Angiodysplasia as a source of intestinal bleeding.

Nine cases of angiodysplasia have been angiographically identified in the past eight years at the two teaching and two major private hospitals in the West Los Angeles-Santa Monica area. In seven patients, repeated massive hematochezia whose source had escaped previous intensive diagnostic studies, was the indication for angiography. Two malformations were found incidentally during an angiogram for an unrelated problem. Four of the patients had had a previous angiogram which failed to show the lesion. Eight of the nine patients had right colon vascular malformations, but one had jejunal angiodysplasia as well. One patient had a midileal vascular malformation which appeared in the right lower quadrant on the study. Six of the seven underwent resection of the implicated bowel, and none have rebled. The series suggests that angiodysplasia may not be as rare as commonly assumed and in four cases escaped detection even angiographically at least initially. The lesions may be multiple and their anatomical site radiologically deceptive. Finally, these vascular malformations may be an incidental finding, and though demonstrable angiographically, may not necessarily be responsible for bleeding in the patient older than fifty years.


Retinal enzyme activities under hypoxic conditions prior to neovascularization.

In an effort to demonstrate biochemical changes occuring in malperfused retinas, oxygen-induced retrolental fibroplasia was produced in kittens. Immediately before the onset of vasoproliferations, that is in the stage of maximal hypoxia, the activities of lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PDH), malate dehydrogenase (MDH) and isocitrate dehydrogenase (ICDH) were determined. The activity of MDH was found to be significantly decreased, whereas the activities of the other enzymes showed no major changes.


[Scanning electron microscopy of cystoid degeneration in the peripheral retina (author's transl)].

Scanning electron microscopy of peripheral cystoid degenerations of the retina as well as of reticular or inner cystoid degenerations shows tunnel-shaped and vault-like cavities which are supported by columns. In marked cases of PCD, fibers of a collagenous nature surround and connect the columns. Inside the columns there are cable-like strands, which are probably stretched neuronal processes. The surface covering of the columns is formed as a porous layer. The columns of the reticular cystoid degeneration are thinner and located in processes of the outer columns. Globular structures persent in both systems of are interpreted as deformed erythrocytes.


[Animal experimental investigations for determining the duration of the "mechanical-effective period" of muscle action potentials and of the "electro-mechanical latency period" of "fast fibres" of external ocular muscles (author's transl)].

A report is given of an animal experimental study for determination of the duration of the "mechanical effective period" of the muscle fiber membrane action potential and the "electromechanical latency period" of "fast fibers" of the external ocular muscles in rabbits in vivo. The studies were carried out with an internationally standardized glass microelectrode technique. The statistical values are based on 250 tests employing the superposition technique. The mean "mechanical effective period" of the muscular fiber membrane action potential was determined with SE=0.52 ms, SD 0.08 ms. The confidence thresholds were 99% statistically reliable with 0.43 ms and 0.55 ms. According to these studies, the duration of the "mechanical effective period" of the "fast fibers" of the external ocular muscles was only one-third off the "mechanical effective period" of the skeletal muscles. The mean duration of the "electromechanical fast-fiber latency period" was calculated with SE=1.97 ms, SD=0.30 ms. The confidence threshold was 99% statistically reliable with 1.86 ms and 2.08 ms. The "electromechanical latency period" of the "fast fibers" of the external ocular muscles was therefore significantly less than the skeletal muscles, lying under the 50% limit of the "electromechanical latency period" of the analogous skeletal musculature. These studies permit determination of the most important electrophysiological parameters which define a threshold value of maximal speed in vision direction changes.


[Dominantly inherited cleavage of the pigment layer of the iris and the ciliary body (author's transl)].

A dominantly inherited cleavage of the pigment layer of the iris has been observed throughout three generations. In the two elder generations, luxation and rapidly progressing opacification of the lenses occurred; after cataract extraction, a cleavage of the pigment layer of the ciliary body could also be seen through the iridectomy. The lenses had reduced sagital and spherical diameters (4X7 mm). Furthermore, a peculiar form of glaucoma and a peripheral retinal detachment has been observed in the eldest generation.


[Binocular confusion in unilateral aphakia (author's transl)].

The five symptoms of binocular confusion of the  unilateral aphakic patient are described. In day vision, without strabismus and without correction, the image of the  aphakic eye considerbly disturbs binocular vision, though the vision is less than 20/400 (first symptom). In night traffic the uncorrected unilateral aphakic patient sees very striking light circles and within those circles of glittering dots around bright light sources of cars or around blinking indicators and stoplights (fifth symptom). The five disturbing symptoms of binocular confusion can be positivity eliminated by an appropriate combination of spectacles and contact lens (combined correction) in regard to echometry and intraocular optics.


[Recurrent corneal edema without ocular hypertension, pigment degeneration combined with deafness, progressive dystrophy of the outer eye-muscles in a patient with proportional dwarfism and diabetes mellitus (author's transl)].

A 27-year-old woman has been suffering from recurrent corneal edema without ocular hypertension since her early childhood. When the cornea is clear, visual acuity-with correction for high myopia-is 5/10 to 5/15 and Nieden I; when the cornea is swollen, it decrease to 5/50 and 1/10, respectively, and Nieden VII. Furthermore, there is an atypical pigment degeneration of the retina combined with deafness, a progressive ptosis since her 10th year of life, and a progressive dystrophy of the outer eye muscles, having developed in the past few years. In addition, the mentally normal developed patient presents a proportional dwarfism (no dysostosis) and a diabetes mellitus. This combination of symptoms is compared with the well known Bardet-Biedl syndrome and the De Grouchy syndrome and is found to constitute a new syndrome.


The intraocular pressure response of glaucomatous eyes to topically applied bupranolol. A pilot study.

Bupranolol 0.5% oily solution applied topically lowered intraocular pressure of glaucomatous eyes significantly. The pressure decrease is related to pretreatment pressure levels. The maximum effect occurred within 4 hours and lasted for more than 24 hours. No objective or subjective irritation could be attributed to the ophthalmic preparation. There was no significant effect on outflow facility, on blood pressure or tear flow. However, bupranolol produces local anesthesia on the eye. The problem of tachyphylaxis is discussed in the treatment of glaucoma with bupranolol eye drops.


Rapid detection of changes in the optic disc: stereo-chronoscopy.

Easy detection of temporal variations of tissue configurations within the optic disc or other structures is possible by means of stereoscopy: Stereochronoscopy. Photographic pictures of the papilla are taken from time to time at exactly the same angle; when any two of them are paired and viewed with a stereoscope, temporal form changes immediately show up as stereo effects (Schirmer [2]). Since continuing glaucomatous damage cannot be diagnosed either by visual field defects or by actual c/d ratios but only by their temporal changes, this method may prove of diagnostic value.


Diabetic retinopathy study. Data acquisition and its reliability.

The documentation of ophthalmologic data of patients with diabetic retinopathy (DR) is described. Special attention has been paid to the standardized grading of opacities of the dioptric media as well as to the assessment of classified arteriolar abnormalities. The reproducibility of these judgments was determined by a double evaluation test. The reliability of the assessment of classified retinal lesions on panorama fundus photographs was reported elsewhere. A further section of the questionnaire that concerns the documentation of the patient's history, of general medical and laboratory findings, and of reasons why individual patients "drop out" from the study, is described in this contribution.


[Frequency of the pupillary response following flicker stimuli (author's transl)].

Pupillary function was tested in 3 different age groups (20-30, 40-50, 60-70 years) of 8 patients each. The pupillary response was picked up by means of a portable IR-reflex-pupillometer, which registered the consensual pupillary light reflex in one eye, while the other eye was stimulated by flashes of different frequencies. Measurements were made of how many Hertz (Hz) the pupil dilated in the dark phases (intervals) between the flashes (flicker-fusion frequency). In the younger age group an average value of 3.15 Hz was obtained, the middle group fused at 2.89 Hz, the older group at 2.61 Hz. These differences are explained mainly by muscular and vascular degeneration of the iris.


[The relationship of amplitude of visual evoked potentials to side length of rectangular stimulus pattern and to abruptness of stimulus alternation (author's transl)].

Cortical potentials evoked by viewing checkerboard pattern reversal stimuli as well as horizontal and vertical rectangular pattern reversal stimuli were recorded. The amplitude of the cortical evoked responses decreased with increasing side length of the rectangular pattern and decreasing velocity of the pattern reversal. Psychophysical and electrophysiologic findings are compared with these data and their clinical relevance is discussed.


Ultrasonic findings in the vitreous space in patients with detachment of the retina.

Ultrasonic observations were made of the vitreous body and the subretinal space of the sick eye and of the vitreous body of the other eye on 32 unselected subjects with idiopathic detachment of the retina. In almost all sick eyes a severe state of degeneration of the vitreous body was observed, and in all cases examined the subretinal space was acoustically heterogeneous. In the other eye degeneration of the vitreous body was often observed, although to a lesser degree than in the eye with retinal detachment. The ultrasonic examination of the vitreous body may yield information as to the disposition of the eye with regard to detachment of the retina.


[The influence of vasodilatators on intraocular pressure and blood pressure (author's transl)].

The influence of different vasodilatators on blood pressure and intraocular pressure has been tested in animal experiments. For that purpose substances with alphasympathicolytic effect (Hydergin, Trental) have been tested as well as substances which are of direct influence on the muscles. In all cases a decrease of the blood pressure was noticed. Furthermore in most of the cases an increase of the intraocular pressure could be seen. This is due to a direct dilatation of ocular vessels. The effects were short-lived and reversible. We tried to find an explanation for the variations of intraocular pressure during the decrease of blood pressure. The low transmural pressure (PTM) and the corresponding low starting point of the muscle tonus seemed to be responsible for this phenomenon. Without doubt the starting point of the blood pressure, the dose, and the cardiac ability for compensation are of great influence in the development of the curve. Only a sufficiently high blood pressure is able to dilate the ocular vessels, so that one has to draw therapeutic conclusions from the constellation blood pressure/intraocular pressure before deciding on treatment.


Age changes of the human optic nerve head. A neurohistologic study.

Eleven human optic nerves from subjects in different decades ranging from the fifth to the ninth were investigated with the silver carbonate method to establish the pattern and frequency of age changes within the optic nerve head and their relationship with the glaucomatous excavation. It has been found that despite the occurrence of age degeneration at the same level of the cribriform lamina, there are definite anatomical differences as compared with glaucoma changes, especially regarding the distribution of axonal damage.


Possible mechanisms of emphysema in smokers: cigarette smoke condensate suppresses protease inhibition in vitro.

