Selective inhibition of leukocyte adherence in women with breast cancer using a variety of tissue extracts. Leukocyte adherence inhibition (LAI) tests for the assessment of tumor immunity in vitro have been based on the assumption that the adherence of the leukocytes is inhibited by specific interaction with an antigenic tumor extract. However, loss of leukocyte adherence could depend on several non-immunological factors including disease state of the leukocyte donor and the presence of a variety of agents, proteins or tissue extracts. We have studied LAI , therefore, using different species and concentrations of serum protein or tissue extracts. Our results show that leukocytes from patients with a variety of diseases adhere to glass in a rather consistent fashion. High concentrations of serum protein or tissue extract inhibited leukocyte adherence. 39 breast cancer patients and 38 female controls were studied with a total of 23 solubilized extracts from breast carcinoma, other tumor and non-tumor tissues. Breast cancer patients showed selective LAI in the presence of 200 microgram per test tube of several breast carcinoma extracts.


Retroperitoneal lymphoma involving pancreas--complementary radionuclide scan and ultrasonography. Radionuclide emisssion tomography and ultrasonography were obtained on a patient with recurrent epigastric pain. In the pancreatic region an ultrasonic scan revealed a conglomerated mass. Following administration of Se-75 selenomethionine, the multiplane longitudinal tomographic scan demonstrated marked concentration of activity in the region of the pancreas which corresponded to a large defect in the hilus of the liver observed on prior liver-spleen scan with Tc-99m sulfur colloid. Surgery revealed a poorly differentiated histiocytic lymphoma in the retroperitoneum. The radionuclide and echographic scans of the retroperitoneal lymphomas briefly discussed, and their complementary role as a diagnostic tool stressed.


The clinical evaluation of 9-0 and 10-0 monofilament Polyglactin 910 absorbable suture for corneal surgery. The 9-0 or 10-0 monofilament Polyglactin 910 absorbable (Vicryl) suture was utilized in combination with 10-0 nylon suture for 35 patients undergoing corneal surgery in order to evaluate the clinical usefulness of a very fine absorbable suture material. The maintenance of wound approximation, degree of tissue reaction, and rate of absorption were observed along with any adverse effects. Adequate wound closure was maintained in all cases. Little tissue reaction was present in the cornea although a slightly increased healing time was observed for the corneal epithelium in five cases. Absorption was complete within six weeks. The clinical usefulness appears to be in patients who might avoid an additional general anesthetic for suture removal by using the absorbable 10-0 Vicryl for small corneal lacerations and incisions.


Lamellar keratoplasty in the treatment of keratoconus: conectomy. The first 52 eyes of 48 keratoconus patients treated with conectomy and followed for a period of time ranging from 6 to 48 months are included in this study. An average change in the refractive power of the cornea of 10.3 diopters was found after conectomy. The mode for the best corrected visual acuity was 20/30, and the average corneal astigmatism was 3.00 diopters. Photodiagnosis evaluation, microsurgical techniques and instrumentation monofilament nylon, use of the donor cornea minus the endothelium and improved postoperative refractive techniques have combined to make conectomy a reliable and successful form of treatment in keratoconus patients. Both penetrating keratoplasty and conectomy techniques have proven to be successful in the surgical management of keratoconus, and it is the surgeon's responsibility to determine the appropriate approach for the keratoconus patient. Both of these procedures will continue to be refined as ophthalmic technology and surgical skills improve.


Cephalosporium endophthalmitis following penetrating keratoplasty. A 69-year-old male with chronic herpes simplex keratitis underwent penetrating keratoplasty, using cryopreserved tissue. Seven weeks postoperatively the patient developed cephalosporium endophthalmitis. Intensive medical and surgical therapy was unsuccessful and the eye had to be enucleated within three weeks. Cephalosporium species are isolated more often in intraocular infection than from corneal ulceration. Although favorable response to Amphotericin-B and Primaricin has been reported, the final outcome has been unfavorable in most of these cases.


Donor corneal endothelium: slit-lamp examination of buttons in storage medium. The integrity of the corneal endothelium is vital to the maintenance of a clear graft. The slit-lamp examination of the cornea from the endothelial surface, as described, allows the exclusion from transplantation of buttons with obvious endothelial trauma or disease. The use of this method at the Wilmer Institute during the last four years has been part of the preoperative assessment of all corneal donor buttons and has helped to reduce the rate of early graft failure.


A method for ipsilateral rotational autokeratoplasty. Rotational ipsilateral penetrating autokeratoplasty is useful in the treatment of certain nonprogressive corneal scars. The procedure alleviates difficulties with the availability of donor tissue and with graft rejection. A method is presented for determining the maximum clear central corneal area that can be obtained by rotational autokeratoplasty and the most appropriate trephine size and placement. Two dimensions must be obtained either at the slit lamp or from photographs: the diameter of the largest circle of clear cornea and the shortest distance from the edge of this circle (edge of the scar) to the center of the cornea. An illustrative case is presented.


A review of chemotherapeutic plaque control. Of the plaque-control agents studied, it would appear that chlorhexidine is the most suitable agent to prevent plaque accumulation and the development of gingivitis. It also is attractive to speculate on the possibilities of a commercially available mouthwash. A trio of antibiotics--kanamycin, spiramycin, and vancomycin--may prove of value in the treatment of severe gingival and periodontal disease. The ultimate role of xylitol has yet to be determined. Regardless of the agent selected, access to the gingival sulcus region seems critical.


Gutta-percha points of apicoectomy. To push or to pull? A gutta-percha root-filling point placed during apicoectomy may be condensed by the application of pressure to its coronal end or tension to its apical end. Scanning electron microscopy clearly demonstrates the effect that these techniques have on the adaptation of the root filling to the canal. The pressure method would appear to produce the more satisfactory result.


Treatment of phantom limb pain with muscular relaxation training to disrupt the pain--anxiety--tension cycle. Sixteen phantom limb pain patients were treated with a combination of (1) progressive muscle relaxation exercise, (2) feedback of stump and forehead muscle tension, and (3) reassurance about normal phantom sensations and the relationship between anxiety and pain. Fourteen of the patients had chronic pain (average of 12 years) and two were recent amputees (5- and 1-week). At the end of treatment, 8 of the chronic patients showed virtually complete relief from pain, 4 showed significant decreases to a point at which they no longer desired treatment and 2 showed no significant change. Both recent amputees showed complete relief from pain. These changes have been sustained for follow-up period of 6 months to 3 years. The 2 unsuccessful patients did not learn to relax and had strong psychological needs for their pain.


[Experimental lymphocytic choriomeningitis of the mouse. Pathologic, virologic and electric correlations (author's transl)]. The brain electrographic activity of mouse experimental LCM has been systematically compared with the pathology and the virus growth in brain. There is an excellent correlation between anatomic lesions and brain electrographic activity which begins in slow waves followed with electric discharges attendant upon clinical paroxysms. The different records have been described and a physiopathological interpretation of these electroclinical paroxysms is proposed.


[Structure and ultrastructure of osteoblasts and of the osteoid tissue in Paget's disease of bone (author's transl)]. Light and electron microscope studies of 64 biopsies from patients with Paget's bone disease reveal the structure of osteoblasts and osteoid tissue. The osteoblasts observed do not differ morphologically from those described in other bone diseases and the woven bone shows no specificity. These cells are possibly hyperactive and our observations show that such hyperactivity may be consequent to the increased and disorganized resorption of lamellar bone tissue by osteoclasts which are known to be abnormal. Osteoblasts do not appear to play any direct role in the pathogenesis of Paget's bone disease.


[Distribution and correlations of serum uric-acid in two French adult populations : 13,885 men and 6,861 women (author's transl)]. Distributions and correlations of serum uric acid (SUA) were studied in 13.885 men and 6.861 women who were between the ages of 20 and 90. In men and women the distribution of SUA is unimodal. The average SUA value is 628 mg/100 ml (SD : 1,19) IN MEN AND 5,05 MG/100 ML (SD : 1,10) in women. 27% of the men and 4% of the women have a SUA level above 7 mg/100 ml. In men and in women correlations of SUA with an obesity index is strong (r = 0,272; r = 0,311). In men partial correlations between SUA and age, blood pressure, cholesterolemia, glycemia and hemoglobinemia diminish when obesity index is fixed. In women these correlations are stronger and do not vary when obesity index is fixed. In men and women the correlation between SUA and creatininemia is strong and do not vary when obesity index is fixed.


