Microangiographic evaluation of the effects of heparin on progressive Masugi nephritis. Unilateral progressive Masugi nephritis was produced in rabbits and studied by microangiography as well as light and immunofluorescence microscopy. The following five groups were studied: Group 1. Heparin was started simultaneously with nephrotoxic serum (NTS) and was given for one week. The animals were then sacrificed along with the untreated controls. Group 2. This was the same protocol as in group 1 but with three weeks' heparin. Group 3. Heparin was started one day after NTS was given for three weeks. Group 4. Heparin was started one to two weeks after NTS and was given for three weeks. Group 5: late effect group. Heparin was started simultaneously with NTS, was given for four weeks, and the animals were then sacrificed 10 to 13 weeks later. Heparin dose was 5,000 U, s.c., per day in all treated groups. The number of glomeruli seen per unit of cortex by microangiography was significantly increased in the first through the third groups, as compared to the controls. Group 1 did not show this increase but there was some decrease of immunofluorescent fibrinogen. The late effect group (group 5) showed no modification by the treatment, suggesting that an initial improvement may have been negated by persistent immunologic insults after heparin withdrawal.


[Problems and complications of the wound closure in cataract operations (author's transl)]. A presentation is given of some complications resulting from wound closure technique following cataract extraction, without postoperative loss of the anterior chamber. Group 1: In 3 cases a filtering bleb developed within the first 10 days postoperatively, due to faulty suture technique. Wound revision was not necessary. Group 2: In 6 cases wound dehiscence only developed after 3 weeks or longer. In 5 of these cases the fistula, and the subsequent dehiscence, occured at the site of a Barraquer silk suture; which appeared to be at least partially responsible for the complication. 2 of these 5 cases required resuturing, the remaining 3 slowly improved spontaneously. In the 6th case, which also required surgical intervention, the fistula was not situated near a suture. Due to the problems encountered with Barraquer silk sutures the same 3 step cataract incision previously employed was closed instead with interrupted Tübinger nylon sutures, the knots being buried whenever possible. The results were analysed in 81 eyes operated upon with this technique. Postoperative astigmatism lay within normal limits. In one case a filtering bleb developed at the site of a suture. Tübinger nylon sutures are now preferred to Barraquer silk sutures due to the better results obtained so far.


[On the correction of posttraumatic unilateral aphakia in children and in adults with artificial intraocular lens implants (author's transl)]. The problems of optical correction of unilateral traumatic aphakia are discussed. The treatment of choice is a combined Cataract-operation with intraocular lens implants. The operation must be done as soon as the eye is free of inflammation. Prescription of bifocal glasses in addition to pseudophakoi is necessary. With this method a "malignant" Strabismus can be avoided and binocular vision, stereopsis as well as minimal grade of aniseikonia can be achieved.


[Clinical studies conducted with a new epinephrine derivative for the treatment of glaucoma (Dipivalyl epinephrine)]. Dipivalyl epinephrine, an epinephrine derivative, has been developed to improve the pharmacokinetic properties of the compound. Our open-label investigation included the administration of dipivalyl epinephrine ophthalmic solution to the eyes of 33 patients with an open-angle glaucoma. Former topical medication of parasympathomimetic agents was continued. The 0.1% dipivalyl epinephrine treatment approximated the results obtained with 1% epinephrine borate or phenylephrine 5% in reducing the intraocular pressure.


[Centennial of the Basle Eye Hospital and its founder Heinrich Schiess]. 100 years ago Dr. Heinrich Schiess has founded with private means through his personal initiative the eye clinic of Basle. In the same year this clinic become the University Eye Hospital by subsidising from the State. The development of the clinic since 1864 in the past 100 years in discussed. At the same time the life of Dr. Heinrich Schiess, since 1876 Professor of Ophthalmology at the Medical Faculty of Basle, is described. Especially mentioned are his contacts with Albrecht v. Graefe in Berlin and in Heiden.


[Determination of digoxin by enzyme immunoassay and radioimmunoassay (author's transl)]. The results of parallel determinations of digoxin in the sera of non selected patients (n = 104) by enzyme immunoassay (EMIT-EIA) and radioimmunoassay (J-125 labeled RIA) were compared with each other. The determinations revealed considerably different concentrations; the values determined by EIA were statistical lower (for EIA 1.09 +/- 0.99 ng/ml, for RIA 1.34 +/- 1.01 ng/ml, p less than 0.01). In sera with hemolysis and in sera of patients with hyperlipidemia and uremia false-negative results were found by EIA. After elimination of these sera an exact concordation of the values of both the methods was obtained (for EIA 1.12 +/- 1.01 ng/ml, for RIA 1.12 +/- 1.02 ng/ml, r = 0.95).


[Experiences with an enzyme-immunoassay for hepatitis B antigen detection in blood donors (author's transl)]. In a comparative study 12,080 sera from unpaid donors were tested simultaneously for Hepatitis B Antigen (HBsAg) by enzyme-immunoassay (EIA) and radioimmunoassay (RIA). A relatively high number of sera reacted positive in the EIA-secreening test but were negative after repeated investigation. This percentage could be markedly reduced when using an automated washing apparatus. After neutralization 0.31 per cent were considered as true positive in EIA and RIA, thus demonstrating that no differences did exist as far as sensitivity is concerned. The EIA needs more incubation time than the RIA, however, the EIA has the advantage of using enzyme-labelled antibodies instead of radio-iodinated reagents. The results are read immediately and no sophisticated equipment is required. The EIA is easy to handle, two technicians can perform 1000 tests per day.


[Comparative studies of growth hormone secretion in acromegaly after isolated and combined application of insulin hypoglycemia, LH-RH- and TRH tests (author's transl)]. Growth hormone (GH) release was measured in 17 patients with active acromegaly following the administration of insulin, LH-RH and TRH given intravenously either combined or each separately. The simultaneous application of insulin and the hypothalamic releasing hormones resulted in a striking increase of plasma GH in 15 out of 17 patients. Inappropriate stimulation of GH release was found in 9 out of the 17 patients with acromegaly, when TRH was given as the only hormone; conversely this phenomenon due to LH-RH application was observed in 4 cases. In insulin-induced hypoglycemia GH release could be stimulated in 5 patients. After selective, transsphenoidal hypophysectomy, 4 of 13 patients still showed a definite stimulation of GH release after the combined use of test substances. Two of these also exhibited a comparable stimulation of GH after TRH, indicating adenoma cells remaining active after operation. The combined insulin-induced hypoglycemia/LH-RH/TRH-test is therefore advisable for patients with acromegaly, since GH release as well as other hypophyseal partial functions can be tested. The performance of individual tests is essential for evaluating selective stimulation of GH release.


Persistence and distribution of Mycobacterium leprae in Aedes aegypti and Culex fatigans experimentally fed on leprosy patients. Laboratory reared Aedes aegypti and Culex fatigans were experimentally fed on untreated lepromatous leprosy patients and the proboscides, guts and faeces of the mosquitoes were examiend at 12 hour intervals to determine the persistence and distribution of Mycobacterium leprae. In A. aegypti, bacilli persisted in proboscis till 156 hours, in gut 96 hours, and in faeces 72 hours after feeding. In C. fatigans--proboscides 144 hours, gut 96 hours and faeces 72 hours after feeding. In A. aegypti solid bacilli were present in proboscis upto 96 hours; in gut 48 hours and in faeces 42 hours after feeding. Corresponding figures for C. fatigans were: 144 hours for proboscis, 48 hours for gut, solid bacilli being absent in faeces. The results are discussed from the point of view of arthropod transmission.


Study of apparently uninvolved skin in leprosy as regards bacillary population at various sites. Slit smears form 16 LL and 4 BL patients were taken from scalp, axilla, inguinal regions and apparently involved skin patch. The bacilli were found in 100% LL and 75% BL patients at all sites. Scalp showed AFB in all LL and 3 out of 4 BL cases. No lesions were seen on the scalp. Bacterial morphology showed no uniform pattern. Contrary to belief, no immune zones were found on the skin as judged by results of bacteriological examination. Our studies do not support the view that the leprosy bacillus has a predilection for sites with relatively low temperature as far as human leprosy is concerned.


Growth of Mycobacterium leprae in thyroxine treated culture medium--a preliminary report. A new approach in cultivation of Mycobacterium leprae in thyroxine treated Lowenstein-Jensen media is reported. The method has been proved to be successful as the organisms multiplied and remained viable in the thyroxine solution added at the bottom of the culture vial, for a period of 18 to 20 weeks of incubation at 37 degrees C. This has been possible due to metabolic stimulating action of thyroxine sodium solution as well as diffusion of nutrients into this solution from the medium. Intracutaneous inoculation of culture fluid on the surface of foot pad in cortisone treated mouse helped in rapid appearance of the specific lesion at the site within 20 days after injection. Both the intracutaneous method of inoculation and treatment of mouse with high doses of cortisone may play some role in shortening the period of development of such lesion.


Malacoplakia of a cadaveric renal allograft: a case report. A case of malacoplakia in a cadaveric renal allograft is presented. Infection and immunotherapy are presented as possible etiologic factors. The pathogenesis of malacoplakia is discussed with reference to histologic findings in this specific case. The suggestion is made that an altered macrophage response in this disease is the reason for this granulomatous lesion of the bladder.


Immunocytological localization of estrogen in human mammary carcinoma cells by horseradish--anti-horseradish peroxidase complex. Tissues from 25 female and 2 male patients of mammary carcinoma were examined by the horseradish--anti-horseradish peroxidase complex to localize the presence of estrogen. Carcinoma cells of 10 females and 2 male patients showed positive staining by this technique. The nucleus and cytoplasmic membrane showed the reaction. This method is useful in identifying the exact location of the hormones or hormone-like substances in the malignant cells and, perhaps, will be of great help in selecting the patients for management.


[Concerning the history of origin of the two finest arias of the opera "arabella" (author's transl)]. The excellent cooperation between the Austrian poet Hugo von Hofmannsthal and the Bavarian composer Richard Strauss lasted from 1906 to 1929. The last joint work was the fantastic comedy "Arabella". It is reported for the first time that two of the finest arias of this opera were conceived and elaborated in a ward of the Frankfurt University Clinic for Rhinolaryngology immediately after an operation on Richard Strauss in 1928. Various interesting medical and musicological details are reported and documented.