To study the possible role of suppression of antiproteases by cigarette smoke in the pathogenesis of pulmonary emphysema in smokers, the following experiments were carried out. Elastin-agarose gels were impregnated with cigarette smoke condensate dissolved in dimethyl sulfoxide or with the solvent alone. This procedure affected neither local pH of the gel nor subsequent physical behavior (diffusion) of antiprotease. Elastases from various sources were then allowed to diffuse through the impregnated gels toward a counter-diffusing sample of antiprotease. The effectiveness of the antiprotease in blocking the enzyme was determined from the extent of elastolysis. The elastin substrates used included beef ligament elastin and dog lung elastin. The enzymes used were porcine pancreatic elastase and pure human leukocyte elastase. The antiproteases tested included human serum, pure human a1-antitrypsin, human bronchopulmonary lavage fluid, and a synthetic chloromethyl ketone inactivator of elastase. The results showed that whole, unfractionated cigarette smoke condensate suppressed all of the antiproteases tested, except for the chloromethyl ketone. These observations are discussed in terms of the protease-pathogenesis model of pulmonary emphysema.


The role of autoimmunity in hypoendocrine and hyperendocrine function: with special emphasis on autoimmune thyroid disease.

There is considerable evidence to suggest that the organspecific autoimmune endocrinopathies are primary disorders of the lympoid system. Although proof is not complete, the basic genetic defect in each condition may be one of immune surveillance, that is, a defect in suppressor "T" lymphocytes. Combinations of two or more of these conditions may be due to the concurrence of two or more specific defects in immune control, as well as the random appearance of the appropriate self-directed "forbidden" clones of lymphocytes. In this concept, there is no need for antigenic alteration (only antigenic availability) to initiate these disorders. Both cell-mediated and humoral immunity seem essential, with roles for immune complexes and "killer" cells as well. Antireceptor antibodies are of particular interest in Graves' disease, where they are stimulatory: other antireceptor antibodies have been found that are blocking antibodies, and others may merely bind without either stimulating or blocking.


Manner and meaning of susceptibility testing of ampicillin-resistant Haemophilus influenzae.

We examined ampicillin-resistant strains of Haemophilus influenzae to compare the percentage of resistant organisms in each strain with the susceptibility to ampicillin by an agar dilution method. Using an inoculum of 10(4) colony-forming units, the minimal inhibitory concentration (MIC) increased with the percentage of resistant organisms in the strain. Laboratory-manipulated strains composed of different proportions of a susceptible and a resistant strain behaved similarly. The survival of isolated colony-forming units (colony MIC) was then determined by spreading inocula over the surface of a set of MIC plates, resulting in separation of individual colonies. This modification of the susceptibility test to the colony level gave end points that were clear and reproducible and that did not vary with changes in incubation time or temperature. True differences in susceptibility among strains were demonstrated by this method, whereas results of the conventional MIC test may reflect only the number of resistant organisms present in the inoculum.


Evaluation of myocardial damage in patients undergoing coronary-artery bypass procedures with halothane-N2O anesthesia and ajuvants.

During a 6-month period in 1975, 102 patients undergoing scheduled coronary-artery bypass grafting were studied by both conventional ECG and heart-specific enzymatic methods to evaluate the incidence and estimate the extent of myocardial damage associated with an anesthetic management protocol using halothane as a primary agent with adjuvant agents. Anesthetic interventions were made to maintain heart rate and systolic pressure at resting levels or below the heart rate systolic pressure product documented during exercise-induced angina. These interventions included adjustment of halothane concentration in all patients, the use of adjuvant agents in 88.2 percent, vasodilators in 26.5 percent, and the precardiopulmonary bypass use of vasoconstrictor or cardiostimulants in 9.8 percent. There were 2 early postoperative deaths. ECG evidence of infarction was observed in 4 surviving patients. Sustained release of heart-specific CPK-MB isoenzyme occurred in 78 percent of surviving patients. Isoenzyme activity was detected in only 1 patients prior to cardiopulmonary bypass (CPB), in 1 patient during CPB, and in all others after termination of CPB. The extent of myocardial damage as estimated by integrating CPK-MB values over time was directly related to number of vessels grafted and to aortic cross-clamp and CPB times. The ECG and enzymatic data both document a low level of myocardial damage associated with this anesthetic management protocol.


Histiocytosis X; follow-up of 43 cases.

Over a 29-year period, 43 cases of histiocytosis X presented in children under the age of 12 years. 29 patients (67%) have survived, and of these, 15 (52%) have a detectable disability. It was confirmed that young age at presentation and evidence of soft tissue involvement were associated with a worse prognosis. The majority of deaths were associated with pulmonary involvement. 14 patients developed diabetes insipidus. 5 of the surviving adults have heights below the 3rd centile. Puberty usually occurred at a normal age. Follow-up studies on 12 survivors showed no evidence of residual abnormality of haematology, deficient lymphocyte function, or yeast opsonization. HLA typing showed no unusual pattern. Mild carbon monoxide diffusion deffects were present in 4 patients and other abnormalities were detected on lung function tests.


Action of nonsteroidal, anti-inflammatory drugs on human and rat peripheral leucocyte migration in vitro.

Using an in vitro system of cell migration from glass capillary tubes, the nonsteroidal, anti-inflammatory agents sodium salicylate, aspirin, ibuprofen, phenylbutazone, and indomethacin were shown to inhibit the migration of human peripheral leucocytes in a dose-related manner. This drug action was not confined to one species, as shown by the modification of rat peripheral leucocyte motility by sodium salicylate and aspirin. The relevance of the human findings to the clinical effectiveness of these agents is discussed.


Coronary artery surgery without global ischemia.

A simple technique for local occlusion of the coronary artery without aortic cross-clamping during the distal anastomosis has been developed. The use of this internal coronary artery occluder, which we developed, represents another step forward in myocardial protection during coronary bypass procedures.


Muscle disease associated with renal failure.

A 54-year-old woman had muscle disease that terminated fatally with complete body paralysis. The patient had renal failure, which progressed concurrently with her muscle weakness. Myoglobinuria was not demonstrated during the active stage of her illness. Renal biopsy specimens demonstrated immune deposits in the glomeruli, and, at autopsy, there was a generalized glomerulonephritis. We believe the muscle disease was a consequence of acute rhabdomyolysis, hyperacute polymyositis, or virus infection. Regardless of the nature of the muscle disease, an immune mechanism may have been responsible for the associated renal failure.


Serum levels of IgE in malignant lymphogranulomatosis.

Serum levels of IgE in malignant lymphogranulomatosis (Hodgkin's disease) were lowered in patients who had been intensively treated, without eosinophilic granulocytes, and in less advanced forms of the disease. High levels were observed in untreated patients with eosinophilic granulocytes in their peripheral blood, and in clinically advanced cases.


Electrical stimulation for the control of pain.

Electrical stimulation for the control of pain is now a well accepted therapeutic modality. Transcutaneous application of electrical stimulation is the most common technique employed and has been used to treat chronic pain, acute surgical pain, and acute pain of other origins. Percutaneous application of electricity to the nervous system through needles electrodes is useful in predicting the efficacy of implantable stimulators and has served the same function as diagnostic nerve block. Implantable stimulators have been used for stimulation of peripheral nerves, the anterior and posterior surfaces of the spinal cord, and the brain. Peripheral nerve stimulators are the most efficacious of the implantable devices. They are used specifically for pain of peripheral nerve injury origin. Their use for pain outside the distribution of the nerve stimulated is not yet proved.


[The lymphomicrocirculatory bed of serous membranes in several human diseases].

Morphological changes in the lymphatic link of the microcirculation of serous coats were studied by the method of non-injection impregnation with silver nitrate in rheumatism, lupus erythematosus, chronic nonspecific pneumonia, pulmonary tuberculosis. There were identified 4 types of the state of lymphatic capillaries and postcapillaries, namely: functioning, dystrophized, sclerosing, and regenerating, reflecting a state of the lymphatic system at a given stage of a disease. Regeneration of lymphatic capillaries, as well as formation of lymphatic cisterns, cysts etc., the author classifies as manifestations of compensatory-adaptive processes of the organism aimed at preservation of the hemato-lymphatic balance. The hemo- and lymphocirculation functions as one integral system.


Inactivation of human alpha 1-proteinase inhibitor by thiol proteinases.

Human plasma alpha1 proteinase inhibitor is the body's principal modulator of serine proteinases (such as those released from phagocytic cells). Cysteine-active-site proteinases, which are not inhibited, have now been found to inactivate this important inhibitor by proteolytic cleavage of a scissile peptide bond. Papain carries out this inactivation catalytically, whereas cathepsin B1 acts stoicheiometrically. Thus thiol proteinases could easily disrupt the delicately regulated balance between serine proteinases and alpha1 proteinase inhibitor.


Control of zinc-thionein synthesis in rat liver.

The rate of [35S]cystine incorporation into hepatic zinc-thionein (a metallothionein) was stimulated, with a maximum of 5-6h, after parenteral administration of 2mg of Zn2+ containing 65Zn. The binding of 65Zn to zinc-thionein was measurable by 2-1/2h and reached a plateau by 18h after the injection. A net increase in the hepatic 65Zn content was observed subsequent to the decrease in the rate of zinc-thionein synthesis. The incorporation of both 65Zn and [35S]cystine into zinc-thionein was inhibited by prior administration of either actinomycin D or cordycepin. A second injection of Zn2+, 20h after the initial injection, yielded a 4.9-fold greater increase in zinc-thionein synthesis compared with that after only one injection; however, this synthesis was also inhibitable by actinomycin D. These data support the concept that hepatic zinc-thionein synthesis responds quickly to changes in Zn2+ status and that Zn2+ is bound subsequent to synthesis of nascent thionein chains. The mechanism of control of zinc-thionein synthesis by Zn2+ appears to involve changes in the amounts of a short-lived, poly(A)-containing RNA whose translation can be derepressed by additional exposure to Zn2+.


On the magnetic field dependence of the yield of the triplet state in reaction centers of photosynthetic bacteria.

The yield of the triplet state in reaction centers of Rhodopseudomonas sphaeroides is dependent on the strength of an applied magnetic field. Reaction centers of the wild type that lack a functional iron complexed to the primary acceptor ubiquinone show a dependence similar to that of reaction centers of the mutant R-26 in which the iron-ubiquinone complex is intact. Apparently, the iron of the iron-ubiquinone complex is not essential to the effect, but it does exert an influence on its extent. Inchromatophores, the effect is about 2-fold decreased; the value of the magnetic field at which half the effect is found is about 500 G, in contrast to this value for reaction centers, which is 50--100 G. The magnetodependence of the triplet yield is discussed in terms of the Chemically Induced Dynamic Electron Polarization mechanism (CIDEP).


