Re-endothelialization of microvascular carotid end-to-side anastomosis in the rat. A carotid end-to-side anastomosis was performed on 25 male and female Wistar rats (mean weight 197.8 gm). The animals were sacrificed at time intervals varying from 0 to 21 days after the operation. The anastomosis was exposed, the aorta cannulated, and the animals perfused with a 2.5% buffered glutaraldehyde solution at a constant pressure of 80 mm Hg. The anastomoses were removed for scanning electron microscopic (SEM) and light microscopic studies. The SEM results indicate that after the acute platelet-fibrin reaction in the first 48 hours, the suture line itself becomes re-endothelialized after 4 days. On the stitches, however, a cellular population consisting of leukocytes transforming into flattened cells was seen after 2 days. The morphology of these cells and their role in the regeneration of endothelium is discussed. This study presents evidence supporting a blood-borne genesis of endothelial cells in vivo.


Possible factors in the adhesion of fissure sealants to enamel. The type of aqueous solution used to wash the enamel surface immediately after etching with orthophosphoric acid affected the tensile bond strength obtained. Washing with a 1% potassium chloride solution was found to effect an improved bond strength, but no difference was observed when different types of water were employed for this purpose. A similar finding of no difference in bond strength was obtained when the possible influence of electrostatic forces was eliminated.


Evaluation of endosseous implant abutments as a base for fixed prosthetic appliances. A preliminary clinical study. In the present 2-year report nineteen Linkow blade implants with a total of twenty-seven perforating posts were assessed. All implants included were considered functionally successful and served as abutments for fixed prosthetic appliances. Periodontal probe and radiographic measurements of bone loss around the perforating implant posts, and registration of plaque and gingival index scores were performed every 6 months. During the first 4-6 weeks after implantation a vertical bone loss approximating an average of 1-2 mm occurred in the neck area of the implants. After this initial resorption, bone loss proceeded at a slower rate. The mean annual crest reduction was approximately 0.1 mm from the first to the fourth examination, as assessed from radiographic measurements. Periodontal probe measurements, showing a mean annual crest reduction of 0.2 mm, usually exhibited higher values than corresponding radiographic measurements at both implants and abutment teeth. At implants there was a significant positive correlation between plaque and gingivitis after 18 and 24 months, but not before that time. No correlation was seen between gingival index scores and the degree of bone resorption.


The effect of time on the marginal fracture behaviour of amalgam. In this study the effect of time on the marginal fracture behaviour of amalgam was determined. Six alloys in clinical service for up to 6 years were used as a data base and occlusal photographs were categorized according to a standard set of photographs depicting varying degrees of marginal fracture. The standard set of photographs was assigned a linear numerical scale, and the index of extent of fracture was considered to be an arithmetic mean based on this linear scale. An observed patient effect and unequal sample size were considered in the determination of both the mean and variance. The results of applying these procedures to the data of this study showed that marginal fracture increased with time for all alloys; that the relative ranking of alloys did not change with time; and that, with certain limitations, early time evaluations can predict long-term behaviour.


Offsetting the increased plaque formation in partial denture wearers by tooth brushing. In two experiments, each running for 2 weeks, plaque formation was studied on forty-two teeth acting as abutments for removable partial dentures. In the first experiment, only ordinary tooth brushing was practised. Plaque accumulation was rapid, yielding scores ranging between 2 and 5. In the second experiment, following instruction in intensive tooth brushing, plaque scores were depressed to approximately 1.5 and below.


Effect of storage in recipient's blood on the immunogenicity of tooth allografts in rabbits. Dental allografts can immunize recipients against skin allografts because some antigens are shared between teeth and skin. The effect of storage in the recipient's blood (ten days, 4 C) on the immunogenicity of subcutaneously allotransplanted rabbit teeth was examined. Storage in blood depressed the antigenicity of teeth, as detected by prolongation of the rejection time of second-set skin grafts in comparison with teeth stored in saline solution, or fresh, nonstored teeth. Further studies are needed to elucidate the mechanism of this procedure.


Microbiologic and antibiotic aspects of infections in the oral and maxillofacial region. An overview of infection as it applies to the oral and maxillofacial region has been provided. The following conclusions are drawn: odontogenic infections are caused by microbes found in the host's oral flora; cultures of purulent material generally will yield three to six anaerobes and one aerobe, (the aerobe is usually a Streptococcus species); Gram stains of purulent material can aid in therapeutic strategies; anaerobic as well as aerobic cultures are necessary to isolate all pathogens; pathogens found in infections of bite wounds reflect the oral flora of the aggressor; early postoperative wound infections are caused by the host's own flora, whereas later infections may be caused by hospital-acquired bacteria; and hepatitis B and herpes simplex virus are occupational hazards. Recommendations have been made for antimicrobial prophylaxis and for treatment. We recognize that some of these selections may be controversial. For instance, the value of prophylactic antibiotics in orthognathic surgery is not well defined; recommendations were made only in certain instances. However, in severe penetrating maxillofacial injuries with devitalized tissue, recommendations for antibiotics were for broad and prolonged coverage. In this instance, use of antibiotics is considered therapeutic and not prophylactic. In each instance, we tried to validate the selection. Our rationale has been to choose the antibiotics most active against the likely pathogens; additionally, consideration was given to drug toxicity and adverse reactions. We regard penicillin as the preferred agent for prophylaxis and treatment of most odontogenic infections. Alternative drugs include cephalosporins, doxycycline, and clindamycin. Erythoromycin and tetracycline are considered less effective than the former agents. Finally, we believe that successful treatment of infection depends as much on changing the microenvironment of the infected tissue by debridement and drainage as on appropriate antimicrobial therapy.


Surgical-orthodontic correction of horizontal maxillary deficiency. Selected maxillary osteotomies in concert with rapid maxillary expansion appliances are dependable adjuncts to treatment of the various clinical manifestations of horizontal maxillary deficiency and the accompanying crossbite. The important diagnostic, treatment planning, and technical considerations necessary for successful surgical-orthodontic correction of horizontal maxillary deficiency were discussed.


Lung expansion, tidal exchange, and formation of the functional residual capacity during resuscitation of asphyxiated neonates. Ventilatory exchange and endotracheal and esophageal pressures were measured during resuscitation of asphyxiated neonates born by cesarean section. In contrast to spontaneously breathing, vaginally born babies, an opening pressure had to be exceeded before lung expansion occurred. Subsequently there was usually a gradual increase in gaseous exchange over the first few lung inflations. A further rise in lung compliance occurred with the baby's inspiratory efforts. The functional residual capacity was formed with or without active inspiratory efforts by the baby, although gaseous retention occurred more rapidly as a result of the infant's inspiration.


Chloramphenicol disposition in infants and children. We studied the pharmacokinetics of chloramphenicol following its intravenous administration as the sodium succinate ester to 54 infants and children. The mean "apparent t 1/2" of chloramphenicol clearance from the plasma was 5.94 hours (range 0.87 to 17.8 hours). The t 1/2 of patients who weighed less than 10 kg was significantly longer than that of those who weighed more than 10 kg (9.02 vs 4.55 hours; P less than 0.0001). There was a discrepancy between the plasma levels of chloramphenicol and total aromatic nitro compounds in four patients; these compounds were cleared at different rates. Repeated dosing (eight to 30 doses) did not produce a consistent effect on the t 1/2. The CSF concentrations of chloramphenicol in 13 patients were 67% (range 45 to 99%) of the simultaneous serum concentrations. We conclude that the marked individual variation in chloramphenicol pharmacokinetics in infants and children requires monitoring of blood concentrations during therapy.


Membranous glomerulonephritis and hepatitis B surface antigen in children. Of 33 children with membranous nephropathy screened for HBs Ag, 14 were found to be HBs Ag carriers, whereas HBs Ag was detected in 3 of 170 and 4 of 100 children with glomerular and nonglomerular kidney diseases, respectively. HBs Ag was often associated with acute hepatitis at onset (five patients) or with elevated transminases values. This high incidence and the prevalence of an unusual subtype (ayw2) suggest a relationship between HBs Ag and the glomerular lesions. Using immunofluorescence, however, HBs Ag could not be detected within the deposits, so that the nature of the relationship cannot be considered as established. The clinical outcome (50% remission), the plasma complement component disturbances, and findings by immunofluorescence did not differ from those observed in children with MGN without detectable HBs Ag.


Activity of the alternative complement pathway after splenectomy: comparison to activity in sickle cell disease and hypogammaglobulinemia. Patients with sickle cell disease and individuals who have undergone splenectomy share defects of certain host defense mechanisms and a predisposition to severe pyogenic bacterial infections. Since patients with sickle cell disease can have deficient activity of the alternative complement pathway, we have tested such activity in sera from splenectomized children and adults. A new kinetic hemolytic assay has been used, and we have compared results to those obtained with sera from patients with sickle cell disease or hypogammaglobulinemia. Sera from six of 58 splenectomized individuals (10%) had defective function of the alternative pathway, compared to 10 of 62 sera from patients with sickle cell disease (16%) and 10 of 18 sera from hypogammaglobulinemic patients (56%). Deficiency of antibody, a rate-influencing component of alternative pathway activity in this system, appears responsible for deficient activity in the hypogammaglobulinemic sera. The molecular basis for the deficiency found in sickle cell disease or after splenectomy is not clear. Defective function of the alternative complement pathway could contribute to the increased predisposition to bacterial infection that exists in these three patient groups.


Effect of toothbrushing with a fluoride-free and fluoride-containing dentifrice on oral hygiene and number of leukocytes in the gingival fluid. The number of leukocytes in the gingival exudate and the oral hygiene index during toothbrushing with a fluoride-free and fluoride-containing dentifrice was investigated in humans during a 3-month period. Significant correlations existed between the average number of leukocytes in the gingival exudate and the oral hygiene indices. The number of leukocytes increased significantly during the period of toothbrushing with the Fluoride dentifrice, whereas in the OHI no change was evident.


