Step function input to the rat kidney by shifting between auto- and alloperfusion. A technique is described that permits instantaneous shifts from autoperfusion of the left kidney of an "experimental" rat to alloperfusion of the same kidney from a "pump" rat (or vice versa). Renal arterial and venous pressures are maintained at normal levels during alloperfusion. The kidney has proved to work satisfactorily during both auto- and alloperfusion as judged from measurements of renal blood flow, urine volume flow, urine osmolality, and fractional extraction of inulin and PAH. The vascular dead space of the system is extremely small. If the blood of the pump rat-experimental rat has been equilibrated with indicator, shifting from auto- to alloperfusion constitutes a practically pure step washin to/washout from the kidney. Reverse effects are obtained by shifting from allo- to autoperfusion. Compared with the bolus injection technique, recirculation problems are minimized because the perfused vascular volume of a single kidney is small compared with the whole-blood volume of the rat.


The neurobiological origins of psychoanalytic dream theory. Freud built his model of the mind and his hypotheses about dreaming directly on the structure of his neurobiological model of the brain, which was developed in the "Project for a Scientific Psychology", written in 1895. Among the concepts modeled in this work were ego, somatic drives as motivationally critical, cathexes of psychic energy, wish fulfillment, and primary and secondary process. From the vantage point of more than 80 years later, the authors indicate the areas in which many of Freud's neurobiological assumptions are inacurrate. Revisions are needed in the neurobiologically derived psychoanalytic concepts, especially those of Freud's wish fulfillment-disguise theory of dreams.


Phenytoin treatment of the binge-eating syndrome. Nineteen subjects completed a 12-week double-blind crossover study comparing phenytoin with placebo in the treatment of severe binge eating. In the placebophenytoin sequence the number of binges decreased during phenytoin treatment from both placebo and pretreatment levels. However, in the phenytoin-placebo sequence, not only did phenytoin reduce the number of binges from pretreatment levels, but there was no reversal of this effect during the placebo period. This sequential effect was unexpected and is still unexplained. The mechanism of phenytoin action and the significance of EEG abnormalities found in 7 of the subjects remain uncertain.


Daily relaxation response breaks in a working population: I. Effects on self-reported measures of health, performance, and well-being. An experiment conducted at the corporate offices of a manufacturing firm investigated the effects of daily relaxation breaks on five self-reported measures of health, performance, and well-being. For 12 weeks, 126 volunteers filled out daily records and reported bi-weekly for additional measurements. After four weeks of baseline monitoring, they were divided randomly into three groups: Group A was taught a technique for producing the relaxation response; Group B was instructed to sit quiety; Group C received no instructions. Groups A and B were asked to take two 15-minute relaxation breaks daily. After an eight-week experimental period, the greatest mean improvements on every index occurred in Group A; the least improvements occurred in Group C; Group B was intermediate. Differences between the mean changes in Groups A vs C reached statistical significance (p < 0.05) on four of the five indices: Symptoms, Illness Days, Performance, and Sociability-Satisfaction. Improvements on the Happiness-Unhappiness Index were not significantly different among the three groups. The relationship between amount of change and rate of practicing the relaxation response was different for the different indices. While less than three practice periods per week produced little change on any index, two daily sessions appeared to be more practice than was necessary for many individuals to achieve positive changes. Somatic symptoms and performance responded with less practice of the relaxation response than did behavioral symptoms and measures of well-being. (Am. J. Public Health 67:946-953,1977)


Daily relaxation response breaks in a working population: II. Effects on blood pressure. A 12-week randomized experiment investigated the effects of daily relaxation breaks on office workers with "normal" blood pressure. Blood pressures of 126 volunteers from the corporate offices of a manufacturing firm were measured biweekly. After four weeks of baseline monitoring,volunteers were divided randomly into three groups: Group A was taught a technique for producing the relaxation response; Group B was "taught" to sit quietly; and Group C was taught nothing. Groups A and B were asked to take two 15-minute relaxation breaks daily. During the baseline period, mean systolic blood pressures (SBP) were 119.7, 118.4, and 114.2 for Groups A, B and C respectively; mean diastolic pressures (DBP) were 78.7 and 75.7 Between the first and last measurements, mean changes in SBP were -11.6, -6.5, and +0.4 mm Hg in Groups A, B, and C; mean DBP decreased by 7.9, 3.1, and 0.3. Between the fourweek baseline period and last four weeks of the experimental period, mean SBP and DBP, mean changes in Group A were significantly greater than those in Group B (p < 0.05) and in Group C (p < 0.001). The same pattern of changes among the three groups was exhibited by both sexes, all ages, and at all initial levels of blood pressure. However, in general, within Group A, the higher the initial blood pressure, the greater the decrease. (Am. J. Public Health 67;954-959, 1977)


Immune response of guinea pigs to Schistosoma mansoni. II. In vitro blastogenesis and macrophage migration inhibition factor production in response to cercarial, adult worm and egg antigens. Guinea pigs infected with Schistosoma mansoni were tested for in vitro lymphocyte response to schistosome antigens and nonspecific mitogens at various times after infection. Production of macrophage migration inhibition factor by peritoneal exudate cells in response to cercarial, adult, and egg antigens reached a peak between 4 and 8 weeks post-infection and diminished rapidly thereafter. In contrast, peak blastogenic responses of blood lymphocytes appeared later than 8 weeks for all antigens and persisted until at least the 24th week. Blastogenic responses to concanavalin A and phytohemagglutinin P were not significantly different in normal and infected animals.


Mandibular reconstruction.

Mandibular reconstruction. The stainless steel 316 mesh tray with cancellous bone offers a method of mandibular reconstruction which theoretically is appealing from the viewpoint of basic osseous healing. The results in fity-two patients at twenty different institutions indicates encouraging results. Further evaluation of this method is recommended.


The use of cervical flaps from irradiated necks in immediate reconstruction. The use of cervical flaps for immediate reconstruction after operation in twenty-one patients in whom the neck received 4,000 to 6,000 r six weeks prior to operation is reported. Successful repair was achieved in a majority of these patients. We conclude that such flaps can be safely used imost instances, assuming they are designed to achieve maximum blood supply or are in an area that received minimal radiation exposure. We recommend this approach only when the radiation given is part of a course of previously planned, integrated therapy combining radiation and operation and when the major portion of the flap has not been exposed to more than 4,000 r.


[Influence of ventilatory pattern on the functional situation of the lung during inhalation anaesthesia. Part I: Spontaneous breathing versus IPPB (author's transl)]. After five hours breathing spontaneously enflurane, halothane and methoxyflurane only the rabbits under enflurane showed, apart from a mild respiratory acidosis, no deterioration of pulmonary functional situation. Halothane and methoxyflurane exhibited under the same conditions a significant worsening of elastic behaviour of the lung. The structural bases of the mechanical impairment were atelectasis, dystelectasis and interstitial edema. Postnarcotic examination of lung extracts in the wilhelmy balance showed no abnormalities in the spontaneously breathing animals. If one compares these findings, indicating an irritation of surfactant by halothane and methoxyflurane with the results after IPPB the conclusion can be made that under these circumstances IPPB represents an additional stress for the alveolar lining layer. From the theoretical point of view therefore it would be advisable in patients with surfactant deficiencies to avoid the combination of halothane or methoxyflurane with IPPB. The use of PEEP will be discussed in part II. The value of periodical sighs could not be established under our conditions. Longer periods of spontaneous breathing seem only advisable under halothane but not under enflurane or methoxyflurane because their respiratory depressant properties.


[The significance of the ventilation pattern for the functional situation of the lung in inhalation anaesthesia. Part II: PEEP (author's transl)]. The present study demonstrates the beneficial effects of PEEP on the functional behavior of rabbit lungs after five hours anaesthesia with halothane and methoxyflurane. Instead of a highly significant decline of lung compliance as was seen after spontaneous breathing and IPPB, PEEP led to a constant though statistically non-significant rise of this criterion. Blood gas values, too, demonstrated clearly the superiority of this ventilatory pattern. In contrast to former investigations there were no histological findings indicating any structural damage to the lung. Postanaesthetic examinations of lung extracts in the Wilhelmy balance showed no deterioration after PEEP. From these experimental findings it is concluded that patients suffering from surfactant deficiencies will benefit from a moderate PEEP during anaesthesia with halothane or methoxyflurane.


[The topography and cytoarchitectonic of the diencephalon of the cow (Bos taurus var. domesticus L.) I. The topography of the diencephalon of the cow. (Bos taurus var. domesticus L.) (author's transl)]. The study contains a comprehensive review of the literature on the brain of the cattle, followed by notes on form and location of the brain in the skull of the cow and of the diencephalon. In addition we point to some possibilities for locating the brain by stereotaxic manipulations. Several structural particularities are discussed, where to a limited extent references to structures of the brains of other domestic artiodactyla are made.


Granule release by polymorphonuclear leukocytes treated with the ionophore A23187. Polymorphonuclear leukocytes (PMN's) incubate three to eight minutes at 37 degrees C in medium containing 1 X 10(-6) M of the ionophore antibiotic A23187 released their cytoplasmic granules into the extracellular medium. Transmission electron microscopy of treated cells showed microfilament bundles extending between adjacent granules within the cytoplasm and between granules and the plasma membrane. Tiny dense projections (beads) 8-12 nm in diameter were observed along segments of the cytoplasmic surface of the plasma membrane with a periodicity of 20-30 nm. These beads were observed on the plasma membrane only in the vicinity of intra- or extracytoplasmic granules. The structural relationships of the beads with the plasma membrane microfilaments suggest they play a role in the process of ionophore-induced granule release from polymorphonuclear leukocytes.


Anomalous origin of a single coronary artery from the innominate artery. This is the third reported case of the origin of a single coronary artery arising from the innominate artery (brachiocephalic trunk). Associated cardiovascular malformations were truncus arteriosus and a single ventricle. The term infant died 12 hours after birth. Heart failure, evidenced by severe pulmonary and hepatic congestion found at necropsy, was probably the immediate cause of death. The origin of a single coronary artery from sites other than the aortic or pulmonary sinuses is extremely rare and is always associated with other severe cardiac malformations. Truncus arteriosus and cor bioculare or trioculare are the usual associated abnormalities.


