in mammalian mitochondria (Forman, H. J. & Kennedy, J. A.: J. Biol. Chem. 250, 4322-4326 (1975)).


Vitamin A induced benign intracranial hypertension. A case of benign intracranial hypertension due to prolonged administration of a low dose of Vitamin A is described in a young male investigated as a brain tumor suspect. Computerized axial tomography showed small and symmetrical lateral ventricles which was consistent with the diagnosis. The syndrome of benign intracranial hypertension and its relationship to chronic Vitamin A toxicity is discussed.


Clinical echocardiography - an overview. Echocardiography is a new diagnostic technique for noninvasive assessment of the size, structure and function of the heart, using pulsed ultrasound. The physical principles underlying the generation of the ultrasonic signal for diagnostic use and the three modes (A, B and M) of displaying the reflected "echo" signal are briefly discussed. A full echographic study of the heart includes evaluation of the dimensions and patterns of movement of its various structures and chambers. The normal anatomic relations and echographic appearances of these structures and the changes they undergo in some of the more commonly recognized clinical conditions are described. Assessment of output and contractile behaviour of the left ventricle and recognition of various congenital heart defects are two of the more recent applications of this technique. Two-dimensional sector and multiscanning devices permit several areas of the heart to be visualized simultaneously in "real time".


T and B cells and cell-mediated immunity in mycosis fungoides. T anb B cells in peripheral blood were evaluated in 13 patients with mycosis fungoides (MF) and in two patients with Sézary's syndrome. T cells were identified by their capacity to bind sheep red blood cells to their surfaces and the B cells were identified by the presence of surface immunoglobulins in immunofluorescence assay. Seven patients with MF and two with Sézary's syndrome were shown to have T-cell values below normal and elevated levels of null cells, i.e., cells with markers for neither T nor B cells. Low T-cell values and elevated Null-cell values were found predominantly in patients with advanced mycosis fungoides (stages III-IV). Furthermore, these patients had impaired cell-mediated immunity, as shown by in vivo skin testing with recall antigens and attempts at sensitization to dinitrochlorobenzene.


Pulse cytophotometric analysis of synchronized cells in vitro. Pulse cytophotometry is a reliable rapid technique rendering a detailed direct analysis of the distribution of cells in G1/10, S, and (G2 + M) phase. We used a Phywe pulse cytophotometer ICP 11 to monitor cell cycle progression of synchronized human lymphoma cells in culture. With mithramycin as the fluorescent dye, sample processing is fast and provides DNA histograms of high resolution and precision. Results obtained from these histograms are in excellent agreement with those obtained by conventional techniques. Thus, we have established the conditions necessary to apply pulse cytophotometry for studies of drug-induced cytokinetic effects on this cell line.


Augmented right ventricular function in systemic hypertension-induced hypertrophy. The contractile properties of right ventricular papillary muscles from the hearts of 15 rats which had developed hypertension 6 weeks following renal artery ligation were compared with those from 14 normal litter-mates. In the experimental group, the heart weight-body weight ratio was increased by 39%, while the right ventricular weight-body weight ratio increased 20%. Right ventricular papillary muscles from the hypertensive rats demonstrated increased tension development at the apex of the length-active tension curve (P less than 0 X 0001), elevated maximal rate of tension development (P less than 0 X 001), and increased maximal velocity of contraction at muscle lengths corresponding to both a light preload and at Lmax (P less than 0 X 05). Resting tension and time-to-peak tension in the muscles from the hypertensive group were not significantly different from the normal group. Thus, improved right ventricular performance, in the presence of increased left ventricular afterload, may indicate the existence of a stimulus to increased function in hypertrophied muscle not yet negated by the adverse effects of direct exposure to stress.


Biochemical and morphological correlates of cardiac ischaemia: Contractile proteins. Experimentally-induced ischaemia in the dog heart was produced by ligating the left circumflex artery. Myosin B isolated from the ischaemic portion of the myocardium differed from myosin B isolated from control tissue in its diminished response to the calcium chelator ethyleneglycol bis (beta-amino-ethylether)-N, N'-tetraacetic acid (EGTA). In the presence of EGTA, ischaemic myosin B required 2.5 +/- 0.5 min for completion of superprecipitation, whereas control myosin B required 6.6 +/- 2.5 min. Likewise, the Mg++ -activated ATPase activity of ischaemic myosin B was inhibited by EGTA to a lesser degree than control myosin B. Experiments with reconstituted myosin B using desensitized control myosin B and regulatory proteins suggest that ischaemia induces changes in the regulatory proteins (troponin and tropomyosin).


