Prevalence and incidence of the diagnosis of gout in Great Britain. A study in gout of the incidence of diagnosis from 1971 to 1975 and of the prevalence at 31 December 1975 was carried out in a representative general practice sample comprising 64 practices and a population numbering 1 in 145 of the total population of Great Britain. The results show an annual incidence in Great Britain from 1971 to 1975 varying from 0.25 to 0.35 per 1000 and an overall prevalence at 31 December 1975 of 2.6 per 1000. The prevalence in England was found to be significantly greater than in the rest of Great Britain and that in Wales to be significantly greater than in Scotland. In 10% of the cases the gout was believed to be secondary, with induction by diuretics being the most frequent cause. The prevalence of primary gout was estimated to be 2.3 per 1000.


Cimetidine-induced neutropenia: a possible dose-related phenomenon. Neutropenia associated with high-dose cimetidine therapy developed in a patient in whom earlier therapy, as well as rechallenge with low-dose cimetidine, did not result in neutropenia. As other factors cannot be implicated, a dose-related toxicity of cimetidine appears likely. Although the mechanism of cimetidine-induced neutropenia is unknown, it may involve the previously demonstrated ability of histamine H2 receptor antagonists to block the histamine-induced initiation of DNA synthesis in bone marrow stem cells.


Extrahepatic portal hypertension: a retrospective analysis. A retrospective analysis of 19 patients with esophagogastric or intestinal varices secondary to extrahepatic portal hypertension was conducted. Nine patients had onset of bleeding during childhood. In six of eight pediatric patients in whom a shunt was performed no major bleeding occurred during the follow-up period. In seven adults with pure extrahepatic portal hypertension the four shunting procedures effected permanent control of bleeding. In two of three adults in whom portal vein thrombosis was associated with liver disease, shunting was successful. An emergency procedure was infrequently required. Multiple recurrences of bleeding episodes prior to decompression was the rule. Postshunt encephalopathy was never seen. In those patients in whom a shunt thrombosed or could not be performed, recurrent bleeding occurred uncommonly, and was readily managed to bedrest and transfusion.


Acute bilateral suppurative parotitis due to Haemophilus influenzae. Report of two cases. Acute bilateral suppurative parotitis developed in two patients with documented cirrhosis of the liver while they were in the hospital. Gram's stain and culture of purulent material obtained from the orifice of Stensen's duct disclosed Haemophilus influenzae as the sole isolate. Both patients were treated successfully with local care and antibiotics. To our knowledge, with one possible exception, infection of the parotid gland due to this organism has not been described previously.


Cell-mediated and humoral types of immunologic immunity in idiopathic pancytopenia. In a majority of 34 patients (including 30 treated with androgens and glucocorticosteroids), the absolute lymphocyte count, percentage of the T population and its reactivity in vitro to PHA, PWM and sheep erythrocytes were normal. In one fourth of cases, serum levels of IgG and/or IgM classes of immunoglobulins were decreased. The deviations in levels of serum immunoglobulins, and in some patients in the lymphocyte count and in the T population and its reactivity to antigens were attributed to complex causes, including immunosuppressive treatment with adrenal glucocorticosteroids. It is suggested that indications for treatment with these hormones in cases of bone marrow aplasia with suppression of the lymphoid system should be restricted.


Cell-mediated hypersensitvity in glomerulonephritis. Proportions and total numbers of peripheral blood T and B lymphocytes as well as their activity measured in the leukocyte migration inhibition test were estimated in 47 patients with acute or chronic glomerulonephritis and in 30 individuals serving as a control group. The obtained results indicated that glomerulonephritis was associated with altered proportions of peripheral blood lymphocytes. In acute glomerulonephritis high B lymphocyte levels were found while chronic proliferative glomerulonephritis was characterized by high proportions and high absolute levels of T lymphocytes. Few months observation of T: B lymphocyte proportions during the disease indicated that exacerbation of the disease was associated with lowered proportions of T lymphocytes. Moreover, it was shown that cell mediated hypersensitivity to GBM antigens was detectable in 80% patients with glomerulonephritis and was absent from patients with pyelonephritis. The latter results indicate participation of cell-mediated hypersensitivity in pathomechanisms of glomerulonephritis in most of the patients.


T and B lymphocytes in the ontogenetic development of man. Cord blood lymphocytes of premature and mature fetuses and peripheral blood of infants and adults were studied by rosette techniques and membrane immunofluorescence. Percentage of lymphocytes carrying surface immunoglobulins, receptors for complement and receptors for uncoated sheep erythrocytes or receptors for Fc IgG was determined. T lymphocyte receptors were found to appear later in ontogeny than the receptors typical of B lymphocytes. Receptors for Fc IgG were the earliest to appear: already in premature fetuses the percentage of lymphocytes resembled the one seen in healthy adults. However, the absolute number of T cells increased during development of fetuses and infants and slightly decreased in adults. On the other hand, the absolute number of B lymphocytes were highest in mature fetuses and decreased in subsequent age groups. In the course of human ontogeny a progressive increase was found in lymphocytes carrying full sets of T or B lymphocyte receptors, paralleled by a corresponding decrease in mean values of "null" lymphocytes free of detectable receptors.


Correlation between the rosette test with neuraminidase-treated sheep red blood cells and acid phosphatase activity in lymphocytes from patients with lymphoproliferative disease. In 14 adult patients suffering from lymphoproliferative diseases, the relation between numbers of lymphocytes determined by the rosette test (nSE) with neuraminidase-treated sheep red blood cells and numbers of lymphocytes giving a positive reaction for acid phosphatase was determined. Statistical analysis of multiple test results in the patients (n = 38) showed highly positive correlation between the two markers. A similar positive correlation in the course of cytostatic treatment was observed in selected patients with type T and B cell lymphoma. The results indicate that determination of acid phosphatase activity can serve as an additional marker of T lymphocytes in groups of patients with lymphoproliferative disease.


Effect of in vitro x-irradiation on human peripheral blood T and B lymphocytes. The effect of in vitro irradiation with increasing in logarythmic progress X-ray doses on lymphocyte viability and on T and B lymphocyte populations was studied in normal adults, patients with myasthenia gravis and in patients undergoing long-term steroid therapy. Decrease in numbers of lymphocytes carrying T or B lymphocyte surface markers was higher than viable cell loss. The decrease showed no linear correlation with X-ray doses applied, which might reflect the existence of radioresistant T and B lymphocytes. A higher so called early radiosensitivity of B lymphocytes was demonstrated. In patients with myasthenia gravis early radioresistance of T lymphocytes was detected. In patients undergoing long-term steroid therapy, an increase in numbers of cells lacking markers of any of lymphocyte populations was found in parallel with a decrease in T lymphocyte number which, in these patients, showed a higher radiosensitivity.


Coronary bypass surgery for unstable angina: a five-year follow-up. A total of 125 consecutive patients who were hospitalized for unstable angina underwent early coronary arteriography. One hundred of them were suitable for operation and were operated on promptly. There were no early deaths. The patients who had surgery have been followed up to 87 months (means, 57 months). Eighty-eight percent of the patients who had surgery returned to work. The actuarial five-year survival rate of those patients was 92%. At an average of five years, conditions of 62% of those who survived surgery were classified as functional class I, and 23% were class II. These data indicate that patients with unstable angina can safely undergo early arteriography and operation with late results that appear to be superior to the results of medical management of similar patients.


[Familial congenital dystrophy of the corneal stroma: Turpin's syndrome (author's transl)]. In 1939, R. Turpin and al. described cases of hereditary and congenital corneal opacities in three generations of one family. The members of this family have since been followed-up regularly by the author, examination of the corneas of the grandmother and the grand'daughter made by electron microscopy, the morphology compared, and an attempt made to establish the progression of the lesion. It so happened that at the same time, witschel and al. published (June, 1978) the results of their examination of the American members of the same family. Their conclusions were the same, in that this familial congenital dystrophy of the cornea is mainly stromal and differs therefore from familial congenital endothelial dystrophies. The author's analysis is complementary to theirs.


The ocular manifestations and functional effects of occupational argyrosis. Thirty employees of an industrial plant involved in the manufacture of silver nitrate and silver oxide underwent ophthalmologic evaluation in an effort to evaluate the frequency and extent of ocular argyrosis. The most frequently noted ocular abnormality was pigmentation of the conjunctiva, present in 20 workers; corneal pigmentation occurred in 15 workers. A direct relationship existed between the levels of pigmentation and duration of employment. Ocular pigmentation was seen more frequently than cutaneous pigmentation. Ten workers noted decreased night vision, but electrophysiologic and psychophysiologic studies of seven of these ten workers demonstrated no functional deficits.


Pars plana surgical approach for various anterior segment problems. Various anterior segment problems can be approached through the pars plana and treated with instrumentation that has been developed for vitreous surgery. Two cases of aphakic bullous keratopathy due to vitreous touch and three cases of subluxated lenses were successfully treated. Of two cases of advanced, persistent hyperplastic primary vitreous, one showed a successful result.


Clinical immunological study of T lymphocytes and EA rosette forming cells in tonsils. Tonsillar E and EA rosette forming lymphocyte subpopulations were studied in 120 tonsillectomized patients. T cell ratios was usually lower in the tonsils than in the blood. EA binding cells were studied with indicator systems of human or rabbit antibody sensitized red cells, respectively. Poorly sensitized human RBCs (EArabbit) bind much better to tonsillar cells than to blood lymphocytes and so this system proved to be specially suitable to study tonsillar EA binding cells. Increase in E and EA rabbit rosette forming cell frequencies were found with the age of patients. Decrease in percentage of T cells and EA rabbit rosette binding cells were found with high frequency of acut tonsillitis and with clinical sysmptoms of chronic local inflammation. The variation of these lymphocyte subpopulations with the local tonsillar inflammatory processes suggest a considerable clinical immunological role of local T cells and of this portion of Fc receptor postive lymphocytes.


[Electrically evoked, computer-averaged vestibular brain stem potentials in the cat (author's transl)]. In cats electric stimuli were applied to the wall of the outer auditory canal. Five hundred stimuli were averaged by computer technique. Thus two potentials with different latencies could be obtained. As these potentials disappeared after selectively resecting the vestibular nerve, it is assumed that these potentials were real vestibular brain stem potentials.


