Selective arterial embolization for control of massive upper gastrointestinal bleeding. Massive upper gastrointestinal bleeding was controlled in 11 of 15 patients by the use of selective injected arterial emboli. Embolization is most successful in the treatment of patients with demonstrated arterial bleeding sites at angiography. This group of patients generally has ulcers and it is this group in whom vasopressin infusion has the lowest success rate. At the same time we were successful in controlling only 1 of 4 patients who were bleeding from diffuse hemorrhagic gastritis, those patients in whom vasopressin infusion is very successfu, We, therefore, now embolize only patients in whom arterial bleeding sites are demonstrated at angiography or in whom vasopressin infusion has failed to control the bleeding from hemorrhagic gastritis. Our experience also indicates that short acting occlusive agents, such as autogenous blood clot mixed with aminocaproic acid, are as successful in controlling bleeding as the more permanent types of embolic material.


Transjugular approach to the liver, biliary system, and portal circulation. More than 5 years of clinical and animal experience with the use of a transjugular approach to the liver, biliary system, and portal circulation is reviewed. It has been of clinical value in connection with hepatic manometry and venography, liver biopsy, and cholangiography. Satisfactory hepatic manometry and venography were achieved by the transjugular approach in all 47 cases where attempted; diagnostic liver specimens were obtained in 71 of 83 patients (86%); and cholangiography was successful in 48 of 52 patients with enlarged intrahepatic ducts (92%). No complications occurred with these studies. In animals, transjugular catheterization was used as a means for portal, mesenteric, and pancreatic venography. These procedures are ready for diagnostic clinical use. Therapeutic techniques explored in animals include intravascular tamponade of gastric coronary vein and the nonsurgical creation of intrahepatic portacaval shunts, both of promise in the future management of massive gastrointestinal bleeding from varices.


Polyvinyl alcohol (Ivalon)--a new embolic material. Successful nonsurgical treatment of gastrointestinal bleeding and arteriovenous malformations by embolization techniques has been previously documented. 1) Compressed Ivalon sponge was found to be a suitable embolic material in animals and in four patients. 2) The material has been extensively used in surgery, and its biocompatibility has been proved. 3) Expansion of the compressed sponge to its original size after embolization makes this material extremely effective. Recanalization did not occur in animals and humans. 4) For the occlusion of larger arteries, Ivalon can be wrapped around the guidewire. Ivalon sponge absorbs blood and serum, unwraps itself allowing withdrawal of the guidewire. 5) Embolization procedures are not without risk since reflux of embolic material may occur. Therefore, these procedures have to be carried out under fluoroscopic control.


Complications of small dose prophylactic heparinization. The observations reported herein on the use of prophylactic small dose heparinization are in no way intended to diminish its value but are reported and reviewed so that certain precautions may be exercised in its use. In fact, the apparent difference in the incidence of pulmonary emboli in the controls and heparinized patients may lend credence to its value. The large controlled series now being studied at various medical centers will help to confirm or deny the value of this factor in the prevention of emboli. Careful preoperative scrutiny of the patient and meticulous intraoperative hemostasis remain important factors when a patient is receiving small dose heparin therapy. Other factors such as concomitant medications, weight of the patient, frequency and technic of administration and dosage must be considered. Additionally, monitoring the hemostatic mechanism with serial hematocrit determinations and laboratory coagulation tests appears to be an important adjunct in small dose prophylactic heparinization.


Combined chemotherapy and cryosurgery for oral cancer. The inadequacies of traditional methods for control of advanced oral carcinomas at their sites of origin prompted evaluation of combined chemotherapy and cryosurgery in seventy-three patients treated since 1969. Our experience with thirty-nine unlikely candidates for salvage by other therapy is the subject of this report. The majority had recurrent disease after other therapy. The observed morbidity potential of combined chemotherapy and cryosurgery with earlier experience led to abbreviations and refinements of method that are described and consist mainly of the following. (1) A two day postcryosurgical infusion (intra-arterial) of 5-fluorouracil (1 gm per twenty-four hours, or less) in lieu of methotrexate, the systemic toxicity and therapeutic efficacy of which seem less predictable with cryosurgery. (2) Electrosurgical subtotal tumor resection at the time of initial cryosurgery to reduce swelling and magnitude of in situ tissue slough. (3) Use of a flexible copper mesh cryoprobe that enhances feasibility of in-depth wide field cryosurgery. (4) Systematic use of multiple marginal wound biopsies as a principal guide to repetitive cryosurgery or other therapeutic adjunct selection. A special warning that available toxicologic data for independent drug therapy may not be applicable in patients after cryosurgery is given. Current experience indicates that negative biopsy after such combined therapy may be 85 per cent reliable in foretelling lesion outcome. Among the thirty-nine patients reported, twenty remain alive from six months to six years, only two of whom have clinically evident recurrent disease. If such could be reasonably accomplished, comparative evaluation of single methods should precede attempts to combine two or more modes of therapy. Since neither chemotherapy nor cryosurgery, as known today, can eliminate nodal metastases, each must be regarded as potentially adjunctive to other methods for achieving the ultimate goal of a cancer-free patient. It is within this context that combined chemotherapy and cryosurgery have been applied to unfavorable candidates for cure with seemingly worthwhile gains. Potential applicability for patients with less formidable stages of disease cannot be extrapolated from this experience. Large scale controlled clinical trials must provide the ultimately conclusive test of efficacy for such combined forms of therapy before decisive revision of traditional standards of practice might result.


A new method for determining the blood quantity in the eye in a unit of time. The principles of rheography with "infinite time constant" are utilized. After applying a suction cup electrode mechanism, by gradual increases of the vacuum, ocular pressure rises above venous pressure, and without modification of arterial inflow, the venous outflow is blocked; in consequence an increase of blood accumulation in the interior of the eye occurs. The electrical impedance variation, as a result of the latter, gives the recorded tracing a "slow" rising curve, that maintains the same pulse morphology. After being analyzed and elaborated on with certain mathematical formulae, this curve makes it possible to calculate the blood flow in the eye in a unit of time. Statistics on normal patients of various ages are reported.


The pattern evoked responses (VER) in optic neuritis. Five patients presenting clinically accepted signs of optic neuritis served as subjects for a study on EP's (evoked potentials); the patients were tested during the acute phase, the chronic phase and at a stage when no impairment was clinically observed. At the acute phase of optic neuritis the VER was massively altered; in the chronic phase delayed latencies depending upon the impairment of visual acuity and visual fields could be recorded. At the recovery stage, while visual acuity and visual field showed no deficit, not only delayed latencies but also reduction in the amplitude at all stimulation frequencies were recorded.


An automatic perimeter for glaucoma visual field screening and control. Construction and clinical cases. An apparatus for static perimetry of the central visual field at 64 points is described. The testing is fully automatic: the test logic is programmed into a mini-computer and the results are plotted as a diagram in polar coordinates. A few cases with small or medium sized visual field defects have been analyzed by conventional methods and by the automatic instrument with satisfying results.


Provoked iris ischaemia in the rabbit. II. Histochemical localization of sodium fluorescein. The distribution of injected sodium fluorescein in the iris and ciliary body of albino rabbits was studied in normal animals and in animals subjected to different surgical procedures. The study was performed with two techniques: whole-mount preparations and the paraffin-section method on freeze-dried eyes. Fluorescein distribution showed marked changes after surgical procedures as a result of reduced blood perfusion. In normal iris vessels no penetration of fluorescein was observed. The permeability barrier was impaired if there were ischaemic conditions in the anterior segment. The results were compared with clinical and iris angiographic studies.


Fundus drawings versus photography.

Fundus drawings versus photography. Under adverse optical conditions (turbidity of the media) a well-trained observer/artist, using slit-lamp stereomicroscopy, is able to display in a drawing considerably more correct information about a fundus than what a fundus camera records. To a lesser degree this holds under favorable conditions too. General advocation of photography for being more objective is questioned; even if true, meme objectivity, i.e. no false information, would not make up for loss of important details. This paper intends to prove these points experimentally on an object (a nummulite shell) unfamiliar to the artist charged to do the drawing. The latter and photographs taken under varying conditions were compared inter se and with a high resolution scanning electron micrograph.


[The alteration of the human ERG in light- and darkadapted state under normal and increased intraocular pressure (author's transl)]. Electroretinograms of 19 human eyes in light- and darkadapted state under normal and increased intraocular pressure (increased by a spring pressure dynamometer) were recorded (Pm = (Ps + Pd)/2). On physiological intraocular pressure the a-wave showed a low increase in amplitude after 25 min of dark adaptation, the b-wave a great one. After increasing the intraocular pressure no significant influence of the state of adaptation to the magnitude of the a- and b-wave could be found.


Vitrectomy in exogenous Candida endophthalmitis. A case of Candida endophthalmitis was clinically diagnosed three weeks after perforating injury. It was successfully treated with vitrectomy and intravitreal injection of 5 mcg of amphotericin B. A Candida speices was cultured from the vitreous aspirations.


Hypersensitivity towards alpha-crystalline in the heterochromia syndrome. In 4 cases of heterochromic cyclitis with cataract, 5 cases of herpetic iridocyclitis, and 5 cases of senile cataract, hypersensitivity to both alpha-crystalline and uveal pigment was investigated by lymphocyte-transformation and leukocyte-migration tests. In 3 cases of heterochromic cyclitis with cataracts, cellular hypersensitivity to alpha-crystalline was proven. Basing on these findings, the role of hypersensitivity to lens proteins in the etiology of heterochromic cyclitis is suggested.


Effects of some phlogistics on the capillary resistance of the rabbit conjunctiva. Applying certain phlogistics (10% ol. sinapis, tinct. capsici, Dionin) and 1.5% histamine solution to the conjunctival sac of rabbits led to a mathematically significant decrease in conjunctival capillary resistance in every experimental animal. The effect occurred 20 to 30 min after application of the various pharmacons.


Side-effects of local anesthetics on the corneal epithelium of the rabbit eye. The toxic side-effects of 0.4% Novesine and Chibro-Kerakain were investigated by scanning- and transmission electron microscopy in 15 rabbit corneae each in intervals of 3, 6, 10, 15 and 60 mins. The lesions following Kerakain were larger and occurred earlier. After 60 mins, the specimens after Novesine application showed an almost complete repair process, whereas after Kerakain the epithelial surface appeared to be functionally impaired.


