[Present state of pain surgery].

This report presented to the Société de Neurochirurgie de Langue Française is based on 34 years of unique practice in neurosurgical management of pain; during that long period the author and his associates have collected an unusually large experience in almost every field of neurosurgical management of pain; they have improved or fully devised several new techniques which allow them to ground an appreciation of the procedures still worthy to be used in various pain syndromes. The first part of the report deals with "Cybernetics of pain". This rather long chapter is based both on classical data and personal observations on man during and following operations, meant to relieve pain. Though supporting HEAD and HOLMES, theory on Control of protopathic by epicritic Stimuli, the authors consider that the type of pain associated with noxious stimulation as representative of just one among other types of pain, not induced by nociception and not associated with protection reflexes. Sensory deafferentation as can be produced by amputations, herpes zoster, dorsal column or medullary lesions, cannot be included in Sherrington's scheme of psychical mechanisms associated with protection reflexes and yet is responsible for most of the chronic unbearable and often intractable pain. Moreover, an important modulation of pain as such depends on conditioning, on inherited and acquired patterns of behaviour and on a multiplicating factor which is provisionally named "algogenic neurosis". The fact that an intact nucleus ventralis posterolateralis is a necessity for a "no pain status" tends to prove that this thalamic nucleus acts as a major inhibiting relay on the pain integrating system and for several additional reasons is the level of integration of epicritic versus protopathic stimuli in case of true nociception...


Luteinizing hormone-releasing hormone in peripheral plasma and hypothalamus of normal and ovariectomized rats.

Plasma and hypothalamic LHRH was measured by specific radioimmuno-assay in intact and ovariectomized rats, and the values were correlated with peripheral plasma (PP) FSH and LH titers. At most stages of the estrous cycle, plasma LHRH was either undetectable or present at very minimal values. An increase in PP LHRH concentration was observed in some animals between 13.00 and 20.00 h on proestrus. The mean elevation in LHRH was greatest in rats when blood samples were taken by decapitation; elevation was somewhat less when samples were taken from etherized rats and minimal when taken from rats bearing indwelling jugular cannulae. LHRH was elevated in approximately half the ovariectomized animals; repeated samples were drawn at 15-min intervals from intrajugular cannulae. In animals with LHRH elevations, LHRH was highly variable, which indicates that it is released in pulsatile fashion. Plasma LHRH and LH titers were correlated in ovariectomized animals. The relatively low correlation between LHRH and LH may be explained by the fact that a pulse of LHRH can elicit LH release over a considerable time span; also, LHRH is cleared much more rapidly from the circulation than is LH, as revealed by the time course of disappearance of exogenous LHRH given by bolus injection. In intact rats, hypothalamic LHRH content was slightly lower at 10.00 h on diestrus day 1 than at other sample times. LHRH was significantly lower 4 weeks following ovariectomy compared to levels in intact rats at any sample time. It would appear that LHRH's resynthesis does not keep pace with its release in ovariectomized rats, resulting in a decline in hypothalamic stores.


Sensitivity patterns of urinary pathogens in the Southland community and a study of sewage flora.

The overall sensitivity pattern of the three main urinary pathogens to the commonly used oral antibodies exceeded 80 percent. The incidence of multiple resistant Escherichia coli was 8 percent. The resistant patterns of the sewage E. coli resembled that of the resistant urinary E. coli. However only one-third of the resistant urinary E. coli showed multiple resistance whereas two-thirds of the resistant E. coli in the sewage showed this feature. The resistance transfer was low in organisms isolated from the sewage. Regular surveillance of this type may be useful as a guide to therapy and may reflect the impact of continued antibiotic usage in the community.


Hypothalamic gonadotropin releasing hormone: physiologic and clinical considerations.

Despite the efforts of a large number of investigators, the role of GnRH in clinical gynecology is uncertain. At present, its greatest utility is in research directed toward the understanding of hypothalamic-pituitary interrelationships. However, a clear understanding of the hypothalamic control of gonadotropin secretion awaits the actual measurement of the secretion of GnRH by the hypothalamus. In addition, a better understanding of the ability of the pituitary to secrete gonadotropins in various disorders of menstruation and maturation will probably be achieved through the determination of the capacity of the pituitary to synthesize as well as release gonadotropins in response to GnRH. Such determinations will probably utilize repeated or continuous infusions of GnRH rather than the currently more popular single injection technique. Finally, GnRH may be useful in the induction of ovulation. A definition of its role in ovulation induction awaits the results of additional clinical studies. Understanding of the nature of hypothalamic control of the pituitary is as yet incomplete. The availability of hypothalamic releasing factors will make it possible to study in greater detail the mechanisms by which the fine regulation of the endocrine system is achieved.


Toxemia of pregnancy. Part II. Immunofluorescent studies with placental connective tissue antisera: the possibility of characteristic lesions.

Seventeen placentas from term gestation complicated by toxemia of pregnancy and 17 normal controls were tested by the fluorescent antibody technic. Antisera to normal placental connective tissue and toxemic placental connective tissue were used. The antisera were obtained by the injection into rabbits of placental extracts rich in connective tissue elements from normal and toxemic placentas. The antitoxemic antisera, after absorption with soluble sonic fraction of normal placentas, stained the following elements exclusively in 14 of the 17 placentas: part of the syncytial knots, fibrillar elements in the adventitia of blood vessels, and amorphous deposition of connective tissue. In each of the remaining three placentas at least two of the lesions were observed. The observation of bright fluorescence in part of the syncytiotrophoblasts and the syncytial knots in toxemic placentas led to the suggestion that they arise late in pregnancy during the disease. The thin fibrillar elements and the amorphous deposition of connective tissue were documented in the various developmental stages in toxemic and normal placentas as well. These findings established possible characteristic lesions in the placenta of pregnancies complicated by toxemia.


Recurrence of vulvovaginal candidosis during pregnancy. Comparison of miconazole vs nystatin treatment.

The efficacy of miconazole and nystatin in the treatment of vulvovaginal candidosis was compared in a multicenter trial involving 94 pregnant patients. All patients had subjective complaints and were mycologically positive. Miconazole 2% vaginal cream was applied once daily for at least 10 days by 45 patients, whereas the 49 others received nystatin tablets for intravaginal application during 7 to 9 days. At the first examination following treatment, the cure rate with miconazole was 83% and with nystatin 68%. Follow-up examinations revealed a significantly lower recurrence rate in the miconazole-treated group. No important adverse experiences were noted.


Cyanoacrylate for closure of wounds in the oral mucosa in dogs.

The local clinical and histological reactions resulting from the use of a tissue adhesive, isobutylcyanoacrylate, were studied in the oral cavity of dogs. In each of 4 animals, 6 pairs of parallel incisions were made in the buccal mucosa. One incision in each pair was closed with adhesive material while the other incision was sutured with silk. The wounds were studied clinically and histologically at intervals ranging from 2 to 21 days. Clinically there were differences in the healing between gland glued and sutured incisions during the first 11 days. After 11 days the healing reactions were approximately the same in both groups. Histologically, the adhesive caused a delayed and disturbed healing of both the epithelium and connective tissue compared with that observed when sutures were used. As a result of this investigation, isobutylcyanoacrylate is not recommended for use instead of conventional and modern suturing materials when closing intraoral wounds.


Ocular infections caused by unusual gram-negative bacteria.

The isolation of 24 strains of gram-negative bacilli from eye infections is discussed. The primocultures were obtained at an incubation temperature of 25 and 30 degrees C, but never at 37 degrees C. These observations show that we have to look for these germs at 30 degrees C in every case of eye infection.


The use of freeze-dried bone in middle-third face advancements.

A considerable quantity of bone is required for grafting in most middle-third face advancements. In many patients, especially children, the additional surgery needed to obtain large quantities of autogenous bone adds considerable time and morbidity to the primary operative procedure. During the past 3 years we have utilized freeze-dried bone allografts processed by the Tissue Bank, Naval Medical Research Institute, Bethesda, Maryland. Eighteen patients undergoing various types of middle-third face advancement have received allografts and have been followed closely for at least 12 months postoperatively. Although the duration of follow-up is limited, the results to date have been encouraging. Osteotomies in all eighteen patients healed. Nine of the eighteen patients studied had no complications and healed uneventfully. Four patients developed infections postoperatively, necessitating partial removal of the graft material, and all subsequently healed without further difficulty. Four patients had intraoral exposure of the grafts postoperatively--three in the pterygoid maxillary area and one in the palate. However, no clinical infections developed in these patients and the exposed grafts healed uneventfully. One patient extruded a small sequestrum of bone, without infection, 2 years postoperatively.


Desquamative gingivitis. Clinical, histopathologic, and immunopathologic investigations.

Desquamative gingivitis is not a disease sui generis but is a descriptive term for a condition that requires thorough clinical evaluation and histopathologic and immunopathologic studies for accurate diagnosis. The present study emphasizes this statement. Six of seven patients with "desquamative gingivitis" were placed in a category of "possible cicatricial pemphigoid." During a 3-year observation period, five of six cases evolved into unequivocal cicatricial pemphigoid. Our studies lend credence to a hypothesis that immunopathologic mechanisms are operative in some forms of desquamative gingivitis.


Surgical correction of mandibular prognathism.

Procedures used in the correction of certain forms of mandibular prognathism are described. All but one of these techniques allow an immediate functional healing, which is considered to be most important. Since no single procedure can correct all the different forms of mandibular prognathism, each case is individually planned and a "custom-tailored" technique is applied.


Cancellous-marrow bone grafts in irradiated tissue.

Discontinuity defects of the mandible have been successfully treated by means of cancellous-marrow grafting techniques. This method of reconstruction has not been widely reported in the repair of defects in mandibles that have been exposed to radiation therapy. In the two cases presented in this article, the patients were previously treated for oral squamous-cell carcinoma by irradiation and partial mandibulectomy. Later, cancellous-marrow grafts were implanted. One patient received 3,000 rads of Cobalt-60 and had the body of the right mandible resected. The subsequent grafting procedure was successful in this patient. The second patient received 6,000 rads of Cobalt-60 and underwent resection of the mandible anterior to the molar region. The subsequent graft failed in this case.


Polypoid spindle-cell carcinoma (pleomorphic carcinoma). Report of a case occurring on tongue and review of the literature.

