A double-blind comparison of clindamycin with penicillin plus chloramphenicol in treatment of septic abortion. The responses to therapy with either clindamycin alone or penicillin plus chloramphenicol in 77 patients with septic abortions were compared in a randomized, double-blind study. Although fever index and duration of hospitalization were similar for both groups of patients, significantly more patients in the group that received clindamycin developed major complications (P less than 0.05). This is believed to result from clindamycin's lack of activity against aerobic gram-negative bacilli. Aggressive management that included early uterine evacuation and broad-spectrum antibiotics effective against both aerobic and anaerobic bacteria was the key to reduced morbidity and mortality rates in treatment of septic abortion. For patients treated with clindamycin, early uterine evacuation appeared more important than antibiotic therapy (P less than 0.005). Bacteremia was documented in a total of 29 patients (38%). Bacteremia was polymicrobial in eight patients (28%) and involved anaerobes exclusively in 18 (62%), aerobes exclusively in nine (31%), and both aerobes and anaerobes in two (7%). The organisms most frequently isolated were Bacteroides (other than Bacteroides fragilis), Peptostreptococcus, and Escherichia coli.


Intraabdominal sepsis: characterization and treatment. Intraabdominal sepsis is frequently present after trauma, surgical resection, or intrinsic diseases of the gastrointestinal tract. When infection occurs it may be generalized or localized in intraperitoneal or extraperitoneal locations as well as in solid organs. The offending microflora is polymicrobial, consisting of both aerobes and anaerobes. Adequate, prompt surgical drainage and the appropriate choice of parenteral antibiotics aimed at both types of bacteria will result in a more favorable postoperative course and will reduce the possibility of local infection and secondary septicemia.


Clindamycin and colitis: a review.

Clindamycin and colitis: a review. Many studies have shown that clindamycin may cause pseudomembranous colitis, a potentially fatal complication. At present, prevention of this complication depends on (1) prescription of the drug only for specific severe infections, (2) early investigation and discontinuation of clindamycin if diarrhea ensues, and (3) vigorous supportive therapy.


Comparison of four aminoglycoside antibiotics in the therapy of experimental E. coli meningitis. Tobramycin, sisomicin, and amikacin were compared with gentamicin in the therapy of experimental E. coli meningitis in rabbits. Meningitis was produced in 40 animals by intracisternal injection of 10(5) E. coli. Three dosages of each antibiotic were administered intravenously over 8 hours. Serum and CSF samples were obtained at 0,2,4,6, and 8 hours for determination of aminoglycoside concentrations and CSF bacteria counts. The four aminoglycosides demonstrated comparable penetration into the CSF. The mean percent penetration (CSF conc./serum conc. X 100%) with the three dosages was 10 to 50% for gentamicin, 8 to 23% for tobramycin, 6 to 16% for sisomicin, and 11 to 23% for amikacin. This variation in penetration reflected individual differences in each dosage group and the increase in percent penetration that was observed during therapy. Sisomicin and gentamicin were consistently bactericidal in vivo. Mean CSF bacterial titers gentamicin were consistently bactericidal in vivo. Mean CSF bacterial titers decreased 3.07 logs in rabbits treated with sisomicin and 2.44 logs in animals treated with gentamicin. Even through CSF concentrations were comparable, the group treated with tobramycin demonstrated only a 0.64 log decrease and the amikacin group had a 0.45 log increase in mean CSF titers. The bactericidal effect of sisomicin appeared to be more rapid than that of gentamicin. During the first 2 hours of therapy CSF titers declined 1.02 logs in animals treated with sisomicin as compared to 0.37 log in animals receiving gentamicin even though gentamicin concentrations were higher (mean 7.4 vs. 4.1 gm./ml.). Sisomicin also demonstrated greater bactericidal activity than the other aminoglycosides in normal CSF in vitro. The results of this study suggest that sisomicin may be of value in the therapy of E. coli meningitis.


Tissue factor generation by human mononuclear cells: effects of endotoxin and dissociation of tissue factor generation from mitogenic response. The effects of the presence of endotoxin in a mononuclear cell culture system have been assessed. Endotoxin was shown to be mitogenic for human peripheral blood lymphocytes and capable of stimulating the generation of tissue factor. Concentrations of endotoxin, found to contaminate many commercial mitogens and antigens, activated mononuclear cells in a time-dependent manner. Generation of tissue factor was detected in cultures harvested from 2 to 72 hours following stimulation with endotoxin. Dose-response curves relating concentrations of endotoxin to mononuclear cell stimulation were determined; as little as 0.001 microng/ml. of E. coli endotoxin was capable of stimulating the generation of tissue factor in the cell cultures. The mitogenic effect of endotoxin was modest, however, and appeared to be unrelated to the ability of endotoxin to active tissue factor. Inhibition of DNA synthesis in the cell cultures by cytosine arabinoside or nonlethal irradiation failed to impair the generation of tissue factor. Endotoxin contamination of various reagents used in cell culture was evaluated with the Limulus assay, which detected as little as 1 X 10(-4) microng/ml. of endotoxin. Endotoxin was detected in preparations of phytohemagglutinin, purified protein derivative of the tubercle bacillus, mumps vaccine, tetanus toxoid, concanavalin A, and pokeweed mitogen. Because of the broad implications of contamination by endotoxin of various reagents, we assessed the specificity of the Limulus assay for the detection of endotoxin in the lectin, concanavalin A, and determined that the reaction was specific for endotoxin. Contamination by endotoxin of mononuclear cell culture systems should be considered as a possible factor in the production of various biological effects attributed to some commonly used mitogens and antigens.


An improved in vitro pyrogen test: to detect picograms of endotoxin contamination in intravenous fluids using limulus amoebocyte lysate. A method for in vitro pyrogen testing using Limulus amoebocyte lysate (LAL) has been described. The method is based upon the measurement of endotoxin-precipitable protein and can be used to measure picogram quantities equivalent to E. coli endotoxin in unknown solutions. When increasing concentrations of E. coli endotoxin are added to a constant amount of LAL and the reaction is allowed to proceed to completion, there is a proportional increase in the protein precipitated by endotoxin. Therefore, by measuring the amount of protein precipitated from LAL, it is possible to determine the equivalent E. coli endotoxin concentration in unknown solutions, when samples of the unknowns are run simultaneously with E. coli endotoxin standards and negative controls. The endotoxin proportional precipitation of protein occurs in reaction mixture showing gelation as well as in reaction mixture where the levels of endotoxin are lower than required for gelation. Determination of precipitated protein provides greater sensitivity for endotoxin detection than the gelation methods currently in use.


The surgical treatment of secretory otitis media in children. Two groups of children with secretory otitis media, 100 in each group, were followed after treatment. The first group was treated with adenoidectomy only, the second group was treated with adenoidectomy and bilateral myringotomies with insertion of grommets. The difference in results between the two treatments was found to be statistically not significant.


Treatment of temporo-mandibular ankylosis with particular reference to the interposition of full-thickness skin autotransplant. In the treatment of the temporo-mandibular ankylosis, the maintainance of separation between the temporal and mandibular raw surfaces, after osteotomy of the bony fusion, constitutes the key to the prevention of recurrence; the great potential of bone to reform is acknowledged by all those who are experienced in this problem. Analysing 168 temporo-mandibular arthoplasties in which different methods have been used in order to maintain the newly created joint space, the causes of failures have been brought out and the difficulties studied. The conclusion is reached that the best results were obtained by the interposition of autogenous full thickness skin. The surgical technique is briefly presented as well as the records regarding the cases followed-up for a period of 2 to 19 years, illustrating the anatomical and functional conservation of the new joints. The experimental investigations concerning the behaviour and fate of the buried skin autotransplants complete the clinical studies, proving the qualities and the value of full thickness skin as an interposition material in arthroplasties.


Oestrogen-induced changes in the secretion of luteinizing hormone caused by continuous infusions of luteinizing hormone releasing hormone in the long-term ovariectomized rat. Oestrogen-induced changes in luteinizing hormone secretion, caused by continuous infusions of luteinizing hormone releasing hormone (LH-RH), appear to depend on the duration of exposure of the pituitary gland to the releasing hormone. The initial oestrogen-induced depression of the potential response of the pituitary gland to LH-RH, which always seems to occur, does not necessarily turn into an enhancement of this potential response. It is suggested that this may be due to the fact that the response of the pituitary gland to LH-RH infusions is a continuously changing parameter influenced by oestrogen.


Immunochemical characterization of gastrin in pancreatic islets of normal and genetically obese mice. Material with gastrin-like immunoreactivity has been extracted from micro-dissected islets and from antral mucosa of normal and genetically obese mice. The islet and antral extracts cross-reacted with antisera specific for the CO2H-terminal portion of human heptadecapeptide gastrin, but did not cross-react with antisera specific for the NH2-terminal region or with an antiserum specific for the entire, intact, molecule. With the antiserum showing highest cross- reactivity, the concentration of immunoreactive gastrin in normal islet tissue (138 pmol/g, standard human G17-I) was approximately 50% that in obese mouse islets (204 pmol/g) and 2% that in normal antral mucosa (6-1 nmol/g). Following fractionation on Sephadex G-50 the principal forms of gastrin in the islet and antral extracts had similar elution volumes to human heptadecapeptide gastrin, although other, probably smaller, forms of gastrin were also noted in the islet extracts.


A clinical study of the use of human chorionic gonadotrophin in weight reduction. Treatment of obesity with human chorionic gonadotrophin was shown to be of no better value than saline in a double-blind crossover study of weight reduction in obese subjects. There was also no significant difference in mood, hunger, or missed injections, and no apparent difference in adherence to diet when the two agents were compared. In contrast, a significant difference was found in the ability of subjects to lose weight in the first four weeks of the study in contrast with the second four weeks, no matter which agent was used. Thus, the initiation of a new therapeutic program, even using an inert agent, has a temporary benefit--a manifestation both of placebo effect and the Hawthorne effect.


Conditions predisposing to suicide: a review. By reviewing causes of death among cohorts of various major disease entities or conditions, one may infer that a large majority of suicides are associated with a relatively small number of conditions. From the available follow-up studies, we might estimate that the following percentage of affected individuals will die by suicide: primary (endogenous) depression, 15 per cent; reactive (neurotic) depression, 15 per cent; alcoholism, 15 per cent; schizophrenia, 10 per cent; psychopathic personality, 5 per cent; opiate addiction, 10 per cent or more. Rough estimates of the number of suicides per year in the United States attributable to each condition might be as follows (using low incidence figures): depression, 12,900; alcoholism, 6,900; schizophrenia, 3,800; psychopathy, 2,000 (?); drug addiction, 900.