The carotenoid shift in Rhodopseudomonas sphaeroides. Change induced under continuous illumination.

The spectrum of the carotenoid shift generated under continuous illumination in the GIC mutant of Rhodopseudomonas sphaeroides, which has a single carotenoid, has been examined under a variety of conditions expected to alter the size of the membrane potential. If the difference spectrum observed was due to a species with the spectrum of the bulk pigment, it would correspond to a change of a variable proportion of the pigment to a form absorbing at a higher wavelength. The maximal change induced by light could be described as a shift of about 10% of the pigment by 7 nm to the red, assuming that the shifted species was spectrally identical to the bulk carotenoid. It is concluded that the changes seen are not easily compatible with a progressive red shift in the whole spectrum with increasing applied potential as would be expected from a simple linear electrochromic mechanism; alternative hypotheses are discussed.


Kinetics of electron transfer between the primary and the secondary electron acceptor in reaction centers from Rhodopseudomonas sphaeroides.

Photoreduction of the two ubiquinone molecules, UQ1 and UQ2, bound to purified reaction center from Rhodopseudomonas sphaeroides induces different absorption band shifts of bacteriochlorophyll and bacteriopheophytin molecules depending on which ubiquinone is photoreduced. This allows us to study electron transfer between UQ1 and UQ2 directly by absorption spectrometry. The results support a model in which electrons are transferred one by one from UQ1 to UQ2 with a half-time 200 micro seconds, and two by two from fully reduced UQ2 to the secondary acceptor pool.


[Study of the phenomenon of specific suppression of the immune response in an adoptive transfer system].

It was revealed that the administration of the spleen cells (SC) of syngeneic animals immunized with a high dose of sheep red blood cells (SRBC) to intact mice led to a marked specific suppression of the recipients' immune response. The donors' SC obtained on the 14th day after the intraperitoneal injection of SRBC had the greatest suppressive activity. The SC of intact animals and mice given rat erythrocytes preliminarily failed to influence the immune response of the intact recipients in their SRBC immunization. Treatment of immune SC with the anti-T-serum (ATS) or the anti-B-globulin (ABG) and the complement considerably decreased or completely eliminated the suppressive activity. Administration of a mixture of two immune SC suspensions one of which was ATS- and another ABC-treated did not produce any suppression of the immune response in the intact recipients. It is supposed that the suppressor cells in the given model were T-lymphocytes expressing the antigens, common of cross-reacting with the B-cells.


[Simultaneous determination of T-, B- and mixed rosette-forming lymphocytes in human peripheral blood].

Preliminary treatment of erythrocyte suspension with trypan blue solution did not affect their capacity to participate in the reaction of spontaneous rosette formation, but permitted to differentiate them in a mixture with other erythrocytes after staining with methyl-green-pyronine on a fixed slide. By using a mixture of such marked erythrocytes sensitized with antibodies and a complement, the presence in the peripheral blood of healthy people of a small lymphocyte subpopulation connecting these two types of indicator particles was demonstrated.


Inhibition of ristocetin-induced platelet agglutination by vancomycin.

Ristocetin and vancomycin are structurally similar glycopeptide antibiotics. Both vancomycin and ristocetin in high concentrations (3.0 mg/ml) cause the precipitation of fibrinogen, plasminogen, and IgG from platelet-poor plasma (PPP). In contrast to ristocetin, vanomycin (0.5-1.5 mg/ml) does not agglutinate platelets in normal platelet-rich plasma (PRP) or formalin-treated platelets in the presence of normal PPP. Preincubation of vancomycin (0.5-1.25 mg/ml) with normal PRP, von Willebrand platelets in normal PPP, or formalinized platelets results in inhibition of platelet agglutination induced by ristocetin (0.7-1.25 mg/ml) or ristocetin and normal PPP. This inhibition can be overcome by increasing the final concentration of ristocetin in the platelet suspension. Preincubation of formalin-treated platelets with the major fraction obtained by carboxymethyl-Sephadex C-50 chromatography of commercial vancomycin also results in inhibition of agglutination induced by ristocetin and normal PPP. Incubation with vancomycin (1.25 mg/ml) does not interfere with von Willebrand factor (vWF) or factor VIII coagulant activities in normal PPP or in Sepharose 4B void volume fractions of PPP. These results indicate that vancomycin interacts with normal, von Willebrand, and formalin-treated platelets and inhibits the binding of ristocetin (or ristocetin-vWF complexes).


Granulopoietic and erythropoietic activity in patients with anemias of iron deficiency and chronic disease.

The serum levels of granulocyte colony-stimulating factor (CSF) and erythropoietin (Ep) were measured in 16 patients with iron-deficiency anemia and 15 patients with the anemia of chronic disease. Levels of both CSF and Ep in the serum of patients with iron-deficiency anemia had an inverse linear relationship to the level of the packed cell volume (PCV). There was no correlation between PCV and the levels of CSF or Ep in the serum of patients with the anemia of chronic disease. The similarity in the behavior of CSF and Ep in iron-deficiency anemia suggests that they may be influenced by similar control mechanisms or have a common cellular or molecular source.


[Cold-lymphocytotoxic antibodies in the sera of cervix-carcinoma patients].

Sera of 120 patients with cervical cancer were screened for cold reacting, complement dependant autolympho-cytotoxins (CoCoCy). These antibodies occurred in 21,7% of the patients in comparison with 11,2% of 116 controls. The highest percentage of CoCoCy-antibodies was detected in the sera of patients with cervical cancer stage I (27,6%). Thus demonstration of CoCoCy-antibodies may be of pathogenetic rather than of diagnostic interest. CoCoCy-antibodies could be seen to reflect autoimmune reactions in cervical cancer.


Prenylamine-induced contracture of frog skeletal muscle.

1. Experiments were performed to determine the influence of prenylamine on excitation-contraction coupling in frog sartorius muscle. 2. Prenylamine (0.2-1.0 mM) produced a biphasic contracture in skeletal muscle characterized by an initial phasic and subsequent tonic contracture. 3. Neither dantrolene nor procaine blocked the prenylamine-induced contracture. Pretreatment with 100 mM K+ blocked the phasic but not the tonic component of the prenylamine contracture. 4. Prenylamine produced a sustained increase in 45Ca efflux at all concentrations that produce contracture. These concentrations of prenylamine also depressed the action potential, muscle twitch and resting potential. 5. Low concentrations of prenylamine (0.05 mM) which produced neither contracture, 45Ca efflux nor 45Ca influx, depressed the action potential, muscle twitch and K+ contracture. 6. The results suggest that prenylamine not only alters calcium mobility but also membrane permeability to other ions.


Clinical findings, early endoscopy, and multivariate analysis in patients bleeding from the upper gastrointestinal tract.

A simple system has been developed to identify patients with upper gastrointestinal tract haemorrhage who run a high risk of continued bleeding or rebleeding. The system is based on six items of patient data available at or soon after arrival in hospital. It was evaluated in a prospective study of 66 patients with upper gastrointestinal tract haemorrhage. Over half of the patients classified by the system into a high-risk category either continued bleeding or rebled after apparent cessation (as against one out of 33 patients in the low-risk category). The high-rish group also had a higher mortality (21%) than those in the low-risk group (nil). The addition or subtraction of early endoscopic findings made little difference to the accuracy of prognosis.


The entry of taurine into the neural retina and pigment epithelium of the frog.

Autoradiographs of frog retinas incubated with radioactively labelled taurine show heavy grain density over (i) cells in the position of amacrine interneurones, (ii) the inner plexiform (synaptic) regions, giving a striated appearance, (iii) photoreceptor cells and their synaptic terminals, and (iv) the pigment epithelium. The inner retina, the photoreceptor cell layer and the pigment epithelium all have uptake systems for taurine with apparent Km's in the high affinity range (Km, 20-50 micron; Vmax, 13-33 nmoles/g/min). In vivo subcutaneously injected taurine was taken up by the pigment epithelium and then passed to the photoreceptors and inner retina over about 10 days. The total level of nucleide in the retina remained constant for at least 6 weeks. There was little or no metabolism of the labelled taurine during this time.


Partial preparative separation and properties of the isoinhibitors of human alpha 1-antitrypsin (alpha 1-protease inhibitor).

Human lapha 1-antitrypsin (alpha 1-protease inhibitor) was chromatographed on a DEAE-cellulose column at pH 6.4. After elution with a linearly increasing concentration of NaCl, five pools (pools I-V) were formed from the eluate, pool I corresponding to the lowest and pool V to the highest concentration of salt. As demonstrated by analytical isoelectric focusing, with increasing concentrations of NaCl the concentration of the cathodal isoinhibitors gradually decreased and the concentration of the anodal ones increased in the pools. Pool I contained only three cathodal and pool V only three anodal isoinhibitors with a limited overlap between the pools. In contrast with the isoinhibitor composition, the sialic acid contents of the pools did not vary with the elution conditions. In line with the chemical evidence, desialylation of the fractions did not affect their electrofocusing positions relative to one another and did not abolish the microheterogeneity of the protein.


The effect of oral contraceptives on colour vision in diabetic women.

The results of previous studies of the effect of oral contraceptives on visual function have produced discrepancies and have lacked specific restraints on the control and experimental groups. We compared 14 diabetics with normal acuity who were taking oral contraceptives with equivalent diabetic and control groups and used the Pickford-Nicholson anomaloscope and the Farnsworth-Munsell 100-Hue test. Diabetics using oral contraceptives showed a definite trend to increases in tritanomaly and extended red-green matching ranges. When these losses were classified by degree of defect a significantly higher incidence of major defects was found among diabetics on "the pill". Partial correlations for colour variables, duration of diabetes and duration of contraceptive therapy revealed a compounding effect. While subjects using oral contraceptives demonstrated trends toward the extreme scores, these effects were found only in one out of every four users.


Deoxyadenosine metabolism and toxicity in cultured L5178Y cells.

The growth of cultured L5178Y cells is inhibited by relatively low concentrations fo deoxyadenosine in the presence of deoxycoformycin, an inhibitor of adenosine deaminase. Cell viability is reduced, presumably as a consequence of the induced state of unbalanced growth which is characterized by inhibition in DNA synthesis, accumulation of cells in G1 or early S phase, a continuation in RNA synthesis, and increasing cell volume. The intracellular concentrations of purine and pyrimidine ribonucleoside phosphates remain essentially unchanged. The significant changes in the intracellular deoxynucleoside triphosphate pools are an increase in deoxyadenosine triphosphate and a decrease in deoxycytidine triphosphate.