Nematospiroides dubius: susceptibility to infection and the development of resistance in hypothymic (nude) BALB/c mice. BALB/c-nu/nu mice and their intact nu/+ littermates are equally susceptible to infection with third-stage larvae of Nematospiroides dubius. Unlike their heterozygous littermates, however, the nu/nu mice are unable to form ganulomata in the intestinal wall and become only partially resistant to rechallenge. Following two or more infections, nu/nu mice maintain a high burden of adult intestinal worms, whereas worms are lost from immune nu/+ mice. Studies in T cell-injected nu/nu mice suggest that a full complement of T cells is needed to develop maximum resistance against the infective third-stage larvae and to expel adult worms. Measurement of serum immunoglobulin levels indicate that infected nu/+ mice have very high levels of IgG1 whereas the levels of IgG2a are reduced. In infected T cell-injected nu/nu mice, IgG1 levels increase with the number of T cells injected, whereas IgG2a levels are variable but always higher than in infected nu/+ mice.


The purification and characterization of bovine C4, the fourth component of complement. The fourth component of complement, C4, was isolated from bovine plasma in high yield, by using simple purification techniques. The protein, like human component C4, is a beta-globulin with a mol.wt. of about 200 000 and consists of three polypeptide chains, alpha, beta and gamma, with apparent mol. wts. of 98 000, 82 000 and 32 000 respectively. The chains of C4 have been separated by methods previously used for human C4. Their amino acid compositions are very similar to those of the human component, but differences in carbohydrate distribution have been observed. The haemolytic activity of bovine C4 is totally destroyed by incubation with bovine C1s, the activated subcomponent of the first component of complement. Component C4, treated in this way, was shown to be cleaved in the alpha chain, which was decreased in mol.wt. by about 9000, corresponding to the removal of subcomponent C4a.


The immunologic and clinical associations of the split products of C3 in plasma in juvenile rheumatoid arthritis. A qualitative counterimmunoelectrophoretic assay for the complement activation products C3c and C3d was used to study plasma from children with juvenile rheumatoid arthritis (JRA) and other rheumatic diseases. Positive tests for C3c,d were found in all patients with active systemic lupus erythematosus (SLE), 7 of 10 patients with active systemic JRA, 16 of 29 with active polyarticular JRA, 7 of 20 with active pauciarticular JRA, and in only 2 of 20 with inactive joint disease. The incidence of positive assays for C3c,d in JRA was increased in the presence of positive latex fixation tests, antinuclear antibody tests, or elevated values for antiglobulins as determined by affinity chromatography, but these associations were not statistically significant. Three joint fluids from children with pauciarticular JRA were negative for C3c,d. These studies show that the subgroups of JRA defined by clinical criteria are heterogeneous by current laboratory parameters and that evidence implicating antigen-antibody complexes in the pathogenesis of JRA is lacking in many patients.


Electronystagmographic study in rabbits on the vestibular effect of vincamine. Vincamine (Vincapront), the alcaloid isolated from Vinca minor L, was tested in rabbits at three dosages (1 mg/kg, 5 mg/kg, 10 mg/kg i.m.) in an electronystagmographic study. The parameters evaluated were: duration, rate and frequency of the post-rotatory nystagmus and the frequency of the per-rotatory nystagmus. While the post-rotatory nystagmus was found to show a reduction in duration and rate, the frequencies did not respond to vincamine. The 1 mg/kg dose had the strongest effect while that of the 10 mg/kg dose was weakest. As these findings may not be explained by sedative or habituation effects we consider the reduction of the post-rotatory nystagmus as an analogue in animal experiments of the vestibular effect seen in man. The electronystagmographic pattern of action corresponds to that of some other antivertiginous drugs.


Immune status in atopic eczema: a survey. We have searched the literature for data on the in vitro assessment of immune status in atopic eczema patients, and have found much confusion. The major findings are tabulated. It is concluded that atopic eczema is a form of immune deficiency, although it is unclear whether this is a primary or secondary defect. Most authors find a T-lymphocyte deficit while eosinophils, B lymphocytes and serum IgE are increased. Serum IgE levels appear to correlated with severity of eczema symptoms. We have previously suggested that T-lymphocyte levels are overestimated in eczema when fetal calf serum is used in the E-rosette assay. Analysis of the literature for the effect of this serum in the assay confirms that there is a T-lymphocyte deficit in atopic eczema, but that the serum masks it. Thus, much of the confusion surrounding this issue can be resolved.


Thymosin-inducible 'null' cells in atopic eczema. Thirty children with atopic eczema were compared with an equal number of age-matched healthy children. The mean peripheral blood T-lymphocyte level was lower in the eczema group (mean 1,197/mm2 as against 1,702/mm3; P = 0 . 003). This difference was abolished in vitro by thymosin, a thymic hormone extract. Positive correlations were found between eczema severity and: eosinophilia; hyperimmunoglobulinaemia E; but not T lymphopaenia. Thymosin-inducible T-cell (Ti) counts correlated with plasma IgE levels, suggesting that these Ti cells may be immature suppressor T cells. If this T-cell deficiency represents inadequate suppression of IgE responses, then a trial of treatment with thymosin appears to be warranted.


Transport of local anaesthetics across chromatophore membranes. 1. Both simple amines and tertiary amino local anaesthetics give rise to an accelerated decay of the absorption change of added pH indicator dyes and a decelerated decay of the endogenous carotenoid absorption band shift, following short flash excitation of Rhodopseudomonas sphaeroides chromatophores. 2. With increasing medium pH, lower concentrations of amine or local anaesthetics are effective. 3. The order of potency of the local anaesthetics concurs with their reported membrane/buffer partition coefficients and concentrations required for action potential blockade in nerve fibres. 4. The data are taken as evidence for rapid transport of the free base across the chromatophore membrane and relatively slow penetration of the protonated local anaesthetic. Protolytic reactions complete the effective dissipation of the trans-membrane pH gradient. 5. Benzocaine, with its unusually low pKa and the quaternary derivative, chloropromazine methiodide do not display this type of behaviour. 6. In the presence of membrane potential-collapsing agents, such as valinomycin/K+ or thiocyanate ions, local anaesthetics decelerate the decay of the cresol red change but have no effect on the carotenoid shift decay. It appears that transport of the unprotonated local anaesthetic although electrically neutral, requires the presence of a membrane potential. 7. In contrast, the non-anaesthetic amines act independently of the membrane potential. 8. Ca2+ interferes with the mechanism of local anaesthetic deceleration of the cresol red change decay in the presence of valinomycin/K+ or thiocyanate but not with other anaesthetic or amine reactions.


Orientation and linear dichroism of the reaction centers from Rhodopseudomonas sphaeroides R-26. Linear dicroism of chromatophores and isolated reaction centers from the photosynthetic bacterium Rhodopseudomonas sphaeroides strain R-26 was studied using a novel technique of orientation. The results are discussed in view of the reaction center structure and its position in the membrane. The advantages of the new orientation technique are also outlined.


Linear dichroism of light harvesting bacteriochlorophyll proteins from Rhodopseudomonas sphaeroides in stretched polyvinyl alcohol films. Light-harvesting bacteriochlorophyll-protein complexes from Rhodopseudomonas sphaeroides 2.4.1 and R-26 mutant are solubilized in sodium dodecyl sulfate and imbedded in polyvinyl alcohol. Stretching induces orientation, and the linear dichroism of visible and near infrared absorption is analyzed. Based on a simple model, angles between the particle axis and the transition dipole moments are found. In the near infrared absorption band of the R-26 light-harvesting protein the dichroic ratio varies from 1.30 to 1.57. Using the absorption curves the band is resolved into two exciton components. In the visible absorption band the dichroic ratio has a constant value of 0.43 for the R-26 protein but varies with wavelength for the wild type light-harvesting protein. This variation is attributed to an additional bacteriochlorophyll not present in the R-26 protein.


The orientations of reaction center transition moments in the chromatophore membrane of Rhodopseudomonas sphareroides, bases on new linear dichroism and photoselection measurements. Chromatophore membranes from Rhodopseudomonas sphaeroides were oriented by drying suspensions on the surfaces of glass slides, Polarized spectra of light-induced absorption changes were obtained between 500 and 1000 nm. As observed earlier, these spectra showed negative bands, reflecting photooxidation of the bacteriochlorophyll 'special pair' in the reaction centers, centered near 870, 810, 630 and 600 nm. These bands have been designated BY1, BY2, BX1 and BX2, respectively, corresponding to two QY transitions and two QX transitions of the dimeric special pair. We found the BY1 and BX1 transition moments to be parallel (within 20 degrees) to the plane of the membrane, whereas the BX2 moment makes an angle of 55--63 degrees with the plane. Using the photoselection technique we found that the angle between the BY1 and BX1 transition moments is 30 degrees, while that between BY1 and BX2 is 75 degrees. The BX1 and BX2 moments were found to be orthogonal, consistent with the prediction of molecular exciton theory for a dimer. By combining these data, we have calculated the orientations of the transition moments of the bacteriochlorophyll dimer in spherical polar coordinates, with the pole of the coordinate system normal to the plane of the membrane. The orientations of the QY and QX transition moments of the two bacteriopheophytin molecules in the reaction center were also computed in this coordinate system by transforming the data reported by Clayton, C.N., Rafferty, R.K. and Vermeglio, A. ((1979) Biochim. Biophys. Acta 545, 58--68). We have derived the transformation equations for two polar coordinate systems: in one, the pole is an axis of symmetry as defined by the orientations of purified reaction centers in stretched gelatin films (Rafferty, C.N. and Clayton, R.K. (1979) Biochim. Biophys. Acta 545, 106--121). In the other, the pole is normal to the plane of the chromatophore membrane. These two polar axes are approximately orthogonal.


Magnetic field-induced increase of the yield of (bacterio)chlorophyll emission of some photosynthetic bacteria and of Chlorella vulgaris. In photosynthetic bacteria, in which the iron-ubiquinone complex X is prereduced, a magnetic field induces an increase of the emmission yield, which is correlated with the decrease in reaction center triplet yield reported previously (Hoff, A.J., Rademaker, H., van Grondelle, R. and Duysens, L.N.M. (1977) Biochim. Biophys. Acta 460, 547--554). Our results support the hypothesis that under these conditions charge recombination of the oxidized primary donor and the reduced primary acceptor predominantly generates the excited singlet state of the reaction center bacteriochlorophyll. In Chlorella vulgaris and spinach chloroplasts, at 120 K, the magnetic field has an effect similar to that found in bacteria, which suggests that an intermediary electron acceptor between P-680 and Q is present in Photosystem II also.


Bacteriocholorophyll a cation radical in solution and in reaction centers of Rhodopseudomonas sphaeroides. Resonance Raman scattering. Resonance Raman spectra of the pi-cation of bacterio-chlorophyll a in solution at 30 K are reported and discussed. Outer (formula: see text) bonds of the pyrroles and the methine bridges are weakened by the ionization, while (formula: see text) and Mg-N bonds remain essentially unaffected. Resonance Raman spectra of reaction centers suggest that the positive charge on P-870+ should be localized on a single bacteriochlorophyll molecule by the lifetime of the scattering process (approximately 10(-13)s).