Spontaneous positive end-expiratory pressure (sPEEP). Spontaneous positive end-expiratory pressure (sPEEP) is a simple, low-cost method of providing low to moderate levels of PEEP as an alternative to continuous positive airway pressure (CPAP), whether used alone or with continuous positive pressure ventilation (CPPV) in intermittent mandatory ventilation (IMV). The therapeutic effects of sPEEP therapy are demonstrated in 7 adult respiratory distress syndrome patients. All patients, initially hypoxemic on a high F1O2, had an acceptable PaO2 (with F1O2 less than or equal to 0.4) within 12 hours of initiation of sPEEP therapy. sPEEP, unlike CPAP and CPPV, does not maintain a continuous positive intrathoracic pressure during inspiration. Therefore, the patient probably does not receive as great a negative effect on venous return and cardiac output. By use of the sPEEP apparatus, the patient receives the therapeutic effect of PEEP.


Effects of testosterone undecanoate administration on LH and FSH response during the standard LH-RH test in healthy male volunteers. The effects of orally administered testosterone undecanoate (TU) on the pituitary responsiveness to the intravenous injection of 100 microgram of synthetic LH-RH were studied in 10 young healthy male subjects. They were given TU in a daily dose of 160 mg for 14 days. The LH-RH Test was performed before the medication, on day 14, and on the 7th day of the post-treatment phase. Pituitary responsiveness remained normal throughout the whole study. A somewhat lower response for LH was observed in the post-treatment phase, most probably attributable to the increased baseline plasma testosterone levels.


Anaphylactic injury--a process of programmed regulation. Anaphylactic injury is a process of tissue destruction mediated by vasoactive amines secreted by basophils and/or mast cells. A cellular model is proposed involving the immunoregulatory properties of basophils, eosinophils and lymphocytes. The interaction of these cells speaks for programmed control mechanisms, the impairment of which leads to expression of anaphylaxis.


A comparison of the bronchodilator effects of the same amounts of terbutaline aerosol given as a single or in divided doses. Inhalation of 0.5 mg of terbutaline, given as a single dose or as two immediately consecutive doses of 0.25 or four consecutive doses 0.125 mg, produced the same degree of effective bronchodilation in 12 asthmatic patients at all measured intervals from 30 seconds to four hours after administration. Each treatment regimen produced equivalent improvement in FVC, FEV1, MMEF, MVV, PEFR, V Max 50% VC and V Max 25% VC. The most sensitive indicators were MMEF and V Max 50% VC. No significant side effects were encountered with this dosage and route of administration. The clinical significance of this study is that in patients who are trained in the proper use of metered dose dispensers a single 0.5 mg inhalation may be sufficient to deliver the required dose to obtain an effective and safe therapeutic response.


Air pollution: its effects on health and respiratory disease--a review. A selective review of clinical and experimental data pertaining to air pollution and its effects on health and disease is presented. Various air pollutants, their effects on health and national air quality standard levels are outlined. The guidelines for asthmatic patients to follow during air pollution episodes are enumerated.


Effect of tetracycline upon transfer of an R plasmid from calves to human beings. Fecal specimens from human subjects in daily contact with calves shedding Escherichia coli containing an R plasmid were analyzed for the presence of E coli and the plasmid. A low level of crossover was found to occur unrelated to whether or not the calves were receiving tetracycline.


Immune responses of the bovine fetus and neonate to Escherichia coli: plaque-forming and intestinal immune responses. The immune responses of 26 Angus-Hereford fetuses and neonates to Escherichia coli O26:K60:NM were studied after bacterin or saline solution was injected (in utero) into the amniotic fluid. Calves were euthanatized at birth or were orally revaccinated; some were challenge exposed with live organisms. The hemolytic plaque assay was used to determine the presence of cells producing immunoglobulins M, G1, and G2 (IgM, IgG1, and IgG2) in 4 segments of the small intestine, mesenteric lymph nodes, and spleen. The passive hemagglutinin activity of intestinal washings was also determined. Anti-O26 passive hemagglutinin activity in the intestinal washings of principal calves was greater than in that of control calves, but in a given segment of the small intestine, usually this activity was relatively small and less consistent than the plaque-forming response. Greater numbers of plaque-forming cells were observed in the small intestine of 14 of the 15 principal calves when compared with the control calves tested.


Frequency of occurrence of viruses associated with respiratory tract disease of cattle in Oklahoma: serologic survey for bovine herpesvirus DN599. Serum samples from 351 Oklahoma cattle were tested for antibodies to DN599 virus by the indirect fluorescent antibody test. Seven cattle (approximately 2%) were seropositive for this virus.


Anthelmintic efficacy of albendazole in cattle: comparison of critical and controlled tests. Twelve calves were experimentally inoculated with 6 species of gastrointestinal nematodes and the liver fluke, Fasciola hepatica. Six calves were administered albendazole at 10 mg/kg of body weight, and the drug efficacy was determined by critical and controlled tests. Albendazole was only 74% effective against Haemonchus contortus (cambendazole-resistant strain), 99 to 100% effective against Ostertagia ostertagi, Trichostrongylus colubriformis, Cooperia oncophora, and Oesophagostomum radiatum, and 54% effective against the liver fluke. Except for H contortus, the critical test provided as accurate a measurement of drug activity against gastrointestinal nematodes as the controlled test provided.


Respiratory aspiration of stomach contents. The aspiration of stomach contents is a common clinical problem of concern to all physicians. Its consequences are varied, depending on the amount and distribution of the aspirate, its pH, and the presence or absence of food, particulate matter, and bacteria. Because multiple factors are involved, aspiration of stomach contents can lead to several distinct syndromes of pulmonary injury, all of which unfortunately have been labeled "aspiration pneumonitis." We review the pathophysiology of each of these syndromes and discuss important diagnostic and therapeutic consequences.


In-vitro cloning techniques for hemopoietic cells: clinical applications. Proliferating populations of neutrophils, monocytes, eosinophils, erythroid cells, and T-lymphocytes from normal subjects or patients with various diseases can now be analysed by colony formation in semisolid cultures. These cultures accurately determine the number and proliferative activity of the precursor cells of each population and can also be used to monitor the levels of specific regulatory factors (for example, erythropoietin, colony-stimulating factor) in the serum or urine of such patients. Studies using semisolid cultures have shown that the leukemic cells in chronic and acute myeloid leukemia remain dependent on the normal regulator, granulocyte-macrophage colony-stimulating factor, for proliferation. The cultures have proved valuable in the prognostic assessment of acute leukemic patients and in monitoring impending changes in the clinical status of patients with acute or chronic myeloid leukemia or myeloproliferative disorders.


[Neurological development of newborn infants with idiopatic respiratory distress sindrome treated with positive pressure (author's transl)]. Thirty three cases of idiopathic respiratory distress sindrome treated with constant positive airway pressure are reviewed. The eighteen survivors treated with a modified Gregory-box where followed up to a mean age of eighteen months. No signs of hydrocephalus were found in any of them. All had a normal neurological examination, head circunference, electroencephalogram and, maturative quotient.


[Taxonomic study of enterobacteria belonging or related to the genus Klebsiella (author's transl)]. This work studies the classification, by numerical procedure, of 122 strains belonging or related to the genus Klebsiella. Four classes can be defined: J (= K. pneumoniae: 29 strains for the most isolated from human faeces), K (related to K. pneumoniae and to K. oxytoca: 24 strains isolated from water), L (related to K. pneumoniae although, tetrathionate-reductase+, m-hydrobenzoate+: 37 strains isolated from water or soil), M (= K. oxytoca: 22 strains for the most isolated from water). The importance of the origins of the strains is emphasized.


[Bacterial cytostimulation by different effectors: purified antibacterial antibodies, concanavalin A and lipopolysaccharide (author's transl)]. The rate of growth of Gram- bacterial strains may be stimulated by various effectors: antibacterial antibodies, concanavalin A and specific lipopolysaccharide. Purification of the stimulating antibodies is brought about by saline dissociation of the bacteria-antibodies complex. Antibodies accountable for the cytostimulation would appear to be specific of the bacterial lipopolysaccharide.


[Plaque assay for Chlamydia psittaci in tissue samples (author's transl)]. Direct isolation of Chlamydia psittaci (var, ovis) from mouse spleen was performed in parallel by plaque assay on McCoy cells and by staining of cytoplasmic inclusions in HeLa 229 cells. There was a significant difference between the frequency of isolation: the plaque technique was highly sensitive and reproducible; it offers a potential tool for investigations requiring the accurate quantitation of Chlamydiae in tissue sample.


[Dwarf colony mutants of "Escherichia coli" study of a strain isolated from an uroculture (author's transl)]. A dwarf colony mutant of Escherichia coli was isolated from the urine of a patient with an asymptomatic urinary infection. This dwarf mutant growths poorly (minute transparent colonies) on Trypticase Soja and Mueller-Hinton agar, and requires thiamine concentration of 3 x 10-11 M.


Overcorrections of the Wies procedure.

Overcorrections of the Wies procedure. The Wies procedure may be complicated by an overcorrection, which is in effect a cicatricial ectropion. Four cases of such a complication are presented. The mechanism of an overcorrection is related to the level of the incision in the lid and to the suture placement. Correction of this complication primarily involves lysing cicatricial bands maintaining the overcorrection. Placement of sutures maintains the lid in a normal position.


[Automatization of bacteriological water analysis: description of a new method for measuring faecal pollution (author's transl)]. The main steps leading to a device for automatic bàcteriological analysis of water are described. The use of a new test for faecal contamination of water, the definition of a new culture method and the choice of a particular bactericidal solution are necessary for the realization of this apparatus. Processes of culture and detection of Escherichia coli are achieved within 13h. The present automatic device allows examination of 120 samples a day.


Corneal perforation in Wegener's granulomatosis treated with corneal transplantation: case report. A 46-year-old man with Wegener's granulomatosis developed corneal ulceration and descemetocele. He was treated with a penetrating keratoplasty which has remained clear for 22 months. With the increased life expectancy of this disease corneal rehabilitation is increasingly important and possible.


Removable purse-string suture of the bladder neck in transvesical prostatectomy. Insertion of the provisional Malament purse-string suture of the bladder neck proved an effective haemostatic method of treating serious haemorrhage following suprapubic prostatectomy. In a series of 15 patients, bladder-neck stenosis developed in one case, but in this patient the technique had been used incorrectly. In the other cases there were no serious complications. The method is suitable for bleeding which cannot otherwise be stopped during the operation.


