Orientation of the oxygen atom at C-6 as a determinant of agonistic activity in the oxymorphone series. The kinetics of various oxymorphones, their 6-methylene analogs and the 6-hydroxy-epimers corresponding to naloxone and naltrexone have been studied in the longitudinal muscle strip of the guinea-pig ileum. Substitution of the oxygen at C-6 by amethylene group slightly increased antagonistic activity of the resulting structures, without significantly influencing agonistic activity relative to the parent compound. The alpha-orientation of the hydroxy group at C-6 enhanced the agonistic property of both naloxone and naltrexone. The beta-compounds, however, were pure antagonists, with potencies similar to those of the parent keto structures.


The site of action of the histamine releaser compound 45/80 in causing mast cell degranulation. A primary amine analog of compound 48/80 (nor-48/80) was purified and attached to Sepharose beads through an albumin link. Suspensions of rat peritoneal cells were passed over the beads in an affinity chromatography column, and the proportion of the mast cells that was retained by the beads was determined. Sixty-seven percent of the mast cells were found to be retained by the column, indicating the existence of a binding site for nor-48/80 on the exterior of mast cells. The beads were larger than the cells, and hence precluded the entry of the nor-48/80 into the cells. Neither the Sepharose beads nor the albumin link was responsible for this amount of binding because control beads without nor-48-80 retained only 22% of the mast cells. Mast cells incubated with large quantities of the beads in a batch procedure released up to 53% of the mast cell histamine, whereas control beads without the polymer released only 18%. This release could not be attributable to soluble nor-48/80 because only trace amounts of radioactive nor-48/80 were released from beads soaked overnight, and these supernatants released insignificant amounts of histamine when incubated with mast cells. These studies indicate the presence of a receptor for 48/80 on the mast cell membrane which can trigger histamine release.


The effects of nerve section and of colchicine treatment on the density of mechanosensory nerve endings in salamander skin. We have shown that when one of the spinal nerves supplying the salamander hind limb is cut or treated with colchicine, the fields of the remaining nerves enlarge in area; whereas nerve section produces Wallerian degeneration, the colchicine-treated nerves conducted action potentials normally and their peripheral fields remained unchanged in area (Aguilar, Bisby, Cooper & Diamond, 1973). Since colchicine-treatment reduced neuronal transport, and nerve-section eliminated it, we proposed that nerve sprouting is regulated by factors normally conveyed to the endings by axoplasmic transport. 1. We have now investigated the effects of colchicine on the thresholds and distribution of individual mechanosensory endings in the skin. If reduction of neuronal transport were enough to cause the threshold to be increased to the point of total unresponsiveness, then this could be a sign of an early stage of degernation in those terminals. It could then be hypothesized that products of degeneration were providing a stimulus for adjacent nerves to sprout. 2. Quantitative physiological studies of the effects of colchicine doses known to interfere with fast axoplasmic transport, indicate that in some experiments the terminal field of the treated nerve was invaded by sprouting fibres from neighbouring axons, when its own endings were unchanged in number, distribution and sensory thresholds. In other experiments the colchicine-treated nerve endings showed an increase in threshold but their function was otherwise unchanged; a similar adjacent nerve sprouting occurred. In a final group, colchicine caused total unresponsiveness of some endings of the treated nerve. 3. When a region of skin was partially denervated by nerve section, the physiological analysis indicated that the number of new mechanosensory endings which sprouted from the remaining axons exactly matched the number lost by nerve degeneration: furthermore the distribution of the endings was normal. It therefore appears that sprouting ceased when the original density of mechanosensory endings in the skin was restored. 4. The possibility that the drug induced sprouting as a consequense of a direct action on the skin is unlikely. With [3H]colchicine, we found that the accumulation of label in the skin of the untreated limb, in which sprouting did not occur, equalled that of the opposite limb. 5. The present results lend support to the original hypothesis of Aguilar et al. (1973), which proposed that collateral sprouting of intact nerves occurs when the supply of neuronally transported factors becomes inadequate to balance out the effects of a postulated target-tissue stimulus. In the Discussion other examples of collateral nerve sprouting, such as that following adjacent denervation, are shown to be explainable by this hypothesis.


The production of denervation-like changes in rat muscle by colchicine, without interference with axonal transport or muscle activity. 1. Rat extensor digitorum longus (EDL) muscles were examined after colchicine treatment of the sciatic nerve. Colchicine was applied in one of two ways: (i) a single sub-epineural injection; (ii) a chronically implanted silicone cuff. 2. After the sub-epineural injection, the entire membrane of muscle fibres became sensitive to iontophoretically applied acetylcholine and the muscle action potentials became resistant to tetrodotoxin. However, the majority of these fibres were found to be normally innervated. 3. These effects were not restricted to the EDL muscle of the colchicine injected side but were also found in the EDL muscle of the contralateral side, indicating that the action of colchicine was systemic. 4. In the treated sciatic nerve there was a partial block of axonal transport of 3H-labelled proteins, which correlated with a partial paralysis of the ipsilateral leg. However, axoplasmic transport was found to be normal in the contralateral sciatic nerve and the contralateral limb was not paralysed despite the supersensitivity of the investigated muscle on that side. 5. When colchicine was applied with a silicone cuff, denervation-like changes were confined to the ipsilateral EDL muscle. However, impulse conduction block at the level of the cuff was usually observed. 6. It is concluded that (i) colchicine can produce denervation-like changes in normally active muscle without blocking axoplasmic transport, through an action probably exerted directly on the muscle membrane, and (ii) that colchicine-cuff experiments failed to provide unambiguous evidence in support of the existence of neurotrophic influences on the muscle membrane.


The relation of axonal transport of mitochondria with microtubules and other axoplasmic organelles. Axonal transport of mitochondria was studied in frog sciatic nerves incubated in agents selected for their known or alleged effect on microtubules or axonal flow. Quantitative data on mitochondria, microtubules, neurofilaments, endoplasmic reticulum, and cross-sectional area of the axon indicate that axonal transport of mitochondria is dependent on microtubules. When more than half of the microtubules are destroyed, the axonal transport of mitochondria is diminished in proportion to the destruction of microtubules. Axonal transport of mitochondria is not related to neurofilaments and endoplasmic reticulum. Changes in the cross-sectional area of axons, even upon reduction to half the normal size, do not noticeably affect mitochondrial transport. Cyanide which blocks oxidative metabolism also blocks axonal transport of mitochondria, but analysis of fine structure indicates that cyanide is destructive to microtubules as well.


Shade modification of porcelain restorations. The described technique of using surface stains to modify shade can often salvage porcelain restorations which might otherwise be unacceptable. The chart (Fig. 2), if placed in the stain kit, can be helpful during chair-side staining.


Setting: a contextual variable associated with empathy. Fifty seven registered nurses working in either a psychiatric or non-psychiatric setting volunteered to participate in a study to measure their empathic ability with patients. Results of the study supported the notion that nurses working in a psychiatric setting are significantly more empathic than nurses working in a non-psychiatric setting (p less than .05). Contrary to some previous research findings, the demographic variables of age, sex, marital status, educational level, and length of experiences were not significantly related to empathy. Setting--psychiatric or non-psychiatric--was the only variable that made a difference.


Uterine protein synthesis during the early stages of pregnancy in the rat. The synthesis of uterine-soluble proteins during early pregnancy in the rat has been examined by means of dual-isotope labelling techniques and subsequent electrophoretic analysis. A protein of similar electrophoretic mobility to the uterine oestrogen-induced protein was observed, and synthesis of this 'presumptive induced protein' was maximal on Day 4 and Day 6 of pregnancy but low on day 5. Pregnancy associated protein synthesis was observed in many regions on polyacrylamide gels, including the beta-lipoprotein, alpha2-macroglobulin, post-transferrin and albumin regions. Synthesis of the post-transferrin species rapidly increased from Day 4 to reach a maximum on Day 6 in the implantation tissue. The temporal pattern of synthesis of post-transferrin protein and and of 'presumptive induced region' suggests involvement in the processes of cell proliferation and decidualization.


Polydispersity of human articular cartilage proteoglycan antigens. Studies were undertaken to define more fully the antigenic properties of human articular cartilage proteoglycans, in anticipation of its potential contribution to alterations arising in diseased states and following cartilage transplantation. Proteoglycans, extracted from normal, adult articular cartilage by dissociative measures, were subjected to purification by cesium density gradient ultracentrifugation, under conditions facilitating both molecular aggregation and dissociation. A polydisperse population of reactive determinants was observed in immunodiffusion and hemagglutination inhibition systems, employing proteoglycan specific antisera on gradient fractions. Highly aggregated proteoglycan species appeared to contain potentially masked antigenic determinants, which were revealed after guanidine dissociation but not hyaluronidase digestion. Polyacrilamide disc gel electrophoresis in sodium dodecyl sulfate, in conjunction with disc elution experiments, confirmed proteoglycan antigenic polydispersity.


Fluorinated Pyrimidine nucleosides. 1. Synthesis of a nitrogen analogue of the antitumor agent 2,2'-anhydro-1-beta-D-arabinofuranosyl-5-fluorocytosine hydrochloride. The nitrogen-bridged compound 2,2'-anhydro-1-beta-D-arabinofuranosyl-2,4-diamino-5-fluoropyrimidinium chloride (2), an analogue of the antitumor agent anhydro-ara-FC (1), has been synthesized. 5-Fluorocytidine was converted into 1-beta-D-ribofuranosyl-2,4-diamino-5-fluoropyrimidinium chloride (4), but cyclization of 4 was not achieved due to a competing side reaction. The nitrogen bridge was therefore introduced by cyclization of 5-fluoroisocytidine (10) to give the 2,2'-imino-bridged compound 16. The latter was converted into 2 by the standard procedure of thiation, S-methylation, and treatment with ammonia. Compound 2, as well as a number of the synthetic intermediates, was tested for activity against S180 sarcoma in mice. None of the new compounds exhibited any antitumor activity.


Synthesis of 5-azacytidine-6-13C and -6-14C. 5-Azacytidine (1) labeled with 13C or 14C at the chemically labile C-6 position was synthesized. A method utilizing hydrolytic opening of the triazine ring followed by recyclization with dimethylformamide dimethyl acetal was used. Urinary and biliary excretion was measured in rabbits following intravenous doses of 1-4-14C and 1-6-14C. Differences in recoveries of the dose from 4-14C and 6-14C demonstrate that ring cleavage of 1 with loss of the C-6 carbon represents a major metabolite route.


