Drug-seeking behavior during methadone maintenance. Six subjects were given the opportunity to work for saline placebo and hydromorphone (4 mg i.v.) several times weekly before and during a period of maintenance on methadone (100 mg p.o. daily). Measures of pupillary change and reports of "liking" in response to hydromorphone dropped to saline control levels when the daily dose of methadone was approximately 60 mg. Half of the subjects continued to work intermittently for hydromorphone for four weeks while they were receiving 100 mg of methadone daily. These data support the assumption that methadone maintenance reduces the reinforcement value of other opiates and behaviors associated with obtaining them.


Physiological mechanisms for cardiac control by nutritional intake after early maternal separation in the young rat. Series of analytic experiments are presented that explore possible physiological mechanisms for the control of cardiac rate by nutritional intake in the pre-weanling rat. The essential properties of the nutrient and the first site of action were studied by using fluids of different pH, osmolality and chemical composition administered intravenously as well as intragastrically. Several probable effector pathways were explored: neuroendocrine (adrenal medullary and adrenocortical, thyroid), cholinergic and adrenergic. Pharmacological blocking agents, surgical removal of glands, replacement hormones and spinal cord trasaction were utilized. Afferent pathways such as vagus and splanchnic systems were approached surgically and the gastrointestinal hormones, histamine, insulin and glucagon, were studied by administration and pharmacological blockade. The evidence tended to rule out a number of possible mechanisms and pathways and to make it appear likely that nutrient acts initially at the gut wall, that the CNS then responds by increasing tone in the classical spinal cardioacceleratory pathways to the beta-adrenergic synapses of myocardium.


A new preparative method for microspectrophotometric DNA-measurement in megakaryocytes, revealing a significant group of cells with a DNA content of 64 N. Microspectrophotometric investigations of Feulgen-stained rat bone marrow megakaryocytes, comparing the traditional smear method and a new 1 G sedimentation and 40 degrees C evaporation (S. E.) method, have shown that the latter reveals a significant group of megakaryocytes (ca. 30 percent) with a DNA content of 64 N. This group is totally absent when the smear method is used.


[Orthorhythmic pacemaker and salvo-like cardiac stimulation. New procedure aiming at the suppression and prophylaxis of cardiac arrhythmia and the determination of electrophysiological measurement magnitudes in vivo]. The orthorhythmic pacemaker (ORPM) represents a new apprach in cardiac stimulation. The use of conventional demand pacemakers is essentially limited to the treatment of bradycardic arrhythmias. The principle of the ORPM consists in early stimulation after premature beats, taking into account the R-R interval of the preceding spontaneous beat. In this "extrasystolic pacing" the escape interval is not fixed; rather, the premature electric stimulus will be fired after an interval, the duration of which can be selected as a fraction of the preceding cycle length. The ORPM enhances the possibilities for treatment of atrial and ventricular tachycardias due to re-entry. The idea of "bursts" of stimulation e.g. the firing of up to ten impulses within a short time, is put into practice in the actual latest ORPM model. It widens the application of the ORPM principle and allows simplified measurement of the refractory period.


[Risk of chronic carbon monoxide poisoning in automobile garages. Results of a study in the Lausanne region]. Clinical and physiologic data on chronic carbon monoxide poisoning are reviewed and the results of an investigation involving 7 garages in the Lausanne (Switzerland) area are reported. The aim was a practical approach to the relationships between carbon monoxide level in the air, COHb and clinical picture. The study covered working conditions (especially ventilation) but did not take into account of other factors (stresses) which may effect the parameters investigated. CO was measured by continuous recording with an MSA Carbon Monoxide Alarm and the hourly and daily averages were determined. The garage personnel replied to a questionnaire and underwent a brief clinical examination including taking of digital blood samples for measurement of hematocrit and carboxyhemoglobin level by the method of COMMINS and LAWTHER as modified by BUCHWALD. One of the garages did not meet present health requirements. Statistical analysis revealed a significant correlation between carbon monoxide and carboxyhemoglobin. The incidence of complaints was highest in poorly ventilated garages. On the basis of COHb level in the total group of employees, together with data from individual histories, it is possible to evaluate the risk of carbon monoxide poisoning in a given garage.


[Behavior of cerebrospinal fluid proteins in degenerative diseases]. 132 cerebrospinals fluids from patients with degenerative diseases of the central nervous system have been analyzed for protein distribution in agar gel electrophoresis. After subdivision into diagnostically well defined groups these patients were compared with 48 with metabolic and psychiatric diseases and with 79 normal controls. The majority of diagnostic groups showed a tendency to permeability impairment. Other outstanding deviations were not found, except for single cases which were not statistically typical of the groups as a whole. However, the "degenerative type" of proteinogram emphasized in the literature predominated not only in the degenerative groups but also in certain other diseases with destruction of central nervous tissue which do not belong to the degenerative diseases in the strict sense. On the other hand, there are some degenerative subgroups without this "typical" electrophoretic pattern. There would thus appear to be grounds for amending the term "degenerative" into "tissue destroying" or "atrophic type", to avoid misinterpretation.


[Vagal effect on sino-atrial node frequency and A-V overdrive in hypersensitive carotid sinus reflex and sick sinus syndrome]. Two syndromes, hypersensitive carotid sinus reflex (HCSR) and "sick sinus syndrome" (SSS) were studied in 28 patients, 6 of whom served as controls. Carotid sinus pressure was performed during sinus rhythm (CSP 1) and atrial stimulation just above the sinus rate (CSP 2). Overdrive suppression was also tested. Vagal stimulation provoked different effects in HCSR and in SSS. The vagal reaction to CSP 1 was more manifest in HCSR than in both SSS and the controls. After CSP 2 A-V conduction was delayed longer in HCSR than in SSS and the controls. Following atropine, the vagal effect on HCSR was more pronounced than on SSS and the controls. With HCSR, the duration of vagal influence on R-R intervals (A-V conduction) was significantly shorter than on P-P intervals (sinus rate). After atropine, there was less vagal effect on A-V conduction than on the sinus rate in HCSR, meaning that A-V conduction was shorter and less affected than the sinus rate by carotid sinus pressure. Prolonged suppression following overdrive established the diagnosis of SSS. This suppression was found not to be affected by atropine. A dependency of suppression on the rate and duration of overdrive could not be ascertained for SSS. The newly formulated "postdrive P-P interval recovery time" subdivided SSS in such a way that two different degrees of severity could be illustrated. The conclusion was that HCSR was caused by an excessive reaction to vagal stimulation rather than by a dysfunction of the sinus node or A-V conduction system. SSS might be based on tissue damage in the sinus nodal region but it did not show increased sensitivity to vagal influence.


RNA processing and RNA tumor virus origin and evolution. The results of molecular hybridization experiments with high-molecular-weight RNA isolated from RNA tumor viruses and DNA from normal cells suggest that RNA tumor virus genomes originate from cell genes. Some RNA tumor viruses (here called class 1) appear to have been generated in recent times in that their RNA is closely related in nucleotide sequence to certain cell genes (class 1 genes). A second class of RNA tumor viruses (here called class 2) is more distantly related to genomic information of normal cells. Structural properties of the RNA of RNA tumor viruses lead us to propose that the tumor virus RNA is originated when RNA transcripts of class 1 genes are processed by a mechanism we call "paraprocessing." We postulate that RNA paraprocessing is normally used only at particular times during differentiation and is characterized by the cytoplasmic appearance of high-molecular-weight RNA chains containing terminal polyadenylic acid (200 residues). Paraprocessing of class 1 gene transcripts in committed or differentiated cells is considered to be aberrant in transcription that can lead to the generation of an RNA tumor virus genome. If the paraprocessed class 1 gene transcript codes for a reverse transcriptase, replication of the RNA becomes possible. Transfer of the replicating RNA to a new cell can result in genetic change such that the virus genome mutates, differing from the original progenitor genes. We propose that this genetic change causes class 1 viruses to become class 2. These ideas are applied to evidence concerning the biology of infection of RNA tumor viruses and concerning the involvement of RNA tumor viruses in human cancer. Genetic change can also occur during the origination of an RNA tumor virus genome by repeated reverse transcription and recombination (45) or by genetic alteration of particularly changeable cell genes ("hot spots") (43).


Recent results in the surgical treatment of Fallot's tetralogy. Tetralogy of Fallot consists essentially of two abnormalities: a large, unrestrictive ventricular septal defect and severe obstruction to the outflow of the right ventricle. A clear understanding of the principles described in this article should result in a mortality of under 5% after complete correction of tetralogy of Fallot.


Effects of major abdominal operations on human blood rheology. Serial blood rheological measurements were systematically carried out in 14 patients undergoing major elective abdominal operations for a period up to 10 days after operation. The measurements included blood viscosity over a wide range of shear rates (0.01 to 208 sec.-minus 1), hematological data, and plasma protein concentrations. Significantly elevated plasma viscosity preoperatively accounted for a normal blood viscosity in the presence of anemia. After an initial drop due to hemodilution lasting for 1 to 3 days after operation, blood viscosity returned to normal by the tenth postoperative day. This was the result of an increased plasma viscosity, primarily due to rise in plasma fibrinogen and alpha2- and beta2-globulin concentrations. The red cell deformability of these patients was normal except for one patient who received seven units of transfused blood. The results of this investigation suggest that abnormal rheological properties of blood and plasma should be considered in therapeutic attempts to improve microcirculatory flow and oxygen delivery to tissues.


Soluble proteins of bronchopulmonary secretions from patients with cystic fibrosis, asthma, and bronchitis. The concentrations of nine plasma proteins were determined by quantitative immunoelectrophoresis in sputum specimens from 29 patients with cystic fibrosis (CF) and from 24 patients with severe asthma and chronic bronchitis. The results suggested that the population of CF patients could be divided into two groups in spite of an absence of difference in clinical status between the groups. Average concentrations of seven plasma proteins in sputum of group I CF patients were identical with those in sputum of patients with bronchitis, but the average concentrations of six of these proteins in sputum from group II CF patients were higher than those in specimens from the bronchitic patients and were similar to corresponding concentrations in sputum from patients with asthma, all of whom were examined while in status asthmaticus. The average concentrations of 14 secretory proteins were the same in all sputum specimens whether or not they were produced by patients with cystic fibrosis, asthma or bronchitis. It was concluded that the concentrations in the bronchopulmonary secretions of proteins associated with host defence were not diminished in patients with cystic fibrosis, and failure to produce adequate concentrations of proteins with antimicrobial activity was unlikely to be responsible for the above average susceptibility to chest infection in cystic fibrosis. It is suggested that there exists a group of CF patients in whom a pulmonary allergic reaction generates an inflammatory response as severe as that characterizing status asthmaticus and that this response could be detrimental.