[Werner kümmel and Karl Beck as pioneers of the diagnostical and therapeutical punction of the frontal sinus (author's transl)]. Short bibiolographical review of Werner Kümmel and Karl Beck especially about their scientifical work concerning diagnostical and therapeutical punction of the frontal sinus.


[Osteoplastic operation of maxillary sinus (author's transl)]. An osteoplastic modification of the Caldwell-Luc operation is described. Starting from two small drill holes a quadrangular lid is cut out of the anterior wall of the maxillary sinus using the reciprocating micro-saw after Feldmann. This allows adequate access to the cavity as in the classic procedure. If required the window can be extended in the superior medial angle with rongeurs. After completing the operation within the cavity the osseous lid is reimplanted and fixed with 3 sutures of chromic catgut, which are threaded through small drill holes. By this prodecure prolapse of fat into the sinus is prevented, postoperative closure of the antral nasal window is less likely to occur, the bony structure of the maxilla is restored. Keeping of the reimplant presents no problem. Sequestration or other complications have not been encountered either in suppurative or in polypous sinusitis.


[Computer-assisted analysis of the echohepatograms of children]. In order to choose the most informative indicators of echohepatograms characterizing affections of the liver the results of an ultrasonic investigation of the liver were analized by using bSM-6 type computer. It was found that such indicators as the number of peaks, their summary amplitude may be made use of in making differential diagnosis of diverse hepatic lesions in children.


Labetalol compared with prindolol plus hydraliazine in the treatment of hypertension: a double-blind cross-over study. The hypotensive action of labetalol, a new drug with alpha-adrenoceptor and beta-adrenoceptor blocking action, was compared with that of a combination of prindolol and hydrallazine. Fourteen patients with mild to moderately severe hypertension completed a double-blind cross-over study with treatment periods of eight weeks. Both treatments were effective and, in the doses which were used, produced clinically significant lowering of blood pressure (reduction of mean blood pressure by more than 10 mm Hg) both in clinic and in home blood pressures in 12 of the 14 patients. The action of labetalol (600 mg twice a day) was approximately equivalent to that of prindolol (15 mg twice a day) plus hydrallazine (50 mg three times a day). There was a tendency for the second treatment (irrespective of nature) to be more effective than the first. However, when the results for each treatment were combined, the fall in the blood pressure due to labetalol was practically identical with that due to prindolol and hydrallazine. There were no toxic effects from either treatment and side effects were mild. Labetalol is a useful hypotensive drug with effect similar to that of a combination of a beta-adrenoceptor blocking drug and a vasodilator.


[Increase in intracellular acid phosphatase activity in dehydrated Saccharomyces cerevisae yeasts]. Endocellular acid phosphatase was found to be activated in the course of dehydration of Saccharomyces cerevisiae and at the beginning of its reactivation. This suggests an increase in the number of lysosomes in the cells. Apparently, a damage of the lysosomal membranes may be one of the factors that cause death of yeast cells upon their dehydration.


Hyperkinesis and diet: a double-blind crossover trial with a tartrazine challenge. A pilot study was conducted on 22 children (19 boys and three girls) aged between four and eight years, who were selected as hyperactive on the basis of developmental history and clinical judgement. Conners' parent-teacher ratings, objective tests of attention, standard perceptualmotor tests and subtests from the Wechsler Intelligence Scale for Children (WISC), were used as response variables. The children were tested before and after four weeks on the elimination diet, after a tartrazine and placebo challenge, and, finally, after a four-week washout period on the diet. Results showed a statistically significant improvement in the mothers' ratings of the children's behaviour after the first four weeks of the diet. The improvement was maintained in a combined analysis of the initial four-week diet period and four-week washout period. This result was not substantiated by the statistical analysis of the results from objective tests. The rating scales and objective tests for the full sample did not show a statistically significant deterioration in the children's behaviour when they were challenged under double-blind test conditions with the Yellow Dye No. 5, tartrazine, and the tests were conducted the day after a two-week challenge period. A comparison of mother ratings of behaviour during challenge and placebo double-blind trial and in the 24 hours preceding tests, in a subgroup of the children who, while on the diet, showed a 25% reduction of symptoms on the Conner's rating scale, indicated a significant challenge effect (P less than 0.025), with mothers reporting more symptoms during the challenge period. Dietary infringements with suspected trigger substances occurred throughout the trial.


[Characteristics of the metabolism and multiplication of dehydrated Saccharomyces cerevisiae yeasts during their reactivation]. The growth of dehydrated and original cells of Saccharomyces cerevisiae 0-14 was studied in the conditions of reactivation. The identical amount of biomass having the economical growth coefficient of 58-59 percent was accumulated in both variants after 6 hours of growth. The composition and quantitative proportions between free amino acids were studied in the cells of the two cultures. Dehydrated cells lost up to 10 per cent of free amino acids in the course of rehydration. The dynamics of changes in the composition of the amino acid pool in rehydrated dry cells differed from that in pressed yeast cells. By the end of reactivation however, the qualitative composition and the level of the amino acid pool were similar in the cells of the two variants. The yield of growth of reactivated cells in the course of following cultivation was by 16 per cent higher than that of pressed yeast cells grown under the same conditions.


Enterotoxin-producing Escherichia coli and diarrhoea among newborn babies in Darwin. Specimens of Escherichia coli O119B14 isolated from 13 newborn babies during an outbreak of diarrhoea in Darwin Hospital were tested for their ability to produce enterotoxin. Of the 13 isolates tested none was found to produce heat-labile enterotoxin. However, isolates from two of the five diarrhoeal faecal specimens were found to produce moderate levels of heat-stable enterotoxin (ST). It seems like that ST-producing strains of E. coli were responsible for the diarrhoea.


An evaluation of oral hexoprenaline sulphate (Ipradol) in exercise-induced asthma. The effect of hexoprenaline sulphate (1 mg) administered orally on the fall in peak expiratory flow rate (PEFR) after exercise was investigated in 20 asthmatic patients. Compared with placebo, the fall in PEFR expressed as a percentage of the resting value (measured immediately before exercise) was less in 16 of the 20 patients in the presence of hexoprenaline sulphate. This consistent amelioration of exercise-induced asthma has not been observed in this laboratory with similar drugs (such as salbutamol and terbutaline). While eight patients were afforded significant protection by the hexoprenaline sulphate, a fall in PEFR after exercise was within the normal range (less than 10% of the resting value) in only four patients.


Bronchodilator effect of hexoprenaline aerosol in bronchial asthma and chronic bronchitis. The bronchodilator effects of aerosols of hexoprenaline (200 microgram and 400 microgram), and salbutamol (200 microgram) were compared in 15 patients with asthma, and nine patients with chronic bronchitis. In both groups of patients, hexoprenaline and salbutamol produced a similar increase in the forced expiratory volume in one second (FEV1), and mean percentage increase in FEV1. Neither drug caused tachycardia or arrhythmia. It was concluded that hexoprenaline aerosol was a safe and effective bronchodilator.


NETS: a new system for neonatal transport. Neonatal transport in the past has often provided inadequate care for the sick neonate in transit. A new service--the Neonatal Emergency Transport Service--has been set up to improve aspects of neonatal transport. The service provides a team of sisters and doctors who travel to the referring hospital with sophisticated equipment to stabilize the infant, and to accompany the infant in transit. The team pays particular attention to temperature control and adequacy of oxygenation and ventilation. The first nine months' operations are reported, and show significant improvement in condition of the infants on admission to the intensive care unit. The natural consequence of this is the fall in mortality and morbidity of the sick and premature newborn infants. Prenatal transfer of the mother at high-risk remains the preferred form of perinatal transport.


Henry Leighton Jones and his contribution to gland grafting. Henry Leighton Jones, the monkey-gland doctor of the Newcastle area during the 1930s, was a man of considerable experience in pharmacy, dentistry, general practice and surgery. His career is outlined in sufficient detail to emphasize that as a result of wide experience and a life of study he may have discovered some important principles of tissue-typing and applied them with success to his gland transplant surgery.


[Melanocytes in the epithelium of the gingival mucosa in different conditions of edentia]. Gingival crest melanocytes were examined in partial and total edentulates (with and without prostheses). Where the epithelium showed signs of epidermisation, the cells displayed their normal form and melanogenetic activity. In the presence of involution (acanthosis, reduction of the surface layers, smallcell infiltration), they withdrew their typical cytoplasmic expansion, while the Dopa reaction revealed poor thyrosinase activity. It is felt that these patterns confirm the epithelio-melanocyte symbiosis theory put forward by Quevedo et al. One total edentulate with a mucosally supported prosthesis displayed Dopa-positive dendritic cells on the gingival corium and tunica propria. These are seen as true melanocytes that had migrated from the epithelium.


[A case of difficult diagnostic interpretation]. Left submandibular adenophlegmon was initially attributed to local dental disease. Recurrence of the symptoms when this was corrected, however, showed that E. coli was responsible, and suitalbe antibiotic management quickly led to a complete cure.


Translation and mRNA decay.

Translation and mRNA decay. Degradation of messenger RNA from the lactose operon (lac mRNA) was measured during the inhibition of protein synthesis by chloramphenicol (CM) or of translation-initiation by kasugamycin (KAS). With increasing CM concentration mRNA decay becomes slower, but there is no direct proportionality between rates of chemical decay and polypeptide synthesis. During exponential growth lac mRNA is cleaved endonucleolytically (Blundell and Kennell, 1974). At a CM concentration which completely inhibits all polypeptide synthesis this cleavage is blocked. In contrast, if only the initiation of translation is blocked by addition of KAS, the cleavage rate as well as the rate of chemical decay are increased significantly without delay. These faster rates do not result from immediate degradation of the lengthening stretch of ribosome-free proximal message, since the full-length size is present and the same discrete message sizes are generated during inhibition. These results suggest that neither ribosomes nor translation play an active role in the degradative process. Rather, targets can be protected by the proximity of a ribosome, and without nearly ribosomes the probability of cleavage becomes very high. During normal growth there is a certain probability that any message is in such a vulnerable state, and the fraction of vulnerable molecules determines the inactivation rate of that species.


Genetic studies of the ribosomal proteins in Escherichia coli. XI. Mapping of the genes for L21, L27, S15 and S21 by using hybrid bacteria and over-production of these proteins in the merodiploid strains. E. coli episomes which cover argG region were transferred to S. marcescens and ribosomal proteins (r-proteins) from these hybrid strains were analyzed by two-dimensional (2D) polyacrylamide gel electrophoresis. Three E. coli r-proteins L21, L27 and S15 could be detected in the ribosomes from the hybrid strains. The relative rate of synthesis of the individual r-proteins were determined for E. coli merodiploid strains harboring these episomes. Over-production of three r-proteins L21, L27 and S21 (but not S15) was observed in the merodiploid strains.


