A review of surfactant principles in the fetal physiology of man and animals. A short review is given of the problems concerning surfactant principles in the fetal physiology of man and animals and our present knowledge of the subject.


Difference in antimalarial activity between certain amino alcohol diastereomers. A striking difference in antimalarial activity between the diastereomers of 6-bromo-alpha-[2-(1-methylpiperidyl)]-9-phenanthrenemethanol, alpha-(3-peperidyl)-3,6-bis(trifluoromethyl)-9-phenanthrenemethanol, and alpha-(3-piperidyl)-2,8-bis(trifluoromethyl)-4-quinolinemethanol was observed. A possible explanation involving the N-O distance and active site binding requirements is suggested.


Synthesis of 5-substituted uracil derivatives. The synthesis of a series of 5-substituted uracil derivatives is described. 5-Bromoacetyluracil (2a) was converted to the glycolyl (2b), glycyl (2c), N,N-dimethylglycyl (2d), 4-imidazolyl (3), and 2-amino-4-thiazolyl (4) derivatives. 5-Formyluracil (5) was used in the preparation of the 2-imidazolyl (6), the 3-acrylic acid (7b), the ester (7a), and the 3-N,N-dimethylacrylamide (8) derivatives. A Mannich reaction converted 5-acetyluracil to the amino ketone 9 which was reduced to give the 3-dimethylamino-1-propanol derivative 10. Compounds 2b,d,3,4,6, and 7b failed to inhibit the growth of Escherichia coli B and Staphylococcus aureus.


Correlation analysis of Baker's studies on enzyme inhibition. 2. Chymotrypsin, trypsin, thymidine phosphorylase, uridine phosphorylase, thymidylate synthetase, cytosine nucleoside deaminase, dihydrofolate reductase, malate dehydrogenase, glutamate dehydrogenase, lactate dehydrogenase, and glyceraldehyde-phosphate dehydrogenase. The inhibitory activity of 1058 inhibitors of the title enzymes has been formulated in 13 equations correlating chemical structure with inhibitory potency. Two types of regions in enzymes have been defined by means of pi and molar refractivity constants. The use of indicator variables has been extensively developed to suggest special enzyme-ligand interactions. Several examples are given of the use of correlation equations in comparing structural features of different systems.


Enumeration of beta-haemolytic streptococci on normal skin by direct agar contact. Normal skin sites in children from a population in which streptococcal impetigo is endemic were examined for the presence of beta-haemolytic streptococci by a direct agar-contact technique. Ninety-eight of 554 samples (18%) were positive for these organisms. Penicillin prophylaxis reduced the frequency of isolation of streptococci from the normal skin for a period of 3 weeks, perhaps accounting in part for the lower isolation rate in this than in earlier studies. Numbers of streptococcal colony-forming units in positive samples were generally low, both in terms of absolute numbers isolated from the surface area sampled and in comparison with numbers of other aerobic flora recovered. The presence of streptococcal pyoderma at the time of agar contact was not necessarily associated with the presence of or with increased numbers of streptococci on samples obtained from normal skin sites. Low counts were consistently found in early summer and higher counts in some samples in late summer. In a simultaneous comparison of paired samples taken from adjacent sites, the frequency of detection of streptococci by direct agar contact compared favourably with that obtained with a moist-swab method. The increased frequency of detection by the agar-contact method appeared to be related to an increased sensitivity for the detection of low numbers of streptococcal colony-forming units on the normal skin.


Transmission of human rotaviruses to gnotobiotic piglets. Faecal filtrates containing rotavirus particles, from children with acute infectious diarrhoea, were inoculated intranasally into gnotobiotic piglets. The piglets developed no symptoms, but birus was readily found by electron microscopy in their faeces during three serial passages. Among 11 piglets tested 3 weeks after inoculation of virus, all had developed fluorescent antibodies against tissue-culture-adapted calf rotavirus but only two had neutralising antibody. Growth of human rotavirus did not occur in either normal or "nude", thymus-deficient suckling mice.


A new method for comparative light and electron microscopic studies of individual cells, selected in the living state. A method is described which permits comparative light and electronmicroscopic studies of cell cultures, cell spreads or single selected cells which have been kept in the Plastic Film Dish (PFD). The PFD is a versatile large surface tissue culture chamber which, for electron microscopy, is mounted with a transparent FEP-Teflon film bottom. Cells are observed, selected and marked on the PFD-bottom with a high power inverted light microscope. The cells are fixed and dehydrated with a semi-automatic device while they are still in situ in the PFD. During the preparation steps for electron microscopy the topographical relationship between individual cells and between cells and cell support is accurately retained. After embedding and polymerization the Teflon film is easily peeled off the polymerized Epon, leaving a replica of the mark around the selected cell. This permits relocation of the selected cells for ultrathin sectioning in a plane plan-parallel to the original cell support. To enable orientated sectioning of selected cells in a plane perpendicular to the cell support, cells are tagged with Letraset-letters after original embedding and polymerization. Subsequently the re-embedded polymerized specimens are orientated in the microtome in a position which permits controlled thin sectioning of the tagged cells in the previously selected plane.


A comparative study in the transmission electron microscope and scanning electron microscope of intracellular structures in sheep heart muscle cells. The internal cellular structures of the sheep ventricular myocardium have been comparatively studied in the transmission electron microscope (TEM) and in the scanning electron microscope (SEM). For TEM studies the tissue was prepared according to standard methods. Thick sections (10 mum) of paraffin embedded material were, after they had been deparaffinized in toluene, critical point dried, coated with gold and examined in the SEM. The comparative TEM and SEM investigations revealed very good correspondence, and it is evident that the described preparation procedure for SEM has preserved the fine structures of myofibrils, mitochondria, T-Tubules and sarcoplasmic reticulum in an excellent life-like pattern. Of special interest was the three-dimensional demonstration of triads and circumferentially arranged T-tubules.


Ice crystal growth in skeletal muscle fibres. Ice crystal growth was studied in rapidly frozen skeletal muscle fibres which were treated with cryo-protective additives (glycerol, DMSO, sucrose) or which were untreated. Freeze cleaving and etching was the basic method, with conventional plastic embedding and cryo-ultramicrotomy arred during freezing in all unprotected fibres. Just below the fibre surface the crystals were numerous but small, while deeper in the fibre they were fewer but larger. The deeper within the specimen a fibre was located, the larger, in general, was the crystal size. The crystal volume density was about 55%, irrespective of crystal size. Ice recrystallization was practically absent at the temperature normally used in cryo-sectioning (-70 degrees C). Anti-freeze treatment eliminated crystal growth. If the anti-freeze agents were used in non-toxic concentrations, however, their effect on crystal growth was very limited. 'Dry'-cut, freeze-dried ultra-thin cryosections of protected and unprotected fibres confirmed these observations, while sections obtained by 'wet' cryo-cutting showed no apparent signs of crystal growth. In plastic sections of frozen and thawed fibres a previous occurrence of crystals was only slightly indicated. In interpreting the ultrastructure in 'wet'-cut cryo-sections of unprotected frozen muscle fibres, the distorting effects of ice crystals through mechanical compression and alterations in sectioning conditions, must be taken into consideration. Crystal growth also strongly limits the possibilities of using 'dry'-cut sections of untreated frozen tissue for analytical electron microscopy; only the most superficial parts of the fibres seem to be suitable for microanalysis.


Doublet frequencies in sequenced nucleic acids. A doublet frequency count (set of frequencies of the 16 possible two-base sequences) can be calculated from the experimentally determined overall sequence of a nucleic acid. In this paper, a statistical methodology is developed for comparing such counts with random, with others of the same type or with doublet proportions found in whole DNAs. The methods are applied to two major categories of sequenced RNAs. It is found that vertebrate ribosomal and transfer RNAs show significant differences from the overall vertebrate DNA pattern, especially in the frequency of the doublet CG. Bacterial rRNA and tRNA, on the other hand, show less dissimilarity from total DNA. In the RNA of the small bacteriophage MS2, the doublet frequencies of the translated regions of the genome resemble those in the host E. coli, whereas those in the intercistronic regions differ substantially. All these findings are discussed in relation to the origin, evolution and selection of the nucleic acids concerned.


The phylogenetic status of Pasteurella pestis. Yersinia pestis has been characterized in terms of fingerprints of digests (pancreatic and/or T1 ribonuclease) of its 16S and 5S ribosomal RNAs. These show clearly that Y. pestis is a member of the Enterobacteriaceae and suggest that within the Family it is most closely related to Serratia and/or Proteus.


Defective monocyte function in patients with genitourinary carcinoma. An assay allowing quantitation of monocyte function, i.e., chemotaxis, was used to study the activity of monocytes in patients with neoplasms of the urinary tract. Twenty-four subjects with various stages of renal carcinoma exhibited a mean chemotactic defect of 34% (P less than 0.005) as compared to normal controls and patients hospitalized with nonneoplastic diseases. Twelve persons with transitional cell carcinoma of the bladder had a 29.8% (P less than 0.01) mean chemotactic defect as compared to the controls. There was no correlation between tumor stage and degree of chemotactic defect;--J Natl Cancer Inst 55: 1047-1054, 1975.


Granulopoiesis in "preleukemic" mice with anemia induced by Rauscher leukemia virus, variant a. To understand further the hematopoietic dyscrasias induced by a variant (a) of Rauscher leukemia virus (RLV), we used Escherichia coli endotoxin to stress the hematopoietic system of control and RLV/a-infected BALB/c mice. During the preleukemic stages of virus infection, there was slight splenomegaly without peripheral blood erythroblastosis. Granulocyte release and tissue mobilization mechanisms appeared unaffected by the RLV/a infection. Both RLV/a-infected and control mice reacted to endotoxin with peripheral granulocytosis and peritoneal granulocyte mobilization, though the circulating granulocyte levels in RLV/a-treated mice initially were lower than those in controls. Spleen of RLV/a-infected animals were larger than those of controls, but both responded to endotoxin with elevated numbers of granulocytes and erythroblasts. Since numbers of bone marrow erythroblasts in both groups of mice were decreased after endotoxin, stem cell competition and/or shunting of stem cells from marrow to spleen may have been involved. Endotoxin also induced rapid falls in hematocrit levels in both groups. These studies suggested that RLV/a-infected mice can be a model to study 1) erythropoietic dysfunction uncomplicated by defective granulopoietic release and tissue mobilization control mechanisms, and 2) progression of evolving granulocytic leukemia.