Murder will out.

Murder will out. A 1974 showing of more than 200 oils and water colors at the Tate Gallery, London, has led to a revival of interest in the 19th century English painter, Richard Dadd (1817 to 1886). In 1843, Dadd killed his father, cutting his throat, because he believed him to be the devil in human form. On a trip to the Near East, Dadd became deluded that the Egyptian god Osiris was directing him to eliminate the devil's influence. Four months after he returned to London he murdered his father, and was institutionalized for the last 43 years of his life. We advance the hypothesis that one particular painting. 'The Fairy Feller's Master-Stroke,' symbolically re-enacts the murder and makes talion restitution. The painting shows minute attention to detail and altogether occupied the artist for 9 years. He also made a water color copy of it entirely from memory, and wrote a 22-page poem explaining the picture with the title, 'An Elimination.' We suggest that this hints at the same theme of undoing. Some art critics have seen in Dadd's other art works a projection of his inner feelings, especially a series of more than 30 water colors entitled 'Sketches to Illustrate the Passions,' amongthem 'Murder,' 'Anger,' 'Hatred,' 'Grief,' and 'Melancholy.' We construe these to support the thesis of redoing and undoing following the trauma of murder. We also mention Dadd's reminiscing, visible in his art, and its usefulness in reaffirming his self-identity. In the art work of Dadd's last 25 years, violent scenes are remarkably absent. Instead, imaginary landscapes and seascenes--the subject matter of his earliest adolescent art--reflect an inward absorption in and continuity of lifelong interests. We suggest that the long process of painting 'The Fairy Feller's Master-Stroke' recapitulated and made restitution for the murder, encapsulating it so that compulsive expression of violent ideation was largely reduced, allowing other memories and activities to be engaged and expressed.


Droperidol in acutely agitated patients. A double-blind placebo-controlled study. Forty-one acutely agitated patients received an i.v. injection of 4 ml of a double blind solution containing either 10 mg of droperidol or placebo. The need for further medication (5 mg of haloperidol after 3 minutes or individually adapted psychotropics after 30 minutes) was used as a parameter for the evaluation of the results. Three minutes after the injection, haloperidol was needed by only six out of 19 patients of the droperidol group, but by 19 patients of the control group. Thirty minutes after the first injection, further medication was needed by only four droperidol patients and 10 placebo patients. No side effects could be attributed to the double blind medication.


Enamel bonding plastic materials in modifying the form of abutment teeth for the better functioning of partial prostheses. The potential uses of enamel bonding sealants and composite filling materials in increasing the retentive form of abutment teeth and covering the preparations for the occlusal supports of partial prostheses were studied in laboratory conditions. The materials tested were Nuva and Concise sealants and composite resins. Extracted permanent human molars, premolars and canines were inserted into acrylic blocks, two teeth in each block. An unretentive clasp framework was made on every test block. A retention prominence was built up separately of sealants and of composite materials occlusally to the tip of each clasp arm. The bond strength and wear resistance of the materials was tested in a device designed for this study. The bond of the prominences was very good, only two out of 114 prominences loosened. The retention gained with prominences was, on average, 18 N measured by the force needed for removal. The decrease in the total retention of the four clasp arms was measured by the force needed to remove the clasp framework. The total retention of the prominences made of Nuva and Concise sealants after 5000 removals was 53 and 50% of the original, when long, flexible clasp arms were used. The corresponding figures for composite resins were 56 and 59%. Short rigid clasp arms caused a distinctly faster abrasion. The prominences made of sealants, in particular, were abraded rapidly, one-fifth of retention being left after 3000 removals.


Reconstruction of alveolar ridge and jaw defects resulting from gunshot wounds. Reconstruction and rehabilitation of acquired defects of the oral cavity is an important dental service. Severe deformities of the jaws may result secondary to gunshot wounds of the oral-facial region. New advances in soft and hard tissue surgical reconstruction can be of great benefit to the patient when coupled with prosthetic rehabilitation. In recent years there has been a significant increase in the incidence of gunshot wounds in the civilian population in the United States, and those of the mouth and jaws are relatively common-place. Gunshot wounds to the face and jaws may cause gross destruction of tissues. Although immediate definitive treatment of wounds reduces the mutilating effect, a significant number of patients require extensive reconstructive procedures. In addition, prosthetic rehabilitation is almost always needed. The purpose of this paper is to briefly review some recent advances in reconstruction of the maxilla and mandible following gunshot injuries.


The construction of a crown for clasp-bearing teeth. A method is described for the fabrication of clasp-bearing crowns. The technique involves the preparation of a thin gold transfer coping, on to which the bulk of the crown is cast in a later stage.


Quantitative evidence for the helicoid relationship between the maxillary and mandibular occlusal surfaces. A method for measuring the transverse inclination of molar teeth is described which enabled significant differences (P less than 0.001) between the three molars to be demonstrated for a sample of English Modern (n 24) and Romano-British (n20) skulls. No significant differences between the transverse molar inclinations were found for the Bronze Age (n 10) or the Neanderthal (n 8) sample.


Repair of a large anterior maxillary defect with a skin-tube and cartilage graft. A case of a traumatic defect of the maxilla is described. The patient sustained an injury in the middle third of his face that involved loss of the anterior portion of the maxilla, the alveolus from the right molar to the left premolar region, and the anterior two thirds of the hard palate with comminuted fractures of the adjacent bones. The resulting defect was successfully closed by means of a skin-tube pedicle and cartilage graft. The discomfort and difficulties in swallowing and speech as well as masticatory disturbance were much improved. The grafted skin took on an appearance similar to oral mucosa and the follow-up examination a year later showed a well-functioning palate. The cartilage, however, seemed to be undergoing resorption.


Replacement of condylar process.

Replacement of condylar process. Three cases of replacement of the condylar process have been presented with their courses and the type of prosthesis that was chosen. Each case has a unique cause with different needs for the use of a prosthesis.


Alteration of free serum amino acids in voles infected with Trypanosoma brucei gambiense. Free serum amino acid pools of field voles, Microtus montanus, were determined over a 24 hr period, and compared to values obtained from voles infected with Trypanosoma brucei gambiense. The majority of amino acids in the control animals demonstrated a diurnal variation, peaking predominantly during the dark portion of the photoperiod. This trend was not evident in the infected animals. In addition, infected voles possessed an apparent state of hypoaminoacidemia, with levels of threonine, serine, valine, isoleucine, leucine, tryosine, and tryptophan typically below uninfected values. Alanine and proline, in contrast, were markedly increased at certain time points. Tyrosine (reduced by approximately 50%) and tryptophan (reduced to levels below detection) underwent the most pronounced drop in trypanosome-infected animals, indicating the possibility of a related alteration in pools of derivative biogenic amines in other tissues. This suggests a role for the latter 2 amino acids in the neuropsychiatric syndromes of African trypanosomiasis.


The "window" orchidopexy for prevention of testicular torsion. Torsion of the testicle is often due to the "bell-clapper" deformity. This deformity is frequently bilateral. Prevention of future episodes of torsion depends upon the creation of a broad area of dense adhesion between the tunica albuginea and the scrotal wall. The results of this study indicate that this may be best accomplished by creating a window in the tunical vaginalis so that during healing a broad area of the tunica albuginea is held in apposition to a raw surface devoid of tunica vaginalis. Simply suturing the testical to the wall of the hemiscrotum does not always result in permanent fixation.


Evaluation of the use of freeze-dried skin allografts in the treatment of human mucogingival problems. The purpose of this investigation was to evaluate the clinical responses to freeze-dried skin allografts when used to correct mucogingival problems in humans. FDS was obtained by the NMRI Tissue Bank after processing by standard procedures. The recipient sites were prepared using the standard partial thickness dissection with apical periosteal separation. Rehydrated FDS was sutured into place to completely cover the recipient sites. Routine postoperative procedures were performed. Evaluations were made by means of calibrated periodontal probe measurements, Kodachromes, and radiographs preoperatively and up to 12 months postoperatively. Fourteen patients received 24 FDS allografts over a total of 56 tooth sites. All treated teeth showed a substantial increase (greater than 2 mm) in the width of the zone of keratinized gingiva at all postoperative time periods (2.88 +/- 1.57 mm at 12 months). Other findings included a mean gain of attachment of 0.40 +/- 1.08 mm, a mean decrease in recession of 0.12 +/- 0.91 mm, and mean decrease in pocket depth of 0.33 +/- 0.53 mm. Patient comfort was good, and there were no untoward sequelae, even in patients receiving multiple grafts. This study indicates that FDS allografts are an acceptable and beneficial material for treatment of mucogingival problems in humans.


Developmental analysis of human figure drawings in adolescence, young adulthood, and middle age. Analyzed 195 human figure drawings (HFDs) of adolescents, young adults, and middle-aged adults in terms of developmental differences in anxiety signs, grouped into aggressive-hostile and insecure-labile categories, and according to sex-role stereotype, as measured by the Broverman Sex-role Stereotype Scale. Adolescent males and females were significantly more likely to obtain more anxiety signs than the two adult groups, although young adults and middle-aged adults did not differ from one another in HFD performance. The most reliable sex difference was that males reveal significantly more aggressive-hostile indices in the HFDs relative to females; no significant sex differences were obtained for number of insecure-labile indices. The degree to which one has adopted a conventional sex-role stereotype was not predictive of anxiety sign differences in HFD performance for either sex or for any age group.


Nonverbal assessment of interpersonal affect. Two nonverbal methods for assessing degree of interpersonal attraction were explored. Twenty children ranging from 11 to 13 years of age were asked to select two liked and two disliked classmates of the same sex. On four different trials, subjects selected one geometric block to represent themselves and one to represent a pre-selected classmate, then placed the figures on a ruled board. Distance between objects was measured and found to be significantly related to degree of peer liking. In addition, subjects were asked to draw each of the four peers. The human figure drawings were rated for total pictorial detail which was found to vary strongly across magnitude of liking for female subjects, and for parts integration which was found to vary with degree of peer liking for both sexes. The degree of rated positive affective tone of drawings was also found to increase with liking. Implications for the use of these two interpersonal assessment techniques in clinical practice were discussed.