Toxicological implications of pesticides: their toxic effects on seeds of food plants. Pesticides are widely used for the protection of economic crops from a variety of noxious pests. The repeated and indiscriminate uses and the extreme stability of certain pesticides have led to their accumulation in plants, animals, soils and sediments, thus effecting widespread contamination of the environment. Soil contaminants are especially serious because they can inhibit or impair the seed germination of our food and feed crops. Seeds can come in close contact with pesticides through processes such as prematurity application, fumigation, seed dressings, and seed treatments. Several reports have indicated the toxic effects of pesticides on seed germination. Possible mechanisms of the toxic action on pesticides during the germination of seeds have been discussed with emphasis on biochemical, histological, and cytological alterations. Bioassay procedures employing seed germination as a smiple, feasible, economical, time-saving indicator of toxicity have been described briefly. Attention is then drawn to the possible potential health hazards arising from the presence of pesticidal chemicals in food plants since the toxicological implications of long term exposure to pesticides are often more far-reaching.


The effect of disodium 5-ribonucleotide on reproductive function over three generations in the rat. Deitary levels of 0.1, 1.0 and 2.0% disodium 5-ribonucleotide were administered to rats of the CD strain over 3 generations, and the growth and reproductive performance were compared with those of a control group. Treatment did not appear to affect parent animals, as assessed by the incidence of mortality, bodyweight change, food consumption, mating performance, Pregnancy rate, Gestation Peroid, and post-mortem findings. Total litter loss, Litter size, Litter and mean pup weights, pup mortality and the incidence of skeletal or other variants in the offspring were unaffected by treatment at any dosage level. Additional organ weight analysis and skeletal staining of 10 males and 10 females from all groups, and the histological examination of 10 male and 10 females  of the control and 2.0% level groups of the third generation did not provide any evidence of effects that could be related to treatment.


[Toxicity by relay. I. General principles of  a new method for the assessment of Toxicity of addivitives to animal feeds]. Chemical substances added for various purposes to the feeds of farm-reared animals may enter the body of these animals. This may lead to the persistence, in food offered for human consumption, of residues which may be potentially toxic under conditions of repeated absorption over the greater part of the life span. The evaluation of the safety of these residues for man poses complex problems. Their ideal solution demands very often a number of careful experiments. The methodology called "toxicity by relay" consists essentially of the submission of the animal feed itself, which is likely to contain a mosaic of residues, to long-term testing in laboratory animals. Provided a satisfactory safety factor can be applied, this methodology can contribute information permittinga conclusion regarding the acceptablity, even provisionally, of the feed additive for the use which is envisaged. In  addition this methodology enables the provision of results  constituting a criterion for the rejection of the additive under test. For these reasons it appears to us an appropriate procedure, taking its place among the tests to be undertaken for the toxicological evaluation of additves to the feeds of farm-reared animals.


Changeable lymphocytotoxic antibody activity in patients with cervical carcinoma. In patients with cervical carcinoma examined over an extended period of time we observed lymphocytotoxic antibody activity more often in patients with terminal invasive carcinoma than in patients with preinvasive carcinoma. Antibody activity was very variable and it is postulated that this man relfect in vivo consumption of such antibodies as a consequence of qualitative or quantitative variations in cancerous tissue mass. In almost all instances we were unable to establish the specificity of the lymphocytotoxic antibodies with respect to known histocompatibility antigens. This suggests that their activity may be directed against a nucleus of HL-A determinants present in all human cell lines.


[Biochemical and physiocochemical characteristics of a type C virus isolated from spontaneous lymphosarcoma of CC57Br strain mice]. The properties of murine oncornavirus produced by cells of spontaneous lymphosarcroma of CC57Br mice are described. In addition to the properties common for C-type RNA tumor viruses such as 60-70 S high molecular weight RNA, the presence of RNA-directed DNA polymerase and murine gs I (intraspecies) antigen and typical morphology in electron microscope, etc., the virus under study is characterized by instability of virions, unusual features of the DNA polymerase system and by the absence of demonstrable oncogenicity either in laboratory animals or in tissue cultures.


[Reproduction of leukovirus RD-114 in diploid and heteroploid human cells]. The capacity of leukovirus RD-114 to replicate in human embryo lung diploid cell cultures and continuous human angiosarcoma cell cultures (AS and 709 lines). Differences in the capacity to support the virus reproduction were observed in the two strains of human embryo lung cells (HEL-1 and HEL-3) and the two continuous angiosarcoma cell lines. No virus reporduction was observed in mouse and rat cell cultures. No cytopathic or transformation changes were caused by the virus in any of the systems examined.


[Fragmentation of gamma globulin preparations manufactured in the USSR]. Gamma-globulin preparations prepared by the alcoholic method from the placental and abortion sera were split during storage under the effect of proteases contained in them; fragments with a molecular weight of 50 000 and 60 000 were formed. The most intensive splitting was seen in the preparations obtained from the precipitates of B placental and abortive sera. Some delay in the gamma-globulin fragmentation could be reached by addition to protease inhibitors--epsilon-aminocapronic acid or cyclocapron.


[Comparative analysis of gamma globulin preparations isolated by means of DEAE-Sephadex and DEAE-cellulose]. Preparations of rabbit gamma-globulin obtained with the aid of ion-exchange chromatography on DEAE-Sephadex contained an admixture of other serum proteins revealed by disc-electrophoresis in acrylamide gel. This impurity can be eliminated by rechromatography of gamma-globulin preparations of DEAE-cellulose in the same buffer solutions which were used for purification of gamma-globulin on DEAE-Sephadex. Better purification of gamma-globulin on DEAE-cellulose can supposedly be attributed to the effective absorption on cellulose basis of euglobulin aggregates which form in the solutions with a low ionic power used for chromatographic isolation of gamma-globulin on ion-exchangers.


[Cytogenetic characteristics of the vaccination process in children, primarily vaccinated against smallpox]. An increased rate of chromosome aberrations in the peripheral blood lymphocytes was observed in children between 1 and 21/2 years of age beginning at 4 days after vaccination. The number of aneuploid cells and chromosome aberrations increased for 1 month but were not found 6 months after vaccination. Administration of measles gamma-globulin in a dose of 0.75 ml before vaccination did not influence significantly the frequency of chromosome aberrations. A direct correlation was observed between the height of the immune response and the rate of chromosome aberrations. The observed changes in the chromosomal apparatus are not specific for the effect of vaccinia virus but indicate sterotypic reaction of the macroorganism in response to an alien antigen.


The effect of progestogens on vaginal cytology. Various progestogens were given to postmenopausal and premenopausal women. The first group consisted of 46 postmenopausal patients and in the postmenopausal atrophic smear, 17 acetoxyprogestogens produced no effect. However, the administration of two 19 nortestosterone derivatives, ethynodiol diacetate and norethisterone increased the Karyopyknotic Index and degree of proliferation of the epithelium, presumably due to their estrogenic metabolites. Low grade hypotrophic smears, consisting of parabasal and intermediate cells, reacted by a decrease in the size of the intermediate cells associated with clumping, and a disappearance from the smear of parabasal cells. In the case of ethynodiol diacetate, its estrogenic effect of elevating the Karyopyknotic Index occurred before the progestogenic effect of clumping and fusing of the intermediate cells. The second group consisted of 370 women using an oral form of sequential contraception, based on administration of 0.05 mg ethinyl estradiol daily for three weeks followed by a combined oral contraceptive containing the same amount of estrogen with varying progestogens for a further week. The anti-estrogenic effect of the various progestogens was then compared by their ability to lower the Karyopyknotic Index. This levelled out after four or five tablets. The most potent progestogen was d-norgestrel in the lowest dose of 0.25 mg and this compound exerted a greater effect than 4 mg norethisterone, 1 mg ethynodiol diacetate or 4 mg megestrol acetate.


Computer analysis of defined populations of lymphocytes irradiated in vitro: I. Evaluation of murine thoracic duct lymphocytes. Computer-assisted morphometric analysis of murine lymphocytes obtained by thoracic duct cannulation demonstrates two populations of cells; the larger population (73 percent) appears to be thymus-derived and the remaining 27 percent is of bone marrow origin. Following exposure to varying amounts of x-radiation, morphologic alterations in both populations are evident. The smaller cell populations are evident. The smaller cell population exhibits some of these changes at lower dose levels than does the larger population. In addition, the character of the radiation-induced changes appears to be different for the two populations of lymphocytes. After 500 rad, the nuclei of the larger population appears unchanged; the nuclei of the population representing 27 percent of the cells have become enlarged and vacuolated and are thought to be edematous. After 2000 rad, the nuclei of the larger population appear pyknotic with coarsely clumped chromatin. In the examined set of cells, the smaller population could no longer be detected after 2000 rad. Such disparate responses to radiation-induced injury may correlate with known differences in immunologic function which serve to distinguish thymic-dependent and bone marrow-derived small lymphocytes.


Topography of the sex chromatin in vaginal histiocytes. Routine vaginal smears with good numbers of histiocytes with kidney shaped morphology of their nuclei were selected for the study of sex chromatin topography. A variable distribution of the sex chromatin was found in 125 nuclei studied: polar in 57.4 percent, ventral in 21.9 percent and dorsal in 20.7 percent of the nuclei. No relationship was found between sex chromatin and cytoplasmic morphology and phagocytic activity.