Insulin secretion from isolated pancreatic islets in the female rat. Short and long term oestradiol influence. An increase in the two phases of glucose-induced insulin response is observed after an oestradiol (E2) treatment or after a direct E2 action on the female rat perfused pancreas. To study such effects, experiments were carried out with isolated islets of Langerhans, and especially with a dynamic method : perifusion of the islets. The same long term E2 permissive effect was obtained with isolated islets submitted to a glucose stimulation. On the contrary, the direct E2 action seen in glucose-stimulated perfused pancreas was found neither with incubation tests, nor with perifusion studies, whatever the experimental conditions (E2 or glucose doses, exposure times, oestrous or spayed rats, 100 instead of 25 islets per perifusion chamber). The differences between isolated islets of Langerhans and the whole perfused pancreas preparation are discussed.


The self-concepts of regular transcendental meditators, dropout meditators, and nonmeditators. Regular meditators, dropout meditators, and nonmeditators were administered the Tennessee Self Concept Scale twice over a six month period (N = 32 Australian men and women). Results showed that regular meditators as compared to dropout meditators were found to have significantly fewer of the characteristics associated with psychosis. Nonmeditators as compared to dropout meditators were found to have significantly fewer characteristics associated with psychosis and personality integration. Regular meditators as compared to nonmeditators have a more positive perception of their behavior. The findings provide a personality description of the dropout meditators which may be useful for screening prospective meditators.


Scientific publications of a medical school faculty. To characterize patterns of scientific productivity in a medical school faculty, the authors assessed the quantity and apparent scientific quality of publications by a large sample of the full-time faculty at Baylor College of Medicine. The apparent quality of an article in a given journal was taken to be the average extent to which articles in that journal are cited. Productivity varied greatly among the faculty members; a few prolific authors produced 10 times as much as the average of their colleagues, and a substantial fraction of the faculty published nothing in a four-year period. When productivity was related to length of academic career, two peaks of scientific accomplishment were noted. The first was for young faculty members whose relatively few publications were of high apparent quality. The second was for more mature faculty whose high productivity was attributable to more publications of less apparent quality.


Immunological studies in thymectomized and non-thymectomized patients with myasthenia gravis. Eleven thymectomized and ten non-thymectomized patients with myasthenia gravis, matched with respect to sex, age, duration and severity of the disease were investigated with respect to routine clinical features, electrophysiological examination, HLA-typing, auto-antibodies, lymphocyte subpopulations in peripheral blood, Concanavalin A-induced release of leucocyte migration inhibitory factor (LIF), in vitro lymphocyte activation by mitogens and antigens and response to primary immunization with dinitrochlorobenzene measured in vivo and in vitro. The following conclusions could be drawn. The immune response to external antigens seems to be normal in myasthenia gravis and thymectomy is not followed by general defects in immune competence; at least as investigated by current techniques. The only reduction of responsiveness demonstrable in the thymectomized group was a decreased release of LIF by Concanavalin A-stimulated lymphocytes. Primary immune responses appear to be increased after adult thymectomy, which may be due to a decrease in suppressor T-lymphocyte activity. A hypothesis is formulated that Concanavalin A-induced release of LIF may reflect the competence of suppressor T-lymphocytes in man.


Immune complexes in newly diagnosed insulin-dependent (type I) diabetics. Soluble immune complexes (AgAb) and islet cell antibodies (ICAb) were studied in 110 insulin dependent diabetics (IDD) within a week of diagnosis and in about a third of the patients after 1, 3, 6 and 12 months. AgAb were studied by the solid phase Clq binding test in all the patients and also by the Raji cell radioimmunoassay in 52 sera at diagnosis. Diabetics at diagnosis showed a significantly higher incidence of AgAb in comparison with the control population. AgAb positivity declined with increasing time from diagnosis to reach the normal range within 3 months. Both the Clq and the Raji methods revealed a significant correlation at diagnosis between the occurrence at AgAb and the presence of ICAb. The possibility exists that AgAb, perhaps comprised of pancreatic antigen and ICAb, may be involved in the pathogenesis of type I diabetes.


Expression of HBsAg on the membrane of hepatocytes in chronic carriers of hepatitis B virus infection. Liver cell membrane localization of hepatitis B surface antigen (HBsAg) was investigated in 31 asymptomatic chronic carriers by a direct immunofluorescence technique. A close relationship was found between absence of inflammatory liver disease, presence of large amounts of HBsAg in the liver and expression of the antigen at the hepatocyte surface. Capping of HBsAg after the addition of anti-HBs serum could be inhibited by factors (temperature, metabolic inhibition) that are known to influence viral antigenic mobility at the cell surface. In two patients with chronic active hepatitis as well as in some cases showing histological features of focal parenchymal necrosis, HBsAg could be detected in the cytoplasm of a few scattered hepatocytes but never at the surface of the cells. Both the cases with CAH and one with focal parenchymal necrosis had IgG bound to the liver cell membrane. These findings are in agreement with the hypothesis that the absence of liver damage in HBsAg healthy chronic carriers is related to immune tolerance to the antigen. In chronic active liver disease the presence of IgG on the membrane of hepatocytes suggests a possible role of blocking antibodies directed against viral antigens expressed at the hepatocyte surface.


The response of young chronically protein-deficient mice to multiple antigenic challenge. Responses to two or more antigens given together or separated by an interval of up to four days were determined in young mice maintained from weaning on a 4% albumin diet, and compared with those of normally-fed controls. Simultaneous challenge with several antigens did not affect antibody production in mice of either dietary group ("Simultaneous Competition") and the responses of normal and protein-deficient mice to sheep or rat erythrocytes were similarly produced by the prior injection of horse or sheep cells ("Sequential Competition"). However, the low protein diet broadened the conditions under which primary and secondary injections of diphtheria toxoid impaired primary responses to tetanus toxoid. These findings are discussed in relation to mechanisms previously proposed to explain antigenic competition, with a view to explaining the effects of protein-deficiency on antibody production.


In vitro fixation of guinea pig complement by renal biopsies. The in vitro fixation of heterologous complement by cryostat sections of human renal biopsy material was studied to determine the mechanism of complement activation. Various types of guinea pig sera with different parts of the complement system inhibited were used, the fixation of complement being detected by direct immunofluorescence. Cases of idiopathic focal nephritis with mesangial IgA (mesangial IgA disease), Henoch-Schönlein purpura (HSP) and mesangio-capillary glomerulonephritis (MCGN) fixed complement by the alternative pathway alone and in systemic lupus erythematosus (SLE) both the classical and alternative pathways were involved. Only one of the seven cases of membranous glomerulonephritis fixed complement and this was by the classical pathway. After prior treatment with C3b inactivator, the in vitro complement fixation in mesangial IgA disease, HSP and MCGN was greatly reduced. In SLE it was slightly reduced and in membranous glomerulonephritis there was no change. This is a convenient method of studying the biological properties of complexes which is believed to reflect the in vivo behaviour of the tissue deposited complex.


Centimeter- and millimeter-wave thermography--a survey on tumor detection. Thermography at centimeter and millimeter wavelengths can measure subsurface temperatures of the human body. Radiative and bio-heat transfer influence the wavelength dependent subcutaneous temperature and spatial resolution. Recent clinical results in treatment monitoring of arthritis, detection of tumors in the neck and brain area, and breast cancer are reviewed.


Skin lesions of the extensor surfaces of interphalangeal joints: surgical approach. A method of immediate grafting of interphalangeal joint skin defects after lesions are excised is presented.


Biofeedback and relaxation training in the treatment of psychophysiological disorders: or are the machines really necessary? The literature on the use of biofeedback and various forms of relaxation training in the treatment of psychophysiological disorders was reviewed; special attention was devoted to studies in which biofeedback and some form of relaxation training were compared. Based on this review, we conclude that there is no consistent advantage for one form of treatment over the other with any psychophysiological disorder for which a comparison has been made, e.g., essential hypertension, migraine headaches, premature ventricular contractions, tension headaches, temporomandibular joint pain, asthma, primary dysmenorrhea, and functional diarrhea. For other disorders in which no comparisons have been made (e.g., Raynaud's disease, sinus tachycardia, peptic uclers, and fecal incontinence) biofeedback seems to be a very promising treatment modality.


A study to evaluate non-fatal rabies in animals. Brains and salivary glands of stray dogs, cats and wild mammals were examined for latent rabies virus. Sera of these animals were tested for rabits neutralizing antibody. Dogs and rodents of the gerbil species were experimentally infected with rabies viruses tryping to produce nonfatal rabies. The following conclusions are made: 1. Naturally occurring nonfatal rabies infection evidenced by recovery of the virus was not present in the stray dogs examined and could not be produced experimentally. 2. Among wild gerbils showing no signs of disease, recovery of (latent) virus was possible but this condition could not be reproduced experimentally. However they could have been in the incubation stage. 3. Development of rabies neutralizing antibody did not occur naturally in wild rodents, but occurred in dogs. Antibody to rabies was detected in surviving gerbils after experimental infection. The antibody probably develops subsequent to sublinical nonfatal infection. 4. Non-fatal infection, indicated either by recovery of rabies virus or detection of neutralizing antibody, was not detected among the examined cats.


Immunocompetence of the guinea pig's middle ear. Immunocompetence of the middle ear was studied in guinea pigs in two series of experiments. The first, afferent phase, consisted of grafting iso and allografts in the guinea pig's middle ear to sensitize the animals which were later to receive a skin graft on the back. The second, efferent phase, first sensitized the animals with a skin graft on their back and later in the middle ear. The results show a rather low capacity of the middle ear to elicit a second-set rejection of the skin grafts. This lack of sensitization is explained by the authors by the concept of tolerance.


Recombination in bacteriophage T1 in the presence of host restriction. When unmodified phage T1 infects restricting host cells at high multiplicities of infection, there is an increase in recombination frequency in all regions of the T1 map compared to the level of recombination in standard crosses when short distances are examined. The enhancement of recombination frequency is not uniform for all regions but is greatest for markers near the center of the map and not so great for markers near the ends. Crosses between markers at the extremities of the map show that there is no increase in recombination frequency under restriction conditions. An examination of phage T1 heterozygotes suggests that an increase of ends created by the process of P1 restriction increases recombination. When T1 crosses are done in the absence of host restriction, recombination defects in the host have no effect on phage recombination and we conclude that phage T1 codes for its own recombination genes. Host recombination functions are also dispensable for the recombination occurring during infection of restricting host cells by unmodified phage at high multiplicities of infection.