Leukemia-associated antigens in man.

Leukemia-associated antigens in man. Rabbit antisera raised against acute lymphoblastic leukemia (ALL) cells were used to distinguish ALL from other leukemias, to identify rare leukemia cells in the bone marrow of patients in remission, and to define human leukemia-associated antigens. Antibody binding was studied with the use of immunofluorescence reagents and the analytic capacity of the Fluorescence Activated Cell Sorter-1 (FACS-1). The results indicated that most non-T-cell ALL have three leukemia-associated antigens on their surface which are absent from normal lymphoid cells: 1) an antigen shared with myelocytes, myeloblastic leukemia cells, and fetal liver (hematopoietic) cells; 2) an antigen shared with a subset of intermediate normoblasts in normal bone marrow and fetal liver; and 3) an antigen found thus far only on non-T-cell ALL and in some acute undifferentiated leukemias, which we therefore regard as a strong candidate for a leukemia-specific antigen. These antigens are absent from a subgroup of ALL patients in which the lymphoblasta express T-cell surface markers. Preliminary studies on the bone marrow samples of patients in remission indicated that rare leukemia cells were present in some samples. The implications of these findings with respect to the heterogeneity and cell origin(s) of ALL, its diagnosis, and its potential monitoring during treatment were discussed.


Distribution of latex-ingesting cells, T cells, and B cells in the peripheral blood of patients with malignant melanoma. The distribution among peripheral blood mononuclear cells of latex-ingesting cells, T cells, and B cells was determined with samples from 38 normal donors and 25 patients with malignant melanoma. The mean percentage of latex-ingesting cells, as well as B and T cells, was significantly reduced in the 25 patients with malignant melanoma, stages I and II, compared to the controls. Several explanations for these unexpected findings were considered; possibly the presence of occult neoplasm was responsible for the observed changes in cell distribution.


Stimulation of lymphoid cells by components of BCG. BCG was fractionated into a delipidated mycobacterial cell fraction (DMC) and lipid by exhaustive chloroform-methanol extraction. The effects of these fractions were tested on mouse spleen cells, nonadherent spleen cells (lymphocytes), thymus cells, and adherent spleen cells (macrophages) in vitro and were compared with effects of the whole bacilli and a methanol-extraction residue (MER). Tritiated thymidine incorporation into spleen cells, purified spleen lymphocytes, and thymus cells was measured as an indicator of activity on these cells; lymphocyte-activating factor (LAF) production was used to measure activation of macrophages. DMC and MER were at least equivalent to, and often exceeded, whole BCG in their stimulation of spleen cells and spleen lymphocytes. DMC was a poor thymic mitogen in contrast to MER, which was as strong as BCG in this regard. Lipid was far less effective a mitogen for all cells tested, and failed to augment the effectiveness of DMC on thymus cells when both were present in the incubation mixture. LAF production was significantly increased by whole BCG (18-fold above controls), whereas each fraction increased production threefold to sixfold. These in vitro results seemed to reflect the known in vivo activity of BCG and its components and suggest further antitumor applications.


Eradication of microscopic lymph nodes metastases after injection of living BCG adjacent to the primary tumor. Guinea pigs with established intradermal tumors and microscopic axillary lymph node metastases were treated with a combination of surgery and BCG. The tumors were excised and BCG was given in attempts to eliminate residual malignant disease. Injection of BCG into established intradermal tumors 7 days before local excision successfully eradicated microscopic axillary lymph node metastases and cured significant numbers of animals. Injection of BCG into dermal tumors 20 minutes or 1 day before excision prolonged survival but did not cure a significant number of animals. Injection of BCG into the skin adjacent to the dermal tumor 7 days before local excision eradicated microscopic axillary lymph node metastases. However, such injection 1 day before local excision did not eradicate metastases. BCG administered by intravenous, intra-arterial, or intranodal injection did not eliminate reidual malignant disease. Several factors were evaluated as possible correlates of successful immunotherapy. The development of tuberculin hypersensitivity, the magnitude of regional adenopathy, and the number of BCG organisms in axillary nodes were not useful correlates. Histologically, the presence of tumor cells, multiple focal granuloma, or histiocytosis in axillary nodes faiiled to correlate with results of therapy. The development of tumor-specific transplantation immunity provided the best correlate of successful immunotherapy.


Suppression of an AKR lymphoma by antibody and chlorambucil. A cell-surface localizing xenogeneic antibody against an AKR mouse lymphoma of spontaneous origin could be bound to chlorambucil without interference with either the alkylating activity of chlorambucil or the immunologic reactivity of the antibody. Exposure of the lymphoma cells to chlorambucil-bound antibody caused greater tumor inhibition both in vitro and vivo than did the synergistic effect of exposure seperately to the antibody and chlorambucil.


Reversal of leukemia virus-induced immunosuppression in vitro by peritoneal macrophages. When spleen cells from mice infected with Rowson-Parr virus (RPV) were cultivated with sheep red blood cells (SRBC), antibody plaque responses were markedly lower than those in similarly cultivated spleen cells from normal mice. Addition of as few as 10(3) spleen cells from RPV-infected mice to cultures of normal aplenocytes markedly depressed the expected immune response. Although RPV-infected mice showed maximum immunodpression in vivo only during the first week after infection, their spleen cells, obtained later in the course of infection, depressed the immunologic responsiveness of normal splenocytes in vitro. Increased doses of SRBC or addition of bacterial lipopolysaccharide to cultures of spleen cells from immunodepressed, RPV-infected mice stimulated antibody formation, and near-normal numbers of antibody-producing cells were evident. Peritoneal exudate (PE) cells, but not thymus, bone marrow, or unfractioned spleen cells, restored immunocompetence to cultures of spleen cells from RPV-infected mice but did not affect the suppressive properties of the infected cells on normal splenocytes. The function of PE cell macrophages in restoring immunocompetence to infected spleen cells in cultures seemed related to a possible antigen-focusing activity of the cells; antibody-producing cell precursors in infected cultures seemed to be preferentially affected by the presence of normal PE cells.


Schistosomiasis as a worldwide problem: pathology. Low-grade schistosome infection is often well tolerated, except for the danger of ectopic lesions; the risk of life-threatening pathology increases with rising worm burdens. At present, quantitative stool or urine egg counts do not reliably measure individual infection intensity, especially in adult patients, and more precise methods are needed on which to base therapeutic decisions. Timely schistosomicidal treatment will prevent or improve bilharzial lesions, often dramatically, but can not reverse established liver pipe stem fibrosis. Pathological studies in Ibadan and Cairo have shown that in schistosomiasis haematobia the frequency of obstructive uropathy increases in relation to the egg load in urinary tissues. Obstruction, in turn, predisposes to bacterial superinfection and is a significant cause of renal failure and death in highly endemic populations. Urinary bilharzial lesions are most active in the young and tend to become inactive in older patients. Urinary tissue egg burdens first rise, plateau, and ultimately decrease with age, most sharply after the fifth decade. The relationship between tissue egg burden and 24-hr urinary egg output varies according to stage of activity, while the severity of disease depends on egg burden regardless of stage. Therefore, during the inactive stage, severe pathology can coexist with a minimal urinary egg output. Both clinical and autopsy statistics show a correlation between the frequency and the intensity of bilharzial infection. Most of the severe pathology occurs in population groups with an autopsy frequency above a threshold of 30%. The clinical and epidemiological implications of these findings are discussed.


Clinical evaluation of niridazole and hycanthone in schistosomiasis mansoni endemic areas. One hundred patients with active schistosomiasis mansoni were treated with niridazole (25 mg/kg/day po for 7 days). The most serious side effects were those connected with the neuropsychic area (convulsion, hallucination, etc.). Therapeutic activity, based on repeated stool examinations, was about 90% in adults and 60% in children. Because of the side effects, as well as the long-term schedule of treatment, niridazole is not recommended for use under field conditions. Seven hundred and forty-five patients were treated with hycanthone (2.5 mg/kg im) after clinical examination. The side effects observed were mild and of short duration (24-48 hr). The therapeutic activity was very high (about 95% cure). So far we have treated more than 9,000 infected patients without severe complications, including hepatic failure and death, which have been reported by some authors. A hycanthone-resistant strain has been isolated from two patients unsuccessfully treated twice with hycanthone and once with niridazole. Considering that an important aspect of the control of schistosomiasis is mass treatment, further studies regarding mutagenicity, teratogenicity, resistance, and toxicological effects of hycanthone are still required before this drug can be recommended for wide use.


A comparative study on the genetic effects of hycanthone and oxamniquine. Oxamniquine (UK-4271; 6-hydroxymethyl-2-isopropylaminomethyl-7-nitro-1,2,3,4-tetrahydroquinoline) is a new schistosomicidal agent currently undergoing clinical investigation in South America. Essentially a complete cure rate against Brazilian Schistosoma mansoni has been seen in adults with a single im dose of 7.5 mg/kg or a single oral dose of 15 mg/kg. These regimens were tolerated without significant toxicity. To assess its mutagenic potential, oxamniquine was examined in a battery of genetic tests designed to detect mutations at the gene and chromosome levels. For comparative purposes, hycanthone, a schistosomicide with extensively studied mutagenic properties, was evaluated in a similar series of tests. Point mutations were measured in a series of histidineless auxotrophs of Salmonella typhimurium in direct plate and host-mediated assays. Gross chromosomal aberrations were assessed in human leucocyte cultures and in bone marrow preparations from drug-treated mice. Effects on germ cells were tested in the dominant-lethal assay. Hycanthone showed significant mutagenic activity in the direct bacterial tests and the in vivo and in vitro cytogenetic assays. No response was detected in the host-mediated or dominant-lethal assays. On the other hand, oxamniquine produced no drug-related mutagenic effects in the cytogenetic, host-mediated, or dominant-lethal tests at doses up to 150 mg/kg administered parenterally. Oxamniquine produced a weak response in the frameshift mutant, TA1538, of Salmonella typhimurium in direct plate tests with and without liver microsomal enzymes. However, this response was achieved only by using a concentration of compound which was several orders of magnitude higher than that required to produce a similar response to hycanthone.