The antigenic determinant of the LH-releasing hormone for three different antisera. Antigenic determinants of LH-releasing hormone (LH-RH) were investigated by testing the cross-reaction of LH-RH analogues and fragments in LH-RH radioimmunoassay (RIA) systems using 3 different antisera against the LH-RH decapeptide. Rabbit antiserum No. 419 was generated against LH-RH adsorbed on polyvinylpyrrolidone (PVP). Antisera Nos. 710 and 742 were produced by immunizing rabbits with LH-RH conjugated either with bovine serum albumin through its C-terminus, or with human serum albumin through the N-terminus, respectively. For antiserum No. 419, the N-terminal (pyro)-glutamic acid and/or histidine in positions 1 and 2 of LH-RH, respectively, were found to enhance the antigen-antibody interaction, but were not indispensable for it. Similarly, the C-terminal amide and glycine-NH2 did not play a major role in these interactions. The LH-RH heptapeptide fragment, corresponding to amino acid sequence from positions 3 to 9, showed a cross-reactivity in this RIA system with LH-RH, although greater amounts than those of cold LH-RH were required for a comparable inhibition of binding of labelled LH-RH. For antiserum No. 710, the LH-RH hexapeptide fragment corresponding to positions 2 to 7 showed considerable cross-reactivity. Histidine in position 2 played an important role but neither the amide group nor the glycine amide group at the C-terminus were essential. For antiserum No. 742, the C-terminal tetrapeptide-amide fragment of LH-RH showed considerable cross-reactivity in the LH-RH, the amide moiety itself being of crucial importance. These antisera may be useful in investigating peptides related to LH-RH in biological materials.


Changes in chromatin morphology after infection of mouse embryo fibroblasts with polyoma virus, detected by image analysis. Nuclear chromatin properties in control, SV40-infected and polyoma-infected cultures of mouse embryo fibroblasts were studied using quantitative image analysis. Distribution of Feulgen-DNA-content per nucleus was found to be similar in all three groups of cultures. No differences in nuclear area, mean optical density of chromatin and area of chromatin at different optical density thresholds were measurable between control and SV40-infected fibroblasts. Polyoma-infected fibroblasts were found to have smaller nuclei, more dense and less homogeneous chromatin than non-infected cells. The changes of chromatin in polyoma-infected cells occur in G1, middle S and G2 nuclei. The results are interpreted as an early manifestation of the cytopathic effect of polyoma virus.


Enzyme inhibition by antibodies.

Enzyme inhibition by antibodies. The interest in the inhibition of enzymes by their specific antibodies stems mainly from the fact that these systems can serve as suitable models in the study of neutralization of biologically active molecules in general. The interaction of enzymes with their specific antibodies generally leads to a reduction in their enzymatic activity. The mechanism of this inhibition is rarely a direct combination of the antibodies with the catalytic site, but is rather due to steric hindrance, namely, barring the access to the active site. In several systems the mechanism of the antibody effect is by conformational changes which it induces on the enzyme. In these cases, the interaction with the antibody may result either in inhibition or in enhancement of the enzymatic activity. In every instance, however, the effect of the antibody is dependent on its narrow specificity, namely, on the regions of the enzyme to which it is directed. The extent of inhibition or enhancement is, therefore, a reflection of the nature and distribution of the various antigenic determinants on the enzyme molecule. Antibodies specific exclusively to defined regions of an enzyme molecule can be prepared. This has been performed for both lysozyme and staphylococcal nuclease by two procedures: a) Selective separation of the relevant antibodies from the anti-enzyme serum by an immunoadsorbent containing a particular immunologically active fragment of the enzyme. b) The use of an isolated antigenic fragment of the enzyme, or a conjugate of it, for immunization. The antibodies thus prepared, specific toward a unique defined region of the lysozyme molecule (residues 60-83, denoted "loop") recognize the structural conformation of the fragment and are reactive with the intact enzyme molecule. Furthermore, a chemically synthesized loop-like derivative was proved immunologically identical with the natural fragment, and when forming a part of a completely synthetic conjugate, elicited conformation-specific antibodies, reactive with native lysozyme. These findings are relevant to the topic of an immunological approach to fertility control from two different viewpoints: In the first place they are informative regarding the specific inhibition by antibodies of sperm enzymes which partake in the fertilization process. Secondly, they encourage the synthetic approach for induction of an immune response toward hormones which are crucial in fertilization or implantation.


Centrifugal Cytology, IV.  The Prearation of fixed stained dispersions of gynecological cells. The Centrifugal Cytology technique has been utilized to produce glutaraldehyde fixed stained dispersions of both conventional Ayre scrapes and Davis pipet (PAPette) samples.  Light microscope studies of dispersions of both types of cells on conventional microscope slides indicated that both the tinctorial and morphological appearance of the cells after Papanicolaou staining was very similar to that observed with conventional smears and that the same criteria could be utilized with the Centrifugal Cytology dispersions to screen the cells for cancer as had previously been used with the smears.  A preliminary study indicated that six out of six positives with no false negatives or false positives were found.  The Centrifugal Cytology technique appears to have promise as a method for preparing suspension samples such as pipets of gynecologic cells.  Scanning electron microscope studies reveal that the squamous epithelial cells are very thin and at least some of them are covered by a network structure.


Characterization of spermatozoal auto-, iso- and allo-antigens. Three approaches are utilized to study and characterize spermatozoal antigens. An immunological approach has demonstrated the presence of spermatozoal auto-, iso- and allo-antigens. Spermatozoal auto-antigens studies by several authors are able to induce the whole spectrum of immune reactions (delayed hypersensitivity, complement-fixing antibodies and anaphylactic antibodies0 as well as of autoimmune aspermatogenic orchiepididymitis (AIAO). Different extraction procedures result in various preparations and even in different independent autoantigens (at least four), one protein, one membrane-linked antigen and at least two glyco-proteins. Spermatozoal iso-antigens stricto sensu are determined by the Y chromosome and present on at least 50% of the spermatozoa. Spermatozoal allo-antigens are also present at the surface of spermatozoa, especially blood group antigens (ABO and MNS systems), transplantation antigens (HL-A, H-2) and also some other unidentified ones. A biochemical approach has mainly been directed towards spermatozoal enzymes that have been directed towards spermatozoal enzymes that have been shown to be antigenic even in the species of origin. This is the case for lactic dehydrogenase LDH-X (a mid-piece enzyme) and for acrosomal enzymes, e.g., hyaluronidase, possibly sorbitol dehydrogenase and trypsin-like acrosomal proteinase (the auto- and allo-antigenicity of the latter having not been established). At least three of these enzymes are known or supposed to play a role in the process of fertilization. A clinical approach has described the presence of spermatozoal-coating antigen(s), such as transferrin or blood group substances from secretors obtained following the admixture of the secretions of the seminal vesicles. Indications were also obtained for the existence of antibodies directed against defined antigens. Several types of localization of antibodies on spermatozoa were described: acrosome (front part), equatorial segment, post-nuclear region, mid-piece and tail. Attempts at fractionation of human psermatozoal antigens are still at a preliminary stage. Whatever the approach, the main interest of these antigens is that they are able to induce, in the species of origin or in a related species antibodies capable of interfering with the normal process of reproduction, especially fertilization..


Immunological interference with fertilization. Rabbit antisera against mouse and hamster ovaries and sheep antisera against rabbit ovary have been used to demonstrate ovary specific antigens in these three species of mammals. That one or more of the specific antigens are located in the zona pellucida which surrounds the egg was indicated in immunofluorescence studies and by the effects antibodies have on the zona. After exposure to the antibody a precipitate forms on the zonae of preovulatory, unfertilized and fertilized eggs and all embryonic stages up to the time when the zona is shed. The precipitate was always seen near the outer surface of the zona suggesting that the active sites of the antigen(s) are located in this region. Trypsin and pronase which usually dissolve the zona were ineffective on the precipitated outer portion but did dissolve the inner, unprecipitated region. Species- and tissue-specificity and chemical nature of the zona are discussed. Important roles for the zona antigen(s) in a number of early events in reproduction were indicated by the effects of antizona antibodies have on fertilization and implantation. Pretreatment of unfertilized hamster eggs with zona precipitating antibodies was most effective in blocking sperm attachment to the zona. When the antibody was added subsequent to in vitro insemination, but before the sperm had passed through the outer region of the zona, sperm penetration was blocked. Mouse embryos treated with zona precipitating antibody and cultured in vitro failed to escape from the zonae, implying that implantation could be inhibited by antibody. Passive immunization of female mice with antizona antibodies and precipitattion of the zonae of hamster embryos in transfer experiments reduced the number of implantation sites. The identification of zona antigens and the effects of zona precipitating antibodies on early reproductive events encourage further studies on the zona in reference to immunological control of fertility.


HL-A, fertility and natural selection.

HL-A, fertility and natural selection. The antibodies occasionally produced in gravid females usually cause no adverse effects and the mother may become hyporesponsive. Exceptions may occur in some cases of abortion where frequency of antibodies appears to be unduly high. Sperm antigens in the mouse include T locus alleles as well as H-2 and H-Y. The T locus is involved in differentiation. T locus alleles are expressed on early but not late embryos. A search for similar factors in man is in progress. The antigenic differences between sperm and mother and between foetus and mother may be important in natural selection. It is possible that the union of sperm with ovum is non-random and that the ovum can select "compatible" sperm through recognition of cell surface markers present on sperm. Immunologic differences between mother and foetus may cause local "graft-versus-host" reactions in the placenta. This leads to increased placental size and may be a factor in hybrid vigour as well as a protective device.


Immunocytological methods for the identification and localization of antigens. Immunocytologic techniques allow the study of antigenic cellular constituents by optical or electron microscopy, Antibodies labelled with tracers such as fluorochromes, enzymes, radioactive isotopes, or large electron-dense molecules form the basis of these techniques. The immunochemical procedures involved in the preparation of such conjugates are well defined. Satisfactory results, however, also depend upon the proper preparation and processing of the tissue or cell suspension being studied.


Long term hazards in immunological methods of fertility control. Long term problems associated with future immunological methods of fertility control include the following: (1) reversibility, (2) unscrupulous use, (3) unphysiological intervention giving rise, among other possibilities, to carcinogenesis, (4) deleterious genetical selection operating on antigens, and (5) deleterious genetical selection operating on the immune response. The first three of these constitute a hazard to individuals, and the last two to populations. None is considered to constitute a threat so serious as to inhibit further research on the subject. We should keep under review future developments in relevant areas of immunology, including particularly cell-cell cooperation as a mechanism in autoimmunity, and immune response genes as the objects of immunoselection. It will be important also to come to terms with the social, political, and economic consequences of any cheap, widely-applicable form of birth control, such as might develop from immunological research. The possibility is raised of wide-spread immunisation against a synthetic immunological determinant, as an aid to fertility control. Another possibility is to make women grandchildless.


Cellular basis of the immune response.