Inhibition of potassium conductance by barium in frog skin epithelium. The effect of Ba2+ (0.5 mM, corial side) upon the transport characteristics of the frog skin epithelium was investigated. It was observed that Ba2+ decreased the conductance of the preferably K+-permeable basolateral border to less than 30% of its control value. Furthermore, Ba2+ abolished the K+ electrode-like behaviour, existing at the basolateral membrane under conditions of zero transcellular current flow, for [K+] below 10--15 mM. Effects upon other parameters of transepithelial transport (electromotive forces and resistance of outer or basolateral border and shunt pathway, respectively) were small and might represent secondary events. It is concluded that Ba2+ inhibits passive fluxes of K+ across basolateral membranes of tight, Na+ transporting epithelia, similar to its influence upon membranes of nonpolar cells.


A dynamic x-ray diffraction study of anesthesia  action. Thickening of the myelin membrane by n-pentane. The structural changes induced in the myelin sheath by n-pentane nerve impulse blockage were studied by small-angle X-ray diffraction using a linear position-sensitive detector. The results show that the thickness of the myelin period lattice increases from 170 to 180 A during n-pentane treatment.


Ultraviolet-induced DNA excision repair in human B and T lymphocytes. II. Effect of inhibitors and DNA precursors. Despite their great sensitivity to ultraviolet light purified human B and T lymphocytes are capable of complete repair provided that the ultraviolet dose does not exceed 0.5 Jm-2. Their capacity to repair, as measured by the restoration of DNA supercoiling in preparations of nucleoids, and their survival are significantly increased in the presence of deoxyribonucleosides. Certain agents which inhibit semi-conservative DNA synthesis (hydroxyurea, 1-beta-D-arabinofuranosylcytosine (arafCyt) either stop or delay the repair process in lymphocytes. The effect of hydroxyurea is eventually overcome spontaneously, but changes in the sedimentation behaviour of ultraviolet-irradiated nucleoids caused by arafCyt can only be neutralized by addition of deoxycytidine. The effective inhibition of repair by arafCyt permits the detection of extremely small amounts of ultraviolet damage and also the estimation of when repair is complete.


Nuclear ribonucleoprotein complexes of amphibian liver. I. Characterization of the complex and its small molecular weight RNA moiety. Nuclear RNA-protein complexes containing small molecular weight RNAs were isolated from hepatic nuclei of Rana catesbeiana tadpoles and frogs according to a procedure normally used for the isolation of heterogeneous nuclear ribonucleoprotein complexes from other eukaryotic tissues. Preliminary characterization of the tadpole nuclear RNP indicated a particle size of 50--70 S in sucrose density gradients and a buoyant density of 1.40 gm/ml in CsCl gradients. When analyzed on SDS-polyacrylamide gels, this complex was observed to contain at least 40 polypeptides ranging in molecular weight from 15,000 to 200,000. Nuclear RNA-protein complexes were also isolated from adult frog hepatic nuclei by the same protocol and the RNA moiety which had been purified from the frog complex was compared with the nuclear RNA isolated from the tadpole particles. Electrophoretic analysis of the nuclear RNA-protein-associated RNA revealed minor qualitative and quantitive differences in the more than 25 discrete bands (4--9 S) associated with each particle. Base analysis of tadpole and frog nuclear RNA revealed a nucleotide composition of approximately 50% adenosine plus uridine nucleotides, with an unusually high content of cytosine residues (approximately 30%). Comparison of the two RNA samples demonstrated a large increase in the adenosine content of frog unclear RNA, and the presence of a minor base in frog nuclear RNA which was absent in the tadpole sample. These results indicated that changes in the RNA content of the amphibian nuclear RNP complex had occurred during bullfrog development.


Nuclear ribonucleoprotein complexes of amphibian liver. II. Changes in the protein moiety during development. Ribonucleoprotein complexes composed of small molecular weight nuclear RNA (4--9 S) and proteins were isolated from hepatic nuclei of Rana catesbeiana (bullfrog) and the protein moiety of this nuclear ribonucleoprotein complex compared during different stages of development. SDS-polyacrylamide gel analysis of premetamorphic tadpoles and adult frog nuclear ribonucleoprotein complexes revealed that while the protein profiles of these two particles were very similar polypeptides of 47,000, 70,000, and 11,000 molecular weight were present in significantly higher concentrations in the frog ribonucleoprotein complexes. Comparison of the chromatin proteins isolated from these two developmental stages demonstrated that these three polypeptides of frog ribonucleoprotein were not contaminants from chromatin. Since these three polypeptides could not be preferentially extracted from the frog ribonucleoprotein complex by 0.5 M KCl or 1 M urea, it was unlikely that these polypeptides were bound nonspecifically to the ribonucleoprotein particle. Polypeptide analysis of the nuclear ribonucleoprotein complexes isolated from tadpoles immersed in the thyroid hormone L-thyroxine revealed an increase in two polypeptides of 37,000 and 45,000 molecular weight during metamorphosis. The absence of reduced amount of these two polypeptides in either the premetamorphic tadpole or adult frog demonstrated that their presence in Rana catesbeiana nuclear ribonucleoprotein was transient during development and specifically associated with tadpole metamorphosis. We conclude from these experiments that the nuclear ribonucleoprotein complex is a dynamic structure during Rana catesbeiana development and that specific changes in its protein composition are associated with discrete stages of amphibian development.


Genetics of classic von Willebrand's disease. II. Optimal assignment of the heterozygous genotype (diagnosis) by discriminant analysis. In classic von Willebrand's disease (vWd), assignment of the heterozygous genotype for genetic studies and diagnosis for clinical purposes (which are not exactly the same) are formidable problems. We have pointed out in the first report in this series that almost 50% of the members of two large kindred who transmitted this disease, and were therefore heterozygous, were scored as normal by the usual tests of hemostasis. This report describes how this large proportion can be significantly reduced by application of discriminant analysis. Using linear discriminants in three variables--coagulation factor VIII (VIII:C), factor-VII-related antigen (VIIIR:Ag), and the ristocetin cofactor related to factor VIII (VIIIR:WF)--we were able to classify as heterozygous more than 80% of the transmitters in the two large kindred. It was of particular interest that the four parents of two related vWd homozygotes could be scored as heterozygous by discriminant analysis even though all their laboratory tests were within the normal ranges.


Separation of blast cell and T-lymphocyte progenitors in the blood of patients with acute myeloblastic leukemia. The peripheral blood of acute myeloblastic leukemia (AML) patients often contains large numbers of two distinct cell populations, both capable of forming colonies in culture under similar conditions. The first population consists of the precursors of blast cells and has specificity for AML; the second population consists of T-lymphocyte precursors, also found in normal blood. The two progenitor populations can be separated by exploiting the capacity of T-lymphocyte (but not blasts) progenitors to form rosettes with sheep erythrocytes (E rosettes). After E-rosette formation, T-lymphocyte precursors can be removed by centrifugation on Ficoll-Hypaque. Such separation has a number of consequences: (1) Blast progenitors can be detected where unseparated mononuclear preparations have yielded either no colonies or only T-lymphocyte colonies (20 of 21 patients). (2) The stimulator requirements of the blast progenitors change, indicating that cell-cell interactions may take place between blast and T-lymphocyte progenitors. (3) It is feasible to characterize blast and T-lymphocyte precursors independently, even though they may coexist in peripheral blood. This may be important if progenitor properties are attributes contributing to the variance in outcome in AML.


Three types of bone-marrow eosinophils of the frog Rana temporaria (an electron-cytochemical study). An electron-cytochemical study of the peroxidase activity in bone-marrow eosinophils of the frog Rana temporaria revealed, in addition to peroxidase-positive granules and larger peroxidase-negative granules, many small peroxidase-negative granules.


Capping and freeze-fracture analysis of Sézary cells. The functional integrity of blood and skin Sézary cells was examined in regard to motility, capping proficiency, and intramembranous particle (IMP) mobility. In contrast with chronic lymphocytic leukemia lymphocytes, which are relatively inert in these respects, variable proportions of Sézary cells are motile and are able to cap and cluster their IMP's. Since these functions may reflect a cell's propensity for diapedesis, these observations may help to explain the inverse relationship between the size of the skin infiltrate and the number of circulating Sézary cells often observed in this condition.


Characterization of lymphoblast Fc receptor expression in acute lymphoblastic leukemia. Lymphoblasts from 18 patients with untreated acute lymphoblastic leukemia were investigated for the presence of conventional cell surface markers (spontaneous sheep red blood cell rosette formation, complement receptors, and surface immunoglobulin). The expression of Fc receptors for both IgG and IgM was investigated using indicator bovine erythrocytes coated with rabbit anti-BRBC (IgG and LgM fractions). The leukemic cells of all patients in this tudy expressed Fc receptors for both IgC and LgM. In contrast with previous reports, null (non-T non-B) lymphoblasts as well as T lymphoblasts demonstrated Fc-IgG and Fc-IgM receptors. However, these two immunologic subclasses of leukemic cells demonstrated significantly different patterns of Fc receptor distribution. These data suggest that expression of Fc receptors is an early event in cellular differentiation in this lymphoid malignancy.


Angiodysplasia as a cause of colonic bleeding in the elderly. Angiodysplasia is being recognized as a major causal factor of colonic haemorrhage in the elderly. Superior mesenteric arteriography in an 86-year-old lady with recurrent haemorrhage revealed the lesion. Confirmation of the diagnosis was made possible by the injection of contrast material into the blood vessels of the removed intestine and subsequent histological examination.


Asthma in the elderly: an epidemiological survey. A random sample of one in eight people aged 70 and over living at home in a south Wales town was surveyed to establish the prevalence of asthma. Subjects attended a screening clinic, where spirometry before and after an inhalation of salbutamol, skin prick testing, blood count, and sputum examination were carried out and a questionnaire answered. Those in whom asthma seemed at all likely were subsequently examined in detail in a chest clinic. Out of 485 subjects eligible, 418 (86.2%) were screened. Twelve (2.9%) had current asthma, of whom three had not previously been diagnosed as asthmatic and four were being treated but were unaware of the diagnosis. A further 15 (3.6%) had mild asthma or a history of the disease, giving a total prevalence of any history of asthma of 6.5%. Only one of the subjects who did not attend the screening clinic was known to have asthma, suggesting that the overall prevalence did not differ greatly from this figure. It was found that the disease might start or remit at any age. Thus in the elderly current asthma is more prevalent in men than women (5.1% compared to 1.8%) and in terms of spirometry is more severe. Two underlying disease processes may perhaps exist that fulfil criteria for asthma in the elderly, one causing sputum eosinophilia and the other a form of chronic bronchitis with reversible airways obstruction.