Internal-external expectancy, maladjustment and psychotherapeutic intervention. This paper reviewed research on the relationship between internal-external expectancy, maladjustment and psychotherapeutic intervention. The implications drawn from the studies reviewed were: (a) externality is related to poor psychological adjustment and (b) psychotherapy can be effectively utilized to modify expectancy.


A cognitive style approach to creative thought. Creative thinking was explored from several approaches to further understanding of the interrelationship of perception, personality, and cognition. College students (N = 45) were administered the Group Embedded Figures Test (GEFT), the Remote Associates Test (RAT), a questionnaire concerning RAT strategy, and two self-report scales. Field independent subjects were found to be significantly (p less than .001) more creative than field dependents. Correlations between the RAT and GEFT and the self-report measures of conformity and creativity, while largely nonsignificant, were in the predicted directions. Results demonstrated that advanced strategy levels and insightful responses were significantly related to high performance on the RAT. Theoretical links between cognitive style and Piagetian concepts were discussed in regard to creative thought. Overall, these findings support the contention that the creative processes should be studied, not as isolated structures, but with relational and multifaceted emphasis.


Potency of synthetic luteinizing hormone releasing hormone preparations in rat anterior pituitary cell cultures. Selected synthetic luteinizing hormone releasing hormone preparations were assayed, and their potencies were determined relative to one sample utilizing primary cultures of enzymatically dispersed rat anterior pituitary cells. Preliminary cell culture experiments indicated that luteinizing hormone releasing hormone had to be in constant contact with cells for continued luteinizing hormone secretion. Luteinizing hormone levels in media reached a maximum concentration after 4 hr of continuous luteinizing hormone releasing hormone exposure. Cell culture bioassay was selected over the bioassay employing chronically ovariectomized steroid-blocked rats due to greater sensitivity and economy. The assay of each luteinizing hormone releasing hormone preparation was replicated four to seven times. Preparations from several companies were less potent (p less than 0.05) than the reference product. Contaminants were disclosed by TLC in preparations with potencies lower than the reference product.


Analysis of sulindac and metabolites by combined isotope dilution-radioimmunoassay. Sulindac, a new anti-inflammatory agent, and its sulfone and sulfide metabolites were conjugated to bovine serum albumin by the N-hydroxysuccinimide active ester procedure. Antiserum from rabbits immunized with each of these haptens exhibited extensive cross-reactivity, precluding differential analyses of the three species by displacement assay without prior separation. Therefore, an analytical method based on a combination of isotope dilution and radioimmunoassay was devised. A known mixture of the three chemical species, each labeled with tritium, was equilibrated with plasma or urine samples, reisolated chromatographically, and quantitated by binding to an appropriate immunoglobulin. The radiolabeled materials thus served as recovery standards as well as labeled antigens for each displacement assay. Sulindac and each of its metabolites in plasma or urine at concentrations as low as 500 ng/sample were differentially determined by this procedure. However, since an extraction is required, several milliliters of plasma can be used for each sample, thus increasing the actual sensitivity of the assay.


Synthetic acetylenic antifungal agents.

Synthetic acetylenic antifungal agents. Several monoamino bis(propynyloxy)benzenes were prepared by a Mannich reaction and tested for antifungal activity against Trichophyton schoenleini, T. mentagraphytes, T. tonsurans, Candida albicans, and Epidermophyton flocossum. In addition, the bis(propynyloxy)benzene intermediates were tested and comparisons were made with standing drugs. The intermediates were found to be the most active, although two Mannich bases possessed considerable activity.


The mechanism of action of dantrolene sodium. Dantrolene sodium is thought to affect some step in the excitation-contraction coupling process. Using a point voltage clamp to determine mechanical thresholds of individual fibers of frog, rat and goat skeletal muscle preparations, we found that dantrolene both raises (moves to more positive potentials) the rheobasic potential and increases the steepness of the strength-duration curve for mechanical threshold. The effect of raising the rheobase reaches a maximum at 1.2 x 10-5M dantrolene whereas the steepness effect occurs only at a saturating concentration (3.8x10-5M),indicating that dantrolene has two sites of action. The rheobase effect is absent below 18 degrees C (suggesting a phase transition) and it is competitively antagnoized by the calcium ionophore A23187 which can release calcium from the sarcoplasmic reticulum. The data indicate that dantrolene raises the rheobase by directly decreasing the release of calcium from the sarcoplasmic reticulum. We propose that dantrolene inhibits the movement of a natural calcium ionophore. Measurements of the voltage-dependent charge movement associated with excitation-contraction coupling showed that dantrolene did not significantly change the amount of charge moved. The time to peak of the ON current was not significantly changed, but that of the OFF current was significantly shortened. This action of dantrolene on the kinetics of the OFF current may account for its effect on the steepness of the strength-duration curve.


Effect of 13-NLE-motilin on gastric secretion, serum gastrin level and mucosal blood flow in dogs. 1. In dogs with gastric fistulas and vagally innervated fundic and antral pouches, 13-norleucine-motilin (13-nle-motilin), a synthetic analogue of motilin, infused intravenously in graded doses produced a dose-dependent increase in gastric acid and pepsin outputs. 2. The motilin-induced stimulation of gastric secretion occurred independently of antral pH and was not accompanied by any alteration in the serum gastrin level suggesting that motilin did not affect the release of gastrin. 3. When infused intravenously in a constant dose against a constant background stimulation with pentagastrin or histamine 13-nle-motilin inhibited both acid and pepsin secretion from the main stomach and fundic pouch. 4. The inhibitory effect of 13-nle-motilin was always associated with a marked reduction in mucosal blood flow but without any change in the ratio of aminopyrine concentration in the gastric juice and blood plasma indicating that this peptide primarily affected gastric secretion but did not limit the gastric mucosal microcirculation.


Attachment fixation for overdentures. Part I. Scientific evidence of both constructive and destructive movements of teeth has influenced the design and selection of attachments for overdentures. Dowel designs that would be acceptable for normal copings must be reconsidered in view of the mechanical effectiveness of parallel-walled dowels and screws. Coping designs for attachment overdentures must provide retention, resistance to rotation, and bulk when joined with the dowel and attachment, without negating the advantage of the reduced crown-root ratio. Splinting with a bar-type attachment (1) has advantages over splinting with a stud-type attachment that outweigh the disadvantages of bulk and (2) provides ease of replacement when one of several remaining teeth is excessively mobile. Part II will consider the various types of bar, stud, and auxillary attachments for the overdenture.


Effects of overdentures upon remaining oral structures. This study provided the following guidelines in the selection of specific designs for overdenture abutments: 1. The Dolder bar, which exhibits more cross-arch involvement than the Zest anchor, will share the occlusal load across the arch, between the abutments and the supporting structures. 2. The posterior edentulous regions will receive some physiologic stimulation with the Dolder bar, for it shares more stress here than the Zest anchor. 3. The forces on the Dolder bar produce stress directed more apically than that from the Zest anchor. Since this force is better tolerated, use of the Dolder bar may be indicated for a short-rooted tooth with less supporting bone. 4. The greater stress concentrated around the abutment teeth by the Zest anchor makes use of this design in a tooth that is periodontally sound and has a long root structure well imbedded in supporting bone seem logical.


A technique for placing names in dentures. A simple technique for placing patients' names in their dentures has been described. All dentures made at the prosthodontic clinic of the University of Washington now have names imbedded in the acrylic resin in the hope that problems of denture identification will be eliminated in the future.


Mylohyoid ridge reductions as an aid to success in complete lower dentures. A common problem of the mylohyoid ridge in the resorbed edentulous mandible is discussed. A surgical technique that is simple, though efficient, is described for the elimination of the anomaly in the ambulant patient. A prosthetic technique is suggested for maximum advantage to be gained from the operation.


Lingual flange design in complete dentures. The lingual design advocated for complete lower dentures involves no changes in current concepts regarding minimum-pressure, functional impression techniques. The sublingual horizontal extension suggested is placed in a biologically acceptable fashion by increasing the area of the denture, which enhances retention and stability.


Subjective reactions to major connector designs for removable partial dentures. Simlated partial denture frameworks were fabricated for 12 dentists (subjects) who had intact dentitions and who had intact dentitions and who had had no previous experience in wearing partial dentures. The outline of the major connectors was modified during a 1 week interval. The data obtained from questionnaires brought about the following conclusions: 1. Preferences in maxillary major connector design were as follows: (1) broad posterior strap, (2) anteroposterior bar, (3) ring-type design, and (4) full palatal coverage. 2. The mandibular lingual bar was chosen over the lingual plate by a 3:1 ratio. 3. The natural palatal metal finish was perferred to the highly polished finish. 4. Metal borders parallel to tongue movement were better tolerated than those lying transverse. 5. Thickening of the posterior strap to permit its narrowing was not clinically feasible. 6. In general, patients adapted best to major connectors that covered the least amount of soft tissues.


A comparison of the casting ability of precious and nonprecious alloys for porcelain veneering. The alloys tested varied with respect to their castability. This variability is related to density. Problems caused by low density may be solved by increasing the casting force. For all parameters measured in the laboratory, Thermocraft, a precious alloy, proved to be the most satisfactory- Wiron S, a nonprecious alloy, was comparable to Degudent Universal, a gold alloy. The application of Wiron S as a successful gold substitute should, therefore, be further investigated clinically. Equipment, investment, and casting techniques, all designed for the casting of gold alloys, were also used for the nonprecious alloys. These are standard facilities readily available in clinical practice. Modifications or technical improvement to these factors may result in more successful application to the other nonprecious alloys.


Repair technique for a fractured crowned tooth. A simple technique is presented in which an existing crown can be replaced on a broken endodontically treated tooth in one appointment. This can reduce the working time and expense required for a new crown.