Cellular basis of the immune response. Lymphocytes, the cells competent to initiate immune responses, can be divided into two major groups: thymus-derived or T cells responsible for "cellular immunity" (e.g. delayed hypersensitivity reactions) and bursa (or bursa-equivalent) derived or B cells which produce immunoglobulin (antibody) molecules and are involved in "humoral immunity". "Accessory" cells, such as monocytes (or macrophages), polymorphonuclear leucocytes and mast cells act in an auxiliary manner by facilitating antigen processing or presentation, or by liberating factors which modify the various manifestations of the immune response. A variety of interactions between T and B cells and between lymphocytes and accessory cells have been described in both cellular and humoral immunity. Antigen-activated T cells produce factors with various activities: some are involved in recruiting inflammatory cells, others activate macrophages and enhance their microbicidal activities, and others modify B-cell responsiveness either by facilitating or suppressing it. These factors are instrumental in T-cell regulation of immune responsiveness. Antibody produced by B cells also plays a role in immuno-regulation, acting either as an immunopotentiating influence or as a negative feedback, e.g. when complexed with antigen, turning off the response of T or B cells. A detailed knowledge of the precise manner in which cells involved in immunity are regulated is essential for an understanding of how the foetus, an essentially "foreign transplant", can survive to term in its immunologically mature "alien" host.


Structure and function of immunoglobulins. There are five major classes of immunoglobulins - IgG, M, A, D and E. Each is made of two heavy and two light chains or polymers of this basic subunit. The structure of each heavy and light chain consists of a variable region involved in antigen specificity and binding and a constant region which is involved in the class specific properties. The different classes of immunoglobulins differ in the biological properties. Of particular interest is the IgA fraction which provides antibodies in all the external secretions - including the reproductive organs. A few speculations are offered as to the possible role of IgA in reproductive biology.


Acute viral hepatitis: factors possibly predicting chronic liver disease. A number of clinical, biochemical, immunological and morphological variables were recorded at first admission of 500 consecutive patients with biopsy verified acute viral hepatitis in the period February 1969-June 1972. In February 1973, 28 of these patients had a morphologically documented chronic liver disease: 4 cirrhosis of the liver, 15 chronic aggressive hepatitis, and 9 chronic persistent hepatitis. 74 patients were followed up until morphological normalization took place. The initially recorded variables in the two groups were compared, and the following factors were significantly higher in the group with subsequent development of chronic liver disease:--frequency of drug addicts, median of the highest gammaglobulin, ANA, SMA, partial destruction of the limiting membrane, incidence of piecemeal necrosis, and pronounced plasma cell infiltration in the portal tracts. These preliminary results suggest that factors in the initial phase of acute viral hepatitis can be helpful to some extent in predicting the course and prognosis of the disease.


A new method for the embedding of small animals and organs in plastic. A new method for embedding of small animal organs in plastic is described. After the material has been fixed in solutions preserving its colour, and dehydrated gradually using an aqueous solution of glycerol and potassium acetate it is embedded in methylmetacrylate. The method is described in detail and involves moulding at minus 5 degrees C.


The histogenetic-embryologic basis for reappearance of alpha-fetoprotein in endodermal sinus tumors (yolk sac tumors) and teratomas. The mechanism of neosynthesis of the human tumor-associated fetal antigen alpha-fetoprotein (AFP) in a variable percentage of patients with testicular, ovarian and extragonadal germ cell tumors has generally been considered unknown or beyond any simple explanation. Of decisive importance is the cellular basis for AFP production 1. in ontogenesis and 2. in malignancy as dependent on an exact tumor histogenesis. Based on (1) the histogenetic-embryologic classification of germ cell tumors and the concept of yolk sac tumor (or endodermal sinus tumor), (2) the available clinical and experimental observations, and (3) the immunofluorescent localization of AFP in the endodermal sinus tumor of the human testis, it is concluded that AFP synthesis in these neoplasms is explained by the fact that they contain yolk sac endoderm, which produce AFP analogous with the physiological AFP synthesis by the fetal yolk sac in early embryogenesis.


Nucleolar size in benign and malignant plasma cell proliferation;. Nucleolar and nuclear size of bone marrow plasma cells has been studied in 26 cases of myeloma, 19 of benign essential monoclonal gammapathy (BEMG) and 9 without an M-component. Bone marrow smears were Feulgen-stained to visualize nucleoli and nuclei. Nucleolar area, nuclear area and the ratio nucleolar area/nuclear area were calculated. The myeloma group differed from the other two groups in having plasma cells with larger nucleoli, larger nuclei and an increased ratio nucleolar area/nuclear area. No difference was found between the BEMG group and the cases without an M-component. In some cases--in which the absence of osteolytic lesions at X-ray examination, a low plasma cell percentage in bone marrow smears or a low M-component concentration initially made the diagnosis of myeloma uncertain--the observation of enlarged nucleoli could help to establish the diagnosis. Three cases were observed in which the onset of myeloma was preceded by a long period of essentially unchanged M-component concentration. In these cases a sudden increase of M-component concentration was accompanied by an increase of mean nucleolar size of bone marrow plasma cells.


Diagnosis of medullary carcinoma of the thyroid by fine needle aspiration biopsy. Fine needle aspiration biopsy has been evaluated as a diagnostic method for medullary carcinoma of the thyroid (MCT) in 18 patients with verified hereditary or sporadic MCT. The typical MCT cell was asymmetrical, sometimes triangular and often with a characteristic red granulation in May-Grünwald-Giemsa staining. Eccentrically positioned, multiple nuclei were common. Amyloid was seen both intra- and extracellularly, staining blue-grey or violet with May-Grünwald-Giemsa and with green birefringence in polarized light after staining with alkaline Congo. The method was simple and quick to perform, causing negligible discomfort to the patient. No complications were seen. An adequate bioptic yield was obtained in 15 patients. In 13 of them (87 percent), including one patient with a normal thyroid at clinical examination, a correct diagnosis was reached.


Immune-indian ink method for detection of hepatitis A associated antigen and antibody. TIndian-ink grains coated with commercial gamma globulin (immune-Indian-ink) were agglutinated by 3 percent of sera from healthy volunteer blood donors; by 4 percent of those from hospital staff in contact with patients suffering from hepatitis; and by 10 percent of those from patients with viral diseases other than hepatitis, In contrast, the rate of positive reactions was 86 percent in the case of sera taken from patients in the acute phase of an illness diagnosed as hepatitis A on the basis of epidemiological and clinical data. Investigation of serum samples taken serially from patients positive in the acute phase of illness revealed that the immune-Indian-ink agglutinating factor does not persist for long in majority of cases. Two months after discharge from the hospital it was present in 18 percent of the patients only. The reaction proved negative when a limited number of cases diagnosed as hepatitis B were investigated. The immune-Indian-ink agglutinating factor was inhibited by all but one of 36 sera taken in the convalescent phase from patients with a diagnosis of hepatitis A. Some sera displaying agglutination with immune-Indian-ink gave a reaction with uncoated Indian-ink, too. Efforts to free the sera from non-specific agglutinating factor by starch-block electrophoresis have led to partial success. Fractionation on Sephadex G-200 columns suggested that in molecular weight (or particle size) the immune-Indian-ink agglutinating factor is smaller than HBsAg and larger than the non-specific agglutinating factor. On the basis of these results it is assumed that the immune-tindian-ink reaction is suitable for detecting an antigen tentatively called IH chi Ag and its antibody (IH chi Ab) specific to hepatitis A.


Complement system studies in systemic lupus erythematosus (SLE). Complement system involvement has been studied in 16 patients with systemic lupus erythematosus (SLE). Circulating conversion products of C3 were observed in 4 cases. Low mean values of C4 and C3 were found, while C3 proactivator (properdin factor B) levels were low in only a few of the patients. The levels of C4, C3 and C3 proactivator were not lower in the 4 patients in whom C3 conversion products could be demonstrated than in the others. It is concluded that the low complement values found in SLE may be caused mainly by deficient synthesis. Signs of complement activation are in this patient material demonstrated early in the disease, and chiefly in patients not receiving immunosuppressive therapy.


The thyroid in ulcreative colitis and Crohn's disease. III. The daily fractional turnover of thyroxine. The daily fractional turnover of thyroxine (T4) labelled with 131 I has been determined in 11 patients with ulcerative colitis (uC) of Crohn's disease and 8 controls. The daily fractional turnover of 131I-T4 was significantly increased in the patient group. The daily total disposal of T4 iodine was not significantly different although it was excessive in 3 of the 11 patients. The amount of T4 in plasma did not differ significantly between the patients and the controls. It is concluded that the T4 metabolism is disturbed in UC and Crohn's disease and that excessive losses of T4 iodine can be a cause of iodine depletion in some patients with longstanding and severe disease.


Antithrombin III: a backward glance o'er travel'd roads. By devising and applying quantitative methods for the assay of thrombin and autoprothrombin C and by developing techniques for their purification, it was possible to obtain information about the function and properties of antithrombin. The inhibitor is a protein for which the initial purification steps consist of removing fibrinogen from plasma by heating to 56 degrees for 3 min, removing prothrombin complex by absorption on barium carbonate, absorbing the antithrombin on aluminum hydroxide, and eluting with phosphate buffer. Antithrombin is limited in its capacity to neutralize thrombin activity, and, under some conditions, the rate of inhibition was accelerated, but equivocal results were involved. Heparin cofactor was found to be essential for retarding the formation of thrombin, and, by inference, it is essential for retarding the formation of autoprothrombin C. Heparin cofactor and antithrombin III are the same. Thrombin absorbs on fibrin, and this has been referred to as the "antithrombin I effect." Interference with the thrombin-fibrinogen reaction by mixtures of antithrombin III and heparin is called the "antithrombin II henomenon." The acceleration of thrombin inactivation at the time thrombin forms is called the "antithrombin IV effect." It was discovered that antithrombin III neutralizes thrombin, as well as autoprothrombin C. The inhibitor and the enzyme form a mutual depletion system. To assay for antithrombin III, a standard quantity of thrombin (about 1,100U/ml) was reacted with antithrombin III for 2 hr. The percent thrombin inactivated was then measured. In random samples of human blood, a wide range of antithrombin III concentration was found. The inhibitor is relatively stable in plasma and serum. It is not changed in concentration when Dicumarol therapy is instituted. Ether extraction of plasma reduces antithrombin III activity. Seitz filtration of plasma did not remove activity. Under special conditions, antithrombin III enhances esterase activity of thrombin. Under special conditions, thrombin regenerates from the thrombin-antithrombin III complex. Antithrombin III neutralizes the activity of prethrombin-E and thrombin-E; consequently, an active histidine center found in the B1 chain of thrombin is not essential for the binding of antithrombin. Autoprothrombin II-A activity was neutralized by antithrombin III. Autoprothrombin C was found to be neutralized by antithrombin III; the amounts required varied with the molecular forms of autoprothrombin C. Thrombin and autoprothrombin C apparently occupy the same binding sites on antithrombin III. An equation was developed to account for all the known characteristics of antithrombin III functions. The kinetic aspects of thrombin neutralization were found to correspond exactly with those of autoprothrombin C. Antithrombin III is a high-capacity inhibitor of the two most powerful enzymes in blood coagulation.