Estrogen receptor and proteolytic activity in human breast tumor nuclei.

We have previously found that human breast cancer cells in tissue culture contain estrogen receptor in their nuclei despite the absence of estrogen. We have now investigated solid human breast cancer biopsies and find that proteolytic activities in extracts from the nuclear pellets of these biopsies interfere with or prevent the measurement of nuclear estrogen receptor when the protamine assay is used. However, the problems of receptor degradation can be avoided by the use of a hydroxylapatite assay.


Antifolates: in vivo kinetic considerations.

The action of antimetabolites in vivo involves the consideration of several interrelated factors. If the mechanism of biochemical action is understood, the next items of priority are whether the active form of the drug gets to the site of action, its concentration at this site, the time course of removal of active drug from this site, and how these kinetics relate to the biochemical inhibition. Studies of antifolates represent some of the approaches used to further understand antimetabolite action in vivo. The interrelationships of blood flow, mixing volumes of tissue compartments, membrane resistance, binding of drug, binding site formation, transport competition, and biochemical kinetics of rate-limiting steps, substrate competition, and salvage pathways are considered from an in vivo point of view.


Regulatory control of tetrahydrofolate coenzymes in folate auxotrophs.

The interrelated enzymic reactions of folate metabolism are presented and key tetrahydrofolate-producing reactions are emphasized. As observed with the methotrexate (MTX)-resistant mutant strain Streptococcus faecium var. durans/Ak, the regulatory roles of serine and purines in controlling their own synthesis by the repression of enzymes required for co-factor synthesis are reviewed. Positive induction of the dihydrofolate reductase activity of this mutant by folate and the antagonism of the folate effect by purines and thymine are discussed. A protective agent of the reductase-active protein, MTX is viewed also as a "positive" inducer of dihydrofolate reductase. Preliminary studies with L1210 leukemia-bearing mice and the murine leukemia ERLD in vitro suggest that citrovorum factor (CF) also triggers a positive induction of the reductase of the small intestine and of ERLD cells without apparently influencing the reductase level of L1210 in vivo. The possibility that control mechanisms, by which MTX and CF indirectly regulate enzyme synthesis in drug-stressed, CF-rescued cells, contribute to the success of high-dose MTX-CF rescue therapy is introduced.


Lipid-soluble diaminopyrimidine inhibitors of dihydrofolate reductase.

On the basis of activity against experimental tumors and potency as inhibitors of human dihydrofolate reductase, two compounds were selected for pharmacokinetic evaluation: metoprine ((2,4-diamino-5-(3',4'-dichlorophenyl)-6-methyl pyrimidine, DDMP, B.W. 197U) and etoprine, the corresponding 6-ethyl analog (DDEP, B.W. 276U). These lipid-soluble compounds readily cross the blood-brain barrier and penetrate rapidly into brain and brain tumors induced in rats by ethylnitrosourea. Both compounds are extensively bound to human plasma protein and their slow elimination from plasma and tissues contrasts with the kinetics of methotrexate. Cerebrospinal fluid levels of "folate" were elevated following oral administration of citrovorum factor to rats but not following equivalent doses of folic acid. The balance between selective action of the drug and selective protection by the vitamin is discussed with regard to differential distribution into separate compartments.


Aspects of the reversal of methotrexate toxicity in rodents.

An ip injection of a Lactobacillus casei dihydrofolate reductase preparation into rats and mice given a single lethal dose of methotrexate (MTX) caused a marked lowering of free MTX in the blood. Alternatives to citrovorum factor as agents for reversing MTX toxicity were explored in mice. dl, L-5-Methyltetrahydrofolate, dl,L-5,10-methylenetetrahydrofolate, l,L-5,10-methylenetetrahydrofolate, and dihydrofolate were also effective MTX antagonists; d,L-5,10-methylenetetrahydrofolate was inert.


High-dose methotrexate with citrovorum factor in osteogenic sarcoma--progress report II.

Vincristine (VCR), high-dose methotrexate (MTX), and citrovorum factor (CF) were administered to 12 patients with classic osteogenic sarcoma with local control. Seven patients (58%) are free of pulmonary metastases for 2+-31/2+ years. With a second adjuvant program incorporating adriamycin (VCR, MTX, CF, and adriamycin), 16 of 20 patients are free of pulmonary metastases for 6+-18+ months. Five patients who developed pulmonary metastases were rendered free of disease by surgical resection. The VCR, MTX, and CF program was also administered at weekly intervals to eight patients with pulmonary metastases or unresected primary lesions. Two complete and one partial response were obtained in four patients with pulmonary metastases and three complete and one partial response were obtained in patients with primary lesions. This program was also administered in combination with radiation therapy to four patients who relapsed on conventional VCR, MTX, CF, and adriamycin therapy following surgical resection of pulmonary metastases. They remain free of recurrent disease for 2+-14+ months. There was no alteration in the incidence of toxicity when compared to earlier investigations. The results indicate that the VCR, MTX, and CF program has had a major impact on the management of osteogenic sarcoma.


High-dose methotrexate with citrovorum factor rescue for the treatment of central nervous system tumors in children.

Eleven patients with brain tumors recurrent after surgery and radiation therapy were treated with high-dose methotrexate (MTX) (300-500 mg/kg) with citrovorum factor rescue (CFR). MTX was given as an iv infusion over 4 hours followed 2 hours later by oral CFR (10 mg every 6 hours X 12). MTX levels were measured in the serum, lumbar cerebrospinal fluid (CSF), and ventricular CSF at 0, 4, 12, 24, 48, and 72 hours from the start of the MTX infusion. MTX concentrations of greater than 10(-6) M were measured in the CSF over a period of 24 hours after the iv infusion. Peak CSF concentrations reached were greater than 10(-5) M. After the response to high-dose MTX with CFR was evaluated, vincristine (1.5 mg/m2) and a nitrosourea (methyl-CCNU or BCNU) were added to this treatment regimen. Two of four patients with recurrent pontine glioma and five of seven patients with recurrent medulloblastoma had favorable objective responses to treatment. It is suggested that high-dose MTX with CFR be cautiously considered for the primary treatment of intracranial neoplasms in children with the hope of increasing the cure rate for children with malignant brain tumors.


Incidence of drug-related deaths secondary to high-dose methotrexate and citrovorum factor administration.

A review of 498 patients treated with high-dose methotrexate (MTX) with citrovorum factor rescue revealed 29 drug-related deaths. Until the important factors in those deaths are identified, the use of high-dose MTX should be limited to institutions that possess the necessary supportive facilities and the ability to measure serum levels of the drug.


The structure of the capsular antigen from Haemophilus influenzae type A.

Structural investigation of the capsular antigen from Haemophilus influenzae type a has shown it to be composed of 4-O-beta-D-glucopyranosyl-D-ribitol residues joined through phosphoric diester linkages between O-4 of D-glucose and O-5 of D-ribitol. Chemical degradations and 13C-n.m.r. spectroscopy were the main methods used.


The in vitro differentiation of density sub-populations of colony-forming cells under the influence of different types of colony-stimulating factor.

The in vitro proliferation and differentiation of myeloid progenitor cells (CFU-c) in agar culture from CBA/Ca mouse bone marrow cells was studied. Density subpopulations of marrow cells were obtained by equilibrium centrifugation in continuous albumin density gradients. The formation of colonies of granulocytes and/or macrophages was studied under the influence of three types of colony-stimulating factor (CSF) from mouse lung conditioned medium CSFMLCM), post-endotoxin mouse serum (CSFES) and from human urine (CSFHu). The effect of the sulphydryl reagent mercaptoethanol on colony development was also examined. The density distribution of CFU-c was dependent on the type of CSF. Functional heterogeneity was found among CFU-c with partial discrimination between progenitor cells forming pure granulocytic colonies and those forming pure macrophage colonies. Mercaptoethanol increased colony incidence but had no apparent effect on colony morphology or the density distribution of CFU-c.


Mobilization of B and T lymphocytes and haemopoietic stem cells by polymethacrylic acid and dextran sulphate.

The leucocytosis which can be evoked by the polyanions dextran sulphate (DS), polymethacrylic acid (PMAA) and the copolymer of PMAA and styrene (PMAA--STYR) was studied in mice. After intravenous administration of these polyanions peak numbers of leucocytes were found in the peripheral blood 3 hr after injection. All three types of polyanions increased the number of lymphocytes, granulocytes and monocytes. Dose--response studies revealed that the nature of the polyanion determined the degree of leucocyte mobilization. The most potent mobilizer was found to be DS. This polyanion could evoke a six-fold increase of the number of peripheral blood leucocytes. By means of the membrane fluorescence technique it could be demonstrated that optimal doses of DS, PMAA and PMAA--STYR mobilized both B and T lymphocytes. The ratio between the number of B and T cells mobilized was greater for DS than for the other two polyanions. Intravenous injection of DS, PMAA and PMAA--STYR also increased the number of circulating haemopoietic stem cells (CFU-S). The most potent stem cell mobilizer appeared to be PMAA--STYR. This polyanion evoked a twenty-five-fold increase in the number of CFU-S.


Fine structure of ependymal cells in the median eminence of the frog and mouse revealed by freeze-etching.

Freeze-etched preparations of the ventricular surfaces of ependymal cells clearly reveal the presence of pinocytotic vesicles opening into the third ventricle and large vacuoles formed by broad cell projections. The density of the vesicular openings is approximately 20 per micron2. The ependymal cells in the median eminence of the frog are adjoined by tight junctions comprised of five to eight interconnected junctional strands, whereas near the median eminence in the mouse only one to two such strands form the tight junction of the ependymal cells. Gap junctions between the adjacent ependymal cells are detected near the median eminence in the mouse but not in the frog.


An improved method of myocardial protection with pulsation during cardiopulmonary bypass.

A new valveless pulsatile assist device (PAD) has been developed that converts roller pump flow into synchronized pulsatile flow. The PAD can also be used as an arterial counter-pulsator (ACtP) before and after cardiopulmonary bypass (CPB). The PAD was employed in 100 adult patients undergoing open heart surgery for coronary artery and/or valvular heart disease. Seventy-three of these patients were NYHA class III or IV, had ejection fractions of less than 0.3, or an LVEDP greater than or equal to 18 mm Hg. Sixty-one patients underwent coronary artery bypass alone, 17 valve replacement alone, three ventricular aneurysm alone, 12 combined coronaries and valves, and seven combined coronaries and ventricular aneurysms. The device functioned as a hemodynamically effective ACtP before and after CPB. During CPB, pulse pressures of 40-50 mm Hg were readily obtained. Urinary outputs during CPB were increased on the PAD when compared to a control group (9.18 +/- 0.68 cc/min vs 3.90 +/- 0.34 cc/min). In addition, during CPB, coronary graft blood flow (CBF) increased an average of 21.4 +/- 6.1% with the PAD, and after CPB, CBF increased an average of 25.0 +/- 5.9%. Free plasma hemoglobins after CPB were not elevated. Only one patient had a perioperative myocardial infarction, and this patient was successfully treated with intra-aortic balloon pumping. It is suggested from these data that use of the PAD may decrease both the incidence of perioperative myocardial infarction and the need for postoperative intra-aortic balloon pumping.