Ionic selectivity, saturation and block in gramicidin A channels: I. Theory for the electrical properties of ion selective channels having two pairs of binding sites and multiple conductance states. A model for the gramicidin A channel is proposed which extends existing models by adding a specific cationic binding site at each entrance to the channel. The binding of ions to these outer channel sites is assumed to shift the energy levels of the inner sites and barriers and thereby alter the channel conductance. The resulting properties are analyzed theoretically for the simplest case of two inner sites and a single energy barrier. This for-site model (two outer and two inner) predicts that the membrane potential at zero current (Uo) should be a Goldman-Hodgkin-Katz equation with concentration-dependent permeability ratios. The coefficients of the concentration-dependent terms are shown to be related to the peak energy shifts of the barrier and to the binding constants of the outer sites. The thory also predicts the channel conductance in symmetrical solutions to exhibit three limiting behaviors, from which the properties of the outer and inner sites can be characterized. In two-cation symmetrical mixtures the conductance as a function of mole fraction is shown to have a minimum, and the related phenomenon of inhibition and block exerted by one ion on the other is explained explicitly by the theory. These various phenomena, having ion interactions in a multiply occupied channel as a common physical basis, are all related (by the theory) through a set of measurable parameters describing the properties of the system.


Ca+2-accumulating components in developing skeletal muscle. This ultrastructural study on the localization of Ca+2 in developing skeletal muscle indicates that the formation of calcium-accumulating components begins during embryonic development. Both oxalate and pyroantimonate techniques are used to localize Ca+2 in distinct cellular components of chick pectoral and sartorius muscles. Two major sites for Ca+2 accumulation are present in ultrathin sections of embryonic and post-embryonic muscles: the terminal cisternae of the sarcoplasmic reticulum and specific lines in the I-bands. Calcium oxalate-accumulating vesicles are present in the smallest recognizable myotubes at the twelfth day of incubation, but calcium-accumulating components are not seen at myofibrillar I-band sites until the fourteenth to seventeenth days of incubation. The fact that myofibrils first form and later in development accumulate a Ca+2-binding component suggests that this Ca+2-binding component is not necessary for the formation of myofibrils, but is added to myofibrils before hatching to serve a probable regulatory role in contraction.


Oncogenicity in marmosets of HL-23V, a type C oncornavirus isolated from human leukemic cells, and comparison with simian sarcoma virus type 1 (SSV-1/SSAV-1). Type C virus produced by dog thymus cells (A7573) that were infected with virus (HL-23V), isolated from cultured leukocytes of an acute myelogenous leukemia patient, transformed marmoset and horse cells in vitro and induced virus-producing fibromas in marmosets. The tumors and transformed foci were indistinguishable morphologically from those induced by simian sarcoma virus, type 1 (SSV-1/SSAV-1). HL-23V was indistinguishable from SSV-1/SSAV-1 by immunofluorescence and neutralization tests, and the nontransforming virus associated with HL-23V completely inhibited SSV-1 focus induction in interference tests. Cell cultures established from a marmoset fibroma produced transforming and nontransforming virus biologically and antigenically indistinguishable from HL-23V and SSV-1/SSAV-1.


Separation of the complement-fixing and early antigens from Epstein-Barr soluble antigen. The Epstein-Barr virus-associated complement-fixing (soluble) antigen (CFSA) and the early antigen (EA) were isolated by ion-exchange chromatography from the P3HR-1 lymphoblastoid cell line activated with 5-iodo-2'-deoxyuridine for 72 hours. As expected, these two antigens were not immunologically identical. The CFSA, but not the EA, was isolated from the RAJl lymphoblastoid cell line by the same method.


Human lung organ-specific antigens on normal lung, lung tumors, and a lung tumor cell line. An antiserum raised in rabbits against a lung tumor cell line (2563) was selected from a library of antisera against normal and malignant human lung, lung tumor cell lines, and fetal tissues and was found by complement fixation, immunofluorescence, and saturation binding assays to contain antibodies for antigens characteristic of those found in normal lung. Studies with the adsorbed antiserum (A49) revealed: 1) An antigen was shared by normal lung and normal kidney (NLK-1) 2) lung tissue-specific antigen(s) were present on normal lung tissue (NL-1); 3) NL-1 was found on both external and internal cell membranes; and 4) NL-1, in addition to being present on normal lung and the adenocarcinoma-derived cell line 2563, was present on 1 of 2 metastatic lung adenocarcinomas but on none of 4 metastatic lung tumors of other histologic types.


Low-molecular-weight RNAs of Moloney murine leukemia virus: identification of the primer for RNA-directed DNA synthesis. The small RNAs of Moloney murine leukemia virus (M-MuLV) were fractionated into at least 15 species by two-dimensional polyacrylamide gel electrophoresis. The pattern of small RNAs is significantly different from that of Rous sarcoma virus. A subset of the virion small RNAs is associated with the genome RNA in the 70S complex. One of the associated molecules, a cellular tRNA, is tightly bound to the genome RNA and serves as the major primer for M-MuLV RNA-directed DNA synthesis in vitro.


Evidence for recombination between N- and B-tropic murine leukemia viruses. After co-infection of Sc-1 cells with N- and B-tropic murine leukemia viruses that differ in their XC plaque morphology, Hopkins et al. (1976) obtained viruses, designated XLP-N, that appeared to be recombinants, since they possess the N-tropism of one parent and the XC plaque morphology of the other (the B-tropic virus) parent. Here we present evidence, based on antigenicity and electrophoretic mobility, that some clonal isolates of XLP-N have inherited gp70 gene of their B-tropic virus parent. In addition to providing evidence that XLP-N viruses are recombinants, the fact that an N-tropic virus may apparently possess a gp70 derived from a B-tropic virus provides evidence, which is in agreement with the findings of others (Huang et al., 1973; Krontiris et al., 1973) that the N- or B-tropism of murine leukemia virus does not reside in gp70.


Primer recognition by avian myeloblastosis virus RNA-directed DNA polymerase. Tryptophanyl-tRNA was specifically labeled at the 3' end with [3H]tryptophan and cleaved in half with RNase under denaturing conditions, and the 3' half was shown to hybridize exclusively at the 5' end of avian myeloblastosis virus RNA. The RNA-dependent DNA polymerase of avian myeloblastosis virus is capable of efficiently binding the 3' half of the primer molecule.


Simian virus 40 tumor-specific proteins: subcellular distribution and metabolic stability in HeLa cells infected with nondefective adenovirus type 2-simian virus 40 hybrid viruses. HeLa cells infected with adenovirus type 2 (Ad2)-simian virus 40 (SV40) hybrid viruses produce several SV40-specific proteins. These include the previously reported 28,000-dalton protein of Ad2+ND1, and 42,000- and 56,000-dalton proteins of Ad2+ND2, the 56,000-dalton protein of Ad2+ND4, and the 42,000-dalton protein of Ad2+ND5. In this report, we extend the list of SV40-specific proteins induced by Ad2+ND4 to include proteins of apparent molecular weights of 28,000 42,000, 60,000, 64,000, 72,000, 74,000, and a doublet of 95,000. Cell fractionation studies demonstrate that the SV40-specific proteins are detectable in the nuclear, cytoplasmic, and plasma membrane fractions. By pulse-chase and cell fractionation experiments, three classes of SV40-specific proteins can be distinguished with regard to metabolic stability: (i) unstable in the cytoplasmic but stable in the nuclear and plasma membrane fractions; (ii) stable in the nuclear, cytoplasmic, and plasma membrane fractions; and (iii) unstable in all subcellular fractions. Immunoprecipitation of infected cell extracts demonstrates that most of the above proteins share antigenic determinants with proteins expressed in hamsters bearing SV40-induced tumors. Only the 42,000-dalton protein of Ad2+ND5 is not immunoprecipitable.


Protein kinase and phosphoproteins of avian myeloblastosis virus. A protein kinase associated with purified virions of avian myeloblastosis virus, BAI strain A, was highly purified by ion-exchange chromatography and gel filtration. On the basis of molecular sieving on Sephadex G-200, the enzyme protein appeared to have a molecular weight of about 50,000 to 60,000; disc gel electrophoresis in sodium dodecyl sulfate-acrylamide gels revealed the presence of at least two polypeptide chains; and isoelectric focusing on acrylamide gels revealed two protein bands with activity. Of the nonviral proteins used as phosphate acceptors, the greatest rate of phosphorylation was obtained with alpha-casein. Potential physiological substrates for this activity included specific virion polypeptide of avian myeloblastosis virus. One of the virion polypeptides found in association with reverse transcriptase activity from avian myeloblastosis virus accepted more phosphate than any of nonviral or viral polypeptides examined on the basis of nanomoles of 32P incorporated per milligram of protein.


Two distinct endogenous type C viruses isolated from the asian rodent Mus cervicolor: conservation of virogene sequences in related rodent species. The cocultivation of a lung cell line from the Southeast Asian mouse Mus cervicolor with cells from heterologous species has resulted in the isolation of two new distinct type C viruses. Both viruses are endogenous to M. cervicolor and are present in multiple copies in the cellular DNA of these mice. One of the viruses, designated M. cervicolor type CI, replicates readily in the SIRC rabbit cell line and is antigenically related to the infectious primate type C viruses isolated from a woolly monkey (simian sarcoma-associated virus) and gibbon apes (gibbon ape leukemia virus). This virus is also closely related by both immunological and nucleic acid hybridization criteria to a type C virus previously isolated from a second Asian murine species, Mus caroli. The isolation of the M. cervicolor type C I virus thus provides further evidence that the infectious primate type C viruses originated by trans-species infection of primates by an endogenous virus of mice. The second virus, designated M. cervicolor type C II, replicates well in various cell lines derived from the laboratory mouse Mus musculus. While antigenically related to type C viruses derived from M. musculus, the M. cervicolor type C II virus isolate can be readily distinguished from standard murine leukemia viruses. Both new type C viruses from M. cervicolor are unrelated to the previously described retrovirus (M432) isolated from the same Mus species. The DNA of M. cervicolor therefore contains multiple copies of at least three distinct classes of endogenous viral genes. An examination of the cellular DNA of other rodent species for nucleic acid sequences related to the genomes of both M. cervicolor type C I and II reveals that both viruses have been highly conserved evolutionarily, and that other species of rodents, such as laboratory mice and rats, contain endogenous virogenes related to those in the DNA of M. cervicolor.