Ultrasonic findings in the vitreous body at different ages and in patients with detachment of the retina. The effect of age on degeneration of the vitreous body was studied in 77 patients and in 123 eyes. The patients were divided into three groups by age, with a mean age of 16, 35 and 72 years, respectively. In the two younger groups the vitreous body generally appeared to be acoustically homogeneous, while the oldest group showed heterogeneity of the vitreous body in a majority of cases. Syneresis of the vitreous body yielded a highly characteristic echogram. A total of 22 eyes with unilateral idiopathic detachment of the retina were examined, and in all of them degeneration of the vitreous body was clearly detected. Examination of the other, "normal" eye revealed only four eyes with an acoustically homogeneous vitreous body. Six patients had severe syneresis in bthe eyes. The evident conclusion is that detachment of the retina even in a single eye is often accompanied by degeneration of the vitreous body in the other eye as well.


[Tension under controlled conditions in the encircling operation (author's transl)]. The complications, which occur in encircling-operations, such as String-Syndrome, scleral Nekrosis, glaucoma-development (due to narrowing the anterior chamber) as well as closure of the central artery most frequently happen, when the globe has been tightened too much. From the calculations we have make using the cerclage element in reducing the circumference and volume (Fig. 2) we have shown that an identation of the sclera more than 3 mm deep is not advisable. The Silicon-Cerclage-Materials, which we use, are tested by the tension-testing machine, which determines the modulus of elasticity. The stress, that is force per sectional area, is determined in relation to the amount of elongation in the material (Fig. 3). A round silicon rod with a diameter of 2 mm and a modulus of elasticity between 150 and 200 p/mm2 proved most effective. In addition, we have conducted experiments with the Cerclage-rods on enucleated human eyes (Fig. 4). In one experiment the intraocular pressure was determined in relation to the pull of the weight upon the globe (Fig. 5). In a second experiment the reduction of the circumference was related to the height of the intraocular pressure (Fig. 6). The elastic Cerlage-rod has the advantage of creeping, when tensed, it tries to regain its original length. However, the globe, owing to the pressure within it, works against the creeping. With the help of the stress-strain diagram (Fig. 7) and the experiments on the human eye we can determine more accurately the degree of the creeping. In index 1 we can see how much the circumference has been finally reduced including the creeping in relation to the height of the intraocular pressure. The intraocular pressure should not be increased above 35 mm Hg. Otherwise: 1. the circumference of the globe will be considerably more reduced; 2. the intraocular pressure will rise much more slowly when compared to results at the lower eye-tension and 3. the volume reducing-effect will diminish markedly. It is important to measure the intraocular pressure before the end of the operation in order to avoid the above mentioned complications.


The treatment of systemic lupus erythematosus (SLE) with the T-cell immunostimulant drug levamisole: A case report. A 23-year-old woman with a nine-month history of SLE, uncontrolled with high daily doses of steroids, was treated with the T-cell immunostimulant drug, levamisole. Following a single oral three-day course of therapy with this agent her immunologic parameters and clinical manifestations underwent marked regression. Continuous two-weekly course of this drug at three days per course have allowed rapid reduction of her steroid and resulted in complete remission of her symptoms. The theoretical considerations for the use of levamisole dovetailed perfectly with the observed response to this agent.


Local, passive transfer of purified protein derivative-delayed tuberculin hypersensitivity by guinea pig thymus-dependent lymphocytes. Delayed skin reactions to purified protein derivative could be produced in guinea pigs by passive transfer of the population of sensitized lymphocytes, which have the ability to form rosettes with rabbit erythrocytes. Because it has been shown earlier that guinea pig thymus-dependent lymphocytes rosette with rabbit erythrocytes, it is concluded that thymus-dependent lymphocytes mediate delayed type hypersensitivity.


Evidence of congenitally nonfunctioning cilia in the tracheobronchial tract in two subjects. Mucociliary transport in the tracheobronchial tract was studies in 2 subjects by having them inhale a radioactively tagged test aerosol and by taking external measurements of the radioacitivity in the lungs for 2 hours. Both subjects had living, yet immotile seprmatozoa; the sperm tails lacked normal dynein arms, which are essential for the bending movements of sperm tails as well as of other cilia. The subjects were classified as suffering from Kartagener's syndrome (situs inversus, chronic sinusitis, and bronchiectasis) and were shown to have an extremely slow, probably absent transport. The results of the study were in agreement with a recent hypothesis explaining Kartagener's syndrome as due to a genetic lack of dynein arms. An estimate of the importance of mucociliary transport as a protective mechanism of the lung may be possible by examining patients suffering from Kartagener's syndrome.


Intestinal bypass in morbid obesity: long-term metabolic sequelae. A review of 51 patients undergoing jejunoileal bypass for morbid obesity is presented. There were two postoperative deaths; the 49 remaining patients have been followed for up to five years. Weight loss has been acceptable, the complications for the most part being transient and easily controlled. We believe that jejunoileal bypass for morbid obesity is a useful treatment modality in carefully selected patients.


Smooth muscle antibody in heroin addicts. The occurrence of autoantibodies and the concentrations of serum immunoglobulins were studied in 102 heroin addicts, 20 former addicts who had abstained from heroin for 1 year or more, and 40 normal control subjects. Antibodies to smooth muscle (46%) and lymphocytotoxic antibodies (30%) were detected in the active heroin users, and there was a significantly positive correlation between these autoantibodies. Absorption experiments strongly suggested antigenic cross-reactivity between smooth muscle and lymphocyte membrane antigens. The presence of smooth muscle antibody in addicts was not clearly correlated with signs of active liver disease. The occurrence of smooth muscle antibody (10%) and lymphocytotoxic antibodies (15%) was significantly lower in the former heroin addicts than among active drug users. A significant elevation of IgM was found in the active heroin addicts. Gamma-M globulin was lower among the former heroin addicts but still elevated when compared with normal controls.


[Neonatal hepatitis with alpha-1-antitrypsin deficit. Apropos of a personal case]. The authors report a case of neonatal hepatitis with alpha-1-antitrypsin occuring in a child of ZZ phenotype. The anatomopathological study carried out on two liver biopsies showed changes of common cholestatic hepatitis developing into cirrhosis, as well as intrahepatocytary globulins. Moreover, these globulins, P.A.S. positive after treatment by alphaamylase, fix an antialpha-1-antitrypsine antiserum. Ultrastructural analysis shows them to be masses of amorphous material, feebly osmiophilic, outlined by a unitary membrane the moniliform aspect of which recalls the ergastoplasmic membrane. These findings are identical to those already made in cases of cirrhogenous neonatal hepatitis by alpha-1-antitrypsine deficit reported in the literature. They point out the irreversibility of the affection which, after a stage of cholestatic hepatitis with or without inflammatory portal fibrosis, develops into cirrhosis. At this stage cholestasis has regressed or disappeared whereas portal sclerosis, often infiltrated with free elements, surrounds hepatic lobules and biliary neocanaliculi. But the globulins are still present and appear to be the specific feature of this deficit. By their ultrastructural and immuno-histochemical features, these globulins would represent a form of accumulation of alpha-1-antitrypsin in the hepatocytes which normally carry out the synthesis of this antienzyme. Accumulation in the hepatocytes proves excretory disturbance of hypothetical mechanism: structural anomaly, changes  in the permeability of the membrane. Its role in the occurrence of hepatitis or cirrhosis lesions is still to be demonstrated but one may think that it consists in absence of inhibition of the enzymatic factors discharged during agressions.


Discoid lupus erythematosus as part of a larger disease spectrum. Correlation of clinical features with laboratory findings in lupus erythematosus. This study compares the immunologic features of a homogeneous group of patients with discoid lupus erythematosus (DLE) strictly limited to the skin (group 1) with those of patients with active discoid skin lesions plus visceral involvement (group 2) and with those of lupus erythematosus (LE) patients with proliferative glomerulonephritis (group 3). Positive antinuclear antibody (ANA) was found in 4% of group 1, 93% of group 2, and 100% of group 3. Low total hemolytic complement (CH50) was found in 4% of group 1, 47% of group 2, and 100% of group 3. Antibodies to native DNA (nDNA) were not found in group 1, were rarely found in group 2, and were present in nearly all patients in group 3. No group 1 patient had subepidermal immunoglobulin deposits in normal skin, 20% of group 2 had this finding, and 100% of group 3 had this finding. The ability to develop chronic discoid skin lesions appears to be associated with a reduced incidence of immunologic parameters of disease activity. The data suggest that patients with active discoid skin lesions rarely have severe renal disease.


Electrophysiological orthosis for the upper extremity in hemiplegia: feasibility study. A versatile two channel stimulator with cutaneous electrodes was designed and built to test the feasibility of multi-channel upper extremity functional electrical stimulation in hemiplegic patients. Preliminary experiments led to the choice of stimulation for hand opening (extensor carpi radialis and ulnaris, extensor digitorum communis) and elbow extension (triceps). Three channel stimulation including the deltoideus muscle was attempted successfully in one patient. Five of eight patients showed substantial improvement with the orthosis and three of these five showed some therapeutic effect over a period of two months. The stimulation was proportionally controlled by the patient by means of movement of the nonaffected shoulder. Functional tasks such as the shifting of an object between two specified areas on a desk were used for evaluation of performance. Tasks that were impossible without stimulation were easily performed with stimulation and after minimal training. The results obtained were significant for the functional rehabilitation of hemiplegic subjects. It is concluded that a more extensive clinical evaluation program including regular long term training of the subjects is justified.


Complications of ornamental Christmas bulb ingestion. Case report and review of the literature. Unusual complications ensued when a 14-month-old boy ingested an ornamental Christmas bulb. Profuse rectal bleeding, a large ischiorectal abscess, and an acute condition of the abdomen necessiated a sigmoid colostomy with drainage of the ischiorectal abscess. Following this, repeated episodes of hemorrhage via the colostomy and rectum required multiple operative procedures. The last of these was a total colectomy with an ileostomy and rectal mucous fistula. The patient subsequently developed intestinal obstruction that required lysis of adhesions and drainage of a chronic subhepatic abscess, due to perforation of the terminal part of the ileum. The patient required five months of hospitalization and further surgery to reconstruct gastrointestinal continuity. Hemorrhage is an infrequent complication of foreign body ingestion, as reported in the literature. We theorize that the problems in this case were the result of the extreme thinness (0.033 cm) and the brittleness of the glass fragments.


Dorsal column stimulation. Its effect on the somatosensory evoked response. Several authors have shown that dorsal column stimulation (DCS) modifies appreciation of pain. We studied the effects of DCS on the somatosensory evoked response (SER) in six subjects. Somatosensory evoked responses to stimulation of the tibial nerve and effects of varying frequencies and intensities of DCS on SER components were recorded. During DCS there was attenuation of late SER components with little effect on early components. Stimulus intensities greater than necessary to relieve pain suppressed all SER components. Our findings suggest that the minimal effective DCS variables to relieve pain are those that produce selective suppression of late SER components.