A case of spindle-cell carcinoma (pleomorphic carcinoma), a rare polypoid tumor of the tongue, is reported. The characteristic clinical, gross, and microscopic features of this peculiar lesion and its common sites of location are presented. Origin and pathogenesis of the sarcoma-like elements of the lesion are discussed and the literature on the subject is reviewed. Sites of apparent transition between the spindle cell elements of the tumor and the overlying epithelium were observed in light microscopic sections, and the electron micrographs of the spindle-cell portion of the lesion demonstrated the presence of tonofilaments and desmosomes in many tumor cells. These findings support the concept that this group of lesions are pleomorphic variants of squamous-cell carcinoma with predominantly spindle-cell pattern. Current evidence in the literature also suggests that metaplastic transformation of the tumor cells into mesenchymal elements may take place in some of these lesions, and that "metaplastic carcinoma" may probably be a more proper designation for them.


The evolutionary significance of phase-separated microsystems.

The source, preparation, and properties of phase-separated systems such as lipid layers, coacervate droplets, sulphobes, and proteinoid microspheres are reviewed. These microsystems are of interest as partial models for the cell and as partial or total models for the protocell. Conceptual benefits from study of such models are: clues to experiments on origins, insights into principles of action and, in some instances, presumable models of the origin of the protocell. The benefits to evolution of organized chemical units are many, and can in part be analyzed. Ease of formation suggests that such units would have arisen early in primondiae organic evolution. Integration of these various concepts and the results of consequent experiments have contributed to the developing theory of the origins of primordial and of contemporary life.


Microbiological and epidemiological study of streptococcal sore throat at a children's clinic: a one-year study.

From October 1973 to September 1974, throat cultures were taken from 578 patients who referred to the Children's Clinic with upper respiratory tract infection. One hundred fifty-one (26%) of the sick children yielded beta-hemolytic streptococci and 427 (74%) of the pharyngitis cases were considered as viral. The most susceptible ages for streptococcal and viral pharyngitis were 5-8 and 2-6 years respectively. The peak seasonal incidence for streptococcal sore throat was from late autumn to early spring. There was a positive correlation between the incidence of upper respiratory infection and streptococcal isolation. From 100 strains of beta-hemolytic streptococci isolated and tested, 86 were group "A", 4 group "C", 2 group "G" and 8 non-groupable. From 86 group "A" strains. 71 (82%) were typable by agglutination ("T"-typing), but only 49 (57%) by precipitation ("M"-typing). The most prevalent "M" types were types 1 and 12. There was 95% correlation between serological and bacitracin disk method for grouping of hemolytic streptococci. All strains isolated were sensitive to penicillin, erythromycin and chloramphenicol, but 11 strains were resistant to tetracyclin.


Colonic malakoplakia in a child: report of a case and review of literature.

The fifth case of colonic malakoplakia involving children under the age of 13 years is reported. Rectoscopic findings were strongly suggestive of a colonic carcinoma. A detailed review of literature on malakoplakia is also made.


Pure red cell aplasia.

The so-called pure red cell aplasia or hypoplasia may occur in various instances: 1- Congenital form, usually occuring in childhood; 2-Drug-induced types; 3-The forms associated with thymoma, carcinoma and hypogamma-globulinemia; and 4-As an isolated syndrome. In the etiology of congenital PRCA some immune mechanisms are considered to be important but the role of a genetic factor in producing the syndrome is more acceptable, although the exact pathogenesis of impairment of erythropoiesis is not clear. Disregarding the drug-induced types of the aplasia, acquired PRCA with or without thymoma is produced by immunologic mechanisms. Finding some factors such as antibody against erythroblast nuclei, inhibitor of heme synthesis and recently a cytotoxic factor that are in gamma G-globulin fraction of plasma of PRCA patients support the idea that the syndrome is of immunologic origin. It seems that the thymoma is only a manifestation of impaired immunologic state, and its role in producing the aplasia is a subject of controversy. Besides, we can not say that all cases of PRCA have the same pathogenesis and further investigations are necessary to provide some informations about the pathogenesis of this syndrome.


Hepatitis B antigen screening in South Australian and Northern Territory blood donors.

A standard counterelectrophoresis method has been used to screen almost 250,000 samples from South Australian and Northern Territory blood donors since 1971. The initial incidence of approximately one hepatitis B antigen positive donor per thousand has diminished as these donors have been excluded from further blood donation. There is a predominance of males in the series, and more of the hepatitis B antigen carriers are in the younger age groups than expected. A higher than expected incidence of hepatitis B antigen positives has been noted in Northern Territory donors. Follow-up of donors found to be hepatitis B antigen positive has shown that the majority remain positive for more than two years without developing overt hepatitis. These individuals may represent a long-term asymptomatic carrier state.


The electron microscopic localization of nephrotoxic antibodies in isolated glomeruli.

Scanning electron microscopy showed that most glomeruli isolated by sieving from normal and nephrotoxic rats were cleanly decapsulated and undisrupted. An anti-IgG antibody-horesradish peroxidase conjugate was applied to such isolated glomeruli and also to slices of renal cortex which were sebsequently embedded in epoxy resin. Linear staining along the glomerular basement membranes of nephrotoxic rats was evident and subendothelial electron-dense deposits were shown to contain anti-glomerular basement membrane antibody. Whereas the linear reaction was faint and limited to superficial parts of glomeruli in tissue slices, it was intense and present in most regions of all of the isolated glomeruli. Thus, the fine details of the distribution of intraglomerular antibody are more clearly and consistently demonstrated in isolated glomeruli than in kidney slices.


Studies on the infectivity of tropical African strains of Plasmodium falciparum to some southern European vectors of malaria.

Preliminary experiments in Garki, Nigeria, with A. atroparvus from Italy have shown a refractoriness to infection with the local strain of P. falciparum. Comparative studies involving A. labranchiae and two strains of A. atroparvus, all from Italy, and one local strain of A. gambiae species B, were carried out at Kismu, Kenya. While oocysts developed in 77% of A. gambiae and, from day 14 onwards, 100% of the oocyst positive mosquitos had sporozoites in the salivary glands, oocysts were seen in only 4% of one of the A. atroparvus strains; the development of these oocysts appeared to be arrested at an early stage. A labranchiae and the other strain of A. atroparvus showed no oocysts. None of the Italian mosquito strains was positive for sporozoites. It is concluded that the importation of falciparum malaria cases from tropical Africa is unlikely to produce epidemics in those southern European areas where A. labranchiae and A. atroparvus used to be malaria vectors.


The use of analytical electron microscopy in the study of three species of Aspergillaceae.

The combination of electron beam scanning and X-ray detection allows to use the scanning electron probe microanalyzer as a sensitive microscope to elemental constitution. This made it possible to investigate three species of the Aspergillus nidulans group: A. nidulans, A. unguis, A. variecolor. Qualitative differences were found between the three species. The application of microanalysis is regarded as a useful addition to more conventional methods used in histochemical studies. The advantages of examining specimens which have not been submitted to fixation, dehydration and embedding are briefly discussed.


Attempts to induce hepatic uridine diphosphate glucuronyl transferase in genetically deficient Gunn rats by grafting of normal liver tissue.

Liver from normal Wistar rats was grafted into the liver of homozygous Gunn rats which are deficient in UDP glucuronyl transferase (UDPGT) (bilirubin) activity. After 3 months, UDPGT activity (bilirubin) remained absent in microsomal suspensions of liver from recipient rats and no bilirubin glucuronide was detected in their bile.


Central nervous system patholgoy associated with mask ventilation in the very low birthweight infant: a new etiology for intracerebellar hemorrhages.

Mask-applied ventilatory support was noted to cause severe head molding in infants with birthweights under 1,501 gm. To determine if this molding was detrimental to the infant, the neonatal course and autopsy findings were reviewed for 106 infants. Twenty significant intracerebellar hemorrhages were found. An association between these hemorrhages and mask-applied positive pressure ventilation was demonstrated (P = .05). This relationship was maintained when all cases of generalized bleeding dyscrasia were removed (P = .021). It is proposed that the distortional forces produced by the mask attachment, together with the buffeting effect of intermittent positive-pressure ventilation, are causally related to the production of intracerebellar hemorrhages by direct contusion, by ischemic stasis, or by altered venous drainage. The authors urge strong caution when dealing with the small premature infant in using any attachment device that causes molding of the cranial vault, particularly in the occipital area.


Cephalexin compared to ampicillin treatment of otitis media.

Cephalexin was compared to ampicillin for the treatment of otitis media in a randomized study. Bacteriologic diagnosis was sought by needle tympanocentesis in 179 children. No overall statistically significant differences were noted between the two groups; however, 20 patients who received cephalexin had a poor response to therapy whereas only five recipients of ampicillin responded poorly. A significant difference (P less than .05) between the two regimens was noted when Hemophilus influenzae was recovered. Fifty per cent of the children with H. influenzae otitis media who were treated with cephalexin responded poorly; no patients receiving ampicillin had a poor response. Our data suggest that the use of cephalexin monohydrate is not warranted for treatment of otitis media due to H. influenzae even when the isolate proves sensitive to this drug in vitro. In selected patients with otitis media caused by Staphylococcus aureus which is resistant to penicillin, cephalexin may provide effective treatment.


The spectrum of ischemic bowel disease in the newborn.

In this review the author's opinion regarding the etiology of most cases of perinatal and neonatal bowel ischemia has been stated. It is recognized that the changes brough about by hypoxia (splanchnic shutdown, bowel ischemia) represent the "soil" on which other "seeds" can prosper. In its simplest form following acute ischemia, the processes of repair take over, leading to functional recovery and a presumably normal bowel. In those patients with more extensive initial damage, degrees of stenosis and even atresia may be expected as a result of the healing of the bowel. Rapidly evolving ischemia may produce perforations; these may be restricted and involve only very small areas of bowel or may be part of a more generalized involvement, possibly even with multiple perforations. In other infants, alterations of bacterial flora could contribute to the clinical picture of "necrotizing enterocolitis," and gas may or may not be present in the bowel wall. If the process of ischemia has been relatively mild, or bacterial overgrowth not particularly marked, some of the more obscure functional syndromes may be noted. The persistence of these obscure syndromes may in turn be related to incomplete phases of regeneration of the bowel that fall short of producing stenosis but lead to a mucosa that is not optimally functional.


Comparison of the reactions of chemically reactive analogs of U-G-A and of A-U-G with ribosomes of Escherichia coli.