[Eosinophilia and respiratory function in the asthmatic subject (author's transl)]. Total eosinophil count (TEC) was done in 13 normal subjects, in 8 subjects before and 90 mn after a "French" breakfast and in 29 asthmatic patients. The geometric mean is higher (p less than 0,001) in asthmatic than in normal subjects : 304 (231-391) versus 144 (101-197). The breakfast does not interfer with the result of the TEC. In asthmatic subjects, a significant inverse correlation appears (r = 0,57, p less than 0,01) between the logarithm of TEC forced expiratory volume in one second and the quotient : vital capacity. This correlation persists whatever may be the subject's age, the duration of the asthma or age at which he first contracted the illness. Asthma appeared after 40 years in 4 of the subjects : their TEC was higher (p less than 0,01) than in subjects who had become asthmatic before the age of forty. The respiratory function was lowered more in these 4 patients than in others who had been ill for the same time (p less than 0,001). The TEC is not related to results of skin testing with usual inhalant allergens (grass pollen, house dust, cat's or dog's dander) or by result of a provocation test (by inhalation of allergen). Eosinophilia and bronchial obstruction are connected by one (or more) factors that may be inhalant allergens in extrinsec asthma and circulating immune complexes in intrinsec asthma.


[Variations in the phagocytic potency of circulating leukocytes from rats which received a thermal injury. Effects of an immunostimulation with Corynebacterium granulosum (author's transl)]. Experiments were carried out to study in vitro the variations of phagocytic activity of circulating leukocytes from rats which received a thermal injury and were either immunostimulated or not by a single iv injection of C. granulosum. The thermal injury which was applied at about 10 percent of the body surface was of an intermediary type ; it developed towards necrosis before cicatrising on about the 30th day. Phagocytic activity was expressed as the percentage of "active" phagocytes or of those cells which phagocytosed Sta. aureus and S. typhi murium. In not immunostimulated rats, the phagocytic activity was profoundly depressed as a result of the thermal injury ; this was most marked at about 8 days after the thermal injury (close to 38% compared with 80% in control-not-burned-rats). The phagocytic potency or circulating leukocytes from burned and immunostimulated rats corresponded at about the 8th day to that of healthy rats. The reported variations are statistically significant, as assessed by the Student "t" and X2 tests. Our study showed that those rats which were burned in our experimental conditions responded favourably to the immunostimulation. It would be interesting to check whether the use of anaerobic corynebacteria in man could represent an adjunct treatment of those septic complications which are so frequent in severe burns.


[Recent results concerning muscular disorders arising from thyroid gland dysfunction (author's transl)]. The hight number of muscular disorders which may be observed clinically in thyroid dysfunction contrast with the paucity of knowledge concerning the mechanisms of action of the thyroid hormones. Those which have been described allowed the following conclusions to be made : 1) The thyroid hormones simultaneously increase the oxydative phosphorylation in mitochondria and the activation of glycogen phosphorylase. 2) They modify the properties of cell membrane without noticialy changing the cytoplasm (light and electron microscopically). These modifications are concommitant with a reduction in resting membrane potential associated with anomalies of Na+ conductance and Ca+ uptake. 3) The appareance and the number of motor units in each muscle is dependant on the hormonal impregnation. However, these diverses actions do not reveal whether the thyroid hormone receptors are in the muscle or if they act via the intermediary of a neuronal trophic factor.


[The classification of Agrobacterium and Rhizobium phages (author's transl)]. All phages studied are tailed, belong to six morphological groups, and are classified by morphological and serological properties and by physico-chemical parameters of the virion and its nucleic acid. Four species of Agrobacterium and 12 species of Rhizobium phages are described, and their relationship with enterobacteria phages discussed. They include 68 viruses, whereas 60 poorly known phages have not been classified.


[Use of hemolysis in gel in the serodiagnosis of rubella. Comparison with hemagglutination inhibition]. The hemolysis in gel test (HIG) was compared with the hemagglutination inhibition test (HI). This new test is simple and time-sparing since it does not require dilution or serum pre-treatment, and can be measured directly in mm. It is not more expensive than the HI method. It has proved sensitive and is not affected by non specific serum hemagglutination inhibitors and is conclusive whenever HI titers are looked upon with suspicion (titers of less than 1/20). It is therefore well adapted to mass screening of immunity against rubella but in the field of recent infections HI method still has its role to play. Using the HIG test as a reference, we measured the loss of Ig to rubella following the three most commonly employed methods for removal of inhibitors: the mean values of 16 sera were 25% of antibodies lost after kaolin pre-treatment, 62% lost after heparine-Mn-Cl2 procedure 75% lost after dextran-CaCl2 treatment.


[Current data on prolactin].

[Current data on prolactin]. Prolactin has been lately singled-out among the pituitary hormones, and as such the object of considerable research in the past 15 years. The frequency of prolactin secreting adenomes is established now. The responsibility of iatrogenic factors (neuroleptics, oral contraceptives) in some hyperprolactinaemias is a known fact. The study of the inhibiting dopaminergic system was a landmark in the treatment of hyperprolactinaemia. During the recent Nice Congress, some issues remained unsettled on the physiological activities of prolactin. The matter is clearer when it comes to prolactin secretion. In equilibrium between inhibiting and stimulant factors, the secretion is controlled by the CNS, influenced by the hormonal environment, and its timing is the object of a retrocontrol. This is a very instructive pattern in endocrinology.


[Chromatography of urinary amino-acid in bismuth encephalopathy (author's transl)]. The urinary excretion of amino-acid have been determined by ionic exchange chromatography for 10 cases of bismuth encephalopathy and for 15 normal controls. The ninhydrine positive constituant reported by Burns in 5 cases of encephalopathy has not been detected. We are thinking it may be related to the use of a rich amino-acid solution during perfusions. We did not find any significant difference between the urinary excretion of amino-acid average value to the two groups. We found an increase excretion when severe encephalopathy were observed. Separate analysis of individual amino-acid excretion showed the following results: i) average percent of tyrosine excretion is lower in controls as in encephalopathies; ii) among the different ratios tested only SER + THR)/TYR and VAL/TYR are different in the two groups.


[Human lung tissue and serum concentrations of cefradin (author's transl)]. This work was performed on samples from 30 patients requiring lung removal. One dose of 2 g of cefradin was injected intravenously before operation. Titrations of the antibiotic was performed simultaneously on large pieces of the excised lung and on the serum.


Brief case presentation on the nature of psychopathy in Structural Analysis theory. A case study is reported which clearly supports the theory and usefulness of Structural Analysis regarding psychopathy. Psychiatric diagnosis, a computer MMPI report, and clinical impressions constitute the data.


Antibiotic resistance and transferable antibiotica resistance Escherichia coli isolated from calves on a modern farm with therapeutic problems and unsatisfactory management conditions. On a farm with therapeutic problems and unsatisfactory management conditions, the occurrence of antibiotic resistance and transferable antibiotic resistance has been studied in E. coli isolated from calves which were 5 and 30 days old. Strains with resistance to up to seven antibiotics as well as transferable resistance against up to five antibiotics were recorded. On an average, 4.2 strains with different patterns and 4.0 different strains with transferable resistance were isolated from each calf. The corresponding figures previously found for healthy control calves were 1.6 and 1.1 strains, respectively. Resistance and transferable resistance were most common against sulphonamide and penicillin.


[Occurrence and distribution of antibiotic resistant E. coli strains in faeces from young pigs and calves in Denmark]. A comparative study of investigations from 1970 (before the prohibition against therapeutically used antibiotics as food additives for growth promotion) and from 1978 respectively proves that the prevalence of young pigs and calves with resistant E. coli has increased significantly from 61% to 92% and from 69% to 86% (tables I and II). Figures 1 and 2 show the prevalence of young pigs and calves with antibiotic resistant E. coli with resistance determinants towards sulfonamides, tetracycline, streptomycin, ampicillin, chloramphenicol, neomycin and furazolidone. This shows that the prevalence of young pigs with resistance determinants towards sulfonamides, tetracycline, streptomycin, ampicillin, and chloramphenicol has increased significantly from 1970 to 1978. The same facts apply to the calves. However, the increase in tetracycline resistance is not significant. Neomycin resistant E. coli for both young pigs and calves were only found in 1978. Figure 3 shows the distribution of the number of resistance determinants per young pig and calf with resistant E. coli. The figure shows the significant tendency that the pigs and calves investigated contain resistant E. coli with more resistance determinants in 1978 than in 1970. The distribution of R-factors among resistant E. coli seems to be reduced at first sight but a closer examination establishes that this only goes for R-factor mediated sulfonamide resistance (the experimental conditions may account for this). R-factor mediated streptomycin resistance has increased while R-factor mediated tetracycline resistance was at the same level. On the basis of literature the causes and risks of an increased distribution of antibiotic resistant E. coli are discussed.


Arthrosis with special reference to the elbow joint of young rapidly growing dogs. I A review of the literature. The terms arthrosis, arthritis, osteochondrosis, osteochondritis dissecans and dysplasia are defined. A short review of the pathological anatomical changes seen in primary and secondary arthrosis is given, and the anatomy of the elbow is briefly described. The literature concerning elbow lesions leading to arthrosis in young, rapidly growing dogs is reviewed.