Lung proteolytic activity and serum protease inhibition after NO2 exposure. Proteolytic activity (PA) of lung extracts was measured in control hamsters and in those exposed to 20 ppm NO2 for 24 hours (acute) and 30 days (chronic). Total PA of these lungs as measured by pH 7.4 caseinolysis was slightly increased after the 24-hour, but normal following the 30-day exposure. Lung extract fractions from NO2-exposed animals display an increased PA at pH 3.0 and 9.0, but are near control levels at pH 7.0. Serum protease inhibitor (PI) activity is significantly increased after short NO2 exposure as compared with control conditions. No significant increase is observed in PI after chronic exposure. Increase in 24-hr NO2 lung extract PA is associated with increase in PI, which may neutralize the augmented proteolysis. These studies are consistent with previous observations that indicate prolonged NO2 exposure does not produce significant emphysema in the hamster lung.


Exteriorization of thoracic duct lymph. Theoretical considerations and an experimental model. Successful manipulation of the immune response will ultimately provide the answers for controlling homograft rejection, reversing autoimmune states, and quite possibly for curing carcinoma and other malignant neoplasms. During the past decade, many new drugs and techniques have been developed that alter the immune state. The theoretical basis for approaching the immune system via the thoracic duct is based on the fact that 90% to 95% of the cells in thoracic duct lymph are thymus-derived lymphocytes. Therefore, by tapping the thoracic duct, we could conceivably manipulate the T lymphocytes and control the cell-mediated arm of the immune system. This has in fact been done in renal transplantation and autoimmune diseases. An experimental canine model was developed that exteriorized lymph flow in a closed system. We describe our experiences with four dogs and we discuss proposed immunologic manipulation.


[A novel model of experimental toxic hepatitis/acute degenerative hepatitis induced by frog virus 3 (FV3) in the mouse (author's transl)]. The i.p. or i.v. injection of frog virus 3 (FV3) in mice produces a hepatitis which leads to the death of the animals within 24 h. This hepatitis is of a purely toxic nature since the virus does not develop at 37 degrees C. The toxic effect of the virus, which can be differentiated from the infectious effect, involves one or more structural proteins. The first pathological changes occur during the first few hours after the injection in the vicinity of the nuclei of the liver parenchyma cells in the form of changes in the chromatin and nucleoplasm. The inhibition of the synthesis of cellular macromolecules and of the function of nuclear enzymes points to the fact that it is the nucleus that is first and foremost attacked. Necrosis and biochemical disturbances in the vicinity of the cytoplasm appear later on. Premedication of the mice with a water-soluble silymarin salt leads to a distinct rise in the survival rate of the animals. The protective function of silymarin is dependent on the dose and on the duration of the premedication. The LD50 of FV3 in those mice which had previously been given silymarin, is approximately three times that of the animals which received no premedication.


Some biological properties of flurbiprofen, an anti-inflammatory, analgesic and antipyretic agent. 2-(2-Fluoro-4-biphenyl)propionic acid (flurbiprofen) possesses peripheral analgesic, anti-inflammatory and antipyretic properties. It does not possess glucocorticoid or adrenocortical-stimulating properties. It is a highly potent agent which in acute pharmacological test systems produced a significant pharmacological effect in single oral doses varying from 0.04 to 0.47 mg/kg. The peak plasma concentrations attained after these doses were generally of the order of 1 to 3 mug/ml. Doses of 0.33 mg/kg/day, which gave peak plasma concentrations of 0.6 mug/ml, produced a significant inhibition of rat adjuvant arthritis, both developing and established. The very shallow dose-response curves for flurbiprofen compared with acetylsalicylic acid, especially in the mouse and the rat test systems, are not due to an unreliable or abnormal absorption, which suggests that in these species the mode of action of flurbiprofen is not identical with that of acetylsalicylic acid.


Two-dimensional immunoelectrophoresis: a new simplified method. A new method of two-dimensional immunoelectrophoresis is described, in which fixed amounts of both antigen (total proteins) and antibody are employed. When applied to normal human sera, it results in the appearance of 15 peaks accounting for the commonest serum proteins with the only exception of alpha 1-acid glycoprotein. Transferrin, measured by Laurell's or Mancini's technique, is used as an internal standard. The height of the transferrin peak at 300 mg% is determined by a calibration curve. The heights of the various peaks are thus expressed as percentages of that of transferrin at 300 mg%. The method appears to be simple, rapid and antiserum-saving.


Association of cold-reactive antilymphocyte antibodies with lymphopenia in systemic lupus erythematosus. In a prospective study 26 of 29 patients with systemic lupus erythematosus had cold-reactive antilymphocyte antibodies cytotoxic for autologous lymphocytes and lymphocytes from normal subjects. The level of antilymphocyte antibodies was highly correlated, by linear regression analysis, with lymphopenia in these patients. The data suggested that both the avidity and the concentration of these antibodies were important determinants in this relationship. A clear association between increased antilymphocyte antibody activity and exacerbation of SLE was demonstrated. Apart from lymphopenia, however, neither type of clinical manifestation nor any particular serologic abnormality appeared to be related to the presence of antilymphocyte antibodies.


Hemorrhagic enteritis of turkeys. Antiserum -- efficacy, preparation, and use. Intestinal and splenic lesions of experimentally produced hemorrhagic enteritis of turkeys were prevented by administering convalescent antiserum. Protection varied with antiserum quality and time of administration after infection. In general, 1.0 to 0.5 ml per poult prevented all lesions and as little as 0.25 to 0.1 ml prevented intestinal lesions when administered within 48 hours of injection of the virus inoculum. Adding phenol to antiserum did not reduce its effectiveness. Convalescent antiserum was useful in controlling field hemorrhagic enteritis.


The nature of a pgiment-protein complex excreted from mutants of Rhodopseudomonas sphaeroides. Pigment-protein complexes excreted from three bacteriochlorophyll-less mutants (mutants 8, 8-29, and 8-47) of Rhodopseudomonas sphaeroides have been isolated and purified. In the absence of detergents the complexes remained in an aggregated state, but were disaggregated by 0.2% Triron X-100. Sepharose 6B gel filtration indicated that the disaggregated complex from each of the mutants had a particle weight of about 165000, and contained 30 +/- 3% protein. This complex was further dissociated by 1% sodium dodecyl sulfate. Sephadex G-100 gel filtration now indicated that the majority of the protein was present as a small polypeptide with a molecular weight of about 9000. The pigment-protein complex from one of the mutants was treated with a bacteriochlorophyll extract. The bacteriochlorophyll was converted to bacteriopheophytin and became bound to the protein, replacing the endogenous tetrapyrrole (a bacteriocholorophyll precursor). The red absorption maximum of the bacteriopheophytin was shifted during this process to 840-865 nm. These properties are consistent with the possibility that the pigment-protein complexes contain a protein normally associated with light-harvesting bacteriochlorophyll in the wide-type strain.


[Spontaneous and induced autoxidation of phospholipids during conformational rearrangements in outer segment membranes of frog retinal rods]. Kinetics of spontaneous and induced by the system Fe+++ascorbate peroxide oxidation of lipids in the membranes of outer segments of frog retina rods has been studied. Free radical oxidation of phospholipids passes the same stages as liquid phase oxidation of alkenes. Docosahexaenoi fatty acid residue of phosphatidyletanolamine is the main substrate of autooxidation. The structural organization of photoreceptor membranes is the factor which controls the reaction rate of peroxide oxidation; and reconstructions in membrane organization (at rhodopsin photolysis) result in the changes of autooxidation rate of phospholipids in the membrane.


[Protein-lipid interactions during lipid peroxidation in photoreceptor membranes]. It has been shown that chemical modification of hydrophobic lipid phase (lipoperoxidation) of outer segments membrane discs of frog retina rods brings about weakening protein-lipid interactions in the photoreceptor membrane. As a result of this extraction of rhodopsin with anion detergent (sodium cholate) in the concentrations not exceeding the critical concentration of micelloformation increases, and spontaneous release of rhodopsin into water phase is observed. At the same time the number of phospholipid molecules extracted in lipoprotein rhodopsin complex from the membranes of outer segments decreases 3-4-fold.


Electrical characteristics of frog atrial trabeculae in the double sucrose gap. The electrical behavior of small single frog atrial trabeculae in the double sucrose gap has been investigated. The currents injected during voltage clamp experiments did not behave as predicted from the assumption of spatial uniformity of the voltage across a Hodgkin-Huxley membrane. Much of the difference is due to the geometrical complexities of this tissue. Nonetheless, two transient inward currents have been identified, the faster of which is blocked by tetrodotoxin (TTX). The magnitude of the slower transient varies markedly between preparations but always increases in a given preparation with increase of external calcium. The fast transient current traces, at small to intermediate depolarizations, are often marred by the presence of notches and secondary peaks due most probably to the loss of space clamp conditions. In many preparations these could be removed by reducing the current magnitude through application of a partially-blocking dose of TTX. Conversely, in the preparations whose fast transient was fully blocked by TTX, notches and secondary peaks in the slow transient could by induced through increasing calcium concentration and thereby the slow current magnitude. Previously used techniques for the measurement of the reversal potential of the fast inward transient have been shown to be invalid. In so far as they can be measured, the reversal potentials of the fast and slow inward transient are in the same neighborhood, i.e. around 120 mV from rest. The true values may be quite a bit apart. The total charge flow in the capacitive transient was measured for different sized nodes and preparations. From these data and estimates of plasma membrane area per unit trabecular volume, specific membrane capacitances of around 3 muF/cm2 were calculated for small bundles. The apparent ion current densities on this basis are approximately 1/10 of those measured in axons. The capacitive current occurring in small bundles decayed as the sum of at least three exponential functions of time. On the basis of these data and the anomalously large stable node widths, we suggest a coaxial core model of the preparation with the inner elements in series with an additional large extracellular resistance.