An evaluation of four variables affecting the bond strength of porcelain to nonprecious alloy. Four variables that could possibly affect the bond strength of the porcelain to nonprecious alloy were investigated. The variables were directional variations of metal preparation using the Paasché Air Eraser with aluminum oxide fast-cut abrasive, atmosphere variations in the furnace from low to high temperature limits of the degassing cycle, time variations at normal atmosphere of 1,850 degrees F. (degassing upper-limit timing), and firing of the opaque layer of porcelain at different temperatures. A total of 162 Ticon alloy interfaces were prepared, from which 81 paired test samples were constructed. Porcelain was fused to the samples and tested under specified conditions of preparation utilizing an Instron Universal testing machine. It was determined that firing the opaque layer at 1,840 degrees F. at a rate of 75 degrees F. per minute more than doubled the mean bond strength of all samples. The time at the upper limit of the degassing cycle also had a significant effect on the bond. As the time increased, the bond strength decreased. Complete bonds between porcelain and nonprecious metals were demonstrated when the fracture occurred in the porcelain and not at the interface. It is recommended that the opaque firing and degassing be done in accordance with the foregoing findings.


'Microstix'--a new diagnostic aid.

'Microstix'--a new diagnostic aid. The usefulness of ;Microstix' as a diagnostic tool in urinary tract infections in general practice has been evaluated. The nitrite component detected only 53 per cent of cases of significant bacteriuria, and gave rise to a nine per cent false positive result. The culture media correctly detected 93 per cent of cases of significant bacteriuria, but this was associated with a false positive result of nine per cent.


Pituitary responsiveness to synthetic LH-RH and pituitary LH content at various reproductive stages in the sheep. In sheep the basal concentration of LH in jugular vein plasma was significantly higher during the first 50 days of gestation in late pregnancy or at parturition. The pituitary response to a single i.v. injection of 200 microng synthetic LH-RH was determined at different stages of gestation and compared with that of anoestrous and cyclic sheep. Pituitary response to LH-RH decreased progressively with advancing gestation: by 56 days after mating the response had declined to 35% and by parturition to 14% of the value in anoestrous sheep. The pituitary response to LH-RH increased after parturition and the pattern of recovery differed in non-lactating and lactating sheep. By 63 days postpartum the response to LH-RH in non-lactating and lactating animals had returned to values similar to those in sheep during anoestrus and sheep during the luteal phase of the oestrous cycle. A decrease in pituitary responsiveness during pregnancy was associated with a decrease in pituitary content of LH. The quantity of LH released in response to a standard injection of LH-RH was linearly related to pituitary LH content.


Studies of pituitary function in lactating ewes. The release of LH from the pituitary of lactating ewes was studied. In Exp. 1, ewes were injected with 50 microng oestradiol benzoate (OB), 2-0 mg testosterone propionate (TP) or oil only (control) on days 5, 10, or 20 after lambing. LH was measured in peripheral plasma samples obtained 20-38 h after treatment, and the ovulations were recorded. The number of ewes in which an LH release was detected, and the amount released, declined between Day 5 and 20 after OB treatment but increased after TP treatment. The releases of LH were not always accompanied by ovulation and the incidence of ovulation was higher in ewes treated with TP. In Exp. 2, lactating ewes were injected with 1 or 5 (at 2-h intervals) doses of 50 microng Gn-RH, on Days 12 or 25 after lambing. LH was measured in peripheral plasma samples collected every 2 h for 10 h and every 3 h for a further 70 h. Release of LH occurred in all ewes, the amount being greater in ewes receiving multiple injections and in ewes treated on Day 25. The incidence of ovulation was higher after treatment on Day 25. Multiple injections of Gn-RH appeared to reduce the incidence of abnormal corpora lutea.


Effects of vaginal-cervical stimulation in seven species of muroid rodents. Six species of muroid rodents (Peromyscus californicus, P. eremicus, P. gossypinus, Mesocricetus auratus, Rattus norvegicus and R. rattus) were given artificlal vaginal-cervical stimulation in an attempt to induce pseudopregnancy. Some females of each species became pseudopregnant, but it was not clear that stimulation patterns mimicking the copulatory patterns of conspecific males were more effective than other patterns of stimulation. In the non-domesticated species (Peromyscus and R. rattus) a few females responded to a variety of stimulus conditions, and no species differences in responsiveness among the wild species were evident. The established laboratory rodents (R. norvegicus, M. auratusy were markedly more responsive to artificial stimulation, suggesting possible effects of domestication on fecundity and reactions to handling- Microtus ochrogaster, an induced ovulator, ovulated in response to vaginal-cervical stimulation only if one intromission from a male was also provided. No other differences in the responses of reflex and spontaneous ovulators were apparent.


Changes in protein synthesis during maturation of sheep oocytes in vivo and in vitro. The qualitative profiles of the proteins synthesized by sheep oocytes at various stages of maturation were determined by electrophoretic separation in one dimension on polyacrylamide SDS gels. No change in protein synthetic pattern was observed in ooce changes had taken place in at least 12 separate protein bands. Marked alterations in the synthesis of some proteins were apparent 15 h after LH; formation of proteins in 5 of the original bands was either reduced or not detectable, while new synthesis was evident from the appearance of 7 additional bands. The pattern of proteins produced by oocytes cultured within the follicle corresponded closely with that observed in vivo: changes in synthesis were initiated about 9 h after addition of gonadotrophin and were completed by 15 h. Oocytes cultured outside the follicle in a gonadotrophin-containing medium did not exhibit a change in protein synthesis and at 15 h only those proteins produced during the early stages of maturation were being synthesized.


P-Aminobenzoic acid derivatives. Mode of action and structure-activity relationships in a cell-free system (Escherichia coli). The agonistic and antagonistic effects of nuclearly substituted p-aminobenzoic acids (PABA) on the folate-synthesizing system of E. coli have been studied in whole cell and cell-free systems. All studied derivatives form dihydropteroic acid analogues in the presence of a cell-free folate-synthesizing enzyme system. A thin-layer chromatographic system has been elaborated to determine the rate of analogue formation in the cell-free system. Physicochemical parameters of the PABA derivatives, such as pKa, pi, and Rm values, have been determined. These values have been used in a structure-activity analysis which revealed that the rate of analogue formation in the absence of PABA is independent of the lipophilic properties. Ionization seems to be the decisive factor for the incorporation. As all studied PABA derivatives are totally ionized under the experimental conditions, the rates of analogue formation are very similar with the exception of compounds bearing bulky groups in the 2 position. The variance in inhibitory power may therefore either be due to differences in the ability of the analogues to serve as metabolites or to competition with PABA.


Synthesis and biological activity of potential antimetabolites. Several known alpha-amino acid analogues and a new compound, N-chloroacetylphosphoramidate, a carbamyl phosphate analogue, were screened as antitumor agents. All gave 50% growth inhibition of cultures of human epidemeroid carcinoma of the nasopharynx at dosage levels of 2-8 mug/ml while showing no activity against L1210 lymphoid leukemia in vivo in BDFi mice.


Synthesis and antitumor activity of 1,2-dihydro-1-(2-deosy-beta-D-erythro-pentofuranosyl)-2-oxo-5-methylpyrazine 4-oxide, a structural analogue of thymidine. 1,2-Dihydro-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-2-oxo-5-methylpyrazine 4-oxide was synthesized by condensation of the silylated pyrazine base with the blocked chloro sugar, followed by removal of the protecting groups. The compound inhibited the growth of leukemia L1210 cells in vitro by 50% at 2 x 10-7 M. At 400 mg/kg/day x 6 it increased the life-span of leukemia L1210 bearing mice by approximately 55%, without apparent toxicity to the host.


A manual method for applying the Hansch approach to drug design. A procedure is described in which an initial small group of compounds is selected, tested, and ordered according to potency. The potency order in the group is then compared to the tabulated potency order calculated for various parameter dependencies relating to hydrophobic, electronic, and steric effects. From this activity pattern analysis the probable operative parameters can be deduced and a new substituent selection made for the synthesis of potentially more potent analogues. Application of the method is illustrated with a series of examples. It differs from a previously described decision tree, single compound stepwise approach in that it involves the batchwise analysis of small groups of compounds, usually the preferred procedure for logistical reasons if the compounds are relatively easy to synthesize.


Synthesis and antiprotozoal activity of 2,5-bis(4-guanylphenyl)furans. Eighteen substituted 2,5-bis(4-guanylphenyl)furans and related analogues, including "masked" amidines in which the guanyl function is incorporated into a heterocyclic ring, have been synthesized and their antimalarial and antitrypanosomal activity has been evaluated. None of the compounds exhibited high orders of antimalarial activity; however, 11 were very active against Trypanosoma rhodesiense in mice. Six compounds, including 2,5-bis(4-guanylphenyl)furan (4) and its 3-chloro (32), 3,4-dichloro (31), 3-methyl (25), 3,4-dimethyl (20), and 3-chloro-4-methyl (38) derivatives, produced cures in mice at submilligram dosage levels; the 3,4-dimethyl (20) analogue exhibited a prolonged curative effect providing protection for 30 days after a single dose against a challenge by T. rhodesiense. These six compounds are somewhat more active in this screen than stilbamidine, hydroxystilbamidine, and pentamidine. The "masked" amidines generally exhibited lower antitrypanosomal activity than their true guanyl counterparts. Compound 4 was synthesized from 1,4-di-p-bromophenyl-1,4-butanedione by cyclodehydrative furanization to 2,5-bis(4-bromophenyl)furan (2) which was allowed to react with Cu2(CN)2 to produce the corresponding bis-nitrile 3. The latter compound was ultimately converted by way of an imidate ester into 4. Similarly, the 3- and/or 4-substituted derivatives of 2 were employed to prepare the other members of the series.


Correction of prior estimate of the biological activity of an N-trifluoroacetyl analogue of D-threo-chloramphenicol relative to chloramphenicol. The inhibitory rate constants, k, for the inhibition of the rate of Escherichia coli generation at various concentrations, C, of chloramphenicol nad its N-trifluoroacetyl analogue were determined in vitro in accordance with kapp = k0 - kC where kapp is the apparent first-order generation rate constant at a drug concentration C and k0 is that constant in the absence of drug. The activity of the analogue was one-tenth that of chloramphenicol in contrast to a previously reported value.


Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds. Twelve esters (C1-C6) of erythro- and threo-2-bromo-3-fluorosuccinic acid and related compounds were tested for antifungal activity against Candida albicans, Aspergillus niger, Mucor mucedo, and Trichophyton mentagrophytes at pH 5.7 and 7.0 in the absence and presence of 10% beef serum in Sabouraud dextrose agar. At pH 7.0 in the presence of 10% beef serum, no consistent pattern in the fungitoxicity of the erythro- and threo-2-bromo-3-fluorosuccinate esters was seen. Increasing the length of the ester function affects fungitoxicity as follows: C2 greater than C1 greater than C3 greater than C4 greater than C5 greater than C6. The most fungitoxic compound in this study was threo-ethyl 2-bromo-3-fluorosuccinate (C. albicans, 14 mug/ml; A. niger, 30 mug/ml; M. mucedo, 9 mug/ml; T. mentagrophytes, 5 mug/ml). Due to the ease of dehydrohalogenation, the fungitoxicity of 2-bromo-3-fluorosuccinic acid esters may be the result of a mixture composed of the parent compound, the bromo- and fluorofumaric acid esters, and HF and HBr of which part may be formed extracellularly and part within the cell.


Cholesterol Stimulation of Penetration of Unilamellar Liposomes by Hydrophobic Compounds. The incorporation of cholesterol into unilamellar liposomes greatly increased the transmembranous movement of hydrophobic ionophores such as nigericin. In reconstituted liposomes containing rhodopsin as the only protein, the presence of cholesterol lowers by 10-fold or more the amount of negericin required to eliminate the light-driven proton gradient. These effects are seen both above and below the transition temperature of the phospholipid used for reconstitution. Cholesterol similarly increases the ability of A-23187, 1799, or NH4SCN to collapse the proton gradient of bacteriorhodopsin vesicles. Cholesterol also lowers the concentration of nigericin or valinomycin required for a rapid translocation of Rb+ into protein-free liposomes. It also lowers the concentration of A-23187 required for the release of Ca45 trapped in protein-free liposomes. In contrast to these observations and in confirmation of previous findings, we observed that cholesterol decreased the permeability of liposomes for glucose. Thus the effects of cholesterol on the permeability of the membrane vary with the chemical nature of the permeating compounds. We have also confirmed that in multilamellar liposomes cholesterol decreases the permeability of Rb+ in the presence of valinomycin. It therefore appears that the effect of cholesterol changes with the size and structural features of the model membranes.


Detection of thymus leukemia antigens on the surface membranes of murine leukemia cells resistant to thymus leukemia antibodies and guinea pig complement. The thymus leukemia (TL) antigens of ASL-1 murine leukemia reversibly disappeared from the membranes of cells exposed to TL antisera; the cells acquired resistance to fresh TL antiserum and complement (antigenic modulation). Three independent methods, however, indicated that the acquisition of complement resistance preceded the complete disappearance of TL antigens from the cell surface. Modulated cells reduced known titers of TL antisera by absorption; they stained positively in immunofluorescence studies involving TL antibodies and fluorescence-labeled rabbit anti-mouse immunoglobulin. TL antigens labeled previously with 125I were recovered by immunoprecipitation from cellular extracts prepared with nonionic detergent. Continued exposure of the cells to TL antiserum led to virtually complete disappearance of the antigens. Similar results were obtained for RADA-1 cells, another murine leukemia that forms TL antigens, although in this instance the cells were resistant to the cytolytic effects of TL antisera and guinea pig complement (GPC) without prior exposure to TL antibodies. The density of TL antigens remaining on the surface of different TL(+) cell types failed to correlate with resistance to TL antibodies and GPC. Cells from F, hybrids of TL(+) and TL(-) mouse strains formed TL antigens and were susceptible to TL antibodies and GPC even though the density of TL antigens formed by the susceptible cells was less than the density of TL antigens formed by modulated cells. Stable somatic hybrids of RADA-1 cells and TL(-) cells formed TL antigens at lower density than did RADA-1 cells and lysed in the presence of aliquots of the TL antisera and GPC used in previous tests.


Passive local anaphylaxis: demonstration of antitumor activity and complementation of intratumor BCG. When an extracellular dye, Lissamine green, or 51Cr-labeled spleen cells were injected iv into C3H mice bearing small, partially necrotic 3-methylcholanthrene-induced transplantable fibrosarcomas (McC3), the tumor content of these circulating elements per unit weight was substantially lower than that of other selected organs. The level of these blood-borne materials was, however, significantly augmented by the intratumor induction of passive local anaphylaxis (PLA). The PLA-induced augmentation was inhibited by administration of the histamine and serotonin antagonist cyproheptadine; comparable increases were also induced by the intratumor injection of a histamine and serotonin mixture or BCG. The weekly intratumor induction of PLA in McC3 tumors resulted in the complete regression of a significant number of the tumors, and this therapeutic effect was eliminated by cyproheptadine treatment. The intratumor injection of BCG induced the regression of approximately 50% of injected tumors, and the combination of this immunostimulant treatment with the generation of PLA was more therapeutically effective than either treatment alone. PLA in the vicinity of solid tumors may, by increasing vascular permeability, potentiate antitumor effector mechanisms, particularly when these are BCG-stimulated. Despite this demonstration of a possible role of anaphylactic reactions in tumor immunity, no definitive evidence was found that active reagin-mediated local anaphylaxis occurred in C3H mice bearing the McC3 tumor, whether or not they were treated with immunostimulants.


Mutagenicity for Salmonella typhimurium of urine obtained from humans receiving nitrofurantoin. Urine samples from 12 humans receiving oral therapeutic doses of nitrofurantoin were mutagenic for Salmonella typhimurium strain TA 100 and nonmutagenic for strain TA 100-FR1. Mutagenic activity of the urine was not increased by treatment with beta-glucuronidase. Spot mutation assay of the chromatogram of urine revealed that the mutagenic activity of the urine was mainly due to unmetabolized nitrofurantoin.


Clinical toxicology of mercury.

Clinical toxicology of mercury. Based on an extensive literature search, general principles of mercury toxicity are outlined with respect to human individuals and populations. For the metal itself, as well as for its most important inorganic and organic compounds, the review discussed behavior in the body, characteristic clinical pictures, assessment of threshold levels, and evaluation as potential environmental hazards. Particular emphasis is placed on those diagnostic signs and symptoms which furnish early warning signals, permitting detection and elimination of overexposures.


Traumatic hemipelvectomy: a case report. Traumatic hemipelvectomy is a devasting injury which few patients survive. A survivor of traumatic hemipelvectomy is described. Immediate and long-term management include prompt resuscitation, vascular control, urinary and fecal diversion, wound debridement, wound closure, and physical and psychologic rehabilitation.


Microbial agents in stools of infants and young children with and without acute diarrhoeal disease. A study on the microbial agents in the stools of 344 infants and young children (206 diarrhoeal and 138 nondiarrhoeal) was carried out. The diarrhoeal group comprised of 120 hospitalised cases and 86 from a community. The numbers of nondiarrhoeal subjects of matching age taken from the same hospital and community were 50 and 88 respectively. It was revealed that bacteria (50-9%), parasites (11-7%), and C. albicans (2-4%) accounted for 65 per cent of the diarrhoea cases, 6-8 per cent having mixed infections. The largest number of cases had EEC followed by P. aeruginosa, Shige-la, V. cholerae, and A, hydrophila and of the parasites G. intestinalis was followed by E. histolytica in order of frequency. Enteropathogenic bacteria and parasites were encountered in 13-0 per cent and 34.8 per cent of the nondiarrhoeal subjects respectively, 7-2 per cent having mixed infections. This group also had EEC as the commonest bacteria and A. lumbricoides was the most prevalent parasite. Except for V. cholerae, A. hydrophila and C. albicans no significant difference was observed in the microbial spectra amongst the diarrhoeal cases in the hospital or community. In the nondiarrhoeal subjects both groups showed a similar prevalence pattern. Incidence of bacterial pathogens was significantly higher in children below two years and intestinal parasites were three times more common in older children.


Shutoff of host RNA synthesis in bacteriophage T4-infected Escherichia coli in the absence of host DNA degradation and nuclear disruption. In contrast to its effect on host DNA synthesis, nuclear disruption in phage T4-infected Escherichia coli B/5 cells has no effect on the shutoff of host RNA synthesis. Host RNA synthesis is shut off normally after infection with T4 multiple mutants that fail to induce both nuclear disruption and host DNA degradation.


UV-induced alleviation of K-specific restriction of bacteriophage lambda. A partial release of K-specific restriction of phage lambda grown in Escherichia coli C was observed when E. coli K strains AB1157 (having wild-type repair of UV-produced DNA damage) and AB1886 (uvrA) were irradiated with UV light before infection. The effect occurred in AB1886 at lower UV fluences than it did in AB1157. Little or no release of restriction was observed when AB2463 (recA) or AB2494 (lex-1) was used. Such release of restriction appears to be another of the UV-induced phenomena associated with "SOS" repair.


Stability of the carrier state in bacteriophage M13-infected cells. Bacteriophage M13-infected carrier cells were shown to be unstable to prolonged growth under all conditions. Carrier Hfr cells were transferred in dilute culture (10(3) to 10(4)/ml), where reinfection was impossible and the physiology of the cell was minimally altered. After an initial period of about 10 generations, during which all cells in the culture remained infected, there was exponential decay in the proportion of infected cells in the culture. Uninfected cells that appeared were M13 sensitive. Hfr and F' males were also transferred serially at high cell densities (10(7) to 10(9)/ml), where high levels of phage should permit reinfection. The proportion of phage-producing cells in the cultures remained constant for 7 to 15 generations and then dropped exponentially on further growth. Non-phage-producing cells appearing in the culture were refractory to infection by M13; in some cases cells scored as non-phage producers for 20 generations were observed to produce phage on further growth in liquid culture. F'trp+ males infected with M13 lost trp+ function almost immediately; this was not regained in these experiments. Infected cells grown in dilute culture or on plates remained infected longer, produced more PFU per cell for a longer period, and retained trp+ function in F'trp+ males for over 90 generations. Non-phage-producing cells that appeared were sometimes phage resistant, sometimes phage sensitive. The existence of a phage-related material accumulating at high cell densities and affecting expression of free episomes, episomal expression in Hfr males, and phage synthesis itself is suggested.


In vivo effects of recBC DNase, exonuclease I, and DNA polymerases of Escherichia coli on the infectivity of native and single-stranded DNA of bacteriophage T7. The effect of several enzymes of the DNA metabolism of Escherichia coli on the biological activity of native and single-stranded T7 DNA was studied by transfection of lysozyme-EDTA spheroplasts prepared from various E. coli mutants. It is shown that the presence of the recBC DNase in the recipient cells decreases the infectivity of native and denatured DNA by about 100- and 10-fold, respectively. Lack of exonuclease I did not stimulate transfection by single-stranded DNA. Separated light (l) and heavy (r) strands of T7 DNA are fully infective, with a linear dependence on DNA concentrations, whereas heat-denatured DNA shows a two-hit kinetics. Single-stranded DNA was observed to depend on a functional DNA polymerase III for infectivity in polAB cells, whereas transfection with native T7 DNA was independent of the host DNA polymerases. The results are discussed with respect to the mode of T7 DNA replication.