The treatment of benign prostatic hypertrophy with flutamide (SCH: 13521): a placebo-controlled study. A double-blind, placebo-controlled study using the antiandrogen compound flutamide in 30 patients with benign enlargement of the prostate is reported. The potency of the compound was indicated by the large percentage of patients suffering from gynecomastia or nipple pain. Flow rate recordings are probably the most reliable and useful examination in this type of investigation, and statistical analysis of the results showed evidence of significant improvement in patients receiving flutamide. No evidence of an effect as compared to the placebo was found when the residual urine, prostate size or histological changes in prostatic biopsies were examined. Subjective effects, when carefully analyzed, provided some evidence of a preference for the flutamide group, especially in the early weeks of treatment, but the fallaciousness of subjective observations is stressed. The various problems associated with the choice and measurement of parameters to be used in this type of investigation are discussed, and the absolute necessity of proper controls and statistical analysis in such a clinical study is illustrated.


Recent progress in ultrasonography of the bladder and prostate. Gray scale transrectal ultrasonography has proved to be a valuable adjunct in the evaluation of patients with tumors of the prostate and bladder. Its application in patients with prostatic disease is in the detection of early asymptomatic tumors, in the accurate staging of local disease and in the following of patients after the institution of specific treatment. Although it is not being used for the detection of bladder tumors the procedure is a reliable means to evaluate the degree of tumor invasion so that proper therapy can be instituted.


Influence of histamine releasing agents on gastric acid secretion of isolated bullfrog gastric mucosa. The influence of histamine releasing agents on gastric acid secretion was studied in isolated bullfrog gastric mucosa preparations. Maximum acid secretory responses in our preparations were obtained by stimulation with tetragastrin (5 X 10(-7) g/ml), histamine (1 X 10(-5) g/ml) and bethanechol (1 X 10(-6) g/ml). Compound 48/80 (1 X 10(-4) g/ml) showed a transient stimulatory action which was followed by a gradual depression of basal acid secretion. The stimulatory phase of compound 48/80 was completely antagonized by burimamide (1 X 10(-5) g/ml), a histamine H2-receptor antagonist. In gastric mucosa preincubated with compound 48/80, the secretagogue action of tetragastrin or bethanechol was not exerted, although this preparation continued to respond to histamine. The effects of Triton X-100, decylamine and polymixin B were quite similar to those of compound 48/80. After pretreatment with compound 48/80, the gastric mucosa preparation became refractory to the stimulatory action of compound 48/80 or Triton X-100. It is thus suggested that endogenous histamine may play an important role in the secretagogue action of tetragastrin and bethanechol.


[Age-specific characteristics of microcirculation in middle-and old age]. The results subsequent to investigations of morphological and functional peculiarities specific for cutaneous capillary circulation in the nailbed of hand and foot fingers of practically healthy young individuals (18--30 years old) and physiologically ageing persons (aged over 60) are reported. In ageing of humans there is demonstrable fading and opacification of the capillaroscopic field of vision background, flattening out of the papillary layer, diminution in the number of functioning capillaries per unit of the skin surface, the presence of non-vascularized zones, the development of intercapillary autoanastomoses and of the subpapillary venous plexus, lengthening of arterial and venous capillary branches, prevalence of spastico-atonic and spastic forms of the capillary loops, slowing down and granular nature of the capillary blood flow. With growing age there become evident a reduction of functioning reserve capillaries, a depression of the skin capillaries sensitivity to the neural effects (heat and cold) and its increase to humoral (adrenalin, histamine, acetylcholine and hypophysin ones. The mechanism behind the said phenomena in ageing is considered. The data obtained are of significance in studying the mechanisms underlying the ageing of the organs and tissues, the understanding of age-specific features of the pathogenesis, evolution and treatment of a number of affections involving the cardiovascular system in persons of advanced and senile age.


Acceleration of canalicular development in lungs of fetal mice exposed transplacentally to dexamethasone. Morphometric techniques were used to compare the volume density of air space (Vva) and the degree of maturation of pulmonary epithelium in normal fetal mouse lung and in lungs of fetuses exposed transplacentally to dexamethasone. Pregnant Bagg-Webster Swiss mice of 16 days' gestation were given injections of either saline or dexamethasone in doses ranging from 0.40 to 12.0 microng. per gm. of body weight, and killed at intervals thereafter. Fetuses were removed and weighed and their lungs prepared for morphometry using osmium-fixed, Epon-embedded tissue. In control lungs, Vva increased 10-fold between days 17 and 19, an increase from 1.5 to 15%. A 25-fold increase occurred during the same period in test fetal lungs exposed to 0.40 microng. per gm. or more of dexamethasone. When the degree of air space development was compared 24 hours after exposure, within a single weight group and, according to dose, a linear increase in air space was found; 0.1-microng. per gm. increment in dexamethasone produced a 0.66% increment in Vva. Body weight was an important determinant, in that fetuses in the lower weight range had much less response. The latter showed an increment of approximately 0.25% in Vva for each 0.1-microng. per gm. increment of dexamethasone. It can be emphasized from the present experiments that a maximal development of Vva could be achieved by amounts of dexamethasone too low to depress fetal or lung weight. The proportion of pulmonary epithelial cells containing osmiophilic granules increased in control lungs from 18% on day 17 to 42% on day 18. Test fetuses (17 days old) examined 24 hours after receiving either 0.40 or 0.80 microng. per mg. of dexamethasone showed no significant increase in this proportion; however, a significant increase in the proportion of cells containing osmiophilic granules was found in fetal lungs exposed to 2.0 microng. per mg. Whereas a significant increase in Vva was found within 14 hours of exposure, no increase in the proportion of cells containig osmiophilic granules was detectable at this time. It was concluded that air space development is a sensitive method for evaluating the effect of dexamethasone as it gives a clear dose-response curve in fetuses exposed to it 24 hours prior to sacrifice. Accelerated maturation of the presumptive type II cell could only be demonstrated within 24 hours by using higher doses than those required to initiate air space development. These observations suggest that the steps invovled in canal formation, which are assumed to reflect alterations in mesenchyme, may have a different sensitivity to dexamethasone than do those initiating the maturation of alveolar epithelial cells.


A cation-retaining layer in the alveolar-capillary membrane. The ultrastructural cytochemistry of the alveolar-capillary "membrane" has been investigated. Dialyzed iron and high iron diamine staining demonstrated a layer containing sulfated mucosubstance at the basal surface of the membranous pneumocytes. In the same layer, fixation with an osmium tetroxide-potassium pyroantimonate solution yielded abundant fine precipitates which were abolished by inclusion of ehtylene glycol bis-N,N'-tetraacetic acid (EGTA) in the fixative. This cation-retaining layer could be interpreted as providing a mechanism for retarding cation transport from the basement membrane to the alveolar space. High iron diamine staining also demonstrated a layer of sulfated mucosubstance on the microvilli of the granular pneumocytes. This layer corresponded with a sialidase-resistant, dialyzed iron-reactive stratum which overlaid the sialomucin-rich cell coat.


Does a bacterial elongation factor share a common evolutionary ancestor with actin? Protein synthesis elongation factor Tu from E. coli shares several physical, chemical, and functional properties with actin-like proteins. Limited tryptic degradation indicates that the two polypeptides have a similar molecular architecture. These observations suggest that they could have evolved from a common ancestor, although more information will be necessary to prove or disprove this hypothesis. A partial sequence, comprising 22 aminoacid residues from the aminoterminal end of the large tryptic fragment of elongation factor Tu is presented.


Myocardial preservation during aortic valve surgery. Assessment of five techniques by cellular chemical and biophysical methods. Five different types of myocardial protection were employed in this series of 168 patients undergoing aortic valve replacement. Two methods of assessing myocardial preservation were used: cellular biological estimations and quantitative polarization measurements. Both parameters showed that either of two methods, continuous perfusion at 32 degrees C. with a beating heart or cardioplegic hypothermic arrest, protected the myocardum best. Intermittent perfusion at 30 degrees C. with a fibrillating heart was the worst means of preservation. Our investigations (both clinical and experimental) have also shown that changes in birefringence, indicative of deteriorating myocardial function, are often detectable before parallel cytochemical changes are apparent.


Celestin tube palliation of unresectable esophageal carcinoma. Celestin tube intubation was performed in 108 patients with unresectable carcinoma of the esophagus and cardia, in 83 per cent as the initial operation and in 17 per cent after exploration. The hospital mortality rate was 16 per cent, including a 7.4 per cent mortality rate from technical causes. The most frequent  causes of death were perforations of the esophagus and cardia and aspiration pneumonia. Nonfatal complications occurred in 13 per cent of surviving patients, obstruction and dislodgment of the tube being the most common. All patients were able to swallow at discharge, and 91 per cent of them could take food by mouth until the time of death. In 9 per cent, additional palliation, usually esophagoscopy or gastrostomy, was required. Ninety-one patients survived one to 21 months (average 5.8 months). The 6 month survival rate was 44 per cent and the one-year survival 9 per cent.


Studies on an adrenal antigen common to man and different animals. Precipitating adrenal antibodies, originally described by Andrada et al., are often associated with patients suffering from the moniliasis-polyendocrinopathy syndrome. The syndrome may include contemporarily several organ-specific autoimmune diseases such as hypoparathyroidism. Addison's disease, thyroiditis, pernicious anaemia, gastritis and ovarian failure and often combined with moniliasis and alopecia. These antibodies seem to differ from those demonstrable by immunofluorescence (IFL) and complement fixation. This conclusion was made as the titres of immunofluorescence antibodies did not correlate with the presence or absence of precipitating antibodies (Krohn et al., Clin Immunol Immunopathol 3:59-68, 1974; Heinonen et al., Ann Clin Res 8:262-265 1976). In this study we describe the subcellular localization and distribution of the precipitable adrenal antigens within some animal species. We found two precipitable adrenal antigens; one of them, designated P-antigen (particulate), was found in precipitable form only in the mitochondrial fractions, and the other, designated S-antigen, could be found in all subcellular fractions of some animal species. Bovine and equine S-antigen could be fractionated on a Sephadex G-200 column, revealing also the soluble nature of the S-antigen. The human S-antigen seemed to differ from the animal S-antigen as in addition to one common antigenic determinant (Sc), the human S contained a second determinant (Sh) not present in the animals. There was no difference in the antigenic character of the P-antigen within different species, although this conclusion is mainly based on the absorption studies.


Non-renin-mediated renovascular hypertension: A new syndrome? In two hypertensive patients with renal-artery stenosis, overactivity of the renin-angiotensin system was ruled out by investigations of renin and aldosterone concentrations and by the lack of a vasodepressor response to angiotensin blockade with saralasin. Nevertheless, hypertension was cured by renal revascularisation. The date suggest that there is a form of renovascular hypertension which is not mediated by the renin-angiotensin system.