Toxin production by Clostridium botulinum type E in fresh herring in relation to the measured oxidation potential (Eh). Recent work has showed high positive oxidation-reduction potential (Eh) values in fresh fish flesh, whereas strongly reducing conditions exist in fish viscera and spoiled fish flesh. The present study has demonstrated that this difference in measured Eh does not significantly influence growth and toxin production by Cl. botulinum type E. In comparison, storage temperature and the spore load in fish markedly influence toxin production. The public health significance of rapid toxin formation and high toxin titers demonstrated in ungutted fish is pointed out.


[Early amniocentesis in twin pregnancies (author's transl)]. Since 1972, we have performed 951 early amniocentesis in 902 pregnant women. There were 19 twin pregnancies, all diamniotic, representing 2.1% of the sample. Diagnosis was always suspected before the amniocentesis. It was confirmed by echography in the 14 cases in which this technique was used. Out of the first 5 cases without echography, we punctured only one sac. In the 14 last cases, the process was successful in 13 cases thanks:--the perfection of echography showing the exact location of the fetuses and the position of the septum--the injection of congo red (12 cases) or methylene blue (2 cases) into the first sac. The indications were as follows: chromosomal aberrations (14 cases) metabolic diseases (1 case), sex-linked disorders (1 cases) neural tube defects (3 cases). No complications due to amniocentesis were observed but three abortions and one fetal death occurred. The reason why is discussed. We have made only one therapeutic abortion.


[Prazosine: a new vasodilator used for treatment of hypertension (author's transl)]. Prazosine, a derivative of quinazoline, acts by relaxing the smooth vascular muscles and blocking postsynaptic alpha-adrenoreceptors. A special protocol was used to treat arterial hypertension in 21 subjects. A small dose (0.5 mg) was given the first day to avoid orthostatic hypotension, then 0.5 mg x 3 on days 2, 3 and 4, followed by 1 mg x 3 on subsequent days. Dosage can be progressively increased up to 30 mg/day. During the first 36 days of treatment, prazosine was given alone. A significant drop in systolic and diastolic arterial pressure was observed in the reclining subject. The effect on orthostatic pressures were nevertheless significantly lower than before initiating treatment. Prazosine induces only a slight increase plasma renin activity. In 9 patients the use of prazosine alone at 3 to 6 mg per day produced not only a drop in arterial pressure but its normalization. In 5 other patients, the administration of prazosine associated with a beta-blocker, acebutolol, induced normalization of arterial pressure. The association of prazosine with a thiazide diuretic was not considered successful. In 5 patients, treatment was interrupted with the appearance of coronary insufficiency, orthostatic hypotension and frequent headaches. Minor side-effects observed in 8 others patients did not require interruption of treatment. Based on the above results, it can be stated that prazosine is an efficient new peripheral vasodilator with good patient tolerance for the treatment of arterial hypertension.


[Critical study of techniques for the detection of "light" rheumatoid factors (author's transl)]. In a number of cases of true rheumatoid arthritis, it is not possible to demonstrate the presence of 19 S "heavy" rheumatoid factors by the Waaler-Rose and globulin latex techniques. However, in some of them, 7 S rheumatoid factors are suspected. Three techniques for the detection of these "light" rheumatoid factors are described and critically evaluated. The authors report their own experience of the immuno-absorption and indirect immunofluorescence technique performed on 156 sera from RA patients. Immuno-absorption is not felt to be a reliable technique on several grounds. Indirect immunofluorescence is of value only in the diagnosis of seronegative rheumatoid arthritis where it provides information in addition to that offered by classical techniques. It is positive in 53.3% of seronegative rheumatoid arthritis sera.


[Plastic surgery using part of the epiploon. Prior vascularisation of the transplant on the dorsal surface of the hand (author's transl)]. The epiploon has proved to be excellent material for reconstructive surgery. The authors present a new technique by which the epiploon may be transplanted into almost any part of the body, using the hand as a vector. The epiploon is implanted beneath the skin covering the hand and acquires a new vascularisation. In a second phase, the epiploon is divided at the point at which it leaves the abdomen. The free epiploon, vascularised by the hand, may then be transplanted into a wide range of areas: head, leg, foot, etc. The epiploic flap formed in this way has many advantages over the Gilles-Filatov tubular skin flap.


Bacteriophage lambda and plasmid vectors, allowing fusion of cloned genes in each of the three translational phases. We have constructed vectors from bacteriophage lambda and from plasmid pBR322 having a single EcoRI restriction site which is immediately downstream from the lac UV5 promotor. Each vector allows the fusion of a cloned gene to the lac Z gene in a different phase relative to the translation initiation codon of the lac Z gene. These vectors were constructed through modification of the initial EcoRI restriction site by S1 endonuclease treatment and then addition of octadeoxyribonucleotides (EcoRI linkers), which shifted the restriction site by 2 or 4 nucleotides. Used in combination these vectors should allow translation of a cloned gene in any one of the three coding phases. The bacteriophages vectors are certified as B2 (EK2) safety level vectors by the French "recombinaison génétique in vitro" committee (D.G.R.S.T.).


Purification of pseudouridylate synthetase I from Salmonella typhimurium. Pseudouridylate synthetase from Salmonella typhimurium has been purified 1,000 fold and is about 90% pure. The enzyme has a molecular weight of 50,000 daltons. In the presence of tRNA there is a change in molecular weight from 50.000 to 100.000. This change does not seem to be due to the formation of a tRNA-enzyme complex but rather to a tRNA induced dimerization. Other properties of the enzyme are described.


The ovalbumin split gene: molecular cloning of Eco RI fragments "c" and "d". The Eco RI fragments "c" and "d" of the ovalbumin gene (1, 2) have been isolated by molecular cloning. Restriction enzyme mapping and electron microscopy have confirmed that the two fragments contain the same ovalbumin mRNA coding sequences. These sequences are split into two regions which have been mapped in fragments "c" and "d". There is no evidence that the ovalbumin mRNA sequences contained in these fragments could be further interrupted. Our results confirm that the presence of Eco RI fragment "d" in some chickens is due to the existence of an allelic variant of the ovalbumin gene which contains an additional Eco RI site within the region corresponding to Eco RI fragment "c". This additional Eco RI site appears to be the main difference between the two alleles. Finally, our results provide a direct demonstration that most of the ovalbumin mRNA sequences are encoded for by Eco RI fragments "a", "b" and "c".


A conserved and unique (AT)-rich segment in yeast mitochondrial DNA. The mtDNA of the cytoplasmic petite mutant of yeast RD1A consists mainly of a perfect head-to-tail repetition of a known sequence of 66 consecutive AT and 2 GC base pairs. We have hybridized complementary RNA made on RD1A mtDNA with the mtDNAs of four different wild-type Saccharomyces strains that differ markedly in restriction fragmentation pattern. The tm's of the four heteroduplexes are identical to the tm of the homoduplex of RD1A mtDNA with complementary RNA of one repeat length. With all four wild-type mtDNAs this complementary RNA hybridizes mainly to a single restriction fragment of about 300 base pairs. This shows the conservation and individuality of at least one (AT)-rich segment in yeast mtDNA. The 300 base pair fragment has been mapped in the vicinity of the oxi-2 locus. The possible role of the (AT)-rich segment in the processing of the primary transcript of this region is discussed.


Primary structure of yeast mitochondrial DNA-coded phenylalanine-tRNA. Mitochondrial tRNAPhe from Saccharomyces cerevisiae isolated by two-dimensional gel electrophoresis was sequenced by fingerprinting uniformly labeled 32 P-tRNA as well as by 5'-end postlabeling techniques. Its sequence was found to be: pG-C-U-U-U-U-A-U-A-G-C-U-U-A-G-D-G-G-D-A-A-A-G-C-m22G-A-U-A-A-A-phi-U-G-A-A-m1G-A-phi-U-U-A-U-U-U-A-C-A-U-G-U-A-G-U-phi-C-G-A-U-U-C-U-C-A-U-U-A-A-G-G-G-C-A-C-C-A. The secondary structure we propose, in order to maximize base pairing in the phiC stem and to allow tertiary interaction between G15 and C46, excludes U50 from base pairing giving a bulge in the phiC stem. No conclusion can be drawn concerning the endosymbiotic theory of mitochondria evolution by comparing the primary structure of mt. tRNAPhe with other sequenced tRNAsPhe. This mt.tRNAPhe lacks some of the structural elements reported to be involved in the yeast cytoplasmic phenylalanyl-tRNA ligase recognition site and cannot be aminoacylated by purified yeast cytoplasmic phenylalanyl-tRNA ligase.


