T-lymphocyte number and function and the course of hepatitis B in hemodialysis patients. To study the relation between general cellular immunity and the course of hepatitis B within a group of chronic hemodialysis patients, T-lymphocyte number and function were investigated in 13 persistently hepatitis B surface antigen (HBSAg)-positive patients, in 32 HBSAg-negative patients, and in 11 patients who had recovered from hepatitis B and compared with that of 21 age-matched controls. Phytohemagglutinin-induced lymphocyte stimulation in vitro and the number of circulating T-cells in the HBSAg-positive group were significantly decreased as compared with those of the recovered group and the controls. Lymphocyte stimulation by pokeweed mitogen and by an antigen cocktail showed the same tendency, but no significant differences between the HBSAg-positive and the recovered groups. Uremic sera from the three patient groups had similar depressive effects on phytohemagglutinin induced lymphocyte stimulation of controls. Serum immunoglobulin G, (IgG), IgA, and IgM were normal in the three patient groups. It is concluded that chronic hemodialysis patients, who have become persistent HBSAg-carriers, have a significantly decreased T-lymphocyte number and function as compared with hemodialysis patients who are able to eliminat hepatitis B virus (HBV). The difference could not be ascribed to the HBV infection itself. This indicates that T-cells play an important role in the elimination of HBV in hemodialysis patients.


Adoptive transfer of variant-specific resistance to Trypanosoma rhodesiense with B lymphocytes and serum. Mice survive an otherwise lethal infection with Trypanosoma rhodesiense if previously inoculated with irradiated organisms. This resistance demonstrates immunological specificity, since even animals inoculated with irradiated trypanosomes were killed when challenged with trypanosomes of a nonhomologous or variant antigenic type. This resistance could be transferred to syngeneic recipients with serum or B lymphocytes. T lymphocytes had no capacity to transfer resistance. Although mice were protected from active infection on challenge at least 25 days after inoculation of irradiated organisms, this resistance could be transferred with spleen cells for only 10 days after immunization. Resistance could be transferred with serum for a minimum of 25 days after immunization. These studies implicate an antibody-mediated mechanism as having a major role in resistance to T. rhodesiense infections.


Gamma radiolysis of thymine in oxygen-free aqueous solution in the presence of electron affinic radiosensitizers: identification of stable products. Radiosensitizers react with nucleic radicals by addition and by electron transfer reactions. We report the steady-state gamma radiolysis of 1 mM thymine in oxygen-free aqueous solutions containing different classes of radiosensitizing drugs: N-oxyl-free radicals (TAN and TMPN), quinones (menadione and naphtoquinone), nitroheterocyclic compounds (metronidazole and 5-nitro-2-furoic acid) and N-ethylmaleimide. Two classes of thymine degradation products were isolated by thin-layer chromatography and characterized by spectroscopic measurements. The main products, irrespective of radiosensitizers, resulting from oxidation reaction were identified as the cis and trans isomers of 5,6-dihydroxy-5,6-dihydrothymine, N-pyruvyl-N'-formylurea, 6-hydroxy-5,6-dihydrothymine and 5-hydroxy-5,6-dihydrothymine. In the experimental conditions used only N-oxyls and to a lesser extent NEM reacted with 5-hydroxy-5,6-dihydrothymin-6-yl radical, giving stable covalently-bonded addition products with a high yield. TAN showed a higher binding ability with respect to TMPN, which is in good agreement with the rate-constants previously reported for these bimolecular reactions.


On the radiation chemistry of some pyrimidine-electron adducts: reaction of pyrimidine negative ions with t-butanol radicals. The rates of decay of the electron adducts of thymine, thymidylic acid and of uracil at pH approximately 8-5 and at wave-lengths of 340 or 350 nm in the presence of t-butanol as scavenger for OH radicals are not influenced significantly by the addition of 0-1 M NaClO4. It follows that the decay reactions do not take place between negatively-charged species. The best explanation seems to be an efficient reaction of the electron adducts with the t-butanol radicals formed by reaction of OH radicals with the t-butanol.


DNA replication and post-replication repair in U.V.-sensitive mouse neuroblastoma cells. Mouse neuroblastoma cells differentiate when grown in the absence of serum; differentiation is reversed on the addition of serum. Differentiated cells are more sensitive to U.V.-radiation than proliferating cells. Whereas addition of serum to differentiated neuroblastoma cells normally results in immediate, synchronous entry into S phase, irradiation just before the addition of serum results in a long delay in the onset of DNA replication. During this lag period, incorporated 3H-thymidine appears in the light density region of CsCl gradientss, reflecting either repair synthesis or abortive replication. Post-replication repair (gap-filling) was found to be present in proliferating cells and at certain times in differentiated cells. It is suggested that the sensitivity of differentiated neuroblastoma cells to U.V.-radiation may be due to ineffective post-replication repair or to deficiencies in more than one repair mechanism, with reduction in repair capacity beyond a critical threshold.


In vitro morphologic transformation of Syrian hamster cells by U.V.-irradiation is enhanced by X-irridation and unaffected by chemical carcinogens. U.V.-exposure of foetal hamster cells (secondary or tertiary sub-cultures) seeded for colony formation resulted in the induction of transformation. The U.V.-effect on colony-forming ability resulted in a D37 of 58 ergs/mm2. The observed transformation frequency induced by U.V.-increases approximately in proportion to increased doses in the range of 7-5-60-8 ergs/mm2 examined. When cells seeded for colony formation were treated with U.V. and later with either benzo(a)pyrene or N-acetoxy-fluorenyl-acetamide, commencing 6 min after exposure to U.V., there was neither an additive nor a synergistic enhancement of the transformation frequency ordinarily observed with either chemical agent alone. In mass cultures that were X-irradiated with 250 R, seeded for colony formation and treated with either 15 or 30 ergs/mm2 of U.V. 48 hours later, the enhancement of transformation was approximately 12- and 6-fold on a colony basis and 6- and 3-fold on a dish basis, respectively. No transformation occurred after X-irradiation only. The enhancement obtained by the pre-treatment with X-ray is imilar to that reported for the combination of X-ray and chemical carcinogens.


DNA strand breaking and rejoining in response to ultraviolet light in normal human and xeroderma pigmentosum cells. We describe a reproducible technique for measuring DNA strand breaking and rejoining in cells after treatment with U.V.-light. Results obtained with normal human cells, xeroderma pigmentosum cells (XP, complementation group A) and XP variant cells suggest that all three of these cell-types can carry out single-strand incision with equal rapidity. However, the breaks so induced appeared to be only slowly rejoined in the XP variant cells and rejoined not at all in XP complementation group A cells. Furthermore, parental strand rejoining was inhibited by caffeine in XP variant cells but not in normal cells.


Deficit in DNA content relative to histones in X-irradiated HeLa cells. The DNA and histone content of HeLa S-3 cell cultures was measured by direct mass assays 21 hours after 1000 rad of X-irradiation, when the cells were arrested in G2 phase. The nuclear DNA content of such cultures was found to be deficient (73% of control values). In contrast, the synthesis of nuclear histones persisted, and the total histone content was close to 100% of control values. When synchronously-growing cultures were irradiated in mid-S phase and examined 3-5 hours later in G2 phase, both DNA and histone content were equal to control values.


Modification of radiation-induced oxic and anoxic damage by caffeine and potassium permanganate in barley seeds. We show that both the immediate and post-irradiation oxygen effects in barley seeds decrease in magnitude in the presence of potassium permanganate and caffeine. This implies that these two types of oxygen effect have features in common. With the removal of the radiation-induced oxygen-sensitive sites, by anoxic hydration, caffeine potentiates the oxygen-independent component of damage, in seeds irradiated in a dry or pre-soaked state. Potassium permangenate, on the other hand, enhances the anoxic radiation damage only in seeds irradiated in a dry state. The possible mode of action of KMnO4 and caffeine in barley seeds is discussed.


Radiation effect on the proliferating capillaries in rat transparent chambers. The revascularization of the devascularized area in rat transparent chambers by the proliferating blood vessels was studied quantitatively on the changes of vascularity. On the vascularizing border, a hypervascular zone about 0-5 mm wide was formed. The border advanced constantly at 0-020 cm a day. Vascular density was fixed in the repaired area. The vascular length and repaired area increased on parabolic curves. The chambers were irradiated with single doses of 50, 100, 200, 400, 1000, 2000, and 4000 rad of 30Co gamma-rays, and the effects on the advance of the border were examined. With 200 rad and more, significant inhibition, greater with bigger doses, was seen in the advance of the borders. Regression of the borders also occurred. Irradiation with over 1000 rad destroyed the hypervascular zones.


Defective immunocompetence in foetal undernutrition. The rate of Ig-bearing lymphocytes (B-cells) and of rosette-forming cells (T-cells) in peripheral blood as well as the lymphocyte response to phytohaemagglutinine (PHA) stimulation were evaluated in 19 small-for-date infants in order to assess both humoral and cellular immunity. A significant decrease of Ig-positive cells and of E-rosettes was found, compared with new-borns of appropriate birth weight, However, the response to PHA stimulation appeared to be impaired in only 3 of the observed cases.


Effect of adenosine 5'-triphosphate-dependent deoxyribonuclease deficiency on properties and transformation of Haemophilus influenzae strains. A transformation-deficient strain of Haemophilus influenzae, lacking adenosine 5'-triphosphate-dependent deoxyribonuclease activity, was isolated by selection for sensitivity to mitomycin. The mutant, designated JK57, possibily showed a moderate sensitivity to ultraviolet (UV) irradiation and treatment with methyl methane sulfonate. Contrary to the wild type, the mutant degraded chromosomal deoxyribonucleic acid (DNA) to some extent. However, after UV irradiation to the mutant degraded considerably less DNA than the wild type and the TD24 mutant of H. influenzae, the latter being equivalent to a recA mutant of Escherichia coli. A TD2457 double mutant, constructed by transferring the TD24 mutation into the JK57 strain, was as sensitive to deleterious agents and as deficient in transformation as the TD24 single mutant; in the double mutant, however, after UV irradiation chromosomal DNA was degraded to the same extent as in the JK57 mutant. The number of transformants per unit of radioactive donor DNA taken up by JK57 recipient cells was approximately 10-fold smaller than in the wild type. Presynaptically, the fate of donor DNA in the adenosine 5'-triphosphate-dependent deoxyribonuclease-deficient mutants was not different from that in the wild type. In contrast to TD24 and the TD2457 double mutant, in the JK57 mutant, recombinant-type activities (molecules carrying both the donor and recipient markers) were formed almost as well as in the wild type. After integration into the JK57 recipient genome, the rate of replication of the donor marker was equal to that of the recipient marker during a number of generations, which suggests that the donor DNA is normally integrated into the JK57 chromosome. It is suggested that transformed JK57 cells pass with a high frequency into a type of cells that can replicate their chromosomes many times but have lost the ability to form visible colonies after plating.