H2-receptor antagonists and antacids in the prevention of acute gastrointestinal haemorrhage in fulminant hepatic failure. Two controlled trials. In two controlled trials, involving 75 patients, on the prevention of bleeding from gastric erosions in fulminant hepatic failure, antacids given four-hourly had no significant effect. Only 35% of intragastric pH recordings taken at two-hourly intervals in the treated group were maintained above 5 with the doses used, whereas this could be consistently achieved with the histamine H2-receptor antagonists, metiamide and cimetidine. In the group receiving these drugs only 1 patient out of 26 bled, compared with 13 (54%) of the controls, a highly significant difference. Blood-transfusion requirements were significantly less in those treated with H2-receptor antagonists.


Immunoparesis and outcome in measles.

Immunoparesis and outcome in measles. In five children with measles who subsequently died and in one with measles in whom chronic bronchopneumonia developed (group A), immunosuppression was more pronounced during the acute rash (i.e., 3-20 days before death) than in six children with measles who recovered (group B). The absolute total lymphocyte-count (T and B cells) was significantly lower in group A. Mean serum-C3 was also lower in group A than in group B. There were no significant differences between the two groups for other complement factors or for serum-immunoglobulins. The mean phytohaemagglutinin stimulation index (S.I.) for lymphocytes from patients in group A resembled that in group B, although the S.I. in both groups was significantly lower than that in healthy controls. S.I.S were lowest in two patients who died. Counts of total white cells, neutrophils, null cells, and those with both B and T cell markers were not significantly different in groups A and B. The total lymphocyte-count (mean 2117 +/- S.E.M. 375 cells/mm3) in a further nineteen patients with measles who had died, studied retrospectively, was significantly lower than that (4487 +/- 540 cells/mm3) in twenty-seven patients with measles who recovered.


Post-thyroidectomy hypocalcaemia: A feature of the operation or the thyroid disorder? It has been suggested that post-thyroidectomy hypocalcaemia is related to the presence of a thyrotoxic osteodystrophy for which a high serum concentration of bone alkaline phosphatase is a marker. Changes in serum-calcium (corrected to a standard albumin concentration of 40 g/l), alkaline phosphatase (A.P.), inorganic phosphate, and albumin were studied prospectively in 54 euthyroid patients with drug-treated Graves' disease, and in 17 controls with simple non-toxic goitre, before and serially after partial thyroidectomy. All data were paired and results indicate that the pattern of biochemical change was the same in both types of patient and that the degree of change was not related to the serum-A.P. concentration in the Graves'-disease patients. Of the patients studied within the first 24 h of operation, 5 out of 12 with Graves' disease and raised serum-A.P. (group I), 9 of 20 with Graves' disease and normal serum-A.P. (group II), and 7 of 15 controls (group III) showed a fall in serum-calcium below the lower limit of the reference range. In all three groups there was a highly significant fall in serum-calcium 24 h after operation but there was no significant difference in serum-calcium between the groups either immediately before or 24 h after operation. Serum-calcium returned to pre-surgical concentrations within 7 days of thyroidectomy and serum-A.P. concentrations by 4 to 6 weeks in all groups. There was no evidence that post-thyroidectomy hypocalcaemia is related to thyrotoxic osteodystrophy and the pattern of the biochemical changes was thought to be consistent with release of thyrocalcitonin at operation.


Treatment of severe intermittent claudication by controlled defibrination. Fifteen patients with severe intermittent claudication were treated by therapeutic defibrination with subcutaneous injections of ancrod for 5 weeks. Mean plasma-fibrinogen was maintained below 50% of the initial value throughout the treatment period. This reduction in plasma-fibrinogen was accompanied by a parallel fall in whole-blood viscosity and a pronounced clinical improvement. Objective measurements showed maximum benefit on the 21st day of treatment, when the mean resting ankle/arm pressure index had increased by 37%, the post-exercise pressure index had increased by 50%, and the time taken for the pressure index to return to a resting value after a constant exercise had decreased by 33%. (The claudication-count had increased by 59%).


Heart-rate variability in brain-damaged adults. To test whether or not the characteristics of the adult heart-rate reflect the condition of the central nervous system (as they seem to do in the fetus), ten patients with neurological deficits of acute onset were studied. No patients had received drugs and none was hypoxic. The findings indicate that the normal cyclic changes in heart-rate are reduced in the presence of severe brain damage. Variability decreases rapidly if intracranial pressure rises, and the rate of return of variability reflects the subsequent state of neuronal function, even when intracranial pressure has been restored to normal. In this limited setting, then, it appears that heart-rate variability may reflect the functional state of the central nervous system.


The aetiological role of maternal vitamin-B6 deficiency in the development of atherosclerosis. Lysyl oxidase is the copper-dependent enzyme responsible for the normal cross-linking of both collagen and elastin which is necessary for their functional integrity. There is now strong evidence that this enzyme is vitamin-B6-dependent. The earliest visible lesion of atherosclerosis, commonly found in human neonatal coronary arteries and probably indicative of the location of future atherosclerotic plaques, is a focal splitting of the internal elastic lamina, the cause of which has hitherto remained unexplained. It is suggested that this lesion is the result of imperfect cross-linking of arterial elastin as well as collagen, and is caused by a maternal deficiency of vitamin B6 which is commonly found in pregnancy and which could thus impair the function of lysyl oxidase. Prophylactic supplementation of maternal diet with adequate vitamin B6 is therefore suggested.


Classification of idiopathic diabetes.

Classification of idiopathic diabetes. A classification of idiopathic diabetes based on autoimmunity suggests that two main types of disease process may result in this syndrome. Type 1 includes classic insulin-dependent juvenile-onset diabetes, insulin-dependent diabetes presenting in later life, and diabetes initially adequately controlled for at least 3 months on oral hypoglycaemic agents but with islet-cell antibody (I.C.A.) in the serum. Type II included classic maturity-onset insulin-independent diabetes and the rarer insulin-independent diabetes presenting at a younger age in patients whose serum is negative for I.C.A. at the time of diagnosis. In terms oer the main factor is a genetically determined diathesis towards islet-cell autoimmunity (type Ia), towards islet-cell damage by appropriate viral infection or other agent in the absence of islet cell autoimmunity (type Ic), or a combination of the two diatheses (type IB). Type-II diabetes has a different genetic basis and the environmental factor is a metabolic or other form of stress rather than viral infection. Both main types have an early potential phase indicated by the presence of I.C.A. in serum (type I) and, in the absence of I.C.A., in serum (type I) and, in the absence of I.C.A., by an appropriate family history of insulin-independent diabetes or giving birth to big babies (type II). Evidence to support this hypothesis comes from HLA and histological studies in man and viral studies in laboratory animals as well as from clinical observation.


Frequency of E. coli K antigens in urinary-tract infections in children. The somatic (O) and casular (K) antigens of Escherichia coli from the urine of patients with acute pyelonephritis, acute cystitis, and asymptomatic bacteriuria, and in the faeces of healthy schoolchildren have been investigated. Typing antisera for sixteen capsular acidic polysaccharide K antigens were used, and five (numbers 1, 2, 3, 12, and 13) accounted for 70% of isolates from patients with acute pyelonephritis. These five K antigens were found to a lesser extent in the three other study groups. Thus, only a few K polysaccharides are associated with virulent properties of E. coli for the upper urinary tract. This finding is similar to the association of only some capsular types of pneumococci, meningococci, and Haemophilus influenzae with invasiveness. The identification of virulence markers for E. coli associated with upper-urinary-tract disease may permit more successful control with reference to preventive immunisation.


Treatment of symptomatic diverticular disease with a high-fibre diet. The therapeutic value of increasing the daily dietary fibre intake was assessed over 3 months in a double-blind controlled trial of 18 patients. Significantly greater symptomatic relief was obtained by those on a high fibre regimen than by those in the control group, despite a marked initial placebo effect. The effectiveness of a high-fibre diet increased over the 3-month period.


Pancreatic somatostatinoma. Clinical features and physiological implications. The first case of a tumour producing somatostatin-like immunoreactivity and bioactivity is presented. The pancreatic tumour was composed of cells indistinguishable from islet D cells. Radioimmunoassay of blood-samples obtained by tumour-vein catheterisation revealed very high levels of somatostatin immunoreactivity. On gel chromatography tumour extracts were found to contain at least 4 different immunoreactive components, one of which eluted in the position of synthetic somatostatin. Extracts from the tumour were potent in inhibiting insulin and glucagon secretion from isolated perfused porcine pancreas. Clinical abnormalities included hypochlorhydria, steatorrhoea, and diabetic glucose tolerance. Conceivably some of these abnormalities may be related to somatostatin hypersecretion from the pancreatic tumour.


Neocortical cholinergic neurons in elderly people. Choline acetyltransferase activity (presynaptic cholinergic system) and high affinity binding of cholinergic antagonists (postsynaptic cholinergic system) were measured in brain tissue removed after death from both mentally normal and demented old people. Muscarinic receptor binding sites in frontal cortex decreased with advancing years only in old people without appreciable morphological evidence of senile degeration. Preliminary data for temporal lobe suggested that also in Pick's disease the density of receptor binding sites is reduced. The markers are not significantly reduced in cases of mixed senile and vascular dementia. However, in non-vascular senile dementia of the Alzheimer type, there were indications that the presynaptic marker is selectively depleted. Therefore, centrally acting anticholinesterases might be beneficial, particularly in the early stages of the disease.


Balkan (endemic) nephropathy and a toxin-producing strain of Penicillium verrucosum var cyclopium: An experimental model in rats. Cultures of an isolate of Penicillium verrucosum var. cyclopium, obtained from stored maize in an area of Balkan (endemic) nephropathy--Vratza, Bulgaria--has consistently induced renal tubular lesions when force-fed to rats for 20 days. The lesions, confined to the lower reaches of the proximal convoluted tublues (pars recta and junctional zone), closely resemble the tubular changes in patients with Balkan nephropathy. Preliminary evidence suggests that this nephrotoxin-producing strain of P. verrucosum var. cyclopium may be implicated in the aetiology of Balkan nephropathy.