Effect of intramyocardial pressure on the phasic flow in the intraventricular septal artery. Phasic flow in the intraventricular septal artery (SA) was measured by an electromagnetic flowmeter in anaesthetized dogs. The ratio of systolic to diastolic flow was less in the intramyocardial artery than in an epicardial (circumflex) artery. The SA systolic to diastolic ratio was further depressed when elevations in intramyocardial pressure were produced. These studies lend insight into the relationships between intramyocardial pressure and coronary arterial flow.


Fine structure of the avian muscle spindle capsule. The capsule of the muscle spindle from the anterior and posterior latissimus dorsi muscles of the adult domestic chicken has been studied with the electron microscope. As in other species, two distinct portions of the spindle capsule are distinguished: an outer capsule and an inner capsule. The outer capsule is structurally similar to and continuous with the perineural epithelium. Outer capsule cells are noted by the abundance of pinocytotic vesicles and a network of 6-7-nm microfilaments. The disposition of these microfilaments is circumferential with respect to the longitudinal axis of the spindle. It is proposed that they may provide a contractile mechanism for the capsule which may be related to the over-all functioning of the spindle during movements of the muscle. The inner capsule is composed of a contiguous network of cells possessing long cytoplasmic processes which envelop the intrafusal fibers and their nerve endings in sensory equatorial regions of the spindle. These cells may elaborate the fibrillar and amorphous extracellular material found in periaxial spindle space. They also possess modified cilia with a "9+0" microtubular pattern. It is suggested that these cilia may behave as sensory transducers, relating fluid changes in the periaxial space to the intrafusal fiber nerve endings. Capillaries of the non-fenestrated variety commonly traverse the outer and inner portions of the capsule and are usually completely surrounded by tenuous overlapping processes of inner capsule cells. These findings suggest that the spindle capsule plays a role as a metabolically-active diffusion barrier to the entrance of substances from the external milieu.


Determinants of left ventricular hypertrophy and oxygen supply in chronic aortic valve disease. Ventricular mass and O2 supply of the myocardium were evaluated in patients with left ventricular hypertrophy due to stenosis or insufficiency of the aortic valve and in control patients without cardiac disease. Calculation of left ventricular mass from the angiogram was verified by autopsy data in seven patients. Total mass, O2 consumption, and coronary blood flow, each was related quantitatively to left ventricular total load (force) in all patients. Left ventricular equatorial tension, however, was greater in proportion to mass in aortic stenosis than in aortic insufficiency patients. This discrepancy could be explained by the more eccentric shape of the left ventricle in aortic stenosis. Oxygen consumption and coronary blood flow per gram of myocardium were normal at rest in patients with hypertrophy. Tachycardia induced by atrial pacing provoked myocardial lactate production in half of the patients with aortic stenosis but in none of the patients with aortic insufficiency. Surgical mortality was related to myocardial mass and lactate production.


Improved method for measuring fibrinogen in plasma, with use of a plasmin inhibitor. We describe a modified procedure for quantitating plasma fibrinogen by use of the thrombin-clottable protein technique. The method is accurate and requires a0out 30 min to complete. During its formation and isolation, the clot is protected from the degradative action of plasmin by an inhibitor, epsilon-aminocaproic acid.


The facet syndrome.

The facet syndrome. Injection of irritant fluid precisely into the facet joint causes referred pain patterns indistinguishable from the pain complaints frequently associated with the "disk syndrome." Even straight leg raising and diminished reflex signs can be obliterated by precise local anesthetic injection into the facet joint. The use of radiographically localized injection of steroids and local anesthetic into the facet joint has been presented as a diagnostic-therapeutic procedure. Clinical experience with a group of 100 consecutive patients suggests that this treatment alone can achieve long-term relief in one-fifth of the patients with lumbago and sciatica and partial relief in another one-third of these patients. This information suggests that the structures related to the facet joint can be a persistent contributor to the chronic pain complaints of individuals with low back and leg pain.


