[Calorimetric study of thermoregulatory mechanisms at the onset of sweating and during the menstrual cycle (author's transl)]. 1 At the onset of sweating, tympanic (Tty), vaginal (Tva) and mean skin (Ts) temperature as well as the sudoral response were studied by direct and indirect calorimetry. Eight women with a normal ovulatory cycle were consecutively exposedt wice to 37 degrees C/20% rh during the follicular phase and again during the luteal phase. 2 Under our conditions, Tty may be used as an index of deep body temperature without any notable influence from ambient temperature. A weighting factor of chi = 0,7 was applied to the internal part of the body for the calculation of mean body temperature Tb. chi was determined by calorimetry, before and after the onset of sweating. 3 The onset of thermal sweating depends on a characteristic Tb corresponding to a specific caloric content of the body. Neither Tty, Tva, nor Ts, alone constitutes the specific stimulus leading to thermolysis by sweating. 4 The set point value (Tb "set") of the thermoregulatory system increases in the luteal phase, compared with that of the follicular phase. 5 Thermal regulation of the proportional control system shows a gain which is not modified during the menstrual cycle. 6 There is no relation between the shift of the set point value (Tb "set") and the increase of urine pregnandiol in the luteal phase. 7 The increase in basal body temperature and its maintenance during the post-ovulatory phase do not seem to be related to an increase in metabolic heat production.


[Discharge pattern of medullary respiratory neurones during thermal polypnea (author's transl)]. 1 In "encephale isole" cats with a spinal section in C7, we have recorded the activity of 108 medullary inspiratory or expiratory neurones during normopnea or polypnea induced by local warming of the anterior hypothalamic region. The neurones were grouped according to their axon destination, their discharge pattern, and the correlation level between their unit activity and the phrenic neurogram. 2 In polypnea, 71% of inspiratory neurones remain active. Their firing rates, which increase during inspiratory discharges in normopnea, decrease during inspiratory discharges in polypnea. However, this inversion of discharge pattern is less marked than with phrenic motoneurones. 3 The reduction of activity in polypnea preferentially strikes certain types of neurones. While bulbo-spinal inspiratory neurones all remain active, the propriobulbar inspiratory neurones can be grouped into those which remain active and whose activity is well correlated with the phrenic neurogram, and those which become silent and showing a poor correlation. As a general rule, activity in polypnea and correlation (in normopnea) go together. 4 In polypnea, 56% of expiratory neurones cease discharging. This activity decrease applies to bulbo-spinal expiratory neurones (5 out of 14) and to propriobulbar expiratory neurones (20 out of 31). Among the expiratory neurones, only those with an elevated discharge firing rate and significant correlation coefficient values remain active in polypnea. At this time they generally exhibit a decreasing firing rate and emit only a few spikes in each burst. 5 The results suggest that during polypnea the genesis of the respiratory rhythm is dependent upon a different mechanism than in normopnea.


Dolder bar joint mandibular overdenture: a technique for nonparallel abutment teeth. A mandibular overdenture technique has been presented that utilizes the Dolder bar joint attachment. Endodontically treated lower canines were retained as abutments. Two techniques for attaching the bar to teeth with divergent root canals were discussed: (1) the Schubiger screw system for those teeth with extremely divergent canals and (2) the Stutz pivots system for teeth with only slightly divergent root canals. The use of the Dolder bar joint offers periodontally involved teeth an improved crown/root ratio and splinting of the teeth. Because the bar is close to the alveolar bone, forces of mastication exert much less leverage to the teeth. Finally, the bar joint offers slight vertical and rotational movement of the denture as well as a stressbreaker action.


Articulator selection for restorative dentistry. There are many types of articulators that can be used for making fixed restorations. While unquestionably the most accurate, the fully adjustable instrument is not feasible or necessary for many forms of simple occlusal treatment. The effects of tooth-hinge axis radius, intercondylar distance, and condylar inclination on occlusal morphology have been discussed. Guidelines have been proposed for matching the type of articulator with the extent of treatment anticipated. The use of small, nonadjustable hinge articulators is not recommended.


Interim overdentures.

Interim overdentures. The construction of an interim overdenture using existing removable partial dentures with natural tooth crowns and artificial teeth can be a simple and economical method of providing patients with dentures while tissues heal and teeth are prepared and restored. A more definite prognosis for both the patient and his remaining dentition can be established before the final overdenture is completed. The procedures necessary to provide three types of interim overdentures have been outlined. Patients tolerate this method of changing their dentitions extremely well.


Treatment planning for fixed and removable partial dentures: a periodontal view. 1. Chronic occlusal trauma of partial denture abutments may be observed in radiographs before other clinical symptoms are noticed. 2. Evaluation methods can determine when teeth are unsuitable to serve as abutments, but these methods may not be reliable to predict the capacity for some essentially normal teeth to accept additional stresses. 3. Whenever a potential abutment is tilted so that axial loading is questionable, no restoration should be made.


Characterization of gold-palladium-silver and palladium-silver for ceramic-metal restorations. Properties, compositions, microstructures, and heat-treatment characteristics of three high-fusing white ceramic-metal alloys were studied. The materials displayed different compositions and as-cast microstructures, but similar tensile properties and heat-treatment responses. Hardness of cast specimens subjected to the porcelain firing cycle was increased by an additional 20 minute heat treatment at 1,300 degrees F.


Complete denture prosthodontics for the radiation patient. The increased use of radiation therapy for the control of oral cancer necessitates that all dentists concerned with the rehabilitation of oral cancer patients be familiar with this treatment modality. Radiologic equipment, the rationale for their use, and the sequelae to oral treatment are discussed. Misconceptions have developed concerning the advisability of prescribing complete dentures following radiation therapy. However, clinical experience in the Maxillofacial Unit at the University of California, San Francisco, indicates that most radiation patients can wear complete dentures. The need to follow sound prosthodontic techniques is advocated, along with a few modifications related specifically to the radiation patient. Patient cooperation and meticulous care during and following the placement of dentures are stressed to minimize the risk of tissue necrosis and to preserve the well-being of the patient.


Obturator design for hemimaxillectomy patients. The retention and stability of the obturator for the patient who has had a hemimaxillectomy are major problems. A removable partial denture with a swing-lock retentive design system will provide retention and stability due to the continuous splinting of the remaining teeth during function and a passive multiple retentive-clasp system during relaxation. However, because of the danger of the possible orthodontic action of the swing-lock system, special care should be taken when using this kind of design, and the patient should be closely observed.


The neutral zone in complete dentures.

The neutral zone in complete dentures. The neutral-zone philosophy is based upon the concept that for each individual patient, there exists within the denture space a specific area where the function of the musculature will not unseat the denture and where forces generated by the tongue are neutralized by the forces generated by the lips and cheeks. The influence of tooth position and flange contour on denture stability is equal to or greater than that of any other factor. We should not be dogmatic and insist that teeth be placed over the crest of the ridge, buccal or lingual to the ridge. Teeth should be placed as dictated by the musculature, and this will vary for different patients. Positioning artificial teeth in the neutral zone achieves two objectives. First, the teeth will not interfere with the normal muscle function, and second, the forces exerted by the musculature against the dentures are more favorable for stability and retention.


A silicone rubber attachment for primary retention of partial dentures. A technique for primary retention of removable partial dentures has been described. A soft-tissue-borne restoration provides an increase in primary retention without an increase in forces to the abutment teeth, and the restoration requires a minimal outlay of time and money.


A study of distortion and surface hardness of improved artificial stone casts. 1. The single-pour technique is as accurate as the double-pour technique except for point 6 (palatal point). Here the double-pour technique has greater accuracy. Impression material thickness over point 6 was approximately 15 mm. 2. The double-pour technique produced specimens which had superficial hardness values significantly higher than those of casts produced by the single-pour technique. 3. Specimens made with slurry water showed no greater distortion than specimens from other techniques. Surfaces of the specimens made with slurry water were significantly harder than those of specimens made with distilled water. Both types of specimens were made with the single-pour technique. 4. No significant difference in distortion was found in specimens produced with varying thickness of irreversible hydrocolloid impression material over the occlusal pins.


Constructing cast crowns to fit existing removable partial denture clasps. A step-by-step procedure has been presented for fabrication of a cast crown to fit an existing partial denture clasp. The procedure can be accomplished in two appointments, and the patient need not be subjected to the incovenience of being without the partial denture between office visits. It is an accurate and easy technique which gives uniform results and eliminates the need for remaking an adequate removable partial denture.


Role of the general dentist in maxillofacial prosthetics. Care of oral cancer patients requires the opinions and coordinated efforts of various consultants or therapists functioning as a multidisciplinary team to treat individual patients' physical, social, and economic problems. The modern medical concept of total treatment of the patient must include dentistry. Every dentist with interest and training in the basic principles of maxillofacial prosthetics can offer invaluable assistance in the treatment of maxillofacial patients.


The use of intraoral cores to repair complete and partial removable prostheses. A technique has been described for repairing fractured dentures. The procedure entails use of an occlusal core to correctly position the broken pieces of the denture. This technique is also applicable for repair of removable partial dentures as well as complete dentures. When the cause of a fractured prosthesis can be traced to occlusal disharmony or poor fit, it is not expected that repairing the denture will solve the underlying cause.


Electron microscopic study of Trypanosoma cruzi periplast in tissue cultures. I. Number and arrangement of the peripheral microtubules in the various forms of the parasite's life cycle. In an electron microscopic study, counts of peripheral microtubules were made in spheromastigotes and trypomastigotes in tissue cultures of embryonic heart muscle cells. In interphase spheromastigotes there were, at the level of the nucleus, approximately 114 microtubules; in dividing forms, there were approximately 222. In trypomastigotes, the number of microtubules varied according to the level of the section--there were fewer than 40 tubules in the pointed ends of an organism, while in the central segment the number of these elements ranged from 60 to 115. The highest number of microtubules was found in the region containing the Golgi complex. The distance between the microtubules was constant, equalling 44 nm, even at the pointed ends of a trypanosome. This suggests that the microtubules course parallel to one another. Cross sections and randomly arranged, variable length, longitudinal sections of the tubules were noted around the kinetosomes in dividing organisms.