Regulation of Bacteriophage P22 DNA synthesis and repressor levels in P22cly infections. A rifampin-resistant mutant of Salmonella typhimurium carries an altered RNA polymerase. Wild-type (c+) phage P22 displays clear plaques and a reduced lysogenization frequency on this mutant host. The cly mutants of P22 were isolated on the basis of their ability to lysogenize such mutant hosts. Two classes of regulatory events, both of which are dependent on P22 gene c1 activity, are necessary for the establishment of lysogeny in P22. The positive events culminate in repressor synthesis; the negative events cause a retardation in phage DNA synthesis. Neither the positive nor the negative events are observed in P22c+ infections of the mutant host. Both effects are found in P22cly infections of the mutant host. Observable results of both the negative and the positive events are exaggerated in P22cly infections of wild-type hosts as compared to P22c+ infections. The cly mutation apparently increases the positive and negative regulatory events so that they are detectable in the mutant host and exaggerated in wild-type hosts. Possible mechanisms that result in the high frequency of lysogenization that characterizes the cly mutation and the nature of the cly mutation are discussed.


Urological complications of renal transplantation can be prevented or controlled. Our incidence of urological complications in 860 consecutive renal transplants in 3.4 per cent. A further reduction in incidence is demonstrated in the most recent 250 transplants of this series. Urological complications have been kept to a minimum by strict adherence to certain principles in donor nephrectomy, management of multiple and small arteries, and the technique of graft implantation. When urological complications were suspected early and judicious use of 131I hippurate scintiphotographic techniques has proved to be the most helpful method to evaluate patients. If a urological complication did occur prompt recognition and treatment were responsible for a high rate of graft salvage, low incidence of sepsis and absence of patient mortality.


Studies of introital colonization in women with recurrent urinary infections. VII. The role of bacterial adherence. The susceptibility of the vaginal introitus to colonization by enterobacteria appears to be the biologic defect that separates women who experience recurrent urinary infection from those resistant to recurrent infection. Colonization of a mucosal surface is mediated in part by the ability of an organism to adhere to the surface. We describe an in vitro model that measures the capacity of different bacterial species to adhere to human vaginal epithelial cells. Different bacteria are demonstrated to vary in their adhesive properties. Escherichia coli is shown to adhere more readily to vaginal cells from women with recurrent urinary infection than to similar cells from control women resistant to urinary infection (p less than 0.001). These studies suggest that biologic susceptibility to recurrent urinary infections in women is related to a defect at the cellular level that encourages or favors bacterial adherence.


Changing attitudes toward urinary dysfunction in myelodysplasia. Alternative methods to supravesical urinary diversion in myelodysplastic children, which protect the upper urinary tracts and provide urinary continence, are now available in the form of prosthetic devices and intermittent clean catheterization with or without ancillary pharmacologic agents. We believe that these alternatives deserve a trial before proceeding to supravesical urinary diversion. Short-term evaluation indicated improvements and stability in most urinary tracts treated by these methods but we recognized that, just as with the ileal conduit diversion, a longer period of followup is required before definite statements can be made about the long-term results. However, if the criteria of sterile urine and bladder emptying at physiological pressure ranges are strictly met we would suspect a favorable outcome.


A technique for the correction of bifid scrotum in patients with hypospadias. A technique to correct a bifid scrotum in patients with severe hypospadias is described. The operation is used as a second stage procedure to 1) repair the bifid scrotum, 2) add length to the penis and 3) correct the tendency for the erect penis to point into the scrotum, eventually interfering with intromission. The procedure, which advances the penis superiorly, detaches the urethra from the prominent median raphe to correct the bifid scrotum, It has been used successfully in 3 patients.


Gamma A myeloma with hyperviscosity and obstructive uropathy. A patient with gamma A myeloma, hyperviscosity and an obstructive uropathy is described. Operation revealed a proteinaceous mass obstructing the right renal pelvis. Immunoprecipitin and immunofluorescent analysis of this mass and concentrated urine demonstrated the presence of gamma A myeloma protein, kappa light chains and albumin. This is the first description of an obstructive uropathy in multiple myeloma owing to a proteinaceous matrix containing paraprotein.


Silicone lymphadenopathy and synovitis. Complications of silicone elastomer finger joint prostheses. We report two complications of silicone elastomer finger joint prostheses. In one patient, the prostheses broke, with silicone particles present in synovium ("detritic synovitis"). In another patient, silicone particles were found in an axillary lymph node five years after insertion of prostheses in the ipsilateral hand (prostheses were intact at the time). Microscopically, silicone particles in synovium and lymph node were identical to particles abraded from a new prosthesis.


Prevention of hyaline membrane disease with plasminogen. A cooperative study. In a double-blind, randomized study, 500 premature infants were treated with plasminogen or placebo intravenously within 60 minutes of birth. There was a substantial decrease in severe clinical respiratory distress, death caused by hyaline membrane disease, and total mortality in the plasminogen-treated infants as compared to the controls.


Infant botulism. Epidemiological, clinical, and laboratory aspects. Clostridium botulinum organisms and toxin were identified in the feces of six infants, aged 5 to 20 weeks, who had illnesses clinically consistent with botulism. Five of the infants lived in California and became ill within a six-month period in 1976; one infant became ill in New Jersey in 1975. Three cases were type A botulism, and three were type B. No source of ingested botulinal toxin could be found in any case. However, one infant with type B botulism had ingested a food containing C botulinum type B organisms, and no toxin was found in it. The clinical findings in these cases include constipation, weak sucking and crying ability, pooled oral secretions, cranial nerve deficits, generalized weakness, and, on occasion, sudden apnea. A characteristic electromyographic pattern termed "brief, small, abundant, motor-unit action potentials" (BSAP) was observed. The sources of C botulinum toxin for these six infants is thought to have been in vivo (gastrointestinal) production following ingestion of C botulinum organisms. Studies are underway to determine the full clinical spectrum, incidence, and potential public health importance of this infectious disease newly recognized in infants.


Chronic nephritis induced by antibodies reacting with glomerular-bound immune complexes. The pathogenesis of chronic membranous glomerulonephritis induced in rats by passive immunization with heterologous antibodies to rat renal tubular epithelial (RTE) antigens was investigated. This model is designated as "passive Heymann nephritis" (PHN) in order to contrast it with classical Heymann nephritis induced by active immunization with homologous RTE in adjuvant. A single i.v. injection of heterologous (rabbit) antibody to RTE evoked chronic proteinuria after a latent period of one to three days. The onset of proteinuria was accompanied by the granular deposition of rabbit IgG and rat beta1C globulin along the glomerular capillary wall. Renal isografts developed PHN only when transplanted within the first three days following injection of the heterologous anti-RTE antibodies. The data suggest that the heterologous antibodies form immune complexes with RTE antigens preexisting in the circulation, and these complexes subsequently deposit in the glomerular capillary walls. Chronic proteinuria is then perpetuated by a host reaction to the foreign protein in the deposits (i.e., rabbit IgG), in a fashion analogous to that seen in the autologus phase of nephrotoxic serum nephritis. These studies indicate that continued glomerular deposition of preformed circulating immune complexes may not always be a requisite for the perpetuation of glomerular injury in immune complex disease.


[The action of Berberin-drops on the intraocular pressure (IOP) (author's transl)]. A double-blind trial was performed on 12 patients with chronic open angle glaucoma with Berberin and Placebo drops. There was no evidence for the hypothesis that Berberin or Placebo cause changes in the bio-regulation of the IOP. The statistical analysis was done by a new procedure (Kannemann 1976). The authors tried to propose generally valid rules for the planning of trials which are supposed to prove or disaprove the connection between various eye-drops and IOP-changes.


[Historic notices of Louis braille and the development of dot-writing (author's transl)]. Louis Braille is called by his first biographer to be the "Johannes Gutenberg for the blind". Being blind himself--caused by a sympathetic ophthalmia after a perforating hurt to his eye--he invented at the age of 16 years a simple and ingenious method enabling blind people to read and write. His system consisting of six elevated and palpable dots was rejected by the teachers of these days, claiming there could be a distance between blind and fullsighted men. Despite this opposition the Braille system succeeded because of its advantages for the blind: Nowadays this method is used all over the world.


An ultrastructural study of the mechanisms of proteinuria in rat nephrotoxic nephritis. Nephrotoxic nephritis was induced in Sprague-Dawley and Munich-Wistar rats by the injection of rabbit antirat kidney serum. A biphasic pattern of proteinuria was induced: the heterologous phase with a peak of proteinuria occurring at 10 to 16 hours, and the autologous phase with a peak at 10 to 15 days. For morphologic studies, glomeruli were fixed by perfusion, or by drip-fixation during good blood flow. In the heterologous phase, glomerular endothelial detachment or loss and leukocytic infiltration were prominent. In the autologous phase, focal detachment of glomerular endothelium and epithelium was commonly found. At sites of endothelial loss, in both phases, endogenous albumin (demonstrated by an ultrastructural immunoperoxidase technique), but not intravenously injected ferritin, showed abnormally deep penetration into the glomerular basement membrane. At sites of epithelial loss, found in the autologous phase, both albumin and ferritin were detected throughout the glomerular basement membrane. It is proposed that, in glomerular disease, leakage of plasma proteins may occur across the glomerular basement membrane at sites of endothelial or epithelial detachment.


Spontaneous rupture of a fenestrated aortic valve. Surgical treatment. Fenestration of the aortic valve is a common anatomic finding. Although spontaneous rupture of the semilunar cusps is infrequent, it leads to rapidly progressive heart failure and death. We present, to our knowledge, the first case of successful treatment by valve reconstruction. A 2 year follow-up demonstrates excellent clinical results.