The effect of long-term oral oestriol succinate therapy on the skin of castrated women. The effect of three years oestriol succinate therapy (2 mg/day) on the skin was studied in 20 castrated women whose average age was 48 years. A control group whose average age was also 48 years, consisted of 7 patients who did not receive any treatment after castration. There was no significant reduction in epidermal thickness during the three year course of oestriol succinate therapy. On the other hand the significant thinning of the epidermis in the control group was observed three years after oophorectomy. The difference between the 3H-thymidine labelling indices in oestrogen and control groups was not significant three years after castration.


Complications of percutaneous transtracheal procedures. The increasing use of transtracheal procedures by various specialties has caused a rash of new complications which have interested the endoscopist. These complications have resulted from the many diagnostic and therapeutic procedures involving the percutaneous puncture of the laryngeal or tracheal air space. The validity of these procedures is not questioned. However, they have spawned a host of diverse and bizarre complications which have led to serious and even fatal problems. The role of the endoscopist as a consultant in both the diagnosis and therapy of these developments must be understood and stressed.


Permanent tracheostomy: a new surgical technique. A new method of permanent tracheal fenestration is reported, utilizing cervical skin and tracheal flaps. It has been performed on four patients without complications and has the advantage of being a quick, simple, one-stage operation that is reversible should conditions change. The procedure is utilized in patients with posttraumatic or postirradiation fibrosis of the larynx, chronic obstructive pulmonary disease and patients with sleep apnea.


Bacterial phytotoxins.

Bacterial phytotoxins. Representatives of all of the major genera of plant disease-causing bacteria have been shown to produce one or more phytotoxins. Toxicological studies on the bacterial diseases of the major food crops have not been extensive. Bacterial phytotoxins belong to a number of classes of organic substances, including peptide, derivatized amino acid, polysaccharide, and glycopeptide. The mechanism of action of these compounds is largely unknown, as is their origin and importance in the disease syndrome. Nevertheless, some progress has been made in these areas in isolated cases. There is a tremendous potential in the future for studies on the bacterial phytotoxins.


[Action of polyene antibiotics on ribosome binding with Candida albicans membranes]. The effect of treatment of the protoplasts and cell membranes of C. albicans with polyenic entibiotics on formation of the ribosomal-membrane complex was studied in vitro. It was shown that amphotericin B and nystatin had no effect on this process. Significant suppression of the ribosome binding with the membranes was observed only in vivo in the presence of levorin. The role of the structural changes occurring in the membranes on formation of the polyen-sterol complex, as well as the role of the lipid components of the membrane in binding of the ribosomes is discussed.


[Spheroplast bacteriocin from strains of the causative agent of pseudotuberculosis and its identification by the antibacterial activity spectrum and the morphology of the inhibition zones]. Capacity for production of bactericin was found in the spheroplasts of the strains of the rodent pseudotuberculosis microbe. The author named it as pseudotuberculocin. The bacteriocin production was not detected in the initial strains of the pseudotuberculosis microbe. Pseudotuberculocin differed in the antibacterial spectrum and morphology of the growth inhibition zones formed on the plates with the indicator strains from the pesticins produced by the strains of the plaque microbe of the marmot and sandword varieties respectively and the cultures of the plaque microbe from the Transcaucasian Upland, as well as from pesticins of the spheroplasts of these strains. Production of a pesticin differing from pesticins of the rod-like forms of these strains by an ability to inhibit the growth of the homologous indicators was shown in the spheroplasts of the plaque microbe of the marmot and sandword varieties. Sensitivity of the plaque microbe strains of the marmot and sandword varieties to the pesticins of the plaque microbe strains and pseudotuberculocin was noted. With an account of the difference in the activity of the tested pesticins and pseudotuberculocin against the strains of the Frederic collection it is recommended to use this property for identifications of pesticins and pseudotuberculocin.


[Antitumor activity of fatty acid derivatives isolated from protozoa]. Water-soluble monoethers of sucrose and fatty acids were obtained from Trypanosoma lewisi and Astasia longa. The maximum tolerated dose of the preparations on their single intraperitoneal administration was more than 25 g/kg. The doses of 10--40 mg/kg were used repeatedly in therapy. Carcinoma 755, Lewis carcinoma, sarcoma 45, sarcoma 37 and sarcoma 180 were sensitive to the preparations. The preparations were inactive against experimental leukemia.


[Effect of carminomycin on the immunological reactivity of the body]. The morpho-functional state of the muscle lymphoid tissue of mice treated with karmionmycin (LD50, 1.1 mg/kg) was studied experimentally. Development of a number of changes evident of the cell disorganization in the lymphoid tissue was shown. The cytological shifts in the thymus and spleen were reversible, while the destructive period in the strumous gland was more prolonged. The morpho-structural normalization of the spleen did not coincide with reduction of its immunological function. The studies on the karminomycin effect on the kinetics of the primary immune response showed dependence of the antibiotic effect on the temporal ratio between the antigenic stimulus and the drug administration. The antibiotic had no effect on the inductive phase of the primary immune response but significantly suppressed its productive phase. On reproduction of the secondary immune response, a decrease in the content of the antibody-forming cells in the spleen was observed, production of the circulating antibodies remaining unchanged.


[Pharmacokinetics of cephalexin and cephradine in surgical patients]. Pharmacokinetics of 2 oral cephalosporin antibiotics, i.e. cephalexin and cephradin in surgical patients with normal function of the liver and kidneys was studied. Both the drugs were satisfactorily absorbed into the blood reaching the maximum level in 1 hour. The antibiotics were determined in close concentrations in the blood serum of the patients during 5 hours of the observation. No differences in the time of a two-fold decrease in the antibiotic serum level and the value of the area limited by the antibiotic blood level were found. Cephalexin and cephradin were excreted with the urine in equal amounts.


[Efficient use of gentamycin in treating suppurative puerperal mastitis]. A total of 80 patients with postnatal purulent mastitis were treated with gentamicins. The main causative agent was Staph. aureus resistant to the traditionally used antibiotic and sensitive to gentamicin, fusidin, rifampicin and semisynthetic penicillinase-stable penicillins. Gramnegative bacteria contaminated the purulent foci after opening. Gentamicin was highly effective in treatment of postnatal purulent mastitis in cases with mixed Staphylococcus-Proteus infection.


[Use of ampicillin trihydrate in transplantation surgery]. Ampicillin trihydrate was used for the treatment of 29 patients with purulent inflammatory processes, such as peritonitis, suppurating operative wound, urinary tract infection after the kidney allotransplantation. The antibacterial activity of ampicillin was preliminarily tested on 517 microbial strains, i.e. staphylococci, streptococci, E. coli, Proteus and Ps. aeruginosa isolated from the surgical patients. The strains of penicillin sensitive staphylococci, streptococci and E. coli were most sensitive to the drug effect, the MIC ranging from 0.03 to 16 gamma/ml. It was shown that the blood retention time of the antibiotic was much more prolonged in the patients with a decreased excretion function of the kidneys. The treatment was performed under control of the clinical, bacteriological and biochemical parameters. The drug was used in a dose of 0.5 g 6--8 times a day for 5 to 15 days. A satisfactory therapeutic effect was registered in 73 per cent of the cases.


[Various methods of using lincomycin for treating acute and chronic hematogenic osteomyelitis in children]. Comparative data on the treatment of 209 children with acute and chronic hematogenic osteomyelitis are presented; 128 patients hospitalized before 1974 were treated with antibiotics, mainly penicillin and streptomycin without sensitivity testing. From 1974 81 children were treated with lincomycin; 80 per cent of the isolates were sensitive to this antibiotic. In lincomycin therapy the method of electrophoresis on the disease focus, intrabone administration of the drug and administration of the drug into the bone cavity together with the blood clot during surgical interventions in cases with chronic hematogenic osteomyelitis were used. A marked decrease in the rate of the chronic forms of the disease was registered (from 77.2 to 8.8 per cent).


[Results of using an accelerated method of determining microbial flora sensitivity to antibacterial preparations in the surgical clinic]. Express diagnosis using 2,3,5-triphenyltetrasolium chloride as the redox indicator provided in most tests rapid and sufficiently precise determination of the microbial flora sensitivity to antibacterial drugs permitting to start in time the antibiotic therapy of the patients. For rapid response it proved to be useful to incubate beforehand the test material taken from surgical patients within 16 to 18 hours and to increase the indicator concentration up to 2--3 per cent.


[Use of carminomycin on adult patients with acute leukemias]. The data on the clinical trials of karminomycin, a new antitumor antibiotic are presented. The drug was used in the treatment of 46 adult patients with leukemia. Karminomycin was used in primary inducing therapy and treatment of relapses. The results of the trials showed that karminomycin had a definite therapeutic activity in treatment of acute myeloblast leukemia at various stages of the process. A rapid effect of the antibiotic provided its use in emergency cases with rapidly progressing variants of the disease.


[Rational use of antibiotics is the basis of their effectiveness and safety]. Many-year studies on the use of antibiotics in the general medical practice are summarized in the paper. The present trends in further improvement of the rational use of antibiotics are presented. It is shown that the present rational and safe antibiotic therapy is determined by 3 main factors: (1) choice of the drug with due regard for its pharmacological properties and spectrum, (2) isolation, identification and determination of the bacterial flora sensitivity to the antibiotic, (3) revealing or prevention of high sensitivity of the patients to the antibiotics chosen.


Detection of antimetabolite activity: effects and transport of tryptophan analogs in Escherichia coli. Simple and rapid techniques were developed that allow detection of the effects of a wide range of tryptophan analogs in Escherichia coli. (i) By using certain supersensitive mutant strains, analogs that were without effect on a wild-type strain were shown to be inhibitory. (ii) Many other analogs could inhibit the utilization of d-tryptophan when present as l-tryptophan replacements in a trp dadR strain. (iii) Another approach was to test the ability of a given analog to reverse the inhibition caused by an inhibitory analog. These combined approaches revealed activities in 26 analogs out of a total of 40 that were inactive by testing solely on a wild-type strain. The route of entry of inhibitory analogs was determined unambiguously by comparing their effect on aroP(+) (aromatic permease) and aroP strains. Uptake studies were also performed to determine whether various analogs compete for entry via the aromatic permease system. Many tryptophan analogs enter the cell via this system. The methods developed here should have general applicability to the testing of analogs of a variety of other metabolites.