Accumulation of bacteriophage T7 head-related particles in an Escherichia coli mutant. Upon infection with bacteriophage T7, a newly isolated mutant strain of Escherichia coli, Y49, produces T7-specific macromolecules including DNA almost normally. However, concatemeric T7 progeny DNA molecules, synthesized in Y49 cells, are later cleaved abnormally, resulting in an accumulation of DNA molecules shorter in size than the T7 genome and a poor production of progeny phage (Y. Yamada, J. Silnutzer, and D. Nakada, J. Mol. Biol. 121:95-111, 1978). The abnormal cutting of concatemeric T7 DNA in Y49 cells is accompanied by a simultaneous accumulation of large amounts of two types of phage head-related particles, proheads and newly found "X particles." Lysates from normal T7 infection of parental cells also contain X particles, although to a lesser amount. Electron microscopic examination of phage head-related particles (i.e., proheads, X particles, and empty heads), gel electrophoretic analysis of proteins in these particles, and kinetic studies on the appearance and fate of these particles suggest that X particles are likely to be intermediary structures between proheads and phage heads probably derived from proheads during the process of T7 DNA packaging. Our data also suggest that empty heads are not precursors to phage heads but are derived from proheads as by-products probably due to an abortive attempt to package T7 DNA. The host mutation in Y49 strain appears to block a step of T7 DNA processing and packaging pathway after generation of X particles from proheads.


Biochemical characterization of temperature-sensitive rabies virus mutants. Biochemical characterization of 70 temperature-sensitive (ts) mutants of rabies virus has been done by following the appearance of viral proteins and RNA molecules in infected cells at both permissive and nonpermissive temperature. The presence or absence of the nucleocapsid protein (N) was demonstrated by treating infected cells with anti-N fluorescent antibodies. At 33 degrees C, all the mutants induced a fluorescence comparable to the wild type. At 39.6 degrees C, the mutants can be classified into three groups. Three mutants induced a fluorescence comparable to the wild type (F+ mutants); 54 mutants induced a faint fluorescence which was proportional to the multiplicity of infection and increased with time (F+- mutants). No fluorescence could be detected for the 13 remaining mutants (F- mutants). The synthesis of all viral proteins was shown to be normal for F+ mutants, indicating that transcription and replication of the virus were normal and that the ts lesion was located in a protein which is not directly required for those functions. The synthesis of all viral proteins was similarly decreased for F+- mutants and undetectable for the F- mutants. This suggests that the ts lesion affects the transcription and/or replication of the virus. By annealing techniques it was demonstrated that the F+- mutants were able to perform some amount of secondary transcription at nonpermissive temperature. No secondary transcription occurred with F- mutants. When detectable (i.e., at higher multiplicity of infection), primary transcription of F- mutants was normal.


Is abortive infection by bacteriophage BF23 of Escherichia coli harboring ColIb plasmids due to cell killing by internally liberated colicin Ib? Infection of Escherichia coli harboring ColIb+ plasmids with bacteriophage BF23+ is abortive and resulted in changes of membrane permeability as measured by efflux of nucleotides and K+. A single pre-early gene product of BF23+ was necessary and sufficient to elicit the abortive response. Appropriate mutations in this pre-early gene allowed a productive infection in ColIb+ cells. Appropriate mutations in the ColIb plasmid also allowed a productive infection with BF23+. A comparison of changes occurring during abortive infection and during killing of sensitive cells by external colicin Ib or Ia, together with certain genetic data, has led to the conclusion that membrane changes accompanying the two phenomena are the result of a common mechanism, namely, the interaction of free colicin with the cytoplasmic membrane.


Salmonella bacteriophage glycanases: endorhamnosidases of Salmonella typhimurium bacteriophages. Twelve bacteriphages lysing only smooth Salmonella typhimurium strains were shown to have similar morphology--an icosahedric head to which a short, noncontractile tail carrying six spikes was attached. All phages degraded their lipopolysaccharide (LPS) receptors as shown by their ability to cleave off [14C]galactosyl-containing oligosaccharides from S. typhimurium cells labeled in their LPS. The oligosaccharides inhibited the alpha-D-galactosyl-specific Bandeiraea simplicifolia lectin agglutination of human type B erythrocytes, indicating that all 12 phage glycanases were of endorhamnosidase specificity, i.e., hydrolyzed the alpha-L-rhamnopyranosyl-(1 leads to 3)-D-galactopyranosyl linkage in the S. typhimurium O-polysaccharide chain. Two of the phages, 28B and 36, were studied in more detail. Whereas the phage 28B glycanase hydrolyzed the S. typhimurium LPS into dodeca- and octasaccharides, the phage 36 glycanase in addition cleaved off tetrasaccharides. Both phage enzymes hydrolyzed the O-polysaccharide chains of LPS from Salmonella belonging to serogroups A, B, and D1, which are built up of tetrasaccharide-repeating units identical except for the nature of the 3,6-dideoxyhexopyranosyl group (R). : FORMULA:(SEE TEXT). The phage 28B and 36 endorhamnosidases hydrolyzed also an LPS from which the 3,6-dideoxyhexosyl substituents had previously been hydrolyzed off. However, neither of the enzymes was active on LPS preparations in which the C2-C3 bond of the L-rhamnopyranosyl ring had been opened by periodate oxidation. Glucosylation at O-6 of the D-galactopyranosyl residues in the S. typhimurium LPS was found to be incompatible with hydrolysis by both enzymes. However, in an LPS glucosylated at O-4 of the D-galactopyranosyl residues, the adjacent alpha-L-rhamnopyranosyl linkages were found to be perferentially cleaved.


Evolution of defective-interfering double-stranded RNAs of the yeast killer virus. We have characterized by T1 fingerprint analysis several defective interfering (DI) double-stranded RNAs of the simple yeast virus ScV. A common sequence of about 0.5 to 0.6 kilobase pairs, including both 3' termini of the parental RNA, was present in each DI RNA. Several DI RNAs had novel T1 oligonucleotides not present in their parental RNA.


The treatment of infection stones with penicillin. The use of oral penicillin therapy is important in the management of renal stones secondary to Proteus mirabilis urinary tract infections. In 16 of 20 patients (80 per cent) with struvite renal calculi infected with Proteus mirabilis a sterile urine was achieved with appropriate penicillin therapy and diminution in stone size occurred in at least 2 cases. The rationale, supporting data and therapeutic uses are discussed.


Simple transvesical repair of vesicovaginal fistula. A simple transvesical repair of uncomplicated small vesicovaginal fistulas was done successfully on 40 consecutive patients. More extensive procedures using combined intraperitoneal-transvesical approaches with extensive dissection and omental flaps probably are necessary for the repair of large, complicated or irradiated fistulas. However, these are not often encountered in urological practice. The method described herein is recommended for fistulas encountered more frequently.


Laboratory diagnosis in the problem of suspected gonococcal infection. Proper laboratory techniques are indispensable for the diagnosis and detection of gonorrhea. While the smear is efficacious in diagnosing symptomatic urethral gonorrhea in men, it is not reliable for cervical, rectal, pharyngeal, or asymptomatic urethral infection. We have seen the development of four systems of culturing geared toward the office practitioner or where a complete laboratory is not available. They are as follows: Transgrow (transport), Neigon JEMBEC (transport or nontransport), Isocult, and Microcult systems. The Neigon JEMBEC system offers a good choice for the office practitioner. The use of proper diagnostic and culturing techniques and routine screening should bring about an increase in the amount of gonorrhea detected, treated, and subsequently removed from the reservoir of infection.


Effect of prostaglandin I2 on cyclical reductions of coronary blood flow. The effects of prostaglandin (PG) I2 and the agents which affect PG and thromboxane (TX) generating systems on cyclical reductions of blood flow in the partially constricted coronary artery of anesthetized dogs were examined. Cyclical reductions were eliminated by PG I2, but not by PG D2, and were augmented by 15-hydroperoxy arachidonic acid and tranylcypromine that inhibited synthesis of PG I2. The cyclical reductions were also eliminated by Cu-chlorophylline that inhibited synthesis of PG E2 and accelerated synthesis of TX A2, but were not by imidazole and 1-methyl imidazole that inhibited synthesis of TX A2. The results in this and in the previous studies indicate that not TX A2 but PG E2 participates as an inducer while PG I2 participates as an inhibitor in cyclical reductions of coronary blood flow.


[Laboratory and clinical studies on cefamandole (author's transl)]. The authors have carried out the laboratory and clinical studies of cefamandole (CMD). The results are as follows: The sensitivity was measured by plate dilution method on 26 strains of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and 14 strains of Salmonella typhimurium isolated from patients. The distribution of sensitivity of S. aureus was 0.39 approximately 3.13 micrograms/ml and the peak of distribution was 1.56 micrograms/ml. The distribution of sensitivity of E. coli was 0.78 approximately greater than 100 micrograms/ml, and K. pneumoniae, 1.56 approximately greater than 100 micrograms/ml. The distribution of sensitivity of Salmonella typhimurium was 6.25 approximately greater than 100 micrograms/ml and its peak was 6.25 micrograms/ml. CMD were given intravenously for 30 and 60 minutes at a single dose of 25 mg/kg body weight to 6 children. The serum mean levels of CMD were 105.3 micrograms/ml at 30 minutes, 15.1 micrograms/ml at 1.5 hours, 1.6 micrograms/ml at 2.5 hours after drip infusion for 30 minutes, respectively, and 34.7, 5.2, 0.6 micrograms/ml at 1, 2, 3 hours after drip infusion for 60 minutes, respectively. And the serum level at 4 hours after administration was not detected. The mean urinary excretion rates were 73.3% in the drip infusion for 30 minutes and 60.7% in its for 60 minutes, up to 8 hours after administration. Half life was 26 minutes. CMD was effective in 18 of 21 cases of bacterial infections. No side effects were observed except for 2 cases with elevation of serum transaminase.


[Clinical evaluation of cefamandole in infants and children (author's transl)]. Clinical trials were carried out with cafamandole (sodium salt) in pediatric infections. Results were as follows; 1. CMD was applied to 13 patients with pneumonia, 1 patient each with submandibular abscess, urinary tract infection and bacterial meningitis. 2. Results were excellent in 1 and good in 13 patients, being overall efficacy rate 93.3%. 3. Slight elevations of GOT and GPT were observed in 1 patient. No other serious side effects were observed or reported.


