Promotion of radiation peroxidation in models of lipid membranes by caesium and rubidium counter-ions: micellar linoleic and linolenic acids. Caesium and rubidium counter-ions increase peroxidation in irradiated micelles of linoleic (18 : 2) and linolenic (18 : 3) acids. The effect is specific to Cs+ and Rb+ in the alkali metal series. The effect is independent of the salts used (Cl-, NO3-, ClO4-) and, therefore, independent of the chaotropic nature, and reactivity with hydroxyl radicals of Cl-, NO3- and ClO4-. The promotion of peroxidation by Cs+ and Rb+ is interpreted in terms of their effect on fatty acid micelle structure. The dependence of radiation peroxidation on lipid structure in the micelles may be significant for studies of peroxidation in highly structured cell membranes.


DNA strand breaks in resistant and sensitive murine lymphoma cells detected by the hydroxyapatite chromatographic technique. Strand breaks were determined in L5178YS and L5178YR cell lines with DOS of 0.75 and 1.75 Gy, respectively, for 7 MeV electrons. The hydroxyapatite chromatographic technique was used to measure the breaks produced by 7 MeV electrons or 7 MeV neutrons immediately after irradiation or after maximal repair. Oxygen enhancement values for survival as well as strand breaks were determined for both cell lines and both qualities of radiation. The results indicate that despite a differential response to the lethal effects of radiation the levels of DNA strand breaks induced in these two lines were identical. Furthermore the values obtained for oxygen enhancement ratios (o.e.r.) and relative biological effectiveness (r.b.e.) for DNA strand breaks were different from those for cell survival. These results show that the difference in radiation sensitivity for cell killing is not reflected by the extent of DNA strand breaks measured by this method.


The effects of various salt and sucrose solutions on the U.V.L. sensitivity of CHO cells. The response of cultured CHO cells to U.V.L. irradiation during treatment with anisotonic solutions shows that treatment with hypotonic sucrose, NaCl or KCl solutions causes an increase in the cellular U.V.L. sensitivity, while exposure to hypertonic solutions causes a large decrease in U.V.L. sensitivity. Cells exposed to 1.8 M sucrose, NaCl or KCl solutions and given a U.V.L. dose of 252 erg/mm2 towards the end of the 20 min solution exposure time have survival levels which are respectively 228,26, and 23 times higher than the controls, i.e. cells irradiated in phosphate buffered saline. Cell volume data obtained using a Coulter counter, and nuclear area data of attached cells obtained using an optical microscope with a micrometer reticle, show that cell and nuclear size are related to U.V.L. sensitivity. That is, as cells shrink and the nuclear area decreases, the cells become more U.V.L.-resistant. During hypotonic treatment with 0.1 M NaCl, the cell volume, nuclear area and U.V.L. sensitivity increased in the first 2 to 4 min of exposure time, but at longer exposure times (greater than 3 to 4 min), cell volume, nuclear area and cellular U.V.L. sensitivity decreased. For 0.1 M KCl treatment the cells initially displayed a rapid increase in volume, nuclear area and U.V.L. sensitivity, but at the longer exposure times no decrease in cell and nuclear size were observed, and a slight increase in U.V.L. sensitivity occurred. Changes in U.V.L. sensitivity were related to changes in nuclear size and cell volume; however, calculations showed that during hypertonic treatment there is an ionic effect as well as an osmotic effect. That is, the cellular U.V.L. survival in equal hypertonic concentrations of NaCl or KCl was lower than in the same concentration of sucrose.


Plutonium in the tissues of foetal, neonatal and suckling mice after Pu-administration to their dams. Twelve-week-old female (C3H x 101)F1 mice were injected intravenously with an ultrafiltered solution of 239Pu in per cent trisodium citrate, and mated to uninjected PCT males. The plutonium content was examined radiochemically and autoradiographically in placentae and foetuses on the 12th and 18th days of gestation, and in neonates during the 24 hours after birth and also at 18 days postnatally. Plutonium was distributed in most tissues of the late foetus and the suckling as it is in adult mice. However, on both the 12th and 18th days of gestation the concentration in the yolk-sac splanchnopleure was much higher than in any other foetal tissue. The amount of 239Pu in 18-day-old sucklings was between two and seven times as great as in 1-day-old neonates because of ingestion of milk from the lactating dams. In the first litter following administration of the radionuclide to the dam, about 0.02 per cent of the plutonium injected was transferred to an individual offspring by the time of birth, and a further 0.08 per cent by the time of weaning.


Effects of 60Co irradiation on virulent Toxoplasma gondii and its use in experimental immunization. The effects of 60Co irradiation on the virulence and immunogenicity of the RH strain of Toxoplasma gondii was studied by infecting batches of mice with graded inocula of tachyzoites that had been exposed to radiation doses ranging from 0 to 20 000 rad. While doses of 15 000 and 20 000 rads appeared to be effective, and 10 000 rad nearly effective in annulling the virulence, irradiation at 5000 rad was only partially effective in rendering the organisms avirulent and could achieve only a prolongation of survival time of the inoculated mice. The survivors of higher irradiation inocula showed no evidence of the development of the parasite in them, but could resist a limited virulent challenge. The use of a booster inoculation improved both the quality and the duration of protective effect.


Ionizing radiation perturbs the switch-on of transcriptase in a model transcription complex in vitro. Ionizing radiation markedly alters the response of the reovirus transcriptase unblocking mechanism to stimulation by K+ ions, which normally trigger the switch-on of transcription in this system. In irradiated subviral particles the concentration of K+ ions needed to trigger switch-on is reduced in a dose-dependent way. The observed alteration of switch-on characteristics appears to correlate with alteration of the electrophoretic behaviour of a single major polypeptide species. These observations have important implications for understanding some of the effects of ionizing radiation on cells, most notably the induction of both latent virus and cell differentiation.


Micturition and the male genitourinary response to sacral root stimulation. The sacral roots, because of their anatomic and functional organization, are well suited to chronic stimulation. Data from our previous experiments on female dogs suggested that effective voiding responses to stimulation could be obtained by using the ventral root of S2, the sacral nerve in canines with the greatest detrusor representation. Elimination of dorsal root afferents from the stimulus field was essential to the minimization of spinal reflex activity. A selective somatic neurotomy was also necessary to attenuate maximally sphincter activity. In the male, the presence of the prostate gland, the greater urethral length, and the erectile response to stimulation might result in compression of the urethra, compromising micturition. Sacral root stimulation was thus studied using both spinalized and nonspinalized male dogs; the results are discussed with a view toward the applicability of sacral root stimulation to effect micturition in male paraplegics, who comprise the largest percentage of this group of patients.


Studies on the competition of polyene antibiotics for sterols. The fractional change in the corrected fluorescence of pimaricin or filipin in the presence of a limiting amount of sterol and a competing polyene antibiotic has been used to estimate the relative affinity of amphotericin B, nystatin, filipin, and pimaricin for stigmasterol and for cholesterol. The relative affinities for cholesterol were filipin greater than amphotericin B greater than pimaricin greater than nystatin, while the relative affinities for stigmasterol were filipin greater than pimaricin greater than amphotericin B greater than nystatin. The data indicate that pimaricin and filipin can both interact simultaneously with about 30% of the cholesterol or stigmasterol. However, the stoichiometry of filipin and pimaricin alone for cholesterol and for stigmasterol in dilute aqueous solutions is 1 : 1. In the experiments which indicated both pimaricin and filipin interact with the same sterol molecule changes in corrected fluorescence and the absorbance spectra were monitored; and these criteria indicated that both pimaricin and filipin had interacted with the sterols. Light-scattering measurements indicate large aggregates were not formed. Although the data shows in dilute aqueous solutions the stoichiometry of filipin and/or pimaricin for sterols is 1 : 1, in more complex solutions, other combinations or interactions are indicated especially for pimaricin.


Structure of the oligosaccharide chains in human alpha 1-protease inhibitor. Two glycopeptides were obtained from alpha 1-protease inhibitor after extensive pronase digestion and chromatography on Bio-Gel P-10 and concanavalin A-Sepharose. these glycopeptides were characterized by compositional analysis and sequential exoglycosidase digestion followed at each step by methylation analysis. The partially methylated alditol acetates obtained were resolved by gas chromatography and identified by mass spectrometry. The proposes structures of the oligosaccharide moieties of the glycopeptides are given below. (formula: see text) The relative amounts of the two glycopeptides isolated from concanavalin A-Sepharose suggest that each protein molecule contains four carbohydrate chains; one large chain (A) and three small chains (B).


Direct visualization of the binding and internalization of a ferritin conjugate of epidermal growth factor in human carcinoma cells A-431. We have prepared a conjugate of epidermal growth factor (EGF) and ferritin that retains substantial binding affinity for cell receptors and is biologically active. Glutaraldehyde-activated EGF was covalently linked to ferritin to produce a conjugate that contained EGF and ferritin in a 1:1 molar ratio. The conjugate was separated from free ferritin by affinity chromatography using antibodies to EGF. Monolayers of human epithelioid carcinoma cells (A-431) were incubated with EGF:ferritin at 4 degrees C and processed for transmission electron microscopy. Under these conditions, approximately 6 X 10(5) molecules of EGF:ferritin bound to the plasma membrane of each cell. In the presence of excess native EGF, the number of bound ferritin particles was reduced by 99%, indicating that EGF:ferritin binds specifically to cellular EGF receptors. At 37 degrees C, cell-bound EGF:ferritin rapidly redistributed in the plane of the plasma membrane to form small groups that were subsequently internalized into pinocytic vesicles. By 2.5 min at 37 degrees C, 32% of the cell-bound EGF:ferritin was localized in vesicles. After 2.5 min, there was a decrease in the proportion of conjugate in vesicles with a concomitant accumulation of EGF:ferritin in multivesicular bodies. By 30 min, 84% of the conjugate was located in structures morphologically identified as multivesicular bodies or lysosomes. These results are consistent with other morphological and biochemical studies utilizing 125I-EGF and fluorescein-conjugated EGF.