Night medication in rheumatoid arthritis. The efficacy of indomethacin 100 mg, diazepam 10 mg, and placebo in producing sleep, relieving night pain, and reducing the severity of morning stiffness, was compared in 18 patients in hospital with active classical or definite rheumatoid arthritis.There was no statistically significant difference in the preference of patients or sleep score among the three forms of treatment. Both indomethacin and diazepam were more effective than placebo in relieving night pain. Indomethacin decreased, but diazepam increased, morning stiffness in comparison to placebo. Neither active therapy produced significant side-effects.


Suppression of LH-RH-induced ovulation in hamsters and rats by synthetic analogues of LH-RH. Peptide antagonists of LH-RH, [D-Phe2, D-Phe6]-LH-RH, [D-Phe2,D-Leu6]-LH-RH, [D-Phe2, D-Ala6]-LH-RH, [D-Phe2, D-Phe3,D-Phe6]-LH-RH, [DesHis2, D-Leu6]-LH-RH, and [DesHis2, D-Phe6]-LH-RH, were examined for their ability to suppress LH-RH-induced ovulation in phenobarbital-blocked hamsters and Nembutal-blocked rats. All of these peptides, with the exception of [DesHis2, Phe6]- LH-RH suppressed ovulation to various degrees, but alos exhibited various degrees of agonistic activities. Complete suppression of ovulation was achieved in rats with 3 mg [D-Phe2,Phe3,-D-Phe6]-LH-RH given in 4 divided doses at 30-min intervals starting 2 hr before the LH-RH injection. It was found that LH levels had to be lower than 5 ng/ml (control: 20-9 ng/ml) to suppress ovulation. However, the extent of suppression of ovulationdid not correlate with the serum LH levels less than 5 ng/ml. The incidence of ovulation induced by the intrinsic LH-RH activity of some of these analogues was similar to or greater than that resulting from administration of LH-RH plus analogue, suggesting that the activity of LH-RH itself was eliminated by pretreatment with the analogues.


Update on the safety and efficacy of clomiphene citrate as a therapeutic agent. Fifteen years have passed since our group first proposed the use of clomiphene citrate as an ovulation-inducing agent. Our 15-year experience with over 2,000 patients has not dampened our enthusiasm for this drug. The benefits have far outweighted the minor side effects or the possibility of multiple births. Serious birth defects were minimal and have been no greater than what one may expect in the general population. Clomiphene citrate has been a boon to womankind and deserves the confidence of both patient and physician: it is a drug with a record of utility and with but minor risks.


Antifungal activity of 4-substituted crotonic acid esters. Twenty-three 4-substituted crotonic acid esters were tested for antifungal activity against Candida albicans, Aspergillus niger, Mucor mucedo, and Trichophyton mentagrophytes. For the analogues of the methyl ester containing substituents in the 4 position, the following order of fungitoxicity was observed: I greater than Br greater than Cl greater than CH3S greater than CH3O greater than F=H. Of the homologues of the esters of the 4-iodo and 4-bromo compounds which included methyl, ethyl, n-propyl, n-butyl, n-pentyl, and n-hexyl, ethyl 4-iodocrotonate was most toxic to the four fungi at pH 7.0 in the presence of 10% beef serum (C. albicans, 18mug/ml, A. niger, 40 mug/ml, M. mucedo, 5 mug/ml, T. mentagrophytes, 4 mug/ml). It is believed that the mechanism of fungitoxicity is due, in part, to a nucleophilic reaction involving SH-containing compounds. This is based on the correlation of fungitoxicity with the order of leaving groups in the nucleophilic reaction and the protection against the toxicity of the test compounds to the fungi by cysteine and glutathione.


Optical probes of membrane potential.

Optical probes of membrane potential. There are two basically different mechanisms for the fluorescence and absorption changes of merocyanine, cyanine and oxonol dyes. The permeant dyes (cyanine and oxonol dyes, with delocalized charges) work by a potential-dependent accumulation mechanism. These dyes show large (up to 80%) fluorescence and absorption changes with suspensions of cells, and the changes are complete in seconds. The impermeant dyes (merocyanine dyes, with localized charges) and the permeant dyes also show optical changes that take place in fractions of milliseconds. The rapid optical changes are relatively small (less than or equal to 5 X 10(-3)) but can often be easily detected in experiments with single cells. The rapid, nonaccumulative, optical changes result from membrane-localized dye movements. Cyanine dye-absorption changes occur because of a potential-dependent partition of dye between the membrane and the adjacent aqueous region at the high dye-concentration side of the membrane. Dimers and larger aggregates are formed in the aqueous region during the change. Merocyanine dyes may also work by the same mechanism. DiS-C3-(5) is presently the best dye for measuring membrane potentials of cells, organelles, and vesicles in suspension, but several other cyanines work nearly as well (P.J. Sims, A.S. Waggoner, C.-H. Wang, J.F. Hoffman, Biochemistry 13:3315, 1974). For each system, the ratio of dye to membrane must be varied until the optimum fluorescence change is found. A separate calibration curve must be obtained for each system. For measuring fluorescence and/or absorption changes in single cells, merocyanine 540 and diBA-C4-(5) work well but produce some photodynamic damage with high intensity illumination. A rhodanine merocyanine (WW-375) gives very large absorption changes and does not damage tissue during strong illumination. As the mechanisms of the optical changes are worked out, it should be possible to design and synthesize more sensitive, less toxic dyes that are easier to calibrate. And, as the mechanisms of the optical changes are worked out, these dyes may be useful for studying the structure and dynamics of excitable membranes.


Dielectric properties of yeast cells.

Dielectric properties of yeast cells. Dielectric measurements were made on suspensions of intact yeast cells over a frequency range of 10kHz to 100 MHz. The suspensions showed typical dielectric dispersions, which are considered to be caused by the presence of cytoplasmic membranes with sufficiently low conductivity. Since the conductivity of the cell wall was found to be of nearly the same value as that of the suspending medium, composed of Kcl solutions in a range from 10 to 80 mM, the cell wall may be ignored in establishing an electrical model of the cells suspended in such media. An analysis of the dielectric data was carried out by use of Pauly and Schwan's theory. The membrane capacitance was estimated to be 1.1+/-0.1 muF/cm2, which is compared with values reported so far for most biological membranes. The conductivity of the cell interior was almost unchanged with varying KCl concentrations and showed low values owing to the presence of less conducting particles, presumably intracellular organelles. The relatively low dielectric constant of about 50 obtained for the cell interior, in comparison with values of aqueous solutions, may be attributed also to the presence of intracellular organelles and proteins.


Permeability of a cell junction and the local cytoplasmic free ionized calcium concentration: a study with aequorin. A technique is devised to determine the spatial distribution of the free ionized cytoplasmic calcium concentration ([Ca2+]i) inside a cell: Chironomus salivary gland cells are loaded with aequorin, and hte Ca2+-dependent light emission of the aequorin is scanned with an image-intensifier/television system. With this technique, the [Ca2+]i is determined simultaneously with junctional electrical coupling when Ca2+ is microinjected into the cells, or when the cells are exposed to metabolic inhibitors, Ca-transporting ionophores, or Ca-free medium. Ca microinjections elevating the [Ca2+]i in the junctional locale produce depression of junctional membrane conductance. When the [Ca2+]i elevation is confined to the vicinity of one cell junction, the conductance of that junction alone is depressed; other junctions of the same cell are not affected. The depression sets in as the [Ca2+]i rises in the junctional locale, and reverses after the [Ca2+]i falls to baseline. When the [Ca2+]i elevation is diffuse throughout the cell, the conductances of all junctions of the cell are depressed. The Ca injections produce no detectable [Ca2+]i elevations in cells adjacent to the injected one; the Ca-induced change in junctional membrane permeability seems fast enough to block appreciable transjunctional flow of Ca2+. Control injections of Cl- or K+ do not affect junctional conductance. The Ca injections that elevate [Ca2+]i sufficiently to depress junctional conductance also produce under the usual conditions an increase in nonjunctional membrane conductance and, hence, depolarization. But injections that elevate [Ca2+]i at the junction while largely avoiding nonjunctional membrane cause depression of junctional conductance with little or no depolarization. Moreover, elevations of [Ca2+]i in cells clamped near resting potential produce the depression, too. On the other hand, complete depolarization in K medium does not produce the depression, unless accompanied by [Ca2+]i elevation. Thus, the depolarization is neither necessary nor sufficient for depression of junctional conductance. Treatment with cyanide, dinitrophenol and ionophores X537A or A23187 produces diffuse elevation of [Ca2+]i associated with depression of junctional conductance. Prolonged exposure to Ca-free medium leads to fluctuation in [Ca2+]i where rise and fall of [Ca2+]i correlate respectively with fall and rise in junctional conductance.


Is the nexus necessary for cell-to-cell coupling of smooth muscle? Electronmicroscopic study of electrically coupled smooth muscles was undertaken to determine the distribution of nexuses in various types of smooth muscle. The study revealed that while nexal structures were commonplace in some types of smooth muscle, they were very rare or absent in others, even though in some cases these cells were only a few nanometers distant from one another. The persistence in thin section of these structures in the main circular muscle of dog intestine after poor fixation, fixation under strain, cell shrinkage, and metabolic damage of various sorts seems to rule out the thesis that they are labile. The absence of nexuses in longitudinal muscle of dog intestine examined both by thin section and by freeze fracture suggests that in this tissue they are absent or very rare in vivo and cannot account for electrical coupling. Nexuses were discernible in thin sections of main circular muscle after a variety of experimental conditions of fixation. Metabolic inhibition or in vitro permanganate fixation partially destroyed nexal contacts. These procedures induced tissue, membrane apposition and an accompanying increase in the number of structures which resemble nexuses at low magnification (nexus-like structures). "Nexus-like" structures occurred in all smooth muscle fixed by in vitro permanganate associated with apposition of membranes and poor preservation of basement membrane. A technique of in vitro permanganate fixation was developed which prevented tissue swelling; consequently "nexus-like" structures were absent in tissues so treated. The suggestion is made that some structures described in the literature as nexuses, following permanganate fixation, may represent "nexus-like" structures. The balance of evidence suggests that nexuses need not be present for electrical coupling of some smooth muscle cells, in which other types of cell-to-cell contacts must be invoked.


Doublet frequencies and codon weighting in the DNA of Escherichia coli and its phages. A compilation of nucleic acid sequences from E. coli and its phages has been analysed for the frequency of occurrence of nearest neighbour base doublets and codons. Several statistically significant deviations from random are found in both doublet and codon frequencies. The deviations in E. coli also appear to occur in lambda and in the coat protein gene of MS2, whereas T4 and other parts of the MS2 genome show different sequence properties. These and other findings are discussed in relation to the hypothesis that rapidity of translation of mRNAs in the E. coli system is dependent on doublet frequency and codon usage patterns.