[The problem of taking dental impressions in acquired microstomia]. Two cases of severe cicatricial atresia of the oral rima with total edentia are reported. These patients present considerable problems when impressions of the dental arches have to be obtained. To make the labial tissues more elastic and in the attempt to increase rimal space, a perilabial collar of resin is made. Using the normal silicon-based synthetic elastomers, a first mould can be obtained directly in the mouth. This in its turn is filled with a more fluid elastic material and set in the mouth. From this initial impression, a chalk model can be obtained and from this an individual silicon mould is made from which a more accurate final impression is possible. In order to adjust the occlusion and test the teeth, a resin plate is prepared. This can be detached from the wax and fitted into the mouth. The standard methods are then employed to make the body of the prosthesis.


Janus green resistance in Saccharomyces cerevisiae: interaction of nuclear and cytoplasmic factors. Janus green B was found to be a specific inhibitor of mitochondrial function in yeast. This is consistent with the Janus green specificity in supravital staining of mitochondria. A mutant of S. Cerevisiae resistant to Janus green B was isolated. It shows cross resistance to oligomycin, ethidium bromide and a weak resistance to chlormaphenicol. The mutant was found to be sensitive to cycloheximide and erythromycin. Genetic analysis of this mutant showed that mitochondrial genes are not involved in the determination of Janus Green resistance. Tetrad analysis suggested that two more more nuclear genes are concerned, but many unusal genetic features suggestive of the involvement of a cytoplasmic element remain to be explained.


Chemical cross-linking of protein to RNA within intact ribosomal subunits from Escherichia coli. Bifunctional reagents, namely bis-(2-chloroethyl)-amine ("nitrogen mustard") and activated esters of 3-(2-bromo-3-oxobutane-1-sulphonyl)-propionic acid ("bromo-ketone reagent") are used to cross-linked protein to RNA within intact ribosomal subunits. The cross-linked proteins are analysed on two different two-dimensional gel electrophoresis sytems, and the existence of a stable cross-linkage is demonstrated by isolating cross-linked protein-oligonucleotide complexes from subunits containing 32P-labelled RNA. Proteins S3, S4, S5, S9/S11 and S13 from the 30S subunit, and proteins L1 and L2 from the 50S subunit were cross-linked to RNA by the nitrogen mustard, together with a number of other so far unresolved proteins. Correspondingly S3, S4, S7, S9/S11 and L12 were cross-linked by the bromoketone reagent, although in lower yield. The reagents should prove useful topographical studies on ribosomal subunits, and arguments are presented favouring the use of non-cleavable and relatively non-specific RNA-protein cross-linking reagents for such studies.


Tn951: a new transposon carrying a lactose operon. A new transposon, Tn951, is described, which derives from plasmid pGC1, originally isolated from Yersinia enterocolitica. Tn951 is 16.6 kb long and presumably flanked by small inverted repeats. It carries the lac genes i, z and y. This lac system is homologous to the E. coli lac operon. However, homology is restricted to 5.6 kb. The DNA sequences surrounding the lac operons on Tn951 and E. coli are nonhomologous. This leads to speculations about the origin of the E. coli lac operon itself.


Laboratoire de Chimie Bactérienne C.N.R.S., Marsielle, France. Mutants of E. coli, completely devoid of nitrite reductase activity with glucose or formate as donor were studied. Biochemical analysis indicates that they are simultaneously affected in nitrate reductase, nitrite reductase, fumarate reductase and hydrogenase activities as well as in cytochrome C552 biosynthesis. The use of an antiserum specific for nitrate reductase shows that the nitrate reductase protein is probably missing. A single mutation is responsible for this phenotype: the gene affected, nir R, is located close to tyr R i.e. at 29 min on the chromosomal map.


A correlation between shortened life span and UV-sensitivity in some strains of Saccharomyces cerevisiae. From a UV-irradiated sample of diploid cells several clones were isolated, which produced cells with a shortened life span. A closer examination of three of these clones showed among other deviations from the wild type a higher sensitivity to UV-irradiation. Three other clones, which were selected from a haploid strains as UV-sensitive mutants, proved to be shortlived as well. In all these strains photoreactivation and liquid holding reactivation were unimpaired. There was no cross-sensitivity to X-irradiation. The correlation between shortened life span and UV-sensitivity is discussed.


[Nucleotide and oligonucleotide derivatives--a research tool of molecular biology]. The work of the authors are discussed, that they have been engaged in since the late forties, on synthesis and investigation of mono- and oligonucleotide derivatives. One class of mixed biopolymers (mono (oligo) nucleotides) is used to demonstrate the effect of covalent and noncovalent intramolecular interactions on the character of various protein-nucleic acid contacts. General approaches to creating regioselective reagents are outlined, that can be widely used for modification of both proteins and nucleic acids. Designing and application of some of such reagents is analyzed.


[Template properties of the decadeoxynucleotide d(pCCACGAAACC) in the RNA polymerase system of Escherichia coli]. The decadeoxynucleotide d(pCCACGAAACC) transcription by E. coli RNA-polymerase was studied. The transcript was shown to be several times longer than the template. The oligonucleotide GpGpGpGpUp complementary to the "contact" of two neighbouring template molecules was found in the pancreatic RNase digest of the RNA-product. This fact is consistent with our hypothesis reported recently. Pentanucleotide d(pGGTTT) may funtion as a primer in the decadeoxynucleotide transcription being incorporated into RNA.


[Study of the structure of tRNA by the energy migration method using fluorescent labels covalently bound to specific tRNA loci]. Optical and fluorescent characteristics of fluorescein covalently attached to 3'-end of tRNAFhe and X-nucleotide in the extra arm of several species of tRNA from E. coli have been studied. The probe is shown to be a sensitive factor indicating the conformational change of tRNA induced by Mg2+ and Na+ ions. By measuring the extent of energy transfer the distances between the fluorescent probe attached to 3'-terminus and X-nucleotide of tRNA and specific binding site of ethidium bromide on tRNA were determined to be 40.5 A and 32.5 A, respectively. The distances measured are in good agreement with the NMR spectroscopy data showing that the specific binding site for ethidium bromide on tRNA is localised near the sixth base pair of the acceptor stem.


[State of DNA slots in mono- and oligonucleosomes and in DNA complexes with individual histones]. The state of the major and the minor DNA grooves in purified mono- and oligonucleosomes and in the complexes of DNA with different histones have been studied by means of methylation of DNA with dimethyl sulphate. In nucleosomes histones shielded major groove by 18--20%. This result agrees well with our previous data obtained with chromatin, nuclei and whole cells. Each of the purified histones H2a, H2b, H3 and H4 as well as N-terminal peptides of H4 histone cause relative shielding of the DNA major groove by 15--18% like whole histone does. H1 histone protects neither DNA grooves from methylation. Our results suggest that histones are buried partly in the major groove of DNA in chromatin and purified nucleosomes. The arrangement of histones in the major groove does not depend probably on their specific organization in nucleosomes.


[Peptidyl transferase center of ribosomes. I. Difference in the substrate specificity of the acceptor and donor portions]. Some model substrates of the peptidyl transferase centre of E. coli MRE-600 ribosomes were synthesised and tested in a cell-free system without a template. In these substances the nucleic bases were linked covalently with the ribose residue or had a limited rotation about the glycosidic bond. 3'(2')-O-(N-formylmethionyl)-8-bromoadenosine 5'-phosphate and 3'(2')-O-phenylalanyl-8,5'-anhydro-8-mercaptoadenosine were shown to possess a high peptide donor and acceptor activity correspondingly. Contrary to that 3'(2')-O-phenylalanyl-8-bromoadenosine was practically inactive as a peptide acceptor and 3'(2')-O-(N-formylmethionyl)-8,5'-anhydro-8-mercaptoadenosine had no peptide donor activity at all. PMR and CD spectra of the compounds synthesised were investigated. The significance of conformation of the model substrates on their activity is discussed.


[Formation of the compact form of DNA in solution after reaction with spermidine]. The formation of compact particles from double-stranded DNA molecules in water-salt solutions containing spermidine was studied. It has been shown that in solutions of low ionic strength (0.01 M NaCl) DNA-spermidine complexes have the form of large particles which scatter UV-light. Electron micrographs show that such complexes formed at certain molar ratios spermidine/DNA may exist both as intermolecular aggregates and as toroidal particles 1500 A in diameter. The CD spectra of solutions containing DNA-spermidine complexes are characterized by the positive band (delta epsilon max = 10) at 265--270 nm. The appearance of the positive CD band may be caused by two factors: interaction between DNA and spermidine may lead to the alteration of the DNA secondary structure "in direction to A-form" or intermolecular aggregation, which may change the initial shape of the CD spectrum. The exclusion of spermidine molecules from DNA-spermidine complexes by Na+ ions in presence of poly(ethylene glycol) which occurs as the ionic strength increases from 0.01 to 0.3 does not lead to decompactization of DNA molecules but is accompained by the appearance of the intense negative CD band at 270 nm.


Biochemical analysis of damage induced in yeast by formaldehyde. I. Induction of single-strand breaks in DNA and their repair. Analysis of sedimentation  profiles in alkaline sucrose gradients showed that, through a metabolic process, formaldehyde (FA) produced single-strand breaks in DNA of exponential phase cells of haploid wild-type Saccharomyces cerevisiae. The production of this type of lesion was dose-dependent. Strains defective in excision-repair of pyrimidine dimers induced by ultraviolet (UV) irradiation showed a reduced capacity to undergo single-stand breaks after treatment with FA. This indicates that the repair pathways of damage induced by UV and FA share a common step. Post-treatment incubation of wild-type cells in growth medium indicate a lag in cell division during which a slow recovery of DNA with a normal size was observed.