Cloning of nematode tRNA genes and their expression in the frog oocyte. Transfer RNA genes of the nematode Caenorhabditis elegans have been cloned in E. coli using the plasmid Col E1 as vector. The tRNAs coded by 3 hybrid plasmids were purified by hybridisation of labelled nematode tRNA with the plasmid DNAs. Each plasmid appears to code for a single distinct tRNA species. The expression of the cloned DNAs was analysed in vivo by injection into nuclei of Xenopus laevis oocytes. Evidence is presented which suggests that these nematode tRNA genes are accurately transcribed and processed in frog oocytes. Analysis of one hybrid plasmid shows that a 300 base pair DNA fragment contains both the structural gene and those regions required for its transcription in vivo. The results show that cloned eukaryotic DNAs from a heterologous source can be tested for functional gene activity in X. laevis oocytes.


The attenuator of the tryptophan operon in E.coli: rho-mediated release of RNA polymerase from a transcription termination complex in vitro. In vivo, termination of transcription at the attenuator site of the tryptophan (trp) operon of E. coli is influenced by the protein termination factor rho. In vitro, termination does not depend on rho factor, and is very efficient in a purified system consisting only of RNA polymerase, the DNA template, nucleoside triphosphates, and buffer. The extent of termination in this system is unaffected over a wide range of salt and nucleoside triphosphate concentration. However, there is a 10-fold stimulation of trp leader mRNA synthesis if rho factor is present during the transcription reaction. This stimulation occurs only at low molar ratios of polymerase to template, and can be blocked by rifampicin. It is thus most likely due to the recycling of RNA polymerase molecules that have been released from the attenuator site by rho factor. In fact, transcription of the trp leader region  in vitro results in the fomration of a stable termination complex which can be observed on sucrose gradients or by binding to nitrocellulose filters. These data indicate that a major function of rho at the trp attenuator is to release completed transcripts from a pre-formed termination complex, rather than to cause the cessation of elongation.


Nucleotide sequence of gene VII and of a hypothetical gene (IX) in bacteriophage M13. A DNA fragment containing gene VII of bacteriophage M13 has been transcribed and the nucleotide sequence of this 169-nucleotides long transcript was determined by RNA sequencing methods. Additionally, the nucleotide sequence of this gene and parts of its neighbouring genes V and VIII has been determined by the dimethylsulphate-hydrazine technique. The reading frame of gene VII has been established by determining the nucleotide changes occurring in the transcripts of two amber mutants of this gene. From these combined data it is apparent that gene VII is only 99 nucleotides long and is immediately followed by the termination codon UGA. Its initiation codon AUG is separated from gene V by only a single nucleotide. It was noted that between the UGA termination codon of gene VII and the initiation codon of the next gene (gene VIII) there is space for another, hitherto unknown gene. This gene (IX) most probably codes for the small polypeptide ("C-protein") present in mature M13 phage particles.


Detection of yeast ribosomal RNA sequences in E. coli infected with hybrid bacteriophage. Yeast ribosomal DNA was inserted into Escherichia coli on a bacteriophage vector and the host cell RNA was then extracted and analyzed for the presence of yeast ribosomal RNA sequences. RNA complementary to yeast rDNA was detected by hybridization. The transcription of yeast rDNA was found to be independent of phage RNA synthesis and to occur on the same DNA strand as rRNA transcription in yeast. However, hybridization to restriction fragments of yeast rDNA suggested that the RNA species detected in E. coli differ somewhat from authentic yeast rRNA.


2'-Deoxy-2'-fluorouridine-5'-phosphate: an alternative substrate for thymidylate synthetase from Escherichia coli K12. The substrate specificity of 2'-deoxy-2'-substituted uridines and their 5'-phosphates towards thymidylate synthetase from Escherichia coli K12 was investigated. Besides the natural substrate 2'-deoxyuridine-5'-phosphate (dUMP), only 2'-deoxy-2'-fluorouridine-5'-phosphate (dUflMP) was a substrate. The KM of dUflMP is 11 times higher than that of dUMP, while the Vmax values are virtually the same. It is concluded that the size of the 2'-substituent and not its polarity (and the concomitant conformational change) determines substrate specificity of thymidylate synthetase.


Participation of X47-fluorescamine modified E. coli tRNAs in in vitro protein biosynthesis. The reaction of fluorescamine with primary amino groups of tRNAs was investigated. The reagent was attached under mild conditions to the 3'-end of tRNAPhe-C-C-A(3'NH) from yeast and to the minor nucleoside x in E. coli tRNAArg, tRNALys, tRNAMet, tRNAIle and tRNAPhe. The primary aliphatic amino groups of these tRNAs react specifically so that the fluorescamine dye is not attached to the amino groups of the nucleobases. E. coli tRNA species modified on the minor nucleoside X47 can all be aminoacylated. An involvement of the minor modified nucleoside X47 in the tRNA: synthetase interaction is detected. Native tRNALys-C-C-A from E. coli can be phenylalanylated by phenylalanyl-tRNA synthetase from yeast, whereas this is not the case for fluorescamine treated tRNALys-C-C-A(XF47). Pre-tRNAPhe-C-C-A(XF47) forms a ternary complex with the elongation factor Tu:GTP from E. coli, binds enzymatically to the ribosomal A-site and is active in poly U dependent poly Phe synthesis. Fluorescamine-labelled E. coli tRNAs provide new substrates for the study of protein biosynthesis by spectroscopic methods.


Antibodies elicited by defined oligodeoxyribonucleotide sequences. Antibodies to the oligodeoxyribonucleotides d(pT)3, d(pT)4, d(pT)6 and d(pA-A-T-T) were elicited in rabbits by immunization with electrostatic complexes of the respective haptens with methylated bovine serum albumin (MBSA). The antisera were assayed by complement fixation using denatured DNA's of various sources as antigens. The specificities of the antibodies were determined by estimating the inhibition of the complement fixation reaction by defined oligodeoxyribonucleotides. The antibodies were shown to be specific for the sequence of the oligode-oxyribonucleotides or parts of it.


RNA-RNA interactions in the binding site of protein L24 on 23S ribosomal RNA of E. coli. II. Sequence analysis of the interacting fragments. A ribonucleoprotein complex containing several RNA subfragments from the 5' part of 23S RNA was recovered after digestion of the reconstituted complex between 23S RNA and protein L24. It was suggested in the preceding paper that the RNA subfragments 4B, 10A and 9, which are widely separated in the sequence, strongly interact. These subfragments were previously partially sequenced by the classical fingerprinting methods. Their sequences have now been completed with rapid new RNA sequencing methods. We propose here a base-pairing model showing how these subfragments may interact with one another.


The interaction of RNA polymerase and lac repressor with the lac control region. We have examined the interactions of lac repressor and RNA polymerase with the DNA of the lac control region, using a method for direct visualization of the regions of DNA protected by proteins from DNAase attack. The repressor protects the operator essentially as reported by Gilbert and Maxam (1) with some small modifications. However, the evidence reported here concerning the binding of RNA polymerase to the DNA of the promoter mutant UV5 indicates that : 1) the RNA polymerase molecule binds asymmetrically to the promoter DNA, 2) RNA polymerase protects DNA sequences to within a few bases of the CAP binding site, suggesting direct interaction between polymerase and the CAP protein at this site, 3) RNA polymerase still binds to the promoter when repressor is bound to the operator, but fails to form the same extensive complex.


Fluorescence studies of the accessibility of the 3' ends of the ribosomal RNAs in Escherichia coli ribosomes and subunits. The accessibility of the 3'-ends of E. coli in various states has been probed by reaction, after periodate oxidation, with the fluorescent dye proflavine semicarbazide. Free oxidized 16S and 23S rRNAs each react with 2 equivalents of dye. The 23S rRNA is equally reactive in the 50S subunit and the 70S ribosome. The 16S RRNA 3'-end is accessible in the 30S subunit. In the intact 70S particle, periodate can reach the 3'-end of the 16S rRNA but the dye cannot. The 5S rRNA is relatively inaccessible to periodate oxidation or dye reaction in the 70S particle. Dye-labelled 16S rRNA will reconstitute into 30S particles but they are inactive in polypeptide synthesis. This is apparently due to the inability of the 30S particles to form tight complexes with 50S subunits. Iodide quenching studies indicate that the environment of the 3'-end of 16S rRNA in the 30S particle is different from that of the free rRNA.


The specificity of in vitro chromatin transcription. The in vitro transcription of chicken reticulocyte chromatin with E. coli RNA polymerase has been studied in several different ways. The amount of globin RNA sequences has been measured by hybridizing the transcript with globin cDNA; we show that under the proper conditions mercurated transcript RNA can be separated from endogenous RNA on sulfhydryl affinity columns. The amount of globin RNA in the transcript is approximately 20 fold greater than that from erythrocyte chromatin or reticulocyte DNA. Although these data could be used to support the hypothesis of specific transcription, we show by RNA/RNA self hybridization of the transcript (which is at least 50% symmetric) and by hybridization of the transcript to unique DNA in vast RNA excess that the bulk of the chromatin transcript differs little from the transcript of naked DNA. Several explanations for these apparently contradictory results are offered with the most likely one being compatible with random transcription of at least most of the sequences in the chromatin.