Facet denervation in the management of back and sciatic pain. Back pain, with or without sciatic radiation, may come from a number of anatomical sites. Radiofrequency facet denervation suggests that a majority of patients seem to have pain referred from distress of the facet joints or the sacro-iliac joints. In those patients who are properly selected and have not had previous surgical treatment, radiofrequency denervation of the appropriate facet joints yields partial to total relief of pain in 82% of cases. The technique for doing this procedure and for selection of patients must be followed very closely but in over 800 patients surveyeyed for this report no neurologic complications have been reported. Facet denervation, when indicated, is proposed as a safe alternative to either chemonucleolysis or surgery.


Morphology and function of the dog ileum after mechanical occlusion. 1. Complete mechanical occlusion of the ileum was produced in dogs and the loops above and below the obstruction were examined functionally and morphologically 4 or 7 days later. 2. The intraluminal pressure in the occluded loop never exceeded 8 cm water. 3. The mucosa above the obstruction secreted water and ions into the lumen in vivo, though it absorbed glucose normally. Mucosal slices also absorbed amino acids and monosaccharides normally in vitro. 4. The mucosa below the obstruction absorbed ions and glucose in vivo and non-electrolytes in vitro to a slightly smaller extent than normal intestine. 5. The morphological changes above the occlusion included shorter, plumper villi and shorter crypts, a reduction in histochemically stainable brush-border enzymes, but an increase in acid phosphatase. Below the obstruction, there was atrophy of the villi and crypts and reductions in all enzymes studied. 6. The results suggest that the mucosa above the occlusion possesses an intact and almost normal epithelial layer, but that it has been stimulated to secrete in vivo, presumably by intraluminal factors. Below the obstruction, true atrophy of the mucosa has promptly developed.


Clinical features of lumbar spinal stenosis. In contrast with patients with herniations of the nucleus pulposus, those with spinal stenosis experience onset of symptoms at a slightly older age; more males are affected than females. The symptoms tend to be somewhat more chronic, and therefore, the patients will have symptoms of back pain for a longer period of time before developing radiating root pains and will not come to surgical treatment until relatively late. Bilateral root symptomatology is more common although examination shows multiple nerve root involvement only slightly more frequently as well as involvement of the L1 to L4 nerve roots. The spinal movements tend to be somewhat better and straight leg raising tests are usually symmetrical and somewhat less restricted in those patients than in the acute disk syndrome. Postfusion and post-chemonucleolysis spinal stenosis will, of course, have the symptomatology of the initial problem, but their recurrent problems would tend to parallel those of spinal stenosis rather than disk herniation.


Type III collagen: A major constituent of rheumatoid and normal human synovial membrane. The findings establish that type III collagen is a major constituent of grossly proliferated rheumatoid and normal synovium. Unlike the collagen of normal synovium most of that in rheumatoid tissue could be solubilised by pepsin at 4 degrees C. Moore than half the pepsin-solubilised collage was identified as type III, the remainder being type I, by CM-cellulose chromatography; SDS-polyacrylamide electrophoresis with and without reduction of disulphide bonds; and amino acid analysis. Moreover, at least half the total collagen in several samples of normal as well as rheumatoid tissue was clearly type III when cyanogen bromide-derived peptides were run on SDS-polyacrylamide electrophoresis and compared with peptides prepared from purified types I and III collagens. This conclusion was supported by the isolation on phosphocellulose and quantitation by amino acid analysis of the collagen peptides alpha(1)CB2 and alpha(III)CB2 from a cyanogen bromide digest of rheumatoid synovium.