Computer analysis of vectorcardiograms in myocardial infarction with special reference to polar vector and planarity of the QRS and T loops. Spatial characteristics of the QRS and T loops in 110 patients with old myocardial infarction were analysed in comparison with 221 normal subjects. Measured were (1) QRS and T polar vectors, (2) initial 20- and 30-msec segmental QRS polar vectors, and (3) length, width, thickness, and ratios of width/length and thickness/length of the QRS and T loops in edgewise and broadside projections. Broadside and edgewise projections were obtained by transformation of the reference frame of the Frank lead system to a patient's own frame based on the polar vector. The recognition rates of abnormality in the QRS and T polar vectors were 66% and 60% of a total of 110 patients with myocardial infarction. The initial 30 msec segmental QRS polar vector showed the highest recognition rate of abnormality in myocardial infarction, i.e., 87% in anterior myocardial infarction, 100% in extensive anterior myocardial infarction and 78% in inferior myocardial infarction. The initial segmental QRS polar vector was abnormally deviated posteriorly and superiorly in inferior myocardial infarction. In anterior myocardial infarction, the initial segmental polar vector was directed inferiorly in more than 50% of the cases, while the vector in normal subjects was located superiorly and to the left. The QRS loop of anterior myocardial infarction was significantly smaller in the width and width/length ratio and significantly larger in the thickness and thickness/length ratio than those of the normal. Poor planarity of the QRS loop was one of the characteristics of myocardial infarction, especially of extensive anterior myocardial infarction. The T loop of myocardial infarction was significantly larger in the width/length ratio than that of the normal. More than 50% of the cases with anterior myocardial infarction showed abnormally wide T loops. The polar vector was a useful index to characterize the spatial orientation and sense of rotation of the spatial loop. In addition, the initial segmental QRS polar vector represented the mild localized abnormalities of the spatial loop. The loop configuration in space was characterized in edgewise and broadside projections.


Pathogenicity of cultivated murine leprosy bacilli of Hawaiian-Ogawa strain in mice. 4) Visceral lesions in mice produced by intraperitoneal infection. The pathogenicity of two substrains (HO-R and HO-S) of cultivated murine leprosy bacilli was examined by intraperitoneal inoculation to various strains of mice (C3H, KK, BALA/c, DDD and C57BL/6). HO-R (Rough Form) was first isolated on 1% Ogawa's egg yolk medium from the leprous lesions produced by original Hawaiian strain (H bacilli). HO-S (Smooth Form) was dissociated in vitro during the 9th to 15th subculture of HO-R on the same kind of medium. In all the mice tested, intraperitoneal inoculation with HO-R bacilli produced progressively severe visceral lesions in the manner similar to H bacilli harvested from subcutaneous leproma. The only exception was, however in DDD strain of mice H bacilli produced only slight visceral lesions even in the later stage of infection. HO-S was much lower in the pathogenicity than the above two strains of murine leprosy bacilli. Visceral lesions produced by intraperitoneal inoculation with HO-S used to be very slight in all the strains of mice except BALB/c. BALB/c strain mice were highly susceptible to intraperitoneal as well as subcutaneous infection with HO-S. From the above observations, it is concluded that the characteristic features of pathogenicity of cultivated murine leprosy bacilli, such as mouse strain differences, are all the same regardless of infection route.


Lipoprotein like antigen on rat renal tubular epithelium. Three lipoprotein fractions were obtained from rat serum by density gradient ultracentrifugation; Fraction A (Fr. A, d less than 1.019), Fraction B (Fr B, 1.019 less than d less than 1.063), and Fraction C (Fr. C., 1.063 less than d less than 1.21). Kidney, liver and heart of rats were investigated by immunofluorescence using fluorescein isothiocyanate (FITC) conjugated rabbit anti-rat Fr. A and anti-rat Fr. C sera. Significant fluorescence was observed only in rat renal tubular epithelium (RTE) suggesting the presence of identical antigenic determinants in it as rat serum lipoproteins. Relatively small doses of each fraction of serum lipoproteins were injected with Freund's complete adjuvant (FCA) in rear foot pads. Two to four weeks after the injection, very mild proteinuria appeared in all rats immunized with Fr. B and Fr. C and three months later serum cholesterol was elevated in 3 of 8 rats. But no deposition of immunoglobulins (IgG, IgM) were observed in glomeruli of all rats examined, and any histological changes could not be found in renal tissue by light or electron microscopic observation.


Asystole and its treatment: the possible role of the parasympathetic nervous system in cardiac arrest. Parasympathetic tone may be high during ventricular asystole because of reflex vagal stimulation from a number of sources. Eight patients in cardiac arrest were treated with cardiopulmonary resuscitation. All eight patients had ventricular asystole as the initial rhythm or as the result of defibrillation. Six patients failed to respond to 5 cc to 20 cc of 1:10,000 epinephrine intravenously (IV). In all eight cases a regular rhythm (sinus in seven, idioventricular in one) appeared within 30 seconds of administration of the last dose of atropine (1 mg to 2 mg IV). Five patients (62.5%) lived 12 hours, three (37.5%) were discharged from the hospital. These results suggest that atropine may be of value in the treatment of ventricular asystole.


Migration inhibition factor activity in sera of patients with chronic lymphatic leukemia. Migration inhibition factor (MIF) activity, expressed as a migration index, was studied in the sera of 48 chronic lymphatic leukemia (CLL) patients and 48 healthy controls. MIF activity was detected in the sera of 50% of the CLL patients. The medical condition of patients in advanced clinical stages (III and IV) and with detectable MIF activity was more stable (after 18-mo follow-up) than was that of the patients in advanced stages but without detectable MIF activity. No relationship was found between the clinical stage of the disease, absolute lymphocyte count, and MIF activity.


Epidemiology of oral and pharyngeal cancers in the United States: review of recent literature. Recent literature on morbidity and mortality patterns, known risk factors, and related sociobehavioral characteristics of oral cancer have been examined. Despite variation in populations and methodologies, alcohol and tobacco were seen as the major independent etiologic agents; these effects were associated with age, sex, and religion-ethnicity. Other factors were suggested, but their correlation was less consistent: geographic location, race, socioeconomic status, nutrition, dental conditions, and concurrent diseases. Social and behavioral components may alter risk, stage of disease at diagnosis, treatment or survival from oral cancer. The impact of sociobehavioral elements on the reduction of the incidence of and the mortality from the disease is an important area needing further investigation.


Enhanced macrophage tumoricidal activity and tumor suppression or regression caused by heat-killed Candida albicans. The growth of line-10 hepatoma in male Sewall Wright strain 2 guinea pigs was totally suppressed when tumor cells were mixed with heat-killed Candida albicans. In a significant number of animals, injection of C. albicans into established tumors 10-12 mm in diameter caused complete, rapid tumor regression. Guinea pigs whose tumors regressed or were suppressed as a result of injection of C. albicans rejected subsequent challenges at distant sites with the line-10 hepatoma, which indicated the development of systemic immunity to the tumor. Untreated control guinea pigs had positive delayed hypersensitivity reactions to intradermally injected C. albicans, which suggested prior natural exposure of the animals to C. albicans antigens. Peritoneal macrophages from mice that had received ip injections of phosphate-buffered saline (PBS) or C. albicans were not cytocidal for mouse 3T12 tumor cells in vitro. However, macrophages from the mice given injections of C. albicans, unlike those from mice given PBS, were markedly tumoricidal in the presence of 1 ng or more endotoxin/ml in vitro. These results demonstrated that heat-killed C. albicans, when inoculated into the peritoneal cavity, increased the tumoricidal potential of peritoneal macrophages.


[Transfer factor (TF) treatment of patients with HBs-Ag-positive chronic active hepatitis. A prospective, controlled study (author's transl)]. It is a clinically and experimentally well supported working hypothesis that infection with hepatitis B virus may result in chronic active hepatitis in patients with suspected immune deficiencies. On this basis, a pilot study was performed in order to evaluate the effect of "specific" transfer factor (TF) in the treatment of HBS-Ag-positive chronic active hepatitis. From the leukocytes of 500 ml venous blood each of 40 volunteers that had completely recovered from acute virus hepatitis B within the last 6 months, a unique TF pool (40 units of TF) was prepared according to the method of Lawrence. Preexaminations indicated that this preparation was able to enhance cellular immune reactions in vitro. Thirteen patients with HBS-antigenemia and chronic active hepatitis (i.e., two liver biopsies within the last 6 or more months with the histological criteria of chronic aggressive hepatitis according to de Groote, elevated serum levels of bilirubin, alkaline phosphatase, transaminase activities, and/or gamma-globulines) were randomized: Seven received s.c. injections of two units of TF each on days 1 and 15, the other six saline. Conversion of skin reactions to some ubiquitous antigens occurred in the TF group, but no significant and constant drop of HBS-Ag serum titers was observed. Although some of the biochemical parameters seemed to ameliorate in the TF group, the differences versus the control group did not prove to be significant within the limited number of patients under observation. The in vitro reactivity of patients' lymphocytes to HBS-Ag, tested by means of the 3H-thymidine uptake, was never found enhanced after TF application. In the used doses, "specific" TF was not effective in the treatment of HBS-Ag-positive chronic active hepatitis; unfavorable side-effects were not observed.


[Current status in the treatment of breast cancer. I. Endocrine management--change of concepts and outlook for the future (author's transl)]. A renewal of interest in endocrine therapy of breast cancer is resulting from the demonstration of steroid hormone receptors in tumor cells sensitive to antiestrogens and the possibility for predicting endocrine responsiveness. Therefore new therapeutical concepts have been developed and some of the established endocrine regimens have been reduced to historical interest. It is more than doubtful that the present schematization in selecting the proper kind of endocrine treatment has any future as methodical difficulties in demonstrating hormone receptors will be overcome and the understanding of their biological function will increase.


A simple method for the detection of antibodies to Encephalitozoon cuniculi in rabbits. Rabbit antibodies against Encephalitozoon cuniculi were detected in an indirect microagglutination test using a bead substrate to which anti-rabbit immunoglobin G light and heavy chain antibodies were coupled. The test was positive using immune whole serum or F(ab)' and F(ab)'2 fragments of immunoglobin G but negative using the F(c) fragment. The reaction was blocked by saturating the beads with rabbit serum or by absorbing positive sera with excess Encephalitozoon cuniculi. The test provided a simple method to detect antibodies to Encephalitozoon cuniculi, did not require elaborate equipment and could be performed using frozen antigen.