Plasma-myoinositol concentrations in uraemic neuropathy. In a series of patients with chronic renal failure managed conservatively, the rise in the plasma-myo-inositol (myoinositol) concentration has been found to be related to depression of sural-nerve conduction velocity. There was no correlation with motor-nerve conduction velocity in the peroneal nerve, or with either of these variables in a series of patients receiving chronic haemodialysis. Despite the negative correlation with sural-nerve conduction velocity, there was no correlation between the plasma-myoinositol concentration and the presence of peripheral neuropathy as assessed clinically. It is concluded that hypermyoinositolaemia may depress nerve conduction velocity, but there is no evidence that it is responsible for the development of uraemic polyneuropathy.


Cadmium and hypertension.

Cadmium and hypertension. The cadmium concentration of renal tissue from 82 patients who had died at the age of 45-65 years has been determined by atomic absorption spectrophotometry; 43 were normotensive and 39 hypertensive. Renal cadmium concentration was higher in normotensives than in hypertensives. When smoking habits were taken into account, renal cadmium concentration was found to be 82% higher in normotensives than in hypertensives. Other workers have found the opposite relationship. It is proposed that this discrepancy might reflect either that variations due to age were not taken into account in previous investigations or that a difference exists between soft-water areas and hard-water areas such as the one studied.


Intrathymic pathogenesis and dual genetic control of myasthenia gravis. We propose a two-step model for the pathogenesis of myasthenia gravis. In the first step, primitive intrathymic stem-cells are induced by abnormal stimuli to differentiate to (abnormal?) myogenic cells. In the second step, immunocompetent T lymphocytes start an autoimmune reaction against these newly differentiated myogenic cells. The clinical stage is reached when autosensitised effector T lymphocytes leave the thymus and either infiltrate the synaptic spaces of peripheral muscles or participate in the formation of autoantibodies, causing the neuromuscular symptoms. At two points the pathogenesis is under genetic control--the first at the differentiation of the stem-cells to myogenic cells and the second at the immune responsiveness of the lymphocytes to these atypical intrathymic muscle cells.


Malnutrition in surgical patients. An unrecognised problem. Indices of nutritional state were measured in 105 surgical patients. The indices were chosen to give information on protein-calorie malnutrition, anaemia, vitamin deficiency. Abnormal values for the various indices were common in the group as a whole and most frequent (50%) in patients who were still in hospital more than a week after major surgery. These patients had a high frequency of anaemia, vitamin deficiency, weight-loss, loss of arm-muscle bulk, and low plasma levels of transferrin and albumin. These abnormalities had gone almost entirely unrecognised, even in patients with sepsis after major surgery, who would benefit from improvement in nutritional state.


A strategy to detect beta-thalassaemia minor. Over the past three years 25 302 adults in Kentucky have been tested for haemoglobinopathies, and of these, haemoglobin A2 was measured on 3734, 1973 with microcytosis and 1761 within the normal range. The best methods of detecting beta-thalassaemia minor using red-blood-cell indices were compared. No method detected all heterozygotes. A new method was devised consisting of three parts: (1) haemoglobin electrophoresis, (2) calculation of the product of the square of the mean corpuscular volume (M.C.V.) multiplied by the mean corpuscular haemoglobin (M.C.H.) measured in units of one hundred, (3) A2 determination on all AA samples with (M.C.V.)2 X M.C.H. less than 1530 and on those with variant genotypes consistent with thalassaemia. In this series this new method detected 137 out of 138 heterozygotes with 4-4% false-positives.


Coronary vasospasm in angina pectoris.

Coronary vasospasm in angina pectoris. Coronary angiography was performed during 34 angina attacks in thirty patients admitted because of recurrent angina at rest. Nineteen (seventeen with S-T segment elevation and two S-T depression) had angiograms during a spontaneous attack, eleven (nine with S-T elevation and two with S-T depression) during an attack induced by intravenous ergonovine maleate. Control coronary angiograms showed a wide range of atherosclerotic obstruction, from normal vessels to severe triple-vessel disease. During the anginal attack, all patients with S-T segment elevation had vasospasm localised to one of the major branches, often resulting in complete occlusion. Attacks with S-T segment depression were seen only in patients with double or triple vessel disease, and here the vasospasm generally affected coronary branches without causing complete occlusion. When appropriately searched for, vasospastic angina seems to be common.


A retrospective analysis of blood-lead in mentally retarded children. Blood-lead concentrations were measured retrospectively in the blood contained on cards used for testing for phenylketonuria in the first two weeks of life. Cards which belonged to 80 of a group of 77 children with mental retardation of unknown aetiology and 77 controls were identified. Of 77 usable cards, 41 were from mentally retarded children and 36 were from controls; 24 mental-retardation/control pairs were found. There was a highly significant trend towards higher blood-lead concentrations in the mentally retarded children. Water-lead concentrations in the maternal home during pregnancy correlated with blood-lead concentrations in the mentally retarded children. These results reinforce the probable association between lead exposure during pregnancy and the development of mental retardation of otherwise unknown aetiology.


25-Hydroxylation of vitamin D in primary biliary cirrhosis. The ability to 25-hydroxylate vitamin D was investigated in thirty-nine patients with symptomatic primary biliary cirrhosis (P.B.C.). In seven previously untreated patients serum-25-hydroxy-vitamin-D (25-OHD) concentration increased after regular monthly injections of vitamin D. After a single injection of vitamin D in eight P.B.C. patients serum-25-OHD did not change significantly over 12 days; in contrast there were significant increases in eight normal subjects and in seven patients with nutritional osteomalacia. Twenty-three of twenty-five P.B.C. patients on regular vitamin-D therapy had normal serum-25-OHD values. These results indicate that serum-25-OHD concentrations become normal in P.B.C. if adequate amounts of vitamin D are presented to the liver as substrate.


Intestinal absorption of 25-hydroxyvitamin D and osteomalacia in primary biliary cirrhosis. Bone histology and intestinal absorption of 25-hydroxyvitamin D3 (25-OHD) were investigated in 11 patients with primary biliary cirrhosis (P.B.C.). 4 patients had osteomalacia, and all these had received long-term cholestyramine. Plasma-25-hydroxyvitamin-D (25-OHD) concentrations after an oral dose of 25-OHD3 were significantly lower in the patients with P.B.C. (especially those with osteomalacia) than in normal controls. Serum calcium and urinary calcium excretion were lower, and serum-alkaline-phosphatase higher, in patients with osteomalacia. It is suggested that absorption of 25-OHD undergoing enterohepatic circulation and of dietary vitamin D is reduced in patients with P.B.C. Absorption of 25-OHD is further decreased by cholestyramine and the development of osteomalacia is thus hastened.


Failure of saralasin to predict a response to surgery in renovascular hypertension. Arteriography in two patients with renovascular hypertension suggested fibromuscular hyperplasia, mainly affecting the right renal artery. When saralasin was infused intravenously there was no fall in blood-pressure in either patient. However, both had a raised renal-vein plasma-renin activity on the affected side, relative to the unaffected kidney. Auto-transplantation resulted in a sustained reduction in arterial pressure in both patients. A negative saralasin test should not necessarily exclude further investigation of young patients with severe hypertension.


Alcohol-induced pseudo-Cushing's syndrome. In 4 patients corticosteroid hypersecretion associated with excessive intake of alcohol led initially to an erroneous diagnosis of Cushing's syndrome. If diagnostic errors are to be avoided, a history of alcohol intake should always be sought in a patient in whom the diagnosis of Cushing's syndrome is entertained. The abnormalities of pseudo-Cushing's syndrome revert to normal on ethanol withdrawal.


Aetiocholanolone and prednisolone therapy in patients with severe bone-marrow failure. Ten patients with bone-marrow failure from myelofibrosis, aplastic anaemia, paroxysmal nocturnal haemoglobinuria, and "hairy cell" leukaemia, who had failed to respond to androgens and/or glucocorticosteroids, were treated with a combination of aetiocholanolone and prednisolone. All patients except one with aplastic anaemia responded with an increase in reticulocytes, haematocrit, red blood cell mass, and blood neutrophils and platelets. These data suggest that aetiocholanolone, and similar 5beta-hydroxy steroids, may be valuable in treating certain patients with chronic marrow failure.


Effect of a single dose of dimethyl sulphoxide on renal amyloidosis. An amyloid-like fibrillar substance was obtained under certain chemical conditions from the urine of 11 patients with amyloid nephropathy who had been given a test dose of dimethyl sulphoxide. This fibrillar material could not be produced in the urine from 9 patients with proteinuria due to other causes. This finding may be useful in the diagnosis of amyloid nephropathy and could lead to a new approach to thearpy.


Newer concepts of psychiatric diagnosis and biochemical research on mental illness. Biochemical studies of psychiatric patients have revealed many abnormalities but have failed to identify specific biochemical changes linked to the pathophysiology of the illnesses. Review of these data in the light of newer concepts of psychiatric diagnosis may help to clarify the relationship between biochemical abnormalities and disabilities. These concepts may also suggest useful directions for future research.


Can rifampicin use be safely extended? Evidence for non-emergence of resistant strains of Mycobacterium tuberculosis. Data on the incidence of primary resistance to rifampicin in Mycobacterium tuberculosis strains have been collected from various countries. Strains isolated from those countries where rifampicin is used for both tuberculous and non-tuberculous conditions (Italy, Argentina, Brazil, and Spain) did not show a higher incidence of primary resistance than did strains from other countries (France, U.K., and U.S.A.) where rifampicin use is confined to tuberculosis. It is concluded that there is no evidence to justify fears of an increased incidence of resistance to rifampicin in M. tuberculosis if rifampicin were used discreetly for treating non-tuberculous infections.


Long-term effects and after-effects of treatment of duodenal ulcer with metiamide. Three therapeutic regimens were investigated to find the best way of treating duodenal ulceration with the histamine H2-receptor antagonist metiamide. Relapse of duodenal ulceration was not prevented by nocturnal administration of metiamide. Recurrence was prevented by continued administration of metiamide for 1 year, but cessation of treatment was followed by rapid relapse or symptomless recurrence of the ulceration. Repeated short courses (1 month) of treatment resulted in slower symptomatic control and more rapid recurrence of the ulceration. The treatment of duodenal ulcer with H2-receptor antagonists requires further investigation.


Phenylalanine metabolism and intellectual functioning among carriers of phenylketonuria and hyperphenylalaninaemia. All members of 63 families who had phenylketonuric or hyperphenylalaninaemic offspring received a phenylalanine tolerance test and an individual intelligence test. Parent carriers (heterozygotes, n=115) displayed a significant relationship (canonical correlation R=0.75, P is less than 0.05) between their ability to metabolise phenylalanine and their intellectual strengths and weaknesses. Mothers of hyperphenylalaniaemic children did not show this relationship. The number of carrier children (n=40) was too small for multivariate or sex analysis, but significant bivariate correlations were found for this group.