Biosynthesis of gastric mucins. In vitro incorporation of radioactive glucose. An in vitro model for the study of the mechanism of gastric-glycoprotein (mucin) biosynthesis is described. Gastric mucosa scrapings were incubated in Eagle's minimum medium with U-14C-glucose. Linear incorporation-kinetics were observed during 4 hours. U-14-C-glucose was incorporated into soluble and cell bound glycoproteins. In the acid hydrolysate of soluble and cell bound fractions all the amino acids separated by high voltage electrophoresis and all the carbohydrates separated by thin layer chromatography contained appreciable radioactivity showing the active conversion of the added radioactive glucose to all the amino acid and carbohydrate precursors used by the gastric cells for the biosynthesis of macromolecular glycoprotens. The carbohydrate/protein ratio of the excreted glycoproteins increases steadily during the 4h incubation period suggesting that the chemical composition of the excreted mucins changes during this period. The cell bound glycoprotein fraction retains a constant composition during the 4th incubation period. The high fucose to hexose ratio of the soluble (excreted) glycoproteins suggests that they are probably identical to the gastric mucins isolated from native gastric preparation. This model is therefore considered a valid one for the study of the regulation of the biosynthesis of gastric mucins as well as for the study of drug action.


Glycosaminoglycans produced in tissue culture by rat lung cells. Isolation from a mixed cell line and a derived endothelial clone. The glycosaminoglycans produced by a mixed cell line of normal adult rat lung and an endothelial clone derived from this line were isolated and examined. Cellulose acetate electrophoresis of media and cells before and after digestion with specific enzymes indicated that all the major glycosaminoglycans except keratan sulfate were synthesized by both cultures. Heparan sulfate and dermatan sulfate were found only in the cell fraction while hyaluronic acid was found in both the medium and the cell fractions. The chondroitin sulfates were isolated from the medium. The endothelial clone produced a 4:1 ratio of glucosamine to galactosamine in the medium from the fifth through thirteenth months of culture. The medium of the mixed cell line initially contained glycosaminoglycans with a glucosamine to galactosamine ratio of 2:1 but after approximately one year of culture, the ratio had changed to 4.6:1 suggesting that the culture contained predominatly endothelial cells.


Thrombosis detection using radionuclide techniques. Radionuclides have been used in the evaluation of intravascular thrombosis for several years. The most widely accepted nonimaging technique is I-125 labeled fibrinogen. It is commonly used for patients who have a high probability of developing a thrombus (e.g., those undergoing surgery). Other techniques are emerging as having value in thrombosis detection. These techniques include radionuclide venography and clot localization scanning techniques utilizing the affinity of clot for small radiolabeled particles, as well as imaging techniques using I-131 labeled fibrinogen. More recently, a number of the above-mentioned techniques have been applied to patient problems. The FDA ban on commercial radiolabeled fibrinogen in the United States has promoted the development of alternative techniques and the use of autologous fibrinogen. A number of other techniques for thrombosis detection have also been explored on a more experimental basis. They include the use of thrombolytic agents such as streptokinase, urokinase, and white blood cells, as well as platelets. The common lung or pulmonary perfusion scan using macroaggregates of albumin or microspheres radiolabeled also gives information as to the presence of thrombosis of embolus within the pulmonary arteries, by showing the effect upon the perfusion pattern. This review will explore in detail the principles, as well as the present and prospective usefulness of the techniques currently available.


["Surgical" laparoscopy indications and value]. From 1971-1973, 1046 patients underwent laparoscopy in the gynecological department; 256 of the cases were surgical problems. In contrast to gastroenterological laparoscopy, surgical laparoscopy was performed in the operating room under general anaesthesia and everything prepared for immediate surgery. Major surgical interventions--if necessary--were performed immediately after laparoscopy. Indications for surgical laparoscopy were the following: preoperative evaluation of nature, extent and eventual metastases of tumors. Preoperative differentiation of acute and chronic appendicitis from other affections, particularly in younger female patients. Suspected intraabdominal hemorrhage of traumatic or non-traumatic origin. Evaluation of pathological palpatory findings in the abdominal cavity. Differential diagnosis of chronic relapsing intraabdominal complaints of unknown origin. Differential diagnosis of putrid, tuberculous or carcinomatous peritonitis with eventual biopsy. Preoperative evaluation of questions concerning surgery of liver, gallbladder or pancreas in connection with occlusive jaundice, hepatic cirrhosis or malignancy. The results of this study show, that by laparoscopy in over 50% of the patients, major surgical interventions could be avoided. Contraindications were primarily limited to pulmonal or cardiac insufficiency. The only complication (intestinal perforation), was adequately dealt with under the given operative conditions.