Incorporation of tritium into cell materials of Rhodopseudomonas spheroides from tritiated water in the medium under aerobic conditions. When Rhodopseudomonas spheroides cells grown aerobically in the dark were incubated in medium containing tritiated water (THO), incorporation of T into the bacterial cell materials occurred under growth and no-growth conditions. The overall T incorporation under no-growth conditions was stimulated by vigorous aeration and was suppressed strongly in the presence of either 10(-3) M KCN or 0.3% HgCl2, indicating that the bulk of the incorporation might depend upon bacterial cell metabolism or respiration. 10 mug/ml chloramphenicol and 20 mug/ml rifamipicin slightly suppressed the T incorporation. The extent of T incorporation was proportional to the concentration of T in the medium. Accordingly, regardless of differences in the concentration of T in the medium, the maximum ratio of T content per hydrogen atom in the cell materials to that of THO in the medium was approximately 0.2 in non-growing cells and 0.5 in growing cells, whereas the value was 0.02-0.03 in cells incubated in medium containing KCN or HgCl2. The non-growing cells aerated in THO medium were lyophilized and fractionated by the modified method of Schneider. More than 40% of the total T incorporated into the cell materials was recovered in the cold PCA-soluble fraction, whereas the distribution of T into fractions solbule in ether-ethanol, hot PCA and alkali was 10 to 20% each. More than 75% of the T extracted in the cold PCA-soluble fraction was volatile. While the amounts of RNA and protein in the non-growing cells decreased on adding chloramphenicol or rifampicin, the distribution of T in these fractions did not change much. Our results on T incorporation into non-growing cells indicate that the major T incorporation into bacterial cell materials is independent of biosynthetic reactions using labeled precursors produced by the assimilation of T into metabolites, but presumably depends on energy-linked conformational changes of macromolecules.


[Ruptured aneurysms of the sub-renal abdominal aorta]. The rupture of an aneurysm of the sub-renal aorta may give rise to several clinical presentations which it is essential to recognise in order to carry out emergency operation, e.g. attack of pain, retroperitoneal hematoma, hemoperitoneum, rupture into a hollow viscus, infective aneurysm. The special characteristics of the treatment concern resuscitation, site and type of aortic clamping, aorto-caval or aorto-digestive rupture or an infective aneurysm raising special problems. It is the vascular collapse which makes the rupture serious, an aneurysm operated as an emergency without collapse, has a mortality which differs little from a non-ruptured aneurysm, e.g. 3 deaths out of 55 operated cases. On the other hand, out of 44 aneurysms operated in acute collapse, there were 31 deaths. The complications observed are linked to the latter, e.g. cerebro-vascular accidents, acute coronary ischemia, acute ishemia of the limbs, which may also be due to embolism during operation, renal complications due to renal shock. The prevention of these complications has permitted us to reduce mortality by 40 p. 100 the last 5 years.


Meningitis due to Haemophilus influenzae type e. Haemophilus influenzae type e was isolated from the cerebrospinal fluid and blood of an 8-month-old child with meningitis.


Factors influencning mitotic yields from suspension cultures of normal and acute leukaemic bone marrows. Cytogenetic studies of bone marrow are often hampered by a paucity of dividing cells. In an attempt to improve mitotic yields we have tried to promote mitotic activity in suspension cultures of bone marrow from both normal and leukaemic subjects.  Enrichment of the media always increases yield and the addition of bone marrow stimulating factor (BMSF) may do so. The best prospect for improving the yield of mitoses in acute myeloid leukaemia is to culture the marrow in an enriched medium with BMSF.


Rosette inhibition test in chronic liver disease. A role has recently been assigned to cell-mediated immunity in chronic liver diseases in addition to the well-known alterations of humoral immunity. We now report the results of the rosette inhibition test for the evaluation of T-lymphocyte "sensitization" in patients with different chronic liver disorders. A cell-mediated immune reaction was found in 81% of patients with chronic active hepatitis and in 71% with primary biliary cirrhosis, whereas patients with chronic persistent hepatitis showed no reaction. The correlation with the incidence of hepatitis B antigen showed that T-lymphocyte sensitization was more frequent in the group of HB-positive patients. Finally, improvement of the test was observed in four out of nine patients given immunosuppressive treatment.


Gastrointestinal microbleeding in normal subjects receiving acetylsalicylic acid, placebo, and R-803, a new antiinflammatory agent, in a design balanced for residual effects. This study was undertaken to compare the relative gastrointestinal toxicity of equipotent doses of acetylsalicylic acid (ASA), 900 MG q.i.d., and a new anti-inflammatory agent, R-803, 300 mg q.i.d., against placebo. Gastrointestinal micro-bleeding was quantitated with the 61Cr-labeled erythrocyte assay. The experimental design was balanced for residual effects in the first week following any treatment. An interesting relationship between stool weight and blood loss was found to influence the microbleeding independently of the treatments themselves. All observed blood loss values were corrected by regression to a reference stool weight of 100 Gm. Final analysis of corrected values was done on arithmetic and logarithmic scales. On both scales, R-803 induced much less blood loss than ASA. A difference of 1.3 ml/day between R-803 and placebo was not statistically significant on the arithmetic scale. On the log scale, a statistically significant difference was found; but since it corresponds to 0.4 ml/day, it was not considered to be clinically significant at this dosage.


Axonal guidance of developing optic nerves in the frog. I. Anatomy of the projection from transplanted eye primordia. Right or left eye primordia of Shumway stage 16-18 Rana pipiens embryos were transplanted to the position normally occupied by the ear, where they developed into externally normal eyes. Ganglion cell density in the retina of the transplanted eye was significantly lower than the ganglion cell density in the animal's normal eyes. No significant difference was observed between normal and transplanted inner and outer nuclear layers. In several preparations a large piece of embryonic forebrain was included in the initial eye graft. Optic nerves from the transplanted eyes penetrated this transplanted forebrain and established a dorsocaudal growth trajectory relative to the ectopic tissue's original anterior-posterior and dorsal-ventral axes. After traversing the forebrain, the transplanted optic nerve fibers penetrated the medulla where they invaraibly grew dorsocaudally to take up and maintain a dorsolateral position in the white matter of the spinal cord. The consistent dorsocaudal trajectory established by the translocated optic tract in the ectopic forebrain and in the hindbrain and spinal cord is very similar to the growth trajectory in the normal diencephalon, suggesting that dorsocaudal growth relative to the three major axes of the neural tube is an inherent property of optic nerve fibers. These results also suggest that the polarity cues which guide normal optic tract growth are not unique to the diencephalic regions of the neural tube.


Axonal guidance of developing optic nerves in the frog. II. electrophysiological studies of the projection from transplanted eye primordia. When a primordial eye was transplanted to the ear position in Rana pipiens embryos, the optic nerve from the ectopic eye penetrated the medulla and invariably established a tract in the dorsolateral white matter of the ipsilateral spinal cord. In response to visual stimulation of the transplanted eye, extracellular recordings with metal microelectrodes were conducted with the spinal cords of post-metamorphic animals. Visual activity in the spinal cord could only be recorded in those experimental animals in which the transplanted optic nerve succeeded in penetrating the medulla. This activity was frequently encountered in the gray matter of the cord well below the dorsolateral position of the transplanted optic tract. The discharge characteristics and adaptation properties of the visual activity were often similar to that of optic nerve fibers from normal eyes suggesting that axons or their collaterals branch off from the transplanted optic tract and arborize within the spinal cord. However, occassionally stimulation of the transplanted eye evoked activity with adaptation and/or response characteristics unlike that of normal optic nerve fibers. Visual activity in the spincal cords of our experimental animals could be driven by moving small dark objects within circumscribed regions in the visual field of the transplanted eye. However we were unable to find any evidene of a systematic mapping of the transplanted retina within these abnormally penetrated spinal cords.


Deficient passive and one-way active avoidance acquisition following medial forebrain bundle lesions in rats. Cathodal electrolytic lesions of the medial forebrain bundle (MFB) at posterior hypothalamic levels in male hooded rats produced a mild, transient hypodipsia and lowered jump thresholds to footshock. The lesions produced marked deficits in passive avoidance performance in a paradigm that paired discrete, linearly incrementing footshock intensities with contact of a water spout following 48 hr of water deprivation. Intraperitoneal injections of DL-5-hydroxytryptophan (75 mg/kg), the immediate metabolic precursor of serotonin, had no effect on the passive avoidance performance of either experimental or operated control subjects. Lesions of the MFB also resulted in deficient acquisition in a one-trial step-through passive avoidance paradigm not using motivation to drink and caused a severe acquisition deficit in a one-way active avoidance task. Lesions of the septal nuclei produced lowered jump thresholds but did not affect acquisition in the first passive avoidance task. The results are interpreted as indicating a lesion-induced deficiency in fear learning, independent of the serotonergic functions of the MFB.


Characterization of T and B antigen-binding cells for beta-galactosidase. III. Independence of antigen-binding cells in normal animals from antigenic stimulation. Antigen-binding cells to beta-galactosidase were enumerated in thymus and spleen of mice of different ages and found to remain at a constant frequency throughout life. Thymic beta-galactosidase-binding cells (ZBCs),6 representing T-binding cells, showed no appreciable fluctuation, whereas splenic ZBCs, a mixture of T- and B-binding cells, were slightly depressed at birth but found at normal frequencies by 1 week of age. In addition, germfree mice, both within the 1st week after birth and after maturity, had nearly as many binding cells as did conventionally reared age-matched mice. These results considered together suggest that the ability of cells of both T and B origin to  recognize antigen, as revealed by their ability to bind beta-galactosidase, arise independently of specific or nonspecific antigenic stimulation, as part of the normal ontogenic sequence of steps of differentiation. This is consistent with the theory of clonal precommitment of T and B cells.


Genetic control of the immune response in rats to the known sequential polypeptide (Tyr-Glu-Ala-Gly)n. I. Antibody responses. In inbred rats, the antibody response to the known sequential polypeptide (Tyr-Glu-Ala-Gly)n (T-G-A-Gly)n is under the control of two independently assorting loci; (co) dominant, Ag-B-linked Ir-(T-G-A-Gly) I, controlling qualitative responsivenss, and a non-Ag-B-linked modifier locus termed Ir-(T-G-A-Gly) II, controlling the level of antibody produced. The antibody response to (T-G-A-Gly)n was solely IgG and the level of antibody produced was dependent upon Ir-(T-G-A-Gly) II for phenotypic response type.