The chemically reactive analog of U-G-A, 5'-(4-(Bromo-[2-14C] acetamido) phenylphospho) - uridylyl-(3'-5') - guanylyl-(3'-5') adenosine has a 20 fold lower affinity to 70S ribosomes than the corresponding analog of A-U-G though the U-G-A analog also preferentially reacts with protein S18 of 70S ribosomes. This reaction programs ribosomes for EF-T dependent Trp-tRNATrp-suIII binding. Therefore, it is concluded that this protein is part of the A'-site of the ribosomal codon binding site. Reaction of the U-G-A analog with 30S subunits lead to a predominant crosslinking of U-G-A to proteins S4 and S18. In contrast, a comparable reaction of the A-U-G analog with 30S subunits lead to a predominant crosslinking of A-U-G to proteins S4 and S12 (Pongs, O., Stoffler, G.A., Lanka, E., (1975) J. Mol. Biol. 99, 301). Since protein S12 is located at the 'P' site of the ribosomal codon binding site, it is proposed that the U-G-A analog does not bind at this site.


Control of RNA synthesis by chromatin proteins.

The effect of chromatin proteins on template activity has been studied. Using both E. coli RNA polymerase and calf thymmus polymerase B we have measured the number of initiation sites on chromatin and various histone-DNA complexes. Chromatin can be reconstituted with histone proteins alone and this complex is still a restricted template for RNA synthesis. The removal of histone f1 causes a large increase in the template activity. Chromatin is then treated with Micrococcal nuclease and the DNA fragments protected from nuclease attack ("covered DNA") are isolated. Alternatively, the chromatin is titrated with poly-D-lysine, and by successive treatment with Pronase and nuclease, the DNA regions accessible to polylysine are isolated ("open DNA"). Both fractions were tested for template activity. It was found that RNA polymerase initiation sites are distributed equally in open and covered region DNA.


Evidence that 16S RNA from E. coli can assume two different biologically active conformations.

We have recently shown that 16S RNA can be extracted from 30S ribosomes by an acetic acid-urea precipitation procedure which yields RNA capable of binding 13 individual ribosomal proteins. This is in contrast to phenol extracted 16S RNA which can specifically associate with only 7 proteins2-7. In the experiments reported here, we demonstrate that the difference in protein binding capacities is due to a relatiely more "open" configuration possessed by the acetic acid-urea 16S RNA. Under identical conditions, acetic acid-urea 16S RNA is more susceptible to limited T1-RNase digestion than is phenol-16S RNA. In addition, acetic acid-urea RNA shows a relatively slower electrophoretic mobility. The observable difference in conformation between the two types of RNA is lost by storage at-70 degrees C. This loss is accompanied by a reduction in protein binding capacity of the acetic acid-urea 16S RNA.


Conversion of Escherichia coli RNA polymerase to a template independent enzyme.

Preparations of RNA polymerase (E.C.2.7.7.6) from uninfected Escherichia coli, T4 infected Escherichia coli, and Acinetobacter calcoaceticus when centrifuged in sucrose gradients in the absence of magnesium ions gave rise to five peaks, all of which were able to form polymers from ribonucleoside 5'-triphosphates in the absence  of template or primer. All of the peaks obtained from the Escherichia coli enzyme appeared to contain the subunit alpha and beta and, in addition, polypeptides which appeared to be derived from the subunit beta.


Integration of synthetic globin genes into an E. coli plasmid.

Rabbit globin mRNA has been purified and used as a template by reverse transcriptase. The resulting duplex molecule consisting of rabbit globin mRNA/cNDA has been linked in vitro to Eco RI cleaved plasmid Col E1 DNA. Transformation of E. coli C6OO by this recombinant molecule has been achieved. Transformed bacteria acquire the colicin EQ immunity of Col E1 and a closed circular DNA species of 4.40-4.45 x 10 (6) daltons in molecular weight, an increase of 2.0-2.5 x 10(5) daltons compared to that of the parent plasmid DNA. In addition , 3H cDNA synthesized from globin RNA hybridized perferentially to the recombinant plasmid DNA.


ATP-analogues as substrates for the leucyl-tRNA synthetase from Escherichia coli MRE 600.

No analogous nucleoside triphosphate was found which acts as well as ATP in binding to and supporting catalysis of leucyl-tRNA synthetase from Escherichia coli MRE 600. However, there are numerous nucleotides which are able to replace ATP, but with lower efficiency. The 6-amino group of the adenine ring and the 2'-hydroxyl group of the ribose ring are essential for binding and catalytic activity. Alterations in the triphosphate moiety of the molecule can cause drastic changes in Km and/or Vmax, whereas alterations of the imidazole ring and substitutions at the 8-position of the adenine ring cause only minor losses of catalytic activity.


Increased isoleucine acceptance by sulfur-deficient transfer RNA from Escherichia coli.

Sulfur-deficient tRNA, isolated from Escherichia coli HfrC, rel-, met-, cys-, lambda, after cysteine starvation, was found to have an increased acceptance of isoleucine in proportion to the deficiency of 4-thiouridine. Isoleucine acceptance was not altered in the presence of other amino acids of CTP, and the higher acceptance was observed over a wide range of magnesium, isoleucine, tRNA and enzyme concentrations. The Vmax value for sulfur-deficient tRNA was more than three times greater than observed for normal tRNA. Methylated albumin kieselguhr (MAK) chromatography revealed three isoacceptor peak for normal tRNA, while sulfur-deficient tRNA  was missing tRNAile, and exhibited a larger, shifted peaks for tRNA normal tRNA, while sulfur-deficient tRNA was missing tRNAille 2, and exhibited a large shifted peak for tRNAile 3 . Treatment with crude RNA sulfurtransferase both lowered the isoleucine acceptance for sulfur-deficient tRNA to that seen for normal tRNA, and restored the missing isoacceptor on MAK. The possibility that thionucleotides may play a role in the aminoacylation of tRNAile in E. coli is discussed.


The kinetics of E. coli RNA polymerase.

Using an assay specific for chain elongation of E. coli RNA polymerase the kinetics of this propagation reaction have been studied. The kinetic behaviour is consistent woth the mathematical model formulated for this multisubstrate enzyme. The effect of increasing salt concentration on the kinetics of the reaction indicated that DNA unwinding is probably a necessary step in the propagation step, although this may not be the rate limiting step under all conditions.


RNA chain elongation on a chromatin template.

The rate of RNA chain elongation has been measured with DNA and chromatin as template. RNA propagation on chromatin is about 50% of the rate found with DNA. Kinetic experiments demonstrate that the inhibition is not due to interference with the addition of the nucleoside triphosphates. Analysis of the dependence of propagation on the Tm of DNA shows that the chromatin proteins interfere with the translocation of the RNA polymerase along the DNA template.


A comparative X-ray diffraction and circular dichroism study of DNA compact particles formed in water-salt solutions, containing poly(ethylene glycol).

Comparative CD and X-ray diffraction studies of DNA compact particules which were obtained in PEG-containing water-salt solutions, have been carried out. Compact particles, formed from native DNA, produce a psi CD spectrum (characterized by a negative band at lambda-270 nm) and a small-angle X-ray diffraction pattern, which shows two reflections: I at 34-40 A and II at 80-90 A (together with its second-order reflection). Compact particules, formed from DNA molecules with partially disordered secondary structure, do not produce the psi CD spectrum and the reflection I, while the reflection II remains unchanged. It is suggested that the spacing of 34-40 A is associated with a side-by-side packing of DNA fragments in "microcrystallization' regions in compact particules and that such "microcrystallization' accounts for the generation of the psi CD spectrum.


The kinetics of binding of U-U-C-A to a dodecanucleotide anticodon fragment from yeast tRNA-Phe.

The kinetics of U-U-C-A binding to the dodecanucleotide (A-Cm-U-Gm-A-A-Y-A-psi-m5C-U-Gp) isolated from the anticodon region of yeast tRNA-Phe are similar to the kinetics of binding of U-U-C-A to intact tRNA-Phe. A large enhancement in binding constant over that predicted for U-U-C-A-U-G-A-A is observed for both the complexes of dodecanucleotide and tRNA-Phe with U-U-C-A. This strongly suggests that both the anticodon loop in tRNA-Phe and the dodecanucleotide can form four base pairs with U-U-C-A. Furthermore, the enhanced stability cannot be attributed to a special conformation of the anticodon loop, but instead the anticodon loop is probably flexible. A likely explanation for the increased binding is the effect of non-base-paired ends. This increased thermodynamic stability comes from a larger entropy gain rather than a larger enthalpy decrease.


Arangement of transfer-RNA -genes in yeast.

The redundancy and the arrangement of the genes for specific transfer ribonucleic acids in yeast were studied by the hybridization techniques developed by Birnstiel et al., e.g.[1]. The redundancy was found to be in the order of 10 genes for tRNA1Met, tRNA3Met, tRNA2Ser, and tRNA-Pro. High molecular weight yeast DNA was fractionated by density gradient centrifugation in cesium chloride and the [32p]tRNAs were hybridized to the single fractions. The results together with earlier findings [2] suggest that the cistrons for these tRNAs are arranged in tandem interspersed by 6 to 10 times longer segments of spacer DNA which varies in (G+C) content for the different tRNA species.


A simple method for DNA restriction site mapping.

When a DNA molecule, enzymatically labelled with 32p at one end, is partially digested with a restriction enzyme labelled tdna fragments are obtained which form an overlapping series of molecules, all with a common labelled terminus. ta restriction map can then be constructed from an analysis of the size distribution of these molecules. This technique has been used for the restriction site mapping of cloned histone DNA (h22) where as many as 35 cleavage sites may be accurately determined in a single experiment.


Florence Nightingale and the Salisbury incident.

Florence Nightingale's astute handling of mismanagement in Free Gifts Stores during the Crimean War underscored her administrative ability. Miss Nightingale went to Scutari ostensibly to nurse the British soldiers, and while there encountered innumerable instances of administrative and managerial ineffectiveness and difficulties. Among these were the problems in the accountability and deployment of supplies as well as the assignment and supervision of female personnel-an untried situation. The article identifies the misdirected organizational management which occasioned the introduction of women into British war nursing and the voluntary participation of the British citizenry in providing supplies and comfort for the Army. Through analysis of Miss Nightingale's and others' private correspondence, the problems of personnel management and supply distribution are brought into sharp focus. The interplay of policies and principles to which Miss Nightingale subscribed, the human frailty of one of her women, Miss Nightingale's illness, and the confusion and stress which characterized the Crimean War are discussed. The compassion, understanding, and rectitude as well as the human values to which Miss Nightingale subscribed in protecting a woman guilty of a breach of trust and felony and the troublesome slanderous attack to which Miss Nightingale was subjected at the instigation of her foes on the home front provide a background for the presentation of the Salisbury affair as an interesting aspect of historical research into the life of the Victorian heroine.