[Effect of trypsin inhibitor of a peptide-protein nature on kallikreins from human and rabbit blood stream]. The effect of three natural trypsin inhibitors--polyvalent Kunitz inhibitor (BPTI), the inhibitor from cow colostrum (CTI) and the inhibitor from soybean (SBTI)--on esterase and kininogenase action of partially purified kallikrein preparations from human and rabbit blood serum is studied. The effect of each inhibitor was estimated from Ki values. The latters show that BPTI, SBTI and CTI are strong inhibitors of both kallikreins. Ki values, as estimated from the hydrolysis rate of N-bensoyl-L-arginine ethyl ester, were found to be for human blood serum kallikrein and BPTI, SBTI and CTI 1,1-10(-9), 4,7-10(-9) and 3,6-10(-8) M respectively and for rabbit kallikrein--1,7-10(-9), 2,3-10(-8) and 2,3-10(-8) M. In the case of kallikrein catalysing more specific kininogenase reaction Ki value for complex of human serum kallikrein with BPTI was 4,8-10(-10) M, for SBTI--1,1-10(-10) M and for CTI--3,6-10(-8) M; for rabbit kallikrein--1,7-10(-9) M, 1,1-10(-9) and 2,3-10(-8) M respectively. The data obtained suggest the high sensitivity of human and rabbit serum kallikreins to the trypsin inhibitor of peptide-protein nature and a close similarity in composition of the active site for both serum kallikreins and trypsin, two spices different kininogenases--from human and rabbit serum had also similarity in molecule conformation and composition active site.


Impaired T-cell transformation in chronic lymphocytic leukemia (CLL): Demonstration of a blastogenesis inhibitory factor. A noncytotoxic serum factor was found in CLL serum which interfered with the response of normal lymphocytes to phytohemagglutinin (PHA) and pokeweed mitogen (PWM). This factor was not produced by B-lymphocytes during short-term culture. This factor may contribute to the impaired lymphocyte responsiveness in CLL. In five of six patients, T-lymphocytes which were purified by passage over nylon wool columns exhibited an impaired response to both PHA and PWM, suggesting that a dilutional effect alone does not fully explain the impaired lymphocyte transformation in CLL.


Growth stimulation of human bone marrow cells in agar culture by vascular cells. Human vascular cells are capable of stimulating granulopoiesis in agar culture of human bone marrow cells. This effect was obtained by including vein fragments in the culture or by using endothelial cells separated from the vein of human umbilical cords as feeder cells. Furthermore, the stimulatory capacity of conditioned medium obtained from cord veins was found to be highly active in comparison to that obtained from peripheral leukocytes. Endothelial cells within the bond marrow cavity are suggested as a local source of factors regulating granulopoiesis in humans in addition to the monocyte.


Terminal deoxynucleotidyl transferase activities in human blood leukocytes and lymphoblast cell lines: high levels in lymphoblast cell lines and in blast cells of some patients with chronic myelogenous leukemia in acute phase. Terminal deoxynucleotidyl transferase, an enzyme which catalyzes the polymerization of deoxyribonucleoside triphosphates, elongating oligo- or polydeoxynucleotide chains, but without direction from a nucleic acid template, is thought to be specific for thymus gland and thymus-derived cells. We have confirmed the observations that high levels are characteristic of thymus gland with both human and calf tissue and that elevated levels may be found in some cases of acute lymphocytic leukemia. High levels were also found in human lymphoblast cell lines with T-cell characteristics, and insignificant activity was observed in leukocytes of patients with chronic myelogenous leukemia not in acute blast phase of the disease, chronic lymphocytic leukemia, human B-cells, and normal human blood lymphocytes even after stimulation with phytohemagglutinin. However, high levels (approximately 200 nmoles/hr/10(9) cells) equivalent to those in thymus tissue and lymphoblast cell lines with T-cell characteristics were found in the peripheral blood blast cells of four patients with chronic myelogenous leukemia in an acute blast phase of their disease. One hypothesis that may explain the present results is that in chronic myelogenous leukemia in acute blast phase of the disease the proliferative blast response may not always be myeloblasts but in some cases it may be lymphoblasts.


B lymphocyte subpopulations in chronic lymphocytic leukemia. We have defined two subpopulations of B lymphocytes in chronic lymphocytic leukemia (CLL). The major variant (termed typical) was characterized by the presence of a relatively homogeneous population of small-to-medium-sized lymphocytes with low-density SmIgM and no evidence of intracellular Ig synthesis. A minor group (termed atypical) was identified by the presence of a pleomorphic cell population with few small lymphocytes. The predominant SmIg was IgG, which was detected intracellularly as well as in the serum. The atypical group appeared to be an arrest at a later stage of differentiation where a switch from IgM to IgG synthesis and secretion had occurred. Clinical correlation suggested several clear-cut differences in clinicopathologic characteristics, but the median survivals for both groups at 2 yr was nearly identical.


Immunologic studies on human factor VIII (anti-hemophilic factor A, AHF) components produced by low-ionic-strength dialysis. Since dialysis of human factor VIII against buffers of low ionic strength yielded two distinct components, and since the factor VIII fraction isolated from normal plasma showed von Willebrand factor activity as defined by the corrective effect on abnormal platelet retention and ristocetin aggregation in von Willebrand's disease, the present studies were performed to determine if the correcting activities could be attributed to one or both of the components. Dialysis of factor VIII against buffers of low ionic strength led, however, to a decrease in factor VIII procoagulant activity and the reduction of the correcting activities, which suggested that the intact aggregate was required for procoagulant activity and for von Willebrand factor activity. In this respect dialysis of factor VIII at low ionic strength differed from dissociation at high salt concentrations. The two low ionic strength components were identified by the use of a rabbit antiserum against factor VIII, and could be distinguished on the basis of specific antigenic structures. Dialysis of factor VIII at low ionic strength led to a decrease in antigenic determinants closely related to factor VIII function. Specific antibodies to the low ionic strength components inhibited factor VIII activity in normal plasma, but the residual factor VIII was higher than that after inhibition with antibodies against intact factor VIII. Both antibodies interfered with von Willebrand factor activity.


Platelet release abnormality associated with a variant of von Willebrand's disease. A family with a platelet release abnormality (PRA) is described. The only son also showed a reduced rate of platelet aggregation in response to ristocetin, markedly reduced levels of von Willebrand's factor (vWf, ristocetin cofactor), and increased mobility of factor VIII-like antigen, features which were suggestive of von Willebrand's disease (vWd). No inhibition of vWf was found in his plasma. Family studies showed no evidence of vWd in the mother. The father's investigations showed a low rate of ristocetin aggregation on one of the two occasions when it was tested and low vWf on two of four occasions. Despite repeated testing, the findings in the father did not conclusively rule out the possibility of mild vWd, and it was impossible to determine whether the vWd in the son was inherited or arose as a mutation. The findings in this family suggest a possible relationship between abnormalities of the factor VIII complex and defective platelet function.


The immunological hazard of Cushing's syndrome. A 24-year-old woman was found to have cryptococcal meningitis and Cushing's syndrome due to an adrenal adenoma. Her meningitis was successfully arrested with fluorouracil. Treatment with metyrapone decreased her cortisol production and produced clinical remission of Cushing's syndrome. On admission her peripheral T lymphocytes were few and hyporeactive. When the overproduction of cortisol ceased the numbers of T lymphocytes and their reactivity returned to normal and she developed in-vitro lymphocyte responsiveness to the cryptococci.


In vivo release of 5-HT in the lateral ventricle of the rat: effects of 5-hydroxytryptophan and tryptophan. The in vivo release of 5-HT was examined in the rat brain. For this purpose, the left lateral ventricle was perfused at a constant rate with an artificial CSF for several hours in animals anaesthetized with halothane. 5-HT was estimated in serial 1-h collected fractions. The amine was first isolated by adsorption on a Sephadex G-10 column and then assayed using the radioenzymatic method of Saavedra et al.37, slightly modified to improve its sensitivity. The quantity of 5-HT released spontaneously during the first hour fraction was 296 pg, it was lower (99 pg/h) in the following fractions. 5-HT released into the CSF may in great part originate from serotoninergic terminals localized in structures surrounding the ventricle. This was suggested by experiments in which exogenous [3H]5-HT or [3H]tryptophan were perfused through the lateral ventricle during a few hours. [3H]5-HT taken up or synthetized was mainly localized in structures surrounding the ventricular space. The acute injection of 5-hydroxytryptophan (100 mg/kg) induced an immediate important and long lasting increase of 5-HT release. In contrast the acute injection of tryptophan (100 mg/kg) led to a transient and moderate elevation of 5-HT release which was only detected during the second hour of perfusion. Curiously a similar pattern of transmitter release was observed following the constant intravenous infusion of the amino acid (70 mg/kg/h) except that the increase in 5-HT release was much more pronounced during the second hour than after the acute injection. Parallel experiments were made to determine the time course of the changes of free and total tryptophan levels in plasma and of those of tryptophan, 5-HT, and 5-hydroxyindoleacetic-acid (5-HIAA) in brain tissues, induced by the acute and long term administrations of tryptophan. Moreover the rate of 5-HT synthesis was estimated using the monoamine oxidase inhibition method 2 and 5 h after both tryptophan treatments in halothane anaesthetized rats. 5-HT levels and the synthesis rate of the transmitter were increased at 2 h (when both tryptophan treatments stimulated 5-HT release). Despite the presence of high tryptophan levels in plasma and tissues and of high 5-HT and 5-HIAA levels in tissues, the synthesis rate of 5-HT (as the 5-HT release) was similar to that of controls 5 h after the onset of tryptophan infusion. These results suggest that some relationships occurred between the changes in 5-HT SYNTHESIs and release after the first hour of perfusion. The absence of effects of tryptophan treatments on 5-HT release during the first hour of perfusion are also discussed.


Improvement in delayed hypersensitivity in Hodgkin's disease with transfer factor: lymphapheresis and cellular immune reactions or normal donors. Passive transfer of delayed hypersensitivity was achieved, with normal transfer factor, in patients with Hodgkin's disease in remission. The cellular immune responses of the recipients improved. It is suggested that, in addition to specific effect the transfer factor (or factors) has a nonspecific effect causing improvement in the state of delayed hypersensitivity of the recipient in general. The average number of E-rosette T lymphocytes was 46.3% after the transfer factor treatment in Hodgkin's disease. The control patients with Hodgkin's disease, not receiving transfer factor, had a value of 37.8%. Removal of 4.9 X 10(9) to 1.08 X 10(10) lymphocytes did not diminish the delayed hypersensitivity of the donor. Side effects attributable to transfer factor were not seen.


Complications of indwelling chemotherapy catheters. Fifty consecutive chemotherapeutic infusions for cancer via precutaneously introduced arterial catheters were reviewed to determine the frequency of angiographic and clinical complications related to the indwelling catheter. Fibrin cloaking along the catheter was found in 20 patients studied by pull-out arteriography and was unassociated with clinical symptoms. Major thrombus formation occurred around the catheter tip in 28% of the infused vessels, all within the hepatic artery. Clinical symptoms developed in only three patients where thrombosis of the hepatic artery had propagated into the celiac axis. Systemic heparinization did not reduce the incidence of thrombus formation but did increase the incidence of mild gastrointestinal bleeding. Several factors may reduce the incidence of complications, such as puncture of a large artery, use of soft, pliable, and small diameter catheters, proper free position of the catheter in the infused vessel, regular angiographic checkups for catheters position, and early evidence of thrombus formation.