Genetic activity spectra of some antischistosomal compounds, with particular emphasis on thioxanthenones and benzothiopyranoindazoles. In this review we note that hycanthone (Etrenol) is mutagenic for bacteriophage, bacteria, yeast, Neurospora, Drosophila, and for mammalian tissue culture cells, and we point out other genetic activities of this thioxanthenone and of related compounds. One alarming genetic activity is the ability of hycanthone to cause transformation of tissue culture cells in vitro in a test designed to detect carcinogens, results that parallel the direct demonstration of carcinogenic activity of hycanthone in the mouse in vivo. These and other results are compatible with the somatic mutation theory of cancer induction. Factors likely to affect the quantitative genetic activity of hycanthone and its congeners are summarized. Attempts are made to weave the more critical experimental evidence into a molecular model that accounts for the genetic activities of this series of compounds. We conclude that hycanthone is a directly acting mutagen that intercalates into DNA and preferentially alkylates deoxyguanosine residues via formation of a strongly electrophilic molecular species, the carbonium ion. Finally, we show that genetic activity can be dissociated from schistosomicidal activity by appropriate modifications in the thioxanthenone molecule. Preliminary experiments on a newly synthesized piperazinyl N-oxide derivative demonstrate no detectable mutagenic activity; yet considerable schistosomicidal activity is retained.


Mutagenicity testing of antischistosomal thioxanthenones and indazoles on yeast. Two antischistosomal thioxanthenones, lucanthone and hycanthone, and four antischistosomal indazoles, IA-3, IA-4, IA-5, and IA-6, have been tested for mutagenicity on stationary phase cells of the yeast Saccharomyces cerevisiae. It was shown that, although there are some gaps in the data, hycanthone and IA-6 are mutagenic at pH 7.0, hycanthone is mutagenic at 5.9, and none of the other compounds is mutagenic at either pH. (Because mutagenicity of these compounds at pH 7.0 appears to be related to the presence of a methoxy group at position 5 of the polycyclic ring, it is possible that IA-4 will be mutagenic on yeast when it is tested at pH 7.0.) An excision-repair-deficient strain of yeast is no more sensitive than other strains. It was found from time-concentration studies on lethality that an inverse relation held: cells exposed to a mutagenic compound are more sensitive when time of exposure was varied and concentration of the compound was held constant, and cells exposed to a nonmutagenic compound are more sensitive when concentration is varied and time of exposure held constant. When the compounds were tested on growing cells of yeast in rich media, none of the compounds is mutagenic, although some are lethal. The kinetic behavior in reversion of yeast exposed to these compounds shows marked departures from similar reversion studies where yeast is exposed to radiation, implicating different physiological mechanisms for the alteration of responses of yeast cells exposed to the different mutagens.


Comparative efficiency of pyrimethamine-sulphormethoxine in malaria suppression given as single weekly, fortnightly and monthly doses. 2. One hundred and seventy inhabitants of the Ilorin area, Nigeria, were observed over a period of five months during the season of maximum malaria transmission while taking pyrimethamine-sulphormethoxine weekly, fortnightly and every four weeks. 2. There was no episode of malaria parasitaemia in the group receiving weekly doses of 25 mg. pyrimethamine and 0-5 mg. sulphormethoxine throughout the course of the trials. 3. There was one episode of asexual parasitaemia at the second month in the group receiving double fortnightly doses, but none by the third or fourth months. 4. The group receiving 75 mg. pyrimethamine and 1-5 mg. of sulphormethoxine had seven episodes of asexual parasitaemia throughout the course of the trial. 5. In all three groups there was no evidence of clinical acute malaria. 6. There were no appriciable side-effects in all groups within a follow-up period of four months. 7. The present trials confirm the advantage of the drug combination which proved to be more effective when given as weekly or fortnightly doses.


[Bilateral cancer of the kidney (author's transl)]. The simultaneous or successive occurrence of bilateral nephro-epithelioma in the adult is a possibility which is much rarer than that of the tumor in the child. The possibility of partial nephrectomy, carried out ex-vivo with renal auto-transplant should the occasion arise and that of total nephrectomy with allo-transplant brought up with their results.


[Study of cellular immunity in the course of nephro-epithelioma. Preliminary study concerning 12 cases (author's transl)]. The cellular immunity of 12 adult subjects suffering from nephro-epithelioma was studied by means of lymphoblastic transformation tests repeated regularly. Perhaps a certain agreement could be observed between the clinical course and the subject's sensitization to the tumor antigens.


Replication and recombination of gene 59 mutant of bacteriophage T4D. After infection of Escherichia coli B with phage T4D carrying an amber mutation in gene 59, recombination between two rII markers is reduced two- to three-fold. This level of recombination deficiency persists even when burst size similar to wild type is induced by the suppression of the mutant DNA-arrest phenotype. In the background of two other DNA-arrest mutants in genes 46 and 47, a 10- to 11-fold reduction in recombination is observed. The cumulative effect of gene 59 mutation on gene 46-47 mutant suggests that complicated interactions must occur in the production of genetic recombinants. The DNA-arrest phenotype of gene 59 mutant can be suppressed by inhibiting the synthesis of late phage proteins. Under these conditions, DNA replicative intermediates similar to those associated with wild-type infection are induced. Synthesis of late phage proteins, however, results in the degradation of mutant 200S replicative intermediate into molecules are associated with membrane, they do not replicate. These results suggest a role for gene 59 product, in addition to a possible requirement of concatemeric DNA in late replication of phage T4 DNA.


Replication of nuclear polyhedrosis virus in a continuous cell culture of Spodoptera frugiperda: microscopy study of the sequence of events of the virus infection. A microscopy study of the sequence of morphogenic events of Spodoptera frugiperda nuclear polyhedrosis virus infection of S. frugiperda cells is presented which orders the sequence of replication and establishes the time scale within which the events occur. The virus entered the cell by 1 h postinfection and was uncoated. The eclipse period was 9 h and the latent period was 12 h. Polyhedron formation was detected by 18 h postinfection and continued until the deposition of the polyhedron membrane was completed by 48 h postinfection. Aberrant morphogenic characteristics of virus repeatedly passaged in the cell culture were also recorded. Adsorption, envelope morphogenesis, and release mechanisms are discussed in light of other data on in vivo and in vitro baculovirus infections.


T7 protein synthesis in F-factor-containing cells: evidence for an episomally induced impairment of translation and relation to an alteration in membrane permeability. T7 infection of F-factor-containing PIFA+, B+ cells is abortive. In spite of the presence of mRNA for all three classes of T7 proteins, only the earliest of the T7 proteins are synthesized. A crucial question is whether the failure of T7 to develop in PIFA+, B+ cells is the result of an inability to translate the late classes of T7 mRNA or, as has been recently suggested (Britton, and Haselkorn, 1975; Condit, 1975), whether it is the result of a more generalized alteration in membrane permeability. We have examined the effects of the wild-type PIFA+, B+ spisome and two sipsomal mutations (pifA- and pifB-) on in vitro translation and membrane permeability. In vivo the episomal mutations allow partial or complete T7 development to occur. We demonstrate that cell-free protein-synthesizing systems from T7-infected PIFA+, B+ cells show a three- to fivefold decrease in the rate of translation of both natural and synthetic mRNA. In addition, ribosomes from T7-infected PIFA+, B+ cells are defective in their ability to bind Fmet tRNAf in response to natural mRNA. By contrast, cell-free extracts from T7-infected pifA-(PIFA-, B+) celld retain the ability to bind Fmet defective T7-infected PIFA+, B+ rigosomes can be restored to full activity by a trypsin-sensitive fraction from uninfected PIFA+, B+ or T7-infected PIFA-, B+ cells. Despite the differences in translational capacity of these extracts, both T7-infected PIFA+, B+ and PIFA-, B+ cells display the same permeability lesions as measured by the loss of ATP from the cells into the supernatant. Mutation of the episome of pifB- prevents the loss of ATP from the cells after T7 infection.


Urinary tract complications in myelomeningocele patients. Urinary tract complications such as urinary tract infection, ureteral reflux, upper tract dilatation and incontinence are common with myelomeningocele. Regular urological evaluations, including measurement of residual urine, uranalysis, urine culture, voiding cystourethrogram, excretory urogram and renal function studies, are essential for the diagnosis and management of such complications. Conservative therapy with Crede bladder expression and urethral catheter drainage has been unsuccessful in managing these complications and preventing upper tract deterioration.


Flexible tip ureteral catheters in clinical practice. An ideal ureteral catheter has been produced and subjected to extensive clinical trial. Its safe, flexible tip permits passage into almost every orifice and ureter, regardless of its configuration, tortuosity or degree of obstruction. The flexi-tip catheter meets all of the criteria of the theoretical ideal ureteral catheter. It would appear to be the catheter of choice for most clinical situations and should be a welcome addition to the urologist's armamentarium.


Carcinoembryonic antigen and bladder carcinoma. The 24-hour urinary carcinoembryonic antigen determinations were performed on 61 patients with different stages of bladder carcinoma. Elevated titers were found in 81 per cent of the patients with active tumors and falsely positive studies were found in 7 per cent. High stage lesions were found to have high carcinoembryonic antigen levels. Plasma carcinoembryonic antigen determinations were elevated in only 45 per cent of the patients with active tumors but further study may be warranted in advanced bladder cancer cases. The 24-hour urinary carcinoembryonic antigen measurements yield the highest percentage elevations in bladder carcinoma and further investigation is required to better define its clinical application.


End stage polycystic kidney disease: management by renal transplantation and selective use of preliminary nephrectomy. The results have been reviewed of 35 renal transplants performed on 31 patients with end stage polycystic renal disease. Patient survival is 81 per cent and 71 per cent of the patients have functioning grafts at an average followup of 3.1 years. The need for pre-transplant nephrectomy was evaluated early in the series and since then the operation has been practiced selectively. Twenty-two patients have received transplants with both polycystic kidneys in situ, while 2 patients have undergone transplantation after unilateral nephrectomy. In the absence of a history of renal infection or significant hematuria it has proved safe and desirable to leave the polycystic kidneys in situ. During the post-transplant period in such cases there has been no difficulty attributed to the in situ polycystic kidneys after more than 450 patient months of immunosuppressive therapy. The size of the polycystic kidneys has not been an indication of nephrectomy in our series and no significant technical difficulties have been encountered with large polycystic kidneys remaining in situ. Hypertension associated with end stage polycystic kidney disease has been controlled easily and has not proved an indication for pre-transplant nephrectomy.