Nucleosome packing in chromatin as revealed by nuclease digestion. Chromatin DNA of rat thymus nuclei was cleaved by Serratia marcescens endonculease. The fragments have been examined by polyacrylamide gel electrophoresis under denaturing conditions. The results obtained are interpreted to mean that the internucleosomal DNA is cleaved by the endonuclease into fragments which are multiples of 10 nucleotides. The 10 nucleotide periodicity in fragmentation of internucleosomal DNA is independent of the presence of histone H1 and is likely to be determined by the interaction of this DNA stretch with the histone core of nucleosomes. Such interaction implies a close association between the nucleosomes in the chromatin thread. Quasi-limit chromatin digest (50--55% of DNA hydrolysis) contains undegraded DNA fragments with length of up to 1000 nucleotides or more. A part of this resistant DNA consists of single-stranded fragments or contains single stranded regions. These data may be accounted for by a very compact nucleosome packing in the resistant chromatin in which one of the DNA stands is more accessible to the endonuclease action.


Origin and direction of replication of the bacteriocinogenic plasmid Clo DF13. Cairn's type replicative intermediates of both the wildtype Clo DF13 plasmid and the copy mutant CLO DF13 cop3 were isolated by dye-buoyant density centrifugation. Replicative intermediates were linearized at the HpaI or Sa1I cleavage site, and examined with the electron-microscope. The data show that replication of both the Clo DF13 wild type plasmid and the Clo DF13 cop3 plasmid, initiates at about 2.8% on the physical map. Replication proceeds unindirectionally and counterclockwise on this map.


The interaction of RNA polymerase II from wheat with supercoiled and linear plasmid templates. Interactions between a plant RNA polymerase II and ColE1 based plasmid DNA templates have been studied. Gel electrophoresis indicates that the enzyme binds to both supercoiled and linear species. Using the totally double stranded pMB9/SmaI fragment it is shown that transcription of completely base paired DNA is ten-fold lower than that of denatured or supercoiled plasmid, and reflects the presence of fewer initiation sites. A small proportion of the transcript remains tightly bound to supercoiled templates. 3' oligodeoxycytidine extensions on pMB9/SmaI serve to promote transcription of the linear double stranded form. Using restriction kinetics it is shown that there is a small enhancement of polymerase binding at the pMB9 tetracycline promoter, but that the selectivity of binding at this locus is lower than for the natural bacterial polymerase.


The DNA sequence at the T7 C promoter.

The DNA sequence at the T7 C promoter. Restriction fragments of T7 DNA which selectively bind E. coli RNA polymerase have been identified. These include fragments located close to the beginning of gene 1 where according to Minkley and Pribnow (1973) there is a promoter called C. The smallest fragment from this region which binds RNA polymerase has been sequenced. It contains a promoter-like sequence, at an appropriate distance from the sequence TACA which Minkley and Pribnow suggested should lie at the initiation site of C. RNA synthesised in vitro from these fragments has been sequenced. The RNA sequence corresponds to the sequence to the right of the C promoter. The C promoter differs significantly from the A1 A2 and A3 promoters in sequence. Its structure and position suggest it plays a role in T7 infection.


Sequence of the gene for isoleucine tRNA1 and the surrounding region in a ribosomal RNA operon of Escherichia coli. A DNA fragment of about 2000 base pairs carrying the gene for tRNA(1) (Ile) has been cloned from a total Eco RI endonuclease digest of Escherichia coli DNA. Sequence analyses revealed that about the first 850 base pairs from one end of the fragment contain a nucleotide sequence corresponding to that in the 3'-end of 16S rRNA. The gene for tRNA(Ile) follows the 16S rRNA gene and both genes flank a spacer sequence of 68 base pairs. The spacer region contains a repeating, a hair pin and a symmetrical structure when the sequence is viewed in the single stranded form. A notable hair pin structure is also observed in the region adjacent to the 3'-end of the tRNA(1) (Ile) gene. In addition, about 850 base pairs from the other end of the DNA fragment have been found to contain the nucleotide sequence of the 5'-end of 23S rRNA. The presence of the genes for tRNA(1) (Ile), 16S and 23S rRNA and the hybridization to tRNA(1) (Ala) suggest that this cloned DNA is part of one of the E. coli rRNA operons carrying these two tRNA genes as a spacer.Images


Long double-stranded sequences (dsRNA-B) of nuclear pre-mRNA consist of a few highly abundant classes of sequences: evidence from DNA cloning experiments. DNA preparations from about hundred randomly selected clones containing mouse DNA fragments were screened for the existence of sequences complementary to long double-stranded regions of pre-mRNA able to snap back after melting (dsRNA-B). Many clones containing such sequences were found. The cloned sequences can be subdivided into three groups: (1) those complementary to about a half (at least to 30-40%) of the total dsRNA, designated as sequences B1; (2) those complementary to a part of sequence B1; and (3) sequences complementary to about a quarter (at least to 15%) of the total dsRNA referred to as sequence B2. The size of DNA sequence complementary to dsRNA is about 400 base pairs. Melting experiments with hybrids show that the members of B1 family are very similar if not identical, while the divergence among B2 sequences is higher, but still the number of substitutions does not exceed 9% of bases. Thus, the major part of dsRNA-B consists of a small number of highly abundant sequences as was suggested earlier on the basis of renaturation kinetics /1-3/. Sequences B1 and B2 are represented by many copies in the mouse genome and in pre-mRNA, and many of them probably do not form hairpin-like structures.


Early outbreaks of 'epidemic neuromyasthenia'. The literature of the outbreaks of 'epidemic neuromyasthenia' (ENM) from 1934 to 1955 has been selected to show that the disease affects other people besides young adult females in hospitals and nursing homes. There have been district epidemics, in which the male: female ratio was almost even and several male outbreaks affecting soldiers in barracks. Some outbreaks appear to have been triggered off by an epidemic of poliomyelitis, and the epidemiology of outbreaks in Iceland in 1948 and 1955 suggests that the normal cytopathological effects of poliomyelitis infection have been suppressed by the new disease. In the Durban epidemic (1955) a toxic metabolite was discovered in the urine of many patients and a markedly increased urinary excretion of creatine was noted in two New York State outbreaks. The results of the transmission of an agent from patients with ENM to monkeys suggest that the neurological disorder might be in the form of mild disseminated lesions scattered throughout the nervous system from the brain to peripheral nerves and associated with perivascular round cell infiltration without significant cellular damage. ENM infection was widespread in the North of England in 1955 and associated with lymphocyte abnormalities, which have persisted in some cases for several years. This suggests a continuous organic process.


Viral causes of psychiatric disease.

Viral causes of psychiatric disease. Current evidence on the role of viruses in the causation of psychiatric illness is reviewed. Herpes simplex encephalitis is relatively well defined but a wider role for this virus, particularly in relation to affective disorders, is suggested by some Scandinavian surveys of antibody titres in psychiatric populations. The extent to which influenzal illnesses and infectious mononucleosis may lead to neurotic, and occasional psychotic, episodes is the subject of controversy. The clinical literature is reviewed on the occurrence of encephalitis-like illnesses with prominent psychiatric and behavioural features. It is pointed out that no reliable criterion exists for differentiating these illnesses from such psychiatric syndromes as schizophrenia. It is suggested that neglect of this borderland area, and perhaps preconceptions concerning the features of 'organic' and 'functional' psychiatric disease, may have led to an underestimate of the possible role of viruses in the causation of psychiatric disease.


[Lesional pulmonary edema].

[Lesional pulmonary edema]. The authors having reported all the possible denominations of syndromes of respiratory distress in the adult mention again the main etiologies, stressing on the last ones. They recall afterwards the different clinical, radiological and biological stages of this syndrome. The hemodynamic profile is defined by normal catheterism data and the presence of a true anatomical shunt. On the other hand several hemodynamic variations are possible. The differential diagnosis is essentially cardiac edema. Finally the authors state that treatment is done only by symptomatic therapies: dehydration and assisted ventilation. They do not make use of membrane oxygenator. Assisted ventilation is essential and is mainly based on a good indication and the optimal use of permanent positive pressure.