Protocols for the dominant lethal test, host-mediated assay, and in vivo cytogenetic test used in the food and drug administration's review of substances in the gras (generally recognized as safe) list. Protocols are described for the dominant lethal and in vivo cytogenetics test in rats and the host-mediated assay, using Salmonella typhimurium and Saccharomyces cerevisiae in mice, as used by the Food and Drug Administration in its mutagenicity review of substances from the generally recognized as safe (GRAS) list. In addition proctolols are described for in vitro mutagenicity tests with S. typhimurium and S. cerevisiae and for statistical treatment for evaluation of data from dominant lethal tests.


[Ureteral replacement by jejunoplasty. New concepts, new techniques (author's transl)]. New concepts and new techniques permit the introduction in the urinary tract, of long or short segments of jejunum cut in a specific fashion. Their dynamic qualities allow not only perfect adaptation to a normal urinary tract, but also stimulate a rapid recuperation of pathological ureters. In addition to the dynamic qualities, the success of this is due to three main reasons: a good preoperative intestinal preparation; a new digestive suture utilised in the ante-mesenteric suture of the jejunoplasty; and finally, the introduction of a new type of running suture for the end to end anastomosis of ureter to jejunum. The anastomosis being leak-proof, the abdominal morbidity is non existent; we can envisage the suppression of catheters and drains. A preliminary study of three cases demonstrates the possible extension of the technique to long ureteral replacement with anti-reflux bladder reimplantation.


[Spontaneous ureterocolic fistula. Concerning one case reviewed in the litterature (author's transl)]. Among the entero-urinary fistulae, the most frequent are those fistulae which unite the sigmoid colon and the bladder. Fistulae between the ureter and the colon are ecxeptional as only two spontaneous ureterocolic fistulae have been reported. With reference to one case, the authors review the different complementary examinations which enable making the diagnosis and discuss the therapeutic attitude, which differs depending on whether the kidney above the fistula is functional or not.


[Recto-sigmoid carcinoma after uretero-sigmoidostomy. One case, with a review of the literature (author's transl)]. A case of recto-sigmoid adenocarcinoma, developing 25 years after bilateral uretero-sigmo dostomy for extrophia vesicae in a 29 year old man. A study of the literature emphasises the long delay before its appearance, the gastrointestinal nature of the tumour and its grave prognosis. The pathogenesis of this lesion is unknown at present, and consideration should be given to the effects of urine on the digestive mucosa and the role of a possible inflammatory granuloma, but also the possibility of a urinary tract origin, despite the apparent histological contradiction.


[Use of the epigastric artery in renal transplantation (author's transl)]. The location, length, calibre and wall-thickness of the epigastric artery make it particularly useful for anastomosis with the polar arteries of grafts with several renal arteries. It proved to be very useful in four renal transplants in man.


[Concerning 490 renal transplants in the rat, Technical study (author's transl)]. The authors carried out 490 renal transplants in the rat, in order to train two laboratory technicians with no previous surgical competence, in this microsurgery. The different techniques of vascular and urinary anastomoses are looked at with their advantages and disadvantages. Two years were necessary in order to obtain a percentage of immediate success of 75 per cent. But, secondary infections and mainly urinary complications in this experiment, prevent obtaining more than 50 per cent of graft which could be exploited on a long term basis, which limits the scientific value of the method.


[Surgical results of renal transplantation (62 cases) (author's transl)]. Over a period of 16 months, 62 renal transplantations were carried out by the same medicosurgical team. The follow-up period being 3 months for the most recent cases, 57 patients are still alive and 44 grafts are functional. No surgical complication was the cause of loss of a graft and even less so that of a transplanted patient. Reestablishment of urinary continuity was carried out by ureteroneosystostomy and no fistula or ureteral stenosis was noted. Only 5 vesical fistulae were related to this technique but they healed with no problem. Parietal infectious complications (32%) were much more preoccupying, and frequently the very cause of the majority of urinary complications. Finally vascular stenosis, found in a little more than 6 p. 100 of cases only lead to surgical restoration on one occasion. These different results are compared with those of other teams published today.


Cleavage of lambda DNA by a site-specific endonuclease from Serratia marcescens. Three sites recognized by SmaI endonuclease, purified from Serratia marcescens SB, have been located on lambda DNA at 0.406, 0.656, and 0.825 fractional lengths from the left end of the DNA molecule.


Properties of condensed bacteriophage T4 DNA isolated from Escherichia coli infected with bacteriophage T4. Methods developed for isolating bacterial nucleoids were applied to bacteria infected with phage T4. The replicating pool of T4 DNA was isolated as a particle composed of condensed T4 DNA and certain RNA and protein components of the cell. The particles have a narrow sedimentation profile (weight-average s=2,500S) and have, on average, a T4 DNA content similar to that of the infected cell. Their dimensions observed via electron and fluorescence microscopy are similar to the dimensions of the intracellular DNA pool. The DNA packaging density is less than that of the isolated bacterial nucleoid but appears to be roughly similar to its state in vivo. Host-cell proteins and T4-specific proteins bound to the DNA were characterized by electrophoresis on polyacrylamide gels. The major host proteins are the RNA polymerase subunits and two envelope proteins (molecular weights, 36,000 and 31,000). Other major proteins of the host cell were absent or barely detectable. Single-strand breaks can be introduced into the DNA with gamma radiation or DNase without affecting its sedimentation rate. This and other studies of the effects of intercalated ethidium molecules have suggested that the average superhelical density of the condensed DNA is small. However, these studies also indicated that there may be a few domains in the DNA that become positively supercoiled in the presence of high concentrations of ethidium bromide. In contrast to the Escherichia coli nucleoid, the T4 DNA structure remains condensed after the RNA and protein components have been removed (although there may be slight relaxation in the state of condensation under these conditions).


Occluded and nonoccluded nuclear polyhedrosis virus grown in Trichoplusia ni: comparative neutralization comparative infectivity, and in vitro growth studies. Nuclear polyhedrosis virus infections of lepidopteran cells often result in the production of both occluded and nonoccluded virus. The characterization of these two different forms has been the subject of several papers. We have divided the nonoccluded virus (NOV) category further into plasma membrane-budded non-occluded virus (PMB-NOV), intracellular NOV, and hemolymph-derived NOV, and have done additional studies investigating the differences between these nonoccluded forms and the alkali-liberated forms from occlusions of the nuclear polyhedrosis viruses of Autographa californica and Rachiplusa ou. The methods used to discern differences and similarities among the forms were serological, biochemical, and visual, all related to their biological acitivity. Neutralization studies revealed that alkali-liberated virus and PMB-NOV had both similar and different antigens. Antisera raised against alkali-liberated virus from occlusions neutralized the alkali-liberated form of the virus, but did not neutralize the intracellular or extracellular nonoccluded forms. Antisera raised against the TN-368-13 PMB-NOV, however, neutralized the alkali-liberated forms as well as all forms of the NOV. Adsorption of this antisera with alkali-liberated virus did not diminish the neutralization titer against the nonoccluded forms, thus confirming the antigenic differences between the alkali-liberated and nonoccluded forms of the virus. Physical-infectious particle ratio calculations indicated that the PMB-NOV of Autographa  californica are about 1,900-fold more infectious than the single-nucleocapsid-per-envelope alkali-liberated particles and about 1,700-fold more infectious than the multiple-nucleocapsid-per-envelope particles, as assayed in vitro. In addition, a study of viral growth kinetics monitored concurrently with the appearance of polyhedra showed that PMB-NOV production is shut down with the onset of polyhedron formation.


Bacteriophage G4 DNA synthesis in temperature-sensitive dna mutants of Escherichia coli. The synthesis of bacteriophage G4 DNA was examined in temperature-sensitive dna mutants under permissive and nonpermissive conditions. The infecting single-stranded G4 DNA was converted to the parental replicative form (RF) at the nonpermissive temperature in infected cells containing a temperature sensitive mutation in the dnaA, dnaB, dnaC, dnaE, or dnaG gene. The presence of 30 mug of chloramphenicol or 200 mug of rifampin per ml had no effect on parental RF synthesis in these mutants. Replication of G4 double-stranded RF DNA occurred at a normal rate in dnaAts cells at the nonpermissive temperature, but the rate was greatly reduced in cells containing a temperature-sensitive mutation in the dnaB, dnaC, dnaE, or dnaG gene. RF DNA replicated at normal rates in revertants of these dna temperature-sensitive host cells. The simplest interpretation of these observations is that none of the dna gene products tested is essential for the synthesis of the complementary DNA strand on the infecting single-stranded G4 DNA, whereas the dnaB, dnaC, dnaE, (DNA polymerase III), and dnaG gene products are all essential for replication of the double-stranded G4 RF DNA. The alternate possibility that one or more of the gene products are actually essential for G4 parental RF synthesis, even though this synthesis is not defective in the mutant hosts, is also discussed.


Shigellosis from swimming.

Shigellosis from swimming. In Augsut 1974, 31 of 45 cases of Shigella sonnei infection in Dubuque, Iowa, were traced to swimming in an 8-km stretch of the Mississippi River. Comparison of the first case in each affected family with neighborhood controls showed a significant correlation between swimming and illness (P less than .0001). A significant association between diarrheal illness and swimming (P less than .0001) was also demonstrated by a retrospective survey of 60 families who had camped at a park beside the river; the attack rate for swimmers who got water in their mouths while swimming was 18%. They had been swimming in water where the mean fecal coliform count was 17,500 organisms per 100 ml; the federal recommended upper limit for swimming water is 200 per 100 ml. A water sample obtained at the park swimming area one month after authorities had banned swimming in the area yielded S sonnei with the same antibiogram, colicin type, and phage type as the isolates from six swimmers.¿


Interaction of rifampin and glucocorticoids. Adverse effect on renal allograft function. Three renal transplant patients experienced progressive loss of renal allograft function during rifampin treatment for Mycobacterium tuberculosis. Previous studies have shown that rifampin causes induction of enzymes in hepatic microsomes that increase the catabolism of glucocorticoids. Evidence is presented that in our patients, the loss of renal allograft function during rifampin therapy was the result of decreased glucocorticoid effect presumably related to increased catabolism of the glucocorticoid drug they received. Thus, the adverse effects of rifampin on renal transplant function might be overcome by increasing the dose of glucocorticoid drug.