Inhibition of Clostridium botulinum by 5-nitrothiazoles. A number of 5-nitrothiazoles with various substituents in the 2-position were tested for inhibition of Clostridium botulinum in a culture medium. Thiazole itself or 2-bromo- or 2-methylthiazole at 30 mug/ml did not inhibit the organism. An amino group in the 2-position of thiazole inhibited at 10 mug/ml. Substitution of a nitro group in the 5-position of 2-aminothiazole increased the inhibitory level to 0.12 mug/ml; acetyl-, propionyl-, or butyroyl-2-amino-5-nitrothiazole inhibited at 0.04 mug/ml. Benzoyl-2-amino-5-nitrothiazole inhibited at 0.16 mug/ml; this increased to 0.01 mug/ml when the benzoyl group carried a nitro group in the m- or p-position; a nitro group in the o-position, on the other hand, inhibited at 0.04 mug/ml. Unsaturated aliphatic acyls decreased inhibition. The greatest activity was exhibited by 2-nonanoyl- and 2-lauroylamides, with minimum inhibitory concentrations of 0.005 and 0.0025 mug/ml, respectively.


Function of the outer membrane of Escherichia coli as a permeability barrier to beta-lactam antibiotics. On the basis of a simple theoretical model, the ease of penetration of beta-lactam antibiotics through the outer membrane of Escherichia coli was measured. The cell envelope was found to act as a diffusion barrier to both penicillins and cephalosporins. The validity of the model and the cooperative action of cell-bound beta-lactamase and outer membrane were further verified by comparing calculated and experimentally determined velocities of beta-lactam hydrolysis by intact cells and sonically treated cell suspensions. The results showed good correspondence at five different antibiotic concentrations. Similar conclusions could be drawn from a comparison of beta-lactam concentrations on both sides of the outer membrane, calculated from enzyme kinetic measurements and minimal inhibitory concentrations for both a beta-lactamase-producing E. coli and its enzyme-negative variant. in the case of benzylpenicillin and cephalothin, however, no correspondence was found. The joint action of several parameters determining the efficacy of penicillins and cephalosporins against beta-lactamase-producing E. coli is discussed.


Plasmids carried by antibiotic-resistant marine bacteria. Antibiotic-resistant bacteria were isolated from seawater samples collected in the Atlantic Ocean off the southeastern coast of the United States. Large numbers of antibiotic-resistant bacterial strains were found to be present in harbor and inshore waters; however, the percentage of resistant strains was higher for several seawater samples collected offshore than for those collected near shore. Bacteria resistant to tetracycline, chloramphenicol, and streptomycin were found in nearly all samples collected, including samples from 200 miles (about 522 km) offshore and at depths to 8,200 m. Sediment samples, in general, were found to contain smaller populations of resistant strains as compared with the seawater samples examined. Antibiotic-resistant bacteria exhibiting phenetic characteristics common to autochthonous marine bacterial species were examined in detail, and several of the isolates exhibited unstable antibiotic resistance, which was transferable to recipient Escherichia coli cells. Deoxyribonucleic acid preparations from 10 strains examined by ethidium bromide-cesium chloride density sedimentation revealed that 6 of the strains contained covalently closed circular plasmid deoxyribonucleic acid.


Comparative study of trichothecin, amphotericin B, and 5-fluorocytosine against Cryptococcus neoformans in vitro and in vivo. Trichothecin (T-cin), amphotericin B (AB), and 5-fluorocytosine (FC) were compared singly and in combination for capacities to inhibit growth of Cryptococcus neoformans in culture and to protect mice bearing infections with this yeast. The minimum inhibitory concentrations for T-cin, AB, and FC were found to be 0.5, 0.2, and 5.0 mug/ml, respectively. In vitro viability studies demonstrated a marked reduction in colony counts with the AB-FC combination and additive effects with the AB-T-cin and FC-T-cin combinations for a 3-day period. In mice infected intravenously with C. neoformans, the mean effective dose for AB was 0.38 mg/kg, and for FC it was 100 mg/kg for a 30-day treatment period. No mean effective dose could be ascertained when T-cin was tested at doses of 0.1 to 50 mg/kg. Despite this, marked beneficial effects were noted in vivo with the AB-T-cin combination, whereas additive effects and indifference were observed for AB-FC and FC-T-cin combinations, respectively. High-dose T-cin controls survived despite having received a cumulative dosage of more than twice the reported (LD(50)) mean lethal dose value.


Binding of thienamycin and clavulanic acid to the penicillin-binding proteins of Escherichia coli K-12. Thienamycin and clavulanic acid are new beta-lactam derivatives with structures markedly different from those of penicillins or cephalosporins. Both derivatives had the same general mode of action as typical beta-lactam antibiotics since they bound to precisely the same proteins as [(14)C]benzylpenicillin. Thienamycin showed high affinity for penicillin-binding proteins 1, 2, 4, 5, and 6 and a lower affinity for protein 3. Protein 2 had the highest affinity for thienamycin, and concentrations from the minimal morphological change concentration (0.1 mug/ml) up to about 0.6 mug/ml resulted in the conversion of Escherichia coli KN126 into large osmotically stable round cells. Above a concentration of 0.6 mug/ml, rapid cell lysis occurred with the release of the cell contents as spheroplasts. Clavulanic acid showed good affinity for penicillin-binding protein 2, moderate affinity for proteins 1, 4, 5, and 6, and low affinity for protein 3. Protein 2 had the highest affinity for clavulanic acid, and concentrations from the minimal morphological change concentration (30 mug/ml) up to about 50 mug/ml produced a mixture of slightly elongated, swollen, bulging, and lemon-shaped cells. Above a concentration of 50 mug/ml, rapid lysis occurred with production of spheroplasts. The properties of thienamycin and clavulanic acid were compared with those of the penicillins, cephalosporins, and amidinopenicillanic acids.


Nonconjugative plasmids encoding sulfanilamide resistance. Nonconjugative plasmids encoding sulfanilamide (Sa) resistance were demonstrated at a high frequency in Shigella and Escherichia coli strains resistant to sulfanilamide. These Sa plasmids were all compatible with the standard plasmids used in compatibility testing. The sizes of seven Sa plasmids were measured by electron microscopy and ranged from 1.79 to 2.08 mum, corresponding to 3.5 to 3.9 megadaltons.


Drug resistance in Streptococcus pyogenes isolated in Japan. Drug resistance of Streptococcus pyogenes strains isolated during 1974 and 1975 in various districts in Japan were surveyed and compared with an earlier survey of 1970 to 1973. Of 1,021 strains, tetracycline-, macrolide antibiotic-, lincomycin-, and chloramphenicol-resistant strains were demonstrated at frequencies of 80.3, 62.3, 60.8, and 57.9%, respectively. Distinct group resistances to penicillin and aminoglycoside antibiotics could not be identified among the strains examined. It was characteristic that quadruple and triple resistances were manifested among the strains resistant to macrolide antibiotics, lincomycin, tetracycline, and chloramphenicol, and they were confined to the T-type 12. The emergence of multiply resistant streptococcal strains was due mostly to the rapid increase in isolation frequency of macrolide antibiotic- or macrolide antibiotics-lincomycin-resistant strains.


R plasmids of the S incompatibility group belong to the H2 incompatibility group. Plasmids of the S and H2 incompatibility groups showed thermosensitive transfer and a bacteriophage inhibition phenotype and were incompatible with one another.


Norleucine accumulation by a norleucine-resistant mutant of Serratia marcescens. A norleucine-resistant mutant was derived from an isoleucine-valine auxotroph of a leucine accumulator of Serratia marcescens. The norleucine-resistant mutant could accumulate norleucine from norvaline in the medium without the addition of methionine, which antagonized norleucine. This mutant constitutively formed homoserine-O-transsuccinylase.


Alternative replica plating technique.

Alternative replica plating technique. A new technique for picking bacterial colonies and a new type of replicator are described.


Microscopic counting and adenosine 5'-triphosphate measurement in determining microbial growth in soils. A microscopic technique utilizing dispersion of fungal hyphae in a Waring blender, filtration through membrane filters (Nucleopore Corp.), and counting on a fluorescence microscope was developed for counting fungal hyphal biomass. Nonfluorescent staining techniques of the soil-filter preparation did not give quantitative recoveries. Water-soluble aniline blue, which binds to the beta-1,3-glucans of the fungal cell wall, made visualization of the hyphae by fluorescence possible. A range of fungi added to soil were quantitatively recovered. Adenosine 5'-triphosphate (ATP) was extracted from soil by lysis of the organisms with CHCl(3) in NaHCO(3), which prevented adsorption of the organic phosphorus to the soil colloids. Centrifugation and removal of CHCl(3) was followed by dilution with pH 7.8 tris(hydroxymethyl)aminomethane buffer. ATP concentrations were measured by using the luciferase-luciferin light reaction. Since NaHCO(3) interfered to some extent with this reaction, the standards were made up in equivalent mixtures of tris(hydroxymethyl)aminomethane buffer and NaHCO(3). Recovery of ATP was rapid and quantitative in a range of soils. Measurement of the ATP and bacterial and fungal numbers in an incubated soil showed that fungal and bacterial population increases were delayed by phosphorus deficiency. Microbial populations were not affected at a later date. The ATP content of the soil system was reduced by phosphorus deficiency throughout the incubation period. This indicated that ATP could be altered without major changes in the microbial populations.


Increased recovery of salmonellae from environmental samples enriched with buffered peptone water. The incidence and persistence of salmonellae in weather pools on the top of Stone Mountain were investigated with lactose and buffered peptone water used as pre-enrichment broths. A total of 162 samples were collected from 16 weather pools over a 3-month period. The use of buffered peptone water increased the recovery of salmonellae by approximately 25%. The combined use of direct enrichment in tetrathionate broth containing brilliant green dye and pre-enrichment in buffered peptone water followed by enrichment in tetrathionate broth made it possible to detect all 37 of the contaminated samples. All of the isolates were Salmonella bareilly, the only serotype recovered in a previous study. All but one of the isolations were made from moist or wet samples. S. bareilly was isolated from rabbit dung and litter collected near the weather pools, but attempts to trap rabbits for study were unsuccessful. Random samples taken along a side of the mountain yielded S. bareilly in weather pools within the upper third of the mountain; below this level, S. weslaco and S. memphis were recovered, but not S. bareilly.