Propranolol, renin and hypertension: a review.

When plasma renin activity is related to sodium balance as evaluated from urinary sodium excretion, a physiological index of normality is obtained along with the ability to detect subtle variations in renin secretion. This has made it possible to correlate more closely the antihypertensive action of propranolol with the renin level. Propranolol reduced renin in all patients but did not lower blood pressure in low renin hypertensive states. It was dramatically effective in lowering blood pressure of high renin and some normal renin patients. Its antihypertensive effect was directly related to the pretreatment renin level and also to the absolute decrement in renin reduction achieved. This was true in malignant, renal, renovasular, and essential hypertension. Altogether, these findings point to the involvement of the renin-aldosterone axis in these hypertensive states. They suggest that a major component of the antihypertensive action of propranolol is consequent to an antirenin effect which is perhaps neurologically mediated. Accordingly, in addition to its therapeutic values, the response to propranolol may provide a pharmacological indicator of the renin involvement in essential hypertension and it also may be a useful adjunct for predicting surgical curability of renovascular hypertension.


Central hypotensive effect of propranolol.

Propranolol is an antihypertensive drug whose mode of action in lowering arterial pressure remains undecided. Animal experiments indicate that an action within the central nervous system (CNS) contributes to the hypotensive effect. Intravenous infusion of propranolol to the conscious rabbit lowers arterial pressure and this is accompanied by a decrease in preganglionic sympathetic nervous activity. This indicates that propranolol decreases sympathetic nervous outflow by a central action and since the dextro isomer of propranolol does not exert such an effect then this action must be related to beta-adrenoceptor blockade.


Propranolol and experimental myocardial infarction: substrate effects.

Propranolol is known to decrease ischaemic damage in developing myocardial infarction. Besides acting on mechanical parameters which help determine the balance of oxygen supply and oxygen demand in the ischaemic tissue, propranolol decreases the myocardial uptake of free fatty acids and increases that of glucose. It is suggested that propranolol may favourably alter developing myocardial infarction in dogs by altering the supply of substrates reaching the ischaemic zone. However, propranolol also decreases enzyme release from isolated rat hearts with coronary ligation at a relative constant arterial free fatty acid concentration. Propranolol causes more marked depression of mechanical function and of heart rate in hearts perfused with free fatty acids than with glucose. It is suggested that the glucose-promoting and anti-lipolytic actions of propranool might be important not only in decreasing infarct size but also in helping to prevent undesirable side effects in hearts with experimental myocardial infarction.


Pharmacokinetics of propranolol: a review.

The pharmacokinetics of propranolol vary according to the route and duration of administration. After i.v. administration, the decline in drug concentrations is biphasic and the drug is cleared very efficiently by the liver, so that its elimination is dependent largely on liver blood flow. Although the drug is some 90-95% bound to plasma, hepatic removal is so avid that both bound and free forms are extracted. Consequently, hepatic elimination is unaffected by drug binding in blood, In contrast, the distribution of drug into the tissues is reduced by plasma binding, so that drug half-life (T 1/2), which varies from 11/2-3 hours among individuals is more prolonged in people with relatively low plasma binding. Recent evidence shows that at all times after i.v. administration the beta-blocking effects of propranolol are related to its plasma concentrations according to the receptor theory. In addition individual differences in the response due to a given total concentration are largely due to variations in plasma binding, the drug's effects being a function of free (unbound) drug in plasma water. After the administration of single oral doses, hepatic extraction remains high and much of the dose is eliminated from hepatic portal blood during transfer from the gut, so that little drug reaches the systemic circulation. In addition, significant amounts of an active metabolite, 4-OH propranolol, are produced so that 2 hours after dosing, propranolol appears more potent that its plasma levels would suggest. With continued administration, the avid removal process becomes saturated, extraction ratio falls and propranolol accumulates some 2-fold. Drug T 1/2 is prolonged to 3-6 hours under these conditions, the ratio of propranolol to its active metabolite increases so that most of its effects can be attributed to the parent drug. Perhaps the most important kinetic fact to emerge is the 20-fold variation in plasma levels found after chronic administration of the same oral dose to different patients. This accounts for most of the individual variation in dosage requirements. Concerning propranolol withdrawal, there is no evidence that the effects of the drug last longer than appropriate for its T 1/2, so that larger doses last longer. Nonetheless, 24-48 hours is more that sufficient for the effects of the drug to dissipate. In view of the rebound angina, arrhythmias and infarction that may occur, abrupt withdrawal should be avoided if possible.


Propranolol in the treatment of angina: a review.

The use of beta-adrenergic blocking drugs in angina pectoris was one of the original indications for these drugs suggested by Black. An anti-anginal effect was demonstrated with the first beta-adrenergic blocking drug, pronethalol, that was used clinically. This benefit in angina was confirmed in the early trials with propranolol in 1964-65. Although some definite anti-anginal effect can be demonstrated with low fixed dosage, evidence suggested that those trials which used a higher and a variable dose displayed a greater anti-anginal action of the drug. After a two dose trial (Gillam and Prichard, 1966,) demonstrated a dose dependent anti-anginal effect, a log-dose response study demonstrated a progressive reduction in angina attacks as dosage was increased (Prichard and Gillam, 1971). While a highly significant effect was found with an average dose of 52 mg a day a progressive reduction in angina attacks was found with logarithmic increases in dosage up to an average of 417 mg a day. Dosage in this trial was adjusted to produce a supine heart rate of 55-60 beats/minute provided this was not prevented by side effects. As the dosage of 417 mg a day was still on the straight line part of the dose response curve and therefore suboptimal, we not adjust dosage to produce a standing heart rate of 55-60. Fully meaningful comparative trials require that optimum dose of the drugs being compared are used. A variable dose comparative trial comparing propranolol and practolol, showed propranolol was the more effective agent. More recently a variable dose comparative trial of sotalol and propranolol indicated propranolol had greater anti-anginal action although sotalol, unlike practolol, was more effective than low dose propranolol. The use of beta-blocking agents in angina pectoris is relatively safe provided that the contraindications of asthma and cardiac insufficiency are observed and that treatment is commenced at a low dosage. The most dramatic change in the sympathetic environment of the heart takes place when treatment with a beta-blocking drug is commenced. The greatest danger of precipitating heart failure is therefore at the beginning of treatment even with a small starting dose. Once treatment has begun even an increase of 25% per dose represents a small pharmacological increment as there is no great change in the sympathetic drive to the heart. The larger dosage of beta-blocking drugs required for optimum treatment of angina may be gradually approached, but it has been my experience that heart failure is not likely to be precipitated at larger doses, provided they are not used initially. In other than mild angina pectoris the average optimum dosage of propranolol is 500-800 mg a day, similar, or perhaps more than the average dose in hypertension.


Haemodynamic effects of propranolol in hypertension: a review.

Like hypertension which is a multifactorial disease, the blood pressure response to propranolol cannot be explained by one mechanism alone to the exclusion of all others. Acute (intravenous) administration of propranolol lowers cardiac output and slows heart rate but does not significantly alter blood pressure. With continued therapy however, blood pressure (in responders) is gradually reduced while cardiac output and rate remains low, indicating a readaptation of total peripheral resistance (TPR) to the new haemodynamic conditions. This relatively complex interplay of factors and the predominant role of TPR in blood pressure response help explain why haemodynamic indices (such as elevated heart rate and cardiac output) were found of little value in predicting response to therapy and the failure of propranolol to control transient pressor responses associated with stress; although the increase of output in response to stress was blocked pressure rose due to increase in TPR. Therefore, despite the obvious cardiac effects of beta-adrenergic blockade, a blood pressure response to propranolol cannot be used as an index of cardiac participation in that hypertension. The long-term changes in TPR were significantly (P less than 0-02) correlated with reduction in plasma renin activity (PRA). This association does not necessarily imply a causal relationship since PRA suppression occurs at lower doses and much more rapidly than alterations in blood pressure. Further, the hypotensive effect obtained by adding propranolol to diuretic therapy was not associated with a significant reduction in PRA. However, the absence of correlation in a group of patients between blood pressure response to propranolol and its effect on other biological variables does not mean that these variables have no role in the hypotensive response. In fact, in some specific conditions the change in one variable might assume particular importance; thus in the markedly hyperkinetic circulation induced by potent vasodilators, reducing cardiac rate and output may play a major role in controlling persistent hypertension.


Propranolol in the treatment of alchoholism: a review.

In the withdrawal phase of chronic alcoholism, hyperkinetic circulation, characterized by increased cardiac output, is the rule. Even in alcoholics who have been sober for a long time, increased cardiac output is very common and these changes are similar to those seen in some patients with labile hypertension. This could be caused by psychic tension. In the withdrawal phase propranolol was found to normalize the circulation and to reverse the decreased peripheral vascular resistance. We observed that the patients seemed to be calm after 40 mg of propranolol by mouth. In a double blind study of propranolol and placebo this effect was confirmed and in another study 120 mg of propranolol a day was compared to 30 mg of diazepam a day (double-blind, crossover). Using different psychological methods all significant differences are in favour of propranolol. The findings are in agreement with other reports. It is our clinical impression that propranolol is a useful drug for psychic tension symptoms in chronic alcoholism. Very few side effects have been found.


Propranolol in the treatment of anxiety.

Since 1964, of 725 patients presenting with anxiety syndromes, 513 were treated with propranolol for periods of several days to over 10 years, some intermittently, others virtually without interruption. Of these, 237 had previously received or were receiving psychotropic drugs, mostly benzodiazepines and/or phenothiazines, which had proved ineffective or deleterious. Dosage was adjusted to achieve an optimum clinical response and a relatively high degree of beta-blockade, as judged by the virtual abolition of orthostatic and hyperventilatory tachycardia. As a rule, 80-320 mg daily sufficed, but increments up to 1200 mg were temporarily required to control bizarre or unusually intense symptoms. With few exceptions, the somatic and psychic symptoms were relieved or moderated and overall functional capacity was restored. Depression, evident in 50% of the patients, usually lifted, but persisted in one-third as a lone symptom responsive to antidepressants. Propranolol requirements usually diminished and lasting remissions were not infrequent. The effects of propranolol contrasted sharply with those experienced by the patients receiving tranquillizers. Single-blind placebo trials involving 76 cases endorsed the specificity of the response to beta-blockade. This long term study reveals that effective control of the somatic and psychic symptoms of anxiety can be achieved with propranolol in appropriate dosage.