Measles in adults. An unforeseen consequence of immunization? An outbreak of measles occurred in California in the first half of 1975, especially in the San Francisco Bay area. Of four adult patients with complicated cases, two were receiving immunosuppressive chemotherapy, and both died from a giant-cell pneumonia. The clinical presentation in such cases may be atypical, and special viral isolation and immunofluorescent techniques may be diagnostically helpful. A significant (P less than .0005) trend toward the occurrence of measles in adolescents was observed in this epidemic, which may also occur in future epidemics elsewhere. With wide spread but incomplete immunization, it is possible for the nonimmunized to reach adulthood without acquiring natural infection. As a result, internists as well as pediatricians will have to consider the possibility of measles and be aware of its serious potential in the immunosuppressed patient.


Apparent recurrence of progressive systemic sclerosis in a renal allograft. A young woman with progressive systemic sclerosis (PSS) and renal failure who received a renal transplant from her mother suffered accelerated loss of allograft function in the absence of hyperacute rejection or severe hypertension. A biopsy specimen and pathologic examination of the transplanted organ showed a fluorescent antibody pattern and vascular changes that were indistinguishable from those in the patient's native kidneys. This clinical sequence is a departure from the relative success of renal transplantation in the few previously reported cases of PSS where it has been used as therapy for renal failure.


Epidemic streptococcal sore throat following a community picnic. Following a picnic, nearly half of the persons who attended became ill. Sixty-three of 139 throat cultures were positive for group A beta-hemolytic streptococci. Forty-seven of the positive cultures were available for typing, 34 of which harbored the epidemic strain, group A beta-hemolytic Streptococcus type T-3/13/B3264. This contrasted with two of 204 controls who had not attended, but harbored the epidemic strain. Food preferences and illness rates implicated the potato salad, and from it the epidemic strain was isolated. The attack rate and case-to-infection ratio among those who attended the picnic was significantly greater for persons over 10 years of age. Prompt institution of chemoprophylaxis could possibly have prevented at least 50% of the cases.


Patterns of fibrin deposition in the glomeruli of diseased kidneys. Immunofluorescent studies were performed on 217 percutaneous renal biopsies on patients with various renal diseases, which were examined in detail to assess the amount, character, and distribution of fibrin deposits in the glomeruli. The fibrin deposits were classified into six different forms on immunohistologic grounds. These were adhesive, adhesive and occlusive, membranous, mesangial, crescent forming, and sclerotic types. The sclerotic type was further subdivided into 2 groups: periglomerular fibrosing, and sclerosis with occlusion types. In many instances, immunofluorescence may reveal a pattern which is commonly associated with a characteristic abnormality on light microscopy. Fibrin deposits were commonly correlated with the presence of glomerular immunoglobulin and betaIc/betaIa-globulin. These findings interpreted as the immune reaction within glomeruli leads to an initiation of the coagulation process. The patrular hyalinization are briefly discussed.


Adjuvant action of capsular polysaccharide of Klebsiella pneumoniae on antibody response. V. Further biological properties of the active substance. The neutral fraction (neutral CPS-K) of Klebsiella pneumoniae capsular polysaccharide (CPS-K) from type 1, Kasuya strain, has already been reported as the active substance responsible for the strong adjuvant effect of CPS-K. The present results demonstrate that neutral CPS-K exhibits further common biological activities with lipopolysaccharide (LPS) isolated from Salmonella enteritidis. The intensity of the lethality in mice of neutral CPS-K by the intraperitoneal route is very similar to that of LPS. Its lethality for mice by the intravenous (i.v.) route is significantly stronger than that of LPS, because the degree of increase in the sensitivity to their lethality by i.v. challenge is smaller for LPS than for neutral CPS-K. The intensity of the pyrogenicity of neutral CPS-K in rabbits is approximately one-tenth of that of LPS as judged by the minimal pyrogenic doses and fever indices. The skin-preparatory potency of neutral CPS-K for the dermal Shwartzman phenomenon in rabbits is also approximately one-tenth of that of LPS compared on the basis of the minimal skin-preparatory doses. When injected i.v., neutral CPS-K exhibits a provocative effect on hemorrhagic reactions in skin sites prepared with neutral CPS-K or LPS.


An improved procedure of specific polysome precipitation with antibody. The specific immunoprecipitation of polysomes prepared from a mouse myeloma, 31C, synthesizing an IgG1 immunoglobulin has been investigated. A reported method in which polysomes were coprecipitated by sequential addition of antibody to 31C myeloma protein, antigen (i.e., the 31C protein) and again the antibody, was used. Salt concentration greatly affected the immunoprecipitation of polysomes. In the presence of 100 mM KCl or NaCl, 10-20% of myeloma polysomes and only 1% of mouse liver polysomes were precipitated with the antibody to myeloma protein. On the other hand, 90% of the both polysomes were precipitated by the same antibody at a salt concentration of 10 mM. Triton X-100 and sucrose had little effect on preventing nonspecific binding of immunoglobulin to ribosomes. Experiments were carried out to obtain an optimal ratio of the amount of polysome to that of antibody and antigen to be added for the coprecipitation of polysomes. To date we have tried 25 mug of the first antibody, 14 mug of antigen added second to the polysomes and 38 mug of the antibody added finally and these were found to precipitate most efficiently one A260 unit of 31C polysomes.


Inhibition by thiopeptin of bacterial protein synthesis. Thiopeptin, a sulfur-containing antibiotic, was found to inhibit protein synthesis in a bacterial ribosomal system. The pretreatment of ribosomal subunits with the antibiotic revealed that thiopeptin may act on the 50 S ribosomal subunit. The elongation of peptide chain on the ribosome is more profoundly blocked by the antibiotic than the initiation of protein synthesis. It was demonstrated that thiopeptin inhibits elongation factor (EF)-Tu-dependent GTP hydrolysis and binding of aminoacyl-tRNA to the ribosome. The peptidyl transferase-catalyzed puromycin reaction is not significantly affected by the antibiotic. Thiopeptin inhibits EF-G-associated GTPase reaction, and translocation of peptidyl-tRNA and mRNA from the acceptor site to the donor site. Protein synthesis in ribosomal systems, obtained from rat liver and rabbit reticulocytes are insensitive to the antibiotic.


Kidney transplant biopsies in the diagnosis and management of acute rejection reactions. In 68 consecutive renal transplant biopsies, histopathologic changes and clinical status of the graft  recipient, both at the time of biopsy as well as one month later, were evaluated by independent observers. Nine histologic features were graded semiquantitatively (scale, 0 to 4): glomerular endothelial swelling, proliferation, exudation and necrosis; interstitial edema and infiltrate: vascular endothelial edema, infiltration and necrosis. The total score for each biopsy was termed the acute rejection index (ARI). The validity of the ARI as a means of evaluation rejection reactions was established by correlating the ARI with a second, overall histopathologic categorization. Clinical status at the time of biopsy was classified by retrospective analysis of all clinical data except the biopsy. The mean ARI of patients with an acute clinical rejection was significantly higher than those of patients with just a chronic clinical rejection or no clinical rejection. The utility of the biopsy in predicting the response of the graft recipient to therapy was evaluated in those 46 patients in whom an acute rejection was diagnosed clinically and in whom a full and complete course of therapy for the acute clinical rejection was given. Of the 28 patients whom the pathologist predicted would response to therapy, 27 did show substantial improvement of their renal function up to one month following institution of treatment. Of the 18 patients whom the pathologist predicted would not respond to therapy, 15 had no clinical response. The data suggest that the transplant biopsy is helpful in 1) establishing the diagnosis of an acute rejection and 2) indicating whether or not the graft recipient will respond to standard immunosuppressive treatment for an acute rejection,


The effect of uremia and transplantation on lymphocyte subpopulations. The in vitro immune response of uremic and transplanted patients was studied by determining lymphocyte surface and functional markers. Because of lymphopenia, the absolute number of T and B cells are diminished in uremia and transplantation. The uremic state had a profound effect of T cell mitogenic response, while the relative number (%) of T cells was not reduced. B cell responses and relative numbers were significantly diminished. The early posttransplant period was associated with a significant reduction in both T and B cell response and relative numbers. All indexes returned toward normal late in the posttransplant course with reduction of immunosuppression and cessation of the uremic state. Horse anti-human lymphocyte globulin treatment caused a significant reduction in T cells and an increase in B cells. Prednisone therapy did not appear to influence the relative number of the lymphocyte subpopulation but did reduce the mitogenic responses. Changes in surface or functional markers did not prove useful in predicting rejection episodes in transplanted patients.


Effect of parathyroid hormone on phosphate reabsorption in the presence of acetazolamide. The hypothesis that parathyroid hormone and carbonic anhydrase inhibitors have a common mechanism or site of action on phosphate reabsorption by the renal tubule was tested by administration of parathyroid hormone in the absence and presence of acetazolamide in thyroparathyroidectomized dogs. Re-collection micropuncture and electron probe microanalysis methodologies were utilized. In the absence of acetazolamide, parathyroid hormone increased fractional delivery of phosphate (and volume) from the proximal tubule from 25 +/- 2 to 38 +/- 3%, P less than 0.025, and increased fractional phosphate excretion from 3.8 +/- 1.2 to 19.9 +/- 3.7%, P less than 0.005 (eight dogs). In the presence of acetazolamide, parathyroid hormone increased fractional delivery of phosphate (but not volume) from the proximal tubule from 50 +/- 4 to 58 +/- 5%, P less than 0.025, and increased fractional excretion of phosphate from 8.7 +/- 2.2 to 31.0 +/- 4.3%, P less than 0.001 (12 dogs). Thus, the effects of parathyroid hormone were additive to the effects of maximal inhibition of carbonic anhydrase indicating that parathyroid hormone and carbonic anhydrase inhibitors have different mechanisms of action on phosphate reabsorption by the renal tubule. In addition, phosphate reabsorption  beyond the point of micropuncture in the late proximal tubule was much more markedly inhibited by parathyroid hormone than by acetazolamide.