Isolation and surface labeling of murine polymorphonuclear neutrophils. Methods for the induction of an exudate of polymorphonuclear neutrophilic leukocytes (PMN) in the peritoneal cavity of C57BL, BALB/c, SJL and CBA mice were analysed. Peritoneal exudates in male mice were highly enriched for PMN (80-90%) three hours after a single injection of calcium caseinate whereas eosinophils comprised less than 1% of the exudate population. Female mice were a less satisfactory source of PMN because the proportion of eosinophilis in the exudate was variable. Purification of PMN from peritoneal exudate cells was performed on the basis of light scattering using a Becton-Dickinson cell sorter or by density gradient centrifugation with graded polyvinylpyrrolidone-coated silica particles (Percoll). Both techniques yielded approximately 97% pure PMN preparations. Electrophoretic analysis of the PMN proteins revealed an abundance of lactoferrin and actin, but several other proteins were also present in high concentrations. Proteolytic degradation of several high molecular weight proteins (greater than 90,000) was prevented by the addition of phenylmethylsulphonyl fluoride (PMSF) and ethylene diamine tetracetic acid (EDTA). Surface iodination, using diphenyl, tetrachloroglycouril (IODO-DEN), indicated that there were six tyrosine-containing proteins present on the external cell membrane. The apparent molecular weights of these surface proteins ranged from 185,000 to 90,000 and the major 125I-labeled protein had an apparent molecular weight of 90,000. Neither actin nor lactoferrin was labeled with 125I unless cell viability was lost during the iodination procedure. Standard conditions for labeling the cell surface only, required low iodide and IODO-GEN concentrations. Biosynthetic labeling of PMN using S-methionine increased the sensitivity of detection for most of the proteins, but some of the granule storage proteins (such as lactoferrin) were not effectively labeled within three hours.


Epidermal growth factor and the control of proliferation of Balb 3T3 and benzo[a]pyrene-transformed Balb 3T3 cells. Benzo[a]pyrene-transformed Balb 3T3 cells (BP3T3) exhibit "normal" growth controls at low concentrations of serum. Epidermal growth factor (EGF) stimulates DNA synthesis and cell division in both Balb 3T3 and BP3T3 cells at physiological concentrations. The growth response of BP3T3 cells to EGF is qualitatively the same as that of 3T3 cells, however, the transformed cells have a lower quantitative requirement. Both 3T3 and BP3T3 cells show a density-dependent response to EGF, but the shift in the dose response curve for BP3T3 cells at high cell density is smaller than that seen for 3T3 cells. One cause of the restricted growth of 3T3 cells at high cell density compared with BP3T3 cells is the increased concentration of growth factor needed for stimulation of 3T3 cells at higher cell densities. A lower rate of depletion of other growth factory by BP3T3 cells may also explain the smaller effect of cell density on the EGF response of these cells.


The effect of homologous local anesthetics of the 4-alkoxy- and 4-alkylamino-benzoic acid-diethylamino-esthylester- hydrochloride series on the glucose transport in human erythrocytes. The homologous compounds of the 4-alkoxy- and 4-alkylamino-series inhibit the exchange transport of glucose in human erythrocytes; they show a competitive inhibition with one or two inhibitor molecules which become bound to a singular site of the transport system for glucose. The importance of length of hydrocarbon chain of the localanesthetics for the mode of their action is discussed.


Stimulation of endothelia cell proliferation by precursors of thymidylate. Bovine corneal and aortal endothelial cell cultures were established from primary explants and subcultured for at least 40 passages. With both cell lines, exogenous thymidine, folate or folinate markedly increased the proliferation of these cells and decreased their serum requirement in Medium 199. Medium 199 supplemented with thymidine was particularly useful for cell survival at low densities; cones were readily produced when single cells were plated as low as 0.07 cells. cm-2. In contrast to the results of others, neither fibroblast growth factor nor epidermal growth factor were necessary for cell proliferation or survival at low densities.


Enhancement of insulin-induced prolactin secretion by fluoxetine in man. Fluoxetine hydrochloride, a specific inhibitor of serotonin reuptake, was given orally to five adult males to study its effect on fasting and insulin-stimulated release of PRL. A 3-day course of fluoxetine (30 mg daily) had no demonstrable effect on fasting PRL levels. Fluoxetine significantly enhanced insulin-induced PRL release. These data suggest that serotoninergic pathways have little or no part in the control of spontaneous PRL secretion in man, whereas they may play a role in insulin-stimulated PRL release.


Conversion of high molecular weight human epidermal growth factor (hEGF)/urogastrone (UG) to small molecular weight hEGF/UG by mouse EGF-associated arginine esterase. Human epidermal growth factor (hEGF) has previously been isolated from urine and appears to be identical to beta-urogastrone (UG), an inhibitor of stimulated gastric acid secretion. A high molecular weight (HMW) form of hEGF/UG has recently been found in human urine which is fully immunoreactive but is less bioactive as measured by receptor binding activity. A specific arginine esterase, the EGF-binding protein from mouse submandibular glands, was capable of cleaving HMW-hEGF to yield a small molecular weight (SMW)-hEGF with full immunoreactivity and bioactivity, whereas trypsin produced a SMW-hEGF with much less bioactivity. SMW-hEGF produced by the arginine esterase appeared to be immunologically, biologically (both by receptor binding and mitogenic activity) and chromatographically similar to highly purified hEGF. These data suggest that HMW-hEGF may play a precursor role in the biosynthesis of hEGF/UG in man.


Immunological abnormalities of aging: an analysis of T lymphocyte subpopulations of Werner's syndrome. Two T lymphocyte-specific antisera, i.e. naturally-occurring auto-antibody to T cells of systemic lupus erythematosus patients (natural T cell toxic autoantibody) and heterologous antiserum against human brain tissue (antibrain-associated T-cell antigen), were used to detect cell surface antigens of human peripheral T lymphocytes. Nylon column-purified T cells from normal aged individuals and patients with Werner's syndrome (a premature aging syndrome) were reacted with these auto- and heterologous antibodies followed by staining with appropriate fluorescence reagents. The cells were subjected to the automated analysis with fluorescence-activated cell sorter. Fluorescence profiles to T cells of both aged individuals of over 90 yr and Werner's syndrome showed a very similar pattern, with a drastic decrease in the population that had high fluorescence intensity stained with either antiserum accompanied by the relative increase in the cell population that had low fluorescence intensity. Natural T cell toxic autoantibody comparable to that detected in systemic lupus erythematosus patients was found in the serum of six out of seven patients with Werner's syndrome, whereas normal aged individuals produced no such an autoantibody. The results suggest that Werner's syndrome has a change in the lymphocyte population very similar to old individuals, and that such a change is caused by the production of autoantibodies reactive to T lymphocytes.


Prostaglandin E inhibition of T-lymphocyte colony formation: a possible mechanism of monocyte modulation of clonal expansion. Prostaglandin and monocyte modulation of a T-lymphocyte cell capable of undergoing clonal expansion was studied. Circulating human mononuclear cells were isolated by density centrifugation. After 24 h in culture with phytohemagglutinin present, the cells were mixed with 0.3% agar and overlayed onto a 0.5% agar layer that contained media and phytohemagglutinin. At day 6, colonies that contained greater than 50 cells were counted. These colonies represented clonal prolifertion of a phytohemagglutinin-responsive T-lymphocyte precursor. This responder cell accounted for less than 0.3% of the starting cell population. Colonies were comprised of cells which, when isolated, formed E rosettes. These colony cells could be shown to have helper or suppressor function as measured by their ability to promote or inhibit immunoglobulin synthesis. By these latter criteria the colony cells were considered to be mature T lymphocytes. The addition of prostaglandin E to the cultures demonstrated a linear, r = 0.82, dose-dependent inhibition of colony formation with a 50% point of inhibition (I50) = 0.18 muM. Low numbers of normal monocytes when added to the cultures mimicked the effect of synthetic prostaglandin E2. A highly significant correlation could be shown for endogenous prostaglandin E levels and colony counts. It appears that monocytes through their synthesis of prostaglandin E2 can restrict the clonal expansion of a circulating T-lymphocyte precursor.


Haemophilus influenzae type b antigenuria in children. Detection of Haemophilus influenzae type b (HIb) antigenuria by latex agglutination has been shown to be sensitive, specific, and rapid. In children, antigenuria persisted for a mean duration of 10 days and a maximum of 18 days. Antigenuria was demonstrated in 25 of 30 patients with HIb infection but not in 62 with other types of infection. In five children, antigenuria confirmed the diagnosis in the absence of bacteriological confirmation. In five other children, antigenuria was not found, but in this group the antigen was detected in another body fluid or HIb was recovered.


A histopathological study of gastric mucosal biopsies in infantile hypertrophic pyloric stenosis. Gastric biopsies from 35 infants with hypertrophic pyloric stenosis have been assessed for histological features of gastritis. No erosions were found, and there was no excess cellular infiltration of the lamina propria compared with a control group. Fresh haemorrhage into the lamina propria was frequent in both pyloric stenosis and control sections.


Frequency of allogeneic helper T cells responding to whole H-2 differences and to an H-2K difference alone. Limiting dilution analysis was used to determine the frequency of splenic T cells that are stimulated by alloantigen to give help in a primary antibody response to SRBC. Several haplotype combinations were tested. A semilogarithmic plot of the fraction of nonresponding culture as a function of the number of T cells added to excess B cells gave a straight line intercepting with the origin. Thus a single cell-type was limiting, which was required to help B cells respond to SRBC. The frequency of syngeneic precursors of T helper cells specific for SRBC ranged from 1/10,000 to 1/55,000 with a mean of about 1/20,000. Allohelpers generated by whole H-2 differences gave precursor frequencies that ranged from 1/1000 to 1/7000 with a mean of about 1/2500. Thus allohelpers to whole H-2 differences were approximately 8-fold more frequent than SRBC-specific helpers. When the stimulation was limited to the H-2K difference between the mutant B6.C-H-2ba and wild-type B6, frequencies of from 1/2600 to 1/7900 allohelpers were found with a mean of about 1/5000, approximately half the frequency of allohelpers to whole H-2 differences. Thus some, but probably not all, of the magnitude of allogeneic halp can be attributed to the high frequency of helper T cells that respond to a given alloantigen.


PPD-induced immunoglobulin production in human peripheral blood lymphocytes. II. Separation of PPD-reactive helper T cells from PWM-reactive helper T cells in polyclonal immunoglobulin production of human peripheral blood lymphocytes. We investigated the relationship bewteen PPD-reactive helper T cells and PWM-reactive helper T cells in polyclonal Ig production of human PBL. Elimination of PPD-reactive T cells by BUdR + light treatment resulted in a loss of helper function in PPD-induced Ig production, but had no effect on helper function in PWM-induced Ig production. On the other hand, elimination of PWM-reactive T cells resulted in a loss of helper function in both PPD-induced Ig production and PWM-induced Ig production. A blast cell-enriched fraction that was generated by PPD and separated by the velocity sedimentation method contained helper function in both responses. On the other hand, blast cell-depleted fractions did not contain PPD-reactive helper function, although the PWM-reactive helper function was evident. These results strongly suggest that PPD-reactive helper T cells are included in PWM-reactive helper T cells.