Simultaneous rate-independent and rate-dependent assessment of intracranial self-stimulation: evidence for the direct involvement of dopamine in brain reinforcement mechanisms. A two-level intracranial self-stimulation (ICSS) paradigm was developed in which both rate-independent and dependent measures of ICSS could be obtained simultaneously. Responses at the first lever resulted in stimulation which decreased in magnitude after every fifth response, while responses at the second lever reset the current available. The current at which the reset responses occurred was defined as the 'reward threshold'. In addition, the rate of responding was determined at each current for which the animals responded during this stimulate-reset sequence. Decreased reward following treatment with the neuroleptic pimozide, a specific blocker of dopamine receptors, was demonstrated by an elevated 'reward threshold'. The same effect could be obtained in control animals by making each stimulation less rewarding, i.e., by decreasing the amount of charge per stimulation. Pimozide increased 'reward threshold' without a generalized disruption of response rates. While rates were decreased at low currents they were unchanged at high currents. 'Reward threshold' was decreased following D-amphetamine treatment, and was accompanied by a dose-related decrease in response rates at high to medium current intensities. These data suggest that neuroleptic attenuation of ICSS is due to diminished reward and not to motor deficits. Further, due to the specificity of pimozide, they suggest a direct role for dopamine in the mediation of reward.


Changes in platelet function and gastrointestinal bleeding following repeated administration of acetylsalicylic acid in the rat and the dog. Two dogs were prepared with Pavlov pouches of the fundic area of the stomach using standard techniques. During treatment periods of 14 days, 200 mg acetylsalicylic acid (ASA) was introduced into the pouch twice daily by insufflation. One hour after each drug administration the pouch was washed with saline and the fluid assayed for blood. Bleeding from the pouch increased to a maximum on the 3rd or 4th day of the treatment period and subsequently declined such that by the 8th day blood loss was minimal and approximated that found during control periods. Platelet aggregation (in vitro) responses to adenosine diphosphate were significantly (p less than 0.01) inhibited on day 3 when aggregation curve heights were reduced by 66.2 +/- 13.11% (mean +/- SEM) from control values. On day 7 and during the ensuing 7-day period when ASA was given twice daily, the heights of aggregation responses were reduced by only 20-30% from controls. These responses were significantly (p less than 0.001) greater than those found on day 3. Similar changes in platelet reactivity were found in plasma from rats given ASA twice daily for 7 days. Aggregation responses to collagen were depressed by 95.5 +/- 4.49% on day 1 following two doses of ASA. As the treatment period continued, the aggregation responses increased in magnitude until the 7th day they were similar in height to those from control animals. The mechanism involved in this adaptation to ASA treatment seen with these platelets is not known.


Is left ventricular decompression necessary during coronary arter surgery? The use of the "no-vent technique" was studied prospectively in 91 consecutive patients undergoing coronary artery surgery. Analysis of the results indicates that left ventricular distension will not occur if cardioplegic arrest is effected, if the venous line is positioned in the right atrium and if left-sided pressures are monitored. The no-vent technique has shortened the operating time, simplified the pump layout and eliminated the hazards associated with venting.


Fate of the graft and native vessel following endarterectomy of the left anterior descending coronary artery. In 16 patients who underwent endarterectomy of the left anterior descending (LAD) coronary artery combined with saphenous vein bypass grafting between Aug. 1, 1976 and July 31, 1978, the results of preoperative and postoperative angiography were comparable. Most patients had obstruction or severe stenosis of the proximal LAD coronary artery together with a poor runoff as demonstrated angiographically. Eighteen vein grafts were placed in the LAD artery and 15 (83%) were satisfactorily patent. Six of 18 grafted arterial segments became occluded distal to the site of graft insertion, but in most cases there was sufficient proximal runoff to maintain graft patency. In this study intraoperative measurements of graft flow were predictive of graft or distal vessel patency, or both. Careful postoperative assessment of the results of this technique seems warranted.


Aortocoronary bypass for critical stenosis of the left main coronary artery. Over a 2-year period 33 patients with symptomatic stenosis (greater than 75%) of the left main coronary artery underwent aortocoronary bypass. Intra-aortic balloon counterpulsation was used preoperatively in only two patients as a therapeutic measure for medically unstable angina. There were no operative deaths. Follow-up study 3 to 27 months (mean 13.3 months) after operation revealed one death. Twenty-two patients were free of pain. The authors conclude that aortocoronary bypass surgery for severe stenosis of the left main coronary artery can be safely accomplished, without prophylactic use of intra-aortic balloon counterpulsation in the majority of cases, with an acceptable operative mortality and morbidity.


High dose methotrexate followed by citrovorum factor reversal in patients with advanced cancer. High dose methotrexate followed by citrovorum factor reversal has been utilized in twenty-six patients with advanced cancer. Four of 10 patients with head and neck cancer had an objective response. One of 7 patients with metastatic osteosarcoma to the lungs had stabilization with twenty treatments over 23 months. One patient with acute lymphocytic leukemia developed marrow aplasia but did not attain remission. The regimen was well tolerated when meticulous attention was paid to hydration, urine alkalinization, renal function and third space fluid accumulation. Life-threatening or lethal toxicity was encountered when these phenomena were not scrupulously observed.


Immunological activity of regional lymph nodes in tumor-bearing mice. Regional (popliteal) lymph node cells (RLNC) from A/Jax mice, inoculated in each hind foot with isogeneic Sarcoma 1 tumor cells, demonstrated cytotoxicity in vitro at Day 14 of tumor growth but lost this ability by Day 21. These noncytotoxic RLNC were capable of suppressing activity of other cytotoxic lymphoid cells, but after incubation for 24 hr in vitro their cytotoxicity was restored and their suppressive activity was abrogated. RLNC responsible for cytotoxicity were removed by treatment with anti-theta serum plus complement. The suppressive effect of RLNC was found to be mediated by a soluble "blocking" factor which was released into the culture medium after 24 hr incubation. The factor was not detected in culture media from RLNC pretreated with anti-theta serum plus complement prior to incubation. Absorption of RLNC culture supernatants with tumor-bearer spleen cells, but not with normal spleen cells, completely removed the blocking factor, while absorption by Sarcoma 1 cells significantly reduced blocking activity. The factor was trypsin sensitive, was retained on an Amicon XM100 filter, and did not demonstrate the presence of antibody to Sarcoma 1 in a radioimmunoassay. Although the exact nature of the factor has not been established, it appears to be a receptor antigen complex from T-cells of tumor-bearing animals.


High-dose methotrexate with leucovorin rescue in ovarian cancer: a phase II study. Methotrexate (MTX) (1--7.6 g/m2) with leucovorin rescue was given to 19 women with stage III-IV ovarian carcinoma after induction of remission with surgical treatment and chemotherapy or after relapse. Adequate hydration with alkalinization prevented nephrotoxicity and no cumulative myelosuppression was observed. Serum MTX levels in nontoxic patients averaged 1 X 10(-6) M 24 hours following a 30-minute iv infusion of MTX at 3 g/m2. Among nontoxic women there was a 50-fold difference in the MTX level which correlated with the mean serum creatinine level. Response was assessed after 6--12 weeks of treatment by laparoscopy in patients with nonpalpable intra-abdominal tumor implants or by physical examination in patients with palpable masses. Despite the high levels of MTX achieved with the weekly schedule, only one partial response occurred among eight patients with visible or palpable metastatic lesions. Progressive disease was observed after 6--12 weeks of treatment in four of eleven women who began to receive MTX without evidence of disease or with lesions of less than 1.5 cm in diameter. MTX at the dose and schedule used in the present study appears to be of no benefit in the treatment of advanced ovarian cancer.


Blood and lymph node T lymphocytes in cutaneous T cell lymphoma: evaluation by light microscopy. Cytology of peripheral blood and lymph node lymphocytes from a group of unselected patients with cutaneous T cell lymphoma (CTCL) was studied by light microscopy. Twenty of 45 patients had circulating lymphocytes with convoluted nuclei recognized in routine Wright-Giemsa-stained peripheral blood smears. Cytocentrifuge preparations of E-rosetted lymphocytes showed that greater than 10% of the T cells had convoluted nuclei in each of 16 patients with positive blood smears and in six of 17 whose blood smears were negative or inconclusive. Peripheral blood involvement with greater than 10% convoluted T cells was most frequent in patients with erythroderma (100%) including those with normal of decreased lymphocyte counts, and was not uncommon in patients with mycosis fungoides in the plaque or tumor phase (42%). The light-microscopic morphology of the abnormal cells found in the patients with the plaque or tumor phase of mycosis fungoides was not distinguishable from that of the erythrodermic patients. Increased percentages (less than 15%) of T cells having convoluted nuclei were also found in the lymph node cell suspensions from CTCL patients with adenopathy (18 of 25 patients). These results suggest that a high frequency of extracutaneous involvement occurs in patient with CTCL, the clinical significance of which remains to be determined.


Cytogenetic abnormalities in patients with cutaneous T-cell lymphomas. Cytogenetic studies were conducted in 36 patients with histologically confirmed cutaneous T-cell lymphomas at the National Cancer Institute-Veterans' Administration Medical Oncology Branch. Aneuploidy was observed in 17 (85%) of the 20 lymph nodes, 23 of the 36 peripheral bloods, and five of the 31 bone marros. Aneuploidy was frequently present even when tumor cells were not noted histologically. These findings indicate that cytogenetic studies can be very useful for the early detection of malignant cells even when only a few such neoplastic cells are encountered. In this study, the cytogenetic abnormalities found to be characteristic of the disease included extensive aneuploidy, with both numerical and structural aberrations, a wide range of heteroploidy, and a lack of clone formation until the terminal phase of the disease. The numerical changes most frequently involved chromosomes 8, 15, 11, 17, 21, and 10, and the chromosome most involved in structural aberrations was chromosome 1, followed by chromosomes 7, 14, 16, 6, and 9. Cytogenetic studies demonstrate that neoplasia in the cutaneous T-cell lymphomas commonly involves areas beyond the skin.