The spectrum of pathologic changes in aortocoronary saphenous vein grafts.

Aortocoronary vein grafts removed at autopsy of 182 patients who died up to 5 years after the bypass operation were examined by light and electron microscopy. During the first month after surgery, graft occlusion was due to thrombi, some of them recent, some organized and recanalized. Intimal proliferation of the graft first appeared 4 weeks after the bypass surgery; several cases of total occlusion of the lumen by this process were seen within 6 months of the operation. A change in the morphological features of the intimal thickening from cellular to fibrotic and hylain-like was observed in several grafts implanted for more than 1 year. Typical atherosclerosis developed in vein grafts in three of the six patients surviving the operation for more than 3 years.


The saphenous vein versus internal mammary artery as a coronary bypass graft.

Controversy persists as regards the efficacy of aortocoronary saphenous vein bypass graft (SVBG) compared to direct internal mammary artery (IMA) anastomosis. In general, the IMA graft (IMAG) is considered to be superior as regards postoperative patency. To avoid preselection bias, 74 consecutive, unselected patients with bypassable lesions of the left anterior descending artery (LAD) were randomized to undergo either SVBG or IMAG to the LAD in 1972-1974. The majority of patients had, in addition, SVBGs to other vessels. Postoperative angiograms, an average of 6 months after surgery, were obtained in two-thirds of the patients. The following observations were made: (formula: see text). In this series there is no clear advantage of the IMAG over the SVBG. The preparation of the internal mammary artery for grafting is tedious and the anastomosis more difficult to perform. The resultant flow in the internal mammary artery graft is less overall than in the SVBG. In over 400 unselected SVBGs to the LAD that have been restudied thus far in our practice, an 86% patency rate has been achieved.


Incidence and mortality of perioperative myocardial infarction in patients undergoing coronary artery bypass grafting.

The incidence of perioperative myocardial infarction (MI) determined by electrocardiogram was examined in 168 consecutive patients having only coronary artery bypass grafting at Yale-New Haven Hospital from July 1974 to June 1975. The incidence of MI and its mortality were correlated with clinical, hemodynamic, anatomic, and operative factors. Perioperative MI occurred in 23% of all patients (39/168); 26 in the inferior, 11 in the anterior, and two in the anterolateral wall. Three factors appeared related to the occurrence of MI: 1) abrupt propranolol withdrawal 24 hours prior to surgery (Prop) (32%, 33/103); 2) left main coronary artery disease (LMCD) (37%, 7/19); and 3) cardiopulmonary bypass longer than 60 minutes (CPB) (23%, 30/128). To more precisely predict MI, combinations of factors were examined. The combination of LMCD and CPB was 39%, (7/18) while the absence of either yielded an incidence of only 5.1% (2/39) (P less than 0.001). The mortality of patients with MI was 15.4% (6/39) while in patients without MI the mortality was 1.6% (2/129). We conclude that the risk of perioperative MI is significantly increased by abrupt propranolol withdrawal 24 hours before surgery, left main coronary artery disease, and cardiopulmonary bypass longer than 60 minutes in patients undergoing coronary artery bypass grafting. The mortality of perioperative MI is high, despite previous reports of the benignity of perioperative myocardial infarction.


Coronary sinus blood flow and sampling for detection of unrecognized myocardial ischemia and injury.

Fifteen patients were studied to detect unrecognized intraoperative ischemia or necrosis in perioperative myocardial infarction (MI) associated with coronary bypass. Simultaneous arterial and coronary sinus blood samples were analyzed for lactate and both total and MB-CPK. Coronary sinus flow measurements were done coincident with sampling in seven patients. Five had perioperative MI diagnosed by positive pyrophosphate scan and electrocardiogram. Although normal initially (mean 19 +/- 5.0%), lactate extraction after thoracotomy, before aortic cross-clamping, became abnormal in 12 patients with more pronounced abnormality in those with perioperative MI (-19 +/- 9.0%). Net efflux of lactate was higher in perioperative MI (mean 0.6 +/- 0.2 vs 0.016 +/- 0.04 mM/L) than in non-MI patients. All patients had detectable total and MB-CPK (mean 295 and 31 IU/L, respectively) and all those with coronary disease had a positive arterial-coronary sinus gradient for MB-CPK (mean 9 IU/L). Perioperative MI patients had a higher gradient than non-MI patients (mean 25 vs 2 IU/L) and with one exception that gradient exceeded 5-7 IU/L. It is concluded that severe ischemia before aortic cross-clamping precedes perioperative MI and may contribute to release of CPK into coronary sinus blood. Improvement in the techniques of anesthesia and intraoperative myocardial preservation are suggested.


Assay of proteolytic activity by gelatin liquefaction (trypsin assay by gelatin liquefaction).

A new assay for proteolytic enzymes and their inhibitors based on the liquefaction of gelatin gels has been developed. The assay is more sensitive than colorimetric tests, can be carried out upon colored or turbid samples and does not require the use of a spectrophotometer. The procedure consists of incubating the test sample with a fluid gelatin solution, cooling the solution so that it sets to a firm gel and then incubating at a warmer temperature until the gel iquefies. The time taken for liquefaction is several days for a sample of pure buffer, about one minute for a sample containing 0.5 microgram of trypsin per ml and longer for samples containing less trypsin, following an empirical calibration. An appreciable decrease in tryptic activity can be detected in the presence of only 0.1 KIU of Trasylol (bovine pancreatic trypsin inhibitor) by this method.


The effect of oral glucose on von Willebrand factor activity in normal and diabetic subjects.

We have previously noted increased platelet aggregation and high von Willebrand factor activity in patients with chemical diabetes. In this paper we have studied platelet aggregation, plasma glucose, insulin, free fatty acids, growth hormone, and von Willebrand factor activity during the glucose tolerance test in six normal and six chemical diabetic subjects. The results suggest that von Willebrand factor activity is suppressed coincident with the rise of glucose and insulin and provide further evidence of hormonal and metabolic control of levels of von Willebrand factor activity.


X-linked aqueductal stenosis.

A family is reported in which eight members of one generation were affected by the syndrome hydrocephalus with aqueductal stenosis. With the exception of one child who lived for several weeks, they all died at or within 10 days of birth. Autopsy of a pair of affected twins showed marked stenosis of the aqueduct of Sylvius with fusion of the lamina quadrigemina. There were no signs of previous or present inflammatory changes or neoplasia. All the affected individuals were males, and the familial and pathological data presented support the concept that aqueductal stenosis in this family was due to an X-linked gene, and may have a developmental origin.


Scanning and transmission electron microscopic study of human pulmonary pneumocystosis.

Histopathologic examinations were performed in 13 autopsy cases with Pneumocystis pneumonia, five of whom were examined with scanning as well as transmission electron microscope. Findings by scanning electron microscopy were compared with those by light microscopy and transmission electron microscopy. By scanning electron microscopy, two principal structural varieties of Pneumocystis organisms, smooth-surfaced organisms and rough-surfaced organisms, could be classified. It was indicated that rough-surfaced organisms and smooth-surfaced organisms correspond respectively to trophozoite-type organisms and thick-walled cysts, recognized with transmission electron microscope. Intraalveolar honeycombed material was mainly composed of dilated trophozoite-type organisms, containing thick-walled cysts scatteredly.


Chromosomal evolution in a haploid frog cell line: implications for the origin of karyotypic variants.

ICR 2A, a haploid cell line derived from Rana pipiens embryos, has remained haploid in number of chromosones and their relative lengths and centromere positions for 500 cell generations. After this time, two new haryotypes appeared; relative length measurements indicate that the first has a translocation from chromosome 4 to 6, the second translocations from 3 and 4 to 6 and 7. The single exchange karyotype is not a precursor for the double exchange according to a statistical analysis. The double exchange karyotype characterized 90% of some cultures although a selective advantage could not be demonstrated for these cells. The observations suggest that a non-clonal or multicellular origin may account for these karyotypic variants.


[Possibilities for the use of lasers in dental surgery].

The use of the Nd:YAG laser in everyday oral surgery in patients with a hemorrhagic diathesis is reported. It proved successful in various hemorrhagic disorders mild forms of hemophilia A. The most essential including step forward seems to be that this may simplify the so far complicated treatment of this group of patients in a hospital, as it may enable outpatient therapy to be performed and considerably reduce the cost of treatment. In addition, the risk of hepatitis is smaller for all those patients in whom missing clotting factors have had to be substituted up to the present.


Studies on DNA synthesis in goat mammary organ culture under the influence of various hormones.

A study has been made of the hormones required for stimulation of DNA synthesis in organ culture of mammary tissue of goats. On culture in Waymouth's medium without added hormones the incorporation of 6-3H-thymidine into DNA was low. The addition of insulin caused a high stimulation of thymidine incorporation. However, the addition of cortisol, prolactin, growth hormone, 17beta-estradiol, progesterone alone or in combination had no effect on DNA synthesis. The minimal effective concentration of insulin was 0.1 mug ml-1. The addition of calf serum caused slight stimulation of DNA synthesis. When the mammary explants were exposed to a combination of serum and insulin, the rate of thymidine incorporation was always additive suggesting that DNA synthesis was affected independently by serum and insulin.


Interaction of thyroid hormones with human muscular tissue, leucocytes and adipose tissue in vitro.

The uptake of triiodothyronine (T3) and thyroxine (T4) by human leucocytes as well as by adipose and muscular tissues in vitro was markedly dependent on the extracellular protein concentration. The presence of extracellular protein was responsible for the difference in the uptake of T3 and T4 by leucocytes (the incorporation of T4 was significantly lower than that of T3), whereas its presence in the medium containing adipocytes did nto influence the incorporation values. In a protein-free medium, the muscular tissue uptake of T3 exceeded that of T4. In this tissue the deiodination of both hormones was likewise significantly different, that of T4 being higher. The conversion of T4 to T3 was also higher in the muscle cells, but represented only about 75% of the total deiodinated fraction. In the remaining tissues, no differences were observed in the uptake and deiodination of T3 and T4. The deiodination of T4 in human leucocytes was found to be considerably dependent of pH of the incubation medium (two deiodination optima, a higher one in acid region) whereas the deiodination of T3 was fairly indifferent to variations of pH (one flat deiodination optimum in the weakly alkaline region).