The present status of bilateral nephrectomy in transplant recipients. Routine use of bilateral nephrectomy in renal transplant patients has been replaced by a careful evaluation of the indications for the procedure and the increasing appreciation of the contributions of non-excretory kidneys. These contributions are identified and the indications are discussed. When bilateral nephrectomy is required the clear superiority of the bilateral simultaneous posterior approach over other techniques is documented.


Chemotherapy of advanced carcinoma of the prostate with 5-fluorouracil, cyclophosphamide and adriamycin. There were 33 patients with clinically relapsing advanced prostatic carcinoma (stages C and D) treated by 2 different combinations of chemotherapy. The 13 patients in group 1 received 5-fluorouracil and cyclophosphamide and 20 patients in group 2 received adriamycin and cyclophosphamide. The over-all response was 69.3 per cent in group 1 and 65 per cent in group 2. Our preliminary results should encourage further evaluation of these drug combinations by other investigators under carefully controlled conditions.


Nitrous oxide as an analgesic in acute myocardial infarction. Nitrous oxide in a concentration of 35% has been shown to ameliorate the pain of acute myocardial infarction. This conclusion was reached on the basis of a double-blind study in 69 patients and a clinical study in an additional 42 patients. The use of nitrous oxide was not accompanied by hemodynamic changes or significant adverse reactions.


Use of free peritoneal patch in reenforcing alimentary tract anastomosis. The use of free peritoneal patch was evaluated for the effect on protection against intestinal anastomotic leakage in dogs. Free peritoneal patch was found to be effective in preventing the anastomotic leakage of the alimentary tract in borderline situation. Free peritoneal patch was more effective when applied with the 'smooth side out' than with the "smooth side in'. The usefulness of free peritoneal patch was also demonstrated in the treatment of the already established fistula of the cervical esophagus.


Mechanism of diuretic response to increased left atrial pressure in the anesthetized dog. The mechanism whereby an increase in left atrial pressure (LAP) causes a water diuresis in the anesthetized dog remains controversial. In the present study LAP was increased by inflation of an atrial balloon in two groups of animals. In the first group of eight intact dogs, mean LAP was increased from 3.4 to 17.6 mm Hg (P less than 0.001). The rise in LAP was associated with a mean increase in urine flow (V) from 0.70 to 1.29 ml/min (P less than 0.001), a decrease in urinary osmolality (Uosm) from 808 to 490 mOsm/kg of H2O (P less than 0.001) and an increase in free water clearance (CH2O) from -0.684 to -0.200 ml/min (P less than 0.025). This diuresis was associated with a mean decrease in antidiuretic hormone concentrations in plasma as measured by radioimmunoassay from 27.6 to 12.3 pg/ml (P less than 0.02). The changes in the urinary indexes and in the antidiuretic hormone concentrations were reversible and returned to control levels when the LAP was allowed to return to normal. A second group of dogs was acutely hypophysectomized, steroid replaced and given a constant infusion of vasopressin. In these animals, mean LAP was increased from 3.0 to 16.0 mm Hg (P less than 0.001) but no significant change in V (0.49 to 0.56 ml/min), Uosm (878 to 845 mOsm/kg of H2O) or CH2O (-0.750 to -0.620 ml/min) occurred. Cardiac output, renal arterial pressure, glomerular filtration rate and solute excretion were comparable in the two groups. We therefore conclude that suppression of antidiuretic hormone release is the primary mechanism whereby increased LAP causes a water diuresis in the anesthetized dog.


[Block-excision of intraocular processes. I. Tumors of the anterior uvea (author's transl)]. Tumors of the ciliary body and peripheral choroid are removed together with the adjacent cornea, sclera, iris and retina as a single "block". A lamellar preparation of the sclera is avoided because extent of the tumorinvasion into the sclera cannot be clinically reconized. The border of the tumor is found by fiber-optic-transillumination and thus the diameter of the block-excision is determined. The resulting defect of the globe is covered by a tectonic corneal graft. From 1971-1974 12 eyes have been operated with this method: 3 malignant melanomas of the iris invading the ciliary body; 5 tumors of the ciliary body and 4 extensive malignant melanomas involving also the peripheral choroid. The diameter of the block-excision varied from 5.5 X 5.5 to 14 X 18 mm. Simultaneous cataract extraction was performed in 5 eyes. Approximately 4 hours of the ciliary-body-circumference are excised. The preliminary results are satisfactory in view of the size of the excised tumors.


[Basaliom of the eyelids (author's transl)]. From 1959-1973 128 patients with tumors of the eyelids were treated at the "Augenklinik im Krankenhaus Nordstadt Hannover"; in 103 cases the diagnosis of basal cell carcinoma was histologically proved. With 62.1% of male patients prevailed the female patients with 37.9%. The age of the patients, localisation of the tumors, previous treatment and duration of involvement are discussed in detail. With the exception of 3 cases, which had a primary or secondary radiation they were surgically treated. A short explanation of the technics is given. In 82 out of 101 surgically treated cases (81%) the patients were clinically healed by a single operative treatment. During our observation there was no recurrence. Together with the number of patients, who were treated for several time, the over-all-cure-rate was 98.2%. Complications of surgical treatment are described and compared with those of other types of therapy. According to our results and as mentioned in the literature basal cell carcinomas of the peri-orbital region should be treated only by ophthalmologists. Lifelong control is necessary because of the extraordinary character of the tumor, which shows many exceptions in regard to basal cell carcinomas on other parts of the body.


[Cardona keratoprosthesis as ultima ratio (author's transl)]. In a 61-year-old patient affected with degenerative keratopathy after attacks of interstitial keratitis a Cardona keratoprosthesis was successfully implanted in the right eye after two fruitless optic corneal grafts in the left eye.


[A report on Ocusert (author's transl)]. The third communication on the drug delivery system Ocusert (Alza Corporation, Palo Alto; Federal Republic of Germany: Chemic Grümenthal) deals with experiences of a 15 month follow-up study. Again we found that the system provides effective around-the-clock control for at least 7 days. During 15 months the system was effective in all patients. In comparison to pilocarpine-eyedrops the Ocusert-system has the following advantages: less pilocarpine-induced myopia and miosis, myopia and miosis extremely constant, minimal local side effects, reduced amount of drug release, almost no therapeutic discomfort for the patient, isolating the patient from the disease and good controlpossibility of the success of the treatment. The problems of a permanent drug release are discussed.


[On the closure of the defect after tumor removal in the medial canthus (author's transl)]. After the excision of the growths different plastic operations (pediculated flap, sliding flap, free transplantation) were performed. The postoperative functional and aesthetic results are discussed.


[Implantable materials (author's transl)]. There is a steadily increasing importance of implants used as substitutions for body functions which have been impaired due to disease, natural abrasion or accident. With the present state of the art, the limitations for the application of surgical substitutions are due to insufficient properties of biomaterials with regard to specific applications as well as to deficiencies in design and function of the implants used. The basis for the improvement and new development of implants is therefore a functionally adequate design in which the specific properties of the material are taken into account with regard to the individual requirements of the implantation site. For orthopedic implants, materials have to be developed which are to a large extent corrosion and degradation resistant, and withstand high mechanical stress. For implants in the cardiovascular system, compatibility with blood is most significant. Present research in this field is concentrated on efforts to improve the thromboresistivity of conventional polymers by different kinds of surface treatments. One possibility is to influence actively the electrochemical interactions between material and blood components, e.g. by the use of redox catalysts.


Serodiagnosis of nosematosis by immunofluorescence using cell-culture-grown organisms. This simple procedure for the detection of serum antibodies to Nosema cuniculi in rabbits and other host species incorporates indirect immunofluorescence and uses as antigen N. cuniculi isolated from urine and cultured in a human fibroblast-like cell line derived from foetal tongue. Examination of rabbit sera from 8 institutions indicated that no institution was free from Nosema infection. The prevalence of infection in 4 separate Australian rabbit colonies varied from 25 to 75%.


The use of the pig as an animal model to study problems associated with low birthweight. Attention is drawn to some of the consequences associated with the postnatal development of low birthweight human infants and the use of the piglet as a model to study such problems. A description is given of the production and methods of rearing of these animals along with an outline of studies currently in progress.


[Effect of positive transverse acceleration on the transmitting properties of human operators]. The results of experimental studies of the effect of +Gz acceleration on the transmissive properties of the man-operator involved in the tracking system are discussed. With an increase of the acceleration value and the exposure time the law of distribution of tracking errors made by the operator varies from the normal to the uniform pattern. The estimates of the quality of tracking of a complex signal upon an exposure of the operator to accelerations of different values are given.


Studies on the primary structure of 14 proteins from the large subunit of Escherichia coli ribosomes with an improved protein sequenator and with mass spectrometry. Fourteen proteins from the large subunit of Escherichia coli ribosomes were analyzed in an improved sequenator. In addition to our previously described modifications of a Beckman sequenator, new valves which work free of a dead volume were constructed. By this and the previous improvements (e.g., a new vacuum system with a recorder, cool traps, automatic conversion) much better results were obtained than before. It was even possible to use (in addition to the standard methods, e.g., thin-layer chromatography and amino acid analysis) mass spectrometry without preceding gas chromatography for identification of the released PTH amino acids. Our experience with the various methods, especially mass spectrometry, is described and the techniques are compared. The results obtained by the described methods on the amino acid sequences of the 14 ribosomal proteins are summarized.


Immunologic defects in lung cancer patients. Ninety-three patients with lung cancer were evaluated by delayed cutaneous hypersensitivity testing. Twenty-eight of these patients were evaluated by in vitro lymphocyte function. Thirty-three patients were evaluated prior to surgery and defects in the immune response were closely associated with unresectable disease. In vitro and in vivo studies indicate an antigen recognition defect in the cellular immune mechanisms of these patients. Preliminary studies suggest that the immunopotentiating agent Levamisole may be able to augment this defective cellular immunity in patients with lung cancer.