[Clinico-anatomical picture of cystic renal dysplasia]. The variety of clinical conditions leading to diagnosis and surgery of cystic renal dysplasia is demonstrated by 5 case reports. Etiological and histological features of this rare developmental abnormality are outlined. Surgical removal of the cystically degenerated renal bud is only indicated if the size of the tumor or vesico-ureteral reflux and inflammation causes lumbar pain.


[Abdominal pain caused by adhesions and their removal at laparoscopy (author's transl)]. Intra-abdominal adhesions as the cause of severe abdominal pain were diagnosed in eight patients because (1) other abdominal diseases had been excluded, (2) certain movements, but only rarely meals, precipitated or increased the pain, (3) laparoscopy had confirmed adhesions and their manipulation had caused pain. After the adhesions had been removed at laparoscopy the pain either disappeared or was decisively reduced.


Regulation of cyanide-insensitive respiration in Neurospora. 1. Inhibition of either mitochondrial transcription or translation in Neurospora crassa results in the rapid production of the cyanide-insensitive pathway of mitochondrial respiration. Protein synthesis on cytoplasmic ribosomes is required for the appearance of cyanide-insensitive respiration in the culture. 2. Removal of the inhibition of transcription of translation results in a rapid return to cyanide-sensitive respiration. Additional protein synthesis in the cytoplasm is required for the loss of cyanide-insensitive respiratory activity while additional mitochondrial protein synthesis has no effect. 3. These studies indicate that a mitochondrial gene product is involved in a negative manner in the regulation of cyanide-insensitive respiration. When the mitochondrial product is present, the pathway is not expressed, when the mitochondrial product is absent, the pathway is expressed. 4. Studies with forced heterokaryons formed from respiratory-deficient mutants having cyanide-insensitive respiration and respiratory-competent auxotrophs indicate that the site of action of the mitochondrial gene product is external to the mitochondrion.


Furosemide, mithramycin, and salmon calcitonin in hypercalcemia. Twenty-nine patients with acute hypercalcemia secondary to carcinoma, myeloma and parathyroid adenoma have been treated with large doses of furosemide, mithramycin, or salmon calcitonin perfusion. With furosemide administration the treatment was successful in 6 of 10 patients. Furosemide was injected intravenously at the rate of 125 mg every 3 hours. With mithramycin perfusion only 2 of 8 patients have a return of the serum calcium levels to normal. With salmon thyrocalcitonin 3 of 10 patients obtained a good result. It can be interesting to suggest the association of furosemide and salmon calcitonin infusion to treat hypercalcemia of myeloma.


Myofibrillar ATPase, DNA and hydroxyproline content of human hypertrophied heart. 70 human hearts were studied less than 36 hours after death. The apex, and in some cases other parts of the myocardium were homogenized, DNA, hydroxyproline content, myofibrillar Ca2+ and Mg2+ ATPase were measured. In normal hearts the DNA and collagen content were 372 +/- 9 mg and 36 +/- 7 mg. Ca2+ and Mg2+ ATPase of the myofibrils prepared from these hearts have shown the same specific activity (35 +/- 5 and 34 +/- 6 nmol/min./mg) as those from fresh biopsies taken during open-chest surgery. The heart weight correlates with the DNA content (r= + 0.58 -p less than 0.01) and with the myofibrillar ATPase (r= - 0.33 - p less than 0.02) but not with the DNA concentration nor with the collagen content or concentration. The main result of this study was the presence of a negative correlation between the DNA content of the heart and the Mg2+ or Ca2+ myofibrillar ATPase (r= - 0.31, p less than 0.05 - r= - 0.45, p less than 0.01). This correlation was analysed with reference to the histological and biochemical studies published by several authors in human or experimental heart hypertrophy and it was suggested that in human heart hypertrophy the decrease of the myofibrillar or myosin ATPase is a direct consequence of the high degree of polyploidy of the muscular cells observed in this condition.