ATP-dependent renaturation of DNA catalyzed by the recA protein of Escherichia coli. The product of the recA gene of Escherichia coli has been purified to near-homogeneity by a simple three-step procedure. Incubation of the recA protein with complementary single strands of DNA, Mg2+, and ATP results in the rapid formation of large DNA aggregates containing many branched structures. As judged by resistance to S1 nuclease and by electron microscopy, these aggregates contain both duplex and single-stranded regions. The renaturation and aggregation of DNA catalyzed by the recA protein is coupled to the hydrolysis of ATP. The recA protein purified from a cold-sensitive recA mutant does not catalyze DNA renaturation or aggregation at 28 degrees C, but does so at 37 degrees C, a finding which correlates with the recombination defect observed in vivo and indicates that this activity is an intrinsic function of the recA protein. These results suggest that the recA protein plays a specific role in strand transfer during recombination and possibly in postreplication repair of damaged DNA.


Interaction of Escherichia coli RNA polymerase with promoters of several coliphage and plasmid DNAs. The interaction of Escherichia coli RNA polymerase (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) with restriction fragments obtained from various E. coli related DNAs was studied in vitro. The DNAs investigated included several coliphage genomes (T5, lambda, T7, fd) and plasmid DNAs (pML 21, pSC101). By using the nitrocellulose filter binding of the enzyme-DNA complexes, fragment-specific relative rates of complex formation as well as complex stabilities were determined. Promoter-specific relative rates of polymerase binding were derived from fragment-specific rates by taking into account the number of major binding sites for RNA polymerase within several DNAs. Estimates of the stability of complexes formed between some major binding sites and the enzyme were obtained by studying the rate of complex decay. Both characteristics--rate of complex formation and rate of decay--varied widely and independently of each other. The promoters reacting most efficiently with E. coli RNA polymerase were found in the early region of coliphage T5 whereas some promoters in pML 21, or for example, the lambda promoter PI, belong to signals binding the enzyme most slowly. Based on the second-order rate constant determined for the interaction of E. coli RNA polymerase with promoters of phage fd, the fastest promoters characterized so far reacted with rates in the order of 10(8) M-1s-1. The hierarchy of promoters established here is of interest from the viewpoint that promoter strength correlates with the rate of polymerase binding. Among the promoters studied here this rate spans a range of 2 orders of magnitude.


Translational and post-translational cleavage of M13 procoat protein: extracts of both the cytoplasmic and outer membranes of Escherichia coli contain leader peptidase activity. The coat protein of coliphage M13 is an integral protein of the host cytoplasmic membrane at all stages of the infectious cycle. Both in in vivo and DNA-directed in vitro synthesis, it is initially made with an NH2-terminal "leader peptide" of 23 amino acids and is termed procoat. We now report that leader peptidase, and activity which removes the leader peptide and converts procoat to coat, is found in both the inner (cytoplasmic) and outer membrane of Escherichia coli. However, only cytoplasmic membranes will catalyze cleavage of procoat in the absence of detergent. Leader peptidase will cleave procoat either during translation or after protein synthesis is complete.


Kinetics of initiation of bacterial protein synthesis. The 30S initiation complex, formed with the 30S ribosomal subunit, mRNA, and fMet-tRNA, has been shown by kinetic analysis with limiting concentrations of Escherichia coli ribosomes to be an obligatory intermediate in the formation of the 70S initiation complex. The formation of the 70S initiation complex began with an induction period and was proportional to the concentration of the 30S complex, which rapidly rose to a peak. The entire time course of the sequential pseudo-first-order, second-order reaction was reproduced accurately by the overall rate expression, in which we used rate constants that were determined by carrying out 30S and 70S complex formation separately. By using limiting concentrations of mRNA, we showed that phage MS2 RNA contained no specific signal that enhanced its rate of 30S complex formation with E. coli ribosomes and initiation factors; the pseudo-first-order rate constants obtained with poly(A3C9G1U1), poly(C15G1U4), and poly(G1U3) were 12-45 times higher than that with MS2 RNA. The observation that the rate constants for binding of fMet-tRNA and AcPhe-tRNA with a given synthetic RNA were comparable indicated that the initiator codon is recognized only indirectly through the initiator tRNA.


Identification of a methyl-accepting chemotaxis protein for the ribose and galactose chemoreceptors of Escherichia coli. The ribose and galactose chemoreceptors of Escherichia coli have previously been identified as the ribose- and galactose-binding proteins. We now report the discovery of a methyl-accepting chemotaxis protein that functions in the transfer of receptor signals from these two binding proteins to the flagella. This protein is distinct from previously described methyl-accepting chemotaxis proteins. Its level of methylation is influenced by D-ribose, D-galactose, and certain structural analogues of them. This methyl-accepting protein is required for chemotaxis toward those attractants; mutants in the trg gene, which do not methylate this protein, are devoid of taxis toward D-ribose, D-galactose, and their analogues. In addition, methylation of the methyl-accepting protein in response to each of these attractants requires the appropriate binding protein. The binding protein's chemoreceptor function is required for such methylation, but its transport activity is not. Because the function of this methyl-accepting chemotaxis protein involves two of the best-characterized chemoreceptors, the discovery of this protein represents a promising base for further study of the linkage between chemoreceptors and flagella in bacteria.


Evidence for transcriptional regulation of orotidine-5'-phosphate decarboxylase in yeast by hybridization of mRNA to the yeast structural gene cloned in Escherichia coli. From a large population of strains of Escherichia coli carrying shear fragments of yeast (Saccharomyces cerevisiae) DNA attached by in vitro recombination to the plasmid vector pMB9, two hybrid plasmids were selected that relieve the pyrimidine requirement of nonreverting pyrF mutants of E. coli. An 1100-base-pair DNA fragment common to the two complementing plasmids was recloned into another plasmid vector, pBR322; these new hybrids retained the ability to specify orotidine-5'-phosphate decarboxylase (orotidine-5'-phosphate carboxy-lyase, EC 4.1.1.23) synthesis in E. coli. Evidence is presented that this common fragment is yeast DNA and thus apparently carried the structural information for yeast orotidine-5'-phosphate decarboxylase, the product of yeast gene ura3. A hybrid plasmid containing the 1100-base-pair fragment was used to measure levels of putative ura3 mRNA from yeast cultures labeled with [3H]adenine, ura3 mRNA was unstable with an apparent half-life of 10.5 min. Under different circumstances previously shown to alter the level of orotidine-5'-phosphate decarboxylase in yeast, a coordinate variation in proportion of labeled RNA complementary to the hybrid plasmid was found. These data support the hypothesis that regulation of the ura3 gene in yeast is at the level of transcription.


Phase variation in Salmonella: genetic analysis of a recombinational switch. The alternative expression of Salmonella genes H1 and H2, which specify different flagellar antigens, results in the oscillation of phenotype known as phase variation. This alternation is controlled by the inversion of an 800-base-pair sequence of DNA adjacent to, or including part of, the H2 gene. The invertable region was presumed to regulate the function of a promoter and to include specific sites at which a recombinational event, resulting in the inversion, could occur. Here we report genetic manipulations of hybrid lambda phage carrying the H2 gene that were used to define the H2 promoter region and the recombinational sites. The H2 gene fragment was inserted on a hybrid lambda phage next to the cheW gene, which lacked a promoter element. In the resulting fusion, cheW gene activity was restored, the expression of the H2 and cheW genes was controlled coordinately by the inversion, and the polarity of transcription and location of the H2 gene could be determined. Evidence from this type of gene fusion suggested that the H2 gene promoter is included in the inversion region. Hybrid H2 phage were constructed that contained substitutions for regions of the H2 gene. In contrast to hybrid lambda containing the H2 gene, which alternate between "on" and "off" states, several substituted lambdaH2 were fixed in the "on" state. A site necessary for the recombinational event must have been removed in these fixed lambdaH2.


Yeast ribosomal DNA genes are located on chromosome XII. Two lines of experimental evidence indicate that the repeating ribosomal DNA (rDNA) genes of the yeast Saccharomyces cerevisiae are located on chromosome XII. First, the rDNA genes are linked mitotically to genes that have been previously mapped to chromosome XII. Second, yeast strains that have two copies of the chromosome containing the rDNA genes in every strain examined also have two copies of chromosome XII; this is not true for the other yeast chromosomes. These data also establish that in mitosis most of the rDNA genes in yeast are not extrachromosomal.


Transplantation of cultured bovine corneal endothelial cells to rabbit cornea: clinical implications for human studies. Rabbit corneas denuded of their endothelium were coated with bovine corneal endothelial cells (from steers) previously maintained in tissue culture for short (20 generations) or prolonged (200 generations) periods. When grafted back into female rabbits, the corneal buttons remained clear and showed no edema. In contrast, denuded corneas coated with bovine keratocytes and grafted into rabbits became opaque and edematous within 7 days and remained so thereafter. Bovine corneal endothelial cells of the grafted corneas, which had remained clear for over 100 days, proliferated actively when put back into tissue culture. The corneal endothelial cells of the graft were characteristic of the male (XY). The chromosome number of the endothelium of the recipient rabbit was 2n = 44 with sex chromosomes characteristic of the female (XX). Results of the karyotype analysis show that there was no invasion of the corneal button by the recipient endothelium and, conversely, no invasion of the recipient endothelium by the endothelium on the corneal button. These results demonstrate that cultured corneal endothelial cells remain functional in vitro and can replace a damaged or nonfunctional endothelium in vivo.