Differences in the age-dependent release of a low molecular weight suppressor (LMWS) and stimulators by normal and nzb/w lymphoid organs. The age-dependent release of soluble suppressors and stimulators of DNA synthesis by cultured thymocytes and spleen cells from C57BL/6 and BALB/c mice was compared with their release by NZB/W lymphoid organs. Spleen cells from the normal strains released high levels of suppressor early in life and gradually decresing quantities with age, NZB/W spleen cells exhibited an early deficiency followed by a later excess in the production of suppressor. These differences were quantitated by dose-response studies. Thymocytes from the normal strains released stimulatory factors throughout life. In contrast, NZB/W thymocytes stopped releasing stimulatory activity and began to produce suppressor after 2 1/2 to 4 months of life. This abnormal elaboration of suppressor by thymocytes occurred 2 months before its reappearance in the autologous spleen cell supernatant. Both the early and late-appearing (less than 1000). This activity was designed as low molecular weight suppressor (LMWS). Its aberrant production by their reported functional immunologic abnormalities. The following items were discussed: the production of LMWS by adherent spleen cells, its relationship to previously described regulators, its partial purification and initial chemical characterization, and exclusion of the naturally occurring inhibitors of lymphocyte activation, cortisol, corticosterone, cold thymidine, and cyclic AMP as the active molecule.


A galactose-inhibitable mitogen for human lymphocytes from the sponge axinella polypoides. Of two galactose-binding hemagglutinins isolated from the sponge Axinella polypoides, axinella I was strongly mitogenic for human peripheral blood lymphocytes, and axinella II was not. Purified T cells responded strongly and B cells weakly to axinella I. Mitogenic response, as monitored by rate of 3H-thymidine incorporation on the third day of culture, was specifically inhibited by Dgalactose, Dfucose, raffinose, or 2-deoxy-D-galactose added within 5 hr of the mitogen. Mitogenic response was correlated with degree of lymphocyte agglutination. The effectiveness of a given sugar in inhibiting mitogenic response to axinella I paralleled its potency in inhibiting precipitation of lectin by blood group substances. If an inhibitory concentration of Dgalactose was add 24 to 40 hr after mitogenic activation, rate of 3H-thymadine uptake at 72 hr was two to twenty times above the rate induced in cultures to which no galactose was added. Dgalactose at a subinhibitory concentration (10mug/ml) enhanced 3H-thymidine incorportion incorporation induced by phytohemagglutinin or Con A, an effect reversible by Dgalactose. These findings suggest that axinella I has tow antagonistic effects on human lymphocytes: a) mitogenic activation and b) depressive activity resulting from depletion of essential galactose moieties.


Functional heterogeneity among the T-derived lymphocytes of the mouse. V. Response kinetics of peripheral T cell subpopulations. The kinetics of the proliferative response and the appearance of effectors of helper activity after stimulation by antigen were examined in T cell subpopulations. As defined in previous papers of this series, one population, T1, is short-lived after adult thymectomy (ATx), and relatively resistant to elimination by anti-thymocyte serum (ATS). Another population, T2, is long-lived after ATx, but highly sensitive to elimination by small doses of ATS. From precursors within the T2 population, effectors of specific helper activity, after priming with antigen, appeared within 1 to 2 days and reached a maximum on day 4. The responding cells reached their peak proliferative response within 24 hr after stimulation by antigen. In contrast, helper activity arising from T1 precursors first appeared on day 3 and peaked on day 5. These cells did not reach their maximal proliferative response until 60 hr after priming. These findings indicate additional useful markers for distinguishing the T1 and T2 subpopulations and are consistent with models for T cell development in which T1 cells are virgin cells and T2 cells are memory cells.


Maturation of b lymphocytes in rates. III. Two subpopulations of memory B cells in the thoracic duct lymph differ by size, turnover rate, and surface immunoglobulin. We examined the ability of large and small thoracic duct cells obtained from Lewis rats primed to DNP to restore the adoptive secondary anti-DNP response in irradiated syngeneic hosts given an excess of T helper cells. The large cells were four to five times more active on a per cell basis than were the small cells. However, the large cells constitute only 7 to 8% of the thoracic duct cells and, therefore, make a minor contribution to the restorative activity of the unfractionated cells. Pretreatment of thoracic duct cell donors with high specific activity 3H-TdR for 48 hr before cannulation markedly reduced the memory B cell activity of the large cells, but had little effect on that of small cells. In addition, the activity of the large cells diminished with time after primary immunization, but that of the small cells remained stable. Immunofluorescent staining of the large and small cells for surface IgM and IgG, and subsequent sorting on the fluorescence-activated cell sorter (FA CS), showed that surface IgM was present on large memory B cells, and that IgG was present on small memory B cells. The experimental results suggest that two subpopulations of memory B cells in the thoracic duct lymph differ by size, rate of turnover, persistence after primary immunization, and class of surface IgG.


Quantitative analysis of the proliferative activity induced in murine thymocytes by concanavalin A. A quantitative analysis of the proliferative response induced in murine thymocytes by concanavalin A (Con A) is described. Exogenous 3H-thymidine labels 35 to 40% of the newly incorporated TMP residues under optimal conditions. The density label 5-bromo-2-deoxuridine (BrUdR) does not affect DNA metabolism in this system. With this nucleoside, it is shown that newly synthesized DNA is the result of semi-conservative replication, not repair. Double labeling of DNA provides a monitor for cells traversing the cell cycle (S phase to subsequent S phase). The average cycle time is 12.5 hr, and the shortest cell cycle time is 10 hr. The growing fraction of active cells is about two-thirds. The data show that different subpopulations of thymocytes begin proliferating after various times in culture. Once effectively stimulated by Con A, some of the cells can traverse the cell cycle at least twice more after the mitogen is removed.


Proliferation of murine thymic lymphocytes in vitro is mediated by the concanavalin A-induced release of a lymphokine (costimulator). Mitogen-induced proliferation of lymphocytes may in theory result directly from the interaction of mitogen with the cells, or indirectly as a result of the mitogen-stimulated release of lymphokines. In the case of murine thymic lymphocytes exposed to concanavalin A (Con A) in tissue culture, we have determined that mitogenesis depends upon a lymphokine. Interaction of the thymic lymphocytes with lectin is necessary, but not sufficient, for mitogenesis. A lymphokine, or costimulator for mitogenesis, is released by normal spleen or thymus cells during the first 16 hr of their exposure to Con A, and in the presence of a phytomitogen it stimulates thymic mitogenesis. Under conditions of low costimulator levels, no mitogenesis follows the interaction of Con A with cells. The response of adult CBA/J mouse thymocytes to phytohemagglutinin (PHA) is very low, compared to their response to Con A. When costimulator is added to PHA, the cells respond as well as they do to Con A. Costimulator does not act through Con A-binding sites on thymus cells. Its production is dependent on both cells carrying omega surface antigen (T lymphocytes) and adherent cells of the macrophage-monocyte series. The adherent population, but not the T cells, may be heavily irradiated without affecting production of costimulator. Costimulator is not a mitogen on its own.


The role of macrophages in thymocyte mitogenesis. The thymic lymphocytes of CBA/J mice respond to the mitogen Concanavalin A (Con A) only in the presence of adherent cells of the monocyte-macrophage series. Depletion of adherent cells abrogates the response, and macrophage-rich population of cells restore it. The need for macrophages and mitogen is completely provided by irradiated splenic macrophages which have been exposed to Con A and washed free of the soluble mitogen. The mitogenmacrophage effect in this case is apparently not due to soluble factors. Even more striking than the effect of macrophages on fresh cultures of thymic lymphocytes is their ability to restimulate quiescent cells 72 hr after their first stimulation with Con A. The quiescent cells respond immediately and quantitatively to Con A in the presence of fresh macrophages. This stimulation, like that of fresh thymocytes, is also controlled by a lymphokine ("costimulator") produced by mixing macrophages, mitogen, ant T lymphocytes. Our data suggest a model in which two signals are required for mitogenesis. First, the interaction of macrophage, T cell, and mitogen elicits a soluble costimulator, which is itself not mitogenic. Secondly, in the presence of costimulator, the mitogen (either soluble, or, more efficiently, bound to macrophages) induces a proliferative response in the T cell.


Reversal of cell surface abnormalities of T lymphocytes in hodgkin's disease after in vitro incubation in fetal sera. The capacity of periphal blood lymphocytes from patients with untreated Hodgkin's disease to form E rosettes with sheep erythrocytes and to respond in vitro to PHA stimulation were found to be profoundly impaired. In 49% of the patients, the percentage of E rosette-forming cells (E-RFC) was more than two standard deviations below the mean for normal donors. Overnight incubation of the peripheral blood lymhocytes from these patients in culture media containing 20% fetal calf serum was followed by restoration of the percentage of E-RFC up to normal levels. Similar results have been observed after incubation in fetal human serum, but not in adult human AB serum or adult bovine serum. Incubation of peripheral blood lymphocytes from untreated patients in20% fetal calf serum also resulted in a remarkable restoration of their capacity to respond normally to PHA. Possible mechanisms involved in these reversible cell surface and in vitro lymphocyte function abnormalities in Hodgkin's disease are discussed.


An improved technique for obtaining E rosettes with human lymphocytes and its use for B cell purification. The standard E rosette method and two previously described methods claimed to give improved E rosetting for enumeration of human T lymphocytes have been compared with respect to the speed of rosette formation, and the mechanical stability of the rosettes formed. Following rosette formation with the three methods, the lymphocyte-erythrocyte suspensions were sedimented on Ficoll-Isopaque to deplete them of rosette-forming cells and red cells. The purified lymphocyte preparations were tested for B and T cell markers to determine the degree of contamination with T cells. One of the improved rosetting methods was clearly better than the others, and led to the recovery of B lymphocytes with a contamination of only 2.0+/-1.9 per cent of T lymphocytes.


Role of karyoplasm in the emergence of capacity of egg cytoplasm to induce DNA synthesis in transplanted sperm nuclei. The behaviour of sperm nuclei was studied both in the cytoplasm of intact toad oocytes undergoing maturation and the cytoplasm of oocytes matured without germinal vesicles. The behaviour of the nuclei of pronase-treated sperm injected in the mature egg cytoplasm was shown to be exactly similar to that of the sperm nucleus after fertilization, i.e. they swelled, synthesized DNA, and divided. No changes in such sperm nuclei could be detected in the cytoplasm of the oocytes matured without germinal vesicles.