On the mechanism of action of triamterene: effects on transport of Na+, K+, and H+/HCO3- -ions. The rat salivary duct epithelium, which actively transports Na+, K+, and H+/HCO3- in a manner similar to renal distal tubules, was used as a model tissue to study the mechanism of action of triamterene on electrolyte transport. 10(-4) M triamterene completely blocked Na+ resorption and lowered net K+ secretion to half that of controls, whereas HCO3- accumlated in the lumen, probably due to a decrease in H+ secretion. The rates of K+ and H+/HCO3- transport in the presence of triamterene did not differ from those determined after omission of Na+ from the luminal fluid. This was considered to be evidence against a direct action of triamterene on transport of K+ and H+/HCO3-. Triamterene rapidly and reversibly reduced the transepithelial electrical potential difference. This was due to almost complete abolition of Na+ conductance of the luminal membrane at 10(-4) M triamterene, whereas K+ conductance was not altered. Triamterene, administered in vitro from the interstitial side of the isolated duct epithelium was ineffective even at the highest concentrations. The activities of the Na-K-ATPase, the Mg-ATPase and the microsomal HCO3-ATPase were influenced by 10(-4) M triameterene in a similiar fashion. These effects were clearly demonstrated only in the homogenate of the duct tissue and not in intact cells in the isolated duct preparation. Therefore they were considered unspecific. The transport studied demonstrate a primary effect of triamterene on Na+ entry from lumen to cell. Influences on net K+ and H+/HCO3 transport are secondary consequences of functional coupling between movement of Na+ and movement of K+ and H+ across the luminal cell membrane.


Studies on the stable inhibition of Na+ + K+-ATPase by cassaine. Exposure of rat brain Na+ + K+-ATPase (ATP phosphohydrolase E.C. 3.6.1.3) to concentrations of cassaine greater than 1 x 10(-4) M resulted in a poorly reversible inhibition of this enzyme. Inhibition did not require the presence of ATP and developed rapidly, but the final amount of inhibition observed was independent of time. The amount of inhibition observed at a given concentration of cassaine was reduced by increasing the concentration of membranes in the system. The inhibition of Na+ + K+-ATPase activity was associated with equivalent inhibition of the phosphorylation and (3H)-ouabain binding reactions of this enzyme, while the uninhibited enzyme was apparently kinetically normal. Concentrations of cassaine which produced this stable inhibition of Na+ + K+-ATPase had no effect on the Mg2+-activated ATPase or the NADH cytochrome-c-reductase activities of crude rat brain microsomal preparations. Cassaine inhibited the cholinesterase activity of rat brain microsomes with a Ki of about 5 x 10(-5) M, but his inhibition was fully reversible. The poorly reversible inhibitory actions of cassaine, thus, appeared specific for Na+ + K+-ATPase. Because this stable pattern of inhibition of the Na+ + K+-ATPase by cassaine required drug concentrations at least one hundred-fold greater than those which produce positive inotropic effects, it appears unlikely that this pattern of Na+ + K+-ATPase inhibition is involved in the cardiotonic actions of this drug.


Cardiotonic site directed irreversible inhibition of Na+ + K+-ATPase by 3-azidoacetylstrophanthidin, a photochemical analogue of strophanthidin. A photochemical analogue of strophanthidin, 3-azidoacetylstrophanthidin (AAS) was synthesized and tested as a cardiotonic steroid (CS) site directed photoaffinity label for Na+ + K+-ATPase (ATP phosphohydrolase, E.C. 3.6.1.3). AAS-inhibited rat brain ATPase with an I50 of about 1 x 10(-6) M readily displaced 3H-ouabain from its specific binding sites on this enzyme and produced a positive inotropic effect in guinea pig atrial strips. In the absence of UV light its interaction with the CS binding sites of Na+ + K+-ATPase appeared reversible. In the presence of UV light and acetylphosphate, AAS produced about 15% irreversible inhibition of Na+ + K+-ATPase, compared with about 5% irreversible inhibition in the absence of either UV light or acetyl phosphate. Since acetylphosphate supports specific glucoside binding at the CS binding sites of Na+ + K+-ATPase these data are consistent with the concept that AAS is a cardiotonic steroid site directed photoactivatable inhibitor of Na+ + K+-ATPase.


Studies in relation to endocrine exophthalmos: the biochemical composition of human retrobulbar connective tissue. As part of studies on the pathogenesis of exophthalmos of Graves' disease, the biochemical composition of human retrobulbar tissue was investigated. The connective tissue was composed of 72.7% lipid, 23.8% water and 3.5% dried defatted tissue. Total tissue glycosaminoglycan (GAG) amounted to 0.18% of dried defatted tissue. Approximately 27% of the total hexosamine and 19% of the total tissue galactosamine were recovered in the GAG fraction. Cellulose microcolumn fractionation of GAG showed that the hyaluronic acid and dermatan sulfate were the two major GAG species.