Effect of granulocytic chalone on acute myeloid leukaemia in man. A follow-up study. Non-pyrogenic preparations of granulocytic chalone have been administered to patient with acute myeloid leukaemia (A.M.L.) who had relapsed after chalone-induced complete remission of the disease. Another regression of the leukaemia was obtained. Normal and leukaemic granulocytes were inhibited without effect on other cell types. Survival was prolonged in 4 other patients with A.M.L. Further investigations are needed to elucidate the therapeutic role of granulocytic chalone.


Rebound thrombocytosis after alcohol abuse: a possible factor in the pathogenesis of thromboembolic disease. Five alcoholic patients had rebound thrombocytosis after withdrawal of alcohol. This rebound thrombocytosis was not always preceded by thrombocytopenia at admission. Two patients had a history of unexplained recurrent venous thrombosis and recurrent pulmonary embolism. It is suggested that recurrent rebound thrombocytosis after alcohol abuse can be a factor in the pathogenesis of thromboembolic disease in some patients.


A specific orally active inhibitor of angiotensin-converting enzyme in man. An orally active inhibitor of the angiotensin-converting enzyme, SQ 14,225 (D-2-methyl-3-mercaptopropanoly-L-proline), was administered to fourteen normal male volunteers to evaluate its safety and efficacy in inhibiting pressor responses to exogenous angiotensin I. SQ 14,225 produced significant blockade within 15 min of oral administration. The magnitude and duration of inhibition were dose-related. After a dose of 20 mg, complete blockade was observed for more than 2 h and partial inhibition for over 4 h. There was no effect on pressor responses to angiotensin II. SQ 14,225 promises to provide a new approach to the diagnosis and treatment of disorders involving over-activity of the renin-angiotensin system.


Prevalence and presentation of hyperprolactinaemia in patients with "functionless" pituitary tumours. Serum-prolactin concentrations were measured in 111 patients who had radiological abnormalities of the pituitary but no evidence of acromegaly, Cushing's syndrome, or Nelson's syndrome. Raised prolactin levels were found in 45 of 64 (70%) patients studied before treatment and in 15 of 47 patients studied after pituitary surgery. The majority of hyperprolactinaemic patients presented with amenorrhoea or impotence; galactorrhoea was uncommon. By contrast, reproductive disorders were rare in patients with normal prolactin levels. It is concluded that pituitary tumours previously described as "functionless" are frequently associated with hypersecretion of prolactin and that such tumours usually present as reproductive disorders. In the investigation of patients with amenorrhoea or impotence serum-prolactin should be measured and skull radiology performed if the prolactin level is raised. Prolactin should be measured in all patients with abnormal pituitary X-rays both before and after pituitary surgery.


A possible virus aetiology in outbreaks of food-poisoning from cockles. In a series of outbreaks of food-poisoning associated with the consumption of cockles, no bacterial pathogens were demonstrable either in faeces of patients or in cockles. However, small round virus-like particles have been detected in a high proportion of the faecal specimens in three of the outbreaks. These particles are similar in size, morphological features and density to particles seen in outbreaks of winter vomiting and non-bacterial gastroenteritis although in preliminary tests they are serologically distinctive.


Complement activation in migraine.

Complement activation in migraine. Forty patients attending the Prince Henry Hospital migraine clinic have been investigated for evidence of complement activation related to migraine. These patients had a history of clinically similar migraine attacks. Levels of serum complement components were determined in nine patients, both in and out of migraine. Comparison of these levels showed significant reductions in C4 and C5 during headache. In a further 31 patients C3 breakdown products were sought when these patients were headache-free. They were detected in the plasma of three patients who proceeded to a migraine attack but not in the plasma of the remaining twenty-eight who did not. These findings suggest the presence of complement activation, which could explain many of the previously reported phenomena associated with migraine.


Varicose veins in tropical Africa.

Varicose veins in tropical Africa. 1259 Tanzanians in a provincial town were examined for varicose veins. 5-5% (6-1% of men and 5-0% of women) of the 1000 people aged eighteen years and over had varicose veins. This prevalence is intermediate between that reported for minimally developed areas (0-1%-0-4%) and the age-adjusted rate reported for Michigan (12-3%). The Tanzanian diet included some refined carbohydrate, and the mean daily stool weight (228 g) indicated a fibre content intermediate between that of traditional African communities (490 g) and western countries (115 g). These findings are consistent with the hypothesis relating varicosities to a fibre-depleted diet. Life-long use of the squatting position for defaecation did not protect against the development of varicose veins.


[Experiences with tracheal-T-tubes in reconstructive surgery of the trachea (author's transl)]. In 19 cases with trachea problems we used the silicon-T-tube described by Montgomery (1965). Following our experiences we can recommend this trachea-endoprosthesis for two principal indications: 1. as symptomatic treatment in cases with non-operable stenoses of the upper airways, 2. as endoprosthesis and laryngeal or tracheal stent after reconstructive surgery. Numerous advantages  compared with traditionally used silver canulas have been noticed.


[Esophageal varices hemorrhage in portal hypertension (author's transl)]. Diagnostic and therapeutic possibilities for esophageal varices hemorrhage in portal hypertension are indicated with reference to 149 patients. In the acute phase, operative measures are to be rejected because the lethality is too high. Conservative treatment with a Blakemore-Sengstaken probe should always be introduced at first. After confirmation of the conditions in the liver, a pressure-reducing anastomosis operation (delayed emergency shunt) must be performed. For this purpose we prefer the terminolateral splenorenal anastomosis.


Endogenous activation of latent collagenase by rheumatoid synovial cells. Evidence for a role of plasminogen activator. To elucidate the mechanism of synovial damage in rheumatoid arthritis, we studied the activation of latent collagenases released from adherent rheumatoid synovial cells in culture. Latent enzyme was not complexed with alpha2 macroglobulin, the prinicpal proteinase inhibitor in serum, and could be activated by trypsin in the presence of alpha2 macroglobulin if sufficient proteinase was added to saturate inhibitor. Latent collagenase bound half as effectively to collagen fibrils as active enzyme. Plasmin was a threefold better activator of latent enzyme than trypsin and could be generated by addition of plasminogen to synovial-cell cultures. Production of both collagenase and plasminogen activator was inhibited by dexamethasone (10(-9) M). These studies emphasize in importance of control of activation in regulation collagenase activity, It is likely that rheumatoid synovium produces both latent collagenase and plasminogen activator; plasmin is activated from its zymogen, plasminogen, present in inflamed tissues, and in turn activates collagenase.


Dimensions of homo- and heteropolymeric sections of DNA synthesized by reverse transcription from globin mRNA matrices. The lengths of globin messenger RNAs, isolated from rabbit and pigeon reticulocytes, and single-stranded complementary DNAs, synthesized from mRNA in presence of RNA-directed DNA-polymerase and oligo(dt) have been investigated by polyacrylamide gel electrophoresis under denaturing conditions. The cDNA preparations contained a fraction which corresponded in length to the alpha and beta chains of the mRNA used as a matrix. The lengthwise distribution of poly(A) sequences, isolated from globin mRNAs, corresponded to a statistical distribution, with a maximum at 75-80 nucleotides and with a maximum length of approximately 150 nucleotides. The lengthwise distribution of poly(dt) sequences, isolated from cDNA, corresponded to the poly(A) sequence distribution. It was concluded that: 1) cDNA is heterogeneous with respect to the length of poly(dt) sequences located at the 5' end of the molecule; 2) there was no selective use as primer of only that oligo(dt) which was located within the complex formed with the 5' end of the mRNA poly(A) sequence; 3) the heterogeneity of poly(DT) corresponded qualitatively to two models of template-primer interaction: selective use as a true primer of the oligonucleotide located in the complex formed with the 3' end of mRNA, and a statistical distribution of primer along the poly(A) sequence; and 4) the heterogeneity of the homopolymeric section of the cDNA may affect the kinetics of hybridization with mRNA, which possibly explains the previously observed [1] anomalous dependence of the hybridization rate on time.


Neostigmine-induced end-plate proliferation in the rat. A study using supra-vital methylene blue. The supra-vital methylene blue technique was used to study motor end-plate morphology in 21 BD-1X rats, treated for 7 to 16 weeks with oral neostigmine bromide, and in five control animals. Motor endings of treated animals showed preterminal, terminal, and ultraterminal sprouting and an increase in mean end-plate length (p less than 0.001). These changes were most prominent after 14 weeks of treatment. After 16 weeks of therapy, mean end-plate length decreased and the proliferative abnormality became less evident. The adverse effect of neostigmine on motor end-plates may have clinical relevance in the management of myasthenia gravis and may be partly responsible for the end-plate abnormalities previously reported in this disease.


[Cytologic diagnosis of stomach neoplasms]. Personal experience in the cytological diagnosis of gastric neoplasis acquired in a series of 104 patients is presented. Three false positives were detected in 29 cases of supposed malignancy and 11 false negatives in 75 patients with tumours thought to be benign. Cytology often proved the determining factor in the planning of surgery, while in some instances it also gave an indication of the histological type involved.


Prenatal diagnosis of neural tube defects. III. A reevaluation of the alpha-fetoprotein assay. Alpha-fetoprotein was measured in 2209 amniotic fluid samples under improved assay conditions. All cases of open neural tube defects had elevated values greater than 5 SD above the mean. The false positive rate based on the 3 SD cutoff is estimated at less than 9.15%. Alpha-fetoprotein assays are recommended for all patients undergoing second trimester amniocentesis, optimally between 14 and 16 weeks' gestation.


[Alpha-fetoprotein in the liver of embryonic and newborn rats]. The localization of alpha-fetoprotein in the liver of embryos and newborn Wistar rats was determined by the method of fluorescent antibodies. This protein was found in the cytoplasm of some hepatocytes, endothelium of blood vessels and erythroid blood cells of embryos and new born rats. It was never found in the blood-forming and Kupffer cells of the liver, as well as in the epithelium of bile ducts. The hepatocytes containing this protein were located in the liver lobes near the central veins. Their number and the intensity of fluorescence decreased with the age of animals.


[Isolation of the cercaria Diplostomum phoxini (Faust, 1918) Arvy et Buttner, 1954 (Diplostomatidae) from fresh water mollusks of the Crimea]. Data on the biology and morphology of cercariae of Diplostomum phoxini (Faust, 1918) Arvy et Buttner, 1954 are given. The cercariae were found in Radix auricularia from the middle part of the Burulcha river (Ukranian SSR, Crimea). In November, 1974 the invasion extensity of mollusks was 16.3%. No cercariae were found in spring and summer samples.