The thyroid in ulcerative colitis and Crohn's disease. IV. Thyroid hormone binding proteins. The thyroxine binding globulin (TBG), thyroxine binding prealbumin (TBPA), albumin, thyroxine (T(4)) and the triiodothyronine uptake test (T(3)-test) values have been estimated in serum of twenty patients with ulcerative colitis (UC) or Crohn's disease. The patient group was compared with twenty healthy control subjects matched for sex and age. The T(4) and the T(3)-test values were similar in the two groups. TBPA and albumin in serum were significantly lower, while the TBG values were significantly higher in the patients than in the controls. Treatment with corticosteroids influenced the results significantly. It is also concluded that in UC and Crohn's disease sometimes both the T(4) and the T(3)-test values can be abnormal so that misdiagnosis of hyperthyroidism is easy to make.


Inhibition of adrenal function in man by heparin or heparinoid Ro 1-8307. Heparin and the heparinoid Ro 1-8307 inhibited the secretory rate of aldosterone in physiological or pathological aldosteronism to the level found in normal subjects on liberal sodium intake. In addition, these compounds inhibited corticosterone biosynthesis, although less markedly than that of aldosterone. Indications of interference with cortisol production have not been found. During drug treatment angiotensin, in doses of 5-10 ng/kg b.wt./min, did not stimulate aldosterone secretion. ACTH responsiveness of the adrenals--indicated by the fractional increases of both aldosterone and corticosterone secretory rates--remained unchanged. In two studies heparin had no consistent effect on plasma renin activity.


The symbolic context of Chinese medicine:  a comparative approach to the study of traditional medical and psychiatric forms of care in Chinese culture. This article explores a distinctly different aspect of Chinese medicine, and of health care in Chinese culture, from that receiving most attention and serious study at present in this country. It examines the symbolic structure and significance of illness and care in the Chinese context by (a) applying concepts developed in anthropology and the cross-cultural study of medicine and psychiatry; (b) examining recent studies of folk and popular forms of health care in contemporary Chinese communities; and (c) raising questions about the congnitive structure, cultural background, and bio-social significance of traditional Chinese healing beliefs and practices. An attempt is made to place this analysis in a comparative framework, so that Chinese cases can be related to health care systems in other cultural settings.


Polymporphism of human C-band heterochromatin. II. Family studies with suggestive evidence for somatic crossing over. An analysis of the inherited pattern of C-band heterochromatin has been made in five pedigrees containing a total of 33 offspring that were available for analysis. The majority of variants were found to be inherited; however, at least seven of the 99 variants were not present in either parent, and an additional seven differed from the parental variant by either a morphological change or the appearance of mosaicism. It is believed that the polymorphism of human constitutive heterochromatin arises from a mismatching of the  repetitive DNA sequences contained in these regions with subsequent unequal crossing over. Further, the observed mosaic patterns provide suggestive evidence that such an event occurs in somatic cells as well as during meiosis.


Massive polyclonal hyperimmunoglobulinemia E, eosinophilia and increased IgE-bearing lymphocytes. A patient (E.M.) with marked eosinophilia and hyperimmunoglobulin E (IgE) has been followed for 4 years. Peripheral blood eosinophilia reached levels in excess of 18,000 cells/mm3 and serum IgE concentration increased to more than 210,000 units/ml (about 0.48 mg IgE/ml). The IgE has both lambda and kappa light chains and is therefore considered polyclonal. The patient has an increase in peripheral blood lymphocytes which stain for surface IgE. Transfer of the patient's plasma (plasmsEM) to a rhesus monkey did not induce peripheral boood eosinophilia. The half life of IgEEM in a rhesus monkey was 2.2 days, which is similar to the half life of myeloma IgE in human subjects. The condition was not associated with defined morbidity except for mild persistent pruritus. Various studies revealed no evidence for atopic parasitic, immune deficiency or neoplastic disease.


Synaptic lamellae in retinoblastoma.

Synaptic lamellae in retinoblastoma. During the electron microscopic examination of the retinoblastoma in a 21-month-old girl, we found numerous synaptic lamellae and synaptic vesicles in addition to other known features. These lamellae and vesicles can be regarded as additional proof of the neural origin of retinoblastoma.


Kayser-Fleischer ring and associated cataract in Wilson's disease. A 22-year-old woman with hepatolenticular degeneration, or Wilson's disease, was note clinically to have Kayser-Fleischer rings and associated cataracts. Histopathologic, histochemical, and electron microscopic study of the cornea showed deposition of copper in the peripheral Descemet's membrane, with excessive accumulation in Hassall-Henel warts. Copper deposits were also noted in the anterior and posterior lens capsule without the presence of degenerative changes in the epithelial or cortical cells of the lens. We propose that cellular activity is required for the depostion of copper material into the thick basement membranes of the cornea and lens, in contrast to the concept of simple diffusion.


Alterations in the upper facial growth of Macaca mulatta resulting from high-pull headgear. Four prepubertal Macaca mulatta monkeys, ranging in age from 13 to 24 months, were used in an investigation of the effects of high-pull headgear (to a face-bow) therapy on the growth of the upper facial skeleton. Amalgam bone implants were placed across the frontomaxillary, frontozygomatic, zygomaticomaxillary, and zygomaticotemporal sutures in each animal. Three of the monkeys wore appliances consisting of a maxillary dental spling, a face-bow, two coil springs, and an acrylic helmet. The fourth monkey (control) wore only a dental splint and a face-bow. A continuous high-pull headgear force of 300 grams per side was applied to the three monkeys for 81, 87 and 89 days, respectively, before death. Procion brilliant red 8-HBS vital stain was administered to all four animals at the start of and 3 days before the end of the treatment period. The facial growth patterns were determined from lateral cephalograms taken before and after treatment, from direct measurement of implant separation at the sutures, and from histologic sections of the four mentioned facial sutures.


Corneal superficial unwettable defect. II. Electron microscopic study. Corneal biopsy specimens of 6 patients with this particular affection were studies with the electron microscope. In addition to the routine electron microscopic methods, staining with ruthenium red was performed on one excised specimen. Marked changes were found in the region of Bowman's membrane, which was altered either superficially or in its total width. Its collagen fibrils became rough and intensively electron-dense, forming a granular or structureless trabecular meshwork. Intertrabecular spaces were filled with special electron-lucent material, which also formed a continuous layer on the surface of the altered Bowman's membrane. Filamentous structures resembling fingerprints were observed in certain areas of these spaces; and after staining with ruthenium red, numerob granules were also visible. Both these structures are considered by the author to be acid mucopolysaccharides. There is further discussed on the correlation of these findings with previous histochemical findings; the author gives special attention to the question whether waxy substances-eye ointment bases-could have been deposited in the pathologically altered Bowman's membrane.


The effects of various fixative-buffer combinations on lung fine structure. A variety of fixatives, buffers and fixation procedures were compared in rat and squirrel monkey lung in an attempt to preserve optimally both the cytologic details of pulmonary parenchyma as well as the acellular avelolar lining layer. In initial experiments utilizing the fixative of Ito and Karnovsky ('68), an electron-dense deposit was observed on the alveolar surface. Experiments were carried out in an attempt to determine what component of this fixative was responsible for the reaction product observed. In addition,immersion fixation of tissue blocks was compared to the whole lung fixation method of Kikkawa ('70). Kikkawa ('70) achieved excellent preservation of the acellular alveolar lining layer by such a fixation technique. In all lungs examined, whenever a phosphate buffer  was utilized with primary aldehyde fixation, an electron-dense precipitate was observed on the luminal surfaces of the type I and II pulmonary epithelial cells. Additional sites of reaction product were pinocytotic vesicles of the type I cells and membranous arrays within the alveolar lumen. Such deposits were never observed when a sodium cacodylate buffer was used. No such granules were observed in areas of lung where the acellular alveolar lining layer had been preserved. The implications of these findings with regard to lung histochemical procedures and the possible relationship of these phosphate buffer-dependent granules to the surfactant system are discussed.


Effects of large doses of intravenous atropine on heart rate and arterial pressure of anesthetized patients. A bolus of 3 mg. of atropine was given intravenously (I.V.) TO 123 ANESTHETIZED PATIENTS. Increases in heart rate were seen in 109 patients (88 percent), while 7 patients (5.7 percent) had no change. A mean increase in systolic arterial blood pressure of 14 mm. Hg was noted. A certain pattern in increases in heart rate and systolic blood pressure was observed. Ninety-six percent of the patients under cyclopropane, fluroxene, ether, ketamine, or regional (spinal or epidural) anesthesia had heart-rate increases, compared with only 77 to 89 percent of the patients anesthetized with halothane, enflurane, or neuroleptanalgesics. Rise in systolic blood pressure was seen in 40 to 50 percent of the former, but only in 31 to 40 percent of the latter group. The arrhythmias observed were transient A-V junctional tachycardias in three instances and bigeminal rhythm in one patient under cyclopropane anesthesia, The administration of a vagolytic dose of atropine to anesthetized patients appears not to be as arrhythmogenic as previously considered.