20 alpha hydroxysteroid dehydrogenase (20 alpha SDH) activity in New Zealand mice T lymphocytes and bone marrow cells: effect of age, sex, and castration. The activity of 20 alpha hydroxysteroid dehydrogenase (20 alpha SDH), a T lymphocyte-associated enzyme, was measured in fetal liver, thymus, spleen, and bone marrow cells from NZB, NZW, and (NZB X NZW)F1 (B/W) mice. There was an age-dependent increase of 20 alpha SDH activity in bone marrow cells, and a decrease in thymocytes and splenic T lymphocytes. Treatment with anti-theta and complement did not reduce the 20 alpha SDH activity of bone marrow and fetal liver cells, but reduced the activity of spleen cells. PHA stimulates both 20 alpha SDH activity and thymidine incorporation in splenic, bone marrow, and fetal liver lymphocytes. The results suggest that the enzyme in the bone marrow and fetal liver is located in pre-T lymphocytes. Enzymatic activity in bone marrow cells taken from female B/W mice (older than 7 months) was 40 to 20% lower than in male mice. Orchidectomy, but not ovariectomy, caused a significant decrease in thymocyte 20 alpha SDH activity. Orchidectomy depressed and ovariectomy enhanced 20 alpha SDH activity of bone marrow cells. The 20 alpha SDH activity of fetal liver cells from B/W mice was twice as high as in either parent strain. No 20 alpha SDH activity was found in fetal liver cells taken from BALB/C SJL or C57BL/6 mice. A model is proposed to explain the age- and sex-related changes in 20 alpha SDH activity of pre-T and T lymphocytes in healthy and pathologic conditions.


Stimulators and inhibitors of lymphocyte DNA synthesis in supernatants from human lymphoid cell lines. Some T and B lymphoid cell lines (LCL) were found to secrete into their supernatants a substance able to stimulate lymphocyte proliferation. This substance produced an increase in [3H]thymidine uptake by mononuclear cells when added to unstimulated cultures (mitogenic effect) or when added to cultures stimulated with phytohemagglutinin (PHA) or pokeweed mitogen (PWM) (potentiating effect). When complete supernatants were used, the potentiating effect was sometimes masked by an inhibitor of DNA synthesis. Fractionation on Sephadex G-100 separated these two activities. The stimulatory substance eluted at a m.w. range of 15,000 to 30,000, and the inhibitor eluted with the albumin peak. B cells with or without monocytes were the most sensitive to the mitogenic effect, whereas T cells were unaffected. Responses to PHA and PWM were potentiated when T cells were present, but the maximum effect was observed when the proportion of T cells was less than 50%. The stimulatory material may be similar to lymphocyte mitogenic factor and may function as a T cell-replacing factor in B cell stimulation.


Inhibition of influenza-immune T cell effector function by virus-specific hybridoma antibody. The in vitro activity of influenza-specific cytotoxic T cells can be inhibited by incubation of the target cells with monoclonal anti-influenza antibodies. Hybridoma antibodies that bind to the virus HA inhibit the cytotoxic activity of TDL for the virus-infected target by as much as 80%, whereas these same antibodies never reduce splenic T cell function by more than 40%. This reflects the fact that TDL from anti-influenza strain A/WSN/33 (HON1) are highly subtype-specific, whereas splenic effector cells from the same mice are cross-reactive for target cells infected with heterologous influenza A viruses. These findings are discussed in the light of previous failures to block virus-immune T cell effector function with heterogeneous antisera produced in vivo, and are considered to favor the idea that at least some of the "virus-immune" T cells are indeed recognizing viral antigens.


Ontogeny of terminal deoxynucleotidyl transferase-positive cells in lymphohemopoietic tissues of rat and mouse. The ontogeny of hemopoietic cells which contain the enzyme terminal deoxynucleotidyl transferase (TdT) was studied in rats and mice. During fetal life, TdT-positive cells were first detected in the thymus, where they appeared on or about day 17 of gestation. TdT-positive cells were not found in fetal liver, spleen, or bone marrow, but appeared in bone marrow and spleen on the day after birth. In the rat, peak levels of TdT-positive cells were attained at 3 to 4 weeks of age in thymus, bone marrow, and spleen, accounting for 67, 3.9, and 2.3% of nucleated cells, respectively. The percentages of TdT-positive cells in thymus and bone marrow decreased gradually thereafter, whereas, TdT-positive cells in spleen were no longer detectable by 7 weeks of age. Normal percentages of TdT-positive cells were found in bone marrow and spleen from neonatally thymectomized rats and congenitally athymic (nu/nu) mice. Dexamethasone treatment resulted in a marked decrease in TdT-positive cells. The results are discussed with respect to the putative role of TdT-positive hemopoietic cells as thymocyte progenitors.


In vitro antibody response to influenza virus. I. T cell dependence of secondary response to hemagglutinin. A good secondary IgG response to the hemagglutinin (HA) of influenza virus has been obtained in vitro in Marbrook-type cultures of influenza-primed mouse spleen cell suspensions stimulated with inactivated influenza virus. Anti-HA antibody was quantitated by a solid phase radioimmunoassay (RIA) by using purified HA as substrate. The T dependence of this secondary response was shown by depletion of T cells and reconstitution with a source of primed or unprimed T cells. The help given by T cells primed to the homologous virus was many times greater than that given by unprimed T cells, although the latter was significant. The system described will allow investigation of the specificity requirements of helper T cells engaged in the anti-HA response.


Studies on the kinetics of hemopoietic stem cells and immune responses to the hapten-carrier conjugate. The correlation between the kinetics of hemopoietic stem cells and immune responses to the hapten-carrier conjugate was investigated. The numbers of both pluripotent stem cells (CFU-S) and myeloid stem cells (CFU-C) in the spleen from mice immunized with the hapten-carrier conjugate were significantly greater than those of the control and the activity of colony-stimulating factor (CSF) in the serum of these mice was markedly elevated. The supernatant of short-term incubation of splenic T lymphocytes from these mice, when stimulated with carrier protein, had high levels of both activities of CSF and helper T cell factors. The study by gel chromatography showed that these factors are similar m.w. substances of 35,000 to 45,000 daltons. But analysis by ion-exchange chromatography demonstrated that they do not have identical biochemical properties. The present studies suggest that biologically active factors produced by T cells stimulated with carrier protein may induce the enhancing effect on the proliferation and differentiation of hemopoietic stem cells and immune responses to the hapten-carrier conjugate.


Modulation of granulomatous hypersensitivity. I. Characterization of T lymphocytes involved in the adoptive suppression of granuloma formation in Schistosoma mansoni-infected mice. The cellular basis of the spontaneous modulation of the granulomatous response to schistosome eggs was analyzed in mice infected with Schistosoma mansoni. Spleen cells of 20 or 32 week-infected mice undergoing modulation, when transferred to 6 week-infected recipients, suppressed the maximal granulomatous response at 8 weeks. Suppression of both naturally forming asynchronous liver and synchronously induced lung lesions was achieved. Specificity of this effect was demonstrated by the suppression of egg granulomas but not antigen-coated bead granulomas developing simultaneously in the lungs of cell recipients. Further characterization showed that suppression was abrogated by pretreating transferred cells with either anti-Thy 1.2 or anti-Iak alloantisera and C. Transfer of macrophage-depleted or fractionated T and B spleen cells confirmed that T cells alone transferred suppression. Moreover, an Ia antigen-bearing (Ia+) subpopulation of T cells was required in the transferred suppression. Moreover, an Ia antigen-bearing (Ia+) subpopulation of T cells was required in the transferred population. An examination of T cells obtained from isolated, dispersed lung granulomas from control and adoptively suppressed mice revealed an increased proportion of Ia+ cells in the latter. It is suggested that Ia+ T cells may be involved in the local modulation of the granulomatous response.


Characterization of a spontaneous murine B cell leukemia (BCL1). I. Cell surface expression of IgM, IgD, Ia, and FcR. The surface marker expression of a spontaneous B lymphocyte leukemia discovered in a BALB/c mouse (BCL1) was examined and found to include a subset of markers known to occur on normal B lymphocytes. The tumor cells bore surface Ig that included both mu- and delta-chains associated with the lambda light chain. Alloantigens coded for within the murine MHC, including H-2D, H-2K, and I-region products, were identified on the tumor cells. Although normal B lymphocytes are thought to express products coded for within both the I-A and I-E subregions, the BCL1 expressed only normal amounts of I-E subregion products. In addition, the H-2 and Ia antigens revealed by 2-dimensional gel electrophoresis exhibited an abnormal pattern of post-translational modifications. The Fc, but not the complement-receptor, was present on the surface of tumor cells. The presence of IgD, Ia antigens, and the responsiveness to lipopolysaccharide (see subsequent paper) have led us to postulate that the BCL1 tumor represents a later differentiative stage than murine B lymphocyte tumors previously described.


Curve -shift analysis of cryopreserved killer T cell function. The conditions for cryopreservation and reconstitution after thawing of cytotoxic effector cells for cell mediated lympholysis (CML) tests are studied. Percentage recovery of functional activity is analysed not by the commonly used method of comparisons at a single concentration of effector cells but by the movement of the curve of functional activity on the axis of cell concentration in culture. By this method the position of the ascending slope of the dose-response curve, at several different effector to target cell ratios, is compared between fresh and frozen-thawed cells. Cooling rates giving optimal recovery were found to vary between experiments. Using simple techniques, optimal cooling rates were found to range from 0.3 to 1.0 degrees C/min, when using dimethyl sulphoxide (10% v/v). Dead cell debris, but not intact dead cells (which take up eosin), were shown to inhibit the lytic ability of functionally active frozen-thawed effector cells. This could be removed by centrifuging the thawed cells over Ficoll-Hypaque. In the recovered population the proportion of cells which excluded the vital dye, eosin, was greater than the proportion of functioning effector cells. This suggested that the cells which excluded eosin contained both functional and nonfunctional, partially damaged effector cells. Thus dye exclusion methods generally over-estimated the functional activity of thawed effector cells. When cells to be used as targets were preserved prior to treatment with phytohaemagglutinin (PHA) no abnormalities were detected in their behaviour to fresh cells.


Measurement of anti-double-stranded DNA antibodies in major immunoglobulin classes. A solid-phase radioimmunoassay for quantitating anti-double-stranded deoxyribonucleic acid antibodies (anti-dsDNA) in IgG, IgM and IgA classes has been devised. A distinct feature of the method is an application of polystyrene tubes coated with poly-L-lysine, through which dsDNA could be bound firmly to a solid phase. Studies on patients' sea as well as normal sera revealed that anti-dsDNA was not qualitatively but quantitatively characteristic of systemic lupus erythematosus (SLE) and that IgG anti-dsDNA levels correlated well with the disease activity.