[Influence of thyrocalcitonin on the adenosine triphosphatase activity and the electrolyte balance of the rat myocardium]. The effect of thyrocalcitonine on the calcium, sodium and potassium levels in the blood plasma of the rats' myocardium and also on the activity of Na+-, K+- and Ca2+- ATP-ase of the sarcoplasmatic cardiac reticulum fragments were studied in experiments with rats. Calcitonine was found to force down the level of calcium in the blood plasma and to raise the sodium content in the myocardium on rats. The drug lessened the activity of the myocardial Na+-, K+-ATP-ase.


A comparison of hysterosalpingography and endoscopy in evaluation of tubal function in infertile women. A comparison of hysterosalpingography (HSG) with endoscopy in the evaluation of tubal function in 117 infertile women is presented. Results were in accord in 55% of the patients. Correction for endoscopic error and the limitations of HSG increased the positive correlation to 74%. Twenty-three patients (20%) with abnormal findings at HSG were normal with endoscopy. Ten patients (8%) had normal HSG but abnormal endoscopic findings. Fifteen patients (12%) with positive findings by HSG had different positive findings at endoscopy. Additional endoscopic findings in 47 patients are listed. Review of 26 patients with endoscopy-confirmed endometriosis revealed that 14 (54%) had a normal HSG and normal history and pelvic examination. Although HSG should be the method of choice as part of the basic evaluation, an infertile woman should undergo endoscopy before the evaluation is considered complete or final.


[The concentration of electrolytes and water in the walls of the frog gall bladder following absorption of an isotonic fluid]. In experiments on isolated gall-bladders (GB) of frogs, the transport rate of NaCl-isotonic solution by GB epithelial cells was inversely proportionate to the sodium content in them. Under oxytocin action (20 mE/ml) the absorption was inhibited and simultaneously the intracellular sodium content increased. Replacement of NaCl by sucrose solution caused a complete inhibition of absorption for 5--15 min. During this time, tissue cells excreted a considerable amount of their sodium, in result of which the intracellular amount of sodium decrease by 2.0-2.5 times. Oxytocin caused the inhibition of both the sodium transport from cells and the Na-K--ATPase activity. Obviously, the inhibitory action of oxytocin upon sodium transport from GB cells is due to a decrease of the transport activity of Na, K--ATPase under the action of hormone.


Effect of streptozotocin on red-blood-cell-reduced glutathione: modification by glucose, nicotinamide, and epinephrine. Previous studies had shown that administration of streptozotocin to rats produces both diabetes and hemolysis and that both could be ameliorated by prior injections of diazoxide. Thus, it appeared pertinent to define the effect of streptozotocin on the red cell. In the present studies, streptozotocin administered in vivo to rats produced a rapid fall in red-cell-reduced glutathione. This effect was duplicated in vitro in incubated human red cells. Furthermore, it was demonstrated that glucose loading prior to bleeding modified the in-vitro red-cell GSH response to streptozotocin and that preincubation of red cells from fasted individuals with glucose, nicotinamide, and epinephrine (but not nicotinic acid) protected against the subsequent effect of streptozotocin on RBC GSH. The pattern of the RBC GSH response under each of these conditions is that which occurs in response to challenge with an oxidant, that is, with appropriate protection, oxidation stress produces an acute rise rather than falll in gsh. further, when glucose was present through both preincubation and test periods (i.e., in presence of streptozotocin) a third pattern of GSH response was observed--no change. The data are compatible with the postulate that the cytotoxic action of streptozotocin is dependent, in part, on an oxidant effect, and that glucose may protect through at least two mechanisms, that adrenergic stimulation can enhance protective mechanisms against redox insults and so contribute to maintenance of cell viability.