Intensity of immunosuppressive therapy and the incidence of Pneumocystis carinii pneumonitis. One hundred and forty-nine children with acute lymphocytic leukemia treated according to a prospective protocol were randomized after induction of remission and central nervous system (CNS) irradiation to receive maintenance chemotherapy with 1, 2, 3, or 4 chemotherapy agents. The incidence of P. carinii pneumonitis (PCP) was 5.0, 2.3, 2.2, and 22.4%, respectively, during the period of maintenance therapy. An additional 31 patients enrolled in the same study were placed in special categories to receive three drugs for maintenance plus supplemental chemotherapy or irradiation because of CNS leukemia on admission, remission failure, ediastinal mass, or generalized lymphosarcoma without bone marrow involvement. The incidences of PCP in these groups were 16.7, 30.0, 35.7, and 0%, respectively, during the period of maintenance therapy.


A study of childhood non-Hodgkin's lymphoma. The pathologic and clinical features of 31 cases of childhood non-Hodgkin's lymphoma (NHL) were reviewed retrospectively using Rappaport's classification and a modification of the Ann Arbor staging system. Twenty-nine (93.5%) of the patients had diffuse and 2 (6.5%) had nodular lymphoma. Diffuse histiocytic lymphoma accounted for 10 cases (32.3%), diffuse undifferentiated for 9 (29%), and diffuse lymphocytic, poorly differentiated for 5 (16.1%). Five cases (16.1%) were unclassifiable. No cases of well-differenitated lymphocytic or mixed cell lymphoma were found. A modified classification was attempted, which included also large basophilic cell (LBC), convoluted T-lymphocytic (CTL), and Burkitt's lymphomas. These pathologic subgroups accounted for 35.4%, 16.1%, and 6.5% of the cases, respectively. The patients were almost equally divided between clinically localized and generalized stages, and their survival was stage-dependent. The overall survival was 32.3%; the 3-year survival was 50% for Stages I and II, compared to 7.7% for Stages III and IV. The gastrointestinal tract was the most common site of origin. In 22% of the cases, the disease originated in extra-lymphatic tissues. Central nervous syste, involvement occurred in 10 of 31 children (32%), and a leukemic picture developed in 6 of 31 (19%). The Ctl lymphomas were confined to the mediastinum, whereas the LBC lymphomas arose mostly in Waldeyer's ring and Peyer's patches. We conclude that the extent of the disease as determined by clinical staging had prognostic significance in childhood NHL. The prognostic value of the histological classification could not be clearly established from our data.


Assay for citrovorum factor (NSC-3590) in the presence of methotrexate (NSC-740). Treatment of certain malignancies with high-dose methotrexate/citrovorum factor rescue has recently been adopted as an effective regimen. A microbiologic assay capable of detecting citrovorum factor in the presence of massive amounts of methotrexate has been developed using a strain of Pediococcus cerevisiae resistant to methotrexate. The assay described in this paper is an inexpensive and rapid method of studying the distribution kinetics of citrovorum factor.


Antibody-dependent lymphocyte killer function in human immunodeficiency diseases. Antibody-dependent cell immunity to the lymphocyte system (ABCIL) has been shown to be a function of a non-thymus-processed cell in the experimental animal. To evaluate its role in the human and to assess its clinical usefulness, we assessed ABCIL in twenty-five patients with various immunodeficiency (ID) syndromes. Our technique measures the lysis of 51Cr-labelled normal human lymphocytes coated with HL-A-specific antibody. Cytotoxicity is expressed as a percentage of 51Cr released after subtracting the spontaneous target cell release. Mean values in normals are 20+/-2 (s.e.). The ten patients with AB deficiency had a mean ABCIL of 7-9+/-2 (Pless than0-01). All eight patients with cellular ID had normal ABCIL (18+/-2), while the ten patients with combined ID had variable results. Effector cell function in the ABCIL test correlated (r=0-74; Pless than0-05) with the percentage of B cells in the peripheral blood. No correlation was found between ABCIL function and serum immunoglobulin levels or rosette-forming cells in the peripheral blood. There is a function for B lymphocytes other than as a precursor of antibody-synthesizing cells.


The effect of Freund's complete adjuvant on the cellular response in mice to sheep erythrocytes. The effect of Freund's complete adjuvant on the cellular response in BALB/c mice to SRBC was studied using techniques based on immunocytoadherence (ICA), inhibition of ICA using an antiserum to the theta alloantigen, and immune adherence (IA). Particular attention was paid to the cellular morphology of the responding lymph nodes, details of which are described.


Electrophoresis of lymphoid cells. A study of Bruton type of agammaglobulinaemia, thymic dysplasia, chronic lymphatic leukaemia and of normal human thymocytes. The mean electrophoretic mobility (EPM) of blood lymphocytes from a patient with Bruton type of agammaglobulinaemia was high with a unimodal distribution pattern. That of blood lymphocytes from a patient with severe thymic dysplasia was low, with a small faster group. The difference between the major groups was about 30%. Thymocytes had a mean EPM 25% lower than that of normal T cells. Blood and spleen cells in a chronic lymphatic leukaemic of B-cell origin had a mean EPM 35% higher than that of the majority of normal B cells.


Susceptibility of inbred rat strains to experimental thyroiditis: quantitation of thyroglobulin-binding cells and assessment of T-cell function in susceptible and non-susceptible strains. Ten inbred strains of rats were immunized with crude homologous thyroglobulin emulsified in Freund's complete adjuvant in order to investigate strain susceptibility to the induction of both thyroiditis and antibody to thyroglobulin. Two strains (LH and AUG) were found to be extremely susceptible and had 100% incidence of thyroid lesions which in general varied from moderate to very severe (mean index of pathology+/-SE, 2-5+/-0-2 and 2-1+/-0-4 respectively). One other strain (HL) also had 100% incidence of lesions but there were consistently mild in character (1-1+/-0-1). Two strains (DA and SD) were variable, with thyroid change varying from negative to severe. Three strains (LEW, WAG and PVG/c) had occasional lesions and the remaining two strains (AS and CAM) showed no thyroid change. Four strains (LH, AUG, HL and DA) consistently produced good antibody responses to thyroglobulin (mean titres+/-SE 7-3+/-0-3, 9-5+/-0-4, 6-9+/-0-3 and 6-6+/-0-5 respectively). In contrast WAG and CAM rats failed to develop autoantibody and the responses of AS, PVG/c and SD strain rats were quite variable. Although the autoantibody response generally correlated well with the presence of thyroiditis in a particular strain, LEW, AS and PVG/c rats often had good antibody levels with minimal thyroid lesions. Females of the most susceptible strains (LH and AUG) were found to have significantly more severe thyroid lesions and higher antibody titres to thyroglobulin than males. The most susceptible strains were all found to be of the Ag-B5 major histocompatibility genotype whilst the least susceptible were of the Ag-B2 genotype. However, wide interstrain variability was noted within the Ag-B5 genotype particularly with respect to the induction and extent of thyroid lesions. It was not found possible to relate the divergence in susceptibility between rat strains of Ag-B5 and Ag-B2 genotypes to differences in respective numbers of thyroglobulin-binding cells within the circulation of the non-immunized animal. Similarly, there were no differences in response between a susceptible (LH) and non-susceptible (CAM) strain to the phytomitogens PHA and Con A.


Cell-mediated immunity in rubella assayed by cytotoxicity of supernatants from rubella virus-stimulated human lymphocyte cultures. Rubella virus-stimulated lymphocytes from rubella-seropositive donors produced in the culture medium cytotoxic activity with preferential action against rubella-infected over uninfected target cells. The ability of lymphocytes to produce the cytotoxic activity upon stimulation by rubella virus correlated with the humoral rubella-immunity status, i.e. no such cytotoxic activity developed in the supernatants of lymphocyte cultures of rubella-seronegative donors. Stimulation of lymphocytes from seropositive donors by rubella virus was also detected by thymidine incorporation, but the correlation of lymphocyte responsiveness to the humoral rubella antibody status was not so clear as in the cytotoxicity assay. Conversion of lymphocytes from unresponsive to responsive to rubella virus following natural rubella infection and after rubella vaccination was demonstrated using both methods. Following vaccination rubella-specific cell-mediated immunity first became demonstrable at 14 days. The responsiveness of lymphocytes to phytohaemagglutinin (PHA) after rubella vaccination was followed by studying thymidine uptake and the ability of lymphocytes to produce lymphootoxin. By both tests marked suppression of PHA response occurred at days 3 and 7 after vaccination.


In vitro activation of human T and B lymphocytes by pokeweed mitogen. In previous in vitro studies the DNA synthesis in human blood lymphocytes induced by low concentration of PWM correlated with the percentage of bone marrow-derived (B) lymphocytes in cell suspensions. No correlation with lymphocyte subpopulations was noted when lymphocytes were activated by high concentrations of PWM. In this paper the hypothesis that low concentration of PWM mainly activates B lymphocytes was tested by measuring the [14C]thymidine incorporation into purified T or B lymphocytes from healthy donors. B lymphocytes were purified to 90--95% by buoyant density centrifugation of T lymphocytes rosetted with sheep red blood cells. T lymphocytes were enriched by passage of lymphocytes through an IgG-anti-IgG-coated column. Low concentration of PWM-stimulated B lymphocytes but not T lymphocytes, while high concentrations of the stimulant activated both cell types. It was also noted that the B- but not the T-lymphocyte fraction contained cells which synthesized DNA in the absence of PWM.


Specific concentration of antilymphocyte antibodies in the serum cryoprecipitates of patients with systemic lupus erythematosus. Antibodies to surface determinants of human lymphocytes, recognized both by cytotoxicity of fluorescent antibody analysis, were shown to be specifically enriched over the serum levels in cryoprecipitates from patients with systemic lupus erythematosus (SLE). The antilymphocyte antibody was shown to be cold reactive and was exclusively IgM. It was distinct from IgM anti-IgG, which was also variably concentrated in the cryoprecipitates. The question whether the antilymphocyte antibodies appear in the cryoprecipitates as complexes because of interaction with surface membrane antigens, or simply because of cold reactive properties, remains to be determined. The possible clinical relevance of the cryoprecipitation of these antibodies in systemic lupus erythematosus is discussed.