Restoration of bronchial artery circulation after canine lung allotransplantation. To evaluate the re-establishment of the bronchial circulation in lung transplantation, we studied 10 immunosuppressed dogs up to 14 weeks after left lung allografting. Selective in vivo bronchial arteriograms were performed repetitively via the transfemoral route. In the early postoperative period, no fillinf og vessels distal of the bronchial anastomosis could be shown. After 12 days, however, continuity of the bronchial arteries across the anastomosis was present, and dye-filled ramifications of these vessels were visualized on the secondary and tertiary bronchi. Reconstitution of the bronchial circulation was also confirmed by postmortem studies after injecting the isolated descending thorasis aorta with colored radiopaque material (microfil). The bronchial mucosa at autopsy was examined microscopically. There was no correlation between its viability and bronchial artery regeneration. Although early ischemia of the transplant bronchus may be after a factor in the bronchial complcations that follow lung transplantation, the present study indicates that this ischemia is not due to failure of bronchial artery regeneration.


Septicemia secondary to impacted infected pacemaker wire. Successful treatment by removal with cardiopulmonary bypass. Infection of an intravenous pacemaker electrode developed in a 78-year-old man after multiple replacements and revisions of the pulse generator and the pacemaker lead. Spread of the infective process to the endocardium was followed by septicemia with Serratia marcescens and Staphyloccus epidermids. Failure of medical treatment and external traction on the pacemaker electrode led to thoracotomy and removal of the pacemaker electrode wires with the use of extracorporeal circulation. The tip of one of the pacemaker electrodes was found imbedded in the wall of the right ventricle and attached to the base of the tricuspid valve. Cultures from the endocardium removed with the electrode rendered the same organisms as cultured preoperatively. There has been no recurrence after 2 years following the removal of the infected electrodes. Although the problem described herein is not frequently found, radical treatment becomes necessary whenever infection and septicemia develop.


The effect of alcohol on the developing organism. Genetical, teratological and physiological aspects. In discussing the effects of alcohol on infants, children and adolescents, it is common to refer first to sociological data and only secondly to medical and biological information, often with scarce experimental support. Recently, however, the genetic, teratological and physiological aspects of the effects of alcohol on the developing organism have been the subject of several investigations, both in man and in experimental animals. It cannot be excluded that genetic factors influence the metabolism of alcohol. The effects of alcohol on some physiological functions vary between different racial groups. A number of studies have revealed teratological effects of alcohol in man, and investigations have also been performed to demonstrate such effects in experimental animals. The development of liver alcohol dehydrogenase activity both pre- and postnatally has been studied. The metabolic capacity for alcohol varies with age, with a maximum during adolescence. As yet, no clear pattern of the effects of alcohol on developing physiological functions can be distinguished, but hypoglycemia seems to be an effect of alcohol on younger organisms which later disappears, while other metabolic functions are rather insensitive in the early developmental stages. Most central nervous effects of alcohol are less pronounced in young experimental animals. The possibilities of extrapolation between experimental animals and man are limited and further studies are needed.


The integrity of the noradrenergic innervation of the cardiovascular system in genetically dystrophic hamsters. Noradrenergic nerves in dystrophic hamsters did not differ, in fluorescence morphology, from those in control hamsters. The responses to noradrenergic nerve stimulation and the sensitivity to noradrenaline of right atria and hepatic portal veins were similar in control and dystrophic animals. The contractility of left atria and their maximal responses to noradrenaline or noradrenergic nerve stimulation at 4 Hz were depressed relative to control. This reduction in inotropic responsiveness may be due to disturbances of excitation-contraction coupling.


Age-related changes in B and T lymphocytes and decline of humoral immune responsiveness in aged mice. The activity of the immune system declines in an age-related fashion, after reaching a peak in young-adult animals. Although this pattern has been well documented, the mechanisms responsible for the decline of immune potential in senescence have not been fully elucidated. At the same time, it has become apparent that the immune response depends on complex interactions among different cell types. We review the results of the analyses of B- and T-lymphocyte function and activity in the humoral responsiveness of aged mice that have been performed in a number of laboratories, with a variety of experimental techniques. We conclude that an increase in T-cell suppressor function is the first immunologic lesion of aging in mice. This is followed by a decrease in T-cell helper function and finally by a loss of B-cell function.


Ribosome editing and the error catastrophe hypothesis of cellular aging. Ribosome editing involves the dissociation during protein synthesis of inappropriate peptidyl-tRNA's, ones whose structure does not correctly complement the codon of the mRNA. This process is one of three stages in protein biosynthesis in which the frequency of errors in cellular proteins is controlled. These stages are reviewed and the implications of ribosome editing are described. A model for stability of the translation apparatus is criticized. Calculations using a revision of the model and experimentally reasonable values for the various parameters show varying time courses for error catastrophes.


Systems analysis of possible mechanisms of mammalian aging. A comparison is made between how bacteria and men use their DNA to accomplish any major biological function. To make this comparison, a modified cybernetic analysis was used. This new type of cybernetic analysis makes a distinction between controlled and regulated systems and may permit an extension of cybernetics into new areas of biology. Prokaryotes have only regulated systems for all major functions, whereas eukaryotes can have both regulated and controlled systems. Several lines of reasoning, including the new cybernetic analysis, suggest that death, as opposed to aging, may be a regulated function in mammals. By analogy with other major regulated developmental functions in mammals, it is also suggested that the hypothalamic-pituitary axis may be the site for the regulation of the time of death. An example of how the pituitary might act on the DNA of peripheral cells to cause possible, severe loss of functional capacity is given by some recent experiments with RNA polymerase activity of liver nuclei from rats of different ages and with different endocrine states.


Pylorus-preserving procedure in partial and total gastrectomy. 1. The operative technique and the postoperative results of the original pylorus-preserving gastrectomy (PPG) and those of the Maki procedure as applied to cases of total gastrectomy are reported briefly. 2. The essence of these operations is to retain the pyloric cuff of 1.0-1.5 cm in length in order to preserve sphincteric function without the use of the drainage procedure. Ingested food was seen to empty gradually and rhythmically through the pyloric ring into the duodenum thereby avoiding dumping syndrome and reflux esophagitis. 3. As gastric acidity is reduced sufficiently by PPG, this method is to be recommended for treatment of intractable gastric ulcer cases and other benign lesions in which the foci are located in the distal half of the stomach. Though the method seems to be also useful in selected cases of duodenal ulcer, stenosis at the level of the pylorus and duodenum may preclude the application of the method. 4. The Maki procedure with jejunal interposition following nearly-total proximal gastrectomy is recommended in patients whose pylorus and its surroundings have remained free of tumor.


Microsurgical techniques in free flap reconstruction. Free flap reconstruction is discussed with emphasis on microsurgical technique utilized in union of blood vessels 1 mm in external diameter. Proper microsurgical instrumentation, magnification and small vessel suture technique are all of importance in achieving a successful microvascular anastomosis. Technical maneuvers employed in identifying and avoiding small vessel thrombosis are presented. Surgical techniques, as presented here, have allowed us to successfully use free flaps to reconstruct large oral cavity defects following ablative cancer operations.


Tumor immunology and immunotherapy.

Tumor immunology and immunotherapy. Tumor cells contain a variety of antigens, including tumor associated antigens. The tumor associated antigens can be clinically useful as markers for detection of cancer and some may also mediate host resistance against tumor growth. Much emphasis has been placed on the detection of circulating tumor associated markers, with radioimmunoassays for carcinoembryonic antigen (CEA) being extensively utilized. At present, CEA does not appear to be promising for initial detection of cancer, but may find an important place in the determination of prognosis and early detection of recurrent disease. Many cancer patients have depressed immunologic competence, yet they frequently have cell-mediated immunity against tumor associated antigens. Several different immunotherapeutic strategies have been developed, to either augment the immunologic responsiveness of the patient or to specifically increase the immune reactivity against tumor associated transplantation antigens.


Haemophilus parainfluenzae and influenzae endocarditis: a review of forty cases. Two cases of bacterial endocarditis caused by Haemophilus parainfluenzae are reported with a review of 33 other cases of H. parainfluenzae endocarditis and 5 cases of H. influenzae endocarditis. Although H. parainfluenzae is usually considered a non-pathogenic microorganism, this review firmly establishes its role as a causative agent in endocarditis. Furthermore, several clinical features were noted which were atypical when compared to findings usually present in patients with bacterial endocarditis. The mean age of the patients was only 27 years. Over 60% of the patients had no identifiable predisposing illness, an unexpected finding in view of the low degree of pathogenicity associated with this microorganism. Polymicrobial bacteremia, usually with viridans streptococci, was found in 11% of patients. Major arterial emboli were documented in 57% of patients, an incidence unchanged from the pre-antibiotic era. Diagnosis of the disease is dependent upon an awareness of the fastidious cultural requirements necessary for isolation of Haemophilus species. Culture media must contain a source of X and V factors. Mortality from H. parainfluenzae endocarditis has been reduced from 100 per cent prior to 1940 to about 12 per cent by use of appropriate antimicrobial agents. Awareness that Haemophilus species can cause bacterial endocarditis is important because the diagnosis is dependent upon utilization of special culture methods and the patient may not respond to some of the empiric regimens used for treating bacterial endocarditis. It should be especially considered as a possible cause of "culture-negative" or "abacteremic" endocarditis.


[Intermittent mandatory ventilation (IMV) -- a new method in the treatment of severe respiratory insufficiency (author's transl)]. The intermittent mandatory ventilation (IMV) is a new method of ventilatory support developed in the USA. It allows the patient to breathe spontaneously as desired and also delivers a mechanical hyperinflation at regular preset intervals. IMV is especially effective in cases of severe respiratory insufficiency after conservative management as well as assisted ventilation have failed and helps avoiding the disadvantages of controlled mechanical ventilation. IMV fully utilises and assists the existing though insufficient spontaneous respiration which is integrated into the total ventilation. Patient acceptance and cooperation has been excellent and their weaning from respirator has been facilitated by a gradual reduction of the hyperinflation. Two cases are reported to illustrate technical details and the practical use of the method followed by a discussion of its advantages and indication.