[Episcleral sealing with a safety-circlage in juxtabasal horse-shoe tear (author's transl)]. Primary cerclage with an additional radial episcleral implant is proposed for horseshoe tears with vitreous traction, but without retinal detachment. At the beginning of the operation, the two sutures of the cerclage on both sides of the retinal pathology are tied with a little stretch of the 2 mm silicone rod. Then the radial plombage is placed beneath the encircling element. Afterwards the rest of the cerclage is drawn up without stretch, and the site of crossing is fixed with two sutures. At the end of the operation the radial implant may be secured against lateral movements by one or two sutures. The whole procedure is aided by parabulbar injection of penicilline and a depot of dexamethasone. The main advantages are the abolition of any difficulties in the localization and fixation of the plombage, and the permanent buckling effect. In 37 cases operated in this way, no complications were observed (follow-up time 1/2-2 years). Contraindication to the proposed technique is a narrow chamber angle.


[Treatment of the diabetic retinopathy with doxium-clofibrate (author's transl)]. 28 patients with non proliferating exudative diabetic retinopathy were treated with 750 mg Doxium and 1500 mg Clofibrate daily during 8.6 months on an average. Before beginning--in the middle of the period of observation--and after finishing the treatment, a retinal fluorescein angiography was performed. The waxy exudates decreased in 11 patients (39.29%) and increased in 8 patients (28.57%). In 9 patients (32.14%) no change of the amount of the hard exudates was observed. The treatment was almost only in those angiopathies successful, in which the fluorescein angiography showed a preponderance of the hyperpermeability over the obliterating process of retinal capillaries.


[Autologous corneal transplants in recurring herpes corneae (author's transl)]. This paper reports the results of penetrating corneal autokeratoplasty of a man 49 years of age with chronic herpetic keratitis in his good right eye. The keratoplasty was taken from the patient's left eye with amblyopia. The diameter in both keratoplasties was 7.1 mm. In both eyes clear grafts were obtained. Visual acuity of the right eye improved to 0.5! One year after the autokeratoplasty the grafts remained clear, showed no immune reactions and no tendency towards vascularization.


[Plexiglas (PMMA) in the anterior chamber. An experimental study on biological compatibility]. For six months the anterior chambers of rabbits were examined at regular intervals with the slit-lamp photograph. The reactions of iris, aqueous, and cornea were observed after implanting one PMMA-disc (0.25 mm thickness and 1.5 mm diameter) through a lancet incision. At the place where the disc touched the iris one could see during the half year period hyperaemia iridis, ciliary injection, atrophia iridis, and foreign-substance-granuloma of the iris with partial adhesion of the iris wrinkles. The cause for these reactions is a toxin in the PMMA. Mechanical irritation and plastic alteration could be excluded by the experimental method.


[Corneal changes after implantation of intralamellar teflon-membranes (author's transl)]. After intralamellar implantation of Teflon-membranes (4,0 mm/0,125 mm) without perforation there is an epithelial thinning over the membrane after 6 days, after 15 days metachromatical staining over the membrane is reduced, after 21 days there is a central defect of the cornea over the membrane and after 28 days the membrane is pushed out of the cornea. When Teflon-membranes (4,0 mm/0,125 mm) are inserted with one central perforation or three perforations of 1 mm epithelial thinning, reduced metachromasia and defects of the cornea over the membrane occurred later. But even these membranes are pushed out of the cornea after some time. The results with thinner Teflon-membranes (4.0 mm/0.05 mm) do not show much difference. The reason for the reduced metachromasia of the cornea over Teflon-membranes seems to be a lower rate of syntheses of glycosaminoglycanes because of the reduced glucose content in this part of the cornea. As the experiments with the intracorneal control-pockets without implantation of a Teflon-membrane show, wound-healing is not responsible for the reduced metachromasia over the membrane.


[Tectonic keratoplasties using cryopreserved corneae (author's transl)]. It is reported on the treatment of severe chronic corneal diseases using cryopreserved corneae being sutured on the diseased cornea. In the majority of the patients (total number 13) defect healing was achieved. The advantages of this surgical procedure are discussed.


[A non traumatic suture for corneal lacerations (author's transl)]. A suturing technique for cases of corneal trauma is discussed, by means of which, the complications formerly incurred with a running-suture may be avoided. Suture infections, ulceration and the formation of scars in the center of the cornea, as well as the subjective "scratchy" feeling reported by patients, can be largely or totally eliminated, because the single knot is buried in the conjunctiva at the limbus.


[Misdiagnosis of "chalazion" (author's transl)]. The diagnosis of the often occurring "chalazion" usually puts no problems in diagnostic and therapeutical view. It must be considered, however, that already small particularities of the clinical findings point to other i.e. benign or even malignant processes. An analysis of a number of cases from 1969 to 1975 of the University Eye Clinic Münster showed in 21 out of 89 histologically examined tissue specimen another diagnosis. In 8 patients a malignant degeneration of tissue was histologically stated. The authors describe some cases, where during a longer period of time the malignant character of the disease was not diagnosed due to the misdiagnosed "chalazion".


[Reconstruction of the upper eyelid (author's transl)]. An excellent rebuilding after complete or nearly complete loss of the upper eyelid can be performed by the following technique: Replacement of lid margin, tarsus and conjunctiva by two free grafts from the right and left lower lid, while the skin-muscle-layer is replaced by a pedicle skin graft.


[Hyperkinetic syndrome (author's transl)]. This review reports on symptoms, prevalence, etiopathogenesis, prognosis and course, therapy as well as on theory of the hyperkinetic syndrome.


[Immunological studies in childhood coeliac disease (author's transl)]. The predominance of IgA-containing plasma cells over IgM-containing plasma cells in the normal small bowel mucosa is well documented. In coeliac patients relatively higher numbers of IgM-positive cells were found by several authors in varying degrees. We investigated the proportion of IgA-, IgM and IgG- containing plasma cells in small bowel biopsy material from 21 coeliac children and 24 controls by means of the immunofluorescent double-staining technique. A greater increase of IgM-cells than has previously been described was found. Additionally anti-reticulin antibodies, precipitating antibodies to gliadin and immunoglobuline levels in the serum were determined and tissue typing was performed in a number of these children, and the correlations of these single results were studied. Although these immunological investigations can not substitute the examination of small bowel mucosa biopsies by means of the dissecting microscope and conventional histological methods, they are a valuable diagnostic aid and could help to avoid unnecessary repeat biopsies. They are of help in monitoring the course and therapy in coeliac patients.


Hyperlipidemias in patients with kidney transplants. Serum lipids in 58 renal transplant recipients were related to duration of follow-up, relative body weight, steroid medication, proteinuria and graft performance. Hyperlipidemia was observed between the 4th month and the end of the first year after transplantation in 83% of the patients. Thereafter, the frequency of hyperlipidaemia appeared to decrease: at 4 to 7 years only 61% of the subjects continued to exhibit abnormal high serum lipids. Three mechanisms leading to hyperlipidaemia were identified: 1) overweight, 2) steroid mediation, 3) proteinuria. A forth apparent mechanism was impaired transplant function.


Transfer of tumor specific immunity with "immune" RNA: prospects for the treatment of human cancer. Ribonucleic acids extracted from specifically sensitized lymphoid cells (I-RNA) have been shown to transfer specific immunoreactivity to normal non-immune lymphoid cells. Evidence for the transfer by I-RNA, of immune responses to tumor-associated antigens of animal and human neoplasms, in vivo and in vitro, is reviewed. Results obtained in our laboratory and in other laboratories indicate that xenogeneic, allogeneic and syngeneic I-RNA extracts mediate specific cytotoxicity to tumor cells, in vitro, and mediate transplantation resistance and tumor rejection responses in vivo. Our results suggest that I-RNA preparations fail to elicit immune responses directed against "self" antigens. By contrast, I-RNA's directed against "non-self" tumor-associated antigens appear to induce lymphocytes to effect specific anti-tumor immune responses. The mechanisms responsible for the failure of I-RNA to initiate immune responses against "self" antigens are not known at present and demand investigation. Preliminary results of a clinical Phase I trial of immunotherapy with xenogeneic I-RNA in selected cancer patients are reviewed. I-RNA might offer promise as a new modality for the immunotherapy of human cancer.


Characterization and distribution of collagen types in arterial heterografts originating from the calf carotis. The immunohistochemical results showed that the distribution of the collagen types in calf carotis is the same as that found in human arteries. Mechanically prepared and ficin-treated vessels showed a removal of cells, elastic fibres and type II collagen. The remaining collagen meshwork was shown by immunohistochemical methods and also by amino acid analysis to be type I collagen. Because of its structural, chemical and immunological properties, the protease treated, aldehyde stabilised Arteria carotis communis of the calf is suitable as a replacement material for arterial segments. Initial successes using man as a recipient support the stated conclusion.


Enteritis in a conventional rabbit colony. Necrotic typhlitis, often accompanied with necrotic liver foci, was frequently observed in a conventional rabbit colony during the years 1965-1969. Although different serotypes of Escherichia coli could be cultured from the diseased caeca, many cases occurred from which no Escherichia coli could be isolated. Assuming that the disease might be bacteriological in origin, tetracycline was administered, and mortality decreased. The prevalence of tetracycline-resistant Escherichia coli strains makes application of an alternative therapy desirable.


An outbreak of rabbit enteritis: pathological and microbiological findings and possible therapeutic regime. Mortality, averaging about 30% of young born throughout the year, was severest at 5-10 weeks of age, from just before weaning until about 4 weeks after, especially in large litters of 10-11 young. The organism most characteristically associated with enteritis was Escherichia coli. Preliminary experiments suggested that restriction of food decreases the death rate from enteritis among young rabbits.


A naturally acquired infection of laboratory mice with Klebsiella capsule type 6. An epizootic causing high morbidity and high mortality in Swiss White and Nude mice over a period of 3 weeks was caused by Klebsiella pneumoniae Capsule type 6, which is considered to be nonpathogenic for mice. Experimental inoculation of this organism into laboratory animals caused death within 36 hours, further substantiating its virulence.


Transmission of enteritis in the Syrian hamster. Twenty-six of 39 Syrian hamsters obtained by this laboratory from a pet supplier had enteritis and showed signs of "wet tail." An enteritis was reproduced in healthy hamsters by oral inoculation of homogenized ilea and jejuna from the diseased hamsters. The most characteristic pathologicfeatures were a variably enlarged distal jejunum and ileum and granulomatous lesions in the ileal subserosal wall. Histologic findings included a greatly hyperplastic jejunal and ileal mucosa that frequently contained submucosal accumulations of inflammatory cells. Often mucosal glands extended into these areas. The gross and histologic lesions produced were identical to those described in proliferative ileitis. Bacterial cultures from infected tissues consistently grew a slow lactose-fermenting Escherichia coli. Although diarrhea could be produced by oral inoculation of the organism, the typical morphologic lesions were not produced.