Role of brain catecholaminergic system in hypothalamic obesity in rats.

Distribution of labelled catecholamines (CA) was studied after intraventricular injection of 3H-norepinephrine (NE) and 3H-dihydrozyphenylalanine (DOPA) in several brain regions of ventromedial hypothalamic lesioned female rats. After intraventricular infection of 3H-NE a decrease in endogenous NE content and a marked increase in labelled NE concentration were observed in the preoptic-basal cortical area and lateral hypothalamus, while no change was found in these parameters in brain areas caudal to the lesion. The 3H-DOPA uptake of preoptic-basal cortical area and also the lateral hypothalamus was lower. No change was found in the uptake of 3H-DOPA in the corpus striatum. These results support the hypothesis that the decreased function of noradrenergic pathways in the medial forebrain bundle plays a role in the development of hypothalamic obesity without any concomitant functional changes in the striatal dopaminergic system.


Steroid metabolism of foetal tissues. V. Comparative studies in a 18 trisomic foetus.

After amniotic fluid and fetal skin biopsy cultures trisomy 18 was diagnosed and the steroid metabolism of tissues from this foetus was studied by double isotope methods and compared with results from foetuses of similar age. The metabolism of 14C-pregnenolone, the aromatization of androstendendione to oestrone and the 5alpha-reduction of testosterone to 5alpha-dihydrotestosterone in this foetus were similar as in other foetuses. The reason for a low oestriol excretion in pregnancy with 18 trisomic foetus is not evident from the data obtained.


In vitro metabolism of [4-14C] androstenedione and [4-14C] testosterone by rabbit placenta.

The metabolism of labelled androstenedione and testosterone in rabbit placenta on day 15 and 28 of gestation was studied in vitro. Extensive ring A reduction was observed. 5beta-Androstane-3alpha,17beta-diol,5beta-androstane-3beta,17beta-diol, 3alpha-hydroxy-5beta-androstan-17-one, 3beta-hydroxy-5beta-androstane-17-one, 17beta-hydroxy-5beta-androstan-3-one and 5beta-androstane-3, 17-dione were formed from androstenedione as proved by crystallization method. Testosterone was metabolized to 5beta-androstane-3alpha,17beta-diol, 5beta-androstane-3beta,17beta-diol and 17beta-hydroxy-5beta-androstan-3-one. The formation of estrogens was not found from any precursor. The results indicate that the rabbit placenta in the mid and late gestation shows delta4-5beta-reductase, 17beta-, 3alpha-and 3beta-hydroxysteroid dehydrogenase activities.


Effect of insulin on glucose metabolism in isolated adipocytes and in diaphragm: effect of age and neonatal nutrition.

Differences in the response of isolated adipocytes to insulin were found in relation to the age and early postnatal nutrition. In old rats (15 months) an impaired stimulation of 14C-glucose incorporation into lipids was found after insulin as compared to young animals (1 or 2 months old). In isolated fat cells from young neonatally underfed rats a higher increase of insulin induced lipogenesis was observed than in controls. The response to insulin, however, was not influenced by neonatal nutrition inold rats. Glucose oxidation in the diaphragm was also lower in older animals (4 months) than in young (1 month) rats. The stimulation of glucose oxidation by insulin was higher in neonatally underfed rats as compared to overfed ones during the suckling period. The rise of glucose oxidation after insulin decreased with age. These results showed that the response of muscular and adipose tissue decreases by age and that nutrition during the early postnatal period may affect the influence of insulin on the metabolsim of glucose in adipose and muscular tissue in young animals.


Binding of synthetic anabolic steroids to testosterone-estradiol binding globulin and to rat prostate cytosol.

The binding of five synthetic anabolic steroids and two natural androgens to testosterone-estradiol binding globulin (TeBG) and to cytoplasmic fraction containing androgen receptors from prostates of castrated rats was compared. The binding affinity to TeBg decreased in sequence: dihydrotestosterone--testosterone--methyltestosterone-methandienone--nortestosterone--dimethylandrostanolone--nortestosterone--phenylpropionate (no binding); in the prostatic cytosol the following fecreasing sequence was found: dihydrostestosterone--methyltestosterone--methandienone--nortestosterone--nortestosterone phenylpropionate--testosterone--dimethylandrostanolone. The law binding to TeBG of 17alpha-methylated steroids possessing at the same time high affinity to cytoplasmic receptors may enhance their effect in target tissues.


Water deprivation for 24 hours increases selectively blood flow in posterior pituitary of conscious rats.

Blood flow was measured by means of 125I-Antipyrin distribution and was found to be increased in the posterior pituitary of conscious rats following water deprivation for 24 h as compared to either normohydrated control or to force hydrated rats (2.86 ml min-1 g-1 vs. 2.36 ml or 2.08 ml, respectively). Other parameters of systemic haemodynamics, blood flow in the brain or in the hypothalamus and in anterior pituitary did not differ in three experimental groups of rats subjected to various water intake. The increased blood flow in the posterior pituitary in dehydrated rats presumably parallels the locally intensified metabolic rats due to the enchanged stimulation of the antidiuretic hormone release.


Optokinetic and vestibulo-ocular reflexes in dark-reared rabbits.

Rabbits were raised in complete darkness for 7 months after birth. Eye movements were measured at the end of this period and in the next 3 months of normal light exposure with chronically implanted scleral coils. Horizontal optokinetic nystagmus (OKN) was tested inside a large drum which was rotated at velocities between 0.06 and 60 degrees/sec. Vestibuloocular reflexes (VOR) were elicited by sinusoidal horizontal oscillation on a torsion swing at frequencies between 0.11 and 2.13 Hz and amplitudes up to 10 degrees. At the end of the light-deprived period (with the eyes still covered) a VOR could be elicited consisting of a normal mixture of smooth and saccadic components and normal phase relations, but the amplitude of the smooth (compensatory) component was reduced to about 1/3 of normal control values. At the first exposure to light an OKN could be immediately elicited which was normal in most respects, except for a reduction of the ratio slow phase eye speed/drum speed to about 2/3 of the value in normal controls. The preference of each eye for anterior motion and the quasiconjugate character of nystagmus in monocular stimulation were unaffected. Also the improvement of the VOR by vision was normal. No abnormal habituation or fatigeability were observed. In the next 3 months of normal light exposure about half of the amplitude defects in both systems were restored, largely in the first week. The remaining defects were apparently permanent.


[Stimulation of the reflex response of the anticoagulant system by intermediate product-1 of prothrombin proteolysis].

Injection of the intermediate 1 of prothrombin proteolysis into the frog's systemic circulation mobilized the anticoagulating and the fibrinolytic potential of the organism. This is not so in frogs with destroyed c.n. s. Electrical activity of the carotid chemoreceptors in considerably higher after perfusion with intermediate 1 of the frog's humorally isolated carotid labyrinth, as well as the total coagulation time, the total fibrinolytic activity, and the non-fermentative fibrinolysis in the systematic circulation. The data obtained suggest that the reflex activation of the physiological anticoagulating system can be induced can be induced by intermediate 1 which has the structure similar to thrombin but no clotting activity.


[Analysis of chrono-inotropy of the myocardium in poikilothermic animals].

Chrono-ionotropic interrelationships were studied in isolated strips of the myocardium of poikilothermous animals (frogs and fishes) in conditions of either stationary or transitional regimens of stimulation. In the stationary regimen, the rhythm-strength relation is simple and corresponds to a parabolic curve. While changing the lesser frequency of stimulation for greater one, both the positive and negative transitional abbreviating stirs were observed, in contrast to literature references. The phenomena of positive and negative transitional stairs were concluded to be unrelated to species while being a general biological form of the myocardium response to change of the stimulation rhythm.


A record keeping system addressing future needs.

Important long-range decisions regarding the provision of dental care and the education of dentists and dental para-professionals will be made by the government and third parties. The quality and interpretation of the data to be used depend on who gathers it. If the dental profession is not in the position to gather the data, others certainly will be. There is a wealth of statistical data in the records of every practice. The record keeping system described provides an organized way to get such information out, with a minimum of additional effort. Rather than making it a series of separate tasks to generate a statistical description of the practice population, the incidence of problems, or the progression of treatments, this record keeping system provides a single comprehensive method. This method grows with a practice, whether individual, group, or clinic. By doing this, it provides a long-range continuous monitor of the practice population and the problems incident to it. The installation of such a methodology in clinics and dental school faculty practices will rapidly contribute to our knowledge regarding dental health care. Adoption in whole or in part by private practioners will provide them with new tools for the delivery of better dental care and practice management.


[Prostaglandin F2alpha- and 15-methyl-prostaglandin F2alpha-application for the treatment of severe uterine bleedings (author's transl)].

The paper reports on intravenous and intrauterine application of Prostaglandin F2alpha and its 15-methyl derivative for the treatment of severe uterine bleedings in obsteterics and gynaecology. The effectiveness of the compounds is demonstrated.


Linkage disequilibrium for two X-linked genes in Sardinia and its bearing on the statistical mapping of the human X chromosome.

The distribution of four X-linked mutants (G6PD, Deutan, Protan and Xg) among lowland and once highly malarial populations of Sardinia discloses a clear-cut example of linkage disequiligrium between two of them (G6PD and Protan). In the same populations the distribution of G6PD-deficiency versus colorblindness of the Deutan type and the Xg blood-group is not significantly different from that expected at equilibrium. These data suggest indirectly that the loci for G6PD and Protan may be nearer to one another than those for G6PD and Deutan.


[Ambulatory hemorrhoidectomy through rubber band ligation-review of the literature].

The value of rubber band ligation in the treatment of haemorrhoids is discussed and the literature on the case histories of 3244 patients who were treated by this technique is reviewed. 36% of the patients found this form of therapy to be painless, 41% suffered little and 14% severe pain. 80% of all patients finally were free of symptoms. Rubber band ligation therefore is an effective method treating internal haemorrhoids. Its advantages are simplicity, relatively little discomfort for the patient, applicability in ambulant patients, no general anaesthesia, low cost and good results with only minor complications. Thus it is an alternative to sclerotherapy and to surgical haemorrhoidectomy.


[The rheumatic foot and its treatment].