Autoantibodies in patients with carcinoma of the breast. Correlation with prognosis. Sera from a hundred patients with operable carcinoma of the breast and seventy-five age-matched controls were examined for antinuclear, smooth muscle, glomerular and mitochondrial antibodies by indirect immunofluorescence technique. Antinuclear and smooth muscle antibodies were found to be more frequent in cancer patients than in controls. The incidence of autoantibodies at the time the diagnosis was established was higher in patients who developed local recurrences or distant metastases within 2 years than in patients free from recurrence.


In vitro differentiation of human marrow cells into T lymphocytes by thymic extracts using the rosette technique. The manner by which human and calf thymic extracts induce precursor cells of human marrow to differentiate in vitro into T lymphocytes has been studied using as a T-cell marker the spontaneous rosette formation technique of human T lymphocytes with sheep erythrocytes (E rosette). These findings confirm previous observations made in the study of the same process using a different T-cell marker, specific antigenicity recognizable by a heterologous anti-human T-cell serum in a microcytotoxicity test. The number of cells revealing evidence of differentiation demonstrated by the E rosette formation technique is smaller than that obtained with the anti-human T-cell serum, indicating perhaps that a different stage of maturation of T lymphocytes is recognized by the antiserum from the one detected by spontaneous rosette formation. Based on the effects of specific inhibitors of nucleic acids and protein synthesis, it can be concluded that these thymic extracts ultimately act by influences exerted in the cell nucleus and that RNA and protein synthesis are required for the differentiation of precursor cells into T lymphocytes induced by thymic extracts. In addition, continued protein synthesis appears to be required for maintenance of receptors for sheep erythrocytes on the cell surface.


The relationship of autoantibodies to depression of cell-mediated immunity in infectious mononucleosis. It has been postulated that autoantibody formation occurs as a consequence of a depression of function of certain thymus-derived lymphocytes (T cells). We have examined cell-mediated immunity, a T-cell function, in infectious mononucleosis, a condition in which autoantibodies are known to develop. We have shown some evidence of depressed cell-mediated immunity in patients with infectious mononucleosis but have been unable to correlate this with autoantibody production. These results do not support the hypothesis that depression of T-cell function leads to autoantibody formation.


Disparity in the production of lymphoblastogenesis inhibition factor by cultured human B and T lymphoid cell lines. A comparative study of inhibitory effects of cell-free supernatants from cultured human B and T lymphoid cell lines on lymphocyte blastogenesis indicated that the inhibitory effect of supernatant from B lymphoid cells on lymphocyte blastogenesis was significantly higher than that of supernatant from T lymphoid cells or from non-lymphoid neoplastic cells. The inhibitory effect of supernatant was reversible and dose-related. The inhibitory effect gradually diminished with time when the supernatant from B lymphoid cells was added to the culture, 1-3 days after the beginning of cultures. The supernatant of human B lymphoid cells was also found to be highly active in affecting the mouse thymus cell response. The biological nature of this inhibitory factor has not been defined. Both B lymphoid cell lines used in the present study contained Epstein-Barr virus (EBV) genomes while the T-cell line and the non-lymphoid neoplastic cell lines were free of EBV genomes. Sensitivity of the supernatant of B lymphoid cells to u.v. irradiation and heat suggests the possibility that the EBV genomes released into the culture medium may be responsible for inhibition of lymphocyte blastogenesis; resistance of this supernatant to DNase suggests that the EBV genomes may be double-stranded DNA.


Thyroiditis in T cell-depleted rats. Influence of strain, radiation dose, adjuvants and antilymphocyte serum. Strain differences in susceptibility to the development of thyroiditis following adult thymectomy and repeated sublethal X-irradiation (4 X 200 rad) were investigated in the rat. Marked strain variation was noted, with AUG and PVG/c rats having the highest incidence and severity of lesion (100 and 80% respectively) whilst CAM rats had a low incidence (9%). WAG and LIS rats occupied an intermediate position. The incidence of autoantibodies to thyroglobulin correlated closely with the strain incidence of thyroiditis (r = 0-87). Fractionation of the sera from thymectomized and irradiated rats by gel filtration chromatography indicated that the bulk of the antibodies to thyroglobulin were of the IgG class. Freund's complete adjuvant, but not lipopolysaccharide, enhanced the rate of development of thyroiditis in thymectomized rats given a shortened series of irradiations. It was not found possible to induce thyroiditis in thymectomized rats by substituting antilymphocyte serum for irradiation as a T cell-depleting agent, despite the fact that the treated rats had markedly reduced responses to phytohaemagglutinin. A combination of thymectomy, three doses of 200 rad, and a development period of 8 weeks were found to be the optimum conditions for induction of severe thyroiditis together with high antibody titres to thyroglobulin. These findings add support for the role of thymus-derived cells in the regulation of autoimmune responses and further suggest that thymectomy, combined with a series of sublethal irradiations, causes a selective depletion of those T cells specifically involved in the suppression of autoimmune reactivity to thyroid components, whilst leaving autoreactive helper T cells unimpaired.


Cytotoxic activity of lymphocytes from patients with Hodgkin's disease. Blood lymphocytes from twenty-three untreated patients with Hodgkin's disease and twelve healthy controls were studied for their ability to lyse tissue culture cells (Chang cells) labelled with [51Cr]chromate. Lysis induced by patients' lymphocytes in the presence of PHA or rabbit IgG antibodies to Chang cells (ACS) was impaired in some, and higher than normal in others. ACS-induced lysis showed some corlation with the content of lymphocytes carrying receptors for human complement (CRL) in the effectory population. No correlation with immunoglobulin-bearing cells was noted. PHA-induced cytoxicity did not  correlate with lymphocyte subpopulations. The observations are consistent with the assumption that effector cells of antibody-induced lymphocyte-mediated cytotoxicity (K cells) may be present among CRL. The K-cell activity and PHA cytotoxicity by lymphocytes tended to decrease at high age, but impaired cytotoxity was also noted in young patients. A preliminary follow-up of patients 1-2 years after the beginning of treatment revealed almost abolished K-cell activity in four patients who died 6--13 months after testing. Patients in incomplete remission or with relapse after treatment had lower mean K-cell activity than those in complete remission. A similar, but less pronounced tendency was found for PHA-induced cytotoxicity. A prognostic role of impaired K-cell activity in Hodgkin's disease is suggested from these data, but requires confirmation in a larger clinical follow-up.


Serum lymphocytotoxins in inflammatory bowel disease. Studies of frequency and specificity for lymphocyte subpopulations. Serum cold-reactive lymphocytotoxin (LCT) was detected in twenty-two of fifty-six (40%) patients with inflammatory bowel disease (IBD). The frequency of LCT detection was similar in Crohn's disease and ulcerative colitis. Cytotoxicity testing against T or B cell-enriched peripheral blood lymphocytes from normal donors, together with absorption experiments, indicated that LCT in IBD was reactive against determinants on both cell subpopulations. Reactivity against T cells from patients with common variable immunodeficiency was significantly less than with normal donor T cells. LCT in IBD could not be related to prior allogeneic sensitization and its presence appeared to be unrelated to disease activity or drug therapy. No correlation was found between LCT and peripheral blood T- or B-cell numbers. The present findings suggest the need for further investigation of the role of infectious agents in the pathogenesis of IBD.


Quantitation of immunoglobulin-bearing lymphocytes and the lymphocyte response to PHA in experimental pyelonephritis. In these experiments the effect of experimental pyelonephritis on the distri-ution of B lymphocytes in the peripheral blood and lymphoid sites in the rat has been determined and the functional capacity of T cells during the course of infection has been investigated. The studies have shown that renal infection affects the distribution of lymphocytes and has a marked effect on the functional capacity of splenic T lymphocytes early in infection. Most of the lymphocytes forming the round cell infiltrate in the kidney have been identified as thymus-derived lymphocytes on their surface labelling characteristics. Evidence is presented to demonstrate the inability of T lymphocytes to function normally in the environment of the kdiney. It is suggested that ablation of cell-mediated immunity may be a factor contributing to the persistence of renal infection.


[Emergency surgery in district hospital: massive hemorrhage after blunt abdominal injury]. In the management and prognosis of severe accident cases there are a number of conditions that occur before hospitalization which cannot be influenced, these are: no immediate medical care by a physician, delay in sending the patient to hospital, long journey time and alcoholic damage to the liver and CNS. Often, therefore, laparotomy for massive haemorrhage after abdominal injuries has to be done on a severely shocked patient with a "zero" BP. Diagnostic criteria in the evaluation of such cases are: the clinical picture, shock index, paracentesis (trial abdominal drainage) with additional laparoscopic examination and IVP. In a series of 45 laparotomies there were 25 single organ injuries; 19 multiple organ injuries and 1 negative laparotomy due to misinterpretation of the trial drainage. 22 splenectomies demonstrate the type of injury occurring in a country area. The good results of treatment despite the difficulties mentioned can, to some degree, be attributed to the technical improvement in vascular clips for large vessels. The Tantalum vascular clip offers the advantage of simple application, sure positioning and immediate arrest of haemorrhage thus reducing the shock phase; additional effects are the permanent indication of the bleeding site, the marking of anastomoses and resections and there being no foreign body reaction (pure Tantalum).


Three distinct forms of nuclear poly(A) polymerase. Poly(A) polymerase activities have been solubilized from rat liver nuclei and purified by chromatography on Bio-Gel A-1.5M, DEAE-Sephadex and CM-cellulose. Three distinct forms of nuclear poly(A) polymerase have been resolved by chromatography on CM-cellulose. According to their sequence of elution from CM-cellulose these enzyme activities have been termed A, B and C. Enzymes A and B are Mn2+ -dependent, enzyme C requires Mg2+. With the same chromatographic step on CM-cellulose the Mn+ -dependent poly(A) polymerase activities were separated from a Mn2+ -dependent enzyme system capable of synthesizing RNA-primed poly(U), poly(G) and poly(C). The effect of different nuclear and cytoplasmic RNA primers on the rate of poly(A) formation suggests enzyme A to be responsible for the elongation of preexisting poly (A) chains.  The phosphorylated derivated derivative of cordycepin, 3'-deoxyadenosine 5'-triphosphosphate (3'-dATP), which is known to inhibit nuclear poly(A) synthesis in vivo, also impairs poly(A) formation in vitro. It is shown that 3'-dATP very probably is not incorporated into poly(A)invitro, suggesting that 3'-dATP primarily affects the catalytic activities of the poly(A) polymerase species rather than directly blocking chain elongation.