Thermosensory transduction in Escherichia coli: inhibition of the thermoresponse by L-serine. Information processing of the thermoresponse in Escherichia coli was compared with that of the chemoresponse. Competition experiments between various chemical stimuli and the thermal stimulus showed that only L-serine was a potent inhibitor of the thermosensory transduction. The concentration of L-serine necessary for complete inhibition of the thermoresponse was about 0.1 mM. L-Serine at this concentration did not inhibit chemoresponses to many amino acids. Pleiotropic aspartate-taxis mutants (tar) showed normal thermoresponse but pleiotropic serine-taxis mutants (tsr) showed decreased or almost no thermoresponse. These results suggest that the thermosensory transducing system in E. coli has an intimate interaction with the chemosensory transducing pathway specific for L-serine. A simple model for the thermosensory transduction is discussed.


Nucleotide sequence of Escherichia coli K-12 replication origin. From subfragments of an EcoRI fragment (9 kilobase pairs) that contained the replication origin of the Escherichia coli chromosome and had been cloned as a recombinant with a nonreplicating DNA fragment coding for ampicillin resistance, small derivative plasmids were constructed. The smallest of these, pTSO151, contained a segment of 463 base pairs as the chromosomal component. Another plasmid, pSY134, constructed from BamHI digests of the EcoRI fragment and mini-F(pMF21), contained a region of 422 base pairs identical with a corresponding region in pTSO151. We conclude that the replication origin of E. coli chromosome is located within this 422-base-pair segment. The nucleotide sequence of this segment is presented.


Nucleotide sequence of the origin of replication of the Escherichia coli K-12 chromosome. The origin of replication, oriC, of the Escherichia coli chromosome was mapped within a DNA segment of 422 base pairs. The nucleotide sequence of this segment was determined. The source of DNA for the sequence analysis was a minichromosome constructed in vivo, consisting exclusively of chromosomal DNA and a minichromosome constructed by cloning in vitro. The nucleotide sequence of the replication origin is characterized by a high degree of repetitiveness due to both inverted and direct repeats. Sequence homologies were found between portions of the replication origins of E. coli and phages lambda and G4. This suggests similarities in some steps in the initiation of replication of the different replicons.


Immunoprecipitation and partial characterization of diphtheria toxin-binding glycoproteins from surface of guinea pig cells. 125I-Labeled membrane glycoproteins that specifically interact with diphtheria toxin and CRM197 protein--but not with diphtheria toxoid, fragment A of diphtheria toxin, or cholera toxin--were detected by use of the lactoperoxidase labeling technique followed by an immunoprecipitation system. These glycoproteins, which adhere to lentil lectin-Sepharose columns, are present on the surface of diphtheria toxin-sensitive guinea pig lymph node cells but are completely lacking on the surface of diphtheria toxin-resistant mouse L cells. The major 125I-labeled glycoprotein that interacts with diphtheria toxin exhibits anomalous behavior, characteristic of glycoproteins, when analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. This demonstration of the biochemical nature of specific diphtheria toxin binding membrane components raises the possibility that the detected components are diphtheria toxin receptors.


Origin and direction of DNA replication of plasmid RSF1030. An in vitro replication system has been used to study the origin and direction of replication of the covalently closed, circular DNA of plasmid RSF1030, a nonconjugative R factor. We have enriched for replicative intermediates in these studies either by isolating them on the basis of their unique structure or by limiting the extent of synthesis in the in vitro system. Circular molecules that have replicated to various extents migrate to characteristic positions in agarose gels, thus providing a rapid and efficient method for isolating partially replicated forms. Alternatively, replicative intermediates can be isolated directly from reaction mixtures that contain dideoxyTTP (ddTTP), a compound that limits the average extent of synthesis in vitro. Electron microscopic analysis of such intermediates linearized with either Hpa I or BamHI indicates that RSF1030 replicates in vitro from a unique origin located 70% from one end of Hpa I-cleaved molecules and 47% from the BamHI site. The unidirectional mode of replication has been confirmed by the order in which the six HincII fragments of RSF1030 DNA are labeled in vitro when synthesis is limited to various extents with ddTTP. Finally, a physical map of RSF1030 has been constructed using the restriction endonucleases BamHI, Hpa I, and HincII, and the origin and direction of replication have been defined relative to the map.


A general method for maximizing the expression of a cloned gene. We present a method, utilizing a combination of restriction endonuclease cleavage and digestion with Escherichia coli exonuclease III and Aspergillus orizae nuclease S1, that allows us to position a restriction fragment bearing the promoter of the lacZ gene of E. coli at virtually any distance in front of any cloned gene. In particular, we have used this method to examine the effect on protein production of gene-promoter separation for the cro gene of phage lambda and to produce plasmids that, upon transformation into appropriate E. coli hosts, direct the synthesis of up to 190,000 cro protein monomers per cell.


Cranio-orbital correction for massive enlargement of the cranial vault. A case is reported in which an immense cranial vault was reduced as part of the rehabilitation of a patient with severe hydrocephalus who had preservation of the intellect. This patient was selected carefully, and we do not advocate such procedures on every hydrocephalic. This patient was recumbent and bedridden prior to the procedure because of the size and weight of his head, but he was able to move freely in a wheelchair and attend a special school after the reduction of the skull.


Inhibition of myofibroblasts by skin grafts. The myofibroblast population was studied by electron microscopy in rat wounds healing by (1) contraction of granulation tissue, (2) by coverage with split-skin grafts, and (3) by coverage with full-thickness skin grafts. In all 3 types of wounds, myofibroblasts appeared early and reached a peak number at two weeks after wounding. At this time, 40 to 50 percent of the wound fibroblasts had myofibroblast characteristics. The granulating wounds contracted rapidly and completely, and had long persistence of myofibroblasts. Split-skin grafted wounds contracted less and had a more rapid decrease in myofibroblasts. The wounds covered with full thickness skin grafts had a minimum of contraction with a very rapid decrease in the number of myofibroblasts until by 4 weeks no myofibroblasts were present. Full-thickness skin grafts thus appeared to influence contracting wounds not by preventing the formation of myofibroblasts, but by speeding up completion of their life cycle.


A new technique for skin grafting in avascular areas: a preliminary report. A 3 X 3 cm, buried, split-skin graft will survive on an avascular bed if it is temporarily covered with a skin flap. Four cases of secondary ear reconstruction are presented, in which this technique was effectively used.


Pilar tumors.

Pilar tumors. We present 5 cases of pilar tumor, and we review the controversy over whether this tumor has a malignant potential. We feel the correct treatment is excision deep to galea, with a one to two cm margin of normal scalp. Presented with a pathology report of "pilar tumor" on a "shelled out" or ruptured sebaceous cyst, we feel the correct treatment is complete excision of the previous scar, going deep to the galea and taking a one to two cm margin of surrounding normal scalp.


Skin abnormalities of the back in diastematomyelia. The presence of congenital skin abnormalities on the back may be associated with a serious underlying spinal anomaly, diastematomyelia. The significance of the progressive development of neurological deficits, due to the presence of a bony or cartilaginous spur in the spinal cord, is stressed. An awareness of this condition should lead to an early diagnosis with a neurological evaluation and, if necessary, prophylactic surgery before irreversible nerve damage develops.


Study of effects of porcine skin and bovine dermis on the healing of split-skin graft donor sites in humans. A study was undertaken of the effects of heterografts (lyophilized porcine skin or bovine dermis) on the healing of split-skin graft donor sites. When compared with a petrolatum gauze dressing, no advantages were found. Some disadvantages developed, however, which led us to discontinue their use.


Study of the delay phenomenon in axial pattern flaps in pigs. A technique, using radioactively-tagged microspheres to measure the blood flow in delayed axial pattern flaps in the pig, is presented. The blood flow was significantly (p less than 0.01) increased in the delayed portion of these flaps, reaching maximal levels after 4 to 12 days of delay. Also, the blood flow to these flaps correlated with tissue survival during the first week after the delay (p less than 0.001).


Problems in the assessment of analyzability. As additional studies of assessment of analyzability have been reported, research has proven very difficult and provided little clarification. This paper reviews the literature, particularly of the last twenty-five years, from the viewpoint of identifying the nature of the problems in developing useful methods of study. Some approaches to these problems, which might provide increased understanding as well as a clearer definition of some inherent limitations, are discussed.