Simplified 48-hour IMVic test: an agar plate method. An agar plate method was developed for the performance of the IMVic (indole, methyl red, Voges-Proskauer, and citrate) tests in lieu of the conventional tubed liquid media. By modifying the composition of the media and adding agar, a single "X"-compartmented petri dish was prepared containing all four IMVic test media. Ease of performance and simplification of the test were achieved by inoculating all four media simultaneously from a single colony (single inoculum) on eosin-methylene blue agar. Tests with 87 cultures, representing 7 genera in the family Enterobacteriaceae, were completed with typical (correct) IMVic patterns for all cultures within 48 h. Parallel tests with conventional media showed that the agar plate method was superior, more sensitive, faster, and simpler to perform, and less time was required to identify Escherichia coli by 72 h.


Evidence for incorporation of thymidine into deoxyribonucleic acid in airborne bacterial cells. As part of an effort to discover whether bacteria might propagate within airborne particles, we studied the incorporation of thymidine into the trichloroacetic acid-insoluble fraction of airborne cells of Serratia marcescens to seek evidence of the possible formation of new DNA. Two aerosols, one of S. marcescens and another of [3H]thymidine ([3H]dT) suspended in growth medium were caused to aggregate in air just prior to directing the aerosols into rotating-drum aerosol storage chambers. The age of the S. marcescens culture and other conditions for maximizing ([3H]dT) uptake were selected on the basis of prior in vitro trials. With 10-h cultures and addition of 2-deoxyadenosine to the [3H]dT, we showed that [3H]dT is incorporated into the trichloroacetic acid-insoluble fraction of cells recovered 6 h after aerosols were stored under the conditions of high humidity and 30 degrees C. Tests conducted in the same manner with Formalin-killed S. marcescens ruled out the possibility of adsorptive carry-over of [3H]dT. As much as 20 times more activity was found in the trichloroacetic acid-insoluble fraction of live cells than of dead cells.


Isolation and purification of a granulosis virus from infected larvae of the Indian meal moth, Plodia interpunctella. A procedure was developed for purification of a granulosis virus inclusion body produced in vivo in the Indian meal moth, Plodia interpunctella (Hübner). Purification was accomplished by differential centrifugation, treatment with sodium deoxycholate, and velocity sedimentation in sucrose gradients. The adequacy of the procedure was confirmed by mixing experiments in which uninfected, radioactively labeled larvae were mixed with infected, unlabeled larvae. After purification, the virus was shown to be free of host tissue, to retain its physical integrity, and to be highly infectious per os. Preparations of purified virus consisted of homogeneous populations of intact inclusion bodies (210 by 380 nm) whose buoyant density was 1.271 g/cm3 when centrifuged to equilibrium in sucrose gradients. Electron microscopy of thin-sectioned virus or of virus sequentially disrupted on electron microscope grids demonstrated three components: protein matrix, envelope, and nucleocapsid.


Synchronization of Escherichia coli by zonal centrifugation. A zonal centrifugation technique that can select the smallest newborn cells in an exponentially growing culture of Escherichia coli B/r is described.


Primary acquired cold urticaria. Double-blind comparative study of treatment with cyproheptadine, chlorpheniramine, and placebo. Eight subjects with primary-acquired cold urticaria were treated with chlorpheniramine maleate, cyproheptadine hydrochloride, and placebo in a double-blind clinical trial. During three separate seven-day treatment periods, each patient took 4 mg of either active drug or lactose placebo three times a day. Objective measurements were made at the beginning and end of each treatment period by establishing the minimum time (MT) of cold stimulus application required to provoke urtication. In addition, the spontaneous appearance of cold urticaria lesions was recorded during each treatment period. The MT required for induction of urtication with a cold stimulus was significantly greater for eight patients receiving cyproheptadine as compared to chlorpheniramine or placebo (P less than .01). The study demonstrated that cyproheptadine had a significant suppressive action on experimental cold-induced urticaria, while placebo and chlorpheniramine proved ineffective.


Systemic antibiotic therapy of secondary infected dermatitis. Systemic cloxacillin therapy of secondarily infected dermatitis cloxacillin therapy become apparent  produces a significant increase in healing when compared to a placebo. The effects of systemic after five days of treatment. A single pretreatment culture was not helpful in directing therapy.


Cicatricial pemphigoid of Brunsting-Perry. Immunofluorescent studies. Six patients with a vesiculobullous eruption of the type described by Brunsting and Perry as benign pemphigoid were studied by direct and indirect immunofluorescence. All six showed linear deposits of IgG but not IgM or IgA at the epidermal-dermal junction. One case also showed C3 deposition and one patient had circulating antibasement membrane zone antibodies in a titer of 1280. These data provide strong evidence that this condition belongs to the cicatricial pemphigoid-bullous pemphigoid spectrum of disease.


New world leishmaniasis. Serologic aids to diagnosis. The increase in travel to endemic areas of South and Central America has led to an increase in the number of cases of cutaneous leishmaniasis diagnosed in the United States. Traditional methods of diagnosis for this disease include microscopical examination of infected tissue, culture of Leishmania on special media, and the leishmanin skin test. The present communication describes a case of cutaneous leishmaniasis and the difficulties that were encountered in diagnosis. New methods of serologic testing allow more prompt and accurate diagnosis.


[Porphyrinsynthesis by propionibacterium acnes (author's transl)]. Strains of P.a. were isolated from seborrheic filaments from 11 persons and investigated according to their production of porphyrins. After growing the organisms during a 5 resp. 10 days cultivation period on solid as well as in liquid culture medium the quantity and quality of the bacterial porphyrins were determined. There existed intense variations in quantity not only when the special strains were compared with each other but also when the same strains were treated with different preparations. The porphyrin-spectrum, as demonstrated by thin-layer-chromatography, showed porphyrins with 2--8 carboxyclic groups, the coproporphyrin standing out in most cases as the most intense band.


Electron microscopic studies in dermatitis herpetiformis in relation to the pattern of immune deposits in the skin. Electron microscopic studies were made in 12 cases of dermatitis herpetiformis: 6 of them with a continuous immunofluorescence line of IgA deposits at the dermo-epidermal junction, and the other 6 with granular IgA deposits in the dermal papillae. Six cases of bullous pemphigoid with a continuous immunofluorescence line of IgG deposits at the dermo-epidermal junction were examined similarly for comparison. In dermatitis herpetiformis with the continuous IgA line the ultrastructural characteristics both of dermatitis herpetiformis and bullous pemphigoid were present, even when the histological and clinical features as well as response to sulphapyridine and sulphones were typical of dermatitis herpetiformis. The ultrastructural pattern was essentially the same as in the cases with clinical and histological characteristics of the mixed dermatitis herpetiformis-bullous pemphigoid form, although in the latter there was some predominance of the characteristics of bullous pemphigoid.


A simple technique for immunoelectronmicroscopic localization of Ig on tissue sections with special reference to cutaneous pathology. A simple technique using immunoperoxidase-labelled antibodies is reported for the ultrastructural localization of fixed immunoglobulins in tissue lesions. This technique allows the immunolabeling of frozen sections of 15 mu mounted on glass slides. These sections are then closed over for ultrastructural examination, using an Epon-filled gelatin capsule, and then returned to the glass slide. After polymerization, the capsule containing the tissue section is separated from the glass by immersion in liquid nitrogen. This technique is applied to the study of fixed Ig in the skin lesions of lupus erythematosus, pemphigus, bullous pemphigoid and dermatitis herpetiformis. The results obtained show a fine localization of fixed Ig, good tissue conservation and easy orientation of the biological material. It can be applied to the study of tissue antigens.


The impact of 1,000 renal transplants at one center. A large, comprehensive renal transplant program has a major impact not only on patient care, but also on the medical center itself and the larger community. The program at this center has advanced from 15 transplants in 1964 to 141 transplants in 1976. Fifty-nine per cent of patients transplanted have functioning kidneys at this time, including 76 children. Rehabilitation was equal to prerenal disease level in 91% of 169 recipients who lived five years with a functioning graft. Basic research in such diverse areas as renal preservation and immunology, as well as clinical research in optimum immunosuppressive therapy, resulted in significant contributions. Refinement of the mixed lymphocyte culture improved living-related graft survival at two years: 100% for HLA-identical and 91% for non-HLA-identical grafts, compared to 66% reported by the Transplant Registry for the combined group. Modification of immunosuppression improved patient survival at two years: 100% and 86% for recipients of living-related and cadaver grafts, respectively, compared to 83% and 65% reported by the Transplant Registry. The complexity of care of the patient with end-stage renal failure has required active interaction between transplant surgeons and almost every major specialty. The vast clinical material has been a great asset for training transplant surgeons, nephrologists, fellows and residents of multiple specialties, and medical students. The medical center's relationship with communities within a 250 mile radius has been strengthened, as reflected in patient referrals and the development of a multi-community-supported organ procurement system, which has allowed us to perform over 100 cadaver transplants per year for the past three years. Thus the performance of 1,000 renal transplants at this center has resulted not only in rehabilitation of many renal failure patients, but also in expanded and improved research and teaching capabilities, bringing support from multiple medical disciplines and the general community.


[Pharmacodynamics of alcoholic and aqueous extracts from the Casimiroa edulis seed]. The hypnotic properties of leaves and seed of Casimiroa edulis (zapote blanco) a tropical fruit, are well known. In the present investigation, pharmacological studies on aqueous and alcoholic extracts were carried out in dogs, cats, rabbits and guinea pigs, using different experimental models. The action of the extracts upon blood pressure, cardiac activity, respiration rate, muscular tone, electroencephalographic activity, sleep and other parameters were studied too. In addition to, studies upon isolated human, cat, rabbit and guinea pig tissues gave information about the extracts effect on smooth muscle activity. It was found that both aqueous and alcoholic extract of the seed of zapote blanco produced marked hypotension in all animal species, which was followed by a sleep-like stage. Also a definitive oxitocic effect in vivo and in vitro was demonstrated suggesting the presence of a potent uterus constricting substance.