Control of B-lymphocyte function. I. Inactivation of mitogenesis by interactions with surface immunoglobulin and Fc-receptor molecules. Mouse spleen cells were incubated with anti-Ig antibodies for 1 h, washed, exposed to LPS for 1 h, washed, and their DNA synthetic responses assayed 2 days later. It was shown that the 1-h incubation with anti-Ig antibodies produced a profound, internal, and long lasting state of inactivation in the B cells. Experiments with anti-Ig fragments and other ligands showed that the inactivation occurred optimally when both surface Ig molecules and Fc receptors were bound simultaneously. The role of the classical capping and clearing cycle was also investigated. It was shown that capping and clearing were neither necessary nor sufficient for the inactivation to occur, and that the signals, but only secondarily the ligands themselves, were transmitted across the membrane. Capping and clearing were viewed as a natural regulatory mechanism by which the B cell attempts to clear its membrane of perturbations and signals from the exterior.


Inhibition of the development of the cellular slime mould Dictyostelium discoideum by omega-aminocarboxylic acids. Four omega-aminocarboxylic acids - epsilon-aminocaproic acid (EACA), trans-4-aminomethylcyclohexane-1-carboxylic acid (t-AMCHA), p-aminomethylbenzoic acid (PAMBA) and omega-aminocaprylic acid (OACA) -- prevented fruiting body formation of the cellular slime mould Dictyostelium discoideum. At concentrations of 40 mM, 75 mM, 10 mM and 5 mM, respectively, they allowed aggregation but prevented all further development at 24 degrees C. At lower concentrations, EACA allowed fruiting body formation but with a reduced number of spores per fruiting body. Only t-AMCHA had a significant inhibitory effect on the growth of myxamoebae. EACA affected development only if it was present between 8 and 16 h after the cells were deposited on the filters. Its effect was enhanced by high salt concentrations and by higher temperature, and was also dependent on the manner in which the cells were grown. Only strains capable of axenic growth displayed this sensitivity to EACA, although strains carrying only one of the genetic markers for axenic growth (axe A) were partially sensitive.


The effect of epsilon-aminocaproic acid on biochemical changes in the development of the cellular slime mould Dictyostelium discoideum. epsilon-Aminocaproic acid (EACA) inhibited the development of Dictyostelium discoideum strain AX2 after the aggregation stage. Biochemical changes that occurred early in development (loss of cellular protein, RNA and carbohydrate; increase in the specific activity of N-acetylglucosaminidase, alpha-mannosidase, threonine deaminase and leucine aminopeptidase) were not affected by concentrations of EACA which blocked development; but biochemical changes that occurred later (synthesis of carbohydrate, increase in the specific activity of UDP-glucose pyrophosphorylase)  were inhibited. Spores from fruiting bodies formed in the presence of low concentrations of EACA were larger, more spherical and less able to survive heat treatment than spores from fruiting bodies of control (no EACA) cells.


Psychopathology observed on follow-up after coronary bypass surgery. Forty-six of 51 coronary bypass patients whose inhospital postoperative adjustment was reported earlier, were studied about 18 months postoperatively. In addition, 32 of 46 cardiac valvular surgery patients were seen as a comparison group. The incidence of postoperative psychiatric symptoms observed in the hospital, eight of 51 (16 per cent), and on follow-up, seven of 46 (15 per cent), was very similar; however, the patients who had these psychiatric symptoms comprised two almost entirely different groups. There were no indications that patients who developed psychiatric symptoms in the immediate postoperative period than patients asymptomatic postoperatively. There was a significant relationship between preoperative psychiatric illness and symptoms in the follow-up period.


The role of intraneuronal amine levels in the feedback control of dopamine, noradrenaline and 5-hydroxytryptamine synthesis in rat brain. The influence of varying brain levels of dopamine, noradrenaline and 5-HT on their respective synthesis rates has been investigated. The first step in monoamine synthesis was studied in vivo by measuring the accumulation of dopa and 5-hydroxytryptophan after inhibition of the aromatic L-amino acid decarboxylase. Variations in monoamine levels were obtained by combined treatment with inhibitors of the decarboxylase (NSD 1015 or Ro 4-4602) and of monoamine oxidase (pargyline). An increase in monoamine levels by pargyline was found to inhibit the synthesis of dopamine, noradrenaline and 5-HT. Conversely, a decrease in monoamine levels induced by the decarboxylase inhibitor Ro 4-4602 appeared to stimulate dopamine and noradrenaline synthesis but had no effect on 5-HT synthesis. The influence of varying levels of dopamine and noradrenaline on the synthesis of these amines could still be demonstrated after blockade of dopamine receptos and of alpha-adrenergic (noradrenaline) receptors by haloperidol, suggesting that the mechanism involved in this feedback control is mediated via end-product inhibition of tyrosine hydroxylase. On the other hand, the stimulating influence of haloperidol on the synthesis of catecholamines does not seem to be directly related to changes in catecholamine levels. It is concluded that the short-term control of catecholamine synthesis presumably involves two independent feedback mechanisms, one intraneuronal mechanism operating via end-product inhibition, and one synaptic mechanism mediated via dopamine and noradrenaline receptors, respectively. Both pre- and postsynaptic receptors may be involved in the latter mechanism.


[Embryonic pineal organ of Lacerta vivipara J. II. Electron microscopic study of 3H-5-hydroxytryptophan (3H-5-HTP) incorporation in the secretory rudimentary photoreceptor cells (SRP). The gradient of biochemical differentiation (author's transl)]. As the biosynthesis of indoleamines in Lacerta vivipara embryos from stage 36 to 40 is concerned, our ultrastructural radioautographic studies reveal a selective incorporation and metabolism of 3H-5-HTP in one of the two "sensory" cell types, the Secretory Rudimentary Photoreceptor cells (SRP). Specific radioautographic reactions are constantly for the most part located on the dense secretory granules which are stored in the basal processes of the SRP and originate in the Golgi complex. During ontogenesis, the amount of autoradiographically demonstrable tritiated indoleamines and the number of dense secretory granules increase at the same rate. The combination of electron microscopic and radioautographic studies shows that, during ontogenesis, a close relation exists between the cytological differentiation of the SRP and their capacity to synthesize and store indoleamines.


Measurements of stiffness of extraocular muscles of the rabbit. 1. The stiffness of the eye and the extraocular muscles of the conscious rabbit was measured and compared with similar measurements made on human subjects. 2. The extraocular muscles of the rabbit developed less than 0.5 g at optimal isometric length when the contralateral eye was in "primary position". Deviations of the eye of the rabbit from primary position were accomplished by an increase in force of the agonist muscle with only a nominal decrease in force in the antagonist. 3. With all muscles attached to the globe, the stiffness of the eye for displacements of up to 35 degrees from primary position was 0.11 +/- 0.03 g/deg. 4. The stiffness of the human eye to lateral rotations was 1.09 +/- 0.24 g/deg. Hence, identical disturbances in force would cause deviations in the position of the eye of the rabbit which are nearly an order of magnitude greater than those of man. 5. The stiffness of the extraocular muscles of the rabbit was sensitive to levels of muscle activation produced either by indirect electrical stimulation or by the vestibuloocular reflex. 6. The implications of these findings for the development of eye position control in animals with good binocular vision are discussed.


Correlation of light-induced changes in retinal extracellular potassium concentration with c-wave of the electroretinogram. 1. Double-barrel, potassium-specific microelectrodes have been used to measure light-induced transient changes in [K+]o in the frog eye cup preparation. These changes in [K+]o have been termed the potassioretinogram (KRG). 2. The KRG consists of two components: a rapid increase in [K+]o in the proximal retina and a slow decrease in [K+]o in the distal retina. 3. The KRG decrease has the rhodopsin action spectrum, is maximal in the photoreceptor layer, persists after aspartate treatment, and has an increment threshold curve which saturates at moderate background intensities. The rhodopsin rods are, therefore, most likely the only neurons which generate this ionic change, although the Müller (glial) cells may also be involved in this process. 4. The KRG decrease has the same time course as the c-wave of the electroretinogram for all variations in the stimulus parameters, including intensity, duration, and chromaticity. 5. It is suggested that the c-wave may be produced by the pigment epithelial cells as they hyperpolarize in response to the decrease in [K+]o around the photoreceptors.


Adaptive gain control of vestibuloocular reflex by the cerebellum. 1. The gain of the vestibuloocular reflex (slow-phase eye velocity/head velocity) was measured in 17 adult cats. 2. The gain of the reflex, in the dark, was 0.90 (+/-0.15 SD) over the frequency range 0.03-1.2 Hz. 3. In the range 0.01-0.15 Hz, the phase behaved as though the overall reflex time constant were 12 s or greater. The cupula time constant is 4 s. Therefore, the central part of the reflex must manipulate the canal signal to improve its low-frequency response by a factor of at least three. 4. When the cats wore left-right reversing prisms chronically and were also rotated for 2 h every day, the reflex underwent large, plastic changes. The gain, tested in the dark, decreased by 93% at 0.05 Hz and 55% at 1.2 Hz. In effect, the low-frequency response was abolished. The process took about 8 days. 5. In the light, with reversed vision, the gain decreased further and, at low frequencies, the eye movements did reverse in direction. 6. When the vestibulocerebellum was removed, the gain, in the dark, rose to about 1.17 and the plastic changes caused by reversing prisms were completely abolished. 7. Reversing prisms create vestibuloocular dysmetria. The change in gain they produce is considered to be an adaptive response designed to reduce image motion on the retina during head movements. The vestibulocerebellum is necessary for this adaptive process. It is proposed that detecting and repairing dysmetria (of natural origin) is an important cerebellar function.


Peripheral nerve stimulation in the treatment of intractable pain. Peripheral nerve stimulating devices were implanted for pain control in 33 patients with a variety of disabling chronic pain conditions, which had persisted despite usual medical and surgical therapy. The implants were placed on major nerves innervating the area of the patient's pain. Records were obtained of each patient's stated relief from pain produced by nerve stimulation, along with assessments of narcotic withdrawal, ability to return to work, sleep pattern, and relief from depression. Based on these five criteria 17 patients were judged to be treatment failures, while eight patients had excellent results, and seven had intermediate results. Twelve of the failures were in patients with either low back pain with sciatica, or pain from metastatic disease. The most dramatic successes occurred in patients with peripheral nerve trauma. The incidence of complications has been low, and two patients have used the stimulator for 5 years without adverse effects. Techniques of peripheral stimulator implantation, possible mechanisms of action, and conclusions regarding peripheral nerve stimulation in the treatment of chronic pain are discussed.