Serum luteinizing hormone and ovulatory response to luteinizing hormone-releasing hormone in the estrous and anestrous domestic cat. A heterologous double antibody radioimmunoassay was developed to measure changes in serum luteinizing hormone (LH) concentrations in estrous and anestrous queens (female domestic cats), following a single injection of varying doses (0--25 microgram) of luteinizing hormone-releasing hormone (LH-RH). No increase in serum LH was detected in any of the estrous or anestrous queens following a single saline injection. Treatment with LH-RH resulted in a sharp increase in serum LH concentration in both estrous and anestrous queens. Ovulations as observed by the presence of corpora lutea at laparoscopy occurred in none of four, one of four, two of four and four of four estrous queens receiving 0, 5, 10 or 25 microgram of LH-RH, respectively. Mean serum LH concentration of the ovulating queens was maintained at a higher level and did not return to basal level at the same time as that of nonovulating queens. The data show that: LH-RH can cause release of LH in both estrous and anestrous queens and induce ovulation in the estrous cat; the magnitude of LH response is influenced by the stage of the reproductive cycle; and the duration during which LH is maintained above basal level may play a significant role in ovulation induction in this coitus-induced ovulatory species.


Cathepsin B activity in stimulated mouse peritoneal macrophages. The activity of cathepsin B was assayed in murine resident peritoneal macrophages, and after stimulation of the cells in vivo and in vitro. The resident cells showed a very low activity of the enzyme, compared to the activities of three other lysosomal enzymes: cathepsin D, acid phosphatase, and beta-glucuronidase which were tested simultaneously. Endocytosis of carrageenan, latex, or carbon particles in vitro induced a prominent rise in intracellular cathepsin B activity. Addition of endotoxin from Escherichia coli in vivo or in vitro, or cell wall products from streptococci in vitro caused no change in cathepsin B activity. There was a release of enzyme activity to the medium after a 72-hour culture of macrophages. However, the release, calculated as a percentage of total activity, was not influenced by any treatments mentioned. All significant rises in enzyme activity could be inhibited by the addition of cycloheximide, and it was concluded that increased enzyme activity was dependent on new protein synthesis.


[Weltanschauung aspects of the problem of man, the biosphere and space]. The paper discusses philosophic approaches to the problem of man-environment interplay. Many important problems humanity faces today are associated with biology. Biomedical and astrophysical studies are being carried out to gain a better insight into the laws governing evolution and further development of the Universe. The emergence of a human society started a qualitatively new stage in the evolution of organic matter. A rapid progress of science and engineering is accompanied by a significant rearrangement of the natural environment and, particularly, of living beings. The biosphere is transforming into the sphere of intelligence, i.e. noosphere. However, natural phenomena are still more powerful than man-made productive forces. Man's excursion into outer space allowed him to look at himself as if from the outside and to evaluate critically his actual role, position and responsibility in the infinite Universe as compared with other forms of life and intelligence. The Universe may be boundlessly great but for human beings there is nothing better than the Earth. Our planet will long remain the base for the existence and development of humanity. Today man ought to take the streering-wheel of evolution and fate of the biosphere into his hands, in order to preserve, through the efforts of many generations, our planet as the gem of the Universe.


Identification of myosin in human epithelial cancers with immunofluorescence. The location of myosin in neoplastic cells from human breast, colonic, gastric, bronchial, skin, esophageal, and renal carcinomas has been examined using an immunofluorescence technique with an antibody raised against human smooth muscle myosin. Normal tissues and fibroblast cell cultures were also investigated. In all the tumors myosin was located in the cytoplasm adjacent to the plasma membrane. Cancer cells appeared more strongly immunofluorescent than normal tissues. The precise pattern of immunofluorescence in neoplastic cells varied with the histologic type of the tumor. Linear immunofluorescence around the outer border of the cytoplasm was the most common pattern observed, but in well differentiated adenocarcinomas, myosin was located chiefly in relation to the microvillous border. In three of the squamous carcinomas a granular pattern of immunofluorescence was observed. Undifferentiated breast carcinomas did not contain more myosin than better differentiated tumors, and the intensity of immunofluorescence was no greater in invasive cancer cells than noninvasive tumor cells. The results suggest that myosin is present in greater amounts in neoplastic cells than normal cells and may be concerned with cell shape and polarity as well as cell movement.


[Intestinal microflora makeup of astronauts before and after space flights]. The composition of the intestinal microflora of 12 cosmonauts was studied before and after space missions of varying duration. Changes in the intestinal microbial coenosis were found prelaunch. The pattern of changes did not vary with an increase in space flight duration. The use of special prophylactic measures exerted a positive effect on intestinal microecology. Bifidobacteria and lactobacilli showed the greatest changes inflight. Therefore, it seems important to arrange preflight sanation of the intestinal microflora as a prophylactic method.


A translation of Finkelnburg's (1870) lecture on aphasia as "asymbolia" with commentary. On March 21, 1870, Dr. D.C. Finkelnburg addressed the Society of the Lower Rhine in Bonn on the popular topic of aphasia. He challenged the prevailing view that aphasia was a disorder of speech only and the emphasis that had been given to the issue of cerebral localization. The disorder, he pointed out, not only extended beyond the speech modality to include verbal comprehension, reading, and writing but also included many extraverbal disturbances of symbolic usage. In support of his argument, he presented five detailed case studies of aphasics (two with autopsy data) who demonstrated a variety of verbal and extraverbal deficits. Because the term aphasia referred specifically to speech disturbance and inadequately signified the full extent of the disorder, Finkelnburg proposed the more generic term asymbolia as a more accurate representation of the nature of the disorder. This translation makes available a previously inaccessible but historically important and still viable contribution to the study of the nature of aphasia.


Speech clinicians' attribution of personality traits as a function of stuttering severity. Thirty-six speech-language pathologists participated in a study to evaluate clinicians' preconceptions of persons who stutter. Each rated a designated construct (the normally fluent individual, the mild stutterer, the moderate stutterer, the severe stutterer) using a personality trait scale. Results indicated that clinicians stereotypically assign negative personality traits to all levels of stuttering severity relative to normal. Their ratings further demonstrated that stutterers are generally considered to be a homogenous group. Differentiation amongst stutterers was made only between the polar ends of the stuttering severity continuum (that is, mild vs. severe). Clinicians' sterotypical trait assignment was not related to their professional experience. Results are discussed with reference to their clinical implications.


Adriamycin in localized and metastatic uterine sarcomas. Seventeen women with metastatic uterine sarcomas were treated with Adriamycin chemotherapy. Only one (6%) had an objective response. In addition, 12 patients with early uterine sarcomas were randomized to Adriamycin versus no adjuvant chemotherapy in order to evaluate the effect of Adriamycin in reducing the incidence of subsequent distant recurrences. Of those women receiving Adriamycin, two developed distant metastasis and two developed life-threatening congestive heart failure. Also, two of the six women who did not receive Adriamycin developed distant metastasis. Therefore, continuation of the randomized trial was considered unjustified.


The value of prophylactic antibiotics in aorat-coronary bypass operations: a double-blind randomized trial. Prospective and retrospective studies were performed to determine the efficacy of prophylactic antibiotics in preventing infections in patients undergoing arota-coronary bypass. One-hundred five patients were randomized in a double-blind fashion to receive either methicillin or saline-placebo for 3 days. The over-all infection rate was 26.7% with 48.9% in the control group and 8.6% in the methicillin group (p less than 0.001). Significant sternal wound infection developed in 21.3% of the control group and 0% of the methicillin group (p less than 0.01). Staphylococcus aureus was the predominant organism causing significant sternal infection (methicillin group versus control group, 5.2% and 21.3%; p less than 0.05). The length of postoperative stay in hospital and the number of days with fever was significantly greater in the control group than in the methicillin group (p less than 0.001). During the same period of time, 160 patients were studied retrospectively. Of these, 150 patients received cephalothin prophylaxis and 10 received methicillin. Comparison of the rates of infection in the cephalothin group to the total methicillin group (prospective and retrospective) showed no significant difference. The study clearly demonstrated that a short course of prophylactic antistaphlococcal penicillin or cephalosporin is justified in aorta-coronary bypass.


Chlamydial infections. Microbiological, clinical and diagnostic aspects. The agent of trachoma, originally regarded as a virus, was described by Halberstadter and von Prowacek in 1907. Since then, studies on Chlamydiae have shown that they are procaryocytic organisms that infect eucaryocytic cells as obligate intracellular parasites. Infections caused by these pathogenic agents occur in a wide range of avian and mammalian species. Chlamydiae are also responsible for several diseases in man, and there is a rapidly growing awareness of their public health significance. The aims of this review are to describe the microbiology and laboratory diagnosis of Chlamydiae and to reflect the clinical spectrum of human chlamydial diseases.


Prostaglandins in the regulation of circulation and blood pressure. Endogenous prostaglandins (PGs) participate in the regulation of local circulation, and presumably also in the control of systemic blood pressure. Vasodilatory PGs synthesized in resistance vessels seem to maintain the basal blood flow in some tissues. Vasoconstriction stimulates the PG synthesis in vessel walls, and the vasodilatory PGs antagonize this constriction in several vascular beds. Circulating vasodilatory PGs or their metabolites may function as antihypertensive hormones. Reports on the effect of intrarenal PG production on renal function are contradictory. The renin-angiotensin-aldosterone and kallikrein-kinin systems have complex interrelations with PGs. PGs may also participate in the mechanism of action of some cardiovascular drugs.


Psychological contributions to chronicity in asthma: patient response styles influencing medical treatment and its outcome. Research is reviewed relating to two aspects of response styles among asthmatic patients, neither of which is a mere derivative of the patient's medical condition. One aspect, indexed by panic-fear symptomatology, appears to be associated with the level of attention directed at breathing difficulties, ranging from symptom disregard (low panic-fear symptomatology) to symptom vigilance (high panic-fear symptomatology). A second aspect, indexed by a derived personality dimension, appears to be associated with the quality of the patient's reactions to acknowledged breathing difficulties, ranging from extreme independence (low panic-fear personality) to helpless and ineffective dependency (high panic-fear personality). Simply, these aspects of patient response styles refer both to the attention directed toward breathing difficulties and to the quality of the patient's reactions in response to acknowledged breathing difficulties. Their importance derives from 1) their interaction with the severity of asthma to influence medical decisions about the intensity of prescribed medications and length of hospitalization during medical treatment and 2) their effect on long-term medical outcome. Awareness of these two aspects of patient response styles should enable differential approaches to be adopted by physicians seeking to counteract psychological contributions to chronicity in asthma.