A method for the induction of a prolonged elevated IgM response without the formation of IgG antibody, by injecting carrageenan-treated mice with multiple doses of sheep erythrocytes. Carrageenan, a known macrophage toxin and immunosuppressive agent, has been studied for its effect on antibody responses following single doses or multiple daily increasing doses of sheep red blood cells (SRBC) injected intraperitoneally (i.p.) in male CBA strain mice. Results showed that lambda carrageenan administered prior to a single i.p. injection of SRBC markedly suppressed both the IgM and IgG responses. However, when carrageenan-treated mice were injected with multiple daily increasing amounts of SRCB antigen, high titers of specific antibody activities were produced in serum while only IgM plaque-forming cells (PFC) were detected in the spleens up to 8 weeks later. Higher serum titers were obtained if Bordetella pertussis vaccine was administered i.p. shortly before the first antigen dose was injected in the carrageenan-treated mice. Direct PFC (IgM) but not indirect PFC (IgG) were detected in suspensions of spleen cells late in the response of these mice. Such treatment may provide a useful method for raising high titers of cytotoxic IgM antibody to other T-dependent antigens. Evidence is presented to show that pertussis vaccine--a known potentiator of the IgG response--does not reverse the inhibitory effects of carrageenan. Results also provide evidence for the requirement of functional macrophages in the induction of helper-cell activity for the thymus dependent IgG response in vivo.


Purification and properties of L cell-derived colony-stimulating factor. CSF was prepared by the growth of L cells in serum-free culture medium. This conditioned medium was subjected to a six-step purification schedule which included ultrafiltration, alcohol precipitation, and separation by DEAE-cellulose, Con A-Sepharose, Sephadex G-150, and sucrose density-gradient centrifugation. The resultant CSF was 1000-fold purified with 50% to 70% recovery of the starting activity. Granulocyte and macrophage colony formation was detected with 5 x 10(-12M CSF; maximum colonies were obtained with 3 ng per marrow culture. Two major peaks of activity were obtained; one was nonadherent to Con A, whereas the other was bound and specifically eluted with alpha-methylglucoside. Both fractions contained carbohydrate residues as they stained avidly with PAS, were inactivated by periodate, and showed altered electrophoretic mobility after treatment with neuraminidase. Following iodination, each purified fraction migrated in a single band in SDS-acrylamide gels. The molecular weight was estimated as 65,000 to 70,000 daltons. Following reduction with mercaptoethanol, the CSF fractions were reduced into subunits with molecular weights of approximately 35,000. These studies confirm the glycoprotein nature and subunit composition of L cell CSF. The methods described herein are useful for the purification of both the Con A-adherent and con A-nonadherent forms of CSF.


Deoxyadenosine inhibits DNA synthesis in cultured human fibroblasts. The rate of DNA synthesis in cultured diploid fibroblasts, nonmalignant human cells, is decreased by 50 microM 2'-deoxyadenosine when adenosine deaminase is inhibited and 2'-deoxyadenosine is phosphorylated to dATP. No inhibiton of DNA synthesis occurs with 100 microM adenosine under identical conditions or with 50 microM deoxyadenosine when adenosine deaminase is not blocked. Inhibition of DNA synthesis may be an important link between adenosine deaminase deficiency and severe combined immunodeficiency if the tissue culture model is relevant to lymphocyte function in man.


Cold-reacting antinuclear factor in sera from patients with IgA nephropathy. ANF was determined in sera from patients with IgA nephropathy to evaluate the autoimmune nature of this disorder. Sera from 33 patients with IgA nephropathy were assayed for ANF by the FANA technique at 37 degrees and 4 degrees C as well as by a hemagglutination technique. In addition, sera from five patients with lupus nephritis and six patients with idiopathic membranous nephropathy were examined. Thirty healthy adults served as controls. Cold-reacting ANF, which was detected predominantly in the class of IgM, was observed in 81.8% of patients with IgA nephropathy. The nuclear staining pattern was "speckled." Sera from healthy adults did not show any positive signs of ANF, whereas those from patients with lupus nephritis demonstrated "shaggy" pattern of ANF. It is suggested that some autoimmune mechanisms may be involved in the development of IgA nephropathy.


Stimulation of chick gut alkaline phosphatase activity by actinomycin D and 1,25-dihydroxyvitamin D3: evidence for independent mechanisms. We observed that inhibitors of RNA synthesis, actinomycin D and cordycepin, stimulate chick duodenal alk Pase activity by means which are additive to the stimulaation by the biologically active metabolite of vitamin D3, 1,12(OH)2D3, and its analogue, 1 alpha OH D3. The protein synthesis inhibitor, cycloheximide, inhibited basal alk Pase activity and blocked its stimulation by actinomycin D and 1,25(OH)2D3. Both actinomycin D and cycloheximide blocked the ability of 1,25(OH)2D3 and 1 alpha OHD3 to raise serum calcium levels. The paradoxical stimulation of duodenal alk Pase activity by RNA synthesis inhibitors additive to the stimulation by 1,25(OH)2D3 suggests that alk Pase activity is controlled by mechanisms other than gene activation. (J LAB CLIN MED 94:88, 1979.)


Alpha-1 antitrypsin elevation in healthy neonates. alpha 1-Antitrypsin concentrations and phenotypes were determined in plasma of 257 healthy newborns. Samples were taken during the first 3 days after birth (time 1) and approximately after 30 days (time 2). We found the alpha1-antitrypsin levels immediately after birth elevated in the three Pi phenotypes M, M1M2, and MS as compared to the concentrations in cord blood and those at the age of 30 days. The concentrations in cord blood were within the normal range for adults. The concentrations (in mg/ml) at times 1 and 2 (+/- S.D.) for the different phenotypes were M: 2.94 +/- 0.58, 1.99 +/- 0.35; M1M2: 2.81 +/- 0.48, 2.01 +/- 0.37; MS: 2.45 +/- 0.5, 1.55 +/- 0.33. These differences were highly significant (p less than 0.001). Samples with the PiMZ phenotype had the characteristically reduced levels and did not show a significant difference in concentration between the two samples: 1.54 +/- 0.25 mg/ml (time 1) and 1.42 +/- 0.34 (time 2). We conclude that the alpha 1-antitrypsin level in plasma of normal infants rises in response to stimuli in the immediate neonatal period, or that perhaps the rise is due to the process of delivery itself. Heterozygotes for Piz can apparently not respond, or respond only minimally, to the same factor(s).


Vestibulo-toxicity of tobramycin.

Vestibulo-toxicity of tobramycin. The case histories are described of two patients with normal renal function who developed permanent complete bilateral loss of peripheral vestibular function during tobramycin therapy. Despite the low incidence of the cochleotoxic and and vestibulotoxic side-effects of tobramycin, it seems advisable to monitor patients on tobramycin therapy for signs of vestibular dysfunction and hearing loss.


3'-deoxyadenosine and implantation of delayed blastocysts in mice. Pregnant mice were ovariectomized 3 days after mating and pregnancy was maintained by progesterone treatment. Different regimens of intraperitoneal injections of 3'-deoxyadenosine were applied 3 days after ovariectomy. Repetition of the injections at 3 h intervals induced a significant rate of implantation by delayed blastocysts. Other types of treatment with 3-deoxyadenosine as well as adenosine injections were found to be ineffective. Paradoxically, 3'-deoxyadenosine treatment had an adverse effect on the overall pregnancy rate found at autopsy.


Clarification of studies on the origin of thymic lymphocytes. The thesis that lymphocytes originate in situ by the direct transformation of epithelial cells within the thymic primordium in anurous frogs is untenable. On the contrary, in both the leopard frog and the African clawed toad, the lymphocytes that first appear in the embryonic thymus are derived from extrathymic lymphopoietic cells that invaded the developing organ. The exact source of origin of the invading lymphopoietic cells remains problematic.


A factor necessary for normal morphogenetic function of anuran endoderm. Cytoplasmic preparations obtained from late blastulae and early gastrulae of normal R. pipiens eggs contain factors which induce delayed lethal effects when injected into normal eggs at the beginning of cleavage. The same preparations can rescue some defective eggs which occur spontaneously (NS eggs), or are produced experimentally (ES eggs), by relieving the specific developmental syndrome displayed by either type of egg. The syndrome involves abnormal endoderm in which cytolysis is time-programmed. The lethal factors as well as the rescue factors are absent in the normal egg cytoplasm prior to the late blastula stage.


Extrapyramidal side effects and increased serum prolactin following fluoxetine, a new antidepressant. Fluoxetine (Lilly 110140) is a potent, specific serotonin (5-HT) uptake blocker which is being tested in man for antidepressant activity. One of 9 depressed patients receiving this drug developed a dystonic reaction, parkinsonian rigidity, and increased  serum prolactin levels, all signs of decreased dopaminergic activity. Homovanillic acid levels also decreased in the cerebrospinal fluid of this subject. We postulate that fluoxetine, via the increase in 5-HT activity resulting from 5-HT uptake blockade, inhibited both the nigro-striatal and tubero-infundibular dopaminergic neurons. These results provide additional evidence for a linkage between serotonergic and dopaminergic neurons in man.


Distribution of anti-HRP antibodies in the central nervous system of immunized rats after disruption of the blood brain barrier. Lewis rats were immunized with horseradish peroxidase (HRP) injected intradermally in the hind foot pads; anti-HRP antibodies in the cerebrum were detected with a cytochemical reaction for HRP in sections incubated with the antigen (HRP), or after intravenous injection of HRP a few minutes before sacrifice. In two groups of animals the blood brain barrier was disrupted by a heat lesion or by a traumatic lesion (insertion of a canula into the lateral ventricle). In animals with a heat or with a traumatic lesion, anti-HRP antibody was detected not only in the vicinity of the lesion but also within the entire cerebral parenchyma and the choroid plexus. By electron microscopy, anti-HRP antibody was seen on the plasma membranes of endothelial cells and pericytes of the capillaries of the brain parenchyma and of the choroid plexus, and on the plasma membranes of the choroid plexus epithelium. Anti-HRP antibody was not seen in a group of immunized animals with an intact blood brain barrier or in a group of animals immunized 30 or more days after the brain lesion. These experiments have shown that significant levels of circulating antibody against an antigen (HRP), which is irrelevant to brain antigens, has access to and achieves a widespread distribution into the brains of animals with a disrupted blood brain barrier.