Incidence of ampicillin-resistant Hemophilus influenzae in otitis media. Ampicillin resistance in Hemophilus influenzae type b causing serious infections is appreciated, but little is known about ampicillin resistance in nonencapsulated strains causing otitis media. The ampicillin sensitivity of 984 middle-ear isolates of H. influenzae from children in Huntsville, Ala. obtained from 1970-1976, was examined: Nine AmpR isolates were found: one in 1973, two in 1974, three in 1975, and three in the first five months of 1976. Seven strains were nonencapsulated; two were type b. All nine produced beta-lactomase. The incidence of ampicillin resistance in strains causing otitis media increased from 0.6% in 1973 to 2.4% in 1976. AmpR H. influenzae infection should be suspected in situations where ampicillin therapy of otitis media is unsuccessful.


Identification of the pace-maker current in frog atrium. 1. The nature and interactions of the membrane currents underlying induced pace-maker activity in frog atrial muscle have been investigated using a double sucrose gap technique. 2. The membrane current which controls the speed of the atrial pacemaker depolarization (the pace-maker current, ip), is shown to be an outward current activated within the plateau potential range of a normal action potential. The subsequent deactivation of ip at more negative potentials unmasks the depolarizing action of time-independent inward membrane currents so that a pace-maker potential can result. 3. The deactivation of ip over a limited potential range (between about -30 and -60 mV) can be reliably recorded by switching on the voltage clamp during an induced pace-maker depolarization. 4. Investigation of the time and voltage-dependent behaviour of ip over a much wider potential range is less straightforward. How ip can be separated from other components of outward current present in the decay tails following square voltage clamp depolarizations is described. 5. The majority of such current decay tails contain three components of outward current. It appears that two of these components, one of which is ip, are true Hodgkin-Huxley conductance systems chiefly carrying potassium ions. 6. The nature of the third current, which decays very slowly at moderate membrane potentials (about -40 mV), is discussed and reasons are briefly given for considering it to result from the accumulation of potassium ions in extracellular spaces. Preliminary evidence that potassium depletion occurs at potentials negative to the resting potential of the trabeculum is also presented. 7. Because of the obvious complexities involved, a quantitative analysis of the atrial outward currents is not attempted here but forms the subject of a following paper (Brown, Clark & Noble, 1976a).


Analysis of pace-maker and repolarization currents in frog atrial muscle. 1. A quantitative analysis of the time-dependent component of outward membrane current in atrial wall trabeculae from Rana catesbeiana and Rana ridibunda has been carried out using a double sucrose gap technique. 2. Separation of the different components of delayed outward current was hampered by the sigmoid onset of one of the outward current systems ixfast and by the development of potassium ion accumulation which prevented current activation from reaching a steady state at positive membrane potentials. Semilogarithmic analysis of positive current decay tails recorded immediately following square voltage clamp depolarizations was therefore used to separate the two membrane conductance components ixfast and ixslow and the third component, attributable to potassium ion accumulation, which was almost invariably present in the tails. 3. It is shown that inaccuracies in this method of semilogarithmic separation of components caused by visual assessment of the i3 (accumulation) line are minor compared with the large changes in the time constants of ixfast and more especially of ixslow which would result from ignoring the potassium accumulation component. 4. Such semilogarithmic separation of the three components of outward current gave separate activation curves for each of the two membrane conductance components, ixfast and ixslow. 5. Measurement of 'total' activation curves in which all components of outward current were represented could be made more easily and fairly reliably. The position and shape of these activation curves on the voltage axis were found to closely resemble those obtained by three component separation. It is therefore suggested that such a simplified analysis reflects the properties of the individual currents sufficiently well for it to be of use in preliminary studies of, for example, drug action. 6. The kinetic properties of the atrial outward currents have been investigated over a wide potential range. Because of the presence of potassium ion accumulation, an indirect method of obtaining the average value of 1/gamma for outward current decay at negative potentials had to be employed. 7. It is shown that some degree of inward-going rectification is associated with the outward current systems of frog atrium. 8. The possible reasons for the differences between the analysis presented here and those presented earlier by us (Brown & Noble, 1969a, b) and by Ojeda & Rougier (1974) are discussed.


Potassium accumulation and depletion in frog atrial muscle. 1. In atrial wall trabeculae of Rana catesbeiana and R. ridibunda very slowly decaying membrane currents have been consistently observed in decay tails following voltage clamp depolarizing and hyperpolarizing pulses. It is not thought that these currents are carried by time-dependent conductance channels but rather result from potassium ion accumulation or depletion. 2. Since voltage clamp techniques generally impose a non-physiological situation on the membranes of excitable cells, evidence that potassium ion accumulation occurs in unclamped atrial tissue is presented. 3. When potassium ions accumulate, the reversal potentials for both atrial delayed conductance mechanisms, ixfast and ixslow, should be shifted in a positive direction, the magnitude of the shifts being a function of the charge transferred during depolarization. Experiments have been performed to test this prediction quantitatively, and as a result, a simple accumulation model is developed. 4. A second important effect of accumulation should be upon the time-independent potassium conductance, iK1. It was found that this effect produces current tails whose decay becomes exponential when the amount of accumulation is small. The time constant of this exponential is shown to be equal to the time constant of decay of accumulation, tauacc. 5. One of the most important assumptions in the accumulation model is that the iK1(Em) relations for different values of [K]O 'cross-over' one another as they do in skeletal muscle and mammalian Purkinje tissue. Experimental verification of this assumption is presented. This 'cross-over' effect allows current changes due to accumulation to show an apparent 'reversal potential' and so to appear like a conductance mechanism. 6. Potassium depletion is shown to occur during hyperpolarizing pulses. This depletion process must be allowed for in a direct kinetic analysis of the pace-maker current, ixslow, at potentials negative to the resting potential (ER).


The influence of non-uniformity on the analysis of potassium currents in heart muscle. 1. A method is described for determining the space constant gamma of heart muscle strips using a sucrose gap technique. 2. The average value of gamma for frog atrial trabeculae was found to be nearly 700 mum. This value is nearly twice the length of the test gap (400 mum). Near the resting potential, the voltage non-uniformity should be about 10%. This was confirmed experimentally by comparing the membrane voltages recorded across the current-passing and voltage-recording sucrose gaps. 3. The non-uniformity during large depolarizations was calculated using a computer model. This model includes the inward-going rectification displayed by iK1 and the delayed rectification that occurs following depolarizations beyond -40mV. A single component of delayed rectification was included. 4. It is shown that even very large non-uniformities have relatively small effects on the shape of the activation curve and on the time course of onset or decay of current. 5. It is comcluded that the fast component of current decay described in a previous paper (Brown, Clark & Noble, 1976b) is not attributable to a non-uniformity artifact.


Noise analysis of drug induced voltage clamp currents in denervated frog muscle fibres. 1. Voltage clamp currents were recorded during iontophoretic application of steady doses of acetylcholine (ACh), carbachol or suberyldicholine to hyperpersensitive extrasynaptic regions of chronically denervated frog muscle fibers. Autocorrelation functions of drug induced current fluctuations were calculated and estimates of conductance gamma and average open time tau of the extrasynaptic ion channels were derived. 2. The average open time of an extrajunctional channel induced by acetylcholine is tauACh = 11 +/- 1-6 msec (+/- S.E.) at -80 mV and 8 degrees C. Carbachol and suberyldicholine open channels of tauCarb = 3-9 +/- 0-4 msec and tauSubCh = 19 +/- 2-5 msec (+/- S.E.) duration under the same conditions. The average open time of the extrasynaptic channel produced by each drug is three to five times longer than the value found for junctional channels in normal fibres. 3. The average open time of the extrajunctional channel is dependent on temperature and membrane potential. Lowering the temperature or increasing the membrane potential increases the average open time of the channels induced by any one of the drugs. 4. The conductance of a single extrajunctional channel opened by the action of acetylcholine is estimated to be gammaextra = 15 +/- 1-8 pmho (+/- S.E.). This is somewhat lower than the value of gammaep = 23 +/- 2 pmho (+/- S.E.) found for the conductance of a single open channel in the junctional membrane of normal fibres. The extrasynaptic channels opened by the action of carbachol and suberyldicholine have similar conductances to those produced by ACh. 5. The autocorrelation function of drug-induced current fluctuations, recorded at the former end-plate region of chronically denervated fibres often shows both a fast and a slow time constant. They correspond in value to the time constant of the autocorrelation function obtained from end-plate currents in normal fibres and from extrasynaptic currents in denervated fibres respectively. This could indicate that two populations of channels exist at the former end-plate region of denervated muscle fibres.


Osmotic reflextion coefficients of capillary walls to low molecular weight hydrophilic solutes measured in single perfused capillaries of the frog mesentery. 1. Individual capillaries of the transilluminated frog mesentery have been perfused with suspensions of human red cells in frog Ringer solution containing 1-0 g albumin 100 ml.-1. The outer surface of the mesentery has been washed with normal frog Ringer solution and with frog Ringer solutions made hypertonic by addition of one of the following solutes: sodium chloride (100 m-mole. 1.-1); urea (100 m-mole.1.-1); sucrose (20-50 m-mole. 1.-1); cyanocobalamin (8-5 m-mole. 1.-1). The temperature of the mesentery was between 14 and 16 degrees C in all experiments. 2. Wtih the mesentery superfused with normal Ringer, the filtration coefficient was determined from measurements of the rate of fluid filtration across the capillary wall, at a series of known capillary pressures (Michel, Mason, Curry & Tooke, 1974). Filtration coefficient varied from 0-69 X 10(-3) to 4-45 X 10(-3) mum. sec-1 .cm H2O-1 with an average value of 1-87 X 10(-3) mum. sec-1. cm H2O-1. 3. When the superfusate was made hypertonic by the addition of a test solute, the osmotic reflextion coefficient (sigma) of the capillary wall to test solute was calculated from the additional rate of filtration, the concentration of test solute in the superfusate and the filtration coefficient. Average values for sigma were: sodium chloride, 0-068 +/- 0-03 (three capillaries); urea, 0-071 +/- 0.015 (four capillaries); sucrose, 0-115 +/- 0-023 (seven capillaries); cyanocobalamin, 0-100 +/- 0-03 (three capillaries). 4. In further experiments, the osmotic reflextion coefficients to sodium chloride, urea and sucrose were determined in the same capillary. Five technically acceptable experiments were carried out. Although there were differences in the value of sigma between different capillaries, in any one capillary values of sigma were of the same magnitude and there appeared to be no significant trend with the molecular size of the test solute. 5. Our findings are inconsistent with the hypothesis that there is a single pathway for water and small hydrophilic molecules across the capillary wall. 6. Our results may be interpreted in terms of an exclusive channel for water in parallel with a channel shared by both water and small hydrophilic molecules. It is suggested that the exclusive water channel may be the membranes and cytoplasm of the endothelial cells and the shared channel may be located in the intercellular junctions. 7. Our data suggest the exclusive water channel represents about 10% of the total filtration coefficient in frog mesenteric capillaries. The shared channel shows relatively little restriction to the molecules investigated. Estimates of the volume flow throught the two channels are made for conditions where hydrostatic pressure differences and osmotic pressure differences are the driving forces.