The alterations of form and function of the rheumatoid foot are derived from the pathomechanical conditions. The latter are used as a measure for the treatment. Type and frequency of inflammatory alterations are studied by x-ray examination and new aspects are stressed. The deformities of the rheumatoid foot can be explained conclusively through the interaction of functional, gravitational, inflammatory and anatomical influences. The deformities of the toes are induced to a great extent by the deformities of the proximal part of the foot. The possibilities of surgical treatment are discussed in detail and systematically. The results of partially own methods are compared with those of other authors, and conclusions regarding the indication are drawn. The conservative treatment is considered under the aspects of the enlarged surgical possibilities. The need of a close cooperation between the different specialists is emphasized.


Evidence for a participation of the kallikrein-kinin system in the regulation of muscle metabolism during hypoxia.

The effect of hypoxia on muscle metabolism was studied in the human forearm by the registration of arterial-deep venous concentration differences of oxygen, glucose, lactate, pyruvate, acetoacetate, and muscular blood flow after short, transient arrest of the forearm circulation. These studies were performed during the intravenous infusion of physiological saline (n=4), of a kallikrein-trypsin inhibitor (n=4), and of kallikrein-trypsin inhibitor plus the intrabrachial-arterial infusion of bradykinin (n=4). Infusion of the kallikrein-trypsin inhibitor significantly reduced the well known hypoxia-induced acceleration of nuscular glucose uptake due to a reduction of blood flow and of muscular glucose extraction. These changes of muscular glucose metabolism were accompanied by more or less striking effects on the balances of oxygen, lactate and acetoacetate. Physiological doses of bradykinin into the brachial artery during the infusion of a kallikrein-trypsin inhibitor restored almost completely the metabolic response during hypoxia. From these data there is further evidence for a participation of the kallikrein-kinin system in the physiological regulation of muscular substrate metabolism.


Population genetics of alpha1-antitrypsin in the Netherlands. Description of a new electrophoretic variant.

Two groups of 708 healthy blood donors and 563 patients affected with chronic obstructive lung disease (C.O.L.D.) respectively, have been screened for alpha1-antitrypsin (alpha1AT) variants by electrophoresis on agarose-polyacrylamide gels at pH 4.7 and isoelectric focusing (IEF). The frequencies of the Pi (Protease inhibitor) alleles are comparable to those observed in the North European populations. As expected, the frequency of the Z gene is higher in the group of patients with C.O.L.D. Also the frequency of MZ phenotypes is higher among these patients, but in this case the difference is not statistically significant. With the aid of the electrophoretic methods described in the text we were able to detect a new electrophoretic variant (M3) showing a mobility intermediate between the M1 and the M2 phenotypes.


Improved medium for clonal growth of human diploid fibroblasts at low concentrations of serum protein.

A new medium (MCDB 104) has been developed which will support clonal growth of WI-38 cells at concentrations of serum protein as low as 25 micrograms per ml (equivalent to 0.05% serum). The principal factors responsible for reduction of the protein requirement are: (a) adjustment of all nutrient concentrations in medium F12 to experimentally determined optimum values for WI-38 cells; (b) supplementation with trace elements; (c) replacement of hypoxanthine and folic acid with adenine and folinic acid; and (d) coating of the culture surface with polylysine. Individually, many of these modifications exert only a small effect on cellular growth at reduced protein concentrations, but collectively their effect has been very substantial. Other strains of fibroblast-like human diploid cells from amniotic fluid, fetal lung and newborn foreskin also will grow at reduced concentrations of serum protein in the new medium.


Quantification of antibodies to the C3d subcomponent of human C3.

Purified soluble C3d has been employed to measure the concentration of anti-C3d antibodies in immune rabbit sera. Multiple batches of C3d, prepared from C3-C3b substrate by treatment with C3b-inactivator (KAF), after labelling with 125I, retained 80% immunoreactivity, and were stable on storage at -50 degrees and +4 degrees. Concentrations of anti-C3d were determined by Scatchard analysis of equilibrium concentrations of bound and free C3d in a mixture of 125I-labelled C3d and anti-C3d. Separation of bound from free C3d was by G-75 Sephadex filtration. Assuming a 1:1 molar ratio in the antibody-C3d complex, anti-C3d antibody concentrations for four rabbit whole antisera and four IgG preparations fell in the range 288-2433 microgram/ml, with Ko values of 6-2 X 10(8)-2-9 X 10(9) litres/mol. One commercial antiglobulin-serum contained 3-6 microgram anti C3d/ml and had a Ko value of 1-7 X 10(8) litres/mol. Values for anti-C3d concentrations measured independently by an indirect method employing 125I-labelled sheep anti-rabbit IgG averaged 20% lower than those obtained with 125I-labelled C3d. Antibody concentrations were correlated with antiglobulin agglutination titres against C3d-coated red cells; a titre of 1 was given by an anti-C3d concentration of 0-5 microgram/ml.


Expression of Fc and complement receptors on T lymphocytes activated in vitro by phytohaemagglutinin (PHA).

In this work T-enriched lymphocyte populations (obtained from Ig-anti-Ig-Degalancoated columns) were studied for their surface markers, especially for Fc and complement receptors, before and after a pulse-PHA-stimulation. It has been demonstrated that activated T lymphocytes express on their surface both of these markers in high percentage. The hypothesis is discussed that B and T lymphocytes differ only with regard to the presence of surface immunoglobulins or the ability of forming spontaneous rosettes. On the contrary the other surface markers may probably be expressed when needed functionally by the cells.


Heterogeneity of B cells reacting with T-cell factors. Evidence for matching T-cell and B-cell subsets.

Spleen T cells have been stimulated with Concanavalin A (Con A) under conditions which lead to the production of non-specific factor (NSF), a substance which replaces T cells for B-cell responses to certain antigens. We have examined the ability of multiple aliquots of B cells to react to the NSF derived from single T cells, and have found great heterogeneity of response. We postulate that there exist subsets of T cells which vary in either the quantity or the quality of the non-specific factor(s) they can produce on stimulation, and that in turn there must also be matching subsets of B cells which may vary in their susceptibility to such factors.


The effects of complement activation by cobra venom factor on the migration of T and B lymphocytes into rat thoracic duct lymph.

Experiments were done to see whether C3 or C3-split products are involved in lymphocyte recirculation, with particular reference to B lymphocytes which have C3b receptors. Rats were injected with cobra venom factor (CVF), and the output of subclasses of lymphocytes was measured in thoracic duct lymph in hourly collections during the subsequent 24 h. During the period of acute C3 activation which lasted for 2-8 h, the output of lymphocytes decreased by 47%, but returned to normal at later times, when C3 levels were reduced to less than 20% normal. There was no effect on the output of C3b receptor lymphocytes, and this receptor was not blocked probably because initial C3 levels in lymph were only 13% of blood levels, so that only small amounts of C3b were generated in lymph. When these lymphocytes were labelled and injected i.v. they migrated with the slow rate which is characteristic of normal B lymphocytes. The main effect of CVF was to reduce the output of T lymphocytes by 58% during the phase of acute C3 activation. When normal thoracic duct lymphocytes were labelled and injected, their rate of reappearance in thoracic duct lymph was only reduced during this phase. It was concluded that recirculation of lymphocytes is not C3 dependent, and that insufficient C3b is generated in lymphoid tissues to block C3b receptors on B lymphocytes during periods of rapid C3 activation. However the migratory rate of T lymphocytes through these tissues is reduced during this period, and it is suggested that this may be due to an effect of C3 split products on macrophages which lie along T-lymphocyte traffic routes.


Suppressive effect of cyclophosphamide on the T-cell system in chickens.

Neonatal administration of 16 mg of cyclophosphamide in inbred chickens resulted in a transient, but profound, deficiency in the in vitro proliferative response of spleen cells. Functional T-cell deficiency was accompanied by a marked morphological degeneration in the thymus and thymus-dependent areas in the spleen.


Rosette formation assays in dogs: lack of specificity of E rosettes for T lymphocytes.

The present study examined the specificity of guinea pig erythrocyte (E) and erythrocyte-antibody-complement (EAC) rosette formation assays with suspensions of canine peripheral blood lymphocytes. Neutrophils, monocytes, and lymphocytes bound EAC but not erythrocyte-antibody (EA) controls. Similarly, all three cell types formed rosettes with guinea pig E. Adherence of guinea pig E to these cells was apparently mediated by natural cytophilic antibodies present in the serum used in the suspension medium. The nonspecificity of the guinea pig E-rosette formation assay with canine lymphocytes renders the technique unreliable for the identification of thymus-derived lymphocytes in dogs.


Reaginic antibody production to Ascaris suum allergen, ASC-1. I. The function of glutaraldehyde-polymerized antigen in the induction of reaginic (IgE) antibodies in the rat.

Rats immunized with a purified Ascaris suum allergen (Asc-1) or with its dinitrophenylated derivate (DNP-Asc-1) produced high levels of reaginic (IgE) antibodies. A second injection of antigen given 30 days later did not result in an anamnestic IgE antibody response. Immunization of adult-thymectomized, lethally-irradiated and bone-marrow reconstituted (ATxB) rats with soluble Asc-1 or DNP-Asc-1 failed to stimulate reaginic antibody production. The administration of glutaraldehyde-polymerized antigen induced in some but not all ATxB rats, low but detectable levels of IgE antibodies. These levels increased following a second injection of nonpolymerized antigen in A1 (OH)3 gels. Priming of animals with polymerized carrier and Bordetella pertussis did not stimulate a primary anticarrier IgE response but led to an enhanced antihapten IgE response following the administration of soluble DNP-Asc-1 in A1(OH)3. The results are consistent with the notion that a sharply reduced but clearly functional T-derived helper cell population could be triggered by the polymerized but not by the soluble form of the immunogen.


Relative responses of an X-ray-resistant hybrid cell-line and its parent line to X-irradiation, ultraviolet light, actinomycin D and cordycepin.

Using colony formation as an assay, a rat-mouse hybrid cell-line (HD1) and one of its parent lines (H4) have been studied as to their abilities to survive exposure to ionizing radiation, ultraviolet light, and the drugs actinomycin D and cordycepin. HD1 cells are more resistant than H4 to ionizing radiation, actinomycin D and cordycepin. Both cell lines respond similarly to ultraviolet light. When both cell-lines were co-treated with actinomycin D or cordycepin, the toxic effect of ionizing radiation was enhanced, whereas that of ultraviolet light (U.V.L.) was unchanged. The data suggest that RNA synthesis is more important immediately after irradiation with X-rays than with U.V.L. and that cells resistant to the toxic effect of ionizing radiation are also resistant to the toxicity induced by inhibitors of RNA synthesis.


Inactivation and mutation of cultured mammalian cells by aluminium characteristic ultrasoft X-rays. I. Properties of aluminium X-rays and preliminary experiments with Chinese hamster cells.