Ventricular dilatation and communicating hydrocephalus following spontaneous subarachnoid hemorrhage. Ventricular dilatation following spontaneous subarachnoid hemorrhage (SAH) is a well recognized phenomenon. Its clinical significance, however, remains controversial. Two phases are distinguished, the acute or early, occurring soon after the ictus, and the chronic or late, developing after the second week. The authors studied the ventricular size in 210 patients with spontaneous SAH through the course of their illness and convalescence by means of serial computerized tomography (CT) scans. Their findings suggest that ventricular dilatation soon after SAH is not always clinically significant and does not necessarily require shunting before definitive surgery. Delayed symptomatic ventricular enlargement (communicating hydrocephalus) occurs in 7% of the patients and can be safely diagnosed on the basis of the clinical picture and CT scan appearances. Treatment with a ventricular shunting system is almost invariably rewarding.


Chemical change and energy production during contraction of frog muscle: how are their time courses related? 1. The heat+work (h+w) and the changes in the levels of creatine, phosphocreatine and ATP were determined for 1, 2, 5, 10 and 15 sec isometric tetani at 0 degrees C under aerobic conditions. The change in the sum of inorganic phosphate and glucose-1-phosphate and glucose-6-phosphate was measured also. The changes in the levels of all these chemicals and of lactate were measured in muscles stimulated for 15 sec under anaerobic conditions. 2. The lactate measurements and a comparison of the results for aerobic and anaerobic conditions showed that during a 15 sec tetanus there was a negligible amount of resynthesis of ATP from reactions other than the creatine kinase reaction. 3. For all durations of stimulation, except 1 sec, a significant part of the h+w could not be explained by the energy from ATP splitting and the creatine kinase reaction. The existence of an unexplained part of the h+w confirms earlier findings. 4. On the basis of its time course, the h+w was divided into the stable part and the labile part. The energy from the observed chemical reactions was always sufficient to account for the stable part of the h+w. 5. Early in the tetanus the unexplained energy is less than the labile part of the h+w. At the end of a 15 sec tetanus the total amounts of unexplained energy and labile h+w are equal. For this reason and others which are discussed it is probable that there is a close relationship between them.


The extracellular compartments of frog skeletal muscle. 1. Detailed studies of solute efflux from frog sartorius muscle and single muscle fibres were carried out in order to characterize a 'special region' (Harris, 1963) in the extracellular space of muscle and determine whether this 'special region' is the sarcoplasmic reticulum. 2. The efflux of radioactive Na, Cl, glusose, 3-O-methylglucose, xylose, glycine, leucine, cycloleucine, Rb, K, inulin (mol. wt. 5000) and dextran (mol. wt. 17,000) from previously loaded muscles was studied. In all cases except dextran the curve had three components, a rapid (A) component which could be equated with efflux from the extracellular space proper, a slow (C) component representing cellular solute and an intermediate (B) component. The distribution space for the B component was 8% of muscle volume in summer frogs and 12% in winter frogs and appeared to be equal for all compounds studied. We tested the hypothesis that the B component originated from the sarcoplasmic reticulum. 3. The C component was missing from the dextran curves. Both dextran and inulin entered the compartment of origin of the B component (compartment B) to the same extent as small molecules. 4. For all compounds studies, the efflux rate constant for the A component could be predicted from the diffusion coefficient. For the B component the efflux rate constant was 6--10 times slower than that for the A component but was still proportional to the diffusion coefficient for the solute in question. 5. When Na and sucrose efflux from single fibres was followed, a B component was usually observed. The average distribution space for this component was small, averaging 1.5% of fibre volume. There was no difference between the average efflux rate constants for Na and sucrose. 6. In an appendix, the constraints placed on the properties of a hypothetical channel between the sarcoplasmic reticulum and the T-system by the linear electrical parameters of frog skeletal muscle are derived. It is shown that the conductance of such a channel must be less than 0.06 x 10(-3) mohs/cm2 of fibre membrane. 7. The conductance between compartment B and the extracellular space can be calculated from the efflux rate constants for Na, K and Cl. The value obtained was 5 x 10(-3) mhos/cm2 of fibre membrane or 100 times the limiting value for the conductance of the T-SR junction. 8. The finding that there is a B component in the efflux curves for large molecular weight substances like inulin and dextran and the small size of the B component in efflux curves from single muscle fibres indicate that the 'speical region' of the extra-cellular space of frog muscle is not the sarcoplasmic reticulum. This conclusion is confirmed by a calculation of the conductance between the B compartment and the extracellular space. The value obtained is incompatible with predicted electrical properteis of the SR-T-tubule junction...


Extracellular space of frog skeletal muscle in vivo and in vitro: relation to proton magnetic resonance relaxation times. 1. The Na and Cl distribution spaces of freshly isolated frog muscles are 16.7 and 12.6%, respectively. These values increase to 25.6 and 23.3%, respectively, on incubation. 2. The extracellular components of both Na and Cl efflux curves are significantly smaller in freshly isolated muscles (approximately 12%) than in incubated muscles (approximately 18%). The fast exchanging A component of the extracellular space is increased more by incubation than the more slowly exchanging B component. 3. The proton magnetic resonance (p.m.r.) transverse relaxation curve for the water of freshly isolated frog muscles did not show the long, slowly relaxing tail present in curves from muscles incubated in Ringer solution. 4. When muscles were incubated in hypertonic solutions the p.m.r. transverse relaxation curves could be resolved into three components whose sizes were consistent with the components present in the sodium and chloride efflux curves. The non-exponentiality of the p.m.r. transverse relaxation curve therfore appears to arise from water in both the A and B extracellular compartments of muscle. 5. Efflux analysis indicated that the cellular Na content of both freshly isolated and incubated frog muscle is similar to that predicted by others (Lev, 1964; Armstrong & Lee, 1971; Lee & Armstrong, 1974) from measurements of intracellular Na ion activity using Na-sensitive micro-electrodes. The remainder of the tissue Na was found in the more rapidly exchanging extracellular compartments. The results of these experiments are inconsistent with the presence of a substantial fraction of bound Na in frog muscle. 6. These experiments show that muscle extracellular space is smaller in vivo than in vitro. Efflux analysis is suggested as the most accurate method of assessing extra-cellular components.


Lack of uniformity in colour matching.

Lack of uniformity in colour matching. 1. The fraction of red in a red--green mixture matched to yellow increased as the intensities of the match constituents were increased sufficiently to bleach appreciable chlorolabe and erythrolabe. 2. All changes in matching found for a given normal trichromat, (i) with increase in the intensities of the matching components, (ii) as a function of time after the onset of very intense components, (iii) with change in the pupil region through which light enters the eye, and (iv) with change in the region of the retina under test, are consistent with the assumption that matching depends upon the absorption of light in three kinds of (individually colour blind) cones, each with its own visual pigment, provided that the lambda max densities of the latter can vary in the range 0.25--1.0 (common logarithmic units) depending upon the subject. 3. Individual differences in matching among normal (as well as among both varieties of red--green anomalous) trichromats, on the other hand, suggest that the extinction spectra of the cone pigments sensitive to long and medium wave lengths may differ from one trichromat to the next.


Effects of nerve impulses on threshold of frog sciatic nerve fibres. 1. The firing thresholds of single myelinated fibres of frog sciatic nerves were monitored as a function of impulse activity in the fibre. The threshold was given by the number of coulombs in current pulses that excited a particular fibre half the time when delivered to the whole nerve. Threshold was tracked by a device that incrementally decreased the number of coulombs in the current pulse whenever the fibre responded and increased the pulse if it did not respond. 2. There was a pattern to the after-oscillations of threshold following activity. The fibres were briefly refractory, transiently superexcitable for about 1-1.5 sec and then entered a phase of raised threshold or 'depression' that lasted for many minutes. 3. Activity produced little change in the threshold curve during the refractory period. Strong depressions following prolonged activity prevented the threshold from returning to the base-line level within the time associated with the refractory period for the same fibre at rest. 4. After an impulse, superexcitability reached a maximum within 7-20 msec. This peak was larger as the number of impulses in a preceding burst increased and as the intervals between the impulses became briefer. Each successive impulse of a burst contributed less to the growth of superexcitability, and after the burst had 6-10 impulses additional impulses contributed nothing. 5. The depression phase was marked by the interaction between build-up, which depended on the activity rate, and recovery, which required as long as an hour or more for the threshold to be completely restored to resting level. These two mechanisms, one causing build-up and the other recovery, led to formation of dynamic equilibria. The threshold level at equilibrium increased monotonically with the activity rate. 6. The processes associated with superexcitability interact with those producing depression. In active fibres showing raised thresholds, impulses are followed by a relative superexcitability that persists for at least as long as an absolute superexcitability (with threshold below the resting level) can be measured in the same fibre at rest. 7. The duration of the superexcitable phase interpreted as a relative change in excitability was roughly the same regardless of the level of depression. 8. The magnitude of the oscillation in threshold was give to ten times larger than the grey region (the range of stimuli for which response is probabilistic). It is concluded that at regions of low conduction safety such as axonal branches, where weak forces can influence whether an impulse will pass, such pronounced and long-lasting after-effects of firing can be expected to modulate conduction of nerve impulses.


Interpretation of light diffraction by cross-striated muscle as Bragg reflexion of light by the lattice of contractile proteins. 1. The diffraction spectrum obtained by illuminating a cross-striated muscle fibre with a narrow beam of monochromatic light generally shows asymmetry of light intensity between left and right spectral lines. 2. The asymmetry of light intensity in left and right spectral lines is reversed when the fibre is rotated by 180 degrees. This indicates that intensities of the spectral lines are determined more by Bragg reflexion than by simple diffraction as in a plane grating. Populations of myofibrils with differing tilt of lattice planes must exist in each illuminated fibre segment to account for simultaneous Bragg reflexion to the left- and right-hand sides. 3. The light intensity of spectral lines shows a complicated dependence on the angle at which the incident beam is directed against the fibre. This 'intensity distribution' seems to reflect the specific myofibrillar arrangement at the site of illumination. 4. The intensity distributions of the left and right first order lines show close correlation if the deflexion of the incident beam differs by twice the Bragg angle. 5. The deflexion angle of the incident beam at which maximum intensity in spectral lines is obtained depends on sarcomere length as predicted by Bragg's formula. 6. Intensities of the first and second order lines are little correlated when recorded at the same beam deflexion, but are well correlated when recorded at beam deflexions calculated from Bragg's formula. 7. When a diffraction line is scanned perpendicularly to the meridional plane, the light intensity shows fluctuations resembling those obtained by beam deflexion within the meridional plane.


Serotoninergic control of MSH secretion in the eel. Ultrastructural study after 5-hydroxytryptophan treatment. Injection of 5-HTP induces a melanodisperson ; MSH cells are markedly stimulated :hormone synthesis (development of Golgi area and endoplasmic reticulum) and release (reduction of secretory granules) are observed. This stimulatory serotoninergic pathway seems antagonistic to the dopaminergic system that inhibits MSH secretion in the eel.