Pulmonary dysfunction in systemic lupus erythematosus without pulmonary symptoms. Pulmonary function was measured in a group of 28 patients with systemic lupus erythematosus (SLE) who were free of pulmonary involvement at the time of the study. When compared with age and sex matched controls, the SLE patients had a pattern of restriction with reduced lung volumes and vital capacity. Diffusing capacity was reduced in proportion to the reduction in lung volume. This is felt to be most compatible with inapparent pleural thickening resulting in impaired lung expansion. There was no evidence of airway obstruction on maximal expiratory flow-volume curves. The effect of cigarette smoking in the SLE patients was a reduction in flows at low lung volumes, which was indistinguishable from the effects in the control smokers. Both SLE and control smokers had a significant reduction in DL/VA when compared with control nonsmokers. Pulmonary function was not influenced by the presence of renal disease.


The insensitivity of frog heart rate to pulse modulated microwave energy. Frey and Seifert (1968) have reported that pulse modulated microwave irradiation of low average energy density can produce tachycardia in isolated frog hearts. In an effort to examine this phenomenon, two types of experiments were carried out: 1. frog hearts were irradiated in situ with 100 mus bursts of microwave energy at either 10.0 GHz or 1.42 GHz; 2. isolated frog hearts were irradiated with 100 mus bursts of microwave energy at 1.42 GHz. No significant changes in heart rate were observed.


T- and B-lymphocytes in chronic lymphocytic leukemia: correlation with clinical and immunologic status of the disease. T- and B-lymphocyte count were correlated with clinical and immunologic status of 59 patients with chronic lymphocytic leukemia. The mean total T-cell count was slightly lower than normal in patients in complete remission, within normal limits in those in partial remission, and significantly higher in those with active disease. The mean total B-cell count, however, was slightly elevated in patients in complete remission and those in partial remission, and markedly elevated in those with active disease. The T-cell count correlated well with the duration of disease in patients in remission: The mean count was within normal range in those patients with disease of less than 3 years, whereas for those patients with disease of 3-12 years, a significant reduction was observed. The T-cell count was well correlated with the status of skin test response of patients with either complete or partial remission; the B-cell count did not correlate with immunoglobulin levels in patients with this disease.


Use of a restriction endonuclease in analyzing the genomes from two different strains of vaccinia virus. A restriction endonuclease from Haemophilus influenzae (Hind III) specifically cleaved vaccinia DNA into 14 fragments. The molecular weights of these fragments were determined by gel electrophoresis and ranged from 0.5 x 10(6) to 30 x 10(6). Hind III digestion of the DNA from the WR and CV-1 strains of vaccinia revealed a small molecular difference in one of the resulting fragments. The average molecular weight of the entire vaccinia genome was calculated to be 125 x 10(6).


Influenza viral mRNA contains internal N6-methyladenosine and 5'-terminal 7-methylguanosine in cap structures. Influenza viral complementary RNA (cRNA), i.e., viral mRNA was radioactive when purified from the cytoplasmic fraction of cordycepin-treated canine kidney cells that were incubated with [methyl-3H]methionine during infection. Approximately 55 to 60% of the methyl-3H radioactivity was in internal N6-methyladenosine, a feature distinguishing this mRNA from those viral mRNA's that are known to be synthesized in the cytoplasm. The remaining methyl-3H radioactivity was in 5'-terminal cap structures that consisted of 7-methylguanosine in pyrophosphate linkage to 2'-o-methyladenosine, N6, 2'-O-dimethyladenosine, or 2'-O-methylguanosine. Methylated adenosine was the predominant penultimate nucleoside in caps, suggesting that cRNA synthesis in infected cells initiates preferentially with adenosine at the 5' end. In contrast to cRNA, influenza virion RNA segments extracted from purified virus contained mainly 5'-terminal ppA and no detectable cap structures.


Chronic painless hematuria and urethral bleeding as the presenting manifestations of Osler-Weber-Rendu disease. A case of a young man with profound iron deficiency anemia, chronic painless hematuria and urethral bleeding is presented. He had the typical cutaneous findings of Osler-Weber-Rendu disease (hereditary hemorrhagic telangiectasia). Appropriate urological studies demonstrated bladder and urethral telangiectases, with no other explanation for the bleeding. Osler-Weber-Rendu disease should be considered in the differential diagnosis of chronic painless hematuria.


Endoscopic electrocoagulation of upper gastrointestinal hemorrhage. Endoscopic electrocoagulation was performed on 40 occasions for 38 patients with bleeding gastrointestinal lesions. Cessation of bleeding was achieved in 95%. Fifteen gastric ulcers, 14 duodenal ulcers, six Mallory-Weiss tears, one gastric varix, one hemorrhagic antral gastritis, and one esophageal ulcer were successfully electrocoagulated. Three duodenal and three gastric ulcers rebled. One duodenal ulcer and one gastric ulcer were successfully reelectrocoagulated. Failure to stop bleeding by electrocoagulation occurred in one Mallory-Weiss tear and one duodenal ulcer. There was no morbidity nor mortality attributed to endoscopic electrocoagulation. A retrospective cost analysis showed that the cost of hospitalization was less in patients treated by electrocoagulation. Patients so treated were hospitalized for a shorter duration.


Effects of BCG (Bacillus Calmette-Guérin) vaccines on immune responses in mice. I. Possible effect of BCG on helper T cells. The effects of killed and living BCG on antibody production against hamster erythrocytes (HRBC) and the 2, 4, 6-trinitrophenyl (TNP) group were studied in SL mice. Killed and living BCG, each in doses of 0.008 mg, 0.08 mg, 0.8 mg and 8 mg per mouse, were intravenously inoculated 7 days prior to primary immunization with HRBC. Secondary immunization was carried out 28 days later with TNP-HRBC. Anti-HRBC and anti-TNP antibodies were estimated by a hemagglutination test. The results showed that pretreatment with killed or living BCG enhanced the antibody production against both HRBC and TNP. Comparing the effects of these two BCG preparations, it was noted that killed BCG augmented the anti-HRBC antibody production more effectively than living BCG. In regard to the anti-TNP antibody production, living BCG exhibited a greater augmenting effect than killed BCG. This difference in the modes of action of killed and living BCG was remarkable when two groups given 8 mg of killed and living BCG were compared. In addition, it was shown that living BCG at a dose as high as 8 mg was able to augment the anti-TNP antibody production, even in the absence of preceding immunization with HRBC.


[Preinfarct stenocardia and acute myocardial infarct from the viewpoint of modern coronary surgery]. The results of aorto-coronary shunting in 36 patients with preinfarction angina and of urgent direct myocardial revascularization in 17 patients with acute myocardial infarction are presented. The surgical mortality comprised 28% in the group of patients with preinfarction angina. Twenty-two patients were followed-up for 8 months to 4 years. Good results were obtained in 9 patients, satisfactory--in 7, unsatisfactory--in 4. One patient died of cardiac insufficiency 1 1/2 year after surgery. The diagnosis of preinfarction angina is a direct indication for urgent coronary angiography and aorto-coronary shunting in case suitable coronary arteries are available for anastomosing. The indications for urgent revascularization of the myocardium in cases of infarction included the inefficacy of drug therapy within 2-3 hours of its onset, an unarrested pulmonary oedema and cardiogenic shock in cases of localized proximal occlusion of the coronaries revealed by elective or urgent coronary angiography. Four patients were operated on in the state of cardiogenic shock (one of them after reversing the state of clinical death), and two patients were operated on with pulmonary oedema. All these patients (with the exception of the one with pulmonary oedema) recovered. Four patients died. The follow-up covered a period of 9 months to 3 years. Good results were obtained in 4 patients, satisfactory--in 3, unsatisfactory--in 4. No late mortality cases were observed. The obtained results permit to analyse the preinfarction angina and acute myocardial infarction from the standpoint of modern coronary surgery.


[The phenotype of heterozygotic females in congenital red-green color blindness (author's transl)]. Varying degrees of deficient color perception along the Deutan axis within one family have been studied and presented. All seven family members exhibit manifest color blindness. The question of the phenotype among heterozygotic females is discussed on the basis of the data found by anomaloscope testing and the hue tests of Farnsworth D-15 and Farnsworth 100.


[Aphakia and contact lenses (author's transl)]. Four possibilities are offered to provide a good correction for aphakic individuals: no correction at all; spectacles; more than 60% adopt this solution, the contact lens which has optical, functional and aesthetic advantages. The intra-ocular lens (the best solution, but it is, not without complications). Since 1956 we have followed up 588 unilateral aphakians. Tolerance of contact lenses after one year is excellent: 61% wear the contact lenses 10-12 hrs. per day, 18% wear them 6-8 hrs. per day and 21% lost courage. There is a parallel between binocular vision and tolerance, which decreased over the years. Three factors are determinant here: state of binocular vision: many factors influence the quality of fusion: nature of the cataract, the moment of adaptation of the lens, loss of accommodation and anisoconie. Surrounding conditions e.g. dusty atmosphere also influence the tolerance; local state of the tissues. 15 years later, the situation has changed. 71.5% gave up the contact lenses completely and only 15% wear them 10-12 hrs. per day. The reasons of this abandonment are: diplopie, inflammation and local complications.


[Diagnosis of Pneumocystic carinii pneumonia by lavage of the bronchial system (author's transl)]. This report deals with a 10 year old girl suffering from an acute lymphoblastic leukemia since 1971. The child was hematologically in full remission, when she developed a pneumonia due to pneumocystis carinii. The diagnosis was established by demonstrating the agent in bronchial secretions. The material was obtained by rinsing the bronchial system. The patient was treated with pentamidine and co-trimoxazol (Bactrim) with good success.