Potential for polyvalent infectious bronchitis vaccines. Numerous antigenic types and subtypes of infectious bronchitis virus (IBV) have been isolated and characterized from field epornitics of infectious bronchitis (IB). Thus obvious failures in obtaining the necessary protection from vaccination have been documented and they underscore the urgent need for vaccines which stimulate a broader spectrum of protection from heterologous IBV challenge than is presently obtained. If polyvalent IB vaccines are to be employed, assurance must be provided that variant IBV serotypes are not indiscriminately spread throughout the country or globe. Furthermore, possible interference, alteration, and reduction in immune response with the component antigens should be critically evaluated. Differences and comparative levels of postvaccinal respiratory signs with the different antigens, used singly and in combination, should be determined. As an alternative to polyvalent IB vaccines, certain Massachusetts-type strains, e.g., a Holland isolate IBV, at different passage levels in the authors' laboratory, have induced heterologous and homologous protection to some serotypes causing vexing field problems. Advantages are present in using a single antigenic type IB vaccine, if it is safe and effective, when compared to polyvalent vaccines. The absence of a serologic relationship to the results of immunity challenge is frequent with IBV isolates, which emphasizes that challenge results are considerably more important. In some IB problems, on a local or regional basis, autogenous vaccines may be indicated. Because of the multiplicity of IBV serotypes, however, it is doubtful that completely effective and safe IB vaccines will be forthcoming in the near future to satisfy the diverse needs of a dynamic poultry industry.


Effect of humoral antibodies on the course of Theileria parva infection (East Coast fever) of cattle. A study was made of the effects of serum and gamma-globulins from vaccinated cattle (donor cattle) given to cattle (principals) exposed to Theileria parva infection (East Coast fever (ECF)). The principals were treated with normal serum, with serum containing high antibody titer against T parva (as evaluated by the indirect fluorescent antibody (IFA) technique), or with globulins prepared from normal and from immune serums. For exposure, the principals were inoculated with standardized suspension of the tick Rhipicephalus appendiculatus containing T parva infective particles. Comparison was made between treatments with normal serum and globulin and treatments with immune serum and globulin, using observations of time lapse after exposure to febrile response (39.5 C), to appearance of T parva macroschizonts, and to death. In addition, hematologic changes were determined. Neither the establishment of infection nor the clinical and hematologic changes in the principals were influenced by their treatment with immune serum or concentrated globulins; all died of ECF. Humoral antibodies did not protect cattle against fatal ECF, nor was enhancement of T parva infection observed.


Investigation into the relationship of M ulcerans to M. buruli and other mycobacteria. The main characteristics of Mycoplasma ulcerans are its remarkably distinct drug sensitivity pattern and its rather poor enzymatic activity. M. microti is clearly distinguishable from M. bovis and M. tuberculosis. Some of the M. buruli strains appear to be identical with M. ulcerans, Whereas others show similarity either to M. microti or to M. tuberculosis. It seems that M. buruli is not a legitimate species.


The fate of cartilage grafts for ossicular reconstruction in tympanoplasty. Summary--Six autograft tragal cartilages and two preserved homograft nasal septal cartilages removed from revision tympanoplasty were examined with histologic and histochemical stains. The implanted cartilage remained in the middle ear from six months to eighteen months without significant inflammatory reaction or evidence of resorption. It appears that the implanted cartilages removed from tympanoplasty have been well tolerated in the middle ear space.


A contribution to the physiology of the perilymph. Part IV: Effect of histamine on the cochlear microcirculation. Summary--Because of the topography of the perilymphatic vascular network, the cochlear microcirculation is especially sensitive to the effect of vasoactive substances reaching the perilymphatic space. The cochlear microcirculation is mainly controlled humorally, via the activity of the metarterioles and changes in the flow properties of the blood. Intracochlear histamine reduces the cochlear circulation even more markedly than after intracarotid administration. No systematic effects of parenteral administration of vasoactive substances can be expected on the cochlear circulation. Reversible auditory disorders after stapedectomy may be explicable by the intracochlear release of histamine. The internal release of histamine after sunstroke and cold stress may play a part in sudden dusturbances of hearing.


Degradation of lindane by Escherichia coli. Lindane was degraded by Escherichia coli isolated from rat feces. About 10% of the added lindane was metabolized by the bacterium in Trypticase soy broth containing the pesticide. A single metabolite, 2,3,4,5,6-pentachloro-1-cyclohexene, was detected and identified by gas chromatography and mass spectrometry.


Etiologic factors in carcinoma of the prostate. A staining method is presented by which azocarmine combines with spermine to form a poorly soluble red precipitate highlighted against the yellow cytoplasm of positive cells achieved by counterstaining with metanil yellow. In the prostate, the spermine-dye complex was abundant in normal acinar epithelial cells, moderate in the epithelial cells of hyperplastic glands, and moderate to absent in carcinoma cells. Spermine is evidently concerned with stabilizing the structure of desoxyribose nucleic acid and probably of proteins, notably several zinc metalloenzymes. Diagnosis and treatment of carcinoma of the prostate should include an adequate basic diet, retention of testes, hormonal treatment oriented toward testicular, pituitary and hypothalamic hormones; zinc--ordinary and radioactive; and utilization of spermine and precursors.


Observations on phagocytosis of urate crystals by polymorphonuclear leucocytes. The sequence of events that may initiate the inflammatory reaction in acute gout has been investigated with specific reference to phagocytosis of urate crystals by polymorphonuclear leucocytes and the results have shown (1) that neutrophil leucocytes avidly ingest microcrystals of sodium monourate, (2) that this causes the rapid degranulation and disintegration of the leucocytes, (3) that fresh leucocytes ingest the debris and crystals liberated by the dead cells, and in their turn degranulate and die, thus possibly establishing a vicious circle in the system.


[Operative treatment of old radial head in childhood (author's transl)]. On 9 old posttraumatic dislocations of the radial head in childhood open reduction was carried out and fixed with ligamental graft 3--19 months after the accident. In 4 cases the result was excellent while 2 cases showed a satisfying result. One out of 3 bad results, found in a 4-year-old child, was supposed to be a connatal dislocation of head of radius. Following our findings good results can be only expected when the operative treatment is carried out not longer than 10 months after the accident. The result does not depend on the operative method.


Parasystolic property of the ectopic focus. Among 4476 ECGs recorded from May 1972 to April 1973, 206 ECGs showed various arrhythmias. All ECGs showing any kind of arrhythmia were recorded for 2 to 4 minutes in order to obtain more than 3 premature beats in one tracing. Of 141 ECGs with premature beats from 126 cases, more than 2 interectopic parasystolic intervals could be measured in 122 cases (96.8% of those with premature beats and 2.7% of all the patients examined). More than 3 coupling intervals could be measured in 117 patients with premature beats. In only 13 of these 117 cases (11.1%), the coupling interval varied less than 0.04 second and less than 0.02 second in 2 cases (1.7%). 1) The parasystolic cycle length ranged between less than 0.20 and more than 2.51 seconds with 82.8% of them being in a range between 0.21 and 1.00 second. 2) The fluctuation rate of the parasystolic cycle length ranged between less than 1.0 and more than 15.1. It was between less than 1.0 and 5.0 in 56,6%, between 5.1 and 10.0 in 30.0% and between 10.1 and more than 15.1 in 13.1%. 3) Fusion beats were observed in 44 of 122 cases in which the interectopic parasystolic cycle length could be determined (36.1%). Of these 44 fusions 14 were found in atrial, 14 in A-V junctional and 16 in ventricular parasystole. 4) Theories of re-entry and ectopic enhancement were discussed.


Comparison of the specificty of human and bovine tuberculin PPD for testing cattle. 1--Republic of Ireland. A tuberculin testing trial in cattle was carried out in the Republic of Ireland to compare the specificity for bovine tuberculosis of a human purified protein derivative (PPD) tuberculin (Weybridge) with that of a bovine PPD (Rotterdam), and to determine whether discrimination between specific and non-specific reactions to mammalian tuberculin is better with doses of tuberculins smaller than those traditonally used for testing cattle. Tests were carried out in 510 cattle, 395 of which were shown by post mortem examination to be tuberculous and 115 non-tuberculous. Three dilutions at five-fold intervals of both mammalian tuberculins were used together with two dose levels of avian tuberculin PPD (Weybridge), and all reactions were measured both by increase in skin fold thickness and by diameter of induration. In the environment of this trial, the bovine PPD was shown to be more specific for bovine tuberculosis than the human PPD, and particularly in differentiating from "skin tuberculosis". There was no indication of greater specificity at lower doses of tuberculin. Measurement of induration diameter proved a satisfactory alternative method of reading tuberculin reactions in cattle under field conditions.


Comparison of the specificity of human and bovine tuberculin PPD  for testing cattle. 2. South-eastern England. A tuberculin testing trial was carried out in eight counties of south-eastern England to compare the specificity for bovine tuberculosis of Weybridge human PPD with that of Rotterdam bovine PPD. The matching of these two tuberculins for potency in naturally infected cattle had already been established, the bovine PPD being approximately one-and-a-half times more potent than the human PPD per unit of weight. In 1110 cattle in 25 herds with histories of long-standing freedom from tuberculosis and in which non-specific tuberculin sensitivity was present, cross reactions were less to the bovine PPD than to the human PPD, showing that in the environment of this trial the bovine PPD was more specific than the human PPD. Induration diameter was a satisfactory alternative to skin thickening as a measure of tuberculin reactions in cattle under field conditions. Due to the steep slope of the dose-response curves of the avian PPD in the different groups of non-tuberculous cattle, the discriminating power of the comparative test, using avian and mammalian tuberculins, was less at lower doses of tuberculin. Concentrations of 1-0 mg per ml of bovine PPD and 0-5 mg per ml of avian PPD are recommended for use in a comparative tuberculin test.


Comparison of the specificity of human and bovine tuberculin PPF for testing cattle. 3. National trial in Great Britain. A field trial on a country-wide basis was undertaken to compare the specificity for bovine tuberculosis of single and comparative tuberculin tests in cattle using either Weybridge human or Weybridge bovine PPD. The tests were made on 10,305 cattle in 179 herds distributed throughout all regions of England, Scotland and Wales. Results showed that a comparative tuberculin test using avian PPD with either human or bovine PPD had a much higher efficiency than a single injection of mammalian tuberculin  in the neck of cattle, and confirmed that a comparative test is still essential in the British environment. Weybridge bovine PPD gave significantly better discrimination between tuberculous and non-tuberculous cattle than Weybridge human PPD when used together with avian PPD in a comparative tuberculin test. The diameter of induration gave an absolute measure of the extent of oedema, if present, and induration diameter used in conjunction with skin thickening increased the sensitivity and specificity of the test. Rules of interpretation were developed and are presented for an intradermal comparative tuberculin test in cattle using Weybridge avian and bovine PPDs.


Concealed AV junctional extrasystoles simulating second-degree sinoatrial block. Concealed AV junctional extrasystoles are described which, conducted in a restrograde manner to the sinoatrial junction, interfere with sinus impulses, thus simulating a second-degree, 2:1, sinoatrial block.