Treatment of migraine with propranolol.

Thirty patients suffering from intractable, repetitive migraine took part in a double-blind single-crossover trial to compare the effect of propranolol (at 120 mg per day) with that of placebo. During propranolol treatment the frequency of migraine attacks was reduced significantly, by more that 50% in 9 patients and by less that 50% in a further 9. In the remainder propranlol showed no advantage over placebo. It is concluded that, as propranolol has only few and mild side effects, it is a useful drug for preventing migraine attacks. As the pathogenesis of migraine is not completely understood, the mode of action of propranolol in preventing attacks cannot be fully explained. It has been possible, however, to relate some of the effects of beta-receptor antagonism to current knowledge of the condition.


Irritable colon syndrome treated with an antispasmodic drug.

It was concluded that the trial had demonstrated therapeutic effects from dicyclomine in comparison with the placebo. Thus, the differences recorded, some of which were statistically significant, were all in favour of the active drug, despite the fact that a carry-over effect was apparent in the patients treated with dicyclomine first.


[Serratia marcescens infection in intensive care units (author's transl)].

The increased incidence of Serratia marcescens infection at the intensive care unit of the Department of Anaesthetics, General Hospital Altona, was investigated. The properties of this microorganism are described and its role in cross infections is discussed. The frequent occurrence of Serratia marcescens in mixed infections and its tendency to grow on tissue surfaces are pointed out. The presence of Serratia marcescens was demonstrated in 23 of 107 patients treated in the intensive care unit; an infection with Serratia was established in 13 of the 23 cases. Four patients died. As vital functions were severely impaired in these cases death could not be attributed solely to the Serratia infection. Preventive and therapeutic measures are reviewed.


[Haemodynamic studies during anaesthesia with etomidate and neflurance in ge-iatric patients].

The influence of combined anaesthesia with enflurance and etomidate on the haemodynamics of the main and pulmonary vasculary systems was studied in geriatric patients. The results showed a decrease in cardiac output with consecutiv fall of the mean arterial pressure and a significant increase in mean pulmonary arterial pressure. According to our experiences there are less complications in cardiac andpulmonary system, when enflurance is combined with etomidate.


[Premedication with doxepin (author's transl)].

The effects of doxepin on the circulation and its anxiety relieving properties were studied in 67 patients who were premedicated with this drug before surgical operations. The findings showed that doxepin is very suitable for premedication on account of its sedative, tranquilizing and analgesic properties. It also reduced secretion of mucus and saliva. In a few cases it caused mild orthostatic circulatory dysregulation. The drug was well tolerated and has proved its value for routine administration.


Improved procedures for the purification of selected vitamin K-dependent proteins.

Improved methods are described to obtain bovine prothrombin, Factor IX, Protein C, and autoprothrombin III (Factor X, Auto-III) in purified form. The prothrombin had a specific activity of 4,340 Iowa units/mg. Theoretically, a preparation of clean thrombin should have a specific activity of 8,200 U/mg, because 47.08% of the protein in prothrombin is lost when thrombin forms. Such thrombin preparations have been obtained (Arch. Biochem. Biophys. 121, 372 (1967)). The prothrombin concentration of bovine plasma is near 60 mg/liter. Protein C, first isolated by Stenflo (J. Biol. Chem. 251, 355 (1976)), was found to be the precursor of autoprothrombin II-A (Auto-II-A), discovered earlier (Thromb. Diath. Haemorrh. 5, 218 (1960)). Protein C (Factor XIV) was converted to Auto-II-A (Factor XIVa) by thrombin. Digesting purified Auto-III with purified thrombin removed a small glycopeptide from the COOH-terminal end of the heavy chain to yield Auto-IIIm. Auto-III thrombin leads to Auto-IIIm + peptide. Auto-IIIm was not converted to the active enzyme with thromboplastin, and furthermore, inhibited the activation of purified native Auto-III with thromboplastin. Auto-IIIm was also not converted to the active enzymes when the procoagulants consisted of purified Factor VIII, purified Factor IXa, platelet factor 3 and calcium ions. The "activation peptide" released by RVV-X from the NH2-terminal end of the heavy chain and the active enzyme (Auto-Cm) were purified. Auto-III was also activated with purified RVV-X. The same "actid of Auto-Cm. Purified Factor IX developed anticoagulant activity when reacted with an optimum concentration of purified thrombin. A suitable reagent for the assay of Factor IX was prepared by removing prothrombin complex from anticoagulated bovine plasma and restoring the prothrombin and Auto-III concentration with use of the respective purified proenzymes.


Stereochemistry of polymerization by DNA-dependent RNA-polymerase from Escherichia coli: an investigation with a diastereomeric ATP-analogue.

The phosphodiester bond formation by DNA-dependent RNA-polymerase (RNA nucleotidyltransferase, nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) can in principle result in retention, inversion, or racemization of configuration at the alpha-phosphorus of the nucleoside 5'-triphosphate being polymerized. As a first step in elucidating the stereochemistry of this reaction, one diastereomer (A) of adenosine 5'-O-(1-thiotriphosphate) (ATPalphaS) was polymerized with UTP in the presence of poly(dA-dT)-poly(dA-dT). The resulting polymer was enzymatically cleaved to uridine 2',3'-cyclic phosphorothioate which was determined to be the endo-isomer by comparison with an authentic sample. This shows that no reacemization had occurred and that isomer A of ATPalphaS gives a phosphorothioate diester bond with the R-configuration. Whether this represents inversion of retention of configuration awaits elucidation of the absolute configuration of isomer A for ATPalphaS.


On the mechanism of genetic recombination: electron microscopic observation of recombination intermediates.

This paper deals with the nature of recombination intermediates. Using the electron microscope to study the DNA of the plasmid colicin E1, we have observed more than 800 molecules that appear to represent intermediates in the process of recombination. Specifically, after isolating colicin DNA and linearizing it with the restriction enzyme EcoRI, we find crossed molecules with twice the normal colicin DNA content. These forms consist of two genome-length elements held together at a region of DNA homology. The molecules can be recovered from wild type and Rec B-C host cells but are not present among the colicin DNA forms isolated from recombination-deficient Rec A cells. We have termed the experimentally observed molecules "chi forms" and believe that they represent the recombination intermediate of the Holliday model.


Circular DNA of a yeast episome with two inverted repeats: structural analysis by a restriction enzyme and electron microscopy.

Small circular DNA molecules from genetically characterized clones of Saccharomyces cerevisiae have been studied by restriction endonuclease analysis and electron microscopy. The circular monomers (6000 bases) are shown to contain two inverted repeats of the same sequence (600 bases) situated opposite each other along the perimeter. Four endonuclease EcoRI fragments are obtained in 1:1:1:1 stoichiometry, and their sum gives a length of about 12,000 bases. The two large fragments and the two small ones differ from each other by 200 bases. We propose a model for the structure of the monomer molecule. Two classes of monomers can be generated by intramolecular recombinations within inverted repeats; they differ by the relative orientation of nonrepeated segments. The structure of dimers as predicted by the model is verified by self-renaturation of single-stranded circles. Inverted repeats in circular molecules may be related to the insertion release faculty of II episome in the chromosomes.


Specific binding of formylated initiator-tRNA to Escherichia coli RNA polymerase.

E. coli fMet-tRNAfMEet and E. coli RNA plymerase (RNA nucleotidyltransferase; EC 2.7.7.6; nucleoside-triphosphate:RNA nucleotidyltransferase) form a 1:1 complex with an apparent association constant of 9.0 X 10(6)M-1 at 37 degrees. The affinity of polymerase to tRNA depends on the tRNA as well as the formyl methionine moiety. Core polymerase has a greatly reduced affinity for initiator tRNA. Optimal binding conditions are similar to those that are also optimal for binding initiator tRNA to ribosomes. Binding of initiator tRNA to polymerase stimulates the transcription of lambda plac DNA, as determined in a crude cell-free system for beta-galactosidase (EC 3.2.1.23; beta-D-galactoside galactohydrolase) synthesis as well as in a highly purified transcription system.


Isolation of a set of hybrid lac repressors made in vitro between normal lac repressor and its homogeneous tryptic core.

Lactose repressor can be renatured from 8 M guanidine-HCl solution. The renatured repressor is tetrameric and shows DNA binding activity. Thus it becomes possible to obtain hybrid tetramers in vitro between normal repressor and repressor defective in DNA binding by simultaneous denaturation and renaturation. In order to facilitate the separation of the different hybrids, we have used a lac repressor derivative that does not bind DNA, which is missing the amino-terminal 59 residues of the polypeptide chain (homogeneous tryptic core). The hybrids resulting from the mixed renaturation of homogeneous tryptic core and normal repressor can be separated by electrophoresis on Cellogel. The hybrids have been recovered, and a preliminary characterization of their DNA-binding properties is reported.


The identification of the mot gene product with Escherichia coli-lambda hybrids.

Molecular cloning techniques were used to construct lambda-E. coli hybrid bacteriophage carrying genes involved in bacterial flagellar motility (mot) and chemotaxis (cheA). A series of hybrid bacteriophage without each of these genes was also prepared. When paralyzed mutants of E. coli were infected with lambda that carried the mot gene, the ability of the bacterium to swim was rapidly restored. The restoration of motility was the result of the synthesis and insertion into the cell membrane of a protein with an apparent molecular weight of 31,000 (the Mot protein). Another polypeptide with a mobility on acrylamide gel electrophoresis which corresponded to a molecular weight of 39,000 was associated with the cheA gene. The presence of this polypeptide alone was not sufficient to restore chemotactic activity to mutant cheA strains. It was suggested that only a portion of the cheA gene was cloned, and thus the 39,000 protein may be a partial product of the cheA gene, or the product of a second mot gene.


DNA dependent synthesis of protein L12 from escherichia coli ribosomes, in vitro.

The in vitro synthesis of ribosomal protein L12 has been obtained in a coupled system with DNA extracted from the transducing phage lambdarifd18 as template. In addition, a second protein (molecular weight of 16,000) with immunological, chemical, and ribosome-binding characteristics similar to L12 is formed in this in vitro system. The synthesis of both proteins is depressed by one-half when guanosine-5'-diphosphate-3'-diphosphate is added to the reaction mixture.


Localization of vasoactive intestinal polypeptide (VIP) to central and peripheral neurons.