The formation of glycosidic bonds in yeast glycoproteins. Intracellular localisation of the reactions. Membranes of Saccharomyces cerevisiae were separated on urografin gradients. The specific activity of the light membranes (endoplasmic reticulum), the Golgi-like vesicles and the plasma membrane in transferring mannosyl residues from GDP-mannose to mannoproteins and to dolichyl monophosphate has been determined. The first mannose of the O-glycosidically linked manno-oligosaccharides is incorporated with the highest specific activity by the endoplasmic reticulum. The incorporation of the second to fourth mannosyl groups is catalysed with increasing activity also by the Golgi-like vesicles  and the plasma membrane. The incorporation of mannosyl groups into weak alkali-stable positions (N-glycosidically linked chains) is carried out with almost the same specific activity by all three membrane fractions, however, dolichol-dependent and -independent steps could not be distinguished as yet. The results are discussed in terms of a sequential addition of sugar residues along the route of export of the mannoprotiens. The dolichol-dependent steps seem to occur on the endoplasmic reticulum and thus very early in the event.


Mode of increase in cell wall polysaccharides in synchronously growing Sachharomyces cerevisiae. The mode of increase in cell wall polysaccharides of yeast (glucan and mannan) during cell cycle was analyzed using cell wall samples obtained from a synchronous culture. The increase in mannan and total glucan proceeded almost linearly throughout the cell cycle except for a short period of their leveling off at the time of cell division. However, the constituents of glucan behaved characteristically: Alkalisoluble glucan and insoluble glucan increased mainly in the former and the later half of the cell cycle, respectively.


Environmentally-induced changes in the neutral lipids and intracellular vesicles of Saccharomyces cerevisiae and Kluyveromyces fragilis. Saccharomyces cerevisiae, grown aerobically or anaerobically under conditions which induce a requirement for a sterol and an unsaturated fatty acid, synthesized approximately the same amounts of neutral lipid and intracellular low-density vesicles, although the neutral lipids in aerobically-grown cells contained more esterified sterol and less triacylglycerol than those in anaerobically-grown cells. Kluyveromyces fragilis synthesized much less neutral lipid and a smaller quantity of low-density vesicles than S. cerevisiae whether grown at 30 degrees C (generation time 1.1 h) or 20 degrees C (generation time 2.1 h). Both yeasts synthesized highly saturated triacylglycerols, relatively unsaturated phospholipids, and esterified sterols with an intermediate degree of unsaturation irrespective of the conditions under which they were grown. Free sterols in the yeasts were rich in ergosterol and 22(24)-dehydroergosterol, while the esterified sterol fractions were richer in zymosterol.


Temperature-sensitive loss of sexual agglutinability in Saccharomyces cerevisiae. Temperature dependency of sexual agglutination in Saccharomyces cerevisiae was found. Of 31 strains tested, which showed normal agglutination when cultured at 25 degrees C, 29 strains lost their sexual agglutinability when they were grown at 37 degrees C.


Choosing an approach for diagnosing schizophrenia. In recent years, many competing concepts of schizophrenia have been described, each with some evidence to support its value. Even more recently, specific evaluation methods and diagnostic criteria have been developed so that each of these concepts can be reliably diagnosed. Because of these advances, it is important for the clinician and investigator working with schizophrenics to recognize the way in which the various concepts are reflected in the several reliable approaches now available for diagnosis and to be able to choose a method of diagnosis that is most likely to be useful. We describe the competing conceptualizations and the related diagnostic approaches that have been developed, and then outline the differences and similarities and advantages and disadvantages of these approaches. An orientation toward using these approaches for diagnosing schizophrenia is suggested that permits employing several approaches simultaneously to provide the greatest chance for determining important relationships among diagnostic, clinical, and research variables.


[Isolation and characterization of pregnancy-specific beta1-Glycoprotein from urine of pregnant women (author's transl)]. With use of the immunoadsorption technique the protein antigenically related to pregnancy-specific beta1-glycoprotein (SP1), was isolated from urine of pregnant women. The physical and chemical properties of this protein were determined and compared with those of SP1. The antigen isolated from urine has a smaller molecular weight and is immunochemically only partly identical with SP1 found in pregnancy serum respectively in the placenta. The protein occuring in urine seems to be a split product of SP1 and is supposedly formed by an enzymatic degradation of the native proteins. The concentration of the protein in urine of pregnant women throughout gravidity was quantitated immunochemically using a modified Laurell-technique. During the first and second trimester of pregnancy values ranged from 0,0-0,4 mg/100 ml. In the last trimester there was an increased in the concentration of urine-SP1 with values ranging from 0,0-3,0 mg/100 ml and a mean concentration of about 1 mg/100 ml.


[Cytology of pleura exudate in lymphoretic sarcoma (author's transl)]. In 2.9% of 1762 patients with pleura exudate, the underlying disease was a lymphoreticular sarcoma. The experienced cytologist has no difficulties to differentiate typical patterns of plasmocytoma, reticulumcell sarcoma or lymphogranulomatosis. But there may be borderline forms which can only be evaluated by critical examination. This holds true especially for differentiated types of lymphosarcoma which resemble the pattern of lymphocytic leukemia or observed through low magnification look like lymphocytic exudate. Therefore the use of oil immersion is necessary for evaluation of the smear. Fluorescence microscopy offers some advantages in special problems.


[Air pollution and cancer (author's transl)]. Several data justify the suspension that air pollution may contribute to cancer risk. These observations are: high risk of lung cancer in coal gas workers; higher incidence of lung cancer in urbanized regions as compared with rural ones and higher incidence in highly industrialized countries as compared with less industrialized; observations in migrant populations; data of comparative pathology. Specific studies of the association between lung cancer and air pollution taking into consideration confounding variables failed to give conclusive evidence of a causal relationship. Obviously the role of air pollution for cancerogenesis in the lung is far less important than inhalation of tobacco smoke. Furthermore there are some findings suggesting a causal association of particulate air pollution and malignant neoplasms of the stomach and prostate.


Carcinoembryonic antigen: immunohistologic identification in invasive and intraepithelial carcinomas of the lung. A total of 58 pulmonary lesions from 48 patients were examined for carcinoembryonic antigen (CEA). The three-layer immunoperoxidase procedure for antigen detection was used with a monospecific anti-CEA antiserum. The control serum was the same antiserum with its specificity removed by affinity chromatography. Normal goat serum was also used as a control. Carcinoembryonic antigen was present in the majority of pulmonary adenocarcinomas and generally absent in the squamous cancers. The major exception was in the well-differentiated squamous lesions where CEA was occasionally found in the keratinizing areas. Of special interest was the finding of CEA in all areas of intraepithelial squamous neoplasia studied.


Exfoliative immunocytology of cervical carcinoma. Fluorescent antibody tracing was applied to exfoliative specimens from 456 women, who were also screened by cytology and partly by histopathology for carcinoma of the cervix. Fixed cervicovaginal smears were treated with autologous serum; the smears then were added labeled antihuman globulin antibody and observed for reactivity. A pattern of cytoplasmic fluorescence was observed in cases that were cytologically diagnosed as severe dysplasia, carcinoma in situ of the cervix, or in cases with positive reactions for malignant cells. Negative Papanicolaou smears appeared nonreactive. A probe into the immunoglobulin class of the antibody that reacted with dyskaryotic and abnormal cells revealed that IgA and IgG but not IgM were involved. The results indicate that a humoral immune response occurs and may be used diagnostically for a demonstration of cellular abnormality in premalignant and invasive cases of cervical carcinoma.


Reflex sweating in patients with spinal cord injury: a review. Sweat glands derive their innervation from the sympathetic nervous system. The spinal sympathetic structures that are located in the intermediolateral areas extend from T1-L2 segments and are under the control of hypothalamic centers. Cord transection abolishes the supraspinal control of sudorimotor function. Since sympathetic innervation does not follow a clear segmental distribution, normal sweating may be preserved at a higher or lower level than skin sensation. Nonthermoregulatory reflex sweating is an indication of unchecked spinal cord facilitation and is precipitated by afferent stimuli from bladder, rectum, and various other sources. It is usually a manifestation of mass reflex or autonomic crisis and occurs particularly in cervical or high thoracic lesions. Transection below T8-T10 is not accompanied by reflex sweating. The phenomenon of thermal relfex sweating is controversial. Although some aspects of nonthermoregulatory reflex sweating are still unclear, proper immediate and continuing preventive management will reduce the incidence of this and other autonomic manifestations. Chemical sympathectomy should be a last resort in case of emergency or when the source of facilitation cannot be ascertained.


A trial of cephalothin sodium in colon surgery to prevent wound infection. A double-blind trial of preoperative and perioperative cephalothin sodium in patients undergoing colonic surgery was carried out to test the value of this drug in reducing wound infection rates. Two studies were performed. In the first trial, 1 gm of cephalothin sodium or a placebo was given intravenously at the beginning of operation, and 1 gm one hour later. In the second trial, the dose of cephalothin or placebo was increased to 2 gm. There was no significant reduction in wound infections in either study in the groups receiving cephalothin, although over two thirds of the organisms cultured from the infected wounds were sensitive to cephalothin. It is suggested that meticulous attention to technique to avoid gross contamination remains the most important factor in the prevention of wound infections after colon surgery.


Principles of abdominal wound closure. I. Animal studies. An experimental study in rats was designed to measure the effect of tissue bite size and tightness of tying on the wound's ability to resist dehiscence from increased intra-abdominal pressure. Abdominal incisions in rats were closed in one of four ways: large tissue bites, tied tightly or loosely, or small tissue bites, tied tightly or loosely. The strongest closure was with large tissue bites and loose ties. The weakest closure was with small bites and tight ties. It appeared that tying sutures loosely was a little more important than taking large bites, although the difference was not significant. Each of these factors was a contributing element.


Principles of abdominal wound closure. II. Prevention of wound dehiscence. Among 4,000 abdominal wound closures, there were 11 dehiscences. In eight, the original wound was closed with retention or large figure-of-8 sutures. When the wounds were resutured, the same basic technique of large tissue bites at close intervals was used, but this time the wounds remained intact. Therefore, it was concluded that the cause of the dehiscence was not poor tissues, but poor technique: the first sutures either had too small bites, were placed too far apart, or were tied too tightly. We describe a closure technique using buried figure-of-eight retention sutures tied very loosely. An additional running suture approximates the fascial edges. This method was used in 126 patients, with but one failure, caused by improper knot tying. In a separate clinical study, no difference in wound tension was found between vertical and transverse incisions.


Pulmonary aspiration: an update.