[Distribution of certain enzymes in totally stained Cestode preparations]. The distribution of succinic dehydrogenase, HApi-diaphorase, glucose-6-phosphatdehydrogenase, alkaline and acid phosphatases and glucose-6-phosphatase was studied by means of the incubation of whole cestodes. Succinic dehydrogenase, NAD-diaphorase and glucose-6-phosphatdehydrogenase are connected in general with the fixating apparatus of the scolex and genital organs; phosphatases -- with the integument tissues, excretory system and calcareous corpuscles. The results obtained are in complete agreement with the available data on the distribution of the enzymes studied. The incubation method of whole cestodes can be useful for field works.


[Study of the method of direct immunofluorescence for differentiation of serotypes of Trichomonas]. It is possible to differentiate the serotypes of Trichomonas vaginalis by the direct immunofluorescent method using the tupe-specific antisera labelled with fluorescin-isothiocyanate. The most decisive factor in expressing the degree of induced fluorescence is the serotype of the protozoa. Evans blue, which has an intensive red fluorescence, totally eliminates the green autofluorescence of T. vaginalis and does not influence the induced specific fluorescence.


[Anaphylactic type of accidents due to myorelaxing agents during general anesthesia. Clinical and biological study]. Six patients who had suffered a reaction to the administration of muscle relaxants at the time of induction of general anaesthesia were explored using skin tests, the Prausnitz-Küstner reaction, the blastic transformation test, the Shelley test and the basophil histamine release test. Fifteen normal subjects were used as controls. The patients who had suffered a reaction showed considerable cutaneous hypersensitivity to muscle relaxants. None of the biological tests carried out revealed an immunological mechanism.


Gains and losses of vascular surgery patients. Understanding the gains and losses experienced by the patient and his family aids in assessing the psychologic sequela of peripheral vascular surgery. Placing the patients' individual responses into the categories of: function, self-directiveness, self-definition, and future orientation offers a way to conceptualize the meaning of the illness to the patient. Factors such as physical mobility and integrity, self-concept and body image greatly influence the adaption process. Conceptually, these elements provide a framework upon which to base nursing intervention. Careful observation, skillful interviewing, and interpersonal support are appropriate nursing considerations when caring for the patient with peripheral vascular disease. The goal of adaption is a successful reintegration of the whole person,which comes from an acceptance of both gains and losses experienced in surviving peripheral vascular surgery.


Factors in the rehabilitation of patients with peripheral vascular disease. At some point in the progression of peripheral vascular disease, a hospitalized patient may require the services of a rehabilitation unit. All patients, however, can benefit from basic rehabilitative care that should begin at the time of initial diagnosis of their disease and be considered throughout their treatment course. The nurse in the clinic , in the intensive care unit, and on the medical and surgical units should be aware of potential factors that may prevent the person with peripheral vascular disease from realizing his full potential. Physical, psychologic, social, economic, vocational, and spiritual needs are all important factors in the rehabilitation process.


Identification of simian virus 40 tumor and U antigens. The synthesis and identity of the tumor and U antigens of simian virus 40 (SV 40) have been examined during productive infection in monkey cells, abortive infection in mouse cells, and in SV40-transformed mouse cells by using sodium dodecyl sulfate/polyacrylamide slab gel electrophoresis to analyze [35S]methionine-labeled radioimmune precipitates. The following observations were made: (i) the tumor and U antigenic sites are on the same 94,000, 89,000, and 84,000 molecular weight species detected during productive infection; a 94,000 species made during abortive infection; and a 94,000 species found in transformed cells. (ii) The 94,000 species is relatively unstable compared to the relatively stable 89,000 and 84,000 species produced during productive infection. (iii) The stable 89,000 and 84,000 molecular weight species are differentially extracted from productively infected cells, which suggests an intracellular compartmentation and/or different affinities of these species for cellular substrates. (iv) The 94,000 species synthesized during abortive infection is more stable than the comparable 94,000 species synthesized in transformed cells. (v) Three tsA group mutants overproduce several unstable species of tumor antigen at restrictive temperature.


Antigenic distinctions of glycoproteins in plasma and mitochondrial membranes of lymphoid cells neoplastically transformed by simian virus 40. Highly purified plasma membranes from hamster lymphocytes transformed by simian virus 40 (GD 248) were compared with the membranes of normal cells by crossed immune electrophoresis, crossed-line immune electrophoresis, and bidimensional isoelectric focusing-immune electrophoresis. Antiserum raised by inoculation of guinea pigs with GD 248 membranes was used as serologic reagent, either directly or after absorption with membranes from normal cells. Bidimensional immune electrophoresis reveals the presence in the plasma membranes of GD 248 cells of at least three antigens not detectable in the membranes from the normal cell population. At least two of these are also present in the mitochondrial membranes of GD 248 cells, but none could be detected in membranes of embryonic fibroblasts. Bidimensional isoelectric focusing-immune electrophoresis indicates that the distinctive antigens of the GD 248 membranes are glycoproteins.


Expression of antigenic crossreactivity to RD114 p 30 protein in a human fibrosarcoma cell line. An antigen crossreacting with the 30,000-molecular-weight protein (p30) of the feline endogenous oncornavirus (RD114) was detected in a well-characterized human fibrosarcoma cell line, HT1080, by indirect immunofluorescence. Three antisera against RD114 p30 gave similar positive results, while two antisera prepared against simian sarcoma virus p30, one antiserum prepared against murine leukemia virus p30, and one antiserum prepared against feline leukemia virus p30 gave no immunofluorescence. The reactivity observed with the antiserum against RD114 p30 was detected in 10-40% of the cells at early passages and was no longer expressed by the forty-first subculture. The reactivity could be removed by adsorption of the antiserum with RD114-infected dog or human cells, but not by uninfected cells or by cells infected with an antigenically unrelated oncornavirus, feline leukemia virus. Neither complete virus particles nor reverse transcriptase (RNA-dependent DNA nucleotidyltransferase) activity was detected in the culture. These experiments suggest that the fibrosarcoma cell line is expressing an antigen related to the p30 protein of RD114 baboon endogenous virus group of oncornaviruses without producing complete virions.


[Evaluation of the method of blood tyroxine determination with the aid of non-immunosorbents]. Tetralute 125I-Column is a set for determination of the total thyroxin content in the serum; this is a valuable test for examination of the T4 content in the blood with the aid of radioactive isotopes. The method is simple, specific, sensitive and precise, and can be used both under laboratory and under clinical conditions. Results of this test coordinate with the data of the protein-bound iodine study and the percentage of the T3 absorption. The work is based on determination of T4 in 2050 samples for a two-year period.


Biological function of gramicidin: studies on gramicidin-negative mutants. By the use of a rapid radioautographic screening procedure, two mutants of Bacillus brevis ATCC 8185 that have lost the ability to produce gramicidin have been isolated. These mutants produced normal levels of tyrocidine and sporulated at the same frequency as the parent strain. Their spores, however, were more heat-sensitive and had a reduced dipicolinic acid content. Gramicidin-producing revertants occurred at a relatively high frequency among the survivors of prolonged heat treatment and had also regained the ability to produce heat-resistant spores. A normal sport phenotype could also be restored by the addition of gramicidin to cultures of the mutant strain at the end of the exponential growth. On the other hand, the addition of dipicolinic acid could not cure the spore defect. These results provide strong evidence that the inability to produce gramicidin is directly responsible for the observed spore defects. Indeed, they unambiguously demonstrate a function of a peptide antibiotic in bacterial sporulation. The possibility that this function consists of the regulation of transcription during the transition from growth to sporulation is discussed.


Human placental lactogen mRNA and its structural genes during pregnancy: quantitation with a complementary DNA. A complementary DNA (cDNA) strand was transcribed from human placental lactogen (hPL) mRNA. Based on alkaline sucrose gradient centrifugation, the size of the cDNA was about 8 S, which would represent at least 80% of the hPL mRNA. Previously we showed that four to five times more hPL was synthesized in cell-free extracts derived from term as compared to first trimester placentas. Hybridization of the cDNA with RNA derived from placental tissue revealed that there was about four times more hPL mRNA sequences in total RNA from term placenta than in a comparable quantity of total first trimester RNA. Only background hybridization was observed when the cDNA was incubated with RNA prepared from human kidney. To test if this differential accumulation of hPL mRNA was the result of an amplification of hPL genes, we hybridized the labeled cDNA with cellular DNA from first trimester and term placentas and with DNA isolated from human brain. In all cases, the amount of hPL sequences was approximately two copies per haploid genome. Thus, the enhanced synthesis of hPL mRNA appears to result from a transcriptional activation rather than an amplification of the hPL gene. The increase likely reflects placental differentiation in which the proportion of syncytial trophoblast increases at term.


Cell-cycle-related changes of 3':5'-cyclic GMP levels in Novikoff hepatoma cells. Intracellular and extracellular levels of 3':5'-cyclic GMP and 3':5'-cyclic AMP were studied in synchronized Novikoff rat hepatoma cells. Intracellular levels of cyclic GMP increased spontaneously from 2-fold (without colcemid) to 10-fold (with colcemid), in proportion to the number of cells in mitosis. As cells entered mitosis, cellular cyclic AMP declined simultaneously with the rise in cyclic GMP. These reciprocal changes in cyclic nucleotide levels were reversed as cells passed out of metaphase and through anaphase. Maximum cyclic AMP and minimum cyclic GMP concentrations occurred during G-1. Less marked reciprocal fluctuations in both cyclic nucleotides were also found in S-phase and early G-2, where the ratio of cyclic AMP to cyclic GMP concentrations first fell and then increased. These changes in cyclic nucleotide ratios were closely correlated with major cell-cycle transitions at the boundaries between G-1/S-phase, S-phase/G-2, G-2/prophase, and metaphase/anaphase. Most, but not all, of the extracellular cyclic nucleotides were extruded when cells traversed mitosis. Colcemid or vinblastine completely prevented the appearance of extracellular cyclic AMP but augmented the appearance of extracellular cyclic GMP in parallel with the accumulation of mitotic cells. These results reflected changes in intracellular cyclic nucleotides and indicated that increased intracellular turnover of cyclic GMP and cyclic AMP occurred before and after metaphase, respectively. Elevated cyclic GMP levels during mitosis and S-phase are consistent with potential modulatory roles for this cyclic nucleotide in proliferation.