Changing disease patterns, changing values: problems of geriatric care in the U.S.A.: an outsider's view. Changing disease patterns coupled with recent shift in societal values bring into focus, among other challenges, the problems of geriatric care, with their medical and social aspects. Medicare and Medicaid were meant to respond to the needs of geriatric care. However there is almost a general consensus that in spite of being valuable in many respects, Medicare and Medicaid have failed to generate considerable change in the overall care for the elderly. The basic characteristics of the American Health care system are not conducive to an approach which envisages geriatric care as a comprehensive primary care level, within a system of health care, combining medical with social activities in a team led by a competent physician. Since such an approach seems to be a most appropriate one, an attitude on the part of the medical profession which concentrates on the medical aspects only and neglects the entire complex of problems, substantial and organizational, associated with geriatric care, may lack utility. The problems the U.S. faces in the health field, geriatric care included, are common for today's industrialized societies. However, certain specific difficulties seems to result from the fact that some components of the health care system insist on solving problems generated by changing disease patterns and changing societal values, with no change in their own structure and their own value system.


Trace elements in human nutrition.

Trace elements in human nutrition. Clinical recognition of the role of trace elements in human nutrition is increasing. Heretofore, many clinicians felt that the development of deficiency states was not likely except in very extreme conditions because the presence of trace elements in nature was so ubiquitous. The increased use of total parenteral nutrition seems to have made this viewpoint untenable. The recognition of additional genetic diseases of trace element metabolism such as Menkes' kinky hair syndrome and acrodermatitis enteropathica has also served to focus clinical attention on trace elements. As time passes, no doubt, additional diseases of trace element metabolism will be recognized.


Dietary fiber.

Dietary fiber. It is obvious that the effects of fiber on colonic functions are complex. The typical "Western diet" which is high in fat and protein and low in fiber may alter the bacterial flora and milieu interieur of the gastrointestinal tract, particularly the colon, to produce a high incidence of colonic cancer. However, the exact nature of the interrelationships between these dietary constituents remains elusive and will undoubtedly be the subject of intense investigation in years to come.


Nutritional management of chronic renal disease. The importance of nutritional evaluation and diet therapy in the overall management of the patient with chronic renal disease is unquestioned. Its application often is limited by a lack of knowledge regarding the requirement for certain nutrients in health as well as the way in which these requirements are modified by chronic disease. However, the most important and often the most difficult task is engaging the cooperation of the patient in the nutritional management of his disease. Acceptance of dietary manipulation depends upon the patient's family structure and the importance of food and mealtime within the particular cultural and ethnic background. Dietary recommendations implemented by the parents of pediatric patients may produce untoward changes in the child's behavior, attitudes toward food, or relationships with other family members. Dietary recommendations must be carefully planned and their effect reevaluated. They should be individualized to the age, intellectural skills, and developmental stage of the patient.


Nutrition in the alcoholic.

Nutrition in the alcoholic. Effective management of nutritional problems in the alcoholic patient requires that the clinician understand the complex interaction of alcohol and nutrition. Nutritional deficiencies should be prevented and, if present, corrected. However, experimental, clinical, and epidemiological evidence indicates that despite adequate diets, ethanol has direct toxic effects on the digestion, absorption and activation of foodstuff. Furthermore, recent studies have shown that even in well nourished populations relatively small amounts of alcohol may have cirrhogenic potential. For these reasons, the overall approach to the management of the alcoholic must involve the control of alcohol intake as well as the prevention and correction of nutritional disturbances.


Serratia marcescens in tracheotomy cultures. Twenty-three consecutive tracheotomies were cultured after an apparent outbreak of Serratia marcescens was noted. Over a period of one year, six cases with positive cultures were found. The importance of these positive cultures in relation to the patient's clinical course is discussed. The treatment of Serratia marcescens septicemia is reviewed.


Identification of ergosta-8,24(28)-dien-3 beta,6 alpha-diol in A delta 8 goes to delta 7 sterol isomerase-blocked yeast mutant. In addition to the monohydroxysterols found in the delta 8 goes to delta 7 isomerase-blocked Saccharomyces cerevisiae mutant erg 2, a noval dihydroxysterol, ergosta-8,24(38)-dien-3 beta,6 alpha-diol, was isolated. This sterol accumulated to the extent of 2.1% of the total sterol fraction when this mutant was treated with 23-azacholesterol, a known inhibitor of the 24-methylene-sterol-24(28)-reductase.


A novel type of coupling between proline and galactoside transport in Escherichia coli. Exit of thiomethylgalactoside (TMG) from preloaded cells induced the accumulation of proline. Likewise, proline exit stimulated TMG accumulation. Since a proton ionophore (carbonylcyanide-m-chlorophenylhydrazone) abolished these effects, a protonmotive force was implicated as the "intermediate" in the coupling reaction. The evidence suggests that the exit of TMG resulted in proton exit, which produced either a membrane potential (inside negative or a pH gradient (outside acid) or both. This inwardly directed protonmotive force provided the energy for proline entry and accumulation. Thus the energy coupling was not via a common transport protein but by proton movements which coupled the two separate H+-dependent transport processes.


La menespausie--the birth of a syndrome. The prevalent assumption that climacteric disturbances appeared when the expectation of life of women assured survival past the menopause cannot be supported demographically. These disorders are largely conditioned by sociocultural factors and, therefore, may be expected to have been initiated when these factors became stressful. Historical examination shows that medicine, or its marginal practitioners, were always involved in the postponement of ageing whenever the status of women depended more on their attractiveness than other social determinants, a logical "geriatric" extension of its traditional cosmetic activities. No menopausal disturbances are however recorded until the social convulsions of the French Revolution, and the regimes which followed, seem to have crystalized the various complaints of the climacteric into a disease-expression, which reified the social stress to which women were subject. This is dramatically reflected, both in the medical writings published in France around the year 1800, and in the naming, for the first time, of this phase of woman's life: La Menespausie, soon shortened to Menopause.


Effect of capsular polysaccharide of Klebsiella pneumoniae on host resistance to bacterial infections. III. Further study of its effects on interactions between peritoneal leukocytes and virulent Salmonella enteritidis. The mechanism for the infection-promoting effect of the capsular polysaccharide of Klebsiella pneumoniae (CPS-K) was investigated using the experimental system in which mice were infected intraperitoneally (i.p.) with a virulent strain of Salmonella enteritidis immediately after i.p. injection of CPS-K. In the peritoneal phagocytes of CPS-K-untreated control mice, approximately 70, 3, and 10% of phagocytized bacteria survived 6, 12, and 24 hr after challenge, respectively, when calculated from the ratio of the number of cell-associated viable bacteria, which was estimated by direct plate count, to the number of phagocytized bacteria, which was estimated by microscopic observation of stained smears. In contrast, almost all of the phagocytized bacteria were viable throughout the experimental period in mice treated with CPS-K. The electron microscopical findings of the phagocytes obtained 12 hr after challenge showed that in the cells of mice treated with CPS-K almost all of the phagocytized bacteria were morphologically intact, with some of them in the stages of cell division, whereas in those of untreated control mice, almost all of the phagocytized bacteria underwent digestive changes. When the reaction product of acid phosphatase was examined by electron microscopy in the phagocytes obtained 12 hr after challenge, the enzyme activity in the phagosomes was very low in mice treated with CPS-K in comparison with that in untreated control mice. Enzyme assays of the lysosomal and extralysosomal fractions of peritoneal cells obtained at various times after challenge also showed that release of acid phosphatase from the lysosomal fraction to the extralysosomal fraction after bacterial challenge was inhibited in peritoneal cells of mice treated with CPS-K.


Interferon and cytotoxic factor (cytotoxin) released in the blood of mice infected with Mycobacterium bovis BCG. II. Influence of time after BCG inoculation on production of interferon and cytotoxin by capsular polysaccharide of Klebsiella pneumoniae or by bacterial lipopolysaccharide and on hyperreactivity to their lethal effects. The time course of the occurrence of hyperreactivity in interferon and cytotoxin responses to the active substance (neutral fraction) of the capsular polysaccharide of Klebsiella pneumoniae (neutral CPS-K) and bacterial lipopolysaccharide (LPS) and of the hyperreactivity to their lethal effects was followed after infection with BCG in SMA and ICR strains of mice. The duration of these hyperreactivities of BCG-infected mice depended on the inoculum doses of BCG. The time patterns of the hyperreactivity to the lethal effects of neutral CPS-K and LPS were similar in both strains of mice, although the maximum toxicity of LPS by the intraperitoneal route in BCG-infected mice on a weight basis was stronger than that of neutral CPS-K. Irrespective of inducer and mouse strain, the time pattern of the hyperreactivity to produce cytotoxin was similar to that of the hyperreactivity to produce interferon. The patterns for these phenomena when neutral CPS-K was used as an inducer were also similar to those when LPS was used. In ICR mice the hyperreactivity in interferon and cytotoxin responses to either neutral CPS-K or LPS decayed significantly earlier than the hyperreactivity to their lethal effects, whereas in SMA mice the occurrence of both types of hyperreactivities seemed to be associated. Therefore, it is suggested that the mechanism for the hyperreactivity in interferon and cytotoxin responses to neutral CPS-K or LPS in BCG-infected mice is not necessarily the same as that for the hyperreactivity to their lethal effects.


Integration of temperature-sensitive nonconjugative plasmid carrying kanamycin gene into conjugative R plasmids. A nonconjugative R plasmid, rMS3, whose molecular weight was 2.4 X 10(7) daltons, possessed a kanamycin resistance gene and was thermosensitive in its maintenance in Escherichia coli strains. We mobilized rMS3 with a conjugative R plasmid, R100 or T-tet, and obtained cointegrates carrying all the parental resistance markers. Various markers of the cointegrates were frequently deleted by P1 transduction and the deletion patterns among the different cointegrates were differed from each other. The cointegrates were thermoresistant, but the thermosensitive replicon could be segregated from the thermoresistant cointegrate by deletion. Some cointegrates between rMS3 and T-tet showed a derepressed state of transferability because of the integration of rMS3 and T-tet showed a derepressed state of transferability because of the integration of rMS3 into the regulator gene of the transfer loci. The genome size of the cointegrate so far tested was the sum of the sizes of the parental plasmids, indicating that the whole genome of rMS3 could integrate into various sites of the conjugative plasmids R100 and T-tet.