Pulmonary aspiration: an update. Pulmonary aspiration of foreign material occurs in many situations. The morbidity of pulmonary aspiration is astounding. even more staggering is the mortality of massive aspiration of gastric contents. Bewilderment exists among most physicians concerning the treatment of this lethal event. The use of corticosteroids in pulmonary aspiration has received much attention and no data exist to advocate their continued employment. Knowledge of the bacteriology of aspiration has resulted in more judicious use of antimicrobial agents. The most significant advance in the treatment of pulmonary aspiration has been the development of positive end-expiratory pressure as an adjunct to mechanical ventilation. Pulmonary aspiration in hospitalized patients is an entirely preventable disease. All physicians must be made aware of the multitude of instances in which aspiration may occur if any hope of averting this disaster exists.


Serratia marcescens pneumonia.

Serratia marcescens pneumonia. Though rare, Serratia marcescens pneumonia is being reported with increasing frequency, especially in patients in intensive care units. We report three cases of S. marcescens pneumonia that presented striking similarities for age, group, type of surgical procedure, and microbiological, hemodynamic, and respiratory patterns. All patients survived after prolonged ventilatory support.


Isolated histiocytic lymphoma of the spleen causing fever and hypercalcemia. Differentiating between primary and ectopic or pseudohyperparathyroidism may be difficllt, but certain aspects of the patient's clinical history as well as laboratory tests may be helpful. We present an unusual case report of a patient who had massive splenomegaly secondary to a localized histiocytic lymphoma. On the basis of a lower serum parathormone level for a given serum calcium increase combined with normal serum phosphorous and chloride values, the diagnosis of psuedohyperparathyroidism was made and was confirmed when the patient's serum calcium level and temperature returned to normal following splenectomy.


Wound infection and topical antibiotics: the surgeon's dilemma. The topical use of antibiotics in surgical wounds is critically reviewed and analyzed. Thirteen experimental and 19 clinical reports are included in this review. Prospective and retrospective clinical studies have been separated. The analysis evaluated clean vs contaminated/dirty wounds, as well as the effects of various antibiotics and combinations. The conclusion reached on the basis of the experimental and clinical data is that the application of carefully selected topical antibiotics to surgical wounds, particularly those that represent a high risk for the development of wound infection, can be expected to diminish the incidence of this complication in a significant fashion.


Mutagenicity studies with praziquantel, a new anthelmintic drug: tissue-, host-, and urine-mediated mutagenicity assays. Praziquantel, a new anthelmintic drug with activity against all species of schistosomes pathogenic to man, and against a wide range of Cestodes, was tested for mutagenic potential. For the detection of both base substitutions and frameshift mutations, Salmonella typhimurium TA 100 and TA 98 were used as tester strains. Using the plate assay with and without added S-9, host-mediated assay and urine-mediated assay without and after incubation with beta-glucuronidase/arylsulfatase, no mutagenic activity could be detected.


[Elaboration of methodology for simultaneous morphological and physiological study of an isolated autonomic neuron and its interneuronal synapse]. Methodical difficulties encountered at simultaneous physiologic and morphologic investigation of an isolated vegetative neuron with a preserved synaptic apparatus and studied under large magnification are discussed in the article. To carry out such investigations, the author suggests two models of morpho-physiological devices and a preparation of the frog isolated vegetative neuron with a preserved synaptic apparatus, which help to solve the following problems: an increase of working distance for the microelectrode; fixation of the object studied; application of physical contrasting techniques.


[Participation of splenic vessels in blood supply to the pancreas (experimental-mathematical study)]. In 60 objects the participation of splenic vessels in human pancreas blood supply was studied roentgeno-angiographically and by means of anatomical preparation. Morphometrical data obtained were treated by computers "Minsk-22" and "M-220-M" to calculate main statistic values and their correlations. Some recommendations of applied importance for pancreas surgery were suggested. Maximal and minimal dimensions of the pancreas segments, which can be used for grafting with the following blood supply restoration in the transplant at the expense of the splenic vessels only, were represented.


[Quantitative characteristics of the immunocompetent cells of the large-intestinal mucosa in acute dysentery]. Histological and immuno-morphological examinations of the large intestine mucosa obtained by aspirational biopsy from 38 adult patients with acute dysentery in the mild, moderately severe and severe forms and from 4 normal subjects were carried out. In each case, a per cent ratio of immunocompetent cells in deep and superficial parts of the mucous membrane proper, the content of interepithelial lymphocytes, the cell density of infiltrate per 1 mm2 of the mucous membrane, the number of cells producing IgA, IgM, and IgG per 1 mm2 of the mucous membrane were determined. As the severity of clinical and morphological manifestations of dysentery increased, the number of cells actively producing immunoglobulins was found to increase and epithelium infiltration with lymphocyte to be enhanced. The main role in the development of local immune response in dysentery is played by IgA-producing cells, and in the moderately severe and severe forms of dysentery the number of IgM-producing cells increases.


[Primary immunologic deficiency syndromes in man]. Current concepts on the immune system, the genesis of human T- and B-lymphocytes, and their functional properties are presented as well as current data on the pathogenesis and classification of hereditary defects of the human immune system. The main forms of immunity deficiency conditions are described. The methods for diagnosis and treatment of different forms of immunologic deficiency are substantiated. The relationship between immunity deficiency conditions and malignancies, allergic and autoimmune processes, and morphological changes in various organs and tissues is described.


[Case of pseudotuberculosis with lesions of the mesenteric lymph nodes]. The author reports for the first time on a case of pseudotuberculosis in a boy aged 9 years in the Karelian ASSR. The disease was diagnosed in the course of a histological investigation of the bioptic specimen of the mesenteric lymphatic node obtained during the operation performed in connection with suspected appendicitis. Histologically there were revealed granulomas with microabscesses therein and around them--very small foci of necrosis and necrobiosis with a positive reaction to fibrin. Granulomas, in contrast to those described in the literature, consisted predominantly of epithelioid, but not of reticular, cells. Their nuclei were poor in DNA, whereas cytoplasm--in RNA and Schick-positive material. Along the periphery of many granulomas there was revealed a zone of reticular cells with markedly pyroninophil cytoplasma (with plasmatization). In the cytoplasma of leukocytes a considerable amount of glycogen was identified.


[Role of the liver in hormone metabolism and in the regulation of their content in the blood]. The normal liver function depends upon the amount of hormones in the blood which is regulated not only by the endocrine glands (EG) but by the liver itself to a large degree. The hormone content in the blood may be normal, when the EG function is increased, if the liver removes them intensively, inactivates them and excretes in the bile. If the hormone excess exceeds the regulatory capacities of the liver, their level in the blood increases. An inflow of an increased amount of hormones damages liver functions, then elimination of the hormone excess decreased or does not occur, and their level in the blood increases further. The function of the corresponding EG is inhibited. When the EG functions decrease, the level of hormones in the blood may remain normal owing to their decreased removal by the normal liver. Thus, the normally functioning liver may for some time maintain the normal balance of hormones when the EG functions are disturbed. The same may happen in the disorders in the liver function, if the EG function normally.


[Lobular carcinoma in situ and lobular cancer (lobular carcinoma) of the breast]. The histological characterization of mammary cancer (MC) is of leading importance for prognosis and choice of therapeutic methods (directed hormonal and chemotherapy). In this respect of interest is the morphological picture of a special form of MC, lobular cancer which is characterized by the most malignant course, marked infiltrative and less manifest destructive growth, multicentricity and multiplicity, as well as bilateral foci of lesions. It probably originates from the myoepithelium. In the national literature, no information on lobular MC is available. Little information is available on the precursor of lobular MC, lobular carcinoma in situ. This problem is insufficiently and inaccurately dealth with in the International classification of mammary gland tumors (WHO). A review of literature on lobular MC, as well as photomicrographs of its structure and that of its precursor are presented.


Primary reticulum cell sarcoma of the brain in Wiskott-Aldrich syndrome. Report of a case. We report a case of Wiskott-Aldrich syndrome in a 3 1/2-year-old boy. The patient developed reticulum cell sarcoma primarily in the brain; a biopsy specimen was obtained, and treatment with irradiation and chemotherapy was begun. Computerized tomography performed after three months of therapy showed remarkable regression of tumor. When the patient died five months postoperatively, no viable tumor was present; death was the result of pneumonia and sepsis. Only two previous cases of lymphoreticular neoplasm confined to the brain and associated with this syndrome have been described. We discuss the relationship between immunodeficiency and the occurrence of neoplasia in this syndrome.


Short-term dose response characteristics of acetazolamide in man. Nine patients with ocular hypertension each randomly received on separate days 0, 63, 125, 250, and 500 mg of acetazolamide (Diamox). In a double masked manner, acetazolamide plasma levels and intraocular pressure were monitored for seven hours following administration. Plasma levels increased linearly with dose, reaching 30 microgram/ml with the 500-mg dose. Maximum plasma levels occurred at one hour, and the minimum IOP was at two hours. The maximum IOP effect was a 30% to 35% fall. The IOP response was related to dose and plasma level, up to a 63-mg dose, which produced an average fall of 8.2 mm Hg. Little further average effect was documented at higher doses or plasma levels. The duration of response was slightly prolonged by 250 mg, but 500 mg showed no greater response. Thus, a 63-mg dose or a plasma level of 4 to 5 microgram/ml was as effective in lowering IOP as higher doses that produced plasma levels of 10 microgram/ml or more.


Organ-cultured corneal endothelium in vivo. We used the clinical specular microscope to examine the endothelium of 14 clear penetrating corneal grafts that ranged from 4 days to 2 1/2 years posttransplantation. All the donor corneas had been preserved in organ culture at 37 C for up to five weeks before grafting. Ten of the transplants were aphakic. The graft endothelial cell density, although less than that of normal corneas of the same age, was similar to that of other transplants done by the same two surgeons using alternate methods of donor preservation. We found a significant inverse correlation between graft endothelial cell density and the age of the corneal donor.


Palatal island flap for reconstruction of oral defects. This communication describes the technique of the palatal island flap and its usefulness in intraoral reconstruction, with a modification for increasing its extension by means of the palatine foramen free-up procedure. The other modalities, with their attendent advantages and disadvantages for intra-oral reconstruction, are briefly reviewed.


[Tissue adhesion using highly-concentrated human fibrinogen on the example of free, autologe skin-grafting (author's transl)]. A report is given about the clinical experiences, made with a biological adhesive-system, consisting in thrombin, native human fibrinogen and clotting factor XIII. We used this adhesive-system in 28 cases of free skin-grafts, without any other kinds of skin-fixation. The highly adhesive properties, the good tissue compatibility recommend this system for using in free skin grafting. Possibilities for use in other kinds of operations in O.R.L. are discussed.