5-Aminolevulinic-acid synthetases from Rhodopseudomonas spheroides Y. Comparison of the purification and properties of enzymes extracted from bacteria grown in different iron concentrations. The two 5-aminolevulinic acid synthetases of Rhodopseudomonas spheroides Y. were extracted from cells grown in a 'low-iron' medium and purified. They have a specific activity 10-fold higher than the 'high-iron' enzymes described by us previously and have the same properties except that they do not contain any iron and have one free-SH group more per mole of enzyme (2 for E1; , for E2) Their inhibition by adenosine triphosphate and iron and their oxidation-reduction sensitivity are discussed in terms of light, oxygen and heme feed-back regulation of bacteriochlorophyll sunthesis.


Perception of linear horizontal self-motion induced by peripheral vision (linearvection) basic characteristics and visual-vestibular interactions. The basic characteristics of the sensation of linear horizontal motion have been studied. Objective linear motion was induced by means of a moving cart. Visually induced linear motion perception (linearvection) was obtained by projection of moving images at the periphery of the visual field. Image velocity and luminance thresholds for the appearance of linearvection have been measured and are in the range of those for image motion detection (without sensation of self motion) by the visual system. Latencies of onset are around 1 sec and short term adaptation has been shown. The dynamic range of the visual analyser as judged by frequency analysis is lower than for the vestibular analyser. Conflicting situations in which visual cues contradict vestibular and other proprioceptive cues show, in the case of linearvection a dominance of vision which supports the idea of an essential although not independent role of vision in self motion perception.


Inhibition of respiration and of respiratory development by different doses of chloramphenicol in frog embryos (Rana pipiens). High doses of chloramphenicol (4.5 and 9 mM) directly inhibited respiration in conjunction with an unusual cleavage anomaly (blastomere refusion) in embryos of the frog, Rana pipiens. Lower doses (2.1-3 mM) did not affect respiration or cleavage and, when added later, did not directly affect respiration or development at any tested stage. Continuous incubation in the latter doses, however, did eventually, by day 6 or 7, produce a parallel retardation of embryonic development and of respiratory development relative to controls, suggestive of impaired mitochondrial biogenesis. A lower continuous dose (0.9 mM) affected neither respiration nor development at any stage.


Optical guiding by photoreceptor cells.

Optical guiding by photoreceptor cells. The potential for any morphological part of a photoreceptor cell to function as an optical waveguide is determined 1) by the dimensionless parameter V as shown by Snyder (IEEE Trans., Microwave Theory Tech. 17: 1133, 1969) and by Snyder, Pask and Mitchell (J. Opt. Soc. Am. 63: 59, 1973), and 2) by the nature of the optical excitation for that part of the cell. The effects of these two factors are considered for the myoids and outer segments of vertebrate photoreceptor cells and for the crystalline tracts and rhabdomers of invertebrate photoreceptor cells. Examples of both guiding and nonguiding myoids, outer segments, rhabdomers and tracts are cited and some consequences for vision are analyzed.


The polycystic organ in senescent athymic nude mice and in euthymic mice. The polycystic organ thought to be the thymic rudiment in "athymic" nude mice increased with age and continues its secretory activity even in senescent nude mice. Only the epithelial lining of the cysts undergoes pressure atrophy. Analogous polycystic structures can be found also in euthymic mice with or without the nu gene. A lymphoepithelial rudiment is found in the thymic area of nude mice; it may represent the true endodermal thymic rudiment and generate the T cells. In addition, a peculiar, sometimes enlarged and thymus-like node is present laterocaudally from the polycystic organ.


Immunopathology of hepatitis B antigen positive and negative active chronic hepatitis. Evidence is presented to suggest that an auto-immune response to a liver-specific lipoprotein antigen on the surface of hepatocytes is responsible for the progressive liver damage in active chronic hepatitis, and that in many cases infection with the hepatitis B virus is important in the initiation of the disease process. B cells appear to play a major role in the auto-immune response and may be activated by T cells reacting with viral antigens on the surface of infected hepatocytes. A postulated defect in humoral antibody production in HBAg-positive cases allows continued reinfection of the liver by the hepatitis B virus, persistence of a virus-directed T cell response and constant activation of B cells reacting with the liver-specific lipoprotein. In the HBAg -negative group the disease is also, in many cases initiated by an acute hepatitis, but here the auto-immune response continues after elimination of the virus because of a defect in the suppressor function of T cells which fail to turn off the autoreactive B cells. The histocompatibility antigen, HL-A8, may be a marker for such a defect in suppressor T cells - its increased frequency in active chronic hepatitis is restricted to the HBAg-negative cases. Finally, the hypothesis suggests how specific immunotherapy, either antibody to HBAg or Transfer Factor, could be given to correct the basic defects which lead to persistence of the auto-immune process.


Platelet hyperaggregation and increased plasma level of Von Willebrand factor in diabetics with retinopathy. In 18 insulin-dependent diabetics (6 without retinopathy, 6 with proliferative retinopathy and 6 with proliferative retinopathy treated by hypophysectomy) matched for age and duration of diabetics, in vitro haemostasis was studied using ADP induced platelet aggregation, ristocetin induced platelet aggregation which allows von Willebrand factor (VIII VWF) assay, and determination of antihemophilic factor procoagulant activity (VII AHF). Using gel filtration-isolated platelets, the ADP induced hyperaggregation previously reported in diabetics with severe retinopathy untreated by hypophysectomy appeared to be related to a platelet and not a plasma factor; the normal results of thrombin induced aggregation suggests that the presumed abnormal platelet factor is related to the platelet plasma membrane. High level of plasma VII VWF was observed in diabetics with proliferative retinopathy while the VII AHF level was within normal limits.


The ultrastructure of hepatocytes in alpha-1-antitrypsin deficiency with the genotype Pi--. The ultrastructural appearance of the endoplasmic reticulum of the hepatocytes was found to be normal in a 5-year-old girl with alpha-1-antitrypsin deficiency with the genotype Pi--. The liver ultrastructure of this variant is therefore different from that of alpha-1-antitrypsin deficiency with the genotype PiZZ in which aggregates of an abnormal, unsecreted alpha-1-antitrypsin accumulate in the endoplasmic reticulum of the hepatocytes. The normal appearance of the endoplasmic reticulum in alpha-1-antitrypsin deficiency with the genotype Pi-- is compatible with the hypothesis, in this variant, synthesis of alpha-1-antitrypsin is completely, or nearly completely, absent; an alternative hypothesis would be that an abnormal alpha-1-antitrypsin is produced by the liver and secreted into the plasma, but disappears rapidly from the plasma.


[Wiscott-Aldrich syndrome. Description of a case]. The Wiscott-Aldrich syndrome with the classical symptomatology (eczema, thrombocytopenia and susceptibility to infections) has been described in a 3-month-old child. The family history, together with the evidence of an immunological deficiency involving both thymus-dependent lymphocyte and immunoglobulin-antibody systems have given important clues to diagnosis. Impairment of immunoglobulin homoeostasis and its relevance to the assessment of heterozygotes is discussed.


[Retrospective studies on stress ulcer]. The files of 100 stress-ulcer-patients (1960-1973) were carefully analyzed. These patients had usually complicated diseases before they developed stress ulcers. Melena was in 84 patients the initial symptom. 56 patients were treated by medical regimen, 34 patients underwent surgery. A partial gastrectomy was the procedure of choice except for poor-risk patients, who underwent vagotomy.


Antileptospiral activity in lower-vertebrate sera. Normal serum from the painted turtle (Chrysemys picta), the snapping turtle (Chelydra serpentina), and the frog (Rana pipiens) were found to possess bactericidal activity towards Leptospira. Leptospires from both the parasitic and biflexa complexes were killed by these sera at high dilutions. This pattern differs from that of mammalian serum, as generally only the biflexa complex leptospires are killed by normal mammalian serum. The activity in C. picta serum was characterized as being complement dependent and not mediated by basic proteins. Because comple-inactivated C. picta serum regained leptospiricidal activity after the addition of fresh rabbit serum, antibody is also likely to participate in the killing activity. Further support that C. picta serum contained leptospiral antibodies was found by the detection of serotype-specific agglutinins.


In vitro bacteriostatic and bactericidal activities of 7 cephalosporin antibiotics on Haemophilus influenzae. A total of 30 recently isolated strains of Haemophilus influenzae were tested for in vitro susceptibility to seven cephalosporins. In order of bacteriostatic effectiveness, the in vitro activity of the antibiotics studied was: cephapirin (median MIC = 0.78 mcg/ml), cephalothin (median MIC = 1.56 mcg/ml), cefazolin (median MIC: 1.56 mcg/ml), cephaloridine (median MIC = 3.12 mcg/ml), cefoxitin (median MIC = 3.12 mcg/ml), cephradine (median MIC = 12.5 mcg/ml) and cephalexin (median MIC = 25 mcg/ml). The bactericidal effectiveness of the seven compounds was studied against one of these strains. No drug was able to kill the selected strain in less than 6 hrs, even at 100 mcg per ml. Cefoxitin exhibited the best bactericidal effects, closely followed by cefazolin and cephapirin.


On the radiation-induced aggregates of lactate dehydrogenase. Radiolysis of lactate dehydrogenase under N2 leads to the formation of aggregates which are enzymatically inactive. These aggregates were isolated by gel filtration. Incubation with sodium dodecylsulphate followed by gel filtration made it obvious that these aggreates consist of protein fragments held togehter by hydrophobic and electrostatic interactions. Disulphide bridges were found to be unimportant for stabilizing the aggregates. All isolated protein fragments were smaller than the sub-units of lactate hydrogenase, indicating peptide-chain breaking as a major reaction in the radiolysis of proteins and in the inactivation process of enzymes.


Evidence for reproductive death of dividing cells in thymus and spleen following whole-body gamma-irradiation of mice. Mice were given whole-body gamma-irradiation with 300 and 800 rad 1 hour or 1 day after the administration of 3H-thymidine. The time-course of the specific activity of DNA in thymus and spleen and the release of radioactivity into the fraction of DNA soluble in 0-14 N NaCl were determined for 28 hours after exposure. The results indicate that on average the loss of mitotically-active cells was delayed compared with the loss of a representative fraction of non-dividing cells. This suggested that different mechanisms might be implicated in the dying process of the dividing and non-dividing lymphoid cells. Using a dose-fractionation method, the total activity of DNA was determined in thymus and spleen at 24 hours after the first exposure and 25 hours after the in vivo labelling of DNA. A parallelism has been found between the results of this experiment and the recovery effect of the Elkind-Sutton type. It may be concluded that the dying process responsible for the loss of the dividing cells from thymus and spleen after irradiation probably involves reproductive death.