Properties of an unusual genetic element in Staphylococcus aureus. A strain of Staphylococcus aureus (M7) contains a transmissible element determining production of penicillinase, and resistance to cadmium ions, neomycin, streptomycin and kanamycin (CPNS). This element was transferred either in toto or in fragments at low frequency from strain M7. The fragment (NS) possesses features typical of chromosomal genes and the fragment (CP), like (CPNS) itself, exhibits plasmid features. The element (CPNS) is transferred in mixed culture at high frequency, up to 10(-3), between other strains of staphylococci. Lysogenisation of the recipient increases the frequency of transfer. The frequency of transduction of (CPNS), (CP) and (NS) from cell-free lysates corresponds well with the transfer frequency of each of these elements in mixed culture. A possible mechanism for the evolution of (CPNS) is discussed.


Laboratory criteria for a diagnosis of systemic lupus erythematosus. Patients with systemic lupus erythematosus (SLE) and other connective tissue diseases were surveyed for the presence of antibodies to normal DNA, antibodies to a ribonuclease-insensitive acidic nuclear protein, and immune deposits in normal skin. While 80% of patients with SLE had abnormal values for at least two of these three tests, none of the patients with other connective tissue diseases had more than one abnormal value. The presence of RBC autoantibodies was found along with one of the other abnormal laboratory tests in 76% of patients with SLE, including 14% of patients not found to have two abnormal tests. None of the other patients tested had RBC autoantibodies. These findings suggest that a set of laboratory tests can be constructed as criteria for a diagnosis of SLE that would be as specific as the presently employed American Rheumatism Association criteria.


[Degradation of ampicillin by urine of patients with complicated urinary tract infections and its protective effect of dicloxacillin (author's transl)]. In vitro enzymatic degradation rate of ampicillin (AB-PC) in urine of patients with complicated urinary tract infection and its protective effect of dicloxacillin (MDI-PC) was studied using a specific fluorometric assay for aminobenzylpenicilloic acid (AB-PA), which is converted from AB-PC by bacterial beta-lactamase. The results showed that average degradation rate of AB-PC in the urine of 10 patients were 12.2%, 21.5%, 34.3% and 48.2% at 15, 30, 60 and 120 minutes, respectively. While MDI-PC prevented the enzymatic transformation of AB-PC in such urinary samples and the average degradation rates at 15, 30, 60 and 120 minutes were considerably reduced to 7.7%, 12.2%, 21.6% and 32.8%, respectively. In vivo urinary excretion rate of AB-PA was compared between a total of 5 patients and 4 healthy volunteers after oral administration of 250 mg AB-PC. It was found that the patients excreted 9.1%, 10.7% and 12.7% of total dose at 0 approximately to 2 hours, 2 approximately to 4 hours, 4 approximately to 6 hours, respectively, while the average excretion rates in healthy volunteers were 1.54%, 2.88% and 7.94%, respectively. In 4 patients cross-over administration study, the combined dose of AB-PC and MDI-PC has been proved to clearly decrease the urinary excretion rate of AB-PA in 2 cases, but there was no significant difference in the average rate between the single and the combined dose.


The inhibitory effect of T-2 toxin on tolerance induction of delayed-type hypersensitivity in mice. Mice injected intravenously with 1 X 10(9) sheep red blood cells (SRBC) showed no delayed-type hypersensitivity (DTH) response to SRBC and were unresponsive to DTH induction by sc injection of an optimal dose of SRBC. However, when treated with T-2 toxin, a mycotoxin, 2 days after the iv injection, mice became to show significant DTH response and to be responsive to the DTH induction by the sc injection. When the spleen cells of the mice receiving the iv injection were transferred to unsensitized syngeneic recipients, the DTH response of the recipients to SRBC was suppressed. However, the suppressor activity of the spleen cells was decreased by T-2 toxin treatment. By the iv injection, cell population of the spleen was increased and that of the thymus decreased. In contrast, by T-2 toxin treatment 2 days after the iv injection, cell population of the spleen was not increased and that of the thymus was markedly decreased. The ratio of theta-bearing cells was increased in the spleen by the iv injection. However, such increase was not observed after the T-2 toxin treatment. The ratio of Ig-bearing cells in the spleen was not changed by the iv injection and the T-2 toxin treatment after the iv injection. T-2 toxin seems to interfere with generation of suppressor cells for the DTH response.


Relationship between monocytosis and T-lmphocyte function in human cancer. This study was designed to: 1) determine the relative number of monocytes in mononuclear cell suspensions derived from the peripheral blood of cancer patients and 2) ascertain if any relationship existed between the numbers of monocytes in those cell suspensions and T-lymphocyte function. Monocytes were quantitated by morphology verified by phagocytosis of antibody-coated erythrocytes. A significant difference (P less than or equal to 0.01) existed between the number of monocytes in suspensions from normal individuals (26.2 +/- 4.3) and cancer patients (38.0 +/- 13.4). The cancer patients were divided into 2 groups: 1) those who exhibited normal in vitro T-cell responses to phytohemagglutinin and 2) those in whom responses were significantly suppressed. The mean number of monocytes in suspensions from the cancer patient group with normal responses was 29 +/- 9, whereas that from the cancer patients with suppressed responses was 47 +/- 11, a highly significant difference (P less than or equal to 0.01). Therefore, the study demonstrated two things: 1) Mononuclear cell suspensions derived from cancer patients exhibited significant monocytosis relative to those from normal individuals and 2) a strong correlation existed between monocytosis and suppressed T-lymphocyte function in vitro.


Human autologous rosettes. II. Prognostic significance of variations in autologous rosette-forming cells in the peripheral blood of cancer patients. The distribution of autologous rosette-forming cells (A-RFC) was determined in 55 samples of peripheral blood mononuclear cells from healthy adult donors and 407 samples from 112 cancer patients. The mean percentage and absolute number of A-RFC were significantly reduced in the cancer patients compared to the healthy adult donors. These values for A-RFC were even more significantly reduced in patients with cancer relapse than in patients with complete remission of cancer. Thus diminution of this pertinent subset of T-lymphocytes has interesting clinical value by its being closely related to an adverse prognosis.


Quantitation of human thymus-leukemia-associated antigen in established hematopoietic cell lines by radioimmunoassay. A competitive radioimmunoassay for a saline-soluble human thymus-leukemia-associated antigen (HThy-L) was applied for quantitation of this antigen in leukemia and normal hematopoietic cell lines. Highly increased quantities of HThy-L were detected in all T-cell leukemia lines tested, regardless of the presence or absence of receptors for sheep erythrocytes. This elevated level of HThy-L in combination with high terminal deoxynucleotidyl transferase and adenosine deaminase activities and the presence of a T-lymphocyte-specific surface antigen appear to represent stable phenotypic characteristics of T-cell lines. Most normal B-cell lines had low quantities of HTy-L. The level of HThy-L was slightly elevated in a considerable number of lymphoma B-cell lines and in all non-T, non-B leukemia cell lines tested. No relationship existed between quantities of HThy-L and an expression of different surface immunoglobulin isotypes in B-cell lines. Low quantities of HThy-L were detected in leukemia myeloid and myeloma cell lines as well as in B-cell leukemia lines originating from patients with B-cells acute lymphoblastic leukemia. Apparently, the increased quantities of HThy-L in T-cell leukemia lines may be related to certain stages of T-cell differentiation at which leukemia cell transformation occurs.


[D-penicillamin-induced IgA-deficiency (author's transl)]. A 6 year old girl developed IgA-deficiency following treatment for chronic hepatitis with D-penicillamine. 4 months after discontinuation of the drug serum IgA and the number of circulating B-lymphocytes were still markedly reduced, in addition secretory IgA was diminished relative to secretory IgM. D-penicillamine should be used only if absolutely necessary and during treatment frequent monitoring of immunoglobulin levels becomes mandatory.


A standardized estimator of the prevalence of alcoholism based on mortality data. Death rates from alcohol-related causes correlated with over-all mortality and reflected general health conditions and demographic characteristics as well as the prevalence of alcoholism.


Surgical treatment of left main and left main equivalent coronary artery disease. There is a tendency to equate left main (LM) and left main equivalent (LME) coronary artery disease in terms of the surgical risk and benefit. Eighty-seven patients with LM disease were compared to 78 patients with LME disease as to operative mortality rate and long-term benefits. One hundred percent follow-up was obtained. Although the two groups were similar preoperatively with regard to age, sex, and ventricular function, the operative results in the two groups differed. There was a significantly higher operative mortality rate in the LM group of patients (12.6% versus 2.5%). However, the incidence of graft patency and relief of symptoms was lower in the LME group of patients. The late mortality rate was 4% in both groups. LME disease appears to represent a subgroup of patients with three-vessel disease and cannot be equated with LM disease.


Detection of human B cells and chronic myelocytic leukemic cells by rosette formation with sheep erythrocytes and fresh human sera. A new method of detecting the C3b receptor is reported. A particular merit of this method is that anti-RBC rabbit antiserum is not required. Rosettes were formed with human B lymphocytes, B lymphoblasts and granulocytes, using sheep erythrocytes (SRBC) sensitized with fresh human serum (FHS). T lymphocytes and T lymphoblasts did not form rosettes. The percentage of cells forming rosettes with this method approximated the percentage of rosettes formed with EACm. However, FHS coated SRBC did not react with most cells of B cell type chronic lymphocytic leukemia (CLL), whereas EACm rosette formations showed a definite reaction. On the other hand, 34--58% of cells of chronic myelocytic leukemia (CML) bound with the indicator red cells. SRBC sensitized with fresh rabbit or guinea pig serum formed rosettes with PBL, tonsil cells, B lymphoblasts and granulocytes. Complement and IgM antibody were required for this reaction, as in EAC rosette formation.


Evaluation of a state-wide neonatal screening programme. A screening programme which was already established to detect phenylketonuria in the newborn period in South Australia was extended to include screening for galactosaemia, homocystinuria, hereditary tyrosinaemia, histidinaemia, maple syrup urine disease and severe alpha 1-antitrypsin deficiency for a trial period. Later, screening for hypothyroidism was introduced. Results suggest that screening for galactosaemia and hypothyroidism are useful additions to the programme. Screening for trrosinaemia and alpha 1-antitrypsin deficiency produced a high number of requests for repeat samples, causing anxiety and no positive benefit to patients. Homocystinuria, an eminently treatable condition, was not detected, nor was maple syrup urine disease, a much less readily treatable condition. Histidinaemia was detected only once. Screening for tyrosinaemia, alpha 1-antitrypsin deficiency, maple syrup urine disease and histidinaemia has been discontinued. Newborn screening in South Australia currently includes tests for phenylketonuria, hypothydroidism, galactosaemia and homocystinuria.