[T-cells in thyroid disease (author's transl)]. Thymus-derived peripheral blood lymphocytes were studied in untreated (n = 18), methimazole-treated (n = 28) thyrotoxicosis, after radioiodine (n = 14), in Hashimoto thyroiditis (n = 7) and in euthyroid goiter (n = 7). The results were compared with normal persons (n = 40) without thyroid disease. There was no significant difference in the total and relative counts of T-cells either between the different groups nor compared with the controls. These findings confirm that T-cells in peripheral blood cannot give any information about activity or prognosis of the various thyroid diseases. Thus T-cells give no further suggestion concerning the possible pathogenetic role of cell-mediated-immunity.


Sternal and costochondral infections following open-heart surgery. A review of 2,594 cases. From a series of 2,594 patients undergoing open-heart surgery, 39 had sternal or costochondral infections. Most of these infections were associated with a number of predisposing factors: prolonged perfusion time, excessive postoperative bleeding, depressed cardiac output in the postoperative period, and a history of re-exploration for the control of hemorrhage. One important factor was the use of bilateral internal mammary artery implants. The prognosis for patients with sternal wound infections appears related to the length of time required for institution of treatment and the adequacy of initial therapy. Most of these infections are caused by staphylococcus, although the more complicated infections often are caused by fungus. The prevention of serious sternal infections depends on a combination of proper preoperative preparation, attention to minute details at the time of operation, and recognition of variables predisposing to wound complications.


Preoperative risk factors and aorta-coronary bypass graft patency. The relationship between graft patency and the presence of presurgical prognostic factors was studied in 636 patients who have undergone aorta-coronary bypass operation. We have found a positive correlation between vein graft patency and both coronary artery constriction score (p less than 0.01) and diastolic blood pressure (p less than 0.05). In patients studied up to one year after surgery, high graft patency was associated with both higher diastolic pressures (p less than 0.03) and higher cholesterol levels (p less than 0.001). However, high cholesterol levels also were associated with coronary arterial obstruction. In patients studied more than a year after operation, high constriction scores before the operation were associated with improved graft patency (p less than 0.03). Our findings indicate that short-term prognosis of the grafts is related mainly to hemodynamic variables.


Total pancreatectomy in the treatment of acute necrotising and hemorrhagic pancreatitis. Indications-technique. The place of total pancreatectomy in the treatment of pancreatitis is still not clear: the author is in favour of this operation and gives the indications, surgical technique, complications and results. The operation is indicated in cases of necrosis involving more than 2/3rds of the whole of the head and part of the body of the pancreas. The duodenum and pancreas should be removed in one piece and intestinal continuity should be restored performing choledocho-jejunal and gastro-jejunal anastomoses. It is important to carry out this operation early, between the 3rd and 6th days, treating all areas  of necrosis before the lesions become the site of uncontrollable infection. Seven patients out of 9 are still alive, on the 25th of July 1975; they all have easily controlled diabetes, a low fat diet and are receiving pancreatic extract. We have recently operated a 10th case, and the patient is alive 2 months later.


[Experimental pulmonary edema: pathophysiological mechanism (author's transl)]. Traumaticed tissue or organs show different reactions to oral and parenteral application of watery solutions. Tissue traumaticed or not does incline to edema. 2. In its central position in blood circulation, its capability of water storage and distribution as well in its regulatory function of the cardiac output, the lung is very suitable for transportation of fluid. 3. If physiologic transportation exceeds a maximum (renal and cardiac insufficiency, high temperature, infusion) and if lymphatics are blocked, edema results in the interstitial and intraalveolare space. 4. Fatal edema is prevented during the first 48 h by applicating proteinase inhibitor drug; Trasylol immediatly after trauma. 5. Edema is significantly diminished applicating Benzopyrone (Venalot), as proven biochemically and electromicroscopically. 6. Taking the findings, it is necessary to considerate a new concept of fluid therapy.


[Reflux esophagitis (author's transl)].

[Reflux esophagitis (author's transl)]. The term "Refluxdisease" consider an esophageal response (either subjective or objective) to injury caused by gastrointestinal contents. Thickening of the basal layer of the esophageal mucosa, reflux esophagitis, endobrachyesophagus, acquired short esophagus and peptic stenosis are different stages of the objective esophageal response. The diagnosis of reflux disease must take account of these findings where appropriated. The various stages of reflux disease can only by recognized and adequately treated following an exact diagnosis that takes into account as may parameters as possible. For this reason fundoplication, which is at present the most effective procedure, should only be performed when the indications are particularly strong.


[Immunological mother-fetus relationship]. The immunology of propagation and growth is a field of medicine which has been developing in the last 3--4 years. On the basis of the literature data on clinical and experimental works from this field the author tries to explain the essence of the immunological mother-fetus relationship. The non-rejection of the fetus as a foreign transplant is made possible by the suppression of the mother's immunologic capacity (cellular and humoral) on the one hand, and the existence of protective mechanisms of the fetus on the other. Dealing in more detail with elements resulting in the reduced immunological reactivity and the increased tolerance of mother towards fetus, the author concludes that this increased tolerance, along with the existence of the intact placental barrier, is the basic factor which allows the survival of the fetus as an allotransplant.


Perioperative myocardial infarction with aortocoronary bypass graft surgery. In 1975, 160 patients underwent aortocoronary bypass graft surgery at St. Vincent's Hospital, Sydney. The incidence of perioperative myocardial infarction varied between 2-5% and 5-6% depending on the criteria used to diagnose pathological Q waves, and thus compared favourably with other reported series. The low incidence suggested that perioperative infarction should be considered as neither a deterrent to coronary bypass surgery nor a significant cause of postoperative relief of angina.


Upper gastrointestinal endoscopy in surgical practice. The use of fiberoptic endoscopy provides an accurate diagnosis in more than 90% of patients with lesions in the oesophagus, stomach and proximal duodenum. It is, however, an expensive and time-consuming investigation and is not always necessary when a satisfactory diagnosis has been made after radiological examination. Groups of patients have now been identified in which endoscopy is of particular value to the surgeon. When there is doubt about the diagnosis after radiological examination, particularly regarding the malignancy of a gastric ulcer, when an upper gastrointestinal haemorrhage occurs, when postgastrectomy patients present with symptoms, and when persistent symptoms occur in the absence of radiological findings, endoscopy is mandatory for an accurate diagnosis to be achieved and rational treatment instituted.


[Experiences with enterally and parenterally applied leucovorin following therapy with high doses of methotrexate in malignant tumors (author's transl)]. 45 patients (43 ovarian carcinoma and 2 chorionepithelioma) were treated with high doses of methotrexate and intramuscularly application of leucovorin according to Mathé et al. In comparison a group of 19 patients (ovarian carcinoma only) was treated with methotrexate and leucovorin-tablets. The toxic effects on leucocytes and platelets were equal in both groups. Due to slightly different doses of leucovorin in both groups an enteral resorption rate of more than 90 p.c. is calculated. Because of the simple way of application the suggested high-dose therapy with methotrexate and leucovorin-tablets seems to be most convenient in the moment.


High dose methotrexate therapy of solid tumors: observations relating to clinical toxicity. In clinical studies performed during 111 infusions of high dose methotrexate (MTX) we have evolved a clinical and laboratory protocol which permits such therapy without prohibitive risk to the patient. The plasma MTX data obtained indicate that pharmacokinetic disposition is dose related during these infusions and that such data are useful in identifying patients at risk from serious toxicity.


[para-Aminobenzoic acid as a sole source of carbon and energy for Pseudomonas desmoliticum]. A strain of Psuedomonas desmoliticum has been isolated from soil. It utilizes, as a source of carbon and energy, p-aminobenozic (PABA), p-fluorobenzoic acids, and some other aromatic compounds. The strain has been isolated by inoculating soil suspensions onto Petri plates with a solid mineral medium containing 0.1% PABA as a carbon source. The preparatory metabolism of PABA was studied in this work; p-hydroxybenzoic and protocatechuic acids were found to be its intermediate products. Enzyme systems catalysing oxidation of aromatic compounds and glucose are inducible.


Effects of various drugs supposed to interact with serotonin on PGO frequency changes induced by reserpine and 5-hydroxytryptophan. Reserpine induced ponto-geniculo-occipital (PGO) spikes in the lateral geniculate nucleus. This was used as a model to evaluate the possible anti-reserpine effects of Org GB 94-1,2,3,4,10,14b-hexahydro-2-methyldibenzo[c,f]pyrazino [1,2-alpha]azepine monohydrochloride-methiothepin, imipramine and atropine. In cats, under local anaesthesia, 3.2 mg/kg of methiothepin (a serotonin antagonist and neuroleptic) increased PGO density while 5-hydroxytryptophan (5-HTP) effects were blocked. A dose of 0.32 mg/kg of imipramine or atropine greatly reduced PGO density while potentiating 5-HTP effects. Org GB 94 had no effect in doses up to 10 mg/kg, where a slight decrease of PGO density was found, while 5-HTP effects were unchanged. At 32 mg/kg, EEG was pronouncedly changed by Org GB 94 but only a short-lasting decrease in PGO density was noted. On the basis of these results it seems improbable that the behavioural effects of Org GB 94 are to be explained by the same mechanism (i.e. serotonin uptake inhibition) as that of imipramine.


Selective and total shunts in the treatment of bleeding varices. A randomized controlled trial. Two types of surgical therapy of bleeding esophageal varices were evaluated in 48 patients by a randomized controlled trial: 24 were randomized for a total shunt and 24 for the selective shunt. In two of the latter, a total shunt had to be performed for technical reasons. The fatality rates (six in the 24 total, and six in 22 selective [performed], and seven in 24 selective [randomized]), the frequency of shunt occlusion (two in each group), and of recurrent gastronintestinal bleeding (three in each group) were similar. Encephalopathy developed more often after a total shunt -- 10 of 24, or one per 58 patient-months -- than after selective (performed) -- one of 22, or one per 593 patient-months (P less than 0.005). Total shunts consistently diverted the hepatopetal mesenteric-portal flow from the liver. Deterioration of hepatic function (maximum rate of urea synthesis) was greater after total than selective shunt (P less than 0.05).