Nutrition of the domestic rabbit.

Nutrition of the domestic rabbit. Recent studies on the nutritional needs of the rabbit were reviewed. Emphasis was placed on fiber utilization by rabbits, digestibility of forage protein, and unique aspects of mineral and vitamin requirements. In spite of the herbivorous nature of rabbits, their ability to digest fiber is low. Indigestible fiber may have a role in preventing enteritis. While lacking the ability to efficiently digest fiber, rabbits do make efficient use of forage protein, in contrast to most other monogastric animals. Differences in serum calcium homeostasis and calcium excretion as compared with other animals were discussed. The interrelationship between vitamin E and selenium appears different in the rabbit compared with other species. The limited information available on rabbit nutrition suggests that rabbits are unusual in their metabolism of several nutrients; because of their wide use in biological research, more extensive information on nutritional and metabolic characteristics of rabbits is needed.


Protein and amino acid requirements of the laboratory rabbit. The arginine requirement of the growing rabbit has been re-investigated and found to vary depending upon the pattern of the indispensable amino acids other than arginine. The requirement was higher on a pattern simulating isolated soy protein than on a pattern that contributed essentially the requirement pattern. The rabbit has been found sensitive to protein quality in the same way as other monogastric animals, including the rat and the chick. Interestingly, soy protein appears to provide a superior amino acid pattern to whole egg. Also, casein may be limiting in arginine for the growing rabbit.


The meadow vole as an experimental animal. A meadow vole colony has been in operation at The Pennsylvania State University for 6 yr. The breeding colony consists of 16 breeding harems of 1 male and 2-4 females per cage. Over 2,500 weanlings have been available each year for various experiments. Primary emphasis has been directed toward determination of the weanling's nutritional requirements. Adults have been used to study plant factors associated with the palatability of forages. This information has been used to devise specific bioassay procedures to study the relative nutritional value of a wide range of cultivated crop species. Weanlings have been used to evaluate the quantity and quality of protein available for growth from cereal grains and soybeans as well as the energy available for growth from temperate and tropical forages. Studies of antiquality constituents with weanlings have led to the indentification of a toxic constituent in crownvetch forage and the verification of undersirable constituents in raw soybeans and forages. Studies with adults have assisted in clarifying the effects of forage saponins and alkaloids on the paltability response of adult voles. Each of these studies have provided some type of new and useful information that has implications in either nonruminant or ruminant responses to crop plants.


Nutritional idiosyncrasies of the golden hamster (Mesocricetus auratus). The golden hamster has a compartmentalized stomach consisting of a forestomach and a glandular stomach. The forestomach is lined with keratinized epithelium and contains an active microbiol population capable of significant cellulolytic activity. This organ is not essential for life and is the first entrance point for swallowed feed. The hamster, while having a protein requirement like that of the rat, utilizes protein much differently. It ranks soybean meal above a fish protein concentrate and does not utilize added crystalline essential amino acids as such. Acceptance of the hamster as a nutritional surrogate of the rat seems unwarranted.


The neglect and abuse of children and youth: the scope of the problem and the school's role. We have attempted to define the spectrum of maltreatment of children seen in our current society. The potential for abuse in the child's caretaker, a child who is somewhat different, and a stressful situation are ingredients which often interact to produce maltreatment. The maltreatment rendered to the child includes many mechanisms ranging from direct blows from a variety of objects, to violently shaking the child, to neglect. The spectrum of the pathological findings is as varied as the means to inflict the trauma or neglect and involves every organ system. The predominate pathology of abuse is located in the central nervous system, bones and cutaneous tissues. The school's role primarily involves awareness of the problem of maltreatment, a method of approach to identify and report "suspected" cases, and the documentation of the injuries or neglect which have been observed. The school plays an important role in the follow-up of individual cases in providing a supporting environment for the child and coordinating with other agencies dealing with the family. The school personnel and all professionals must work together if adequate services are to be provided to protect children and rehabilitate families.


Diaphragm pacing: histopathological changes in the phrenic nerve following long-term electrical stimulation. Phrenic nerves were obtained at autopsy from 7 patients with chronic ventilatory insufficiency. One or both nerves had been subjected to electrical stimulation to pace the diaphragm for about 2 months to 4 years. Sections of the nerves made from above, at the level of, and below the site of application of the cuff electrode were studied microscopically. In most specimens, focal areas of demyelination were seen ranging from severity from swelling and fragmentation of isolated fibers to focal myelin destruction with phagocytic activity and total removal of myelin with fibrosis. Some axone loss was seen. The fact that the nerves from 2 patients, each stimulated for about 2 years, showed no changes suggests that injury to the nerve was not caused by the electrical stimuli but rather was secondary to the technique of application and fixation of the cuff electrode to the nerve.


The effect of a target date based utilization review program on length of stay. This study was conducted to determine whether implementation of a specific formalized concurrent utilization review system which involved making a prior determination of length of stay had any more effect on average length of stay than continuance of a utilization review method not involving assignment of such a target date. The system studied was the Pre-Discharge Utilization Review (PDUR) program used for Medicaid patients in Pennsylvania. Analysis was conducted using discharge abstracts for Medicaid patients under age 65 who were discharged with one of 14 common diagnoses for certain Allegheny County hospitals in 1972 and 1973. Comparisons were made for each individual diagnosis to control for possible differences in case mix. Results indicate that there was no general reduction in length of stay which could be attributed to the PDUR program.


Cost and quality control of laboratory services: the New York City medicaid centralized laboratory proposal. Faced with constantly increasing costs for the provision of laboratory services to Medicaid recipients, the New York City Department of Health last year attempted to implement a program to fundamentally restructure the organizational patterns and financing mechanisms of New York City's clinical laboratory industry. The program, based on competitive bidding, gave one laboratory in each of New York's five boroughs exclusive rights to process Medicaid lab samples and replaced presently existing fee-for-service reimbursement mechanisms with a unique system combining unit pricing and capitation. This paper outlines the principal provisions of the City's proposed contract, analyzes the underlying motivations of the City's decision, and describes the reactions of the existing laboratory service delivery system. In addition, the generic problems of implementing effective administrative techniques for cost and quality control of laboratory services are discussed.


[Complications in modern treatment of posttraumatic osteomyelitis (author's transl)]. Several conditions must be accomplished for successful treatment of posttraumatic osteomyelitis, as there are stability in fracture region, surgical debridement, wound irrigation, cancellous bone transplantation and skin grafting. All this surgical methods involve possibilitis of complications. The most of them can be avoided observing certain rules of management.


Flap reconstruction in major surgery of the head and neck. The challenging restoration of form and function in radical surgery of the head and neck demands sound concepts and proper execution in reconstruction. Flaps are most frequently employed in reconstruction, following major surgery because of their rich blood supply and cosmetic superiority. Of the many types of flaps known, the midline forhead flap, temporoforehead flap, mastoid-occipital flap, tongue flap, and deltopectoral flap have enjoyed most popularity. The design and application of these flaps are discussed. Our techniques in reconstruction of the oral cavity, hypopharynx, esophagus, nose, Andy-Gump deformities (anterior jaw complex resection), pharyngo-orocutaneous fistulas, and radionecrosis of the mandible are presented.


The actions of parathyroid hormone on bone: relation to bone remodeling and turnover, calcium homeostasis, and metabolic bone disease. Part IV of IV parts: The state of the bones in uremic hyperaparathyroidism--the mechanisms of skeletal resistance to PTH in renal failure and pseudohypoparathyroidism and the role of PTH in osteoporosis, osteopetrosis, and osteofluorosis. In early chronic renal failure, the state of the bones resembles that of type II primary hyperparathyroidism. Cortical bone becomes thinner and more porous, and there is increased extent of surface remodeling. These changes are followed in turn by osteomalacia and osteitis fibrosa, although sometimes these may be alternate rather than successive stages. Bone turnover is less than would be expected for the elevation of PTH level, probably because of 1,25 (OH)2D3 deficiency. The resorption velocity and lamellar bone appositional rates are depressed, but woven bone appositional rate may be increased, possibly because of hyperphosphatemia. Bone mass reflects the summation of three independent processes: loss of lamellar bone due to hyperparathyroidism (depending on the extent of insulation by osteoid); accumulation of partly mineralized osteoid because of osteomalacia; accumulation of woven bone because of osteitis fibrosa. Osteosclerosis may be growth-related metaphyseal, subchondral or diffuse axial, and periosteal neostosis may also occur. Some patients on hemodialysis lose bone because of planing rather than lacunar or dissecting resorption, combined with depression of both lamellar and woven bone formation. Hyperparathyroid bone disease tends to improve slowly after renal transplantation. Persistent hypocalcemia reflects a defect in the calcium homeostatic system and cannot be explained solely by the known stimuli to secondary hyperparathyroidism. The increment in plasma calcium in response to PTH infusion is subnormal, both in early chronic and in acute renal failure, probably because of 1,25(OH)2D3 deficiency. This is also the most likely explanation for the depressed level of blood-bone equilibrium. The activity of all three of the PTH responsive cell systems in bone is depressed in renal failure, probably because all three require 1,25(OH)2D3 in order to function normally. In pseudohypoparathyroidism, as in chronic renal failure, hypocalcemia results from a defect in the regulation of the blood-bone equilibrium. The bone-remodeling system shows all gradations of response, from slight depression of bone turnover to overt osteitis fibrosa, but bone turnover is never as low as in PTH deficiency. These differences may reflect the presence or absence of resistance to PTH of the osteoprogenitor cell as well as of the calcium homeostatic system, or may be due to varying degrees of 1,25(OH)2D3 deficiency, as in chronic renal failure. An increase in plasma calcium in response to PTH can occur either in the untreated state or after treatment with vitamin D because either the error-correcting or remodeling system remains responsive to PTH. Pseudohypoparathyroidism may be subdivided into three types, depending on whether the urinary cyclic-AMP response to PTH remains defective despite treatment with vitamin D, improves with treatment, or is normal before treatment. Only the former is associated with the genetic syndrome of Albright's hereditary osteodystrophy...


Preparation and counts of particles in electron microscopy: application of negative stain in the agarfiltration method. The agarfiltration method, published by Kellenberger and Arber in 1957, has been adapted to negative stain with sodium phosphotungstate and uranyl acetate. The technique is described in detail including all recent improvements. The precision obtainable in particle counts is discussed for agarfiltration and sprayed droplets.