Dose-rate effects of 8-methoxypsoralen plus 365-NM irradiation on cell killing in Saccharomyces cerevisiae. Tow types of dose-rate effect that alter the survival response of haploid yeast cells to 8-methoxypsoralen (8-MOP) plus treatment with irradiation at 365 nm were studied. (1) When the concentration of 8-MOP was varied between 9.2 X 10(-5) and 2.3 X 10(-8) M and the dose rate of 365-nm irradiation kept constant, the efficiency of the irradiation for killing increased relatively to that of 8-MOP whe the concentration of 8-MOP decreased. This indicated that there was no strict reciprocity between radiation dose and concentration of drug. (2) When the dose rate of radiation was varied between 0.66 X 10(3) and 108 X 10(3) J m-2 h-1 and the concentration of 8-MOP was kept constant, the survival of wild-type cells increased strikingly at low dose rates of radiation as compared with high dose rates. Cells responded more to changes at low dose rates than to equal changes a high dose rates. The high resistance of wild-type cells to 8-MOP plus radiation delivered at low dose rates absent from rad 1-3 cells defective in excision-repair. This suggests that the dose-rate effect seen in wild-type cells depended at least in part on an active excision-repair function. At low dose rates of radiation, the shoulder of the survival curve for rad1-3 cells, i.e. the ability to accumulate sub-lethal damage, was increased by a factor of about 2 when compared with that seen at a high dose rate. Thus it is likely that at low dose rates a repair function other than excision-resynthesis may operate in rad1-3 cells.


Heritable translocation test on random-bred mice after prolonged triethylenemelamine treatment. Heritable translocation and dominant lethal tests were conducted with random-bred Swiss albino male mice. The animals were provided drinking water containing triethylenemelamine (TEM) for 4 weeks, and were then mated for 3 successive weeks for analysis of dominant lethality and production of F1 progeny. Potential translocation carriers among F1 males were selected after two breedings and confirmed by cytogenetic analysis. Translocation heterozygotes were obtained in offspring of the TEM-treated groups, but not in the control groups. In F1 males produced from the first week of mating, the frequencies of translocations were 0, 1.78 6.2 and 10.0% for the control group and groups receiving TEM at 0.0125, 0.025 and 0.050 mg/kg/day, respectively, and in those produced from the third week of mating, the values were 0 and 2.1%, respectively, for the control group and the group receiving TEM at 0.050 mg/kg/day. F1 males from the second week of mating were not studied for the induction of heritable translocations. TEM-induced dominant lethality and heritable translocations were most prominent in the first week of mating after 4 weeks of treatment. In addition, heritable translocations appeared to be a more sensitive endpoint than dominant lethal mutations for the measurement of mutagenic effects of TEM.


A critique of the collaborative cytogenetics study to measure and minimize interlaboratory variation. A statistical reanalysis was performed on the data fecently reported on a 6-laboratory, collaborative cytogenetic study to measure and minimize interlaboratory variation. Three of the laboratories had mean values significantly different from the others on most of the 6 indexes of chemically-induced aberration; one laboratory with values higher and two with values lower. Furthermore, relative variability of the values around the means was consistently lower in one of the 6 participating laborabories. The results of the reanalysis of this collaborative study demonstrates that significant interlaboratory differences exist and that these should be adjusted or diminished before rat cytogenetic analysis can be an effective test system for evaluation of a compound for mutagenic potential.


Concurrent quality assurance in hospital care. Report of a study by Private Initiative in PSRO. To test the feasibility and effects of incorporating concurrent quality assurance (CQA) into the concurrent utilization reviews required by PSRO's, adherence to essential criteria of medical care and attainment of expected immediate outcomes were monitored prospectively in 5604 cases of seven conditions in 24 experimental and 26 control hospitals in five PSRO areas. CQA was not consistently associated with improved documentation in records, but was associated with slightly better adherence to treatment criteria in all five PSRO areas (P less than 0.03). Adherence to pooled documentation or treatment criteria was unrelated to outcomes. However, failure to adhere to disease-specific scientifically validated treatment criteria was associated with unsatisfactory outcomes in bacterial pneumonia (P less than 0.01) and acute myocardial infarction (P less than 0.02). CQA was professionally acceptable, technically feasible and compatible with PSRO reviews. Given adequate physician support, CQA can produce slightly greater adherence to treatment criteria. If the criteria are valid, adherence may lead to improved immediate outcomes in some diseases.


Asymptomatic structural liver disease in hemophilia. In a study of persistent abnormalities of liver-function tests in hemophilic patients deficient in factor VIII or IX and treated with factor VIII or IX concentrates, we examined 14 liver biopsies from 13 anti-HBs-positive patients. None had any symptoms of liver disease. All had chronically abnormal levels of alanine aminotransferase. Histologic studies showed chronic persistent hepatitis in eight patients, chronic active hepatitis in four and fatty infiltration with portal fibrosis in one. Indirect immunofluorescence of antiserums containing anti-HBs or anti-HBc (or both) revealed nuclear and cytoplasmic fluorescence in the hepatocytes of eight of 12 patients. Specificity testing of these antiserums confirmed that hepatitis B viral markers are present in the hepatocytes of these anti-HBs-positive patients. These histologic derangements are probably related to frequent treatment with blood products obtained from multiple donors and to the persistance of hepatitis B virus in hepatocytes despite the presence of circulating anti-HBs.


Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning. To determine whether tumors containing carcinoembryonic antigen could be detected by administration of a radiolabeled, affinity-purified, goat lgG having 70 per cent immunoreactivity against carcinoembryonic antigen, 18 patients with a history of cancer of diverse histopathology received an average total dose of 1.0 mCi of 131l-labeled lgG. Total-body photoscans were performed with a gamma scintillation camera at various intervals after administration of the radioactive antibody. Ordinary photoscans proved difficult to interpret because of blood-pool background radioactivity, thus necessitating the computer subtraction of radioactive blood-pool agents from the antibody's 131l activity. Tumor location could be demonstrated at 48 hours after injection in almost all cases studied. The scans were negative in patients without demonstrable tumors or with tumors apparently devoid of carcinoembryonic antigen. Circulating antigen levels of up to 350 ng per milliliter did not prevent successful tumor imaging after injection of the radioantibody.


Role of the renin-angiotensin system in post-transplantation hypertension in patients with multiple kidneys. To define the role of the renin-angiotensin system in post-transplantation hypertension we studied 12 hypertensive recipients of renal transplants. The patients received saralasin acetate, an angiotensin II antagonist, while on a normal sodium diet and again after seven days of sodium restriction. In six patients with only one kidney, saralasin did not lower blood pressure on either diet; salt depletion did not lower systolic or diastolic blood pressures. In six patients with more than one kidney, salt depletion also did not lower blood pressure; however, salt depletion plus saralasin lowered their systolic pressures from a mean (+/- S.E.M.) of 146 +/- 9 to 128 +/- 8 mm Hg, and mean diastolic pressures fell from 103 +/- 5 to 89 +/- 5 (P less than 0.001). In four of five patients renal-vein renin activity was greater in one or more host kidneys than in the transplant kidney (or kidneys). Although pre-transplant blood pressure was the same in both groups, post-transplantation hypertension is more likely to be angiotensin II-dependent in patients with more than one kidney.


Polyamines and brain tumors.

Polyamines and brain tumors. Although their precise functions are unknown, the polyamines have been linked to cellular proliferation and division. The demonstration of a definite correlation between growth rate and the synthesis of the polyamines in tissues has led to the hope that such correlations might extend to polyamine concentrations in physiologic fluids. Polyamine determinations may then offer a simple index of tumor burden and growth rate. Studies of the relationship of cerebrospinal fluid polyamine levels to the presence of brain tumors indicated that thes determinations may assist in the early diagnosis of brain tumors, in the longterm evaluation of tumor therapy, and in the short-term evaluation of the efficacy of specific therapies.


Corticosteroid therapy in patients with brain tumors. Since the first half of the last decade, numerous authors have testified to the clinical usefulness of corticosteroids in patients with brain tumors. The mechanism of benefit of these agents is controversial. Although it is clear that corticosteroid therapy reduces cerebral edema around brain tumors, mounting experimental evidence suggests that steroid compounds also may have a direct antineoplastic effect on brain tumor cells. The principal disadvantage of such therapy is that it makes difficult the evaluation of the tumor's response to oncolytic agents simultaneously administered. The most effective dosage of steroid varies; some patients require 96 mg dexamethasone daily before the maximum effect is achieved. These differences in response may be due to varying degrees of peritumoral edema, normal differences in steroid metabolism, and complex drug-to-drug interactions. Corticosteroid therapy may increase the incidence of gastrointestinal bleeding in neurosurgical patients, but this low risk is acceptable in view of its many advantages.


Prognostic factors for patients with brain tumors. Patient characteristics of 225 patients entered into a clinical trial conducted by the Brain Tumor Study Group (69-01) were examined for their relationship to survival time. In the clinical study, all patients received surgery and were randomized to control treatment (no further treatment), X-ray therapy (XRT), 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), or BCNU + XRT. When treatment was considered as a possible prognostic factor, the patient characteristics most related to survival were: XRT (receiving XRT favorable), age (young, favorable), symptoms of seizures and cranial nerves (both favorable), BCNU treatment (yes, favorable), encapsulated tumor (yes, favorable), and parietal tumor (no, favorable). When treatment was not considered a possible prognostic factor, the patient characteristics most related to survival were: age (young, favorable), biopsy (operation biopsy only, unfavorable), seizures (yes, favorable), cranial nerve symptoms (yes, favorable), and parietal location of tumor (yes, unfavorable). Knowledge of prognostic factors can be used for stratifying patients in clinical studies, for testing the comparability of groups of patients, and in the analysis of the results of clinical studies.


Brain tumors: criteria of response and definition of recurrence. The criteria for determining response to therapy and establishing brain tumor recurrence are presented. Basing their conclusions on a series of more than 500 patients, the authors contend that serial scintiscans and computerized axial tomograms can be used to determine accurately the response to therapy and recurrence or tumor regrowth. The problems in evaluating response and tumor recurrence are discussed, with emphasis on those relating to concurrent glucocorticoid therapy and medical conditions such as infection, hematomas, and drug side-effects.


Therapeutic trials in the management of metastatic brain tumors by different time/dose fraction schemes of radiation therapy. Two consecutive studies have been performed by the Radiation Therapy Oncology Group on patients with metastatic brain tumors. Approximately 1,000 patients were entered into each trial. Treatment schedules of varying dose-time fractionations were used. Results were evaluated on the basis of improvement in general performance and neurologic function status. Survival also was recorded. Patients who received corticosteroids in conjunction with radiation therapy experienced a more rapid improvement in neurologic function than patients who did not receive steroid therapy. This was noted particularly in patients with poor neurologic function status. However, by the 4th week this difference had disappeared. Survival times were not altered by the addition of steroid therapy. Preliminary results of the second study suggest that ultra-short fractionation schedules are less effective than the longer ones used in the first study. A dose of 3,000 rads given in 10 equal fractions for a period of 2 weeks appeared to be the most satisfactory schedule for most patients with intracranial metastases.