[Morphogenetic features of Sulfobacillus thermosulfidooxidans]. The morphogenesis of Sulfobacillus thermosulfidooxidans BKM B-1269 was studied by electron microscopy at the vegetative stage of growth on a medium with pyrite as the source of energy. Young growing cultures of this organism were found to be very polymorphous: along with rod-like cells of various dimensions (0.6--0.8x1.0--3.0 mcm) which were predominant, coccoid, pyriform, clavate and dumbbell-like cells were also encountered. Certain cells have a tendency for branching. The cells can divide by sudden breaking of the parent cell along a partition being formed. These breaks are often incomplete, thus giving rise to cellular aggregates in the shape of palisades, bent chains, rings and Y-formations. The above characteristics of S. thermosulfidooxidans morphogenesis suggest that the genus Sulfobacillus is related to Corynebacterium-like organisms and actinomycetes. However, this genus differs in its morphology from bacilli though both (as well as actinomycetes) are capable of spore formation.


[Composition and certain properties of Candida albicans cells with a low level of resistance to polyene antibiotics]. The lipid and protein composition of Candida albicans, strain R3, with a low resistance to polyene antibiotics does not differ much from that of the parent, susceptible culture. Nevertheless, the rate of potassium release from the cells and the incorporation rate of 14C-amino acids in the cells of C. albicans, strain R3, under the action of amphotericin B are lower as compared to the susceptible culture; therefore, the resistance of C. albicans, strain R3, must be due to a decrease in the degress of its disordered selective permeability. Sterols isolated from the cells in both strains were found to be capable of binding to polyenes at a high rate in solution. However, sterols from the strain R3 with a low resistance to polyenes, when incorporated into a synthetic lipid membrane, increase its permeability slower than sterols from the susceptible strain, which suggests that sterols from the low-resistant strain R3 are possibility involved in the phenotypic manifestation of resistance.


[New remote hybrids between Saccharomyces and Schizosaccharomyces]. Crossing the cells of Saccharomyces (diploid) and Schizosaccharomyces (haploid) cells as well as using genetic markers (adenine dependent mutants) and selective media produced remote hybrids. The hybrid cultures possessed the intermediate type of inheritance in a number of properties. Along with budding typical of Saccharomyces, partitions characteristic of Schizosaccharomyces were encountered. The shape and size of cells and some physiological properties were found to vary in the course of vegetative growth (no spores were formed by the hybrid cultures). Conditions are discussed which favour remote hybridization of yeast cultures.


Cimetidine and gastric ulcer healing: a double-blind controlled trial. The effect of cimetidine in the daily dose of 1200 mg on the healing rate of chronic gastric ulcer was assessed in a randomized double-blind trial in 48 patients. Cimetidine was found to accelerate the healing of chronic gastric ulcers in the ambulant patients, but it conferred no additional benefit on the patients in hospital. No significant side effects were observed.


[Structure and physico-chemical properties of bacterial flagella]. The structural organization of bacterial flagella was studied with Bacillus brevis and Escherichia coli MS 1350. The presence of a spherical body at the basis of a flagellum was confirmed. The structural organization of ingredients of the flagellar appratus, its inner and outer part, was investigated. The molecular weight of protein subunits in the filamentous portion of the flagellum was assayed as well as their amino acid composition. The mode of attachment of the flagellum to the cell is discussed.


[Dynamics of the number of soil bacteria calculated by different methods]. Temporal changes in the incidence of soil bacteria were estimated using different methods such as luminescent microscopy, direct count according to Vinogradsky, growth on MPA. The method of Vinogradsky gave less stable results as compared to luminescent microscopy. The method of calculating microorganisms was found to influence the results obtained while studying the temporal dynamics of bacterial incidence in sod-podzolic soil.


[Use of cytofluorometry to determine the amount of DNA in yeast cells]. The purpose of this work was to test the possibility of using a luminescent variant of the Feulgen reaction with the reagent auramine-SO2 for staining yeast cell nuclei in order to determine the content of DNA in them. Reproducibility and stability of results obtained by this method suggest that it can be used to control the ploidy of the nuclei from yeast cells belonging to one and the same species.


Chronic lymphocytic leukemia in association with a second lymphoproliferative disorder: response to chemotherapy in two cases. The development of either histiocytic lymphoma or Hodgkin disease in association with pre-existing chronic lymphocytic leukemia has been described in the literature as a terminal event. We describe two patients in whom the diagnosis of a second malignant lymphoma was made during life and who achieved objective clinical response after a change in therapy to a more aggressive combination of drugs. We conclude that patients with chronic lymphocytic leukemia who have had a sudden change in their clinical course should have thorough reevaluation, looking specifically for the development of a second lymphoproliferative disorder. If this is discovered, more aggressive therapy should be initiated.


Orbital rhabdomyosarcoma in a neonate.

Orbital rhabdomyosarcoma in a neonate. A newborn with a pleomorphic rhabdomyosarcoma of the eyelid was treated by chemotherapy, surgery, and radiation therapy and experienced a good response. The nine previous cases in the literature are reviewed and this patient's therapy discussed.


Evolution in the structure and function of carboxyl proteases. A model for the structure and function of extracellular carboxyl (acid) proteases can be established from three amino acid sequences and four crystal structures of these enzymes. The carboxyl proteases from gastric and fungal origins are very homologous in both primary and tertiary structures. The molecules consist of about 320 residues organized with a secondary structure which is primarily comprised of beta-strands and very similar tertiary structures. An apparent binding cleft, which can accommodate a substrate with about eight amino acid residues, contains near its midpoint the active center residues Asp-215, Asp-32, and Ser-35. These three residues are hydrogen bonded to each other. An intracellular carboxyl protease, cathepsin D, is very homologous to the extracellular enzymes in N-terminal amino acid sequence and primary structure location of active center residues. The tertiary structure of cathepsin D is probably similar, as well. However, cathepsin D contains a unique hydrophobic "tail" made up of about 100 residues added on the C-terminal side. Cathepsin D precursor is over 100,000 daltons in molecular weights, as contrasted to the gastric carboxyl protease zymogens, which are about 40,000 daltons. Carboxyl proteases contain two lobes symmetrical in peptide chain conformations. Each of the lobes also consists of two homologous structural units. These structural characteristics suggest that the original gene was coded for only about eighty amino acid residues and that gene duplication and fusion has taken place twice to produce a single chain carboxyl protease with four basic structural units in two symmetrical lobes. The formation of the zymogens and the cathepsin D "tail" must have resulted from various gene fusions. Partial sequence comparisons also suggest that cathepsin D may be an evolutionary ancestral chain for gastric carboxyl proteases.


Arginyl residues and anion binding sites in proteins. The functions of a number of amino acid residues in proteins have been studied by chemical modification techniques and much useful information has been obtained. Methods using dicarbonyl compounds for the modification of arginine residues are the most recent to have been developed. Since their introduction about 10 years ago, they have led to the identification of a large number of enzymes and other proteins that contain arginine residues critical to biological function. These reagents are discussed in terms of their chemical reactivity and mechanisms of action and in relation to the unique chemical properties of the guanidinium group. Butanedione, phenylglyoxal and cyclohexanedione are the most commonly employed arginyl reagents, and their relative advantages are examined. A survey of the functional role of arginine residues in enzymes and other proteins is presented in which nearly 100 examples are cited. The prediction that arginine residues would be found to serve a general role as anionic binding sites in protein has obviously been validated. The genetic and physiological implications of the selection of arginine for this important function are discussed.


Improved method for the specific immunoprecipitation of albumin. The immunoprecipitates of many antigens are frequently contaminated by coprecipitation of unrelated substances. A method to overcome this type of contamination in the immunoprecipitation of albumin is described. The insoluble albumin-antibody complexes are solubilized by a brief treatment at high temperature in the presence of sodium dodecyl sulfate, and after dilution the mixture is submitted to a second immunoprecipitation.


[Influence of the structure of photoreactive ATP analogs on the affinity modification of phenylalanyl-tRNA synsthetase. Modification of the enzyme at two types of nucleotide sites]. ATP gamma-(p-azidoanilidate) (1) and ATP gamma-(p-azidobenzyl)-methylanilidate (2) were shown to be competitive inhibitors for ATP and amino acid in tRNA aminoacylation catalyzed by E. coli MRE-600 phenylalanyl-tRNA synthetase (E.C.6.1.1.20). Low concentration (10(-5)--10(-6) M) of either ATP, gamma-anilidate or GMP stimulates the aminoacylation of tRNA suggesting their interaction with some nucleotide binding sites of the enzyme other than catalytic ones. Covalent photobinding of (1) to the enzyme does not inhibit aminoacylation, nor does it prevent nucleotides from activating the enzyme. UV-irradiation of the synthetase in the presence of (2) results in complete inactivation of the enzyme which can be prevented by phenylalanine or phenylalanine-ATP to save 50% of the enzyme activity but not ATP and tRNA. The photobinding of (2) to the enzyme in the presence of phenylalanine and ATP removes the activation of the enzyme by nucleotides suggesting that both the catalytic and effector sites of the synthetase are blocked in the same manner by compound (2).


[Effect of rifampicin on the synthesis of bacterial RNA polymerase mRNA by means of hybrid plasmids]. We studied the rate of synthesis of beta- and beta'-subunits of DNA-dependent RNA polymerase and the rate of beta-polypeptide mRNA synthesis in rifampicin-treated bacteria. The antibiotic doses used did not significantly inhibit the total RNA and protein synthesis in rifampicin-sensitive bacteria. For RNA-DNA hybridization experiments a pOD162 plasmid was constructed carrying a fragment of the rpoB gene and no other chromosome DNA regions. It is found that low doses of rifampicin cause an absolute and differential increase in the rate of synthesis of the specific mRNA for the beta-subunit, suggesting a stimulation of the corresponding gene transcription. However the absolute transcription stimulation does not fully correlate with the relative acceleration of beta-mRNA and the corresponding polypeptide synthesis. The stimulating effect of rifampicin on the beta-polypeptide synthesis was demonstrated also in a coupled system of transcription and translation directed by lambda rifd 47 DNA. The possible mechanisms of the rifampicin action are discussed.