Treatment of migraine attacks with an analgesic combination (Mersyndol). The relief of acute migraine attacks with an analgesic/antihistamine combination containing paracetamol, codeine phosphate, doxylamine succinate and caffeine (Mersyndol) compared with that achieved with a placebo has been studied in a double-blind, crossover trial. Mersyndol emerged as significantly better than placebo in the complete relief of migraine pain, and was clearly superior to placebo in partially relieving the pain of migraine. These results suggest that it could be a useful alternative to ergotamine, and a comparative trial with ergotamine is suggested. Side effects with this combination were fairly common but mild, and consisted mainly of drowsiness caused by the antihistamine component.


The evolution of counterpulsation techniques. Assisted circulation techniques are an outgrowth of extracorporeal pump oxygenator systems developed in the mid 1950s. But the differences in physiology of total perfusions and of parital perfusions for assisting circulation delayed the clinical application of the intra-aortic balloon. The problems and risks in providing circulation assistance and the approaches used to overcome them are discussed. The various counterpulsation techniques are described and data presented to demonstrate the increased survival in patients with myocardial infarction and cardiogenic shock.


[Effects of lowly dosed gestagen pill Exlutona on carbohydrate and fat metabolism (author's transl)]. Due to the precautions stopping of megestrol containing oral contraceptives the prescription of oral contraceptives has again become problematic. Oral contraceptives taken over a longer period can cause occasionally side effects which then cause a stopping of these medicaments. In order to get a survey of possible effects on the carbohydrate and fat metabolism 60 patients at the age of 16-26 years who had not been pregnant were observed over a longer period and their laboratory parameters (serum insulin, triglycerides, cholesterol, total lipids) were controlled. Significant changes were only found in the total lipids in the sense of a reduction of the total lipid level. A marked reduction was found with the triglycerides. Basing on these results and taking into consideration the occasionally occurring menstrual irregularity this lowly dosed gestagen pill Exlutona can be recommended not only to young girls but also to patients who often suffer from a relative contraindication because of adiposity, hypertension and subclinical diabetes.


[Experiences in the treatment of rheumatoid arthritis with 90-yttrium-silicate (author's transl)]. In 29 patients suffering from rheumatoid arthritis 90-Yttrium-silicate was instillated 48 times into the knee. An improvement was seen in 41 cases. The success lasted in 3 of 10 so far observed cases more than one year. No side effects were seen. Less than 1 p.c. of the instillated substance was leaving the joint.


The development of mechanical assistance to the failing human heart. Mechanical systems designed to support the failing heart temporarily or permanently are briefly described. Of these systems, most are still in the experimental laboratory, but several devices have had limited trial in patients. One for temporary use, the intra-aortic balloon pump, is now routinely used as adjunctive support for selected patients undergoing open-heart surgery. The development of these systems followed experimental demonstration that by manipulating arterial pressure and flow, it would be possible to increase coronary blood flow and diminish left ventricular work.


An investigation of the binding sites of proteins S8, L23 and L24 on the ribosomal RNAs of Escherichia coli by electron microscopy. An electron microscopic method was used to investigate the binding regions of proteins S8 on 16S RNA, and proteins L23 and L24 on 23S RNA. Regions of the RNA that were not stabilised by the protein were completely denatured in 80% dimethyl-sulfoxide. The lengths of these denatured RNA regions were compared with that of the whole denatured RNA. Conclusions are drawn concerning the approximate location of the three proteins and these results are correlated with both RNA structural data and RNA sequence data on the RNA binding regions of the proteins.


Altered synthesis and stability of RNA polymerase holoenzyme subunits in mutants of Escherichia coli with mutations in the beta or beta' subunit genes. Bacteria with specific temperature sensitive lethal mutations in the gene for the beta' subunit of RNA polymerase synthesize both the beta and beta' subunits at a several fold higher rate at 42 degrees C than wild-type cells relative to total protein. Synthesis of the alpha and sigma subunits proceeds at essentially the wild-type rates under these conditions. In contrast, a mutant with a temperature sensitive lethal mutation in the beta subunit gene synthesizes beta and beta' at 42 degrees C at slightly lower rates than wild-type, while alpha and sigma synthesis is not significantly altered. In all of the mutants at 42 degrees C, newly synthesized alpha subunits are stable, while the beta, beta' and sigma subunits are rapidly degraded. The apparent uncoupling of betabeta' and alpha subunit synthesis seen in the beta' mutants at 42 degrees C might suggest that the synthesis of these subunits is at least in part controlled by different mechanisms.


Characterization of yeast ribosomal DNA fragments generated by EcoR1 restriction endonuclease. The action of Escherichia coli restriction endonuclease R1 (EcoR1) on DNA isolated from Saccharomyces cerevisiae (strain MAR-33) generates three predominent homogenously sized DNA fragments (species of 1.8, 2.2 and 2.5 kilo nucleotide base pairs (KB). Many DNA species of molecular weight greater than 2 million daltons can be recognized upon incomplete EcoR1 digestion of yeast DNA. Four additional DNA species ranging from 0.3--0.9 KB can be identified as the second major class of EcoR1-yeast DNA products. Hybridization with radioactive ribosomal RNA (rRNA) and competition with nonradioactive rRNA show that of the three predominent EcoR1-yeast DNA species, the 2.5 KB species hybridizes only with the 25S rRNA while the lighter 1.8 KB species hybridizes with the 18S rRNA. The intermediate DNA species of 2.2 KB hybridizes to a small extent with the 25S rRNA and could be a result of the presence of the 2.5 KB DNA species. The mass proportions and hybridization values of these 3 DNA species account for about 60% of the total ribosomal DNA (rDNA). The 5 Eco-R1-yeast DNA species of less than 0.9 KB (4 major and 1 minor species) hybridize to varying degrees with the 2 rRNA and can be grouped in two classes. In one class there are 3 DNA species that hybridize exclusively with the 18S rRNA. In the second class there are 2 DNA species that besides hybridizing predominently with the 25S rRNA also hybridize with the 18S rRNA. The 7 EcoR1-yeast DNA species (excluding the 2.2 KB DNA species) that hybridize with the two rRNA account for nearly a 5 million dalton DNA segment, which is very close to the anticipated gene size of rRNA precursor molecule. If the 2.2 KB DNA species is a part of the rDNA that is not transcribed or 5 sRNA then the cistron encoding the rRNA in S. cerevisiae has at least 8 EcoR1 recognition sites resulting in 8 DNA fragments upon digestion with the EcoR1. Consideration is given to the relationship of the rRNA species generated by EcoR1 digestion and the chromosomes containing ribosomal cistrons.


Transcription of Escherichia coli ribosomal DNA in Proteus mirabilis. Transcription of Escherichia coli ribosomal DNA introduced into Proteus mirabilis on F14 is described. We have developed an assay for E. coli coded ribosomal RNA involving fingerprinting of ribonuclease T1 digests of RNA isolated from ribosomal subunits. Sequence differences in the ribosomal RNA of the two species have allowed us to detect E. coli coded 16S, 23S, and 5S ribosomal RNA in ribosomal subunits of the E. coli-P. mirabilis hybrid. The proportion of E. coli coded rRNA in the hybrid is found at a level which is compatible with the number of E. coli (and P. mirabilis) ribosomal DNA sequences. The resulting ribosomal RNA appears in ribosomes in a form which indicates extensive compatibility of E. coli coded ribosomal RNA with P. mirabilis ribosomal proteins and maturational factors.


Growth of coliphage BF23 on rough strains of Salmonella typhimurium: the bfe locus. Coliphage BF23 develops in Salmonella typhimurium rough strains. The phage is neither restricted nor modified by S. typhimurium. The growth patterns of the phage were slightly different in S. typhimurium than in Escherichia coli, although phage propagated on S. typhimurium is identical to the phage propagated in E. coli by several criteria used. Mutants of S. typhimurium resistant to BF23 were isolated and found to map (by P22- and Pl-mediated transduction) in the same position as bfe mutants of E. coli. The order of genes was: metB - argC - bfe - rif - purD - metA. Phage BF23 does not form plaques on smooth S. typhimurium strains, since the phage fails to adsorb irreversibly to smooth cells. Nevertheless, on solid agar, the phage prevents growth of many (but not all) smooth strains. Moreover, UV- and alkali-inactivated phage BF23, although unable to form plaques on sensitive hosts, retains the ability to prevent growth of the host on solid medium. This ability is sensitive to protease and resistant to DNAse and RNase. Heat treatment of the phage causes rapid loss of the cell-growth-preventing-ability whereas the ability to form plaques is lost much more slowly. These results lead to a proposal that phage BF23 virions carry a colicin-like factor that kills sensitive cells.


Expression of the guanine operon of Escherichia coli as analyzed by bacteriophage lambda induced mutations. Studies were made on two guanine-requiring strains of Escherichia coli isolated independently as a result of insertion of prophage gamma into one of the structural genes of the guanine operon. These mutants do not exhibit any detectable guaB function but express the guaA function constitutively at a low level, presumably due to transcription from the pI promoter on the prophage. Various types of plaque-forming gua-transducing phages were generated from these lysogens. The approximate location and the mode of substitution of the gua genes in the phage genome were determined. These results clearly indicate that the gene guaB is located closer to the operator-promoter region of the gua operon than is guaA, and the gene order is "operator"-guaB-guaA.


A simple method for the isolation and characterization of thymidylate uptaking mutants in Saccharomyces cerevisiae. The mutant tmpl--10ts which confers thermosensitive auxotrophy for thymidylate is employed for the selection of 5'-dTMP uptaking mutants. At the nonpermissive temperature yeast cells phenotypically wild type for thymidylate uptake can grow for only 3 to 4 generations in the presence of 10(-2) M 5'-dTMP. Thymidylate utilizing mutants (tum mutants) were isolated which can grow in the presence of 12 to 24 mug 5'-dTMP/ml. Genetical analysis revealed one of these mutant strains to be a double mutant, tuml tum2. For normal growth haploid thymidylate auxotrophic strains require approximately 360 mug 5'-dTMP/ml when tuml and 24 mug 5'-dTMP when tum2 is present, respectively. Cells prototrophic for thymidylate (TMP) harbouring tuml tum2 will also take up 5'-dTMP and incorporate it specifically into their DNA. Thymidylate utilization in such strains is independent of functional mitochondria, as similar incorporation of labelled 5'-dTMP is found in isogenic strains with rho+, rho- and rho0 status. Optimal stimulation of the 5'-dTMP uptaking principle in haploid TMP strains is found at 4 mug5'-dTMP/ml when tuml and tum2 are present.