[Methods for the detection of antibodies to native (double stranded) DNA (author's transl)]. Three different methods adequate for routine work, i.e. hemagglutination, counterimmunoelectrophoresis and radioimmunoassay, were used in the past in our laboratory to detect antibodies to native (double stranded) DNA. There was a high incidence of false positive or false negative results by counterimmunoelectrophoresis. Hemagglutination reaction was less sensitive in detecting anti-nDNA than was radioimmunoassay. Natural DNA preparations and a synthetic polynucleotide (3H-dAT) were used as antigenic substrates in radioimmunoassay providing well correlating binding values.


[The PABA-peptide test: a method in diagnosis of exocrine pancreatic insufficiency (author's transl)]. The synthetic peptide N-benzoyl-L-tyrosyl-p-amino-benzoic acid is selectively metabolized by chymotrypsin. Its derivates are excreted in urine and are taken as a measure of exocrine pancreatic insufficiency. The results of PABA-peptide test, of chymotrypsin activity and of the fat content of faeces were compared with each others in 25 patients suspicious to exocrine pancreatic insufficiency. The results correlate well. Because of the practicability the PABA-peptide test is suggested as an additional routine-method in diagnosis of pancreatic functions although it does not substitute any established method.


[Gastrointestinal hemorrhage into the duct of Wirsung caused by chronic pancreatitis and carcinoma of the pancreas (author's transl)]. Report on 3 cases of gastrointestinal bleeding from the pancreas. In 2 patients with pancreatic pseudocysts and carcinoma of the pancreas a hemorrhage from the papilla Vateri due to a communication with the common pancreatic duct was observed endoscopically. In the third case a pancreatic pseudocyst had ruptured into the stomach. In the 2 cases with bleeding from the papilla routine gastroscopy with prograde optical fiberscope revealed blood in the duodenum, while the cause of bleeding could be established only with a side viewing duodenoscope.


Evaluation of overall toxicity of high-dosage methotrexate regimens. The occurrence of overall toxicity was analyzed for 43 patients with osteosarcoma who received 349 high-dosage courses of methotrexate (HD-MTX) with citrovorum factor (Leukovorin) "rescue" (CF). The dosages of HD-MTX ranged from 50 to 350 mg/kg. Overall toxicity was assessed on the basis of five manifestations of toxicity: stomatitis, dermatitis, myelosuppression, liver dysfunction, and kidney function abnormalities. The great majority (91.4%) of the infusions were well tolerated, but 8.6% were associated with moderate or severe toxicity. Stomatitis and serum glutamic-oxaloacetic transaminase (SGOT) changes were the most frequent postinfusion findings. Three patients died from causes related to MTX toxicity. Dose, age, sex, and number of prior infusions were investigated by logistic regression analysis for prognostic effect on frequency of moderate to severe overall toxicity. Age and number of prior infusions had significant (P less than 0.06) effects on overall toxicity. Patients older than 15 years with greater than 10 prior infusions constituted the "high risk" group with a risk of moderate to severe toxicity 6.3 times that of the younger patients with fewer than 10 infusions.


Identification of two serum components regulating the expression of T-lymphocyte function in childhood myasthenia gravis. We studied serums and cells from nine children with myasthenia gravis to determine whether there were alterations in the distribution or function of different T-lymphocyte subpopulations. The low numbers of E-rosette-forming T lymphocytes and their failure to respond to antigen by producing normal suppressor T cells were correlated with the presence of an IgG antibody directed toward the theophylline-sensitive T-cell subset; this activity could be blocked by d-tubocurarine. Incubation of normal T lymphocytes with serum from patients rendered the cells "myasthenia-like" when assayed for E-rosettes and for antigen-induced suppressor-cell function. A second, non-IgG factor found in patients' serums had activity like that of thymic hormone and induced T-cell maturation in normal bone marrow. This factor was not inhibited by d-tubocurarine; its activity was strongest in the two patients most severely affected, and it disappeared after thymectomy in both these patients. We conclude that in childhood myasthenia gravis there may be two independent serum factors; one an IgG antibody directed at a subset of T lymphocytes, blocked by d-tubocurarine and apparently unaffected by thymectomy, and the other a thymus factor that induces T-lymphocyte maturation.


Needle biopsy of intrancranial lesions guided by computerized tomography. Biopsies can be performed directly with computerized tomography (CT) head scanners with some difficulty. The small scanning orifice does not allow enough room for needle placement; therefore, biopsy is difficult. In contrast, the scanning orifice of the CT body scanner is large enough to permit biopsies without hindrance. Over 300 CT-guided abdominal biopsy procedures have been performed at the Cleveland Clinic Foundation. We are reporting the technique and the results of 14 CT-guided brain biopsies. There were no complications in the series and an accurate diagnosis was made for 13 of the 14 patients.


[Evaluation of immunologic reaction of the body in patients with acute cerebrovascular diseases by means of the rosette test]. In 63 patients with brain ischaemia and 29 healthy subjects the rosette test was done and clinical observations were conducted parallelly. The percent of peripheral blood lymphocytes forming rosettes spontaneously was 53.7% in the group of patients, while in the control group it was 63.4%. The difference was statistically significant.


Bilateral interhemispheric subdural hematomas. Interhemispheric subdural hematomas are rare. Bilateral interhemispheric subdural hematomas in a patient with a ventriculoperitoneal shunt for hydrocephalus were diagnosed by computerized tomographic (CT) scan after mild head trauma. The value of CT scanning, the clinical presentation and treatment, and a review of the literature are presented.


[Evaluation of certain leukocyte subpopulations in the peripheral blood and cerebrospinal fluid in multiple sclerosis]. Using a mixed rosette technique the counts of lymphocytes forming rosettes E and EA and non-rosette-forming lymphocytes were determined in the peripheral blood and cerebrospinal fluid in 15 multiple sclerosis patients and 17 controls. A rise was observed in the percent and absolute value of non-rosette-forming lymphocytes in the peripheral blood and cerebrospinal fluid in these patients. Various immunological aspects of this fact in the pathogenesis of multiple sclerosis are discussed.


[Selective arterial perfusion with antienzymes in experimental acute pancreatitis. Preliminary experience]. Authors analyze some results obtained treating, with selective arterial perfusion (using antienzymes), experimental acute pancreatitis in dogs (fifteen). The first dogs' group was used to perform several experimental acute pancreatitis; the second group was treated by selective arterial perfusion and was related to group of dogs treated by i.v. antienzymes drugs. Histological and biochemical data are discussed. The results obtained with arterial perfusion are preliminary referred as better than classic i.v. antienzymes drugs therapy.


Ergotism with therapeutic doses of ergotamine tartrate. Two cases of acute ergotism are described in patients taking therapeutic oral doses of ergotamine tartrate and concomitant triacetyloleandomycin. Both showed satisfactory response to infusion of sodium nitroprusside with normal perfusion being obtained in the affected limbs. The treatment of ergotism with sodium nitroprusside is reviewed and the apparent interaction of ergotamine and triacetyloleandomycin is discussed.


Uncontrollable postpartum bleeding: a new approach to hemostasis through angiographic arterial embolization. A case of severe postpartum hemorrhage is reported. Three separate surgical procedures failed to reveal the source of bleeding, and standard surgical techniques, including bilateral ligation of the hypogastric arteries, were unsuccessful in producing hemostasis. However, angiography successfully identified the specific bleeding vessel, and transcatheter embolization with Gelfoam fragments quickly and effectively stopped the hemorrhage. The authors consider angiographic embolization to be an effective alternative approach to the control of pelvic hemorrhage and recommend that the technique be considered prior to surgical intervention.


Studies on the use of membrane markers for the differential diagnosis of malignant lymphomas. Lymphoid cells isolated from lymph nodes, spleen and the peripheral blood were examined using the rosette test with sheep erythrocytes (E), immunofluorescent staining of the surface immunoglobulins (SmIg) and the combined test (SmIg + E). The studies were performed on 48 patients with untreated non-Hodgkin lymphoma, 14 Hodgkin patients, 5 patients with lymphadenitis and on 132 controls. In the control group the following percentages of B-T lymphocytes were obtained: blood (n = 100); T-68 +/- 9, B-20 +/- 6, 0-11 +/- 7, BT-1 +/- 1, lymph nodes (n = 24): T-62 +/- 13, B-19 +/- 11, 0-18 +/- 8, BT-1 +/- 1, spleens (n = 8): T-45 +/- 9, B-33 +/- 9, 0-23 +/- 7, BT-1 +/- 1. In non-Hodgkin lymphoma lymph nodes a statistically significant increase of B and 'null' cells was noted in comparison to controls and to the Hodgkin lymphoma group. The characteristics of the Hodgkin nodes did not differ significantly from controls. After arranging the non-Hodgkin lymphomas according to the Kiel classification it was observed that the low-grade malignant lymphomas subtype most often an immunological 'B type' and 'mixed B/0' type was present whereas the high-grade malignant lymphoma group showed a distinct majority of 'null' cells. It was concluded that the surface  markers studied allow a differentiation in most cases between the non-Hodgkin lymphomas and other disorders of the lymphoid system. They are not sufficient to distinguish the subtypes of non-Hodgkin lymphomas but do give interesting information about the more exact nature of the disorder.


Colony-stimulating and colony-forming cells in peripheral blood as prognostic markers in acute myelogenous leukemia. Colony-forming cells (CFC) and colony-stimulating activity (CSA) in peripheral blood cells have been studied before and repeatedly during treatment of 32 patients with acute myelogenous leukemia. WBC obtained after Isopaque-dextran separation were cultured in vitro by a double-layer agar technique. Before treatment 19 patients out of 32 had CSA and all had CFC; both CSA and CFC were found in 19 patients. In follow-up studies during treatment, CSA was mainly unaffected during the leukopenic phase, while CFC were suppressed. No CFC were found at WBC counts below 1,000/mm3. This seems to imply that CFC are more sensitive to chemotherapy than colony-stimulating cells. 14 patients entered remission; all of them had CSA. 16 out of the 18 nonresponders lacked on or both types of cells. The presence of CSA and CFC in peripheral blood therefore appears to be a sign of favorable prognosis, while the absence of CSA and/or CFC implies lack of response to treatment. The conclusion from this study is that the presence of both CFC and CSA in peripheral WBC is a sign of a good prognosis. Absence of CFC and/or CSA in the initial sample indicates that the patient is unlikely to respond to conventional therapy with cytotoxic drugs. The presence or absence of CSA alone has a higher prognostic significance than the presence or absence of CFC.