Correlation of animal brain tumor models with human neuro-oncology. The paper reviews the histopathology and cytopathology of a number of experimental animal brain tumor models to determine their relevance to human neuro-oncology. The models discussed include brain tumors produced by local implants of carcinogenic hydrocarbons and by the administration of resorptive N-nitroso compounds, some of the cell lines derived from the latter, tumors resulting from the intracerebral inoculation of oncogenic viruses, and the differentiating neuroepithelial component of a transplantable mouse teratoma. The structural and biochemical criteria that can be applied for the identification of the various stages of neuronal and glial cell maturation are highly precise. They reveal a wide diversity of tumor cell types that are now available in experimental neuro-oncogenesis.


Immunosurveillance and cancer: epidemiologic observations. To evaluate the immunologic surveillance theory of cancer, we reviewed the epidemiologic observations that have been made on cancer risk among population groups with immune deficiency. Lymphoproliferative neoplasms predominate in various groups, most notably renal transplant recipients treated with immunosuppressive agents and patients with primary immunodeficiency syndromes. In some immune disorders, specific forms of nonlymphoid neoplasia seem to occur excessively, although the patterns are not clear-cut or consistent. The available epidemiologic evidence fails to support the concept that immunosurveillance mechanisms are generally involved in carcinogenesis but does provide clues to immunologic processes that may predispose to particular neoplasms.


Nasopharyngeal carcinoma: opportunities for international collaborative research in Malaysia and Hawaii. Malaysia and Hawaii have several advantages for epidemiologic and laboratory studies on nasopharyngeal carcinoma. Both have multiethnic populations with different incidence rates of nasopharyngeal carcinoma and different life-styles. Malaysia has large populations of Chinese, Malaya, and Indians, and the number of cases of nasopharyngeal carcinoma at any one time is comparatively large. Incidence rates for 1968--72, age-standardized to the World population, for Guangdong hua (Cantonese Chinese) in Malaysia were 24.3/100,000 for males and 12.0/100,000 for females. In Hawaii, the ratio was 12.9/100,000 for males and 6.7/100,000 for females. The small number of cases in Hawaii would require that research in that State be conducted in collaboration with research elsewhere with larger case numbers.


Cancer and chronic disease surveillance in British Columbia. The British Columbia Health Surveillance Registry recorded morbidity information on a number  of chronic and disabling diseases. The Cancer Register, the largest within the agency, achieved good ascertainment of neoplasms within the Province. In 1973, a total of 8.397 new cancer cases, excluding cases of carcinoma in situ, were diagnosed and reported. The general register ascertained congenital anomalies and other physical and mental disabilities within British Columbia. At the end of 1971, approximately 20,111 anomalies had been recorded. The Record Linkage Program currently underway in British Columbia will eventually link records of cancer, congenital anomalies, live births, marriages, and other vital events on a continuing basis for research purposes.


Possible use of short-term tests for carcinogens in experimental epidemiology. This brief overview pointed out the feasibility of applying the recently developed short-term bioassays for carcinogens/mutagens to the field of epidemiology. The simplicity and economy of these test systems permitted their adaptation for large-scale screening for intrinsic and extrinsic carcinogens with an eye to detecting subpopulations with elevated sensitivity to particular carcinogens.


Survey of cancer incidence in Alaskan natives. A survey of cancer incidence among Alaskan Natives for the 5-year period 1969--73 revealed fewer cases overall than expected in relation to rates in the United States. However, significantly increased risks were seen for certain sites: the nasopharynx in both sexes (with excesses over 15-fold), the liver in males, and the salivary glands, gallbladder, kidney, and thyroid in females. Compared with earlier reports, the observations suggested marked changes in cancer incidence among Alaskan Natives over the past two decades, with declines in esophageal and invasive cervical cancers, and increases in neoplasms of the lung, colon, and rectum.


History and status of the Cancer Surveillance System of Western Washington. A cancer registry for a population of over 2 million people was established in 1973. Although the population is predominantly white, the presence of people of Oriental stock provides a potential for migrant studies and international comparisons. Over 7,900 resident cancer cases are detected annually, and a good system for evaluating completeness of reporting and quality of collected data has been devised. To utilize the resources that the registry represents, we have a competent staff of epidemiologists and biostatisticians with academic appointments at the University of Washington and interests in cancer etiology, evaluation of care, and teaching.


Brain stimulation for the suppression of the intractable pain. Stimulation of the brain has been shown to effectively suppress the clinical pain states due to central nervous system lesions. The effective stimulation site is within the somatosensory system. Stimulation in the periventricular gray matter can produce profound analgesia and effective clinical relief of chronic pain states when they are due to lesions involving the peripheral structures. This system probably is effected by activating a descending tract in the dorsal lateral fasiculus of the spinal cord impinging upon neurons in lamina 5 and lamina 1 of the dorsal bone. Stimulation in this system has not been found to be effective in patients with central lesions, which might have been anticipated in view of the anatomical relationships presented.


Effects of lesions in various structures of the suprachiasmatic-preoptic region on LH regulation and sexual behavior in female rats. Lesions of the suprachiasmatic nuclei (SCN) completely eliminated phasic LH release in ovariectomized rats as measured by the positive feedback response to estradiol benzoate (EB)/progesterone or the response to mating. Basal LH levels and the negative feedback response to EB were not affected. Lesions of the medial preoptic area (MPOA) or bed nucleus-dorsal MPOA also inhibited phasic LH release in ovariectomized rats as measured by positive feedback. However, the inhibition was not complete if there was no damage to the SCN, and the degree of inhibition was correlated with the size ofthe lesion. Basal LH levels and negative feedback were not significant affected. It is suggested that both the SCN and MPOA are involved in phasic LH release, the former in its role as a neural regulator of circadian rhythms and the latter as part of a diffuse system possibly including estrogen-sensitive and/or LH-RH neurons. Sexual behavior (lordosis) in hormone-primed, ovariectomized rats was not significantly affected by lesions of any structure in the suprachiasmatic-preoptic region.


The effect of systemic administration of dopamine and apomorphine on Plasma LH and prolactin concentrations in conscious rats. The effect of systemic administration of various doses of dopamine (DA) and apomorphine (APM) on plasma gonadotropin and prolactin (Prl) concentrations in ovariectomized (OVX) as well as in ovariectomized, estrogen-progesterone (OEP)-primed rats bearing indwelling jugular venous catheters was evaluated. Intravenous (i.v.) infusion or pulse injection of 0.9% NaCl had no significant effect on plasma titers of LH or Prl. I.v. infusion of DA at 4 micrograms/kg-b.w./min induced a progressive increase in circulating LH concentration in OEP rats while infusion at a similar dose in OVX animals had no effect on plasma LH. I.v. injection of 100 micrograms DA or APM significantly increased LH at 15 min in OVX rats. Similarly, in OEP rats 100 micrograms of DA elevated plasma LH at 30 and 90 min while APM induced a significant elevation of plasma LH at 15 min after injection. In OVX rats injection of DA i.p. at a dose of 5 mg/kg-b.w. did not alter plasma LH levels, but a dose of 50 mg/kg-b.w. produced a significant reduction in plasma LH concentration. APM injected i.p. at either 5 or 50 mg/kg-b.w. doses was nearly equally effective in lowering plasma LH and the suppressive effect was significantly greater than with similar doses of DA. A single injection of LH-RH (100 ng in 0.2 ml of 0.9% NaCl) in animals pretreated 15 min earlier with an effective dose of APM (5 mg/kg-b.w.) produced a peak increase in LH titers 15 min after injection. The increment in plasma LH following LH-RH in APM-treated rats was comparable to that in rats which had received saline instead of APM. Prl levels were significantly lowered by each dose of DA and APM in OVX as well as in OEP rats. There was no significant change in plasma FSH titers induced by either drug in any of the experiments. It is concluded that DA may have different actions depending upon the dose and the endocrine state of the animal. Thus, i.v. infusion of low doses of DA in OEP animals or by pulse injection in both OVX and OEP rats can elevate plasma LH by activating the release of LH-RH from the hypothalamus, while large doses of DA in OVX animals may suppress the release of LH-RH.


Minimum adequate levels of personal health care: history and justification. By giving everyone paper rights to health care, Americans may end up doing little better, at much greater cost, and feeling worse about it. The key to providing greater equity may be to find a way of defining the minimum that all should have. Most countries somehow define these limits for publicly provided services from education to cash assistance. But for health care benefits there are no simple limiting criteria--especially when professionals have the exceptional luxury of using whatever resources they choose. A realistic floor requires toughly maintained ceilings.


[Symptoms of difficult interpretation or of unusual practical finding in pneumology. Error in the therapeutic indication in pulmonary diseases. Surprises at the operating table in thoracopulmonary surgery]. The most recent reports on the subject of "Hard to interpret or exceptional pneumopathies. Errors in pneumological symptomatology. Surprises at the operating table" are discussed. Attention is called to innovations in radiological and isotopic technique and to new possibilities for surgical, diagnostic or resolutive action. Personal cases of lung diseases classifiable within the subject are presented and discussed. Cases were part of isolated groups, some observed at the Saint-Feyre Centre in France, and are given as an appendix to the present publication. The intention is to lay stress on the justifiable embarrassment, or otherwise, and the responsibilities of the chest and lung surgeon. Emphasis is laid on the complexity of pulmonary surgical symptomatology.


Low-temperature pasteurisation of human milk. Human milk was pasteurised at 62.5 degrees C for 30 minutes. This treatment resulted in a 99.99 percent drop in the bacterial count of the milk. Only non-pathogenic organisms remained, and both Escherichia coli and Staphylococcus aureus were destroyed. There was some reduction (less than 50 percent) of the activities of specific antibody to E. coli and lactoferrin, but lysozyme was stable and the pasteurised milk remained effective at inhibiting in vitro growth of E. coli.


The observer interaction variable in evaluation of socialising properties of pimozide (Orap). Eighteen chronic, institutionalised patients were randomly assigned to two groups for the purpose of a double blind trial of pimozide (Orap). The results of the study indicated an increase in socialisation, as measured by the Venables scale, for both groups, and no significant difference in this variable between placebo and active preparation groups. It is suggested that greater observer interaction may be responsible for the observed increase in socialisation previously attributed to pimozide.