Rous sarcoma virus genome is terminally redundant: the 5' sequence. When Rous sarcoma virus RNA is transcribed into DNA by the reverse transcriptase, a tRNA primer is elongated into DNA. The primer is near the 5' end of the virus genome; the first major DNA made is a "run-off" product extending 101 bases from the primer to the 5' end of the template. We have studied this DNA molecule to determine the sequence of the first 101 bases at the 5' end of the Rous sarcoma virus genome (Prague strain, subgroup C). Twenty-one bases at the extreme 5' end are also at the 3' end of the virus genome (see D. E. Schwartz, P. C. Zamecnik, and H. L. Weith, this issue, pp. 994-998), and thus this virus is terminally redundant. The existence of this sequence repetition immediately suggests mechanisms by which the growing DNA copy can jump from the 5' end to a 3' end of the template and become circular. The sequence also displays a possible ribosome binding site and enough secondary structure to permit a possible 5'-5' linkage of viral RNA molecules.


Rous sarcoma virus genome is terminally redundant: the 3' sequence. A sequence of 20 nucleotide residues immediately adjacent to the 3'-terminal poly(A) in Rous sarcoma virus (Prague strain, subgroup C) 35S RNA has been determined by extension of a riboguanylic acid-terminated oligothymidylic acid primer hybridized at the 5' end of the 3'-terminal poly(A) with purified reverse transcriptase (RNA-directed DNA polymerase; deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase, EC 2.7.7.7) from avian myeloblastosis virus. The sequence is 5'GCCAUUUUACCAUUCACCACpoly(A)3'. This same nucleotide sequence, excluding the poly(A) segment, has also been found at the 5' terminus of Rous sarcoma virus RNA (W. A. Haseltine, A. Maxam, and W. Gilbert, this issue pp. 989-993), and therefore the RNA genome of this virus is terminally redundant. Possible mechanisms for endogenous in vitro copying of the complete RNA genome by reverse transcriptase which involve terminally repeated nucleotide sequences are discussed.


Benign prostatic hyperplasia: etiological considerations. The evidence for a hormonal etiology of BPH in man and the dog has been reviewed. Experimentally, although the administration of testosterone or dihydrotestosterone or dihydrotestosterone plus estradiol failed to produce BPH in the dog, treatment with androstanediol or androstanediol plus estradiol produces many of the features characteristic of canine prostatic hyperplasia. This development may provide an experimental model for exploration of the pathogenesis of prostatic hyperplasia.


Androgen receptors in male sex tissues of rats and humans. A brief description of physicochemical properties of the androgen receptors in the various target tissues is given. It is suggested that androgen receptors in all organs and species are very similar if not identical. It is also suggested that apparent differences in steroid binding are not due to differences in steroid specificity of receptors, but rather due to organ specific differences in target tissue metabolism. A short discussion of our studies on androgen receptors in the prostate, epididymis and testis of human being is also included. The properties of these receptors are similar, if not identical to those described in rats, and we have not been able to demonstrate differences in androgen receptors of non-neoplastic and neoplastic tissue. From studies on testosterone metabolism it is demonstrated that human prostate is metabolizing testosterone to DHT much faster than the seminal vesicles. Furthermore, there is a drastic reduction in DHT formation in tissue from prostatic cancer compared to normal and hyperplastic prostatic tissue.


Disseminated intravascular coagulation in prostatic disease. DIC may complicate prostatic disease either in its acute type during resection of the prostate causing excessive intra- or postoperative bleeding, or in its chronic type in cases with adenocarcinoma of the prostate with haematogenous metastases. Pathogenesis, diagnosis, clinical course, differentiation of the condition against consumption of clotting factors by primary fibrinolysis, and treatment are discussed. The course in four characteristic cases is demonstrated.


Cryosurgery of prostate adenoma: evaluation of the method. For a small group of high-risk patients with prostate adenoma, cryosurgery should be the method of choice (about 5-10+ of all cases). This intervention is only a palliative measure. The regrowth of residual adenoma is minimal. The clinical importance of this new technique is greater for those urological schools preferring the open surgical approach compared to those mainly performing transurethral resection.


Histamine-releasing effect of a corticotrophin derivative. I. Histamine-releasing effect of a nonadecapeptide in comparison with that of other histamine liberators. The histamine-liberating properties of a synthetic polypeptide (an a synthetic polypeptide (an alkylprolyl derivative of beta1-19-corticotrophin) were investigated under a variety of experimental conditions. It was found to be more potent in this respect than Compound 48/80, Melittin and Triton X-100. The degree of cell destruction observed in conjunction with the release of histamine induced by C 44 680-Ba suggests that the mode of action of the substance more closely resembles that of Compound 48/80 than that of Triton.


[Purification of a beta lipoprotein fraction rich in Lp(a)]. A Lp (a) rich fraction was prepared from  heparin/manganese chloride precipitated beta-lipoproteins, by using DEAE cellulose chromatography and gel filtration on Sepharose 4 B.


Surface staining of small intestinal biopsies. Small intestinal biopsies are most often by routine examined under a stereo-microscope, prior to embedding for histological examination. This is done in order to get a view of the appearance of the mucosal pattern, especially villus configuration. The distinctness of the surface pattern however, is improved considerably if the biopsies are stained with Alcian Green and/or PAS before they are examined. In the present paper a detailed description is given of staining of small intestinal biopsies as whole mounts. The difference between the unstained and the stained biopsies is illustrated by a few examples.


Identification of different antigenic determinants within the synthetic multichain co-polymer poly(Tyr,Glu)-polyAla--polyLys as recognized by the chicken. I. Significance of the polyAla--polyLys backbone and identification of poly-D-alanine as the antigenic determinant in backbone-directed responses. The multichain co-polymer poly(Tyr,Glu)-polyAla--polyLys, designated (T,G)-A--L, is normally thought to present only the poly(Tyr,Glu) sequences, designated (T,G), as antigenic determinants. Evidence is presented indicating that at least two different determinants in the (T,G)-A--L antigen are recognized by chickens. Studies in a partly inbred high-responder chicken strain reveal two major determinant systems: the (T,G) and the A--L in the (T,G)-A--L antigen. For one serum the antigenic determinant of the A--L backbone is shown to be a poly-D-alanine.


Characterization of an inhibitory allogeneic effect on humoral responsiveness in vitro. Evidence is presented that the induction of a humoral response is inhibitable by a thymus-derived cell (TI) that acts on the antigen-sensitive precursors of both the thymus-derived cooperating and the bone marrow-derived antibody-secreting cell-that is, the tC and B cell respectively. The inhibition of induction of the tC and B cell by the TI cell is shown to be reversed by increasing the effective level of cooperation. This competitive interaction between the inhibitory (TI) and cooperating (TC) systems is postulated to be part of the mechanism for regulating the class of the response, cell-mediated or humoral. The following properties of the inhibitory system were demonstrated: [1] The tI cell--the antigen-sensitive precursor of the TI cell--is both paralyzable and inducible. [2] The TI cell appears during the induction of a cell-mediated response and, if not identical to the effector cytotoxic ('killer') TK cell, the TI cell is induced in parallel with it. [3] The effector function of the TI cell, like that of the TK cell, is H-2-restricted.


The absence of a human thymus lymphocyte antigen (HTLA) on basophils and mast cells. Basophilic granulocytes and mast cells of different species have been reported to originate from thymocytes and other lymphocytes. These observations were recently confirmed when evidence was given that thymic antigen is present on rabbit basophilic granulocytes. In the study reported here, human leukocytes were tested by the immunofluorescence technique and the immunoelectron-microscopy technique to ascertain whether a human thymus lymphocyte antigen (HTLA) could be detected on their surface. We could demonstrate the presence of HTLA on T lymphocytes but not on basophilic granulocytes, nor on mast cells in Cryostat sections of various tissues.


The inhibitory action of the pineal extract on TRH. The effects of a single dose and of 5 doses (5 days) of a bovine polypeptide pineal extract (PE) on the pituitary TSH reserves and on the blood level of thyroid hormones were studied on hypothyroid patients. The blood levels of PBI, total T4 (radiocompetitive), free T4, T3 and TSH (RIA) in basal conditions and during the TRH test (i.v. administration of 200 mug TRH), In the presence and absence of the treatment with PE were determined. Thirty minutes following i.m. administration of PE a decrease was noticed in the high level of the basal TSH in all the patients as well as maintenance or even exaggeration of the TRH response. After 5 days of PE administration a decrease was noticed in the basal TSH, with preservation of a strong response of the TSH release after TRH administration. In these patients a slight decrease was observed in PBI, total and free T4 and T3, when their initial level was close to normal. The results show the results show the intervention of the pineal extract by inhibiting the endogenous TRH.


Genetic basis of memory in cell-mediated immune response. The present experiments were undertaken to delineate the role of LD and SD antigens in terms of memory in cell-mediated immune response (CML). Using recombinants that differ for either the H-2K or H-2D determinants (SD-different) and other recombinants differing for the central region of H-2 (LD-different), we have investigated this question. The results indicate that priming to SD determinants leads to a more rapid and higher response when cells are restimulated in vitro with either the same SD antigen alone or the same SD plus an LD antigen  and tested on target cells that possess either the SD antigen alone or both the LD and SD antigen. Antigens in the central regions of H-2, which includes LD, serve as the stimulus both for the helper T cells and for the cytotoxic T lymphocytes. Priming with a high dose of LD antigens leads to memory in the cytotoxic T lymphocyte recognizing the cytotoxic target antigens coded by the central region of H-2. Nevertheless, memory could not be detected when priming was done under the same conditions as for SD antigens. Moreover, a primed helper T-cell response does not facilitate the development of increased CML on restimulation in vitro with the LD antigen used for priming and a new SD antigen. Thus, it seems that memory in CML is in the cytotoxic T lymphocyte and not in the proliferating helper cells.


Staphylococcal protein A in immunoferritin techniques. Protein A (pA) of Staphylococcus aureus, by virtue of its reactivity with the Fc portion of a variety of mammalian immumoglobulins (IgG), can be used for electron-microscopical immunoferritin techniques. The conjugation of pA with ferritin (pA-F) by means of bis(4-fluoro-3-nitrophenyl) sulfone results in a highly specific marker for IgG in indirect labeling experiments. Native pA can be used as a noncovalent bridging agent between specific antibodies and antiferritin capturing the marker molecule. The use of pA and pA-F is demonstrated with a model system involving human erythrocytes and two rabbit antisera directed against different surface antigens of the human erythrocyte membrane.