Induction of protein X in Escherichia coli. Certain treatments that damage DNA and/or inhibit replication in E. coli have been reported to induce synthesis of a new protein, termed protein X, in recA+ lexA+ strains. We have examined some of the treatments that might induce protein X and we have, in particular, tested the hypothesis of Gudas and Pardee (1975) that DNA degradation products play an essential role in the induction process. We confirmed that UV irradiation, nalidixic acid treatment, or thymine starvation result in protein X synthesis in wild type strains. However, we found that UV irradiation, unlike nalidixic acid, also induced protein X in recB strains, in which little DNA degradation occurs. Furthermore, we found that the presence of DNA fragments resulting from host-controlled restriction of phage lambda DNA did not affect protein X synthesis. We conclude that no causal relationship exists between the production of DNA fragments and induction of protein X. The presence of the plasmid R46, which confers enhanced mutagenesis and UV resistance on its host, did not affect protein X synthesis. Growth in the presence of 5-bromouracil, which does not result in production of degradation fragments, resulted eventually in a low rate of protein X synthesis. In dnaA mutants, deficient in the initiation of new rounds of replication, UV irradiation induced protein X, again unlike nalidixic acid. Thus, the inhibition of active replication forks is not an essential requirement for protein X induction.


ppGpp cycle in Escherichia coli.

ppGpp cycle in Escherichia coli. Kinetics of accumulation and degradation of ppGpp and pppGpp were analysed in spoT+ and spoT strains of Escherichia coli. The experimental data in this paper indicate that on degradation ppGpp is not converted to pppGpp but instead is converted to GDP which is in turn phosphorylated to GTP. In addition the data are consistent with the idea the pppGpp is a direct precursor of ppGpp. We propose that ppGpp is metabolised according to the following pathway: GTP-pppGpp--ppGpp--GDP--GTP, which we call the ppGpp cycle. Coupled with the observations in spot strains we assume that ppGpp blocks its own synthesis by inhibiting the synthesis of pppGpp but not the interconversion of the two nucleotides.


X-ray-transmission computed tomography.

X-ray-transmission computed tomography. The immediate goal of clinically based x-ray-transmission computed tomography (CT) is to provide a measurement of the x-ray linear attenuation coefficient in cross section with the ultimate goal of impacting on patient management and care. To do this with the accuracy needed for clinical goals requires the careful integration of x-ray physics, detector technology, and mathematical reconstruction theory. Performance evaluation and quality assurance are necessary adjuncts to a CT scanning program. A number of investigative studies are underway.


Studies on ribosomal protein biosynthesis in an RNA polymerase temperature sensitive E. coli mutant. In E. coli strain XH56 the synthesis of all RNA species is blocked upon shifting the culture to the non-permissive temperature. The decay of specific messenger RNA species coding for individual ribosomal (r) proteins was followed by measuring the rate of r-protein synthesis by pulse labelling at various times after the shift. The half-lives of the average 30S r-protein and 50S r-protein mRNA species are identical (1.75 min) and shorter than those of the average messenger coding for total cell proteins (2.75 min). Most individual r-protein messengers have a half-life in the same range (1.50-2.00). Only a few r-protein messengers have significantly longer half-lives: S1 (2.80 min), S17 (3.29 min), L29 (2.30 min), L31 (2.30 min), L32 (2.33 min) and L16 (2.60 min). The results indicate that the degradation of most individual r-protein mRNA species is not specifically controlled. After a few min at the non-permissive temperature, all protein synthesis is blocked. The restart of r-protein synthesis was followed after shifting the culture back to the permissive temperature. The recovery of cell growth is very slow. During this period preferential r-protein synthesis was observed. Moreover differential rates of bisynthesis of r-proteins was obtained, it may be indicative of specific regulatory process(es).


The extrachromosomal control of nonsense suppression in yeast: an analysis of the elimination of [psi+] in the presence of a nuclear gene PNM. When a [psi-] strain of yeast mutates to [psi+], the efficiency of suppression by certain ochre suppressors is increased. The [psi+] phenotype is inherited extrachromosomally. There is a nuclear gene, PNM, which, when mutant, causes loss of the [psi+] phenotype. PNM- is dominant to PNM+ and a heterozygous diploid gradually loses the ability over successive generations, to produce PNM+ [psi+] spores. This paper describes the kinetics of this elimination and the data obtained are discussed in relation to two models of the molecular nature of the [psi] genetic determinant--one considering the [psi] determinant as an autonomous nucleic acid, the other treating the possibility that the [psi] nucleic acid is that which codes for rRNA in the nuclear genome.


Saccharomyces cerevisiae 2-mum DNA. An analysis of the monomer and its multimers by electron microscopy. The non-tandem inverted duplication in the 2-mum DNA of Saccharomyces cerevisiae has a length of 0.19 mum and is located asymmetrically along the molecule. The majority of the dumb-bell structures that are formed upon denaturation and self-annealing of the 2-mum monomer consists of the renatured inverted duplication sequences as double stranded stem and two single stranded loops of 0.67mum+/-0.06 mum (S-loop) and 0.86 mum+/-0.05 mum (L-loop) length. Two additional size classes which comprised 5-10% of the measured molecules had contour lengths of around 1.7 mum and 2.1 mum. The smaller dumb-bells contained two S-loops and the larger dumb-bells contained two L-loops as was shown by heteroduplex mapping with an HindIII fragment from the L-loop. Two models which assume illegitimate or site specific recombination, are presented to explain the generation of double S-loop and double L-loop molecules. At least part of the 4-mum and 6-mum circular molecules present in the yeast supercoiled DNA fraction are shown to be dimers and trimers of 2-mum monomers, but often with inverted loop segments most probably due to intramolecular recombination between sequences of the inverted duplication.


Re-examination of F plasmid replication in a dnaC mutant of Escherichia coli. The replication of an F' plasmid in a dnaC mutant, thermolabile for initiation of chromosomal replication, has been re-examined using a novel DNA-DNA annealing assay. Plasmid replication ceases rapidly at non-permissive conditions, consistent with a direct role for the dnaC product in the replication of F.


A new technique for selection of sensitive and auxotrophic mutants of E. coli: isolation of a strain sensitive to an excess of one-carbon metabolites. An E. coli strain deleted in the region malasd is used for the selection of conditional or auxotrophic mutants. Thermosensitive and auxotrophic strains have thus been isolated on plates. After selection in liquid medium, a strain has been isolated which is sensitive to excess one-carbon metabolites. It carries two mutations, smg A1 (near metA and arg H), probably identical to relC, and smgB (between asn and ilv), probably part of the E. coli membrane ATPase.


Escape synthesis of RNA polymerase subunits and termination factor rho following induction of prophage lambda in Escherichia coli. Synthesis of RNA polymerase subunits and of transcription termination factor p was studied after thermoinduction of prophage lambdac1857 located at several unusual sites on the chromosome of Escherichia coli. When a lysogen carrying the prophage at the bfe gene was induced at 42 degrees C, the rate of synthesis of core polymerase subunits (alpha, beta and beta') rapidly decreased, followed by a marked increase after about 10 min. The latter increase was observed specifically in the "bfe lysogen" and not in any of the other lysogens tested. Similarly, the rate of synthesis of p factor increased appreciably in the induced ilv lysogen carrying the prophage at the ilv gene, and possibly in the bfe lysogen as well, but not in other lysogens examined. Taken together with other evidence, these results suggest that the enhanced syntheses of beta and beta' subunits of RNA polymerase and of p factor observerd represent "escape synthesis", resulting from the close linkage of the prophage genome to the respective structural genes. In contrast, omega factor synthesis was stimulated upon induction of any of the lysogens used without respect to the site of prophage location, suggesting the involvement of an entirely different mechanism.


Relative order of glg mutations affecting glycogen biosynthesis in Escherichia coli K12. Mutations affecting the glycogen biosynthesis in E. coli can be mapped at three different loci, glg A, glg B and glg C lying between asd and mal A. Transduction tests suggest the following order for the genes in this region: mal A--glg A--glg C--glg B--asd.


Mutagenic DNA repair in escherichia coli. V. Mutation frequency decline and error-free post-replication repair in an excision-proficient strain. Mutation frequency decline (MFD) is an irreversible loss of newly-induced suppressor mutations occurring in excision-proficient Escherichia coli during a short period of incubation in minimal medium before plating on broth- or Casamino acids-enriched selective agar. It is known that MFD of UV-induced mutations may occur before DNA containing pre-mutagenic lesions is replicated, but we conclude that MFD can also occur after the damaged DNA has been replicated on the basis of the following evidence. (1) Mutation fixation in rich medium (i.e., loss of susceptibility to mutation frequency decline) with ethyl methanesulphonate mutagenesis begins immediately, whereas with UV it is delayed for 20--30 min. (2) The delay in mutation fixation after UV can be explained neither by inhibition of DNA replication nor by a delay in the appearance of error-prone repair activity in the irradiated population. (3) MFD at later times after UV irradiation is more rapid and is less strongly inhibited by caffeine than is MFD immediately after irradiation. (4) Excision is virtually complete 20 min after 3 J m-2 UV but at that time virtually all mutations are still susceptible to MFD. We have presented evidence elsewhere that in bacteria there is an alternative error-free excision-dependent type of post-replication repair of potentially mutagenic daughter strand gaps. We suggest that this process is inhibited at tRNA loci in the presence of nutrient broth or Casamino acids, possibly because of a broth-dependent change in the structure of the single-stranded region including the tRNA locus.


Genetic effects of some new bifunctional and water-soluble analogs of the anti-cancer agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in Saccharomyces cerevisiae. A series of 1,1'-polymethylenebis-3-(2-chloroethyl)-3-nitrosoureas, 1-(omega-hydroxyalkyl)-3-(2-chloroethyl)-3-nitrosoureas, 1,1'(4-methyl-m-phenylenebis)-3-(2-chloroethyl)-3-nitrosourea, 2-[3-(2-chloroethyl)]-3-nitrosoureido-2-deoxy-D-glycopyranose (chlorozotocin and 1-(2-methanesulfonyloxyethyl)-3-(2-chloroethyl)-3-nitrosurea were examined for their genetic activities. BCNU was simultaneously tested as an established, clinically used reference compound. A diploid strain of Saccharomyces cerevisiae, heteroallelic at the gene loci ade2 and trp5, was used as a test system for the induction of mitotic gene conversion (intragenic recombination). All compounds showed strong genetic effects. In the series of aliphatic bifunctional nitrosoureas, 1,1'-ethylenebis-3-(2-chloroethyl)-3-nitrosourea (1) was the most active compound. The water-soluble derivatives, including chlorozotocin, displayed all genetic effects of the same order of magnitude. There was no correlation between genetic activity and chemotherapeutic potential of the test compounds.