Host-parasite interactions during pregnancy. The point that host defense against infectious disease is exceedingly complex scarcely needs further emphasis. We have tried to show that pregnancy is a state which has the potential for altering any of the many facets of host defense, and in some instances presented evidence that pregnancy does alter resistance to infection. Some diseases are either more severe during pregnancy or more prevalent during pregnancy, suggesting a softening of the host defenses. However, both monocytic and polymorphonuclear leucocyte phagocytic systems seem to be more active during pregnancy. Transferrin is increased in pregnancy. The immune system in pregnancy is either normal or slightly depressed. A number of other factors have been mentioned for which no information exists as to the effect pregnancy has on them. Despite the information reviewed, it is not possible to say that pregnancy has a net positive or negative effect on host defense; the effect, if any, depends ostensibly on the disease entity. That the host defenses may be somewhat enhanced by pregnancy while susceptibility to certain diseases is increased is paradoxical and serves to underscore the fact that our understanding of host defense in pregnancy is abysmally deficient. Probably no concept is made more clear by this paper than the idea that in the area of host defense in pregnancy there is as much space as any researcher may choose to fill.


Microinvasive carcinoma of the uterine cervix. MICA is the transition stage from intraepithelial growth to clinical invasive cancer. The early invasive growth must be accepted as an indication that the lesion is significant; it may be self-healing but it is objective evidence of progression and invasion remains the most significant indication of malignancy. The subjective changes of CIS, nuclear enlargement, pleomorphism of nuclei, altered nuclear-cytoplasmic ratio, etc., are transcended and the recognition and diagnosis of MICA should be facilitated for the pathologist. Treatment which tends to be conservative is more widely accepted, but the disease can be lethal and the most serious complication appears to be, like CIS, vaginal recurrence.


Oral contraceptive potencies and side effects. A set of empirical results is used to test a model that assigns rankings to oral contraceptives in terms of relative hormonal potencies. The association between the observed incidence of side effects attributed to excess of estrogen and progestin and their incidence as predicted by the model is analyzed. Results of the study show the model to have incorrectly predicted the observed ranking order of symptoms associated with excess estrogen. Further, while the model correctly predicted the oral contraceptive with the highest progestogenic potency (Ovral), the observed ranking order of the other two preparations is shown to be the reverse of that predicted by the model.


Comparison of quinestrol and Tace for relief of postpartum breast discomfort. A single 2-mg dose of quinestrol was demonstrated safe and effective for controlling postpartum lactation and for alleviating breast discomfort. A double-blind comparison to Tace 72 mg every 12 hours for 2 days, and to placebo, was made in 134 patients. The single oral dose of quinestrol showed efficacy equal to the 2-day regimen of Tace. Both were superior to placebo.


The venous drainage of the cervical vertebrae of the ox (Bos taurus L.). The venous drainage of the cervical vertebrae of the ox was studied in 16 animals (Friesland, Jersey and Guernsey cross-breeds), ranging from near full-term foetuses to adults. The extra- and intraosseous veins of the cervical vertebrae are described and illustrated. The nutrient vessels are derived from the vertebral, deep cervical, occipital and internal jugular veins. In addition to the dorsal and ventral external venous plexuses, a lateral external venous plexus is described. The intraosseous veins correspond in the main to the arteries. They are described and illustrated with reference to the available literature. In both young and adult animals anastomoses between epi- and metaphysial vessels are reported. The role of the internal ventral vertebral venous system as a collateral pathway is stressed and comments are made on its possible functional role.


Failure to induce in rabbits effective immunity to a mixed infection of Fusobacterium necrophorum and Corynebacterium pyogenes with a combined bacterin. Failure to induce in rabbits effective immunity to a mixed infection of Fusobacterium necrophorum and Corynebacterium pyogenes with a combined bacterin. Onderstepoort Journal of Veterinary Research, 44 (4), 253--2;6 (1977). Rabbits were immunized with alum-precipitated, oil adjuvant and an untreated bacterin composed of F. necrophorum and C. pyogenes. Immunized rabbits were challenged intradermally with a mixture of F. necrophorum and C. pyrogenes. Immunized rabbits were challenged intradermally with a mixture of F. necorphorum and C. pyrogenes. Initially a low level of initial transient resistance could be demonstrated but a solid immunity could not be established.


[Ultrastructural characteristics of human spermatozoa with elongated head (author's transl)]. In most spermatozoa with elongated head persists an abundant complex membranous system between the post-acromial zone and the post-nuclear region. This system has a periodical structure, the apparently spherical unit of which is 120 A in diameter; it develops between the two sheaths of the nuclear envelope and seems to be continuous with the innermost one. This system can be seen in spermatids during normal spermiogenesis and in most cases it seems to be eliminated either with cytoplasmic droplet or by swelling into the nucleus. Now, a comparable but permanent structure is located all around the head of the normal spermatozoon at the height of the posterior part of the post-acrosomial sheath. This latter system is organized under plasma membrane and only visible on the ultrathin sections made with an appropriate incidence. For some authors it might contribute to maintain the integrity of the head and that of the neck of the spermatozoon and so it might be comparable to a system of septal desmosomes. For other authors periodic structures might favour adherence and fusion of spermatozoon with ovocyte during fertilisation. The particular membranous system that we describe persists often in the spermatozoon with elongated head, by its exuberance it can trouble or delay the fusion of the two gametes at the moment of fertilisation, which might explain the sterility of men bearing this anomaly.


[Cerebrospinal fluid distribution of metampicillin (author's transl)]. In order to avoid other antibiotics which interfere with plasma and CSF level determination of a given antibiotic the authors use a chemical method of established specificity. 15 patients presenting with purulent meningitis were given a standard daily dose of metampicillin and divided into 3 groups of 5. On days 2, 4 and 6 after onset of disease plasma and CSF specimens were taken at respectively 1, 2 or 4 hours following metampicillin I.V. injection according to patient group. All patients were cured between days 7 and 21 of therapy. Tolerance was good. --there was no correlation between dose injected and plasma level of drug,--CSF distribution of metampicillin was good and stayed identical throughout the disease period,--peak CSF drug level was delayed as compared to plasma level, occurring more than 4 hours after I.V. injection of metampicillin.


Heart rate and cardiac function curves. Their dependence on the age of the myocardium and the compliance of the ejection circuit. Isolated, perfused hearts from 16 rats aged from 13 to 17 months were studied to examine the effects of age and of the compliance of the ejection circuit on heart rate and cardiac function curves. Heart rate was found to diminish both with age and with decreasing compliance of the ejection circuit. Cardiac function curves were also substantially modified by these two factors. It was found that old hearts adapted better to a reduced circuit compliance. This suggests that, in the intact animal, changes in the mechanical properties of the heart muscle may be an adjustment to the reduction in arterial compliance which accompanies ageing.


[Immunosuppressive phenomena in experimental tumor systems (author's transl)]. During the growth of spontaneous or chemically-induced tumors in animals, it has been reported that T lymphocytes are present in the spleen and/or the thymus which are able (i) to specifically block tumor rejection by syngeneic immunized animals in in vivo transfer experiments, and (ii) to specifically inhibit the in vitro cell-mediated immune reactions. The relationship between both types of suppressor cells is unclear. On the other hand, mitogen insensitive cells, acting in vitro in a non specific way on normal cell mitosis and cell-mediated cytotoxicity induction, and having macrophage characteristics, are described in viral and non viral tumor bearing hosts as well as in non tumoral animals after hematopoietic hypoplasia. The various suppressor cells types and their possible mechanisms of action are discussed along with soluble factors when present in experimental tumor systems, but the role of these cells in tumor pathogenesis is not yet clear.


[Ribonucleoproteins containing heterogeneous nuclear and messenger cytoplasmic RNA. Characteristics, structure and relations (author's transl)]. Following the study of Spirin, many authors have shown that cytoplasmic messenger RNA and heterogeneous nuclear RNA are complexed with specific proteins to form ribonucleoprotein particles (RNP). These RNP are heterogeneous in size and present a high protein to RNA ratio. Different observations suggest a polymeric structure for nuclear ribonucleoproteins but their protein composition is more clearly complex than that of cytoplasmic ribonucleoproteins. If we accept the following processing: heterogeneous nuclear RNP leads to free cytoplasmic RNP leads to polysomic RNP, the question arises as to what extent proteins originally present in nuclear RNP are conserved. Proteins more or less tightly bound to RNA have different roles: packing and protection of RNA, regulation during gene expression processing.


Use of modified automated polybrene test for screening IgG sensitized RBC in routine laboratory. An automatic method for the screening of RBC sensitized by IgG, using the polybrene reagent was utilized. We compared data drawn from the analysis of the automatic routine test in 4799 patients with the results obtained by the direct anti-IgG antiglobulin test. We give evidence for the highest sensitivity of the polybrene test with a good overlap of the results of two methods.


[Effect on serum aluminium levels of continued ingestion of aluminium gels by patients with chronic renal insufficiency (author's transl)]. Atomic spectrometric absorption without flame allows reliable determination of serum aluminium levels (S.A.). Serum level in 59 normal subjects taking no aluminium gel (A.G.) is 24.3 +/- 8.4 microgram/l. Similar value were observed in 27 patients with renal insufficiency even severe who do not take A.G. Mild elevation of S.A. (40 +/- 12 microgram/l) was observed in 21 dialysed patients receiving no A.G. S.A. elevation is related to the aluminium content of dialysis fluid. A.G. intake in patients with renal insufficiency is followed by increase of S.A. The levels increase in relation with the daily dose of A.G. The highest values are observed among dialysed patients. In 41 dialysed cases A.S. values are between 70 and 600 microgram/l. In 17 patients dialysed for a mean period of 47 months mean serum A.S. is 165 +/- 40 microgram/l. The precise role of aluminium intoxication in the genesis of the dialysis encephalopathy syndrom remains controversial. From a clinical point of view aluminium intoxication should be looked for in any patient with encephalopathy who is taking aluminium gels and/or who is dialysed.


RNA-protein cross-linking in Eschericia coli 30S ribosomal subunits: a method for the direct analysis of the RNA regions involved in the cross-links. A prerequisite for topographical studies on ribosomal subunits involving RNA-protein cross-linking is that the cross-linking sites on the RNA should be determined. Methodology is presented which offers a solution to this problem, using as a test system 30S subunits in which protein S7 has been cross-linked to the 16S RNA by ultraviolet irradiation. The method is based on a gel separation system in the presence of a non-ionic detergent. When a ribonucleoprotein fragment containing RNA-protein cross-links is applied to this system, non-cross-linked protein is removed, and simultaneously the cross-linked RNA-protein complex is separated from non-cross-linked RNA. Oligonucleotide analysis of the S7-RNA complex isolated in this manner showed it to consist of a region of RNA from sections P-A of the 16S RNA. A single characteristic oligonucleotide was absent from this region, and it was tentatively concluded that this missing oligonucleotide contains the actual site of cross-linking.