Current concepts in immunoregulatory T-cell neoplasms. Normal T cells play a crucial role in the regulation of humoral immune responses by acting as potentiators (helper cells) or inhibitors (suppressor cells) of the B-cell transition into immunoglobulin-secreting plasma cells. Certain patients with leukemias or lymphomas of T-cell origin may provide a resource for obtaining homogeneous populations of cells which act as either helper cells (eg, some but not all patients with Sézary's syndrome) or suppressor cells (eg, some patients with acute of subacute T-cell leukemia). The clinical and theoretic implications of such immunoregulatory cell neoplasms are discussed.


Murine T-cell heterogeneity.

Murine T-cell heterogeneity. Immunoregulatory lymphoid cells that mature under the influence of the thymus gland (T cells) have been implicated to a major extent in the induction or at least the perpetuation of malignant neoplasms in man. Those T cells are thought to inactivate, suppress, or neutralize the normally occurring tumoricidal effector cells and thereby facilitate the unchecked growth of the neoplasm; the term "suppressor T cells" is therefore used to denote their individual activity. This concept implies that there is a balance between the effector cells and the suppressor cells in healthy subjects and that perhaps enrichment and activation of those cells involved in the defense against neoplastic growth, and specific depletion and elimination of those cells involved in suppression or inactivation of the former in patients with malignant diseases, may provide new modalities in cancer immunotherapy. Most of the studies that form the basis of this concept have been derived in animal models, particularly the mouse. The existence of cell-surface markers which have been used as phenotypic tools has provided the knowledge that distinct subpopulations of lymphoid cells do exist. The phenotypic characterization of lymphoid cells involved in functionally dinstinct immunologic events has been the object of intensive investigation. Therefore, the purpose of this paper is to briefly document our current knowledge of the functional heterogeneity that exists in murine T cells based on the differential expression of these cell-surface markers.


Antithymocyte globulin in the management of cutaneous T cell lymphoma. Four patients with cutaneous T cell lymphoma were treated with iv administered horse antithymocyte globulin. Evidence of a beneficial response was obtained in three of the four patients. Limited sensitivity of neoplastic T cells to complement-mediated lysis in the presence of the antithymocyte globulin was identified, suggesting that other mechanisms may be responsible for the observed clinical responses.


Long-term serial angiographic studies after coronary artery bypass surgery. Twenty-six patients underwent repeat coronary angiography 5--8 years after saphenous vein coronary artery bypass surgery (SVCABG). These patients were selected from the first cohort of 117 patient who had SVCABG because they had obtained essentially complete relief of angina, and because all grafts were patent at initial angiography 11.2 months (mean) after surgery. Of the 39 grafts (1.5 grafts per patient) patent at 1 year, 34 (87.2%) were patent at reexamination 76 months (mean) (range 65--103 months) after SVCABG. Graft occlusion could not be predicted by the early angiographic appearance of the graft itself or its proximal or distal anastomosis. In some cases, narrowing or irregularity consistent with intimal hyperplasia appeared to progress, while in others it developed at late follow-up. Progressive narrowing occurred in 96% (22 of 23 grafted vessels) of the native coronary arteries proximal to the graft anastomosis. Progresssion to a stenosis greater than 75% or total occlusion was seen distal to the graft anastomosis in eight of 39 grafts (20%). Of 103 non-bypassed major vessels, 56% showed some progression of disease and half of these progressed to significant stenoses (greater than 75% luminal narrowing). There were no apparent predictors to indicate whether progression in nongrafted coronary arteries would occur preferentially in a previously stenotic or nonstenotic vessel, although 80% of vessels with initial stenoses greater than 75% progressed to total occlusion.


Plasma lipid distributions in selected North American populations: the Lipid Research Clinics Program Prevalence Study. The Lipid Research Clinics Program Epidemiology Committee. Cross-sectional age- and sex-specific plasma lipid distributions (means, medians and selected percentiles) are given for 48,431 white participants in visit 1 of the Lipid Research Clinics (LRC) Prevalence Study. This study consisted of two visits in which 10 LRCs screened participants selected from well-defined North American target populations that included a broad range of sociodemographic subgroups. These data confirm findings from earlier studies in developed countries, showing age-related differences in plasma lipid levels. However, for overall distributions, the LRC data showed slightly lower cholesterol and markedly higher triglyceride values than those previously reported for North America. Some variation in plasma lipid values was evident among the clinic populations. The large number of participants within most subgroups permitted a variety of analytic and comparative studies. For example, data from the large pediatric population revealed a drop in plasma cholesterol levels in adolescent males and females. Males aged 20--50 years had higher cholesterol levels than females in the same age group, and higher triglyceride levels between ages 20--70 years. Numbers were also sufficient for meaningful comparisons between lipid distributions of females who were taking sex hormones and those who were not: In females taking sex hormones, cholesterol and triglyceride levels were higher for subjects younger than 45 years, but slightly lower after age 45, than lipid levels in females not taking hormones.


Loss of the improvement of angina between 1 and 7 years after aortocoronary bypass surgery: correlations with changes in vein grafts and in coronary arteries. Improvement of effort angina following pure aortocoronary bypass graft surgery was related to postoperative control angiographic studies of grafts and coronary arteries in 75 unselected patients. Clinical and angiographic evaluations were carried out at approximately 1 year and at 5 to 7 years after surgery. At 1 year, 61 (81.3%) were improved (52 without angina and 9 with partial improvement by at least two functional classes), whereas 14 were unimproved (18.7%). At approximately 6 years, loss of improvement (reappearance of angina or aggravation by at least two functional classes) was observed in 22 of the 61 improved patients, representing an attrition of 36.1% over a 5-year period. Graft occlusion or a narrowing of over 50% was observed in two of the 39 patients in whom improvement had continued (5.1%), whereas it was found in six of the 22 patients (27.3%) whose results deteriorated (p less than 0.05). Similarly, progression to occlusion of a preexisting stenosis of over 50% or appearance of a new stenosis of over 50% in a major coronary artery (distal to a graft or in an unbypassed artery) was observed in five of the 39 patients with continued improvement (12.8%) and in 11 of the 22 patients whose condition deteriorated (p less than 0.01). Changes in a graft or in a coronary artery were noted in 63.6% (14/22) of the patients with loss of improvement as compared to only 18% (7/39) of the patients whose improvement did not deteriorate. Improvement of angina was also evaluated in all survivors among our first 500 cases who had preoperative effort angina and pure bypass surgery with or without angiographic studies. Of these 260 patients, 70.4% were angina-free or improved by two to three functional classes at 1 year, and only 41.9% at 7 years after surgery. It is concluded that the effect of aortocoronary bypass graft surgery is transient in a high proportion of patients and that deterioration of results is related to late graft modifications and progression of atherosclerosis, particularly in ungrafted coronary arteries.


Temporary left ventricular bypass: factors affecting patient survival. Circulatory support (range, 2 hours-8 days) was undertaken in eight cardiac surgical patients (with two survivors) exhibiting intractable cardiogenic shock. A paracorporeal, pneumatic, xenograft-valve pump was interposed between the left ventricular apex and ascending aorta. Pumping lowered left atrial and ventricular pressure while maintaining cardiac output (1.8--2.6 l/min/m2). Following implantation, plasma hemoglobin and erythrocyte mechanical fragility values were elevated but decreased to normal when renal function was not impaired. Mild thrombocytopenia was noted in three patients and was severe in five others with persistent hemorrhage. Anticoagulation agents were used during tapering of pump flow (three patients) after 100, 105 and 120 hours of bypass. Otherwise, for the major portion of the interval of mechanical circulatory support, anticoagulants were not administered. Despite this fact, no systemic embolization was detected in any of the patients. It appears that assist pump support can be life-saving in acute left ventricular failure in patients following cardiac surgery.


Mild ventricular dysfunction following cold potassium cardioplegia. The long-term effects of cold potassium cardioplegic arrest was examined in 40 patients who underwent myocardial revascularization. Comparisons between resting ejection fraction (EF), end diastolic volume (EDV), and segmental wall motion were made between the preoperative and postoperative catheterization (mean postoperative recatheterization, 6 months). A 2.93 graft per patient ratio was found in this group of patients, with 108/117 grafts visualized at the time of recatheterization. The EF was 60% +/- 3% before surgery and 62% +/- 3% after surgery. A correlation coefficient of 0.91 was determined for the entire series. The EDV was 151 +/- 16 cc before coronary artery bypass graft (CABG) and was unchanged post CABG at an end diastolic volume of 137 +/- 15 cc. Analysis of preoperative wall motion of 33 patients demonstrated 111 depressed segments, 68 normal, and 52 hypercontractile; at recathetrization, there were 100 depressed, 66 normal, and 65 hypercontractile segments. Although there was essentially no deterioration of myocardial function for 37 out of 40 patients, three demonstrated a reduction in EF, the largest reduction being 15%. These three patients had a cardioplegic arrest time greater than 70 minutes. An inverse relationship between percent change in EF and the length of cardioplegic arrest was observed, with an r value o - 0.57 (p less than 0.01). These data suggest that prolonged cardioplegic arrest times may be associated with mild dysfunction. Cold potassium cardioplegic arrest up to 70 minutes was associated with no change in EF, EDV, or wall motion in this series of patients.


Rate-pressure product and myocardial oxygen consumption during surgery for coronary artery bypass. Rate-pressure product (RPP) is a sensitive index of myocardial oxygen consumption (mVO2) in awake people. We wished to determine whether this relationship persisted under anesthesia and in the face of concurrent large changes in myocardial contractility and left ventricular filling pressures. In 16 patients scheduled for coronary artery bypass surgery, we inserted coronary sinus and Swan-Ganz catheters, and a central aortic catheter via the brachial artery, before induction of anesthesia with either morphine (2 mg/kg) or halothane, chosen in random order. We measured aortic, pulmonary, and venous pressures, cardiac output, systolic time intervals, and thermodilution coronary sinus flow. We calculated mVO2 as coronary sinus flow times myocardial arteriovenous oxygen content difference. We found significant correlations between mVO2 and heart rate (r = 0.57), systolic blood pressure (r = 0.52), the index delta /delta T (r = 0.53, and RPP (r = 0.78). Multiple regression of RPP and delta P/delta T against mVO2 increased their correlation (r = 0.86), while multiple regression of RPP and pulmonary wedge pressure against mVo2 did not significantly improve the correlation of RPP alone (r = 0.75). We conclude that hemodynamic changes anesthesia and surgery do not decrease the sensitivity of RPP as an index of mVO2.