The oxygen-enhancement ratio for reproductive death induced by 3H or 125I damage in mammalian cells. The oxygen-enhancement ratio (o.e.r.) for 3H- and 125I-induced cell death at 4 degrees C was determined in cultured Chinese hamster cells. The o.e.r. for cell death induced by 3H-thymidine was 3-2, essentially the same value as that previously reported for X-ray induced cell death. For cell death induced by 125I-iododeoxyuridine (125IdUrd), the o.e.r. was less than 1-4. The lower o.e.r. for 125I-induced death was not due to the presence of the base analogue itself, since cells that had incorporated unlabelled IdUrd and were X-irradiated had an o.e.r. of 2-8 and cells that were inactivated by 3H-IdUrd damage at 4 degrees C had an o.e.r. even greater than 3. These results suggest that 125I-decay damage, like high-linear-energy-transfer radiation damage, is only slightly increased by the presence of oxygen.


DIP and DIP+2 as glutathione oxidants and radiation sensitizers in cultured Chinese hamster cells. Two diamide analogues, diazene dicarboxylic acid bis (n'-methylpiperazide) or DIP, and its bis-N'-methyl iodide salt, or DIP + 2, were tested for their ability to penetrate cultured Chinese hamster cells and oxidize intracellular glutathione. DIP penetrated the cells at a reasonable rate at 18 degrees C, 160 nmoles being required to oxidize the endogenous glutathione of 2 X 10(6) cells, but it penetrated very slowly at 0 degrees C. DIP +2 did not effectively oxidize glutathione in Chinese hamster cells, possibly because it did not enter the cells. DIP became toxic after about 10 min of exposure, but its toxicity could be moderated by using anoxic conditions. DIP, but not DIP +2, sensitized anoxic Chinese hamster cells to X-radiation by a factor of 1-5, an effect that was due entirely to removal of the shoulder from the survival curve.


Incorporation of tritiated thymidine of high specific activity into DNA of the mouse oocyte. Radicals produced by X-irradiation at 77 K and at 300 K of cytosine. HCl crystals have been analysed by electron spin resonance spectroscopy. Four radicals have been identified: the anion radical of the cytosine molecule, the radical resulting from H-addition at position C6, the radical resulting from H-addition at position O2, and finally a radical resulting from addition of a Cl- to nitrogen N3. Hückel molecular orbital calculations are presented, which support the hypothesis according to which in unsaturated pyrimidines the site of hydrogenation or protonation depends on the state of the molecule.


Sensitization of thymine and uracil to ionizing radiation by p-nitroacetophenone. p-Nitroacetophenone (PNAP) alters the radiation chemistry of thymine and uracil in de-aerated aqueous solution. In the case of thymine, it increases the yield of radiolysis products by a factor of almost two, and cis glycol of thymine is the major product. With uracil, the yield of the dimeric product, which is the major radiolysis product in de-aerated aqueous solution, is considerably reduced and the yield of cis glycol is increased. When the irradiation is carried out in N2O-saturated solution, PNAP enhances the yeild of glycol by a factor of two. The effects of cupric sulphate on the radiation chemistry of uracil are analogous to those of PNAP. A mechanism, involving a reaction between PNAP and the hydroxyl radical adduct of the pyrimidine proceeding through a one-step process, is postulated for the enhanced formation of glycol.


The role of T-lymphocytes in the reactivation of presumed ocular histoplasmosis scars. The surprising finding of viable lymphocytes in clinically inactive scars gives more credence to the immunological theory regarding reactivation of histoplasmosis scars. We feel that the T-lymphocyte theory can explain the mechanism by which an inactive scar becomes active upon reintroduction of the antigen. The clinical course of the disease as well as the response to corticosteroid therapy and photocoagulation are also consistent with this hypothesis.


Hereditary corneal dystrophy in the Manx cat: a preliminary report. A progressive, apparently inherited corneal dystrophy is described in an inbred line of Manx cats. Initial changes in the cornea are seen at four months of age and characterized by anterior stromal edema. Progressive worsening of the condition produces severe bullous keratopathy with eventual breakdown of both epithelium and stroma. Light microscopic and ultrastructural studies in the advanced disease state revealed marked edema of the corneal stroma, disintegration of collagen material, and the formation of epithelial bullae. Ultrastructural evidence shows a normal endothelium to be present. The pathogenesis of this corneal dystrophy is not clear and further studies are underway.


Ampicillin-resistant Haemophilus influenzae pneumonia and empyema in an infant. Ampicillin-resistant Haemophilus influenzae type b was isolated from the pleural fluid of a 15-month-old infant with pneumonia and empyema. The patient was cured when chloramphenicol treatment was substituted for ampicillin.


[Indication and timing of conservative surgery of peripheral neurogenic vocal cord pareses (author's transl)]. 1. In every case of a vocal cord paresis, its cause should be carefully sought. 2. "Pseudopareses" of the vocal cord can be excluded by electromygraphy. 3. In all cases of neurogneic vocal cord praeses and regardless of aetiology, immediate phoniatric training is indicated for acceleration of nerve regeneration as well as electrostimulation for the prevention of muscular atrophy and ankylosis of the cricoarytenoid joint. 4. If such therapy is neglected, the functional results of spontaneous regeneration, neurolysis and nerve plasty are doubtful. 5. If in cases of mechanical lesions of the recurrent nerve one decides to operate, electromyography of the larynx and a mobility test of the cricoarytenoid joints to be done first. 6. Compression or overstretching of the nerve should be followed by neurolysis after 5 months, unless the nerve has regenerated spontaneously. 7. When the recurrent nerve has had to be served it should be repaired by anastomosis as soon as possible. 8. Judging by our experience in regeneration of the laryngeal nerves, we feel that operations for opening or closure of the glottis are indicated only after 2 years.


Physical size of the donor locus and transmission of Haemophilus influenzae ampicillin resistance genes by deoxyribonucleic acid-mediated transformation. The properties of donor deoxyribonucleic acid (DNA) from three clinical isolates and its ability to mediate the transformation of competent Rd strains to ampicillin resistance were examined. A quantitative technique for determining the resistance of individual Haemophilus influenzae cells to ampicillin was developed. When this technique was used, sensitive cells failed to tolerate levels of ampicillin greater than 0.1 to 0.2 mug/ml, whereas three resistant type b beta-lactamase-producing strains could form from the colonies in 1- to 3-mug/ml levels of the antibiotic. DNA extracted from the resistant strains elicited transformation of the auxotrophic genes in a multiply auxotrophic Rd strain. For two of the donors, transformation to ampicillin resistance occurred after the uptake of a single DNA molecule approximately 104-fold less frequently than transformation of auxotrophic loci and was not observed to occur at all with the third. The frequency of transformation to ampicillin resistance was two- to fivefold higher in strain BC200 (Okinaka and Barnhart, 1974), which was cured of a defective prophage. All three clinical ampicillin-resistant strains were poor recipients, but the presence of the ampicillin resistant genes in strain BC200 did not reduce its competence. Sucrose gradients of DNA from ampicillin-resistant transformants of BC200 and from the original ampicillin-resistant strains showed that: (i) all the DNA preparations had high molecular weights; (ii) donor activity for ampicillin resistance sedimented heterogeneously and in parallel with genome DNA up to the highest molecular weights observed (100 x 106 to 200 x 106); and (iii) genetic transformation of ampicillin resistance from strain BC200-amp90383 required the physical integrity of a linearly integrated segment of DNA having a molecular weight of about 25 x 106 to 30 x 106.


Single-stranded regions in transforming deoxyribonucleic acid after uptake by competent Haemophilus influenzae. About 15% of donor deoxyribonucleic acid (DNA) is single stranded immediately after uptake into competent Haemophilus influenzae wild-type cells, as judged by its sensitivity to S1 endonuclease. This amount decreases to 4 to 5% by 30 min after uptake. Mutants which are defective in the covalent association of recipient and donor DNA form little or no S1 endonuclease-sensitive donor. At 17 C donor DNA taken up by the wild type contains single-stranded regions although there is no observable association, either covalent or noncovalent. The single-stranded regions are at the ends of donor DNA molecules, as judged by the unchanged sedimentation velocity after S1 endonuclease digestion. The amount of single-stranded donor remains constant at 17 C for more than 60 min after uptake, suggesting that the decrease observed at 37 C is the result of association of single-stranded ends with single-stranded regions of recipient cell DNA. Three sequential steps necessary for the integration of donor DNA into recipient DNA are proposed: the synthesis of single-stranded regions in recipient DNA, the interaction of donor DNA with recipient DNA resulting in the production of single-stranded ends on donor DNA, and the stable pairing of homologous single-stranded regions.


Lipid A, the active part of bacterial endotoxins in inducing serum colony stimulating activity and proliferation of splenic granulocyte/macrophage progenitor cells. An analysis of which component of lipopolysaccharides (LPS), the lipid or the polysaccharide (PS), is active in stimulating the murine granulopoietic system has been performed. LPS with different structures, isolated from different mutant strains of Salmonella and chemical degradation products of lipopolysaccharides have been used. Lipid A obtained by acid hydrolysys of the LPS and complexed to bovine serum albumin (BSA) (lipid A-BSA) was shown to be active in generating serum colony stimulating factor (CSF) and in increasing the splenic colony forming cells (CFC) levels, although it was less active than the parent LPS. The polysaccharide (PS) showed no significant activity at the concentrations used. LPS (glycolipids) from R mutants of Salmonella minnesota were active to the same extent as the LPS. The fact that even the most defective LPS from the R mutant R595 which contains lipid A and KDO only is a potent endotoxin, points unequivocally, to lipid A, as the active principle in stimulating the granulopoietic system.


Distribution of coronary artery disease in patients with isolate aortic valve disease. Forty-four adult patients with isolated aortic valve disease underwent coronary arteriography. Seventy precent of patients required aortic valve replacement (AVR). Of 28 men who underwent AVR, 59 percent of those with severe aortic stenosis, 33 percent of those with severe aortic regurgitation and 50 percent of those with mixed aortic stenosis/aortic regurgitation had associated coronary artery disease. Thirty-six percent of men with aortic valve disease not requiring AVR had significant coronary artery disease (CAD). CAD was not found in the 5 female patients studied. In the patients with CAD, the left anterior descending artery was involved 84 percent of the time. Next in frequency were the right coronary artery, the proximal left circumflex artery, and the obtuse marginal artery. Multivessel disease was the rule. All but one patient with significant CAD had angina pectoris, but many patients with angina had normal coronary arteries. The frequent occurence of significant CAD in adult male patients with isolated aortic valve disease argues for the performance of selective coronary arteriography in all such patients in whom AVR is a consideration.