Preliminary clinical experience with a new radioisotope-powered cardiac pacemaker. A small light-weight nuclear-powered pacer has been developed. The pulse generator weight 61 Gm. and occupies a volume of 33 sq. cm. It is a standard R-wave inhibited (VVI) demand pulse generator. The unit has met all United States and foreign atomic energy commission safety specifications including mechanical shock, industrial fire, accidental crush, cremation, impact, and corrosion. Its calculated life is in excess of 20 years. The unit has been shown to be insensitive to electromagnetic interference (EMI) over a wide range of commonly encountered sources of interference. An extensive dog testing program has been carried out and is continuing. The United States Atomic Energy Commission (AEC) has issued a license to conduct clinical trials. These began in October, 1974, and a total of 30 units of 30 units have been implanted so far. An equal number of chemical battery-powered pulse generators has been implanted in a control series of 30 patients. Preliminary results have been gratifying.


The effects of carbon dioxide on pulmonary mechanics in hyperventilating, normal volunteers. Transpulmonary pressure, air flow, and end-tidal carbon dioxide levels were measured in normal human volunteers during hypocapnic, eucapnic, and hypercapnic hyperventilation. Respiratory rate and tidal volumes were well matched at a minute ventilation of 52 L. on three inspired gas mixtures: 21 per cent oxygen and 79 per cent nitrogen; 5 per cent carbon dioxide, 21 per cent oxygen and 74 per cent nitrogen; and 12 per cent carbon dioxide, 21 per cent oxygen and 67 per cent nitrogen. Respiratory rate, tidal volume, lung compliance, resistance, and resistive work per liter were calculated with a digital computer. In 13 experiments in 7 normal volunteers, no net bronchoconstriction or bronchodilatation was observed when eucapnic hyperventilation was compared to hypocapnic or hypercapnic hyperventilation. During hyperventilation of this degree, a change in bronchomotor tone owing to alteration in arterial or alveolar PCO2 either does not occur or else is masked by other reflexes or mechanical factors acting on the bronchi.


Orthognathic surgery. Review of mandibular body procedures. In a clinical diagnostic approach to orthognathic deformities, the patient's past medical and dental histories and the indications and potential complications of mandibular body ostectomy and osteotomy are important considerations. The need for a team approach in the diagnostic, orthodontic, and surgical phase of the treatment is also important. The mandibular body procedure has a definite place in the armamentarium of the oral surgeon because certain mandibular deformities can be corrected only by this method. Predictable and stable results can be expected in indicated cases if one adheres to the principles of exacting surgical technique, precision immobilization, and neuromuscular balance. Presurgical and postsurgical orthodontic treatment enhances the functional and esthetic correction and furnished indispensable surgical fixation appliances for precision segment immobilization.


Who responds to sugar pills?

Who responds to sugar pills? Among 288 cancer patients undergoing controlled trials of oral analgesics there were 112 who received 50% or greater pain relief from placebo formulations. Patients who responded to placebo had a greater response rate to active drugs. They also had a higher incidence of central nervous system side effects to placebo. Patient groups showing as increased placebo response included those with a high level of education, farmers, those with a professional occupation, women working outside the home, and patients who were widowed, separated, or divorced. Those resistant to placebo were patients with a low educational level, unskilled workers, housewives, married women without children, and smokers. It is theorized that placebo response is a type of autohypnosis phenomenon resulting from exaggerated oral-dependency needs. Particularly vulnerable to placebo effect is the very self-sufficient individual with heavy responsibilities who is thrust into the unaccustomed dependency of disabling illness.


Sindbis virus replication in vertebrate and mosquito cells: an interpretation. This paper summarizes recent comparative studies of Sindbis virus (SV) replication in cultured Aedes albopictus (A. albo) or (A. aegypti (A. aeg) and BHK21 or chick embryo (CEF) cells. 1. Viral growth kinetics and yields are similar in A. albo cells at 28 degress C and in vertebrate cells at 37 degrees C. A. albo exhibit no CPE and yield persistenetly infected cultures. 2. SV grown in A. albo cells lacks sialic acid but is antigenically and in terms of particle/PFU or particle/HAU ratios equivalent to SV derived from vertebrate cells. The contrast to VSV in the latter respect is discussed. 3. SV from persistently infected A. albo or A. aeg cells is temperature-sensitive, thermolabile, and produces small plaques. Partial characterization of these mutants, of RNA associated with their replication, and their high reversion rate to ts+ upon serial undiluted passage in GHK21 cells are presented. 4. Hostdependent differences in the generation of defective-interfering (DI) SV particles and of low molecular weight viral RNA species have been observed upon undiluted serial passages in BHK21 and CEF. In contrast, serial passage in A. albo cells appears not to produce DI particles or small RNA species nor do these cells "recognize" as such DI particles from BHK21 cells. 5. Possible implications of these observations fro the natural life cycle of arthropod-borne togaviruses are discussed.


Replication of Semliki Forest virus.

Replication of Semliki Forest virus. Replication of Semliki Forest virus, a typical alphavirus, takes place in the cytoplasm of many eukaryotic cells. The virus genome, the 42 S RNA, directs the synthesis of at least two RNA-dependent RNA polymerases. By the aid of these enzymes complementary 45 S RNA is synthesized; it serves as a template for the synthesis of positive RNA strands with sedimentation values of 45 S and 26 S. In BHK cells close to 200,000 molecules of each RNA species are produced per cell. Both 26 S and 42 S RNAs are associated with polysomes synthesizing viral structural proteins. The 26 S RNA is a duplication of the nucleotide sequences coding for the virion proteins. These are translated as a polyprotein with the capsid protein at the N-terminal end followed by the envelope proteins E2 and E1. Usually only small amounts of nonstructural proteins are synthesized at the exponential phase of virus growth, indicating that a translational control operates in Semliki Forest virus-infected cells. One of our temperature-sensitive mutants, ts-1, directs, however, the synthesis of two nonstructural proteins with MWs of 78,000 and 86,000 when grown at the nonpermissive temperature. The assembly of the viral nucleocapsid begins by association of the capsid protein with the 42 S RNA, which is still serving as a messenger. In this process a cytoplasmic structure sedimenting at about 65 S is presumably one of the capsid protein donors. The 140 S nucleocapsid buds through the host cell plasma membrane whereby the capsid protein interacts with the envelope proteins creating a specific viral envelope devoid of host proteins. Altogether 5,000 to 20,000 virus particles are released from each cell by the end of the growth cycle, representing about 10% of the 42 S RNA molecules synthesized during the infection.


Processing of alphavirus-specific proteins in infected cells. The RNA of the alphaviruses contains the genetic information for both the non-structural and the structural polypeptides. The former are contained in the initial two-thirds of the sequence (from the 5'-terminus) and are read directly from the virus particle RNA, but whether post-translational cleavage is involved or not is not known. The genes for the structural polypeptides are in the final one-third of the genome, and are probably not read directly but are transcribed selectively to produce a sub-genomic messenger RNA with only one initiation site. Translation produces the structural pooypeptides and post-translation cleavage does occur. However, the rate at which cleavage occurs is variable--cleavage to release the core polypeptide occurs while the nascent polypeptide is still attached to the ribosome, while cleavage to form two of the virus envelope glycoproteins occurs as the virus buds from the cell. The cleavage mechanism which leads to release of the core polypeptide also takes place in vitro and may be catalysed by the structural polypeptide itself.


Translation of Semliki forest virus 42S and 26S RNAs in a cell-free system derived from Escherichia coli. The SFV 42S RNA and the intracellular 26S RNA have been translated in a prokaryotic cell-free system, the E. coli S30. About half of the [35S]methionine-labelled products directed by both RNAs had molecular weights larger than 20,000 on polyacrylamide gels. Both products contained tryptic peptides which comigrated with all the capsid and envelope protein-derived peptides. The most striking difference between the prokaryotic and eukaryotic systems lay in the translation of the 42 S RNA: The "42S RNA-specific nonstructural" peptides, which predominate in the eukaryotic systems, were apparently absent from the product translated by the prokaryotic system.


The structure of togaviruses and bunyaviruses. This article reviews the properties of arthropod-borne and nonarbo togaviruses and members of the Bunyaviridae family. Averaged information is given on the morphology and substructure of the virion, its physical properties, its chemical composition and the function of its constituents. Special attention is given to distinctive traits which might be useful for virus classification.


The structure of Uukuniemi virus, a proposed member of the bunyaviruses. Uukuniemi virus, a proposed member of the new large Bunyavirus group of arboviruses, has an interesting structure which differs in many respects from that of other enveloped RNA viruses. The surface structure reveals a clustering of the two glycoproteins into distinct capsomere-like subunits, arranged in a T = 12 icosahedral lattice. The genome is found in at least three pieces that appear to represent unique virus-specific RNAs. The ribonucleoproteins corresponding to the RNA species are circular, according to electron micrographs. The virion contains an RNA-dependent RNA polymerase suggesting that Uukuniemi virus is a negative-strand virus. This paper summarizes the data obtained on the structure of Uukuniemi virus and discusses its relationship to other members of the Bunyavirus group.


Hemodynamic consequences of cardiac dysrhythmias. To understand the hemodynamic changes produced by arrhythmias is to understand cardiovascular physiology. The changes in rate are accompanied by changes in contractility, receptor stimulation, peripheral vascular response, and flow to other vital organs. In addition, one must keep in mind the underlying pathology of the cardiovascular system. As a therapeutic program is initiated and adjusted, it must be done in accordance with the changes produced in the hemodynamics as well as the rhythm.


The tachycardia-bradycardia syndrome.

The tachycardia-bradycardia syndrome. The tachycardia-bradycardia syndrome (paroxysmal atrial fibrillation, flutter, or tachycardia followed by sinoatrial block or sinus arrest resulting in Stokes-Adams attacks) is an important clinical entity that requires familiarity by the clinician. Pathologic studies and physiologic mechanisms as revealed in the electrocardiogram indicate multiple disturbances in the conduction system of the heart (sinus node, atria, and atrioventricular junctional tissues). The electrocardiogram establishes the diagnosis. Pacemaker implantation with supplementary drugs has provided a satisfactory means of therapy. With proper treatment the prognosis of patients with the tachycardia-bradycardia syndrome has improved to the extent that the primary determinant of mortality is no longer the arrhythmia, but the underlying cardiac and/or systemic pathology.


[New evaluation of effect of total colectomy and intestinal sterilization following portacaval shunt]. The effect of total colectomy and "intestinal sterilisation" following chronic portocaval shunt was investigated in 96 Sprague-Dawley rats: while both therapeutic procedures are of no significant impact on serum ammonia concentrations there is a significant reduction of brain octopamine, a known false neuro-chemical transmitter, and a clear response on aromatic amino acid levels in brain and plasma. The interference with central and peripheral neurotransmitters is suggested as an alternative mechanism in experimental encephalopathy.