Ability of modified forms of phenylalanine tRNA to stimulate guanosine pentaphosphate synthesis by the stringent factor-ribosome complex of E. coli. tRNA(Phe) of E. coli, modified at its 4-thiouridine ((4)Srd) and 3-(3-amino-3-carboxypropyl)uridine (nbt(3)Urd) residues, was tested for its ability to induce (p)ppGpp synthesis. The (4)Srd residue was derivatized with the p-azido-phenacyl group, cross-linked to Cyd(13), and the borohydride reduction product of the cross-link was prepared. The nbt(3)Urd residue was derivatized with the N-(4-azido-2-nitrophenyl)glycyl group. None of these derivatives had more than a minor effect on the affinity of the tRNA for the stringent factor-ribosome complex, and no effect at all on the maximum velocity of (p)ppGpp synthesis, either at 2 or 82 mM NH(4)Cl. These two regions of the tRNA which are on opposite faces of the tRNA molecule do not appear to be structurally important for recognition by the stringent factor-ribosome complex. They may provide useful sites, therefore, for the introduction of photoaffinity or fluorescent probes with which to study tRNA-stringent factor recognition.


Perspectives in coronary prevention.

Perspectives in coronary prevention. The seeds of premature coronary heart disease are often sown in childhood and it is the developing arteries of children which are the most susceptible. Paediatricians and all who work with them have the earliest and most promising opportunities for prevention. Coronary protection can be added to the potential advantages of breast feeding and to ensure appropriate fatty acid balance throughout weaning. It is reasonable to accept the strong consensus of opinion on diet reflected in the reports of the eighteen national committees. They are: to reduce total fat intake to 30-35% of the energy, to restrict consumption of saturated fat, cholesterol, sugar, and salt, to increase unrefined carbohydrate and polyunsaturated fat, and to maintain a P/S balance of 1.0-1.5:1. Food is the fundamental coronary risk factor, but others may add insult to injury. Smoking, hypertension, obesity, lack of exercise, and stress, each of which is related to behaviour, may start in childhood. Smoking doubles the overall risk CHD and increases it ten times in males under 45 years old. Good habits, including food preferences and eating patterns learned early, are those most likely to be continued. School meals require and should match revised nutritional education. The co-operation of the food industry is essential and can be anticipated, but it requires a clear lead by paediatricians. The nutritional advice should come from the medical profession. Every contact with children and their parents provides an opportunity for enquiry and giving advice.


Essential fatty acids and the vulnerability of the artery during growth. Essential fatty acids not only control blood lipid levels, but are the precursors of prostaglandins responsible for regulation of platelet aggregation. Dietary deficiency of essential fatty acids may play an important role in the development of coronary heart disease, particularly during the early growth period.


The origins of atherosclerosis.

The origins of atherosclerosis. The presence of atherosclerotic lesions in young adults suggests that early stages of atherogenesis occur during childhood. The relationship of intimal lesions in childhood to fully developed  atherosclerosis is briefly discussed. Factors likely to promote lipid accumulation within the arterial wall and proliferation of connective tissue elements are reviewed with particular emphasis on endothelial cell injury and the possible consequences of this for intimal smooth muscle cell proliferation.


[Usefulness of pancreatic scintilography in clinical diagnosis]. Our experience in pancreatic scintigraphy is presented in this paper. It was used as radioactive substance 75 semetionina. 21 patients with pancreatic pathology and 6 controls constituted the clinical material. The scintigraphy studies showed an homogenous distribution of the radioactive material in the control group. In 7 cases a defect of concentration was showed. The diagnosis of carcinoma were made with surgery in all of them. Similar findings were demonstrated in cases of pancreatic pseudocyst. Irregular distribution was noted in patients with pancreatitis. We concluded that in same instances pancreatic scintigraphy can be useful for differential diagnosis in the clinical field.


Specific binding of tRNAMet to 23S rRNA of Escherichia coli. tRNAMetf binds to 23S rRNA of Escherichia coli, forming a complex with a melting temperature of 75 degrees (in 0.6 M NaCl). The regions within the RNAs that bind to each other have been isolated and their nucleotide sequences have been determined. The interacting region in tRNAMetf is 17 nucleotides long, extending from G5 in the acceptor stem to D21 (D = 5.6-dihydrouridine) in the D loop. The sequence in 23S rRNA is complementary to that sequence except for an extra Up in the middle and allowing a Gp.D base pair. We propose that association of these two sequences may play a role in initiation of protein synthesis by tRNAMetf. In addition, part of this sequence in 23S rRNA may also stabilize tRNA binding to the ribosome during elongation of nascent polypeptides.


"Pretranscriptional capping" in the biosynthesis of cytoplasmic polyhedrosis virus mRNA. The in vitro synthesis of cytoplasmic polyhedrosis virus (CPV) mRNA was previously shown to be dependent upon the presence of the methyl donor S-adenosylmethionine (AdoMet). We now find that the competitive inhibitor of methylation, S-adenosylhomocysteine (AdoHcy), also stimulates CPV mRNA synthesis efficiently, resulting in the synthesis of viral mRNAs containing 5'-terminal GpppA and ppA, rather than m(7)GpppAm as observed with Adomet. In addition to AdoHcy, other AdoMet analogues, including S-adenosylethionine and adenosine, also stimulate CPV mRNA synthesis but to a smaller extent than does AdoHcy or AdoMet. In order to study the relationship between cap formation and mRNA synthesis, nucleoside triphosphates were replaced in the RNA-synthesizing reaction mixture (containing AdoMet) by the corresponding beta,gamma-imido analogues, which are resistant to nucleotide phosphohydrolase, an enzyme involved in cap formation. Although mRNA synthesis occurred in the presence of UMP-pNHp or GMP-pNHp, none was observed when AMP-pNHp was substituted for ATP. Because the ATP molecule that becomes the 5'-terminal nucleotide of CPV mRNA must be cleaved at the beta-gamma position during cap formation, the results suggest that, in this viral transcription system, cap formation is prerequisite to mRNA synthesis-i.e., a "pretranscriptional" event.


Stuttering: high-level mistranslation in animal and bacterial cells. In both bacterial and mammalian cells, extreme starvation for certain amino acids resulted in translational errors that could be easily detected by two-dimensional polyacrylamide gel electrophoresis. On two-dimensional gels, the faulty proteins were shown as a trail of spots with molecular weights similar to those of the authentic proteins but separated in the isoelectric focusing dimension, a phenomenon we call "stuttering." The direction of charge shift depended on the amino acid substituted and could be predicted from misreading of pyrimidines for purines at the third position of the codon. It is expected that this phenomenon will provide a rapid means of measuring the fidelity of the translational machinery from cell type to cell type.


Two chromatographically separable forms of Escherichia coli elongation factor Tu. Two forms of the elongation factor Tu from Escherichia coli have been separated by chromatography on DEAE-Sephadex A50. Obvious chromatographic artifacts have been ruled out by investigation of the elution profile of GDP (a component of the column buffer as well as a ligand of Tu) and by rechromatography of the two components, either separately to give the component peaks or together to give a double peak. The two components have been confirmed as Tu by the poly(uridylic)-dependent polyphenylalanine synthesis and by the distribution of the Tu protein as quantitated from sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Complexes with the elongation factors Ts and G have also been ruled out by activity profiles and by quantitation of the protein distribution, again on gels. The distribution of the two forms between ribosomal and supernatant fractions has been examined: one is bound preferentially to the ribosomal fraction and the other is found in the supernatant fraction. The possible significance of this is discussed.


Tetrakis(acetoxymercuri)methane: a polymetallic reagent for labeling sulfur in nucleic acids. Tetrakis(acetoxymercuri)methane binds to the sulfur atom of 6-thioguanosine and also to the 4-thiouridine residue of Escherichia coli tRNAVal. A 4:1 complex is formed between 6-thioguanosine and tetrakis(acetyoxymercuri)methane. Addition of 3 equivalents of N,N-dimethyl-2-amino-ethanethiol hydrochloride to tetrakis(acetoxymercuri)methane effectively blocks three of the four mercury atoms, rendering the compound monofunctional toward 6-thioguanosine. Under appropriate conditions, tetrakis(acetyoxymercuri)methane, in the presence or absence of N,N-dimethyl-2-amino-ethanethiol hydrochloride, binds to the 4-thiouridine residue in E. coli tRNAVal without forming intermolecular crosslinks. These results suggest that tetrakis(acetoxymercuri)methane will be a useful polymetallic reagent for labeling sulfur sites in polynucleotides. It may also prove to be a valuable reagent for preparing heavy metal derivatives of proteins for x-ray crystallographic study.


Replica plating and in situ enzymatic assay of animal cell colonies established on filter paper. We have developed a simple technique for the replica plating of Chinese hamster ovary (CHO) cells. In this procedure cells are allowed to divide for 8-16 days between the plastic surface of a petri dish and a disc of Whatman no. 50 filter paper, weighted down with glass beads. The culture medium can be replaced when necessary without disturbing the growing colonies. Cells from each developing colony grow into the fibers of the paper, while others remain attached to the plate. The cell colonies transferred to the paper are viable and can be replica plated to a new petri dish with high resolution. In this way several inositol auxotrophs have been identified in a stock of mutagen-treated cells without prior enrichment. Alternatively, the cells on the paper can be rendered permeable in situ, which permits autoradiographic screening for specific biochemical defects, as reported previously for Escherichia coli [Raetz, C. R.H. (1975 Proc. Natl. Acad. Sci. USA 72, 2274-2278]. This technique is applicable to other common cell lines and is especially useful for the identification of single colonies defective in the synthesis of DNA, RNA, protein, and membrane lipids.


Precursors of three exported proteins in Escherichia coli. Arabinose-binding protein, maltose-binding protein, and lambda receptor are synthesized in vitro on membrane-bound polysomes from Escherichia coli. All three proteins are exported from the cytoplasm of E. coli and all three are made in vitro in a form a few thousand daltons larger than the authentic protein. The larger form of arabinose-binding protein is also detected in vivo by pulse labeling. It is concluded that the larger forms of the exported proteins are precursors containing an extra sequence. In contrast to the above, when the intracellular protein elongation factor Tu is synthesized in vitro on free polysomes, it is not detectably larger than the authentic form.