The localization of the vasoactive intestinal polypeptide (VIP) has been studied with immunohistochemistry and radioimmunoanalysis. VIP immunoreactivity is present in gastrointestinal nerves, which constitute a quantitatively important nerve population that may be intrinsic to the gut wall. VIP-immunoreactive neurons are also found within the ventromedial hypothalamus and give off processes that travel latteral to the third ventricle. Results of radioimmunoanalysis strongly indicate that the immunoreactive material represents true VIP. Thus VIP, at present a gastrointestinal hormone candidate, appears to represent a new neuronal peptide occurring in both the central and peripheral nervous system.


Localization of the neurofilament protein in neuroblastoma cells by immunofluorescent staining.

Neurofilament protein (54,000-56,000 daltons) has been localized in murine neuroblastoma cells by indirect immunofluorescent staining with antisera to purified calf brain neurofilament protein. In some cells with only short processes, specific staining of fibrous material was present in the perinuclear region while in other cells similar fibers, coiled to varying degrees, were present in other regions of the cytoplasm. In cells with longer processes a stained fiber extended throughout each process. The staining pattern observed followed the distribution of bundles of 100 A filaments as determined by electron microscopy. The fibers did not stain with antisera to tubulin or tropomyosin. The observations reported strongly indicate (i) that neurofilament protein isolated from calf brain is antigenically related to a component of the bundles of 100 A filaments in neuroblastoma cells, and (ii) that the neurofilament protein is an integral part of bundles of 100 A filaments in neuroblastoma cells, while neither tubulin nor tropomyosin is present in these bundles.


Specialized transduction of colicin E1 DNA in Escherichia coli K-12.

Genetic studies were made on E. coli K-12 TM96, which carries recombinant molecules constructed by in vitro combination of colicin E1 DNA and a DNA fragment of E. coli for guanine synthesis derived from transducing phage. The recombinant molecules existed as stable plasmids within the cell and contained genes for colicin E1 immunity and the guaA enzyme (xanthosine 5'-monophosphate aminase) together with a part of the lambda genome, R through J: (R-A-F-J)+. A block of the lambda genome, int through Q, was not detected in the recombinant molecule. Thus, this recombinant molecule was named ColEl-coslambda-guaA, and the specialized tranduction of the ColEl-coslambda-guA DNA into various E. coli K-12 cells by lambda phage was described. Lysates prepared by lytic infection of lambda phage onto TM96 or by induction of TM96(lambda) lysogens contained transducing particles which could transduce gua-deleted E. coli to stable guaA+ cells. These transductants were proved to have similar genetic properties as those of TM96. The frequency of transduction was not affected by the presence of an attachement site for lambda, prophage lambda, colicin E1 plasmids, or the recA property within gua-deleted recipient cells. Transducing particles were resistant to EDTA treatment and most of them had an average density of about 1.472. This value corresponds to that of lambda phage particles, which contain about 72% of the lenght of lambda DNA.


Growth of transplanted tails of infant rats in adolescent allogeneic recipients.

The tails of newborn rats, consisting of slender continuous cones of avascular cartilage, were transplanted in subcutaneous spaces of allogeneic adolescents; colloidal carbon was injected in a vein before the transplants were harvested on days 7-28. Between 97 and 100% of the transplants were accepted, underwent differentiation into bone with bone marrow, and grew at a brisk rate. Acceptance was recognized by (i) a zebra-stripe effect, visible in the gross, resulting from accumulation of carbon in reticuloendothelial cells; (ii) increase of alkaline phosphatase [or-thophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] and of incorporated 45Ca in the transplant; and (iii) the presence of dense cortical bone with lacunae populated with osteocytes demonstrable by histology. Differentiation of the cartilaginous transplant into bone with subsequent growth of the transplant occurred in recipients fed sucrose as their sole ration.


The hydrolysis of biologically active peptides by bovine lung tissue factor (thromboplastin).

Tissue factor apoprotein and relipidated tissue factor preparations extensively hydrolyze bradykinin, Lys-bradykinin, Met-Lys-bradykinin, substance P, [Asp1, Ile5]-angiotensin II, [Asp1, Ile5]-angiotensin I, and human fibrinopeptide A while acting more slowly on [Sar1, Ile5]-angiotensin II, [Me2Gly1, Ile5]-angiotensin II, bradykinin potentiating pentapeptide from B. jararaca, luteinizing hormone-releasing hormone, melanocyte stimulating hormone-release-inhibiting factor (Pro-Leu-Gly-NH2), and oxytocin. No hydrolysis of thyrotropin-releasing factor or bradykinin potentiating nonapeptide from B. jararaca is observed. Relipidated and apoprotein tissue factor act at identical rates under the conditions of the assay. Dansylation and chromatography of tissue factor-peptide incubation mixtures further indicate that relipidated and apoprotein tissue factor also hydrolyze peptides by identical mechanisms. No fewer than six bonds are hydrolyzed in bradykinin while the angiotensins and substance P are degraded to constituent amino acids. Only the N-terminal alanine is released from fibrinopeptide A. 2-Mercaptoethanol greatly inhibits the hydrolysis of bradykinin by relipidated tissue factor.


Noxiptilin (Agedal)--a new tricyclic antidepressant with a faster onset of action? A double-blind, multicentre comparison with amitriptyline.

Five psychiatric hospitals in Norway took part in this double blind clinical trial, in which noxiptilin (Agedal) was compared with amitriptyline in hospitalized patients with primary depressive illness. According to total randomization, each patient received either noxiptilin or amitriptyline in semiflexible dosage, usually to a maximum dialy dose of 200-250 mg, for at least three, and possibly six weeks. Thirty patients received noxiptilin and 32 received amitriptyline for at least three weeks. The "total" improvement was assessed in two different ways: 1) By direct global assessment; according to this method, there was a non-significant tendency towards greater improvement on amitriptyline after three and sex weeks, in female and male patients alike. 2) By percentage reduction in total score on Hamilton's rating scale for depression; according to this method, there was a significantly greater improvement on noxiptilin after one week in female but not in male patients. After 2, 3 and 6 weeks there were no significant differences. Thus, this trial seems to support earlier claims that noxiptilin has a faster onset of action than amitriptyline. The two drugs did not differ significantly in their effect on any single symptom, nor in their effect on different types of depression. Both drugs had a better effect in patients with duration of present illness less than three months, than in patients with a duration longer than three months. Noxiptilin had a significantly better effect than amitriptyline in patients with insidious onset of present illness, whereas there was a strong (but non-significant) tendency for a better effect of amitriptyline in patients with a more acute onset of illness. No satisfactory explanation can be offered for this unexpected finding.


[The assessment of neuroleptogenic extrapyramidal syndroms in psychopharmacological research (author's transl)].

Methodological questions of clinical observation and classification of drug-induced extrapyramidal symptomatology are discussed. In our experimental approach we examined two groups of 20 acute schizophrenic patients each. The patients were treated for 4 weeks under double-blind conditions with the butyrophenone derivative Haloperidol and with the benzoxazepine derivative Loxapin respectively. The extrapyramidal disturbances appearing under these medications were studied. The patients were examined by means of the EPS-scale by Simpson and Angus weekly, before, during and after this treatment as well as under a subsequent therapy with a longacting neuroleptic. Extrapyramidal disturbances appearing between these fixed rating times were noted in a check list. According to a classification propased by Chien and Di-Mascio the symptomatology of extrapyramidal disturbances under neuroleptic therapy can be divided into "permanent neuroleptic manifestations" on the one hand and "paroxysmal neurodysleptic manifestations" on the other. While Haloperidol caused more distinct symptoms of permanent neuroleptic manifestations, acute neurodysleptic reactions appeared more frequently under Loxapin therapy.


Effect of lithium on neuroleptic-induced tardive dyskinesia compared with placebo in a double-blind cross-over trial.

15 hospitalized patients suffering from neuroleptic-induced tardive dyskinesias participated in a double-blind cross-over study of lithium sulphate and placebo. Each drug was given for 3 weeks. The results were evaluated by means of the video-tape technique. Lithium sulphate induced a slight, but significant reduction in the tardive dyskinesia. Lithium had, in addition, a suppressive effect on psychomotor agitation and aggression. The concentrations of homovanillic acid and 5-hydroxyindoleacetic acid were determined in the cerebro-spinal fluid from five patients. It is concluded that lithium can be used with advantage in the treatment of tardive dyskinesia with only moderate intensity, particularly when the movement disturbances are accompanied by psychomotor restlessness. Finally, the effect of lithium on the central aminergic transmitter substances is discussed in relation to the existing hypotheses on the pathophysiology of tardive dyskinesia.


[The significance of standardized evaluation scales in psychiatric diagnosis as exemplified by the therapeutic intervention with desmethyl-loxapine (author's transl)].

Taking into account the particular problems of psychiatric classification the advantages and disadvantages of standardised rating scales are discussed. The authors come to the conclusion that these instruments at present are irreplaceable in psychopathological research because of their reliability in transmitting information and the possibility of quantifying psychopathological syndromes. The use of four rating scales which are little known yet within German speaking countries in demonstrated by means of a psychopharmacological investigation on the clinical effects of Desmethyl-Loxapine. These rating scales are: 1. the Hamilton-Psychiatric-Rating-Scale for Depression 2. the Wittenborn-Psychiatric-Rating-Scale 3. the Structured Clinical Interview (Burdock and Hardesty) and 4. the Befindlichkeits-Skala (Condition-Scale). Desmethyl-Loxapine was given in an open study as an antidepressant to 16 patients with different depressive syndromes. The results of treatment which lasted 3 to 4 weeks are discussed. The good therapeutic efficacy of Desmethyl-Loxapine was mainly due to its marked anxiolytic effect. All accomplished clinical examinations showed an excellent tolerance of this drug.


[Pilot study of 2-pyrrolidon-acetamid (generic name: piracetam) (author's transl)].

Ten chronic schizophrenics were tested by clinical observations, psychological tests (FPI, LEV, d 2) and ratings with the Wittenborn-Psychiatric-Ratings-Scales (WPRS) before and after taking 2-pyrrolidon-acetamid. The improvement of obstructive, apathy, withdrawal and affective flatness in seven patients justify a double-blind psychometric evaluation concerning the effect of Piracetam on the schizophrenic deficiency states.


Numerical analysis of cardiopulmonary blood volumes in 113In(m) radiocardiography.