Association of antibodies to ribonucleoprotein and Sm antigens with mixed connective-tissue disease, systematic lupus erythematosus and other rheumatic diseases. Extractable nuclear antigen contains ribo-nuclease-sensitive (ribonucleoprotein) and ribonuclease-resistant (Sm) components. To determine the diagnostic usefulness of antibodies to these antigens, a multicenter study was undertaken in which serums were analyzed for these antibodies and the findings compared with clinical and other laboratory characteristics of the patients. Of 100 patients with hemagglutinating antibodies to ribonuclease-sensitive extractable nuclear antigen, and only the same antibodies by immunodiffusion, 74 per cent had typical features of mixed connective-tissue disease; 12 features of systemic lupus erythematosus, eight those of scleroderma and six an undifferentiated mild connective-tissue disease. Of 27 patients with hemagglutinating antibodies to ribonuclease-resistant extractable nuclear antigen (and Sm antibodies by immunodiffusion), 85 per cent had typical systemic lupus. Thus, antibodies to nuclear ribonucleoprotein and Sm are of diagnostic use; if the serum contains only ribonucleoprotein antibody in high titer, it is likely that the patient has mixed connective-tissue disease.


[Effect of vestibular, somatic and autonomic afferent impulsation on the activity of individual neurons in the nuclei of the cat vestibular complex]. Responses of single vestibular neurons were studied in cats under adequate and electric stimulation of different afferent sources (labyrinths, mixed nerves, n. vagus, n. depressor, limb movements). Different types of responses to the employed stimulation as well as evoked activity as bursts followed by depression of background firing are described. The activity of vestibular neurons is shown to depend on extralabyrinthal stimulation. The role of muscle-joint receptors is distinguished from natural stimulation of the vestibular apparatus during the head tilting. Somatotopic organization of vestibular nuclei and convergence of different afferental impulses to the neurons forming the vestibulospinal tract are discussed.


[A new valve controlled system for ventricular drainage. (Technical description and clinical results)]. A new valve controlled system for continuous ventricular drainage has been described. The clinical experiences (114 patients) are very satisfactory, even after a drainage duration of 15 days. The main advantages of the method are the resistance of all connexions against traction, the fixed position of the ventricular catheter, the variable opening pressure of the valve and the insensitivity to air or gas bubbles, at last the protection of the valve against blood and protein clots by use of filters. We have used the system for the continuous monitoring of the ICP and for diagnostic purposes (ventriculography, examination of cerebrospinal fluid) with good results.


Radiodiagnosis of intracranial pearly tumours with particular reference to the value of computer tomography. The radiological appearances of 22 histologically proven epidermoid and dermoid tumours occurring in four sites are presented - (1) the petrous apex and cerebellopontine angle, (2) the suprasellar region, (3) the cerebral hemispheres and (4) the cerebellum and 4th ventricle. Pathognomonic radiological changes are only uncommonly demonstrated by conventional neuroradiological techniques. Computer assisted tomography employing an EMI scanner has demonstrated diagnostic appearances. The availability of detailed density changes occurring within the tumours together with additional intracranial information makes computer tomography the investigation of choice.


[Spontaneous ventriculostomy developing in non-communicating hydrocephalus of unestablished etiology]. The authors report a case of exceptionally rarely occurring spontaneous ventriculostomy in the region of epiphyseal recess in a patient with increasing non-communicating hydrocephalus. This case is the fourth one diagnosed intravitally in a group of 22 cases published as yet. Positive ventriculography was the method establishing the diagnosis of this condition during life. Restoration of communication in intracranial cerebrospinal pathways with bypassing of the blockade by development of spontaneous ventriculostomy is regarded as a trial of self-treatment of the organism. The observations demonstrated that this bypassing in a group of 22 cases published as yet. Positive ventriculography was the method establishing the diagnosis of this condition during glife. Restoration of comis, in such cases, creation of ventriculo-atrial communication for reduction of intracranial pressure.


Ventriculography with Amipaque.

Ventriculography with Amipaque. Greater diagnostic accuracy of lesions of the third and fourth ventricles and aqueduct has resulted from the use of positive contrast ventriculography with the watersoluble medium Amipaque. The examination is performed more easily than with gas ventriculography and has caused no distress or complication in 47 patients.


Plasma alpha-1-antitrypsin levels in early and late carcinoma of the cervix. Previous studies have demonstrated a rise in serum alpha-1-antitrypsin at advanced stages of malignancy. These, together with results of animal experiments with another anti-proteinase, aprotinin, have prompted studies of the plasma alpha-1-antitrypsin in the early stages of malignancy, using cervical carcinoma as a model. Measurements were made in three groups of individuals; negative cervical-smear women volunteers; hospitalised women with a positive result from the cervical-smear test; hospitalised women with a clinical cervical carcinoma. Elevated plasma alpha-1-antitrypsin levels were found in the "smear-positive" and "cancer" groups. Possible explanations for this increase are discussed and it is concluded that it occurs in direct response to the early stages of development of the tumor. Once a frank carcinoma has developed, maximal response has been attained, regardless of the degree of invasion or metastasis.


Inactin concentration in plasma of rats during anaesthesia and the effect of this concentration on short circuit current of isolated frog skin. Inactin, given to rats for anaesthesia at a dose of 100 mg per kg body weight results in an arterial plasma concentration of 10.6 +/- 1.14 mg%, measured 40 min after the onset of anaesthesia. When similar concentrations of Inactin or Amytal were applied to frog skins the decrease in the in vitro short circuit current is dose dependent. With Inactin, the inhibition was, at least in part, reversible and the electrical conductance was not affected. Amytal however was found to depress SCC and electrical conductance irreversibly. The data are discussed in regard to active renal transport processes.


The intracellular electrical potential profile of the frog skin epithelium. The potential profile of the frog skin epithelium incubated in Cl-Ringer was reinvestigated with improved technique. Under open circuit conditions (PDtr up to 120 mV) the potential profile was demonstrated to be trough like in contrast to the stair-step like potential profile reported by previous investigators which has probably been recorded after injuring of the punctured cells. In 67 successful impalements the potential difference across the basolateral membranes was 108 +/- 2 mV. The potential across the outer, epithelial-facing membrane was inversely related to the transepithelial PD, but was found to be negative (with respect to the epithelial bathing solution) in all punctures. Electrogenic sodium transport might be responsible for part of the potential difference across the basolateral membranes which correlatee directly with the short circuited state was -73 +/- i mV and decreased with increasing short cirucit current. It is suggested that these changes result from variations of the outer membrane sodium conductance.


Ionic mechanism of inotropic effect of prostaglandin E1 on frog atrial muscle. Prostaglandin E1 increases the amplitude and duration of cardiac action potential and exerts a positive inotropic effect on the frog heart. In voltage-clamp experiments, prostaglandin E1 increases both, the slow inward current and the delayed outward as well as the two components of the heart contraction. These results imply that calcium influx and the release of intracellular calcium are involved in the inotropic action of prostaglandin E1.


[Life-threathening tracheal obstruction following intubation in a case of Willebrand-Jürgens disease]. A case of severe dyspnoea is reported which occurred in a 21-years-old woman with Willebrand-Jürgens disease four days after intubation during a dental operation. A 34 Charrière catheter was introduced into the glottis after a 22 Charrière catheter had failed to pass the obstruction. The patient was then artificially ventilated by means of a Spiromat and was subsequently tracheotomized after her cardio-pulmonary condition had become stabilized. The cause of the dyspnoea was a fibrin clot of 5-6 cm length. Three weeks after the tracheotomy and one week after extubation the patient was discharged from hospital in a satisfactory condition. The factors responsible for the development of the fibrin clot are discussed. If there is persistent stridor and aphonia after extubation a laryngologist should be consulted.


Evidence for the lack of feedback regulation of gene activity and for the absence of subunit exchange between lactate dehydrogenase tetramers in vivo. Frog and rat lactate dehydrogenase (LDH, L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) isozymes, highly purfied by affinity chromatography, were injected into newly fertilized from (Rana pipiens) eggs to study the effect of the injected isozymes on the expression of the LDH genes of the developing frog embryo. From these experiments three conclusions can be drawn: (i) homologous and heterologous LDH, even when present in more than twice the normal amount of LDH, does not play any role in the switching on or off of the frog LDH genes or in regulating the level of gene activity. No evidence was found in support of any feedback regulation of LDH synthesis by the LDH molecule itself. (ii) Injected rat LDH is very stable in the frog embryo, and the contrary to what can be demonstrated in vitro, all the isozymes show the same stability. No evidence was found for selective degradation of any of the injected five isozymes. (iii) The fact that the injected isozymes disappear 12 days after the injection without forming hybrid molecules between themselves or with the stored or newly synthesized frog LDH is evidence in favor of the hypothesis that the tetramer is the degradative unit of LDH, not the monomer as others have postulated. The LDH tetramers do not dissociate the recombine under the physiological conditions present in frog cells.


Cells that express viral antigens but lack H-2 determinants are not lysed by immune thymus-derived lymphocytes but are lysed by other antiviral immune attack mechanisms. Murine F9 teratoma cells do not express major transplantation antigens detectable by either serologic or alloreactive assays of thymus-dependent lymphocytes (T cells). Such cells can be infected with lymphocytic choriomeningitis virus or vaccinia virus, do express viral antigens on the cell surface, and can release infectious virus in amounts equivalent to those of other H-2 bearing murine cell lines. Immunologic injury of virus-infected F9 cells occurs after the addition of specific antiviral antibody and complement or of specific antiviral antibody and unsensitized lymphoid cells (antibody-mediated cell-dependent killing). In contrast, injury does not follow the addition of immune cytotoxic T cells. These results indicate that possession of H-2 antigens is not a requirement for a cell's infection by or production of virus. Further, expression of viral antigens on the cell's surface, although adequate for antibody-mediated immune injury, is by itself insufficient for direct T cell-mediated lysis. The major transplantation antigens thus probably represent the cell surface structures that are crucial for T-mediated cell wall damage that results in chromium release.


Studies on insulin action. V. Structural requirements of primers for subsequent accumulation of D-glucose at 0 degrees C in insulinized frog muscles. Systematic analysis was made of structural requirements for possible priming action of D-glucose and 40 related compounds in the presence of insulin to enhance subsequent labeled D-glucose uptake at 0 degrees C. It was concluded that a major portion if not all of the H-bonding groups on the D-glucose molecules are involved although their relative importance varies. Free OH and H on C-1, and upward orientation of OH and downward orientation of H on C-3, are the most important. Orientation of OH, H, and CH2OH on C-2, C-4, and C-5 are also important, but their perturbations are not nearly as detrimental to the priming action as those on C-1 and C-3.