Improved survival after surgical therapy for chronic angina pectoris: one hospital's experience in a randomized trial. Between 1972 and 1974, 121 patients with chronic stable angina pectoris and operative coronary artery disease, excluding significant left main coronary obstruction, were randomized to either medical therapy (60 patients) or surgical therapy (61 patients) as part of a larger Veterans Administration Cooperative Study of Surgery for Coronary Arterial Occlusive Disease. At the time of randomization, medical and surgical groups were similar with regard to clinical and hemodynamic features as well as degree of left ventricular impairment and extent of coronary disease. Follow-up to June 1, 1978, reveals significantly improved survival in surgical patients from 3 through 6 years after randomization. Sixteen cross-over patients (13 medical to surgery, and 3 surgical without surgery) do not appear to influence results. Results of this randomized study from a single hospital differ from the preliminary results of the larger cooperative study, primarily because of a higher mortality in the medical group. The medical mortality in our group is in keeping with other reports of the natural history of patients with angina pectoris, and we propose that the population of patients we randomized closely simulates the usual type of patient with chronic angina being considered for surgical treatment. Our good surgical results thus contrast significantly with the survival of medically treated patients, and this separates our study from the body of the Veterans Administration Cooperative Study.


Blood flow in sequential vein grafts.

Blood flow in sequential vein grafts. In 69 patients undergoing coronary artery bypass grafting for complete coronary revascularization, blood flow was measured in 140 grafts with 243 distal anastomoses (3.52 bypasses/patient). Total blood flow in single grafts and double and triple sequential grafts did not differ significantly, although mean distal flow decreased successively with single (85 cc/min), double (51 cc/min), and triple (32 cc/min) sequential grafts. Total myocardial flow did not vary significantly regardless of the number of grafts placed. Flow measurements in patients with double sequential grafts showed greater than 20% overlay in flow between the two distal anastomoses. The data suggest significant but incomplete collateral supply between adjacent coronary beds consistent with the concept of any individual area of myocardium being a capacitance bed supplied in part by a number of adjacent coronary branches.


Survival following mitral valve replacement for mitral regurgitation due to coronary artery disease. Forty-six patients who underwent mitral valve replacement for mitral regurgitation due to coronary artery disease during 1970-1975 were identified. Forty patients underwent aortocoronary bypass procedures at the same operation. The survival rate at the fourth postoperative year was 73% in the 22 patients in whom the preoperative left ventricular ejection fraction exceeded 0.35, 38% in the 16 patients in whom the preoperative left ventricular ejection fraction was 35% or less, and 25% in the eight patients in whom aneurysmectomy was performed at the time of mitral valve replacement (p less than 0.05 for the former group compared to the latter two groups). Heart failure, present preoperatively in 41 patients, was improved in most of the long-term survivors. Neither the angiographic extent of coronary artery disease nor whether mitral valve replacement was performed in the acute (within 2 months in 13 patients) or chronic phase of myocardial infarction were distinctly correlated with survival.


Safe early revascularization for continuing ischemia after acute myocardial infarction. Early revascularization following myocardial infarction (MI) is reported to have a high risk of extension of and hemorrhage into infarction with resulting high mortality and morbidity. To evaluate this issue, 80 post-MI patients (aged 32-74 years) with unstable angina pectoris resistant to maximal medical therapy were reviewed. All patients underwent early uncomplicated angiography and subsequent revascularization; 55 (69%) were less than 10 days post-MI, and 25 (31%) were 10-30 days post-MI. Intraaortic balloon pumping was required in 72% for relief of intractable angina or hemodynamic instability. Of the 80 patients, 19% had single vessel disease (VD), 31% double VD, and 50% triple VD. The mortality rate from coronary bypass surgery was 7/80 (8.8%), with four cardiac and three noncardiac deaths. Two patients suffered a perioperative MI (2.5%). At a mean follow-up period of 33 months, there had been only one late death and one recurrent nonfatal MI; 96% of the patients had no significant angina. In patients with continuing ischemia immediately after MI, myocardial revascularization can be safely performed without further injury to the myocardium, and with excellent long-term results.


Aortocoronary bypass surgery: a 7-year follow-up. Follow-up of 748 consecutive patients who underwent aortocoronary artery bypass grafts was obtained for 5 to 94 months (average, 59 months). Operative mortality of 2.5% did not vary with number of vessels bypassed. There was a linear 3.5% annual recurrence rate of angina, and average annual late infarction rate of 1.4%. The cumulative survival rates did not differ for the number of grafts performed or for men and women, but did differ for left main coronary stenosis and impaired ejection fractions. The late cumulative survival rates for the entire group approached those of the general U.S. population.


Immunological parameters and alpha 1-antitrypsinin chronic urticaria. Serum immunoglobulins, complement and alpha 1-antitrypsin were assayed in forty-eight patients with chronic urticaria. Thirteen cases had chronic cold urticaria and thirty-two had chronic idiopathic urticaria. Elevated mean serum IgM was found in chronic cold urticaria. Seven patients had partial immunoglobulin deficiencies. IgE was elevated in sixteen cases of chronic idiopathic and in two with chronic cold urticaria. Eight patients had depressed serum total haemolytic complement activity. Low C3 and normal C4 serum protein concentrations in four cases suggested alternative complement pathway activation. Twenty of forty-six patients were atopic, although specific allergies responsible for the urticaria were not identified in any of them. alpha 1-antitrypsin levels were normal in all patients. The data suggest that the aetiology and pathogenesis of chronic urticarias in this study are heterogeneous. No evidence of abnormality of the protease inhibitor system in either chronic idiopathic or chronic cold urticaria was found.


Automated measurement of the elastase-inhibitory capacity of plasma with a centrifugal analyzer. We describe an automated method for measuring the elastase-inhibitory capacity of plasma. We use a GEMSAEC centrifugal analyzer and succinyltrialanine-p-nitroanilide as an elastase substrate. The method is fast (80--100 samples/h) and accurate (CV = 3.6%). The detection limits are from 20 to 300% of the normal value. The elastase-inhibitory capacity is well correlated with the trypsin-inhibitory capacity and with the immunochemically determined concentration of alpha 1-proteinase inhibitor (alpha 1-antitrypsin). Because elastase is not inhibited by other plasma inhibitors, this method can be used as an enzymatic technique for measuring the concentration of plasma alpha 1-proteinase inhibitor. In an apparently normal population, this concentration was 40 +/- 11 mumol/L.


Pi phenotypes of alpha1-antitrypsin in Southern England: identification of M subtypes and implications for genetic studies. Phenotypes of alpha1-antitrypsin (A1AT) were determined by isoelectric focusing in blood samples from 926 healthy Caucasians living in South-West England. Three subtypes of the most common allele product (M), designated M1, M2, and M3, were identified. Routine determination of these subtypes should considerably amplify the usefulness of the A1AT polymorphism in population genetics and, in view of the possible association of clinical disorders with heterozygous deficient M phenotypes, may enhance the value of Pi determinations in clinical genetics.


[The effect of so-called electrodynamic potentials on experimental reaction-poor pseudarthrosis]. The effect of the magnetic field and the alternating current according to the Kraus-Lechner model was investigated on experimental pseudarthroses in beagle dogs. The evaluation of 16 pseudarthroses showed no effect of the method Kraus-Lechner on healing.


[Electromagnetic stimulation of infected experimental pseudarthrosis in a left-right study of beagles]. Electromagnetic AC-stimulation according to the method of KRAUS was applied in 9 infected ununited ulnar fractures in the beagle. New cortical bone formation, bridging of the bone defect and the number of blood vessels in bone and soft tissue was assessed. Electromagnetic stimulation had no significant influence on bone healing or on the number of vessels.


[Myocardial blood flow distribution immediately following experimental aortocoronary bypass and 1 year postoperatively]. A 75--90% stenosis of the left circumflex coronary artery (CCA) was induced over a period of 40 days in 11 mongrel dogs. Coronary blood flow and the distribution of myocardial blood flow (MBF, tracer-microspheres) was measured at rest and after maximal coronary dilatation in 8 dogs before and within 1 hour after coronary bypass. In 3 dogs these measurements are performed 1 year after bypass op. During coronary stenosis distribution of myocardial blood flow in the area supplied by the CCA was unhomogeneous, the subendocardium receiving less. Within 1 hour after opening the graft, MBF to the subendocardium was improved but the unequal distribution not completely abolished. One year after bypass op, however, the quantity and distribution of MBF appear to be normal although revascularized myocardium was perfused in part via coronary collaterals.


CO2-hysteroscopy today.

CO2-hysteroscopy today. A survey of intra-uterine endoscopy over the last years is given showing the increased demand for hysteroscopy for diagnosis and therapy of intra-uterine diseases. Its indications include the search for unknown causes of uterine bleeding or sterility. It is also applied for various therapeutic reasons such as for example the search and removal of lost or embedded intra-uterine devices. The different methods of hysteroscopy--particularly the CO2 hysteroscopy, which we developed, are described. The new examination procedures such as for example the extensive penetration test applied in cases of sterility and others, which through the advances made in technology are now possible, are also discussed.


Chronic cerebellar stimulation in the treatment of epilepsy. Six cases of intractable epilepsy who were subjected to chronic cerebellar stimulation are reported. They had all been treated with a wide range of anticonvulsant drugs without success. The ages varied between 17 and 55 years. Three were genetic-inherent, 2 were of unknown etiology, and 1 was symptomatic (infection? trauma?). Four had generalized major convulsions and 2 had a mixture of major and minor attacks, 1 with a strong temporal lobe component. Stimulation was commenced in all cases as soon as the patients had a postoperative seizure. Headache occurred in all cases and necessitated reduction in the strength of the stimulation to between 2 and 4 V in all cases except 1. Occipital nerve block temporarily relieved 1 patient, but posterior root section of C2-C3 and part of C4 did not prevent headaches in another case. Two patients were greatly improved and managed to hold employment whereas formerly they had been unemployed. One patient felt 50% improved but there was no reduction in his seizure frequency; another had a 50% reduction in seizures but felt no better. One patient was noted to be improved intellectually although her seizures were more frequent. The remaining patient was unchanged. One patient committed suicide and another drowned. One prosthesis became infected and had to be removed.


Mycoplasma neurolyticum: a potent mitogen for rat B lymphocytes. A mitogen prepared from Mycoplasma neurolyticum has been demonstrated to induce extensive transformation of in vitro cultured rat B lymphocytes. The data summarized in this report show that rat thymus cells as well as hydrocortisone-resistant thymocytes were not activated by this mitogenic agent. On the other hand, spleen cells obtained from thymectomized, lethally irradiated and bone marrow-reconstituted rats were extensively activated by M. neurolyticum. Furthermore, M. neurolyticum was shown to induce the development of antibody-producing cells, as attested by the appearance of direct plaque-forming cells against sheep red blood cells and trinitrophenylated sheep red blood cells in spleen cell cultures exposed to this mitogen. It was also demonstrated that stimulation of rat lymphocytes by this mitogen was inhibited by anti-rat immunoglobulin antibodies. In view of these data, it was suggested that M. neurolyticum, which activates mouse B lymphocytes, is a potent mitogen for rat B lymphocytes as well. This mitogen is a significantly more powerful mitogen for rat B lymphocytes then any other known mitogens. The availability of such mitogenic material in the rat system will enable studies on control mechanisms of action and differentiation of rat B lymphocytes.