Corneal monosporiosis. A review and report of 1 case. Reviewing the world literature and including some personal communications and our own case, we have found 14 cases of keratomycosis by Monosporium apiospermum or by its perfect state Petrillidium (Allescheria) boydii. A table with only the 12 well-documented observations was prepared.


Meretoja syndrome. Lattice dystrophy of the cornea with hereditary generalized amyloidosis. The clinical history as well as the general and ophthalmic pathology of a woman with the Meretoja type of hereditary systemic amyloidosis and lattice dystrophy of the cornea is described. Extraocularly, amyloid could be demonstrated in all the arterial walls, the peripheral nerves and in the glomeruli; intraocularly, amyloid was seen in the cornea and the sclera.


The management of dental extractions in cases of thrombasthenia complicated by the development of isoantibodies to donor platelets. Two cases of thrombasthenia, a rare hereditary disorder of platelet function, are presented. The oral surgical and dental management of these cases is discussed in the light of the development of isoantibodies to transfused platelets in one of the cases and in another case encountered. The problems of obtaining donor platelets matched for platelet and HL-A antigens are discussed. Emphasis is placed on the use of local hemostatic measures and antifibrinolytic agents in the management of hemorrhage in this disorder and the avoidance of platelet transfusions as far as possible. Conservative dentistry and early preventive dental advice are considered desirable in order to avoid extractions.


Menière's disease: morphological findings in eighth nerve and vestibular end organs. 37 patients with advanced Menière's disease were operated on by translabyrinthine 8th nerve neurectomy or middle fossa vestibular neurectomy. Cochlear and vestibular nerves, epithelia of the utricular macula and ampullar crista of horizontal canal were studied. All specimens were fairly well preserved and the microscopic studies suggested that there is no general deterioration of these structures even in long-standing, advanced Menière's disease, but some minor deviations from normal are present in individual cells.


Ventriculography with positive contrast medium in early infancy. 42 ventriculographies (PV) were carried out in infants between 10 days and 10 months of age using positive contrast medium. Indications, technique of PV and complications are discussed; PV is compared with CT and it is concluded that PV is a simple method of clarifying the causes of a macrocephalus in infancy without great technical effort and that the roles of CT and PV are valuable diagnostic modalities which are complementary.


[Rubber band ligation. Ambulatory treatment of hemorroids (author's transl)]. The rubber ligation, ambulatory treatment of hemorroids due to J. Barron, consists in the strangulation of hemorroidal packs by an elastric ring, assuring the destruction by ischemic necrosis. Widely spread in France since 1968, the treatment forms the subject of a retrospective enquiry among 30 french proctologists, after ten years of experiment. It bears on 1074 patients and 4122 ligatures. The prolapsus disappeared in 60% of the cases and disminished in 32%. The hemorragies have stopped in 69% and these results go on beyond four years in 87% of the cases. Less heterogenous statistics and more precise indications would improve these results which, however, confirm the efficience of the treatment.


[Prognostic value of delayed-hypersensitivity skin tests and rosette studies in acute non-lymphoid leukemias]. Delayed hypersensitivity skin reactions to Tuberculin and Candidin were studied in 28 patients with non lymphoid acute leukemias. The reactions were found negative in most patients during blastic crises, whereas delayed skin reactions to Candidin were positive during remissions. The possible prognostic significance of the depressed delayed hypersensitivity response in such patients deserves further studies. Alterations of circulating T lymphocytes were observed, including low percentages of E and active E rosette-forming cells during blastic crises, and persisting low E and E active rosettes in some patients in remission; such abnormalities were less frequent in patients with remission of long duration. The percentages of EA and EAC rosettes-forming cells were found normal during blastic crises and remissions. In some patients in remission, lymphocytes were found to bind sheep erythrocytes either uncoated or coated with IgM antibodies, this penomenon which is not observed with normal lymphocytes may reveal persisting abnormalities of a yet undefined nature.


Cytochemical and ultrastructural characters of human peripheral blood lymphocytes according to their surface markers. The human peripheral blood lymphocytes are characterized by different surface markers: The B lymphocytes by the EAC rosettes and surface immunoglobulin and the T lymphocytes by the E-rosettes. Each lymphoid population has been studied for cytochemical parameters (Acid phosphatase, beta-glucuronidase) by light microscopy and for ultrastructural characteristics by micromanipulation and immunoelectronmicroscopy. It has been shown that the studied enzymes are markers for T cells with high affinity for sheep red blood cells and that the separation of lymphocytes by the rosette techniques leads to homogenous cell populations at the ultrastructural level. A classification of peripheral lymphocytes according to their immunocytochemical profile is discussed.


Heterogeneity of failure of visual acuity in Graves' disease. The eye manifestations of Graves' disease are usually mild and self-limiting. Occasionally they follow a progressive course leading to visual loss and total blindness. The ocular manifestations bear no relationship to the metabolic state and may appear before, during or after onset of thyrotoxicosis. Characteristically they become evident at about the time of onset of hypermetabolism. Various factors responsible for the failure of visual acuity are discussed with case illustrations.


Research directions in psychiatric epidemiology. A sufficient number of studies of geographically defined populations have now been done so as to make it clear that when all the various kinds of mental illnesses are lumped together, the total prevalence rates commonly amount to 20% or more. These findings imply major challenges to theory, policy, administration, and practice in the health field, and point to a need for vastly more information and understanding. This article sketches some of the directions such investigations might take.


[Effect of estrogens on the development of the leukocyte migration inhibition reaction in vitro in malignant neoplasms]. Effect of estron and estradiol hormones on the blood leukocyte migration inhibition test was studied in vitro. Blood autoplasm and water-salt extracts from the gastric tumour tissue were used as antigens. Marked inhibition of the blood leukocyte migration was noted in the majority of oncological patients in the presence of homologous tumour antigens or blood autoplasm. The effect of leukocyte migration inhibition was eliminated if leukocytes were preliminary incubated with estrogens, and then washed, or if the hormones were introduced into the medium together with the autoplasm or with the extracts from the tumour homologous tissue. It is suggested that estrogens block the antigen receptors on T-lymphocytes.


Brief group therapy in myocardial infarction rehabilitation: three- to four-year follow-up of a controlled trial. A trial of brief group therapy as part of a rehabilitation program for postmyocardial infarction (MI) patients was carried out. Forty-four patients surviving their first MI were randomly allocated to either group therapy or control group status and were followed over 4 years. An additional group of 17 patients were referred for post-MI group therapy sessions after the termination of the controlled experiment and were followed for 3 years. Patients who received group therapy had significantly less follow-up coronary morbidity and mortality, and returned to work at significant higher percentages than control patients. Although neither group therapy nor control group patients meaningfully altered conventional coronary risk factors, group therapy patients (in the controlled trial) successfully altered selected coronary-prone behaviors. Educational information regarding the physiological and psychological aspects of coronary heart disease, presented in the group therapy sessions, was forgotten over follow-up. It is concluded that the supportive aspects of the group therapy experience played the most important role in determining the rehabilitation advantages seen for treatment patients.


Transcatheter therapy in angiography: indications, techniques, and illustrations. This paper reports the history, methods,and indications currently accepted for transcatheter management of two distinct pathologic states. Reported are numerous cases from available literature and five cases from our own experience, supported by illustrations from angiography performed in this institution. It is hoped that the technologist has gained an understanding of the indications and methods for performing transcatheter therapies and that the growing interest in this adaptation of radiologic capabilities will serve to enhance the technologist's scope of operation as a member of the health-care team. The future of diagnostic angiography cannot be predicted, pending full evaluation and implementation of the rapid advances in other diagnostic modalities. The future of transcatheter therapeutic measures, however, appears worthy of continued vigorous investigation.


Haematological correlates of phytohaemagglutinin-induced lymphocyte transformation in horses. The purpose of these investigations was to assemble and compare data which might illustrate a functional relationship between phytohaemagglutinin-induced transformation of equine lymphocytes in vitro and the haematological profiles of the lymphocyte donors. Statistically significant correlation between transformation and a haematological parameter was taken as evidence that both may be part of a common regulatory system. There was no evidence that transformation in vitro was affected by artefactual variation in the cellular composition of the cultures. Transformational behaviour of lymphocytes in autologous plasma showed significant correlation with donors' total leucocyte, neutrophil and T cell count. Different batches of donor plasma varied in ability to support the transformation and this ability was found to correlate significantly with the total leucocyte, eosinophil, lymphocyte and T cell count of the original blood. It is concluded that previously reported variation in transformation ratios of normal equine lymphocytes is attributable to regulatory mechanisms affecting circulating blood as a whole and that helminth parasitism may be among the primary causal agents which modify the mechanism.


Alpha1-antitrypsin deficiency: genetic, clinical and functional correlations in a three generation family. alpha1-antitrypsin (alpha1-AT) deficiency is a hereditary condition transmitted as an autosomal codominant trait. Fully deficient homozygotes develop chronic obstructive pulmonary disease at an early age. It remains controversial whether heterozygotes develop some degree of airway disease at an early age which results in severe obstructive disease later in life. We studied 12 alpha1-AT-deficient members of a family spanning three generations by extensive pulmonary function tests, clinical history and genetic determinations. 3 of the subjects were homozygotes and showed important clinical and lung function abnormalities by the age of 30. Two out of 9 heterozygotes, a female and a male, had decreased dynamic compliance, elevated closing volume and low PaO2. 3 showed clinical and physiological abnormalities (elevation in functional residual capacity and residual volume, low FEV1/FVC and elevated closing volume); however, these alterations could be attributed to their smoking habits or concomitant medical condition. The remaining 4 subjects were normal. None of the heterozygotes showed alterations in the static elastic recoil of the lung or static compliance.


[Scintigraphic characteristics of coxopathies: etiologic importance]. Morphological and quantitative studies of the uptake of diphosphonates labelled with technetium 99m were done on 179 pathological hips : 106 aseptic osteonecroses of the femoral head, including 20 at an early stage, 11 algodystrophias (transitory osteoporoses of the hip), 20 coxarthrosis, 16 cases of Paget's disease, 12 isolated malignant lesions of the femoral neck. The location, extent and intensity of the uptake are very variable and depend not only on the etiology of the lesions but also on their stage of evolution. Bone scintigraphy provides, for numerous pathological hips, pieces of information which complete the results of the clinical, radiological and biological study, with which it should always be compared. It can shed light on the etiologic diagnosis of a painful hip at the beginning of its evolution, before the appearance of rare x-ray signs, thanks to certain very precise characteristics of the labelling. This is the case for algdystrophias, osteonecroses, coxitis and strain fractures of the femoral neck.