Replacement of class instruction in histology by audio-tape and booklet self-instruction sessions. A system of self-instruction in histology is described, using audio-tape and booklet instruction to supplement the microscopical examination of tissue sections. A pilot test demonstrated a slight superiority in retention of knowledge among students using this system, compared with those in the conventional class.


Amniotic fluid alpha1fetoprotein in the diagnosis of neural tract malformations. Amniotic fluid alpha1fetoprotein levels were determined in 400 pregnancies. The normal range for alpha1fetoprotein in amniotic fluid was defined by 350 samples from normal pregnancies. Elevated levels of alpha1fetoprotein were detected in 17 out of 18 pregnancies which gave rise to infants with neural tract abnormalities. The significance of this test in the antenatal diagnosis of neural tract abnormalities is discussed together with the possible reasons for "false negative" and "false positive" results. There were no complications in an individual series of 105 consecutive amniocenteses.


Large peptides of bovine and guinea pig myelin basic proteins produced by limited peptic hydrolysis. Bovine and guinea pig myelin basic proteins were cleaved with pepsin at pH 3.0 or pH 6.0 (enzyme/substrate, 1:500, w/w), and the peptides were isolated and identified. At pH 3.0 cleavage of the bovine protein occurred principally at three sites: Phe-Phe (88-89), Phe-Phe (42-43), and Leu-Asp (36-37). Minor cleavages occurred at Leu-Ser (110-111), Phe-Ser (113-114), and Ile-Phe (152-153). A study of the time course of the hydrolysis  showed that the reaction was biphasic; nearly all of the protein was cleaved at Phe-Phe (88-89) before significant cleavages at other sites occurred. At pH 6.0 cleavage of the bovine protein occurred almost exclusively at a single site, the Phe-Phe bond at position 88-89, resulting in bisection of the protein. Treatment of the guinea pig protein with pepsin under the same conditions resulted in the production of peptides which were identical with those of the bovine protein in chromatographic and electrophoretic properties and in N-terminal and C-terminal residues but which differed slightly in amino acid composition.


Complexity of cytoplasmic RNA in different mouse tissues measured by hybridization of polyadenylated RNA to complementary DNA. The kinetics of hybridization of polyadenylated RNA from mouse L-cells with complementary DNA (cDNA) synthesized with reverse transcriptase revealed three classes of differing abundance. The simplest interpretation requires three frequency classes representing polyadenylated RNA; 5, 45, and 50 percent of the total polyadenylated RNA and about 3, 300, and 7600 different RNA sequences of 6 times 10-5 daltons, respectively. The complementary DNA synthesized with L-cell polyadenylated RNA as template hybridized efficiently with RNA from different mouse tissues, indicating that most species of the L-cell RNA in the highand middle frequency class are present in all mouse tissues. Kinetics of hybridization of complementary DNA synthesized with cytoplasmic polyadenylated brain RNA as template suggested a higher complexity for brain RNA. Thirty-five percent of this brain cDNA failed to hybridize with L-cell RNA. This complementary DNA fraction, isolated by hydroxylapatite chromatography, represented approximately 11,000 RNA sequences specific for the brain. On the other hand, hybridization of complementary DNA synthesized on polyadenylated mouse liver RNA with L-cell RNA failed to demonstrate differences between these two groups of polyadenylated RNA.


Exposure of histone antigenic determinants in chromatin. The exposure of antigenic determinants of histones present in "native" chromatin was studied by: (1) testing their ability to elicit anti-histone antibodies and (2) measuring their ability to interact with anti-histone sera. To this end, antisera specific to purified histone fractions and to purified rat liver chromatin were elicited in rabbits. The anti-chromatin sera did not react with pure histone fractions and pure histone fractions F2b, F3, F2a1, and F2a2 failed to inhibit the complement fixation resulting from the binding of anti-chromatin to chromatin. These results suggest that in native chromatin, determinants in these histones are not immunogenic. Histone F1, however, inhibited the reaction between chromatin and anti-chromatin. Antisera elicited by histone fractions reacted weakly with "native" chromatin. The maximal complement fixations (obtained with 5-10 mug of chromatin DNA) were as follows: 60% with anti-F2b, 20% with anti-F1 and anti-F3, and less than 5% with either anti-F2a1 or anti-F2a2. Studies of the interaction between anti-histone antibodies and chromatin in which chromatin was used as an immunoadsorbent indicated that antibodies against different histones were adsorbed to a different degree by the same amount of chromatin. Differences in the immunoadsorbing capacity between sonicated and nonsonicated chromatin were found. Quantitative adsorbtion studies revealed that in the "native" chromatin structure, antigenic determinants of F1 and F2b were more available to interact with homologous antibody than those of F3 and F2a1 and that determinants in F2a2 were the least available. It could be calculated that the "equivalent antigenicity" of the histones in chromatin was 9.6% for F1, 3.2% for F2b, and 0.90% for F3 and F2a1. Upon sonication these values did not change for F1 but increased two-, three-, and fourfold for F2b, F3, and F2a1, respectively. Digestion of chromatin with trypsin totally abolished the ability of chromatin to adsorb anti-histone antibodies.


Inhibition of photosystem II by uncouplers at alkaline pH and its reversal by artificial electron donors. When chloroplasts are aged for 5 min at pH 9.6, or are exposed to uncouplers at pH 8.5-9.0, electron flow from water to Hill acceptors is inhibited. Both treatments induce rapid millisecond dark decay of delayed light emission. 3-(3,4-Dichlorophenyl)-1,1-dimethylurea-sensitive electron transport through Photosystem II can be regenerated in both types of inhibited chloroplasts by the artificial electron donor, 1, 5-diphenylcarbohydrazide. Neither treatment inhibits electron flow through Photosystem I. Uncouplers at alkaline pH, when added in the light, are less effective in producing the inhibition than when added in the dark. These results are interpreted as indicating inhibition of the oxygen-evolving apparatus by alkaline intrathylakoid pH.


Mitochondria from human term placenta. II. Characterization of respiratory pathways and coupling mechanisms. Pathways of electron transport utilized for respiration in human term placental mitochondrial preparations were differentiated and characterized through the use of classical respiratory chain inhibitors and multiple sources of reducing equivalents. Mechanisms of associated energy conservation and utilization were examined in the preparations with uncouplers and inhibitors of phosphorylation. Inhibition by rotenone, antimycin A and cyanide established the classical electron transport chain as the major pathway of respiration with glutamate and succinate as substrates. Approximately 20% of glutamate-supported respiration was insensitive to inhibitors and may proceed by the cytochrome P-450 linked pathway of electron transport. Approximately 50% of ascorbate-N,N,N',N'-tetramethyl-p-phenylenediamine supported respiration was insensitive to 10-3 M cycanide and must utilize an undefined by-pass of cytochrome oxidase. A rotenone- and antimycin-insensitive, exterior pathway for NADH oxidation was demonstrated which could be artificially linked by exogenous cytochrome c to the cytochrome oxidase region of the classical electron transport system. Glycerol 3-phosphate also supported oxidative phosphorylation yielding ADP/O ratios of 2.  Respiration of placental mitochondria was stimulated by 2,4-dinitrophenol and gramicidin. With succinate, dinitrophenol-stimulated respiration exceeded that obtained in the presence of ADP. Oligomycin and atractyloside prevented the stimulation of respiration by ADP. Thus, respiration appeared coupled through normal mechanisms to ATP formation and ion transport. A preferential coupling of respiration to the energy-utilizing processes of steroid hormone biosynthesis may exist.


Phosphoprotein phosphatases for myelin basic protein in myelin and cytosol fractions of brain. Phosphoprotein phosphatase (phosphoprotein phosphohydrolase EC 3.1.3.16) activity for myelin basic protein was found to be present in the myelin fraction of rat brain. The enzyme activity was in a latent form and solubilized by 0.2% Triton X-100 treatment with about 50% increase of activity. The cytosol fraction from bovine brain also had phosphoprotein phosphatase activity for myelin basic protein, which was resolved into at least two peaks of activity on DEAE-cellulose column chromatography. Myelin basic protein was the best substrate for both the solubilized myelin fraction and the cytosol enzymes among the substrate proteins tested. The Km values of the solubilized myelin fraction were 4.2 muM for myelin basic protein, 7.4 muM for arginine-rich histone, 8.0 muM for histone mixture and 14.3 muM for protamine, respectively.


Activity, isoenzyme pattern, and synthesis of UDPglucose 4-epimerase during differtiation of Physarium polycephalum. 1. The specific activity of UDPglucose 4-epimerase (EC 5.1.3.2) increases by about 50% during the first 24 h of starvation-induced differentiation (spherulation) of Physarum polycephalum. 2. At all stages during differentiation, the enzyme activity is very sensitive to actinomycin-C and cycloheximide, inhibitors of transcription and translation, with a half life against cycloheximide of about 20 min (if added 12 h after the induction of differentiation). 3. The isoenzyme pattern, as revealed by isoelectric focusing in sucrose gradients, does not change during spherulation. One main band with a pI of 6.7, with a shoulder (pI 7.6) and a minor band (pI 6.0) was observed in extracts both from growing and differentiating cultures. 4. Density labelling experiments using deuterated amino acids with subsequent analysis by equilibrium density gradient sedimentation in 15-35% (w/w) metrizamide gradients revealed a rather slow rate of enzyme synthesis, which is in contrast to the observed high sensitivity against actinomycin-C and cycloheximide.