The migration of lymphocytes in the fetal lamb. The migration of 51Cr-labeled autologous lymphocytes from intestinal or prescapular lymph was compared in fetal lambs and adult sheep. A subpopulation of lymphocytes present in intestinal lymph of adults which migrated to the small intestine was not found in fetal intestinal lymph. There were marked differences in the migration of fetal and adult lymphocytes to the lungs and liver. In spite of the absence of circulating antibodies or immunoglobulins and of extrinsic antigen in the immunologically virgin sheep fetus, the circulation of lymphocytes through the spleen and lymph nodes of fetal lambs was more intense than in the adult.


A duration-dependent negative potential in the cichlid electroretinogram. A negative potential can be evoked in the local electroretinogram of the cichlid fish Cichlasoma octofasciatum by light stimuli of duration longer than 70 msec. This response superficially resembles the proximal negative response, but differs in some waveform components and dependence upon stimulus configuration and duration.


Differences in in vitro incorporation of tritiated deoxycytidine and tritiated thymidine into human lymphocytes. Human lymphocytes stimulated in vitro by PHA or PWM incorporate 3H-CdR into DNA, but less well than 3H-TdR. More 3H-CdR is incorporated in populations enriched for T cells. No 3H-CdR is used by cells stimulated by lipopolysaccharides under circumstances in which 3H-TdR is incorporated. We conclude that human T cells and B cells differ in their ability to use 3H-CdR.


Helper T cell interactions.

Helper T cell interactions. Studies of the relationship between carrier-primed helper T cell dose and the antibody response to a hapten on that carrier reveal evidence for two synergistic T helper cells. One of these two T cells is absent in agammaglobulinemic mice. This finding is not due to suppression; instead, T helper cells from these mice interact synergistically with T helper cells from normal mice, as would be predicted if two populations of cells are present in normal mice, while only one is present in the agammaglobulinemic mice. These findings, taken together with studies in similar systems, suggest that one of the two T helper cells recognizes immunoglobulin on B cells, while the other is specific for carrier. It remains to be determined whether both cells show the phenomenon of major histocompatibility complex restriction, or whether this a property of one of the cells only. It is also not clear whether the Ig-recognizing T cell is also carrier specific, or whether its apparent carrier specificity in this system reflects an ability of the carrier to bring together Ig and an I region gene product into a unique configuration on the B cell surface.


Influence of vitamin E and selenium on immune response mechanisms. Vitamin E and selenium have both been shown to have immunostimulatory effects in a variety of species when administered in quantities in excess of established deitary requirements. Responses to each nutrient appeared to be independent of the nutrition of the other. Deficiencies of vitamin E and selenium conversely caused suppression of the immune response system, particularly, cell mediated mechanisms. Suppression was shown to be associated with serum factors coating lymphocytes from dogs deficient in vitamin E and selenium. Oral supplementation with vitamin E transformed or removed the suppressive factors, dietary selenium had no effect. In vitro peripheral lymphocyte blast transformation tests corroborated observations of in vivo studies. Reducing agents and synthetic anti-oxidants eliminated suppressive effects in vitro. Suppression was most marked in dogs fed diets highest in polyunsaturated fatty acid (PUFA) content, providing conditions most conductive to lipid peroxidation in vivo. The essential fatty acids linoleic and arachidonic have been shown to similarly influence immunoregulatory mechanisms in vivo. The effect may be a direct one since plasma membrane fluidity of lymphoid cells increases the probability of modification of cell--antigen interactions by PUFA. However, their effect may also be an indirect one. PUFA are known precursor substances of E anf F type prostaglandins which have been shown to affect immediate and delayed hypersensitivity by stimulating synthesis of cyclic AMP. More definitive studies are needed to resolve this question.


Gastrointestinal angiodysplasia associated with aortic valve disease: part of a spectrum of angiodysplasia of the gut. Twelve patients with angiodysplasia of the gastrointestinal tract were seen at The Mary Imogene Bassett Hospital are presented. Six share the features of gastric or duodenal angiodysplasia, advanced age, and aortic valve disease. Of these 6 patients, 4 who bled repeatedly were treated with endoscopic coagulation of areas of gastric and duodenal angiodysplasia. Six patients with other types of gastrointestinal angiodysplasia are presented for comparison. Two had gastric angiodysplasia and no aortic valve disease, 2 had hereditary hemorrhagic telangiectasia, 1 had received irradiation, and 1 could not be classified. We suggest that angiodysplasia of the gastrointestinal tract can be regarded as a spectrum with a clearly inherited etiology on one extreme and an acquired etiology on the other. A subset of these patients may be associated with aortic valve disease. Angiodysplasia of the upper gastrointestinal tract may account for a significant fraction of previously unexplained bleeding. It is hoped that this paper will aid in their more frequent recognition.


The identification of urogastrone in serum, saliva, and gastric juice. Urogastrone, a peptide isolated from human urine, is known to cause inhibition of gastric acid secretion and proliferation of fibroblasts in culture; furthermore immunofluorescent localization techniques show it to be present in submandibular and Brunner's glands. Serum, saliva, and gastric juice samples have now been fractionated upon Sephadex G-200 and G-50 and the immunoreactive urogastrone located using a specific radioimmunoassay. Biologic activity was shown by mitogenic studies with 3T6 fibroblasts. In serum, the major immunoreactive component was ca. 1-2 X 10(5) daltons, but trypsin treatment then gave a smaller biologically active species in the same position as pure urogastrone on Sephadex G-50. Both saliva and gastric juice showed major components at the position defined by urogastrone, and these also stimulated the uptake of [H]thymidine into the fibroblasts. It is concluded that a urogastrone-like molecule can be released enzymically from a high molecular weight serum precursor and that the small biologically active peptide is also a normal component of saliva and gastric juice.


Hemorrhage from esophageal varices after placement of the LeVeen shunt. Transient bleeding from esophageal varices was noted in a patient with alcoholic cirrhosis and a patent end-to-side portacaval shunt after placement of a LeVeen shunt for unmanageable ascites. Pressure measurements of the portal systemic gradient, obtained at the time of bleeding and 12 days later, suggest that the variceal hemorrhage was induced by the rapid infusion of ascitic fluid into the systemic circulation. Principles of management for variceal hemorrhage after LeVeen shunt placement are discussed.


Immune status in Crohn's disease. 3. Peripheral blood B lymphocytes, enumerated by means of F(ab)2-antibody fragments, Null and T lymphocytes. In the peripheral blood of patients with Crohn's disease (CD) the numerical distribution of the three major B lymphocyte subsets was determined by the identification of surface immunoglobulins using F(ab)(2)-antibody fragments. T cell counts were also obtained and the number of null cells was calculated. Twenty-eight patients with Crohn's disease including 14 patients with previously untreated and very short-standing disease (group CD 1) and 14 patients with long-standing and/or previous drug treated disease (group CD 2) were compared with 28 sex and age-matched normals as well as with 13 patients with acute inflammatory bowel disease (group D). Patients in group D and inactive patients of group CD 1 showed a significant absolute lymphocytosis due to an increase in both the three B cell subsets and the T cells, without changes in the null cells. While the proportion of T cells was normal, there was a significant relative B lymphocytosis and a relative null cytopenia in these patients. Active CD 1 patients, however, showed significantly lower absolute lymphocyte and T cell numbers. In group CD 2, there was a significant absolute lymphopenia caused by an equal decrease in B and T cells. Highly active CD 2 patients showed higher absolute null cell counts than inactive patients. With increasing disease duration there was a significant decrease of the relative and absolute B cell concentrations. The data obtained suggest that T and B cell populations in the peripheral blood are reduced in certain patients with Crohn's disease and that this occurs secondarily to activity of disease, chronicity of disease, and the effects of therapy.


Major transplantation antigens in host responses to infection. There is increasing support for the concept that in all of their varied immunologic functions, T lymphocytes act through a dual specificity. In the case of intracellular viral infections, the recognition required for cytolysis involves both a "self" component, coded for by the genes that specify the major transplantation antigens, and an "X" component, provided by viral antigens expressed on the target-cell surface.


Density-gradient separation of spleen-cell subpopulations from Marek's disease virus-infected chickens. Ficoll gradient separation of spleen-cell suspensions has shown that depressed T-cell mitogen reactivity in cultures of JM-VS and MD cells results from selective depletion of mitogen-responsive T-cells.


Rejection of tumor cells in vitro: morphological studies on killer T cells and damaged tumor cells. The in vitro destruction of a methylcholanthrene-induced guinea pig sarcoma (MC-D) by killer T lymphocytes was investigated by light and electron microscopy. Various degrees of cell damage ranging from slight to extensive were observed. In cells with slight injury, dilatation, vesiculation, fragmentation and degeneration of the rough surfaced endoplasmic reticulum were the most characteristic findings. In cells with extensive injury, widespread nuclear and cytoplasmic alterations were evident and many of these cells were fragmented into smaller portions and finally transformed into granular membranous and amorphous debris. Cytoplasmic vacuoles filled with electron-lucent material were frequent in extensively damaged cells. Killer lymphocytes resembled closely antibody-forming plasma cells when examined with light microscopy but lacked the extensive network of rough surfaced endoplasmic reticulum, and did not produce immunoglobulin. It is suggested that these extensively differentiated T-derived killer cells are end cells similar to those of B lymphocyte-derived plasma cells. Viral particles resembling closely C-type viruses were observed in mixed killer cell MC-D cultures.


A serological study of somatic antigens from Haemophilus influenzae and two related species. Somatic antigenic preparations from Haemophilus influenzae strains, types a-f, and from non-capsulated H. influenzae strains obtained from the oral cavity of healthy individuals were analysed with the double-diffusion technique by means of antisera against the capsulated strains. The somatic precipitinogenic pattern of each of these strains, consisting of 12--20 lines, was very similar. In addition, the somatic antigenic pattern of one H. parainfluenzae strain and one strain tentatively designated H. haemoglobinophilus were studied. Precipitinogens common to H. influenzae as wel as strain-specific precipitinogens were demonstrated in these strains. It is concluded that immunodiffusion analyses might be of value for taxonomic studies of the genus Haemophilus.