[Early recognition of a rejection crisis following kidney transplantation by determination of a low-molecular protease inhibitor in serum and urine]. The dynamic of the lowmolecular acid stable inhibitor in serum and urine was investigated in 10 patients with kidney transplants. The same was done with serum creatinin levels. In kidney transplantation changing serum levels and excretion of acid stable proteinase inhibitors early indicate the starting function of the kidney transplant. Rapid reduction of the inhibitors serum level and massive excretion are sign of the functioning of the kidney transplant even though creatinin levels remain elevated. An increasing inhibitor concentration in serum indicates the beginning of a rejection crisis. This is an easy check-up which takes only a few minutes.


[Thermography: a method for the assessment of rejection time in skin transplants]. It is possible to register the rejection time of allografts quantitatively by the method of thermography. Results are congruent with a micromorphological state, but only partially with the macroscopic pictures.


[T- and B-lymphocytes in patients with kidney transplants]. T and B cells were estimated in kidney allograft recipients under immunosuppressive therapy by spontaneous rosette formation with sheep erythrocytes and fluorescent staining with anti-immunoglobulin serum. Pronounced lymphopenia could be shown in all patients when compared with normal as well as uremic controls. Under standard immunosuppression with azathioprine and oral steroids T cells were reduced to 840 +/- 215 and B cells to 286 +/- 69 per mm3 blood. Lymphopenia was further augmented by additional intravenous treatment with prednisolone in high dosage (1g). Under these conditions a prevailing reduction of T cells was found.


[Immune response following portal and caval anastomosis of kidney transplants in the rat]. The technique of renal transplantation in the rat was modified by anastomosing the renal vein to the portal vein. Transplantation of DA-kidneys to BDE-Han-rats did not result in a prolongation of survival time in this strong histoincompatible system. No differences were found in the immune response on the 7th postoperative day.


[Pulmonary homotransplantation in the dog with contralateral ligation of the pulmonary artery and subsequent contralateral pneumonectomy]. Five mongrel dogs underwent a left side pulmonary homotransplantation and simultaneous contralateral pulmonary artery ligation using a standardized operative technique. The contralateral lung of the recipient was successfully removed on the first postoperative day. From the present study may be concluded that the transplanted lung is able to provide adequate respiratory function immediate postoperatively and is able to tolerate the total cardiac output in the presence of increased vascular resistence of the recipient contralateral lung.


[Hormonal tendolysis in animal experiment]. After testing a new method of postoperative immobilisation the tendon of the m. flexor digit. longus of 49 adult rabbits was tenotomised and resewn. Comparing to a control-group a distinctly less accentuated reaction and scarring of the connected tissues as well as calcified reactionless necrosises can be found in the histology depending of the dosage of the postoperative cortison-treatment. The cellular alterations are described in details. For a definite judgement rupturing-tests will be necessary.


Experimental replacement of esophagus by tissue tube in dogs. After subcutaneous implantation of a silastic rod 1.2 cm in diameter covered by a lacelike polyester fibre mesh an autogenous tissue tube can be prepared which was used for segmental esophageal replacement with satisfactory results in 5 out of 7 dogs.


Continuous positive airway pressure in the prophylaxis of the adult respiratory distress syndrome (ARDS). Alternate patients believed to be at risk for developing ARDS were placed on CPAP for the first twenty-four hours post upper abdominal surgery. Ten of the 58 controls developed ARDS, requiring prolonged mechanical ventilation with a 30% mortality rate. Only one of the 59 CPAP patients developed evidence of ARDS. This patient, however, is believed to have had fluid overload, and responded quickly to diuretics and was extubated within two days. Thus, prophylactic CPAP has greatly decreased our postoperative morbidity and mortality related to respiratory causes.


[Quantitative bacteriological evaluation of intraoperative peritoneal lavage in animal experiment]. In a model experiment with albino rats the effectiveness of intraoperative peritoneal lavage has been tested by means of defined lethal staphylococus aureus infections. A positive result can only be expected, if intraperitoneal lavage is started immediately after bacterial contamination. In this can a 10% decrease in the total number of germs be expected. If the lavage is done up to 15 or 30 min after the germ application the efficiency rate declines to less than 1%. In addition bacteraemia could be proved already 15 min after germ application. These results clearly show the limits of peritoneal lavage with physiological saline.


[Computer-aided diagnosis for pancreatic function test (author's transl)]. The use of multivariate nonlinear discriminant analysis raised the rate of correct classification for 585 pancreatic function tests from 84 percent by the doctor to 93 percent by computer analysis. In addition to the "normal" and "pancreatic" disease groups, a group of 388 patients was found in whom secretion levels were neither normal nor typical of pancreatic disease. For this group, nonpancreatic gastroenterologic disease was established with a diagnostic accuracy of 98 percent. Representation of secretion data by Andrews' method for the differentiation of pancreatitis from carcinoma allows moderately sensitive but highly specific testing.


[Surgical treatment of benign and semimalignant tumors (author's transl)]. The differential diagnosis of of benign, semimalignant (or, more correctly, potentially malignant) tumors from malignant tumors or pathologic tumorlike changes is often difficult. Routine angiography and scintigraphy certainly help a great deal in differential diagnosis. The major causes of threatened or pathologic fractures are primary bone tumors and pathologic tumorlike changes. In this connection, a spontaneous fracture is a sign of a benign tumor.  Excochleation or resection, with subsequent filling of the defect with homologous bone chips and fixation with a metal aid if necessary, has proved successful as a treatment for benign and potentially malignant tumors and for tumorlike changes. Joint replacement and amputation are necessary only in exceptional cases.


[Treatment of Dupuytren's contracture (author's transl)]. Surgical treatment of Dupuytren's contracture improves function but cannot remove the cause of the disease. Strict selection of cases, knowledge of the anatomy, the use of incisions appropriate to the local alterations, an atraumatic operative technique, and careful aftercare are essential for positive results. The literature cites success rates of between 60 and 85 percent. Recurrences cannot always be avoided but the frequency can be reduced by meticulous removal of all diseased and normal connective tissue in this area.


[Construction of the vagina by means of split-skin or mucosal grafts (author's transl)]. Of the various methods of lining the vaginal canal with skin, i.e. split-skin, corium, and mesh grafts, the mesh graft offers the best results in terms of both take and shrinkage. The plastic surgeon's principle of performing construction or reconstruction work with similar or neighboring tissue is best met by the use of small-bowel composite grafts in the case of the vagina. Mucosa-muscularis grafts of sufficient size can be taken from the small bowel with relatively low risk; they take very well and the results also appear most appropriate from the anato-mical and physiological aspect.


[Construction of the vagina with transposition of the signoid colon (author's transl)]. Sigmoid transposition for reconstruction of the vagina in congenital aplasia was first carried out at the 2nd Surgical University Clinic in Vienna in 1904 by P. Albrecht. This operation was not frequently used because of possible complications thought to be inherent in the method. In 1954 the author redesigned some essential parts of this procedure with suggestions for avoiding the complications mentioned above. Of 23 patients operated on with this modified technique, in 21 the immediate result was perfect. Necrosis developed in two cases without general symptoms.


[Skin replacement on the penis (author's transl)]. For skin replacement on the penis and scrotum, only a free split-skin graft (about 0.45 mm in thickness) can be considered in cases where local flaps are not available. The transplant is fixed on the denuded penis with a special thermoplast splint, which ensures healing in. Additional sedation is necessary. Pedicle flaps taken from some distance away are too voluminous for the penis and not adequate. Cases with eschars and granulation tissue must be carefully cleaned to avoid hypertrophic scars. Covering can also be achieved with mesh-grafts in these cases.


[Surgical treatment in coronary heart disease (author's transl)]. This paper describes the operative techniques appropriate to the treatment of coronary heart disease. The chapters deal with general preliminaries and indications for surgery, the selection of bypass material, surgical instruments for coronary opertaions, the methods of extracorporeal circulation, the distal coronary anastomosis, the proximal aortal anastomosis, intraoperative monitoring of results, intra- and postoperative myocardinal infarction, the fate of venous bypass grafts, operative treatment of the ruptured ventricular septum and papillary muscle, and ventricular aneurysmectomy.


[The history of wound dressings (author's transl)]. The introduction of antisepsis and asepsis brought about decisive changes in the dressing of wounds. For thousands of years, dressing material had been regarded as protection for wounds, absorbent material, or a base for healing substances, while healing per secundam intentionem by the production of "pus laudabile" was the general rule. With the advent of antisepsis, dressings became a type of medication, healing the wounds per primam intentionem. Different materials have been used over the years, but the most important steps in the development of new dressings were made in the nineteenth century, with the introduction of a degreased cotton and of medicated plasters.


[Thoracic surgery: history and present status (author's transl)]. Following adoption of the differential airways pressure principle (Sauerbruch), continuous positive airway pressure breathing, together with earlier physiological and clinical preliminary reports on artificial lung ventilation, was a major step on the way to intratracheal anesthesia, which was brought to perfection only after World War II. Up to then, the earlier method that Sauerbruch had used in his pioneer work had been prevalent in thoracic surgery. Since Sauerbruch's death, surgery of the heart and thoracic vessels has developed most successfully, while pulmonary tuberculosis now has hardly any surgical significance.


[Experimental surgery in pancreas/autotransplantation (author's transl)]. We have described to technique of one stage intraabdominal heterotopic pancreaticduodenal autotransplantation which has resulted in long term survival of dogs in good health. Malnutrition related to pancreatic exocrine hypofunction occurs initially but gradual recovery by 3 months nutrition is normal. In contrast, endocrine function is well preserved throughout the postoperative period except for a few days immediately after transplantation. Tolbutamide testing showed a significant prolongation of hypoglycemia as compared to controls although glucose tolerance curves were normal. There was no fibrosis after pancreas-autotransplantation. This experimental model is useful for long term evaluation of heterotopic transplantation of the pancreas. Denervation and lymphatic interruption of the pancreas may cause a transient but not definitive influence on pancreatic endocrine or exocrine function.