Modulation of RNA polymerase specificity by ppGpp. ppGpp alters the initiation specificity of RNA polymerase holoenzyme in vitro in a direction which mimics the stringent response in vivo. The transition temperature for opening rRNA promoters is increased by the nucleotide, that for opening phi80 promoters is unaffected. This implies that RNA polymerase can discriminate between different types of promoter. ppGpp may act by effecting a structural change in the enzyme.


Evidence that the gene uvrB is indispensable for a polymerase I deficient strain of Escherichia coli K-12. Conclusive evidence in presented to show that the gene uvrA is dispensable, but the uvrB is indispensable for an Escherichia coli strain carrying gene polA1. We constructed strains E139 (sup-126 polAl uvrB59) and E159 (sup-126 polAl uvrA43) where mutations polAl, uvrB59 and uvrA43 are amber mutations and mutation sup-126 is an amber suppressor mutation effective at 30 degrees C but not at 42 degrees C. At 42 degrees C, strain E139 is inviable but strain E159 viable whereas both are viable at 30 degrees C. Revertants of E139 viable at 42 degrees C occurred spontaneously at a frequency of about 3 X 10(-4). One of the revertants was shown to be caused by suppressor mutation, designated spu, rather than back mutation of the gene uvrB59 or polAl or amber suppressor mutation. Viabilities of the revertants varied from 10(-3) to 1.0 at 42 degrees C compared with those of 30 degrees C. At 42 degrees C, all the revertants with normal viabilities at 42 degrees C were non-filamentous in contrast to the filamentous character of E139. However, strain E159 was viable at 42 degrees C despite its filamentous character. We conclude that the gene uvrB is involved not only in excision repair but also in normal growth in a polA background.


Influence of cultural conditions and mutations on the composition of the outer membrane proteins of Escherichia coli. Various Escherichia coli strains differ in the composition of their major outer membrane proteins. However, all E. coli K12 strains tested possess the same major outer membrane proteins a, b, c and d, although quantitative differences were detected. The influence of growth conditions on the composition of the major outer membrane proteins of E. coli was analyzed. It was found that neither the growth phase at which the cells are harvested, nor the fatty acid composition of the phospholipids has a considerable influence on the composition of these proteins. However, the composition of the growth medium, and, to a less extent, the growth temperature, have a pronounced influence. Certain mutants, changed in the composition of their lipopolysaccharide, are deficient in protein b. Also mutants deficient in protein c and d respectively, are described. Proteins b and c of E. coli K12 were found to be associated with peptidoglycan. Protein bands, corresponding with flagellin and pilin respectively, were identified.


Heptose-deficient mutants of Escherichia coli K12 deficient in up to three major outer membrane proteins. Mutants of Escherichia coli K12, deficient in up to three major outer membrane proteins b, c and d have been constructed. Mutants that lack the lipopolysaccharide sugar heptose are deficient in protein b. All heptose-deficient strains are supersensitive to lysozyme, various antibiotics and detergents. They excrete the periplasmic enzyme ribonuclease I. Mutants deficient in proteins c and/or d have the same sensitivity towards these compounds as the parent strain. Cells of single, double and triple mutants are all rod-shaped. Electrophoretic analysis of cell envelope proteins indicates that in some mutants the protein deficiency is partially compensated for by increased amounts of one or two of the other major outer membrane proteins. Heptose-deficient strains have an increased amount of 2-keto-3-deoxyoctonate.


Phage T4 infection restricts rRNA synthesis by E. coli RNA polymerase. RNA polymerase from T4 infected cells supplemented with E. coli sigma polypeptide has a lower affinity for rRNA promoters than RNA polymerase from uninfected cells. The pattern of transcription by the phage modified polymerase is qualitatively similar to that of the vegetative polymerase in the presence of ppGpp. We suggest that E. coli polymerase holoenzyme normally exists in at least two conformational states, one with a high affinity for rRNA promoters and another with a low affinity, and that T4 infection stabilises the low affinity form.


Mapping of the polA locus of Escherichia coli K12: orientation in the amino- and carboxy-termini of the cistron. Three mutations of the polA cistron, the structural gene for DNA polymerase I of E. coli, have been ordered by three factor transductional crosses. The three mutant polymerase species have altered properties which may be ascribed to defects located in different portions of the polypeptide chain. Our data indicate that the amino terminal end is encoded by the end of the polA cistron nearer to metE and that transcription and translation proceed clockwise on the E. coli circular map towards the rha locus.


Properties of plasmids constructed by the in vitro insertion of DNA from Rhizobium leguminosarum or Proteus mirabilis into RP4. Plasmids have been constructed by insertion of DNA from Rhizobium leguminosarum or Proteus mirabilis into RP4 (an R factor of group P). Such recombinant plasmids retain the wide host range of the parental plasmid, being as efficiently transmissible as the unmodified RP4 and are stably maintained in rapidly growing cultures. The recombinant plasmids, even though each contained a DNA sequence absolutely identical with that of the host strain, are no more efficient at mobilizing the transfer of chromosomal genetic information from that host strain than was unmodified RP4. We therefore conclude that an unknown factor must be essential in the process of chromosome mobilization and rate limiting for that process.


ColE plasmid replication in DNA polymerase I-deficient strains of Escherichia coli. Replication of the non-conjugative plasmids ColE1, ColE2 and Col3 has been examined in a number of DNA polymerase I-deficient strains, two of which contain the amber mutation polA1 along with either of two temperature-sensitive supF amber suppressors. These latter two strains produce reduced amounts of DNA polymerase I polymerizing activity of similar, if not identical properties to that produced by polA+ strains. Our results indicate that the ColE plasmids require different amounts of DNA polymerase I for stable plasmid maintenance. Moreover whereas all three plasmids are maintained in a strain defective in the 5' leads to 3' exonuclease activity of DNA polymerase I, ColE2 and ColE3 are not stably maintained between 30 degrees and 43 degrees  in a number of DNA POLYMERASE I-deficient strains that are temperature-sensitive for ColE1 replication.


Characterization of a ts beta' mutant RNA polymerase of Escherichia coli. RNA polymerase isolated from ts XH56, a conditional lethal mutant unable to grow and synthesize RNA at 42 degrees, was found to be temperature sensitive in vitro. The mutation affects the beta' subunit as determined by mixed reconstitution of isolated subunits from wild-type and mutant enzyme. The mutant RNA polymerase is unstable; addition of glycerol stabilizes the enzyme and increases its activity on native DNA. In addition, the mutant enzymes is sensitive to high ionic strength. Both high temperature and high ionic strength do not affect chain elongation; thus, the mutation renders the enzyme unable either to bind to or melt out promotor sites. From these data we conclude that the beta' subunit plays an important role in promotor selection.


Relation between drug-induced central nervous system effects and plasma levels of diazepam in man. Pharmacodynamic effects and plasma levels of diazepam were studied in healthy male volunteers at different dose levels. Responses to diazepam were quantified, using instruments which measured body sway (statometry) and psychomotor performance (stressalyser tests). High dose-related correlations were obtained between drug-induced changes in test parameters and drug plasma levels, both with regard to stimulant and depressive effects. Techniques were devised for evaluating and comparing the efficacy and usefulness of different types of tests, taking into account critical thresholds, slopes and error estimates, correcting for changes in predrug levels and control (nondrug) trials.


Effect of active metabolites of chlordiazepoxide and diazepam, alone or in combination with alcohol, on psychomotor skills related to driving. The interaction of the main metabolites of diazepam and chlordiazepoxide with alcohol was measured in two double-blind crossover subacute experiments on 40 healthy young volunteers. The drugs were administered for 2 weeks each. The variables measured were choice reaction time and accuracy, eye-hand coordination, divided attention, flicker fusion, proprioception, and nystagmus. ChL, MO and O significantly enhanced the alcohol-induced impairment of psychomotor skills whereas DMD did so only exceptionally on some subjects in the choice reaction test. It is concluded that the diazepam-alcohol interaction on psychomotor skills is mainly due to the parent compound. No correlations between the serum levels of the agents and the changes of performance were found.


Mechanism of the mutagenic action of hydroxylamine. X. Certain specificities in the mutagenesis of N-hydroxy and N-methoxy analogs of cytosine and adenine derivatives. In contrast with N4-methoxycytidine, N6-methoxyadenosine and the corresponding 2'-deoxynucleosides, N4-hydroxycytidine readily penetrates cells of Escherichia coli. Apparently this explains the non-mutagenicity of the N-methoxy compounds when added to an E. coli suspension, and the potent mutagenic effects of the N4-hydroxy analogs under the same conditions. 1-Deazaadenosine and N9- and N1-hydroxyalkyl-substituted adenines and cytosines, inhibitors of adenosine and cytidinedeaminases, are also incapable of crossing the E. coli cell wall.


The genetic instability and mutagenic interaction of chromosomal duplications present together in haploid strains of Aspergillus nidulans. Previous work has shown that strains of Aspergillus nidulans with a chromosome segment in duplicate (one in normal position, one translocated to another chromosome) are unstable. Deletions occur from either duplicate segment. The present work has shown that when a chromosome I duplication and a chromosome III duplication are together in a haploid, deletions from the intact III duplication generally precede deletions from particular sections of the I duplication. Furthermore, the III duplication can enhance to some (but not major) extent the frequency of deletions from the I duplication. After the III duplication becomes reduced in size as a result of the loss of chromosomal material from the translocated duplicate III segment, such a reduced III duplication can greatly enhance the frequency of deletions from the I duplication. In other words, a III duplication of reduced size can promote far more deletions from the I duplication than the intact III duplication. The major increase in the deletional instability of the I duplication as promoted by the reduced III duplication is confined to the translocated duplicate I segment. The reduced III duplication can induce deletions from a section of the translocated duplicate I segment in accord with a temporal programme, and it appears that a particular region of the I duplication is far more under the mutagenic influence of the reduced III duplication than another region. Moreover, there is indication that there is a differential effect of two generally different genetic backgrounds on the susceptibility of duplication-regions to deletion. Possible mechanisms involved in such chromosomal instability are proposed. A manner in which genetic instability may be related to development is also proposed.