A theory of streamline flow of a viscous liquid was applied to the calculation of cardiac and pulmonary parameters (minute volume, stroke volume, right heart, pulmonary and left heart blood volumes) in a radiocardiographic model based on the modified gamma function. The practical feasibility of the formulations was tested using a physical flow model. The cardiopulmonary blood volumes measured from 14 normal subjects were consistent with the results obtained by more complex techniques. The present method is manageable on a small computer and is well suited to clinical routine use in connection with standard single detector 113In(m) radiocardiography.


Diagnostic radiology of the colon and rectum. Review of the European radiological literature.

European radiological literature of the year 1975 reviewed, concerning colon diseases. Subjects like colon preparation, appendicitis, lymphoid hyperplasia, juvenile polyposis, villous adenomata, angiography in bleeding diverticulosis and lymphomata of the colon have been described in that year. Most attention is paid to the colon with oral laxatives and without enemas.


Renal prostaglandins for induction of labour-a dual clinical advantage in toxemia of pregnancy.

Prostaglandin A is known to be an  antihypertensive vasodepressor agent produced by the kidney and has the basic potentialities of a hormone. No information is available at present concerning its effect on the human pregnant uterus and whether it can be used as an oxytocic compound to induce labour. The uterine stimulating and labour inducing ability of PGA1 was evaluated in 10 cases; seven patients were suffering from pregnancy toxemia while three were normal pregnancies near full term. Cardiotocographic tracings showed that uterine activity was markedly stimulated to a degree sufficient to induce labour. Continuous i.v. infusions at a rate of 0.25-1.0 mug/Kgm/min given over a fixed period of only 6 hours resulted in delivery in all cases except one following the discontinuation of administration. Beneficial effects on blood pressure were observed in toxemic subjects. Potentially serious FHR patterns and occasional hypertonus during therapy were seen and stress the need for more information to evaluate the safety, optimum dosage and duration of infusion as well as the place of this approach in clinical practice for the management of pregnancy toxemia. The absence of antidiuretic effect, the hypotensive response and uterine stimulating property of PGA1 indicate a possible advantage in toxemia of pregnancy as compared to oxytocin infusions.


Prevention of hyaline membrane disease with plasminogen. Preliminary report of a cooperative study.

Five hundred premature infants were treated in a double blind, randomized study with intravenous plasminogen or placebo within 60 minutes of birth. There was a significant decrease in severe clinical respiratory distress, death due to hyaline membrane disease and total mortality in the plasminogen treated infants as compared to the controls.


Experimental infection of the bovine udder with the induced L phase of Streptococcus agalactiae.

Two out of 30 strains of Streptococcus agalactiae produced stable L phase variants when passaged on hypertonic agar containing penicillin. Streptococcal L phase variants were inoculated into six quarters of cows. The cows were observed for three months but the L phase was not reisolated and no reversion took place, the cows remaining free from streptococcal infection.


[Preparation and biological trials of antimalarial sulfa embonates].

With the purpose of obtaining salts of sulfonamides with low toxicity but prolonged action, embonates of seven known sulfonamides, with antimalarila activity, were prepared by double exchange reaction between embonic acid and the antimalarial agents. Six of the seven embonates prepared showed activity against Plasmodium berghei in experimentally infected mice, one of them being significantly more active than the original sulfonamide (sulfadimethoxine).


[Study of isolated nerve fibers in primary hypertrophic neuritis].

This report describes pathological changes of myelin, cells and axons of teased nerve fibers from three cases (two having a family history) of primary hypertrophic neuritis with onion bulb formations seen in aptic and electron microscopy. Segmental demyelination and subsequent remyelination occurred in most myelinated fibers isolated. Besides this classical pattern, in some fibers large pseudo-wallerian ovoids of myelin with preservation of the axon, demonstrated by silver counterstaining, were found. This pseudo-wallerian degeneration is thus a primary demyelination and axonal degeneration remains a rare finding. A quantitative evaluation of the different patterns of myelin degeneration has been established. The study of cellular proliferation has shown clustering of nuclei scattered along the fiber. In some fibers the changes of the myelin sheath are encountered without Schwann-cell accummulation, while in others cellular proliferation is prominent without obvious myelin abnormalities. Cellular proliferation has also been seen in unmyelinated fibers (Remak fibers). In some neural tubes devoid of axis cylinders striking Schwann-cell accumulation remains, giving may in some places to fusiform enlargement of the "Schwann-cell tube". These "Schwann-cell tubes" appear as one of the late stage changes occuring in hypertrophic neuritis.


[Quantitative and qualitative study of ABH antigens of cis AB blood group].

Fourteen cis AB blood samples belonging to 6 families from Belgium, France, Japan and Germany were studied with quantitative agglutination and fixation assay. Results showed that ABH antigens of cis AB erythrocytes significantly differ from "trans" AB controls: the H amount is higher than in trans AB and similar to that of A2 controls; the A amount is similar to that of A2 cells; the number of A sites per cell as measured with a 125-I labelled IgG anti-A from a rabbit ranges from 170 000 to 580 000 in cis AB samples; the A1 reactivity seems to be related to the A antigen density of erythrocytes more than to a specific A1 antigen; the B reactivity is quite normal with immune anti-B sera but weak with naturally-occurring anti-B from A individuals. The reaction of B antigen of cis AB cells with a naturally-occurring anti-B from an A1O person exhibits a weaker enthalpy change than in trans AB cells. Most cis AB sera have anti-B activity, essentially at 4 degrees C. In saliva A and H substances are found in normal amounts but B substance is only evidenced by inhibition of autologous cells agglutination. Data obtained from this study do not favour any proposed hypothesis to explain the cis AB gene formation (crossing-over between A and B genes or A gene mutation).


[I antigenicity of the Bombay red cells].

Different homogeneous IgM cold agglutinins have been used to determine the antigen site density of Oh and OHm erythrocytes in comparison with O (H). The equilibrium constants and the delta Ho and delta S o have been measured. When H antigen is absent on the O red blood cells, there is no apparition of new I and i antigenic sites. Competition between gene products converting i into I and Hh genes for a common precursor substance appears unlikely. Nevertheless, the affinity of all antibodies tested increases with Oh and OHm cells and the thermodynamic parameters are accordingly modified. These results could be explained by: either a lesser steric hindrance in the absence of H antigen, the I determinants that are normally hidden by H antigen become more accessible, or by a modification of the molecular environment, as the interaction between fucosyl and N-acetyl residue of the penultimate sugar on the basic oligo-saccharidic chain is abolished. The structure of some I determinants may be modified, particularly of those which include the beta-D-Glu-NAc. Another explanation for these peculiar reactivities could be the substitution on the Bombay cells of this fucose by a neuraminyl residue. In the Sch. siblings, a heterozygous Hh subject was evidenced. His thermodynamic characteristics are nearing those of the hh propositus; the hypothesis of a competition between fucosyl and neuraminyltransferases for the same substrate is then proposed.


[Polyagglutinability due to Hempas antigen].

A new antigen has been recently discoverd in patients with congenital dyserythropoietic anemia type II. The acronyme Hempas was proposed for this disease as a remind of the main morphological feature of erythroblasts (hereditary erythroblastic multinuclearity) and the characteristic serological findings (positive acidified serum test). The patients red cells are agglutinated and lysed by an IgM cold reacting antibody present in the serum of most normal subjects and not previously recognized. This behaviour is thus reminding of cells carrying antigens such as T, Tn, Cad or acquired B. As for T and Tn cells, sialic acid and electrophoretic mobility are reduced, but in contrast, agglutinability of Hempas cells is enhanced by enzyme treatment. Agglutination by anti H and anti Pr specific reagents is reduced. I and mainly i activity are strongly increased. The relationship between the membrane abnormalities of Hempas red cells and the failure of normoblasts to divide their cytoplasm i still largely unknown.


[Current evaluation of the classical Werner test and its correlation with current in vitro E.T.R. technics].

The authors evaluated the current standing of the classical 131I uptake test, together with its subsidiary stimulation and suppression tests, and its correlation to clinical diagnosis and the in vitro ETR (Effective Thyroxine Ratio) technique. In the 349 cases studied, a good correlation was found between the previous diagnosis--made by means of 131I uptake test--and the clinics and symptomatology, and very particularly, the in vitro ETR test. The authors conclude that the combination of both tests is sufficiently reliable for the diagnosis of thyroid dysfunction.


Dapsone in rheumatoid arthritis.

After a preliminary period of observation, 71 patients with consistently active rheumatoid arthritis (RA) were given dapsone 50 mg daily for one week, then 100 mg daily. There was a significant improvement in subjective clinical state and there were significant falls in serum C-reactive protein (CRP) and the ESR; the Rose-Waaler titre (RW) did not fall. The results were compared with those in 78 patients who had gold. Subjective clinical improvement was slower with gold, but from six weeks the pattern of changes in clinical score, CRP and ESR was similar for both drugs. The RW fell during gold treatment. The results suggest dapsone is effective in RA; over-all it appears to be slightly less effective than gold but much less toxic.


[Mutagenic activity of pesticides (author's transl)].

The mutagenicity of sixty pesticides was investigated in three strains of Saccharomyces cerevisiae using reversion from histidine and methionine auxotrophy as a measure of the induced mutation. Mutagenesis was observed in twenty three compounds; the strains employed exhibit different susceptibility to the mutagenic action. In view of the data obtained the possible mechanisms of action of the different class of compounds are discussed.


Mild stimulation of serum immunoreactive insulin (IRI) release following large doses of intravenously given glycine to children of normal pituitary function.

In healthy, sexually immature children of both sexes serum IRI levels rose more than expected from random inter-individual variation (i.e. more than 3 standard deviations of the basal level) in 10 out of 21 subjects loaded by glycine. The IRI release by glycine though moderate and not constant is, however, unquestionable. The growth hormone (GH) secretory response to glycine did not change according to the occurrence and/or magnitude of IRI release. It was concluded that GH and IRI stimulatory properties of glycine given intravenously in large doses are completely unrelated.


Nonsecretory myelomatosis without intracellular immunoglobulin. Immunofluorescent and ultramicroscopic studies.

A patient with multiple myeloma is reported with severe hypogammaglobulinaemia but without monoclonal immunoglobulin (M-component) in the serum or Bence Jones protein in the urine. In May-Grünwald-Giemsa stained bone marrow film 45% of the cells resembled plasma cells. Marrow immunofluorescent studies showed no increase of immunoglobulin containing cells. Ultrastructural studies showed a large number of cells with a well developed rough endoplasmic reticulum and other morphological features characteristic for plasma cells.


Microbiological aspects on peritonsillar abscesses.