Control of blood glucose in diabetics using an artificial pancreas. Studies have been performed using an on-line computer system programmed for blood gucose control of insulin and dextrose infusion (artificial pancreas). The aim of these studies was to test performance of the artificial pancreas and to suggest directions for future optimisation. Blood glucose stabilisation studies of diabetic volunteers were extended throughout the day and included three main meals and light exercise periods. Monitoring of blood glucose profiles of the same diabetics after depot insulin were performed on a separate occasion for comparison. The presence of insulin antibodies did not impair operation of the artificial pancreas. Most of the insulin infused by the artificial pancreas was to initially correct hyperglycaemia with relatively little required to subsequently maintian euglycaemia. The afternoon intra-meal average infusion rate was 0-9 U/hr. It is suggested that correction of fasting hyperglycaemia and maintenance of euglycaemia in diabetics be treated as separate control problems for the artificial pancreas. The overall ability of the artificial pancreas to control blood glucose to a degree not attainable by conventional insulin therapy is confirmed, in this case under conditions which include patient activity.


Tissue defects in the limbs: replacement with free vascularized tissue transfers. The use of free vascularized tissue transfers in reconstructive surgery is an exciting new development. Such procedures require careful planning and meticulous attention to detail. Illustrative cases are described to indicate the value and scope of this concept, which has been made possible by the development of microsurgery.


The microsurgical basis of Fallopian tube reconstruction. A rational approach to the reconstruction of the Fallopian tube, blocked either intentionally or by disease processes, can only be made on the basis of sound anatomical and physiological understanding. It would accordingly not be logical to expect the tube to function normally again after too great a disorganization by sterilization procedures followed by traumatic restorative operations. It is therefore recommended that any sterilization should be carried out by a midtubal atraumatic Pomeroy method, tissue being conserved for possible future reconstruction, and that a proven microsurgical technique be utilized for the best results of reconstruction to be obtained. This paper briefly details the anatomy and physiology of the Fallopian tubes, evaluates a microsurgical tubal repair in the rabbit, reports a series of tubal repairs in women, and suggests a working protocol for future tubal surgery.


Ophthalmic microsurgery.

Ophthalmic microsurgery. The introduction of microsurgical procedures to ophthalmology has resulted in an increased success rate with established operations. New operations which can only be performed with the operating microscope have also been developed. As long as certain basic principles are followed, surgery with the microscope has wide application, and lies within the expertise of all surgeons.


Fitting problems of the artificial lower limb: the surgeon's contribution. Difficulties are experienced by the artificial limb maker and fitter when fitting prostheses to some lower extremity amputation stumps. These difficulties, due partly to operative techniques, are outlined, and suggestions are made for their correction.


Isolation of Salmonella spp. from dead gulls (Larus californicus and Larus delawarensis) from an Idaho irrigation reservoir. An epizootic of unknown etiology resulting in the death of about 500 sea gulls (Larus californicus and Larus delawarensis) in 24 hr occurred on an irrigation reservoir in southwestern Idaho in April 1975. Salmonella spp. were isolated from necropsy specimens from 2 of 6 gulls examined. No Salmonella spp. were isolated from fecal specimens or dead gulls collected at a nesting site.


Biochemical study of KB-cell receptor for adenovirus. Three different approaches were used in an attempt to characterize the KB-cell receptor for adenovirus: affinity chromatography, immunoadsorption and cross-linking with a cleavable bifunctional reagent. The first system used an affinity gel consisting of adenovirus-fibre projection linked to Sepharose matrix by an intermediate bis(aminopropyl)amine arm, the amino groups of the fibre ligand being preserved by prior citraconylation. The second system consisted of adenovirus complete penton capsomere attached to anti-(penton base) antibody and cross-linked to polyacrylamide particles with glutaraldehyde. In this latter affinity model, the penton-fibre projection was appropriately oriented outwards, as in the virus particle. Both affinity systems permitted isolation from a KB-cell plasma-membrane extract of fibre-binding and penton-fibre-binding protein material, which inhibited adenovirus attachment. The penton-immunoadsorbent appeared more efficient and more specific than the affinity column of fibre-bis(aminopropyl)amino-Sepharose gel in specific activity of inhibition of adenovirus attachment. The third method consisted of reversibly cross-linking KB-cell receptor proteins with adenovirus particles by means of a cleavable di-imidoester and isolation of the complexes by sucrose-density-gradient centrifugation. Polypeptide analysis on sodium dodecyl sulphate/polyacrylamide gel of labelled KB-cell surface proteins, selected by the different procedures, showed that three major protein subunits of 78000, 42000 and 34000mol.wt. were common to the three selection systems. A possible model for the structure and function of the KB-cell receptor for adenovirus is discussed.


The manipulation of cellular cytochrome and lipid composition in a haem mutant of Saccharomyces cerevisiae. 1. The ole-3 mutant of Saccharomyces cerevisiae has an early lesion in the pathway of porphyrin biosynthesis. 2. This results in the loss of all haem-containing enzymes, including the mitochondrial cytochromes, and prevents the synthesis of components whose formation requires haem-containing enzymes, including unsaturated fatty acids, ergosterol and methionine. 3. The pleiotropic effects of the primary lesion are reversed by growing mutant ole-3 aerobically in the presence of intermediates of the porphyrin-biosynthetic pathway, and the present work reports the degree of manipulation of lipid and respiratory-cytochrome composition. 4. Supplements of delta-aminolaevulinate in the range 0.5--500 mg/l result in a progressive increase in the cellular content of unsaturated fatty acids and respiratory cytochromes, cause the replacement of lanosterol and squalene by ergosterol, and an increase in total sterol content. 5. Haematoporphyrin and protoporphyrin IX have similar but less extensive effects on cellular composition, whereas haematin allows unsaturated fatty acid synthesis and some sterol synthesis, but has no effect on the formation of respiratory cytochromes. 6. These results suggest that growth of the organism in the presence of defined amounts of delta-aminolaevulinate will be useful in the investigation of the role of lipids and cytochromes in the function and assembly of mitochondrial membranes.


The effects of altered membrane sterol composition on oxidative phosphorylation in a haem mutant of Saccharomyces cerevisiae. 1. The sterol, unsaturated fatty acid and cytochrome contents of cells of a delta-aminolaevulinate synthase mutant of Saccharomyces cerevisiae are manipulated by growing the organism in media containing defined supplements of delta-aminolaevulinate and other porphyrin intermediates. 2. If unsaturated fatty acids are added to the growth medium as Tween 80, sterol content and respiratory cytochromes alone are manipulated. 3. In the presence of delta-aminolaevulinate (10-50mg/1) cells exhibit moderate to high respiratory activity, but growth yields are low, indicating a loss of oxidative phosphorylation. This is associated with the depletion of membrane lipids, either unsaturated fatty acids and sterols together or sterols alone. 4. Sterol depletion leads to the loss of coupled mitochondrial oxidative phosphorylation in vitro. 5. The lesion in oxidative phosphorylation is associated with an increase in the passive permeability of sterol-depleted mitochondria to protons. 6. Arrhenius plots of mitochondrial permeability to protons indicate that the activation energy for proton entry increases as the sterol content of the membranes decreases. 7. Studies on a cytoplasmic petite mutant isolated from strain ole-3, which lacks a functional membrane-bound protein-translocating adenosine triphosphatase, indicate that proton permeability of the petite mitochondria varies as a function of sterol composition in the same way as that of ole-3 grande mitochondria. This indicates that sterols alone are probably directly responsible for the increased proton entry, owing to a reorganization of the lipid in the membrane. 8. Supplemented ole-3 cells with a normal lipid composition and normal or higher than normal respiratory activities have a growth efficiency only 65% of that of the wild-type, indicating that a further lesion in energy metabolism may be present.


[Studies on synergistic behaviour and pharmacokinetics of the combination sulfonamide/trimethoprim. IV. A comparative study on potentiating the trimethoprim effect by various sulfonamides and critical observations on its dosing (author's transl)]. The maximum possible inhibitory effect of sulfonamide-(SA)-trimethoprim (TMP) combinations on E. coli is obtained with rather small concentrations of SA according to the results obtained with bacterial growth kinetic studies. In these studies the TMP concentration (significantly below the minimum plasma level) was kept constant and the SA concentration varied. An "antagonistic" effect of high SA concentrations on the synergistic effect of the combination and a reduction of the inhibitory effect of TMP has been observed. According to the results of the bacterial growth kinetics obtained with E. coli and pharmacokinetic studies presented, the suggested dose for the combination 2-sulfa-4,5-dimethyl-oxazole/TMP seems to be sufficient, the dosage regimen is correct, whereas the amount of 3-sulfa-5-methyl-isoxazole (SMZ) in the dose proposed for the combination SMZ/TMP seems to be unreasonably high and the dosage scheme is incorrect.


[New antihypertensive agent of the imidazoline series: 5-fluoro-methyl-imidazolidinylidene-benzamine-monohydrochloride (flutonidin)]. A New Antihypertensive of the Imidazoline Series: 5-Fluoro-2-methyl-imidazolidinylidene-benzamine-monohydrochloride. 5-Fluoro-2-methyl-imidazolidinylidene-benzamine-hydrochloride (flutonidin, ST 600), a new antihypertensive imidazoline compound, was tested over 3 weeks in 20 patients with moderate to severe hypertension. Blood pressure was significantly lowered in both supine and upright position. In nearly 2/3 of the patients treated normalization of blood pressure was achieved. Side effects like sedation, dry mouth or orthostatic complaints were present in 30%. Toxic effects were not registered. It is recommended to reduce the dosage slowly especially in the aged to prevent, in part severe findings after abrupt withdrawal.


On the nature of rheumatoid rice bodies: an immunologic, histochemical, and electron microscope study. The nature of rice bodies was studied, utilizing histochemistry, immunofluorescence, and scanning and transmission electron microscopy. Rice bodies were found to consist primarily of fibrous material, most of which was fibrin with small amounts of collagen. Channels containing a variety of viable cells permeated the rice bodies. Blood vessels occurred in a few rice bodies indicating a former connection with the synovial membrane. Nonvascularized rice bodies might represent a further degeneration of the vascular type. Rice bodies seem to be a nonspecific response to inflammation.