Irradiation with ultrasoft X-rays produces electron tracks of short defined lengths in the irradiated material. This property is of particular interest in distinguishing between different models of radiation action on living organisms. The production, absorption and dosimetry of aluminium K characteristic X-rays of energy 1.5 keV are described. Quantitative experiments on mammalian cells with these X-rays are possible, and they were found to be considerably more effective than gamma-rays in inactivating Chinese hamster V79 cells in vitro.


Inactivation and mutation of cultured mammalian cells by aluminium characteristic ultrasoft X-rays. II. Dose-responses of Chinese hamster and human diploid cells to aluminium X-rays and radiations of different LET.

The induction of inactivation and mutation to thioguanine-resistance of two types of cultured mammalian cells, V79 Chinese hamster and HF19 human diploid, was studied after irradiation with aluminium K characteristic ultrasoft X-rays, helium ion track intersections of different LET, 42 MeV d-Be neutrons, and hard X- or gamma-rays. The form of the dose-response curves was different for the two cell-types, and there was an overall difference in radiosensitivity, the human cells being the more sensitive to all radiations. However, for both inactivation and mutation-induction, the relative responses of both cell-types to these radiations was similar. Aluminium X-rays were considerably more effective than hard X- or gamma-rays and were at least as effective as helium ions of 20-28 keV micron-1, although aluminium X-rays produce tracks of very limited range (less than about 0.07 micron). Single track effects by aluminium X-rays cannot, therefore, extend beyond about 0.07 micron, and the subcellular sites involved in inactivation and mutation cannot be greater than this dimension or else the effectiveness of aluminium X-rays would be similar to that of low-LET radiations. This observation is in contradiction to models of radiation action which require relatively large sensitive sites; for example the 'theory of dual radiation action' requires a site diameter of about 0.4 micron to explain the shape of the dose-response curves for V79 hamster cells.


Lack of genetic and cytogenetic effects in mice fed on irradiated wheat.

Experiments were conducted to test the mutagenicity of wheat irradiated with 20 and 200 krad gamma-rays by feeding male and female mice for various periods starting from weaning time. The results obtained from dominant lethal tests, specific locus mutation test, studies on chromosome rearrangements in males and gonadal cell survival studies indicated no positive evidence for genetic and cytogenetic effects.


The effects of chronic irradiation on the breeding performance of the guppy, Poecilia reticulata (Osteichthyes:Teleostei).

The effects of chronic irradiation on the life-time breeding performance of the small tropical fish, Poecilia reticulata, have been investigated at mean dose-rates of 0.17, 0.40 and 1.27 rad hour-1. The total fecundity was markedly (P less than 0.001) reduced at all dose-rates owing to a decrease in mean actual brood-size and an increase in temporary and permanent infertility. Minor progressive changes in the interbrood time with age and dose-rate were noted. The neonatal death-rate, incidence of abnormalities, and survival and sex ratio of the offspring were unaffected by irradiation. The brood-size data have been used to derive estimates of the dominant lethal mutation rate which are of the same order as those determined for mammals. Histological studies indicate that functional sterility is not necessarily dependent on the destruction of the gonads, and it is possible that radiation effects on pituitary function are responsible for much of the observed infertility.


A pulse-radiolysis study of the reaction of hydrated electrons with N'-formylkynurenine and related compounds: electron-transfer reactions with nucleic acid components.

The reactivity of N'-formylkynurenine (FK) derivatives towards eaq has been investigated. The reduced transient species have been characterized (lambda max approximately 340, 440 nm, epsilon lambda max approximately 3000-1000 M-1 cm-1, pKa approximately 7.8). Owing to the strong FK electron affinity, electron-transfer reactions occur from purine (except guanine) and pyrimidine electron adducts to FK (k approximately 2-7 x 10(9) M-1 s-1). As some FK derivatives bind to DNA (or polynucleotides) the protective effect of complexation on FK-DNA (or polynucleotides) adduct formation has been investigated.


Inactivation and mutation of cultured mammalian cells by aluminium characteristic ultrasoft X-rays. III. Implication for theory of dual radiation action.

Microdosimetric distributions for aluminium K characteristic ultrasoft X-rays and 4He ion tract intersections are calculated and used to analyse recent biological results obtained with these radiations. Results on inactivation and mutation-induction to thioguanine resistance of both V79 Chinese hamster cells and HF19 human diploid fibroblasts in vitro are analysed in terms of the Kellerer-Rossi "theory of dual radiation action". The small quantum energy of the aluminium X-ray photons and the very short length of the secondary electrons which they produce highlight the inadequacy of the model. It is shown that the model predicts r.b.e. values in conflict with those observed unless an additional variable is introduced, but that the introduction of such a variable creates mathematical inconsistencies. The experimental evidence is contrary to the conventional usage and basis of the model.


Effect of salt solutions on radiosensitivity of mammalian cells. I. Specific ion effects.

The radiation isodose survival curve of cells subjected to a wide concentration range of sucrose solutions has two maxima separated by a minimum. Both cations and anions can alter the cellular radiosensitivity above and beyond the osmotic effect observed for cells treated with sucrose solutions. The basic shape of the isodose curve can also be modulated by changes in temperature and solution exposure times. Some of these alterations in radiosensitivity may be related to changes in the amount and structure of cellular water or macromolecular conformation or to the direct effect of the ions, expecially at high solute concentrations.


Effect of salt solutions on radiosensitivity of mammalian cells. II. Treatment with hypotonic solutions.

Chinese hamster (V79) cells were treated with hypotonic NaCl, NaCl-ouabain, KCl, LiCl, NH4Cl, NaNO3 or sucrose solutions and irradiated at various times during exposure to the solution. The extreme increase in the radiosensitivity of these cells, mainly characterized by changes in DO, could be attributed to increases in the cell water-content and possibly the decrease in total cell water structure. The various ions may exert their specific effects on radiosensitivity by influencing the above water-related factors.


The health team training model: a teaching-learning approach in community health.

Health science students worked as members of interdisciplinary health teams as the teams provided services to multiple-problem Appalachian families. The family became the focus of attention in care delivery while the Problem-Oriented Medical Record (POMR) and the family health plan were used by the teams to provide services. Intra-team issues that evolved included communication, decision making, leadership style, and role identity.


Bacterial, serum and cellular modulation of granulopoietic activity.

The interaction human peripheral blood lymphocytes, monocytes, gram-positive bacteria and human serum in the release of colony stimulating activity (CSA) has been studied. CSA was assayed by the soft agar technique using human and murine bone marrow cells. It has been demonstrated that gram-positive organisms and their products can stimulate release of CSA by mononuclear cells. Human serum is also effective in promoting release of CSA. Release is further modulated by interactions between lymphocytes and monocytes, and lymphocytes may serve to control the modulation. The serum component is sensitive to temperature inactivation suggesting that it may have a specific physiologic role in regulation. Bacterial products, on the other hand, are not subject to temperature inactivation and require the presence of human serum for activity to be expressed.


The detection of in vitro monocyte-macrophage colony-forming cells in mouse thymus and lymph nodes.

In vitro monocyte-macrophage colony-forming cells (CFC) have been detected in the thymus (30/10(6) cells) and in the cervical (22/10(6)) and mesenteric (20/10(6)) lymph nodes (LN) of the mouse. Thymus and LN derived CFC differed from bone marrow derived CFU-c in several characteristics parameters: (1) sole specificity of PMUE to induce colony formation (CF), (2) apparent singular line of monocyte-macrophage differentiation, (3) a marked 6- to 10-day lag period prior to initiation of CF, and (4) significantly slower rates of appearance of colonies in culture after initiation of CF. Two of these parameters are shared with those CFC detected within alveolar space, peritoneal exudate and pleural effusion. These are the delay prior to CF and the singular monocyte-macrophage differentiation. These similarities suggested that T-CFC and LN-CFC are probably of similar origin and represent, as suggested by Lin and Stewart ('74), a population of progenitor cells exclusively for monocyte-macrophages.


Decreased in vivo and in vitro colony stimulating activity responses to bacterial lipopolysaccharide in C3H/HeJ mice.

Mice of the C3H/HeJ strain exhibit low inflammatory and immunological responses to certain bacterial lipopolysaccharide (LPS) preparations. Lymphocytes from C3H/HeJ mice also show defective LPS-induced mitogenesis. We tested the colony stimulating activity (CSA) response of C3H/HeJ mice. As controls we used mice of the congenic C3HeB/FeJ strain, which are good responders to LPS. Serum was obtained three hours after intravenous administration of LPS. Serum CSA was determined in agar cultures of bone marrow cells from AKR mice. The serum CSA response of C3H/HeJ to 10 microgram LPS was approximately 8-fold lower than that of control C3HeB/FeJ mice. In contrast, both strains showed similar serum CSA-induced by Poly I:poly C. Peritoneal macrophage cultures were also incubated with 0.1-10.0 microgram LPS and culture media assayed for CSA. The response of C3H/HeJ macrophages was about 6-fold lower than that of macrophages obtained from the control mice. The results show that the lower responsiveness of C3H/HeJ mice to LPS also extends to the production of CSA. The in vitro findings indicate that the postulated defect in the LPS receptor of B lymphocytes may also be present on macrophages.


3-O-methylglucose transport by rat thymocyte subpopulations.

Rat thymocytes can be separated into two subpopulations by centrifugation for 20 minutes at 1,600 g in an 18/26/36% (w/v) discontinuous gradient of bovine serum albumin. Approximately 13% of the cells band at the 18/26% interface (light cells) while the remaining cells band at the 26/36% interface (heavy cells). In vitro and in vivo studies of 3H-thymidine incorporation indicate that the light cells are 2- to 3-fold enriched in the rapidly dividing lymphoblast subpopulation of thymocytes as compared to heavy cells. Light cells transport the non-metabolizable glucose analogue 3-O-methylglucose (3-MeGlc) approximately four times faster than heavy cells. The time course of 3-MeGlc uptake is biphasic for light, heavy and unfractionated thymocytes. While the half-times of the rapid (1 minute) and slow (20-45 minute) phases of uptake are similar for all three types of cells, the contributions of the rapid phase to total uptake are 50% for light cells, 20% for unfractionated thymocytes and 10% for heavy cells. The results show that 3-MeGlc transport activity differs markedly within certain thymocyte subpopulations. The correlation between the contributions of the rapid phase of uptake and the proportion of lymphoblasts in the thymocyte fractions suggests that the lymphoblast and small lymphocyte subpopulations might be responsible for the rapid and slow phase of 3-MeGlc uptake, respectively.