Characterization of lymphocytes which inhibit proliferation of human T cells exposed to lymphocyte-derived mitogenic factors. Culture supernatants of PHA-activated human lymphocytes (active SUPs) contain factors which are strongly mitogenic for fractionated peripheral T cells. This stimulation is suppressed by certain non-T lymphocytes. It is shown that these suppressor cells can inhibit an ongoing response of T cells to active SUP and that this inhibition is reversible. Using various rosette sedimentation techniques for fractionating subpopulations of lymphocytes it is concluded that the suppressor cells lack membrane-associated receptors for C3 but possess receptors for the Fc part of IgG. This subset of lymphocytes may be an important regulator of lymphocyte proliferation during immune responses.


Intestinal goblet cell differentiation in Nippostrongylus-infected rats after transfer of fractionated thoracic duct lymphocytes. Adoptive immunization of Nippostrongylus-infected rats augmented goblet cell differentiation in the intestinal epithelium. After fractionation of immune thoracic duct lymphocytes (TDL), cells lacking surface immunoglobulin (sIg-) were the most potent stimulators of goblet cell differentiation. Moreover, TDL drained from rats harbouring a primary infection were more effective than TDL from hyperimmune rats.


Immunosuppression in experimental African trypanosomiasis. Polyclonal B-cell activation and mitogenicity of trypanosome-derived saturated fatty acids. Changes in antibody responses in adult mice infected with Trypanosoma congolense and subsequently challenged with unrelated antigens (sheep red blood cells and pneumococcal polysaccharide) were studied. Immune responses were significantly depressed within 1 week of infection, and complete suppression of both IgM and IgG responses to both types of antigen was established 15 days after immunization. Coincidentally with the development of high parasitaemias, background IgM plaque-forming cell responses to sheep red cell antigen significantly increased in non-immunized T. congolense-infected animals. Autolysates of T. congolense and chloroform-soluble extracts of the autolyzed trypanosome were found to be mitogenic in vitro for the spleen cells of normal mice. Fractionation of these extracts by thin-layer chromatography indicated that the mitogenic activity migrated with the free fatty acids. Substitution of the relevant saturated and unsaturated free fatty acids in the autolyzed trypanosome extracts with commercial pure fatty acids in the mouse spleen cultures indicated that the mitogenicity was due to palmitic and stearic acids. It is suggested that the general immunosuppressing effect of trypanosomes may be attributed, at least in part, to the polyclonal activation, and subsequent depletion and/or clonal exhaustion of B-cells as a result of blastogenic stimulus from the parasites. This may operate, at least in part, through the generation of B-cell mitogenic saturated fatty acids.


T cell defect in essential mixed cryoglobulinaemia. Peripheral blood lymphocytes from untreated patients with essential cryoglobulinaemia were studied for their surface markers and for their in vitro mitogenic reactivity. No differences in lymphocyte subpopulations were observed between cryoglobulinaemic patients and normal controls. Cultures of separated lymphocytes were stimulated with different concentrations of phytohaemagglutinin, Con-A and pokeweed mitogen. Incorporation of [3H]-thymidine in patients' cultures was compared with that of normal controls. Significantly decreased reactivity to phytohaemagglutinin and Con-A, but not to pokeweed mitogen, was found in all patients studied. The depressed mitogenic reactivity to phytohaemagglutinin and Con-A might be referred to a qualitative T cell defect.


Peritoneal cell population of mice infected with Mesocestoides corti as a source of eosinophils. A prominent feature of the inflammatory cellular response in the peritoneal cavity of Mesocestoides corti-infected mice is a marked and sustained increase in the number of eosinophils. In intact mice, the total number of nucleated cells in the peritoneal cavity rises from less than 5 X 10(6) to more than 50 X 10(6) and, at certain time points, in excess of 50% of these cells are eosinophils. Peritoneal eosinophils are absent in infected hypothymic nude (nu/nu) mice of three genotypes, and eosinophils counts can be elevated in infected nude mice by injection of peripheral lymphoid cells or thymocytes. The peritoneal cells of M. corti-infected mice are a convenient starting cell population for eosinophil purification.


Cellular cooperation in lymphocyte activation. III. B-cell helper effect in the enhancement of T-cell response. T and B cells were purified from human tonsil and peripheral blood by the removal of phagocytic cells, followed by filtration through a nylon fiber column (NC) and E-rosette formation. Purified T and B cells contained less than 1% of other cell types. The responses of T cells to concanavalin A (Con A) and soluble protein A were greatly enhanced in the presence of autologous B cells. Participation of B cells in T-cell enhancement was confirmed by the following observations: (a) purified B copulation, which was separated further from adherent B cells, retained its enhancing activity. (b) Another adherent cell-free B-cell preparation, which was purified from the NC-passed fraction, and (c) no T lymphoid but some B lymphoid cell lines, elicited strong T-cell enhancement. It was also found that the enhancing capacity of B cells required no metabolic activity, but rather an intact cell form and direct cell-to-cell contact with responding cells. The stimulatory determinants on B cells were resistant to trypsin and neuraminidase treatment. In this paper a hypothesis will be presented that at least two signals are prerequisite for the effective activation of T cells.


Double strand-breaks and DNA-to-protein cross-links induced by fast neutrons in bacteriophage DNA. Coliphage T7 was suspended in tryptone broth and exposed to a mixture of fast neutrons and gamma radiation. Plaque survival, double strand-breaks and DNA-to-protein cross-linkage were examined and the results compared with those found in phage exposed to gamma radiation alone. Neutral sucrose density sedimentation patterns indicate that neutron-induced double strand-breaks sometimes occur in clusters of more than 100 in the same phage and that the effeciency with which double strand-breaks form is about 50 times that of gamma-induced double strand-breaks. Neutron-induced protein-to-DNA cross-links probably also occur in clusters with enhanced efficiency relative to low LET radiation.


Alterations in the survival of X-irradiated cells by 2,4-dinitrophenol depending on ATP deprivation. The dose-survival curve of cultured melanoma cells was changed by post-irradiation treatment with 2,4-dinitrophenol (DNP). The parameters of the curves were Do = 147 R and n = 5 . 6 for untreated cells and Do = 143 R, n = 7 . 9 and Do = 142 R, n = 2 . 0 for the cells treated with 10(-5) M DNP and 5 x 10(-5) M DNP in phosphate-buffered saline, respectively. The content of ATP in the cell decreased to 5% of the control level after treatment with either concentration of DNP. The recovery of ATP content was rapid and complete after 2 hours' incubation in culture medium after the removal of 10(-5) M DNP, but was retarded and incomplete after 4 hours with 5 x 10(-5) M DNP. Thus prolonged ATP deprivation with a high concentration of DNP results in an inhibition of recovery and a reduction in the n-value.


Cell survival following multiple-track alpha particle irradiation. In experiments in which mammalian cells were irradiated with 5 . 6 MeV alpha particles from a Tandem Van de Graaff machine, we have confirmed the finding of others that the mean lethal dose (Do) is about 60 rad. However, on measuring the area of the nuclei of the flattened cells as they were irradiated, we found that this mean lethal dose corresponds to the passage of not one or two alpha particles per cell nucleus as expected but to between 10 and 20 particles. This allows for the possibility that the direct action of alpha particles on the nucleus may be the important event in carcinogenesis.


Effects of high-LET neon (20Ne) particle radiation on the brain, eyes and other head structures of the pocket mouse: a histological study. A study was made of tissues from 130 pocket mice after a single head-only exposure to high-LET 20Ne particle radiation at 1000, 100 or 10 rad (nominal surface dose) with the view of obtaining base"line data regarding the effectiveness of HZE (cosmic-ray) particles during spaceflight. First seen at 2-3 weeks after exposure, necrotic neurons in the cerebrum reached peak incidence (0 . 04 per cent at 1000 rad, 0 . 003 per cent at 100 rad and less than 0 . 0005 per cent at 10 rad) after 4-5 weeks and decreased to low levels thereafter. Incidence in the cerebellum was lower. Neuroglia, cells of the subependymal matrix and dentate gyrus precursor cells suffered acute damage at 1000 and at 100 rad. At 1000 rad, enlarged hyperchromatic neuroglia, first noted at 3 weeks, increased in number up to 7 months, then declined. Alterations in the retina and olfactory epithelium were seen at 1000 rad, and reaction in the scalp at 100 rad. Damage was incurred by dentinoblasts at 10 rad. Changes similar to those observed in pocket mice were found in the brains of gerbils and C57B1 mice.


Response of mouse intestine to 14 MeV neutrons. At the Hamburg-Eppendorf Hospital neutron facilities the relative biological effectiveness (r.b.e.) of d,T-neutrons was determined with respect to survival of mouse intestinal crypts. (CBA/Rij x C57BL/Rij)F1 mice were irradiated to the whole body at different depths inside a tissue-equivalent phantom. Irradiations were carried out with a collimated neutron beam at about 6 rad/min given in single doses ranging from 450 to 1000 rad. For reference, gamma-rays from a 60Co therapy unit were used. The number of surviving intestinal crypts per circumference of the jejunum was determined 3 1/2 days after irradiation according to the method of Withers and Elkind. The number of surviving stem cells was calculated on the basis of Poisson statistics. The doses necessary to reduce survival to ten crypt stem cells per circumference amounted to 689 +/- 19 rad for neutrons and 1449 +/- 29 rad for 60Co gamma-rays. From these figures an r.b.e. of 2 . 1 +/- 0 . 1 is obtained. Measurements at different depths in the phantom did not show any variation of r.b.e. with depth along the axis of the neutron beam.


Response of plateau-phase mouse embryo fibroblasts to ultra-violet light. Clonogenic survival was measured in plateau-phase cultures of the 10T1/2 mouse cell line exposed to 254 nm ultra-violet light. The survival curve was found to be biphasic, Do for the two components being 37 and 1191 erg/mm2 respectively. This extreme resistance at higher doses can only be partly accounted for by the increased cytoplasmic absorption of U.V.L. due to an increased thickness of plateau-phase cells. When the cultures were held for 24 hours in plateau phase in conditioned medium after irradiation, recovery yielding a 1.4-fold enhancement of survival was found at higher doses. This recovery process was inhibited by neither caffeine nor cycloheximide. When caffeine was given for 48 hours after sub-culture, the effect on survival was also negligible. We propose that this plateau-phase recovery process is associated with excision repair of DNA adducts induced by U.V.L. Delayed sub-culturing favours the excision mode of repair and renders the post-replication mode less necessary.