In 37 patients with unilateral quinsy put was collected with a syringe technique and bacteriologically examined. Beta-hemolytic streptococci were isolated from 17 abscesses; in 8 of these, however, together with other bacteria, mainly anaerobes. Anaerobic bacteria, often more than one species, were found in 28 abscesses. Streptococcal serology including AST-O, Streptozyme and separate ADNAse test showed high titres or titre rises in 22 out of 30 examined cases. There was one case with beta-hemolytic streptococci in the abscess but negative serology. In the remaining cases a possible primary etiological role of anaerobes is suggested. The effect of combined surgical drainage and treatment with antibiotics (ampicillin or penicillin V) was good.


Streptococcal types in impetigo and acute glomerulonephritis among children in Addis Ababa.

Studies on the streptococcal epidemiology  of impetigo in children below 12 years of age in Addis Ababa indicated that most streptococci isolated belonged to the classic serological impetigo strains. Streptococcal type 9 seemed to be a new impetigo strain. Several cases of severe acute glomerulonephritis on impetigo basis were observed during the study.


Vaccination against meningococcal group A disease in Finland 1974-75.

Meningococcal group A polysaccharide vaccine was used in children 3 months to 5 years of age in the winter 1974-75 during an epidemic caused by sulphanamide-resistant group A meningococci. In 3 provinces, the vaccine was offered on a double-blind basis, using Haemophilus influenzae type b polysaccaride vaccine as control. Approximately 100 000 children were vaccinated with either one of the vaccines. In the Kymi province, approximately 22 000 children representing 90% of the child population of this age received the meningococcus vacine. Infants below 18 months received a booster dose of vaccine 3 months after the first dose. The meningococcus vaccine caused local symptoms in 71%, mild systemic reactions in 37%, and high fever (38.5 degrees C or more) in 1.8% The haemophilus vaccine produced fewer side effects. No clinical infections caused by group A meningococci were reported in the first 6 months after vaccination among those who had received the meningococcal vaccine. At the same time, group A cases continued to appear in other age groups and other areas of the country.


Yersinia enterocolitica infection in patients with acute surgical abdominal disease. A prospective study.

The rate of yersiniosis in patients with acute abdominal disease was studied in a 16-month prospective investigation in 1972-1973 of 205 acutely ill patients referred to a surgical clinic of a Copenhagen City hospital with complaints of abdominal pain suggestive of appendicitis. Yersinia enterocolitica, biotype 4, was isolated from 11 patients (5.4%), 8 of whom were children. Yersinia was grown from faeces in 8 cases and from appendix of all 9 patients operated upon. Rising or falling agglutinin titres larger than or equal to 100, indicative of yersiniosis, were found in 22 patients (10.7%) including all bacteriologically verified cases. Eight additional patients (3.9%) had less significant titres larger than or equal to 100, suggestive of recent or present infection. 28 patients (13.7%) had insignificant titres, including 3 with antibodies against serotype 9. In all cases except these 3, antibodies were against Y. enterocolitica, serotype 3. A differential diagnosis between Y. enterocolitica infection and other types of appendicitis could not be made within this highly selected group of patients using available clinical data. All cases were rather mild and self-limiting. It is suggested that in future epidemiological and other studies of yersiniosis, early bacteriological and serological examinations be carried out.


A NEW Escherichia coli O-group, O159, associated with outbreaks of enteritis in infants.

An outbreak of enteritis occurred amongst babies in a nursery unit. 25 babies were affected and 5 required intravenous therapy; there were not fatalities. From 24 of the 25 babies affected, an Escherichia coli with a previously undescribed O-antigen was isolated. An outbreak of diarrhoea had taken place in the same hospital a year before and re-examiniation of cultures of E. coli isolated at that time showed that 5 of the 15 babies affected had been excreting E. coli with the same O-antigen. Isolates from 10 of the babies were tested for enterotoxin production in the infant mouse model and 4 gave a positive response. The new O-antigen has been accepted into the international serotyping scheme and has been designated E. coli O159.


Streptococcus zooepidemicus (group C streptococci) as a cause of human infection.

Cervical lymphadenitis with high fever and respiratory distress in a 3-year-old boy is reported. Group C streptococci were isolated from the boy's throat and these were identified as Streptococcus zooepidemicus. The patient recovered after treatment with penicillin. Strep. zooepidemicus is extremely rare as a causative organism of human infections. Even symptomless carriers are very rare. Group C streptococci isolated from humans normally belong to the species Strep. equisimilis.


Neonatal osteomyelitis caused by group B streptococci.

A 3-week-old infant with a group B streptococcal osteomyelitis is described. On admission swelling and fluctuation were combined with local erythema in the right ankle joint region. Group B streptococci, type Ib, were isolated both from blood and from the local focus in the ankle. The diagnosis was further confirmed by X-ray examination showing a lytic lesion in the talus. The child was successfully treated with penicillin, initially in combination with kanamycin.


A study on the mutagenic activity of styrene and styrene oxide.

Styrene oxide is multagenic, without metabolic activation, to S. typhimurium strains TA 1535 and TA 100, which have been devised to detect mutagens causing base-pair substitutions. Styrene seems to be mutagenic toward the same strains, but only after metabolic activation. The toxicity of both styrene and styrene oxide make the construction of reliable dose-response curves rather difficult. Diethylmaleate and 3,3,3-trichloropropene oxide enhanced the mutagenicity of styrene oxide in the presence of homogenate; this result indicates the participation of epoxide hydratase and glutathione S-oxide transferase in the metabolism of styrene oxide. These two chemicals did not influence the mutagenic activity of styrene. Styrene glycol and 4-tert-butyl-brenzcatechin were not mutagenic to any of the strains studied. Results show that further, more detailed experimental and, possibly, epidemiologic studies are warranted.


Effect of a short, heavy exposure to lead dust upon blood lead level, erythrocyte delta-aminolevulinic acid dehydratase activity and urinary excretion of lead delta-aminolevulinic acid coproporphyrin. Results of a 6-month follow-up of two male subjects.

During 1 h two healthy volunteers, not earlier exposed occupationally to lead, inhaled about 100 mg of lead as a mixture of lead oxides and lead sulfate. Maximum blood lead (PbB) concentrations of about 0.5 mg/1 and minimum blood cell delta-aminolevulinic acid dehydratase activities (ALAD) (6% of the preexposure values) were observed within 38 h after exposure. PbB and ALAD returned to preexposure levels after about 300 and 150 days. A highly significant correlation between ALAD and PbB was seen even at lead levels in the range 0.1-0.2 mg/1. Delta-aminolevulinic acid, coproporphyrin and lead in the urine (ALAU, CPU, and PbU, respectively) increased. The peak levels occurred after about 15 h for ALAU and CPU and after about 24 h for PbU. There was a very good correlation between log PbU and lin PbB. ALAU increased already at PbB levels of about 0.3 mg/1.


Antibacterial synergism: a proposal for chemotherapeutic potentiation between trimethoprim and sulfamethoxazole.

Sulfamethoxazole and other sulfa drugs are moderately potent inhibitors of Escherichia coli dihydrofolate reductase. They also significantly potentiate the inhibition of this enzyme by trimethoprim. The molecular basis for inhibition potentiation is the simultaneous binding of trimethoprim and sulfa by the enzyme. This potentiation may explain the synergism observed when these drugs are used in antibacterial chemotherapy.


Structural studies on des-pentapeptide (B26-30)-insulin. I. The preparation and properties of des-pentapeptide-insulin.

It has been suggested in our previous reports that the B-chain C-terminal peptide sequence of the insulin molecule plays an important role in the primary biological activity of this hormone. It is interesting, therefore, to study the structure-function relationship of a series of related insulin analogues. An improved method has been used in this paper for the preparation of des-pentapeptide (B26-30)-insulin (DPI) suitable for the growth of single crystals. These crystals possess 88% of the receptor binding activity of insulin and exhibit hormonal activity of 20 I.U. per milligramme in the mouse convulsion test. In the presence of zinc ions, DPI cross-reacts immunologically with insulin antibody.


Anaerobic infections: diagnosis and treatment.

Anaerobic bacteria outnumber aerobic bacteria in normal flora in the oropharynx and gastrointestinal tract. They are important and frequent causes of infection, although they often go unrecognized except in the classic and very distincitve clostridial infections and intoxications-gas gangrene, botulism, and tetanus. Although anaerobic infections often originate close to a muscosal surface where anaerobes are part of the normal flora, they may occur anywhere in the body via direct of hematogenous spread. Clues to diagnosis include a foul-smelling discharge, gas, necrotic tissue, abscess formation, the unique morphology of certain anaerobes on Gram's Stain, and failure to obtain growth on aerobic culture despite the presence of organisms on Gram-stained direct smear. Predisposing conditions include aspiration, vascular insufficiency, trauma, malignancy, and previous antimicrobial therapy. Clinical suspicion requires confirmation of diagnosis by appropriate collecting, transport and culturing of specimens while excluding contamination with anaerobes from the normal flora. Treatment usually requires a combination of surgical and medical measures. Penicillin G is the drug of choice for virtually all anaerobic infections except those caused by Bacteroides fragilis, which require chloramphenicol or clindamycin. Investigational agents also appear promising in the treatment of anaerobic infections.


Serologic diagnosis of syphilis: an update.

Tests used in the serologic diagnosis of syphilis can be divided into two main groups: nontreponemal (reagin) tests and treponemal tests. The most widely used nontreponemal test is the Venereal Disease Research Laboratory (VDRL) slide test, and the standard treponemal test is the manual fluorescent treponemal antibody-absorption (FTA-ABS) test. These tests and other newer tests available for the serologic diagnosis of syphilis are reviewed, with emphasis placed on their current clinical usefulness.


Renal failure in infectious mononucleosis.

An 18-year-old man developed generalized lymphadenopathy and interstitial renal disease which progressed to irreversible renal failure. Serologic studies evidenced the recent onset of infectious mononucleosis, and prior exposure to Epstein-Barr virus was demonstrated. Lymph node, liver, and renal biopsies showed mononuclear cell infiltration consistent with infectious mononucleosis. Although renal involvement in infectious mononucleosis rarely is severe, an association between infectious mononucleosis and renal failure is suggested in this patient.


Fournier's gangrene of the penis.

Fournier's gangrene is a rare, fulminant, though generally localizaed disease of the scrotum and penis. Three cases are presented in which the sexual practices of the patients may have played a role in the etiology. Hospitalization, parenteral antibiotics, and appropriate surgical treatment are required.