The phosphorylation site associated with the oxidation of exogenous donors of electrons to photosystem I. 1. The Photosystem I-mediated transfer of electrons from diaminodurene, diaminotolune and reduced 2,6-dichlorophenolindophenol to methylviologen is optimal at pH 8-8.5, where phosphorylation is also maximal. In the presence of superoxide dismutase, the efficiency of phosphorylation rises from smaller than or equal to 0.1 at pH 6.5 to 0.6-0.7 at pH 8-8.5, regardless of the exogenous electron donor used. 2. The apparent Km (at pH 8.1) for diaminodurene is 6-10-minus 4 M and for diaminotoluene is 1.2- 10- minus 3 M. The concentrations of diaminodurene and diaminotoluene required to saturate the electron transport processes are greater than 2 mM and greater than 5 mM, respectively. At these higher electron donor concentrations the rates of electron transport are markedly increased by phosphorylation (1.5-fold) or by uncoupling conditions (2-fold). 3. Kinetic analysis of the transfer of electrons from reduced 2,6-dichlorophenolindophenol (DCIPH2) to methylviogen indicates that two reactions with very different apparent Km values for DCIPH2 are involved. The rates of electron flux through both pathways are increased by phosphorylation or uncoupling conditions although only one of the pathways is coupled to ATP formation. No similar complications are observed when diaminodurene or diaminotoluene serves as the electron donor. 4. In the diaminodurene yields methylviologen reaction, ATP formation and that part of the electron transport dependent upon ATP formation are partially inhibited by the energy transfer inhibitor HgC12. This partial inhibition of ATP formation rises to about 50 percent at less than 1 atom of mercury per 20 molecules of chlorophyll, then does not further increase until very much higher levels of mercury are added. 5. It is suggested that exogenous electron donors such as diaminodurene, diaminotoluene and DCIPH2 can substitute for an endogenous electron carrier in donating electrons to cytochrome f via the mercury-sensitive coupling site (Site I) located on the main electron-transporting chain. If this is so, there would seem to be no reason for postulating yet another coupling site on a side branch of the electron transport chain in order to account for cyclic photophosphorylation.


A partial reaction in photosystem II: reduction of silicomolybdate prior to the site of dichlorophenyldimethylurea inhibition. Silicomolybdate functions as an electron acceptor in a Photosystem II water oxidation (measured as O2 evolution) partial reaction that is 3-(3,4-dichlorophenyl)-1, 1-dimethylurea (DCMU) insensitive, that is, reduction os silicomolybdate occurs at or before the level of Q, the primary electron acceptor for Photosystem II.  This report characterizes the partial reaction with the principal findings being as follows: 1. Electron transport to silicomolybdate significantly decreased room temperature Photosystem I side of the DCMU had no effect on the fluorescence level, consistent with silicomolybdate accepting electrons at or before Q.  In the absence of DCMU, silicomolybdate is also reduced at a site on the Photosystem I side of the DCMU block, prior to or at plastoquinone, since the plastoquinone antagonist dibromothymoquinone (DBMIB) did not affect the electron transport rate.  3. Electron transport from water to silicomolybdate (+ DCMU) is not coupled to ATP formation, nor is there a measurable accumulation of protons within the membrane (measured by amine uptake).  Silicomolybdate is not inhibitory to phosphorylation per se since neither cyclic nor post-illumination (XE) phosphorylation were inhibited.  4. Uncouplers stimulated electron transport from water to silicomolybdate in the pH range of 6 to 7, but inhibited at pH values near 8.  These data are consistent with the view that when electron flow is through the abbreviated sequence of water to Photosystem II to silicomolybdate (+ DCMU), conditions are not established for the water protons to be deposited within the membrane.  Experiments reported elsewhere (Fiaquinta, R.T., Dilley, R.A. and Horton, P.(19741 J. Bioenerg. 6, 167-177) and these data, are consistent with the hypothesis that electron transport between Q and plastoquinone energizes a membrane conformational change that is required to interact with the water oxication system so as to result in the deposition of water protons either within the membrane itself or within the inner oxmotic space.


Migration of ribosomes along the axons of the chick visual pathway. The axoplasmic migration of ribosomes has been detected in the visual system of the chick. Monocular injection of radioactive uridine or an amino acid mixture was followed by sedimentation analysis in sucrose or cesium sulfate density gradients, of ribosomes prepared from the retinae of injected eyes and the left and right optic lobes. By this means both RNA and protein components of ribosomes were found to migrate from the retina to the innervated contralateral optic lobe. Following denervation of the distal nerve segment by eye removal, the stability of the transported RNA was reduced, suggesting its presynaptic location. The transport of RNA was not significantly imparied by intraocular injection of inhibitors of informational RNA or mitochondrial RNA synthesis prior to injection of radioactive uridine but was depressed by a low dose of actinomycin D.


Axoplasmic transport of a brain-specific soluble protein. The rate and extent of axoplasmic transport of the brain-specific soluble protein (14-3-2 protein) has been investigated in the avian visual system. 1-day-old chicks were injected monocularly with tritiated proline, Incorporation of the isotope into the 14-3-2 protein synthesized within the retina of the injected eye, as well as the appearance of the labeled protein in the optic lobes was determined at 6 h and 6 days. These time periods were chosen to distinguish between the rapid and slow phases of axophlasmic flowmfollowing preparation of high-speed supernatant fractions, dialysis, chromatography on Sephadex G-150 and immunoprecipitation with specific antiserum, identification of the labeled 14-3-2 protein was carried out by sodium dodecylsulfate-polyacrylamide gel analysis of the radioactive immunoprecipitates; 6 days after isotope administration, approxo% of the 14-3-2 protein synthesized in the chick retina had been transported to the contralateral optic lobe. By contrast, at 6 h no labeled 14-3-2 protein was detectablemthus, transport of this neuronal protein appears to be relatively slow process with little or no rapid component.


A new uroflowmeter for routine clinical use. A uroflowmeter has been produced using a simple strain gauge transducer system with a performance that has been optimised to provide various micturition parameters with an accuracy consistent with the known physiological range. The total cost of the uroflowmeter is around L140 including the digital read-out. The results from over 300 patients have been collected and the flow curves of over 100 of these have been obtained. It is hoped that we can define a set of clinically significant parameters from each flow curve and correlate these against their associated urological conditions. Since, with the majority of patients, only one test is carried out, the parameters would also have to be significant for a single result.


[Reproduction of the anaphylactic reaction of isolated human smooth muscle organs and the effect of several adrenotropic substances]. A comparative study was carried out of passive sensitization of the lungs, bronchi, small and large intestine by the blood sera of patients sensitive to ambrosia pollen. Passive sensitization and subsequent anaphylactic contraction were reproduced on the isolated bronchi, lungs and the ileum. Development of this reaction was less constant in the large intestine, jejunum and the appendix. The value of anaphylactic reaction of human smooth muscle displayed significant changes with the treatment of the muscles by agents selectively acting on the beta-adrenergic receptors of these organs.


Stimulation of neutrophil oxidative metabolism by the alternate pathway of complement activation: a mechanism for the spontaneous NBT test. The reduction of nitroblue tetrazolium dye by human neutrophils was measured in the presence of serum in which the complement system had been activated through the alternate pathway by interaction with inulin. Neutrophils incubated with serum inulin supernatants reduced the dye and showed a general increase in oxidative metabolism. The oxidation of glucose-1-14-C by supernatant prepared from selectively depleted sera indicated that the neutrophil-stimulating factor(s) was generated through the alternate pathway of complement activation. The possibility that inulun had been ingested as a particle was ruled out by light microscopy and radiolabeling studies. The failure of neutrophils stimulated by the serum-inulun supernatants to migrate after exposure to a chemotactic agent suggested that the site of neutrophil-complement interaction was on the cell membrane. It is concluded from these results that biologically active fragments generated through the alternative pathway of complement activation can stimulate neutrophil metabolism in the absence of phagocytosis. Interaction of such fragments with circulating neutrophils in vivo and the subsequent metabolic activation of these cells is one explanation for the spontaneous reduction of nitroblue tetrazolium dye in vitro by neutrophils from patients with certain infections and inflammatory disorders.


Cytochemical study of acute promyelocytic leukaemia. Five cases of acute promyelocytic leukaemia (A.P.L.) are investigated for peroxidase, PAS, toluidine blue, astra blue, alpha-naphthyl esterase, double esterase incubation (naphthol-AS plus naphthol-AS-D chloroesterase), and cellular lysozyme activity. These cytochemical investigations may contribute further characterization of the morphologic type.


Conformation therapy using the tracking cobalt unit. A description is given of the principles and application of the tracking technique using an automated cobalt teletherapy unit. The technique is a combination of moving table and arcing techniques which is used to shape the irradiated volume to match the tumour volume in three dimensions. The method has the additional advantage that corrections can be made for variations in dose rate along the tumour axis resulting from changes in body outline and the presence of inhomogeneities. An outline of the treatment planning procedure and the way the machine executes the planned treatment is given. Isodose distributions ar presented for two cases for which the technique was employed. The first of these illustrates the treatment of an oesophageal tumour, showing how the technique can be used to compensate for an irregularly shaped tumour in a part of the body having a large variation in cross section. The second shows how the technique copes with a tumour having a regular shape but having an awkward orientation in the body. Brief reference is made to work at other centres using moving table and three-dimensional shaping techniques which employ synchronous shielding.


Maternal serum alpha-fetoprotein levels in multiple pregnancy. Maternal serum alpha-fetoprotein (AFP) levels were higher in 10 twin pregnancies and one triplet pregnancy than in 22 control singleton pregnancies matched for maternal age, parity, and the time of gestation at which the serum sample was taken. In twin pregnancies the average AFP levels were double those found in singleton pregnancies and the level in the triplet pregnancy was even higher. Raised maternal serum AFP values due to multiple pregnancy should not cause unnecessary amniocentesis in the diagnosis of anencephaly or spina bifida if an ultrasound investigation is routinely performed first.


Serum alpha - fetoprotein levels in patients with cystic fibrosis and their parents and siblings. Patients with cystic fibrosis (C.F.) showed raised serum levels of alpha-fetoprotein (AFP). A moderate but significant increase in serum AFP was present in their parents and some siblings. There was no correlation between the clinical severity of the disease and serum AFP concentration. Samples from control groups with gluten-induced malabsorption and bronchiectasis had normal levels. Persistent synthesis of AFP may be an associated marker of C.F. genes, and estimation of serum AFP might help in detecting heterozygote carriers in families at risk.


Family unit in a children's psychiatric hospital. The need for effective management of disorders of parent/child relationships is repeatedly stressed. Despite the bulk of theoretical work on the subject there is little information on the practical management of the clinical problems that arise. We describe a unit designed and staffed for the management of such disorders. In our view it meets a need in a way that could be difficult or impossible for most paediatric, psychiatric, and social services as they are at present organized.


A simple fluorescence of staining technique for in situ soil microorganisms. A simple, rapid straining technique using the magnesium salt of 1-anilino-8-naphthalene sulfonic acid is described. Treatment of soil with an aqueous, membrane-filtered solution (3.5 mg/ml) of the salt causes the soil microorganisms to fluoresce when examined with light from a mercury arc light source.