[Complementarily addressed alkylation of Escherichia coli ribosomal RNA in complexes with particular conformation]. Among the number of complementary complexes of 23S RNA with alkylating derivatives of complementary oligonucleotides ((Ap)3-5 ARCl, (Cp)5CRCl and (Np)5NRCl) some complexes of peculiar conformation are observed. The rate constant of alkylaation within the peculiar complexes is four fold greater than that within the rest complexes. The latter are alkylated via an active intermediate that is formed in the first rate determining step by two step alkylation. Both individual 23S RNAs and one in the rRNA mixture are alkylated in the peculiar complexes. But 16S RNA is alkylated only by the two step alkylation. There is a single binding site in the rRNA  that is alkylated with the alkylating derivatives of the definite nucleotide sequence at the definite base. The reagments with different sequences can alkylate different bases. The alkylating derivatives of hexa-nucleotide isoplits that are complementary to rRNA alkylate up to 45 +/- 10 complexes simultaneously. The conformation of these complexes enables alkylation with the higher rate constant mentioned above.


[Transcription initiation: influence of ionic strength and actinomycin D on the kinetics of the open promoter complex formation between Escherichia coli RNA-polymerase and T7 DNA]. A membrane filter assay has been devised to study the influence of ionic strength (0--150 mM NaCl) and actinomycin D on the kinetics of the open promoter complex formation between E. coli RNA-polymerase and [3H]DNA of T7 phage. The dependence of the complex formation rate upon the ionic strength is non-monotoneus with a maximum at 75--100 mM. The addition of one actinomycin molecule per 200 base pairs decreases the open promoter complex formation rate at ionic strength less than 100 mM. A promoter site selection model including liner diffusional selection is proposed which is in a good agreement with the experimental results obtained.


Structure and function of intracellular proteoglycans. Proteoglycans are generally thought of in terms of extracellular function, but there is evolving evidence that they are also an important constituent of secretory granules. Although the mast cell appears to be uniquely endowed with granule proteoglycan heparin, the peripheral blood elements such as basophils, neutrophils, and platelets contain predominantly chondroitin sulfates which have not been fully characterized and are presumed to be of granular origin. Coupled activation-secretion of the rat mast cell and the human platelet, respectively, has demonstrated the release of a proteoglycan-protein complex. It is suggested that the intracellular proteoglycans serve as the granule matrix to allow the storage of structurally diverse chemical mediators, their transport during the cell secretory response, and, finally, their discharge from the granule to the microenvironment. The granule constituents of the rat mast cell differ after discharge in their bioavailability thereby suggesting that the proteoglycan may have a regulatory function in the extracellular environment.


[Internal structure of ribosomes using different types of emission]. A review is made of the experimental results obtained by the author and co-workers on the study of the structural organization of the RNA and the protein in ribosomes by the method of joint use of light, X-ray and neutron scattering and by the method of contrast variation in neutron scattering. Two rules are formulated for the folding of the ribonucleoprotein strand in ribosomes: (1) in each ribosomal subparticle the RNA is concentrated predominantly closer to the center of the particle whereas the protein has a more peripherical localization; (2) the compact ("crystallic") packing of hydrated RNA helices is an essential feature of the nucleus (nuclei) organization of the particles. An analysis of the experimental data on neutron scattering by ribosomal proteins has been done and the globulin conformation in solution of some of these proteins has been established. The widespread concept according to which the majority of ribosomal proteins on the ribosome and in solution are enlongated expanded structures is disputed. It is suggested that all, or almost all, ribosomal proteins are usual globular proteins recognizing the specific sequence of RNA on the periphery of the particles, and , hence, that the formation of functional centrers on the ribosome is, in principle, analogous to the formation of functional centers of other complex proteins with a quaternary structure.


[Chemical modification of the complex of tRNA Phe with phenylalanyl-tRNA synthetase from Escherichia coli]. Alkylation of E. coli tRNAPhe, bound to the cognate synthetase was investigated. The alkylating reagent is a derivative of 2-chloroethylamine: 2',3'-O-[4(N-2-chloroethyl-N-methylamino)-benzylidene]-uridine-5'-methylphosphate. It was found that the enzyme protects from the reaction D-stem (guanosine G24) and the region of juxtaposition of acceptor stem and D-stem (S4U8 and C13) in the tRNAPhe.


The mutagenicity of nitrosopyrrolidine is related to its metabolism. Various cell fractions from rat liver were tested for their ability to convert nitrosopyrrolidine (NO-PYR) to products which were mutagenic to E. coli in liquid-incubation assays. Microsomes alone produced only a small number of tyr+ revertants, approximately 40/10(8) survivors), while the S100 supernatant produced none at all. However, the S8 Fraction or combinations of microsomes and the S100 supernatant, yielded 300-400 tyr+ revertants/10(8) survivors. Neither products of the microsomal, nor microsome + supernatant reactions were mutagenic in the absence or presence of cellular fractions. These results suggest that bacterial mutagens are formed during the microsomal metabolism of NO-PYR to 2-hydroxytetrahydrofuran by alpha-hydroxylation, but not during the metabolism of 2-hydroxytetrahydrofuran by the S100 supernatant enzymes. Possible roles of the supernatant enzymes in the formation of mutagenic intermediates during the initial alpha-hydroxylation of NO-PYR are discussed.


Azide-induced mutagenesis in gram-negative bacteria is recA-and lexA-independent. Azide-induced mutagenesis was investigated in Salmonella typhimurium and Escherichia coli. Azide was highly effective in inducing mutation in uvrB, uvrB recA and uvrB recB mutants of S. typhimurium. The mutagenic effect of azide was also observed in uvrA lexA mutants of E. coli K12 and E. coli B/r. These results suggest that azide-induced mutagenesis is due to mis-replication of DNA.


MMS mutagenesis in strains of Escherichia coli carrying the R46 mutagenic enhancing plasmid: phenotypic analysis of Arg+ revertants. Arg+ revertants of E. coli AB1157 and derivative strains were selected after MMS mutagenesis and subjected to a phenotypic analysis which permitted the partitioning of revertants into 4 classes. The distribution of these revertant classes was influenced by mutations affecting DNA-repair systems, mutagen treatment and revertant-selection methods. Introduction of the R46 plasmid into strains also affected this mutational specificity, and it was concluded that the plasmid's mutagenic enhancing effect does not merely augment the cellular error-prone capacity to repair MMS damage to DNA.


Genetic effects of formaldehyde in yeast. III. Nuclear and cytoplasmic mutagenic effects. Low concentrations of formaldehyde induce nuclear mutations when yeast cells are allowed to grow in the presence of this compound. The induction of reversions is a linear function of the concentration and depends upon the repair capacities of the treated cells. A strain defective in excision-repair (rad3-12) is more mutable by formaldehyde than the isogenic wild-type whereas a strain blocked in the mutagenic pathway (rad6-1) is not mutable after the same treatment. Allele specificities were found. In particular the lys1-1 mutation is not reversible by formaldehyde. Higher concentrations of formaldehyde induce efficiently the cytoplasmic "petite" mutation in non-growing conditions when a lethal effect is noticeable. The growth phase as well as the physiological state influence this mutagenic effect. The mutagenic effect of formaldehyde in yeast is discussed in relation with the repair processes involved.


MMS induction of different types of genetic damage in Aspergillus nidulans: a comparative analysis in mutagenesis. Methyl methanesulphonate (MMS) was used to test the induction of gene mutation, somatic crossing-over and mitotic non-disjunction in A. nidulans. Gene mutation was tested by inducing mutants resistant to 8-azaguanine and revertants of methG1 in a haploid strain. Somatic crossing-over was tested in heterozygous diploids, both with a selective method, i.e. inducing homozygosis to FPA resistance in a heterozygous fpa A1/+ strain, and with a non-selective method, i.e. identifying the frequencies of colour sectors. This latter method was also used to estimate the induction of non-disjunction because additional markers were present which permitted us to distinguish the two types of colour segregant. Generally, 3 different experimental procedures were used, namely the "plate test", i.e. plating of conidia in agar media containing MMS, and two types of "liquid test", i.e. brief treatment of quiescent or pre-germinated conidia in MMS solution before they were plated on agar media. Point mutations were induced with about equal efficiency with each method, whereas crossing-over was induced preferentially when germinating conidia were exposed to MMS. On the other hand, non-disjunction was induced in germinating and quiescent spores with equal efficiency, but such segregants were not recovered with the selective (fpa) method. The results are discussed for both their practical use in the mutagenic testing procedure and their theoretical implication.


Hodgkin's disease.

Hodgkin's disease. During the past two decades, new approaches to the diagnosis and treatment of Hodgkin's disease have contributed to improved rates of survival and probable cure. Currently, patients with Hodgkin's disease are treated according to the stage and symptoms of their disease. The degree of certainty necessary for determining stage depends on the potential effectiveness of the therapeutic options available in a given case. Certain cases have been identified where treatment with a single modality has been disappointing, and the use of both radiotherapy and chemotherapy may be considered for these. Such decisions can be made only by evaluating the effectiveness of salvage after relapse following single-modality treatment and assessing the added hazards of initial treatment with both modalities.


A controlled study of short-term prednisone treatment in adults with membranous nephropathy. Seventy-two adults with the nephrotic syndrome without renal insufficiency had a membranous type of renal histology on biopsy. These patients were randomly allocated to at least eight weeks of alternate-day treatment with prednisone or placebo in a multicenter study. Deterioration of glomerular filtration rate was significantly more rapid in placebo-treated than in prednisone-treated patients, and ultimately 10 of 38 given placebo but only one of 34 given prednisone were in renal failure (creatinine more than 5 mg per deciliter [440 mumol per liter]) or dead (P less than 0.02). In male patients and in those with nonselective initial proteinuria, there was a trend (not reaching statistical significance) toward more rapid deterioration of renal function. Age, admission blood pressure, serum creatinine, daily total protein excretion, and severity of histologic changes did not predict the subsequent course. We conclude that a short course of alternate-day prednisone therapy was beneficial in our group of patients with idiopathic membranous nephropathy.