Focal glomerular sclerosis: contrasting clinical patterns in children and adults. In a retrospective clinicopathological study, 48 kidney biopsy specimens from 16 children (mean age, 7 years) and 17 adults (mean age, 33 years) with histological evidence of focal glomerular sclerosis (FGS) were examined using light, immunofluorescence and electron microscopy. The histopathological findings were related to the clinical course of each patient. At the clinical onset of the disease, the nephrotic syndrome was seen more commonly in children (12/16) than adults (7/17), while the incidence of both hypertension (children 1/16 versus adults, 9/17) and renal insufficiency (children, 0/16 versus adults, 7/17) was greater in adults. Despite a shorter average follow-up, (adults 3 10/12 years versus children, 7 years), the incidence of hypertension (adults, 13/17 versus children, 7/16) and renal functional impairment (adults, 13/17 versus children, 3/16) remained greater in the adult patients. One child and three adults died in renal failure while two adults underwent transplantation and on requires regular dialysis therapy. Nine of 15 pediatric patients treated with corticosteroids experienced partial or complete remission in either their nephrotic syndrome or level of urine protein excretion, while just 3 of 6 adult patients treated with corticosteroids experienced a partial remission, but never became protein-free. There was an excellent correlation in all patients between the degree of functional renal impairment and the extent of glomerular and nonglomerular histopathological damage in the kidney. It is concluded that in the adults, FGS represents a more severe and progressive disease process and is less responsive to therapy.


[Electron microscopic studies on the retina of the honey bee (Apis mellifica): II. Investigations on reactions of the fine structure of the rhabdomeric tubuli after exposure to various experimental influences, especially to light of different wavelength (author's transl)]. Electron microscopic studies were made on the fine structure of the rhabdomeric tubuli of the honey bee-eye after exposure to white and monochromatic light. Several preparation and fixation techniques were tested. A method to irradiate the eyes in vitro by high intensity of white or monochromatic light was developped.


[Quantitative image analysis as a scanning method in histopathological routine diagnostics applied for instance to chronical liver diseases (author's transl)]. A method is given by means of which histological image contents can quantitatively be determined with the help of electronic image analysis. A case of a chronical liver disease is quoted as instance for the application of the method in routine diagnosis. A possibility is shown to open quantitative and reproducible computation to descriptive histopathology.


[Effect of nitrogen and phosphorus in the medium on the level of reserve carbohydrates in the cells of a dividing baker's yeast culture]. Changes in the content of reserve carbohydrates (trehalose, glycogen) were studied in the cells of baker's yeast during their continuous cultivation at various doses of nitrogen and phosphorus in the medium. The content of reserve carbohydrates in the cells, and their viability, increased with a decrease of nitrogen in the medium. Phosphorus displayed the opposite effect, which was however insignificant within the range of its concentrations used in the experiments.


[Isolation of pure methanotrophic cultures and their properties]. Pure cultures of obligate methanotrophic bacteria were isolated from natural habitats and cultivated on media containing silica gel which provided more elective conditions than media with agar. According to their morphology, fine structure, cultural, physiological and biochemical properties, the bacteria were identified as Methylosinus trichosporium, Methylosinus trichosporium var. methanolicum, Methylocystis parvus, Methylocytis parvus var. fuscus, Methylomonas methanica.


[Irregular growth of Escherichia coli under periodic cultivation conditions]. Uneven growth of Escherichia coli ML 30 was found in periodic conditions of cultivation on a defined medium containing maltose or glucose as a source of carbon. This is demonstrated by changes in the slope of the logarithmic curve expressed in units of optical density, and the curve of the specific growth rate plotted against time. The uneven pattern of growth can be revealed only if samples are taken every 15 min. Variations in the growth rate are accompanied with irregular utilization of carbon sources, acidification of the medium, accumulation of organic acids in the cultural broth, deviations in the enzyme activity and the content of polymers in the cells. According to the dynamics of the aforementioned parameters, the growth phase of E. coli is complex and can be subdivided into five different cycles. Such a synchronization of growth is presumed to be due to changes in the composition of the growth medium.


[Total count, biomass and production of microorganisms in the water of the South Sea]. The total number of microorganisms in waters of the Southern Ocean was determined by direct count in capillaries of Perfiliev and Gabe. Ninety samples of water, obtained at depths from 0 to 7,000 m in the Atlantic, Indian, and Pacific sectors of the Southern Ocean, have been analyzed. The number of microorganisms in these samples varied from hundreds to dozens of thousand cells in 1 ml of water, being in most cases thousands of cells in 1 ml of water. An increase in the concentration of cells, as compared to higher and lower horizons, was registered in some layers of subsurface, intermediate, and deep waters.


Massive air embolism in a neonate with respiratory distress. The occurrence of massive air embolism in a neonate during treatment with intermittent positive-pressure respiration and positive end expiratory pressure is reported as a note of caution. It is possible that this complication may indeed be more common. Careful post-mortem examinations (including radiological examinations) are advocated in order that the true incidence of this devastating event shall be known.


Alprenolol in angina pectoris. A comparative study of the tablet form and slow-release formulation. In a double-blind crossover trial in angina pectoris patients, alprenolol in a slow-release formulation (Aptin Durules) was compared with ordinary Aptin tablets. Four hundred mg per day in tablets given four times a day produced the same increase in exercise tolerance five hours after last intake as did an equivalent dose of slow-release formulation given twice per day nine hours after intake. Aptin Durules in double the dosage had a considerably greater effect. An optimal, sustained and antianginal effect of alprenolol is best achieved by giving 400 to 800 mg per day of slow-release formulation with 10 to 12 hours' dosage interval.


The healing of gastric ulcers by zinc sulphate. A double-blind trial of zinc sulphate given by mouth (220 mg, three times a day) and placebo was undertaken in patients with benign gastric ulcers. The drug was given for a three-week period and the healing of the ulcers was estimated from results of barium-meal X-ray films taken immediately before and after this period. There were ten patients taking zinc sulphate and eight patients taking placebo. The two groups of patients were comparable in all respects, including initial ulcer size. Patients taking zinc sulphate had an ulcer healing rate three times that of patients treated with placebo. This difference was significant (P less than 0-05). Complete healing of ulcers occurred more frequently in the patients taking zinc sulphate than in patients treated with placebo. The placebo group contained more patients whose ulcers did not heal at all, than the group taking zinc sulphate. No side effects from zinc sulphate were noted. There was no evidence of zinc deficiency in any of the patients.


Example of a human ovum in a cervicovaginal smear fact or artefact? A further example in a cervicovaginal smear of a structure with the morphological features of an unfertilized human ovum is reported. Previously published case reports of similar objects are reviewed, and alternative sources of bodies which could be incorrectly identified as ova are discussed together with suggested methods of establishing precise identity.


Mutagenic DNA repair in Escherichia coli. II. Factors affecting loss of photoreversibility of UV induced mutations. The photoreversibility of UV-induced mutations to Trp+ in strain Escherichia coli WP2 uvrA trp (unable to excise pyrimidine dimers) was lost at different rates during incubation in different media. In Casamino acids medium after a short initial lag, photoreversibility was lost over about one generation time; in minimal medium with tryptophan, photoreversibility persisted for more than two generations; in Casamino acids medium with pantoyl lactone photoreversibility was lost extremely slowly. The rate of loss of photoreversibility was unaffected by UV dose in either Casamino acids medium or in minimal medium. The same eventual number of induced mutants was obtained when cells were incubated for two generations in any of the three media before being transferred to selective plates supplemented with Casamino acids. Thus in each the proportion of cells capable of giving rise to a mutant was the same and only the rate at which these cells did so during post-irradiation growth varied, suggesting that there might be a specific fraction of pyrimidine dimers at a given site capable  of initiating a mutagenic repair event, and that the size of this fraction is dose dependent. Segregation experiments have shown that error-prone repair appears to occur once only and is not repeated in subsequent replication cycles, in contrast to (presumed error-free) recombination repair. The results are discussed in the light of current models of UV mutagenesis.


Cytoplasmic inheritance in Saccharomyces cerevisiae: comparison of first zygotic budsite to mitochondrial inheritance patterns. Zygotic first budsite in Saccharomyces cerevisiae was studied in relation to defined mitochondrial inheritance systems: both petite and drug resistance. It was hypothesized that a highly asymmetric inheritance pattern would be correlated to a high frequency of first budsites on the petite or drug resistant end of the zygote (i.e., that portion of the zygote which was originally the drug resistant or petite haploid before zygote formation). The data collected did not support the hypothesis. For drug resistance, the budsite pattern is identical for a highly biased and a moderately biased inheritance pattern. In a grande by grande cross there is a high probability of the first bud appearing on the conjugation bridge, with lower but equal probabilities of the first bud appearing on one end or the other of the zygote. A grande by petite cross changes this pattern to a high probability of the first bud appearing on the grade end of the zygote, with a lesser probability of the first bud appearing on the conjugation bridge and virtually no budding of the petite end. This phenomenon is independent of degree of neutrality or suppressiveness of the petite strain used, however. The difference between a grande and a grande by petite pattern may be due to the relative functional ability of the mitochondria in each end of the zygote. Tests using antimitochondrial drugs suggest that selection of first budsite on a zygote is a complex phenomenon, not simply dependent upon mitochondrial phenotype. In conclusion, selection of the first zygotic budsite appears to be independent of mitochondrial inheritance patterns.


The mating reaction in yeast. I. A new mutation involved in the determination of mating-type. The isolation and preliminary characterisation of a mutation, not linked to the mating type locus, but which apparently alters the mating type directed sequence of events during sexual conjugation is described. Haploids of the alpha mating type carrying this gene will now mate with other alpha haploids, creating diploids homozygous for the alpha mating type locus. This gene can be carried, but not expressed, in a haploids, however in a/alpha diploids homozygous for this gene mating is now possible with both a and alpha haploids giving either a/a/alpha or a/alpha/alpha triploids. Using these strains mating-deficient mutants have been isolated and preliminary results on their characterisation presented.


The stoichiometry of the ribosomal proteins of Escherichia coli. A ribosome preparation from E. coli made without stringent washing procedures has been shown to contain the same relative amounts of nearly all the ribosomal proteins as ribosomes in intact cells. Stoichiometric measurements on all the proteins of this preparation except for L8, L20, L31 and L34 have been made using an isotope dilution technique. When the scatter of the values obtained, the uncertainty in the molecular weights, and the losses occurring during extraction are taken into account, none of the proteins except L7/L12 is present at a level significantly different from one molecule per ribosome. There are multiple copies of L7/L12. These data suggest that the ribosomes of Escherichia coli are homogeneous in vivo.