Bioassay of inhibitory activity of gastrone on basal HCl secretion in rats with chronic gastric fistula. The authors evaluated the applicability of the rat with gastric fistula to the bioassay of gastrone, endogenous inhibitor of gastric acid secretion and the role of anticholinergic mechanism in this inhibition. 104 individual bioassays were performed on 25 rats with chronic gastric fistula out of which 34 tests were performed with gastrone, 49 controls with saline and 21 with atropine. In rats serving as their own controls, a statistically significant reduction of the volume of basal gastric secretion and of the basal HCl output by 56 and 59%, respectively, occurred after intravenous administration of 40 mug gastrone B. This was demonstrated in the first 4 h after gastrone and was statistically highly significant (p less than 0.001). There was no significant difference, however, in the concentration of HCl in the gastric juice after gastrone and after saline. The inhibitory effect of gastrone on HCl output at the intravenous dose of 40 mug was greater than that of 0.1 mg/kg atropine intravenously, while that of 50 mug gastrone was about equal to that of 0.4 mg/kg atropine. The gastrone inhibitory activity on gastric acid secretion in rats appears to be unrelated to anticholinergic mechanism. The advantages of the bioassay of gastrone activity using rats with chronic gastric fistula over the rats with pyloric ligation are discussed.


The sorbitol pathway: effect of streptozotocin induced diabetes and the feeding of a sucrose-rich diet on glucose, sorbitol and fructose in the retina, blood and liver of rats. The sorbitol, fructose and glucose content of the retina, blood and liver from normal and streptozotocin diabetic rats fed either a starch- or sucrose-rich diet for 15 days has been determined. The sorbitol and fructose level in the retina was much higher than that in either the liver or blood and was significantly increased in diabetes on either diet. Such increases in the sorbitol concentration did not occur in either the liver or the blood during diabetes, and the possibility that the sorbitol pathway can play an important metabolic role in the diabetic retina has been discussed. The feeding of a sucrose- as opposed to a starch-rich diet did not significantly alter the concentrations of glucose, sorbitol or fructose in the normal rat retina but caused a marked elevation in the diabetic state.


Degradation of neocarzinostatin by blood sera in vitro and its inhibition by diisopropyl fluorophosphate and n-ethylmaleimide. Inactivation of antitumor antibiotic, Neocarzinostatin, which occurs in vivo or during incubation with serum in a test tube, was found to depend on the dose of serum and incubation period. The inactivation process was accompanied with degradation of Neocarzinostatin to a smaller molecular size with concomitant loss in antigenic activities at a slower rate. Apparent increase, close to about 250% of control, in the antibiotic activity was found before the inactivation, in the presence of diisopropyl fluorophosphate, or about 200% in the presence of N-ethylmaleimide. The present findings suggest that the degradation process partly depends on proteolysis by serine type proteinase(s) and partly on the involvement of sulfhydryl groups. These results imply two possible applications; one for chemotherapy with Neocarzinostatin in combination with inhibitors of proteolysis and the other for drug design through the modification of amino acid residues on Neocarzinostatin molecules which provide the enzyme binding sites such as lysine and arginine for the proteolytic catalysis.


[Intra-abdominal bleeding following subcutaneous heparin application in septic abortion (author's transl)]. Report on intra-abdominal hemorrhage following inexpert injection into the abdominal wall of calcium-heparin concentrate (Calciparin, Nattermann, Cologne) in a patient with septic abortion. A hematoma developed in the abdominal muscles which perforated via the parietal peritoneum into the abdominal cavity.


[Population genetics of the inhabitants of Northern European USSR. I. Data on the structure of 6 villages in Archangel Oblast]. The paper deals with two demographic characteristics of 6 villages in the Archangelsk Region of the RSFSR (river Peosa region) significant from the genetical standpoint. These data were obtained by means of the examination of 843 persons (75,07% of the total number of inhabitants) and of the analysis of complete list of inhabitants permanently living in the villages studied. The proportion of the reproductivity age class was 28.94%, the numbers of men and woman among them being about equal. The average number of children per family in families that have already completed their reproductive period was 3.87, the variance being 4.51 (the data obtained on the basis of examination of over 90 families). The average age of marriage was established to be about 24 years, the duration of each generation being about 32 years. The average index of endogamy per village was observed to be 58.40%, the contribution of the gametes of the preceding generation per village being 72.86%. The migrational influx of gametes from other localities per total of 6 villages was 2.52%. It was shown by the comparison of the character of migrations with mathematical models that the matrix migrational model is the most adequate one.