Cell-cell interactions in conjugating Escherichia coli: purification of F pili with biological activity. A mutant of the F sex factor has been isolated that produces more F pili per cell than does the wild-type F factor. F pili have been purified in milligram amounts from cells carrying either the mutant or the wild-type sex factor. The technique described yields F pili of up to 99% purity that can specifically bind to Escherichia coli cells and that bind to and reversibly inactivate male-specific bacteriophages. The F pilin subunit has a molecular weight of 10,750 and purified F pili have a buoyant density of 1,200 g/cm3.


Novel properties of bacterial elongation factor Tu. We have characterized novel properties of the bacterial protein synthesis elongation factor Tu which indicate that it may function as a structural protein. Under appropriate conditions, elongation factor Tu polymerizes to form filaments and, more often, bundles of filaments. It is also the predominant component of a complex of proteins from Escherichia coli that undergoes reversible polymerization in the presence of KCl and MgCl2. In addition, purified elongation factor Tu binds tightly to DNase I in the presence of 10 mM MgCl2. In crude extracts the factor shows no binding in the presence or absence of MgCl2. These properties suggest that elongation factor Tu may have certain actin-like properties and that it has cellular functions other than its role in protein synthesis.


Phenotypically cryptic EcoRI endonuclease activity specified by the ColE1 plasmid. An endonuclease having EcoRI specificity is produced by bacteria containing the ColE1 plasmid. Such bacterial cells fail to express restriction or modification functions in vivo, and phage or plasmid DNA obtained from ColE1-containing cells has unmodified EcoRI sites that are cleaved in vitro by purified EcoRI endonuclease or by enzyme extracted from bacteria that carry ColE1. No EcoRI DNA methylase activity associated with ColE1 has been detected. The finding of phenotypically cryptic ColE1-dependent EcoRI endonuclease activity and the absence of any detectable EcoRI modification system in ColE1-containing cells suggest a control mechanism that appears to prevent functional expression of the ColE1-determined enzyme in vivo.


Evidence for unaltered structure and in vivo assembly of microtubules in transformed cells. By using immunoperoxidase cytochemistry at the light and electron microscopic level, microtubles were visualized in a number of "normal" nontumorigenic and transformed tumorigenic cell lines. A well-defined cytoplasmic microtubule complex exists in both normal and transformed interphase cells. The distribution of this complex closely correlates with the cell shape and the degree of cell spreading. Our data support the idea that these properties determine the pattern of the cytoplasmic microtubule complex, rather than the reverse. Ultrastructural observations of immunoperoxidase-stained tumor cells showed characteristic microtubules in cells in which the microtubules were poorly resolved at the light microscopic level. The results suggest that microtubule assembly and structure are unaltered in transformed cells. However, this conclusion does not exclude the possibility that some of the microtubules' functions might be impaired in a yet-unknown way.


Entrapment of metaphase chromosomes into phospholipid vesicles (lipochromosomes): carrier potential in gene transfer. Transfer of genes from one type of cultured mammalian cell to another by using isolated metaphase chromosomes has been reported with a frequency of one per 10(6)-10(8) cells. Very recently a rate of 16/10(6) has been reported with Chinese hamster ovary cells [Spandidos, D. A. & Siminovitch, L. (1977) Proc. Natl. Acad. Sci. USA 74, 3480-3484]. To increase the frequency of gene transfer, we isolated metaphase chromosomes from hypoxanthine guanine phosphoribosyltransferase (HGPRT) positive cells, entrapped them in liposomes, and fused the lipochromosomes with HGPRT-negative cells. Lipochromosomes were prepared with cholesterol and egg lecithin, using isolated metaphase chromosomes from a mouse-human somatic hybrid cell line (A9/HRBC2); the entire X chromosome, including the HGPRT, glucose-6-phosphate dehydrogenase, and phosphoglycerate kinase genes, is the only recognizable human genetic material retained by the hybrids. Enclosure of the chromosomes in the lipid envelope was confirmed by electron and fluorescence microscopy and differential centrifugation. These lipochromosomes were fused with HGPRT(-) mouse cells (A9) in the presence or absence of polyethylene glycol and transferents were selected in hypoxanthine/aminopterin/thymidine (HAT) medium. The frequency of transfer was at least once per 10(5) cells, a minimum 10-fold improvement over previous methods. The selected cells contained HGPRT activity similar to the amount found in the A9/HRBC2 cells. Starch gel electrophoresis verified that the observed HGPRT activity in the transferents is due to the human enzyme. Human glucose-6-phosphate dehydrogenase and phosphoglycerate kinase were also identified electrophoretically in the transferents. Karyotyping with C and Q banding did not reveal the presence of the whole human X chromosome or a visible extra fragment of a human chromosome associated with the mouse genome. The biochemical data strongly suggest, however, that transfer of a portion of the human X chromosome has occurred in these transferents. Thus, at least three X-linked genes have been transferred from one cell to another with high frequency, using metaphase chromosomes.


Cell adhesion to substrates containing adsorbed or attached IgG. When most mammalian cells are propagated in tissue culture, they are attached to a solid surface. This surface is commonly covered with a layer of serum protein. In this study we looked at the effect of the protein layer on the interaction between the cells and the surface by precoating the surface with various pure protein molecules. We found no differences between surfaces covered with pure protein layers and those covered with serum proteins except when antibody molecules were used. In all cases the cell types used avoided surfaces covered with antibody molecules. Previously, other investigators have established that some cells belonging to the immunology system are attracted to such surfaces.


Isolation and characterization of enterotoxin-deficient mutants of Escherichia coli. The genes controlling the production of two types of enterotoxin of Escherichia coli, one heat-labile (LT) and the other heat-stable (ST), are found on plasmids. The absence of a direct selection procedure has made it difficult to isolate mutants affecting toxin production. However, the availability of a naturally occurring "recombinant" plasmid, carrying genes for LT and ST formation and also for resistance to tetracycline, streptomycin, and sulfonamides, made it possible to use comutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine to enrich for such mutants. We have isolated and characterized 58 LT- mutants and 7 ST- mutants. Among the LT- group we found amber mutants, temperature-sensitive mutants (most of which produce unusually heat-labile LT), and "leaky" mutants with reduced LT activity. The majority of the tested LT- mutants produced immunologically crossreacting material, in most cases in wild-type amounts. Among all 17 of the LT- mutants that could be transferred, the mutation was found to be on the plasmid. In contrast, only one of four transferrable ST- mutants appeared to be a plasmid mutant.


Neurons containing beta-endorphin in rat brain exist separately from those containing enkephalin: immunocytochemical studies. Well-characterized antisera to porcine beta-endorphin were used to localize immunoreactive sites in cryostat sections of formaldehyde-fixed rat brain by indirect immunohistochemistry. Specificity was established by absorption of immune sera with synthetic peptide fragments. Specific immunoreactivity was localized to neuronal perikarya in the basal tuberal hypothalamus, and to varicose nerve fibers which were distributed to midline nuclear areas throughout the diencephalon and anterior pons. These patterns of reactivity were unaffected by preabsorption of the immune sera with millimolar concentrations of Met5- or Leu5-enkephalin or alpha-endorphin. The beta-endorphin immunoreactive structures were morphologically separate from those cells and fibers reported to react with antisera to the enkephalins. One anti-beta-endorphin serum gave additional immunoreactivity with myelinated axons in limbic cortical zones; when absorbed with purified rat myelin basic protein, only the specific patterns of immunoreactivity remained. Thus, discrete beta-endorphin-containing neuronal circuits exist in rat brain and are anatomically distinguishable from enkephalin-containing nerve cell and fiber pathways.


Cooperativity concepts in protein binding models--problems of cooperativity definition, detection, identification and measuring. Cooperativity in protein-ligand binding cannot yet be treated as a urinary phenomenon (neither in investigating nor in modelling), although imaginable to rest upon some few general principles only. Knowledge of atomic details of protein-ligand interactions is still limited. Instead of a physico-chemical explanation and definition of cooperativity, a series of schematic concept has been established throughout the literature. Some dominating or merely observable features are isolated and intermixed with plausibly invented mechanistic details. These cooperativity concepts are put together and partly generalized here. From comparing these concepts with the state of binding theory on the one hand and with the nature of measured binding data on the other, some problems of understanding cooperative effects and of detecting, measuring and identifying them are pointed out. For special cases, suitable criteria and measures are recommended and graphic and mathematical techniques discussed. The limited significance and generality of current cooperativity terms is emphasized. Some different levels of understanding have to be distinguished.


The peripheral hearing mechanism: new biophysical concepts for transduction of the acoustic signal to an electrochemical event. A theory of peripheral function in hearing is proposed. It accounts for temporal discrimination among simultaneously received wave and pulse signals, cochlear analysis of acoustic input, and transduction of acoustic energy into biochemical energy by means of resonance and ion-shuttling involving the tectorial membrane and hair-cell complex. The postulated mechanism is such that it can accommodate the enormous range of intensity accessible to the mammalian ear. Synthesized by the theory are numerous empirical observations and experimental results reported by a broad gamut of disciplines but hitherto not unified. Additional support derives from the characteristics of an artificial "cochlea" and an electret (protein) microphone or "ion exchange microphone" with implications for enzyme conformational change.


Biological ion exchanger resins: XI. Actin in Escherichia coli. The 45,000 molecular weight component of an "actin-like" fraction (A-L fraction) from E. coli is identified as actin. Passage of skeletal muscle myosin through the A-L fraction specifically removes the 45,000 molecular weight band visible on electrophoresis prior to passage. Examination of the myosin after passage exhibits a new band on electrophoresis at 45,000 molecular weight.


[Differential indications for desipramine--results of a controlled multiclinical study]. The antidepressants desipramine and imipramine were compared within the framework of a multiclinical study performed under the conditions of a controlled clinical experiment. There has been found a time-different remission of affective symptoms, which was not detectable for the inhibition of drive. The tachythymoleptic action of desipramine is discussed with reference to these results. Evaluation of the possibility of controlling affects shows different ranges of activity of desipramine and imipramine, with desipramine influencing especially negative psychoenergetic symptoms in the area of drives and emotions and imipramine, restrictive symptoms in addition to differential phenomena of the psychomotor expression.