Genetic control of chromosome instability in Aspergillus nidulans as a mean for gene amplification in eukaryotic microorganisms. A haploid strain of Aspergillus nidulans carrying I-II duplication homozygous for the leaky mutation adE20 shows impreved growth on minimal medium. The duplication, though more stable than disomics, still shows instability. Several methods were used for detecting genetic control of improved stability. (a) visual selection, using a duplicated strain which is very unstable due to UV sensitivity, (adE20, biAl/dp yA2; uvsB). One stable strain showed a deletion (or a lethal mutation?) DISTAL TO BIA on the segment at the original position (on chromosome I). This deletion reduces crossing over frequency between the two homologous segments. As the deletion of the non-translocated segment (yelow sectors) must be preceded by crossing over, the above reduces the frequency of yellow sectors. A deletion of the translocated segment (green sectors) results in non-viability due to the deletion, and such sectors do not appear. The net result is a stable duplication involving only 12 C.O. units carrying the gene in concern. (b) Suppressors of UV sensitivity (su-uvsB) were attempted using the above uvs duplicated strain. Phenotypic revertants were easily obtained, but all were back mutations at the uvsB locus. (c) Mutations for UV resistance higher than that of the wild type were not obtained, in spite of the strong selective pressure inserted. (d) Recombination deficient mutations (rec), six altogether, all uvs+, did not have any effect on stability.


Properties of plasmids produced by recombination between R factors of groups J and FII. Recombinant plasmids have been produced both by transduction of genetic material from FIIR factors into Proteus mirabilis strains carrying plasmids of group J and by insertion of a transposon conferring streptomycin and trimethoprim resistances into a J group R factor. The transposon-carrying derivative and one of the transductants were shown to be members of group J whereas another transductant was shown to be compatible with members of this group. This recombinant plasmid was able to eliminate but not to be eliminable by R factors of group FII. A model for the origin of this anomalous compatibility characteristic is presented based on the assumption that the recombinant plasmid carries part but not all of a complex of binding sites for the repressor of replication [Uhlin and Nordström (1975)].


Genetic analysis of mutants of Escherichia coli defective in dicarboxylate transport. Mutants of E.coli deficient in dicarboxylate transport can be mapped at three different loci. The dctA locus is linked to xyl and the dctB and cbt loci are linked to gal. Transduction tests reveal that the likely order of genes in the gal region is dctB-cbt-nadA-galK.


Prophage induction and cell division in E. coli. III. Mutations sfiA and sfiB restore division in tif and lon strains and permit the expression of mutator properties of tif. In E. coli K12, cell filamentation promoted by tif is enhanced by the lon mutation; in contrast, prophage induction and repair of UV-irradiated phage lambda, also promoted by tif, are not affected by lon. From a tif lon double mutant, "revertants" having recovered the ability to divide at 41 degrees were isolated, among which most (95%) had also lost their Lon filamentous phenotype after ultraviolet (UV) irradiation. From these 95% of revertants: (1) 94% are suppressed for the whole Tif phenotype, by additional mutations that render them deficient in DNA repair, as judged from their high UV sensitivity; some have been characterized as recA mutants. (2) 1% have recovered a control on cell division at 41 degrees or after UV irradiation by means of secondary mutations altering neither the other phenotypic properties of tif and lon, nor the repair and recombination ability of the cells: in particular, this class of "revertants" remains thermoinducible upon lysogenisation; the mutations which specifically suppress filamentation have been mapped at two loci, sfiA and sfiB, cotransducible respectively with pyrD and leu. In the remaining 5% of revertants that still exhibit an UV-induced filamentous growth, 3% can be tentatively classified as true tif+ revertants; 2% behave as tif thermodependent revertants, showing suppression of the Tif (and Lon) phenotype only at 41 degrees: 2recAts have been identified in this class. Non-lysogenic tif lon sfi and tif sfi strains remain viable during prolonged growth at 41 degrees. Under these conditions, tif expresses mutator properties, which can be conveniently analyzed in this sfi background. The action of lif, lon and sfi mutations is tentatively interpreted on the basis of a negative control of cell division specifically associated with DNA repair.


Biogenesis of mitochondria 40. Phenotypic suppression of a mitochondrial mutation by a nuclear gene in Saccharomyces cerevisiae. A mutant has been isolated which carries a nuclear mutation capable of suppressing certain aspects of the phenotype imposed by a specific mitochondrial mutation. The mitochondrial mutation [tso-r] confers cold sensitivity to growth on nonfermentable substrates and resistance to oligomycin. When both the mitochondrial and nuclear mutations are present in the same cell the cell is phenotypically cold resistant but retains a high level of oligomycin resistance. The extent of cold sensitivity suppression is dependent upon other unspecified nuclear genes. The molecular basis for the suppression may involve interactions between cytoplasmic and mitochondrial ATPase.


Manganese mutagenesis in yeast. IV. The effects of magnesium, protein synthesis inhibitors and hydroxyurea on AntR induction in mitochondrial DNA. The induction of antibiotic-resistant mutations in yeast mitochondrial DNA by manganese is decreased when the manganese-containing medium is additionally supplemented with magnesium. At equimolar concentrations of manganese and magnesium the former is no longer mutagenic. Amino acid starvation, cycloheximide, chloramphenicol and erythromycin have very little, if any, effect on the mutagenicity of manganese. Hydroxyurea itself seems to be slightly mutagenicity of manganese. Our results show that manganese acts as an error-producing factor in DNA replication probably through a direct interaction with mitDNA polymerase(s).


Synthesis of E colicins in Escherichia coli. Mitomycin C treatment of Escherichia coli cells containing one of the ColE plasmids results in specific inhibition of chromosomal protein synthesis and a high rate of protein synthesis from about 35% of the plasmid genome, whereas similar treatment of plasmid-free cells has no measureable effect on protein synthesis. In the case of ColE2- and ColE3-containing cells, the antibiotic colicin protein (molecular weight about 78000) and two others (molecular weight about 11000 and 6000) are coordinately synthesized in the approximate molar ratio 1:4:1, while in ColE1-containing cells only the colicin protein is synthesized in large amounts. Partially purified colicin E2 isolated from the outer cell surface is associated with the two small proteins in the approximate molar ratio 1:1:1, indicating that not are they only synthesized coordinately but are released as a ternary complex.


Physical studies of a plasmid mediating tetracycline resistance and hydrogen sulfide production in Escherichia coli. Tetracycline resistance and hydrogen sulfide production have been previously found to be plasmid-mediated in a naturally-occurring strain of Escherichia coli; both functions are specified by a single conjugative plasmid called pIP231(Te-H2S); pIP231DNA was isolated as covalently closed molecules in dye-buoyant density gradients. The base ratio of the DNA was found to be 50% GC by density gradient analysis. Electron micrographs of plasmid molecules showed a contour length of 20 +/- 2 mum (40 +/- 4 X 10(6) daltons). Between one and two copies of pIP231 molecules per host chromosome were found in E. coli K12.


Genetic control of invertase formation in Saccharomyces cerevisiae. I. Isolation and characterization of mutants affecting sucrose utilization. Nine sucrose nonfermenting mutants have been isolated from yeast strain EK-6B, carrying the tightly linked SUC3 and MAL3 genes. These mutants are allelic to the SUC3 gene recessive in nature and none of them has detectable levels of either internal or external invertase. A single point mutation leading to the loss of both invertases suggests that either SUC3 is a control gene or codes for a polypeptide which is shared by both invertases.


DNA repair in Proteus mirabilis. III.Survival, dimer excision, and UV reactivation in comparison with Escherichia coli K12. Measurements of UV sensitivity of wildtype cells (wt) and UV senistive mutants of E. coli and P. mirabilis suggest that the increased sensitivity of P. mirabilis (wt) is due either to incomplete repair of DNA lesions or to additive lethality probably as a result of UV induction of defective phage(s) present in P. mitabilis (Taubeneck, 1967). Direct estimates of the rate of pyrimidine dimer excision and a comparison of the UV reactivation capacity of E. coli and P. mirabilis for the temperate phages lambda and pi 1, respectively, support this conclusion.


Genetic consequences of transfection with heterduplex bacteriophage lambda DNA. The role of rectification of heteroduplex heterozygotes in the formation of recombinant genotypes involving closely linked markers has been examined. Heteroduplex molecules of bacteriophage lambda DNA, heterozygous at several alleles, have been constructed and the genetic composition of phage present in infective centers derived by transfection with such molecules has been determined. Allele loss and concomitant recombinant formation is frequent, and appears to reflect marker specificity as well as specificities imposed by whether or not the transfection recipient is permissive or nonpermissive for DNA duplication of the transfecting genome. The observations support the proposal that many, perhaps most, of the events involving separation of closely linked markers occur by rectification of non-recombinant heterozygotes.


Genetic analysis of mutants of Escherichia coli K12 and Salmonella typhimurium LT2 deficient in hydrogenase activity. A genetic study of mutants deficient in hydrogenase activity was performed. In E. coli, the affected gene (hyd) is located at 51 min, between cys C and nal B; in S. typhimurium, it probably lies in the homologous region of the chromosome.


A mutant of Escherichia coli deficient in pyruvate formate lyase. A genetic study was performed on a mutation which has caused loss of pyruvate formate lyase. The gene affected is designated pfl and is located close to ser C, i.e. at 20 mn on the chromosomal map of E. coli.


The mating reaction in yeast. II. Spontaneous occurrence of omni-mating types. Meiosis in diploids of Saccharomyces cerevisiae either homozygous or heterozygous for the dmt gene result, in about 5% of the meiotic products, in spores which have undergone an interconversion at the mating-type locus. Some of these interconversions appear to be the result in the generation of spontaneous omni-mating strains. This phenomenon has now been quantitated and the distribution of mating-type loci in these "natural" amni-mating types determined.


Mapping of gshA, a gene for the biosynthesis of glutathione in Eschericha coli K12. A mutation affecting the activity of the first enzyme in glutathione biosynthesis in E. coli K 12 has been mapped. The mutant allele called gshA is located by transduction in the pheA-nalB segment. The linkages with pheA and tyrA provide a convenient method for transfer of gshA to other strains and so introduce a very low level of non-protein sulfhydryl groups into the E. coli cells.