Patterns and issues in multiaxial psychiatric diagnosis. The multiaxial diagnostic model, consisting in the systematic formulation of a patient's condition according to separate clinical variables of aspects, is receiving increasing attention in several parts of the world. This innovative model promises to improve diagnostic reliability and validity and involves many methodological challenges. This paper reviews patterns and issues in the conceptualization of axial content, number and organization of axes, dimensional versus categorical scaling, and evaluation and further development of multiaxial systems.


The clinical evaluation of obsessionality: a development of the Leyton Obsessional Inventory. The Leyton Obessional Inventory gives both an indication of the range of obsessional symptoms present and the degree of resistance and interference associated with each symptom. A new method is described in which the covariation of resistance and interference is represented in the form of a matrix. The results, using this method, can give a unique picture of the quality of the patient's symptoms from the clinical standpoint and provide useful guidelines for treatment and follow up. Automatic data-provessing is offered for the convenience of clinicians and researchers wishing to utilize the test in this form.


Schizo-affective psychosis: definitions and incidence. Eight definitions of schizo-affective psychosis have been compared in a sample of psychotic first admissions. Their mutual concordance is very low (mean 0.19) showing that there is very poor agreement about the meaning of the term 'schizo-affective' at present. Ten patients (4.5% of admissions and 8% of psychotic admissions within the age group studied) satisfied 3 definitions, a figure which demonstrates the numerical importance of this group of unclassified mental disorders.


[A miniaturized method for some biochemical tests of bacteric identification (author's transl)]. A miniaturized method for some biochemical tests of bacteric identification was presented. Results of quality control and comparisons with traditional method were reported.


[The normal and pathological proteic, immunological and cytoimmunological features of synovial fluid (author's transl)]. The A. describes the normal pathological proteic, immunological and cito-immunological features of synovial fluid. According to these features, the synovial fluid have been classified into 3 groups: a) non-inflammatory, animmune fluids (without pathological immunitary features); b) inflammatory, normoimmune fluids (having immunological features with normal physiopathological reactions); c) inflammatory, iperimmune-disimmune fluids (with complex and abnormal immunological features). Histologically, they correspond to: a) non flogistic artrosynovitis (synoviosis, simple synovitis); b) inflammatory arthrosynovitis without tipical features (they are also described as cronic aspecific arthorosynovitis) or characterized by pathohomonic features (tubercolar synovitis, gouty synovitis. ecc.); c) rheumatoid arthrosynovitis (and inflammatory arthrosinovitis rheumatoid like). There is a generical correlation between histological aspects of groups a) and b) and humoral values of synovial fluid. Tipical correlations have been found between histological features of RA and humoral values of synovial fluid. These are expression of individual immunological reactivity of tissues in presence of rheumatoid factors. The tissutal reactivity can subiecy even to endogenous or exogenous causes.


Lower respiratory infections: how infants differ from adults. Largely for anatomic reasons, the peripheral airways of infants are more susceptible to inflammatory narrowing than are those of adults. When infection occurs in the lower respiratory tract of an infant, the primary effect is likely to be on the smaller airways, not the alveoli. The results are airtrapping and atelectasis. This airway obstruction often causes severe respiratory embarrassment. It is recognized on chest films by generalized hyperinflation and irregularity of aeration. Small airway obstruction is a common and important manifestation of lower respiratory infection in infancy. True consolidative pneumonia is much less frequent.


Knowledge-based computer-assisted diagnosis of chest radiographs. The computer can produce structured radiologic content which can potentially keep the radiologists current in radiology literature. As the radiologist continues to make observations and uses the available information, he has at his fingertips with the computer the current information to offer appropriate differential diagnosis and suggest appropriate patient follow up. The computer allows the radiologist to learn and grow rather than guess and hope.


Hysterosalpingography with Amipaque.

Hysterosalpingography with Amipaque. The authors report their initial experience with Amipaque (metrizamide) in hysterosalpingography. Amipaque was compared to Isopaque Cerebral in 37 patients, using a double-blind design. Excellent radiographs were obtained with both agents. No statistically significant difference in discomfort and pain was found up to 24 hours after the procedure. However, the aftereffects indicate that Amipaque might be less irritating to the pelvic peritoneal cavity.


Computed tomographic evaluation of abdominal and pelvic abscesses. The CT characteristics of abdominal and pelvic abscesses in 29 patients were analyzed. The pathological development of an abscess as it relates to the CT appearance is discussed. Findings such as low-density areas within a soft-tissue mass or a definable wall or rim, while seen in abscesses, can be seen in other pathological entities as well, such as hematomas, noninfected inflammatory masses, and cystic or necrotic tumors. The most specific CT sign of an abscess was extraluminal gas, seen in 38% of patients.


Radiobiological considerations in the use of total-body irradiation for bone-marrow transplantation. On radiobiological grounds, a therapeutic advantage should result when total body irradiation (TBI) in preparation for bone-marrow engraftment is given as a fractionated course, rather than as a single exposure at logistically reasonable dose rates. This is because cells of hemopoietic origin in general show less capacity for repair of sublethal radiation injury than do cells of other organs. Dose-limiting lung tolerance, in the context of fractionated TBI, is estimated to be at least 12 Gy (without correction) in increments of 2 Gy regardless of dose rate. A practical method for delivering TBI using a high-energy linear accelerator is described.


Alteration of perirenal fat secondary to diffuse retroperitoneal infiltration. Inflammatory effusions and diffuse neoplasia in the fatty retroperitoneal space, which can alter the perirenal fat, can be recognized radiographically because of density differences. The opacity of fluid and tumor accentuates the remaining fat which conforms to the renal contour. This perirenal fatty border appears as a lucent strip when the perirenal fat is not violated and as abnormal perirenal streakiness when the perirenal fat is infiltrated by fluid or tumor. Six cases are described.


[Security at work in terms of risk factors (author's transl)]. Accident epidemiology aims at determining those factors which are associated with an increased risk. Here accidents at work are considered in which any given situation involves: one or many individuals (I); one or many tasks (T); one or many machines or production tools (M); an environment (E). Eight factors are proposed for each of which one of the above components is dominant. Each factor is defined and examples are given. In addition, where applicable, the following are given: subfactors; references to studies which demonstrate the association between risk and factor; one or several possible action mechanisms; proposals enabling a quantitative evaluation to be made for statistical purposes; suggestions for prevention. The factors are: Individual disposition (I) or liability. Worker's inexperience (I). Stress (T) imposed on the worker. Recovery (T) (an exceptional task must be performed in order to regain normal work conditions). Catachresis (M) (a tool is used for an unusual purpose or a machine is required to exceed normal work load). Material wear (M) or damage. Interference (E) between partially independent processes. Insufficient information (E) concerning the state of the system.


[Bactericidal power's assessment of eight antiseptic products intended to surgeon's hand-washing (author's transl)]. A standard hand-washing technique was used in order to test the relative effectiveness of eight both detergent and alcoholic preparations intended to surgeon's hands disinfection. A single four or seven minutes washing with alcoholic solutions was shown to eliminate a much larger proportion of the skin flora than could be removed by a single four or seven minutes hand-washing with detergent antiseptic preparations. Authors have also determined effect of wearing surgical rubber gloves after skin disinfection and compared viable bacterial counts in hand washings immediately after the antiseptic treatment and when gloves had been worn for one hour.


[Applications and limitations of immunological techniques in the sero-epidemiological analysis of parasitic risk (author's transl)]. In order to be applicable to sero-epidemiology, serological reactions must lend themselves to micro-techniques and automation. Their results, notably concerning malaria, sleeping sickness, amoebiasis, schistosomiasis and filariasis, complement those of direct parasitological examination. Serology is often more accurate, but is also more costly and should be reserved for those cases in which other analytical methods are either impossible or too undependable (low transmission level). Serological methods generally involve little risk or false negativity, but they can be falsely positive and improvement of the specificity of available testing procedures is at present one of the major technological problems of parasitic sero-epidemiology.


BCG in the immunotherapy of non-Hodgkin's malignant lymphomas: preliminary results of a controlled trial. Thirty-three patients exhibiting non-Hodgkin's malignant lymphoma with one or more criteria of poor prognosis and in whom complete remission had been induced by an association of chemo + radio + chemotherapy were randomized to either receive BCG or no further treatment. The present results indicate that BCG may be useful to maintain remission in about one-third of the patients, but these results are not yet significant.


Preliminary results of chemoradiotherapy followed (or not ) by active immunotherapy of stage III and IV lymphosarcoma and reticulosarcoma: correlation of the results with WHO categorization. One hundred and one patients with advanced (stage III and IV) LS and RS at the first presentation of the disease or on relapse were treated with a regimen combining initial chemotherapy, complementary radiotherapy on "icebergs," supplementary chemotherapy, and finally, active immunotherapy. The overall complete remission rate was about 79% for LS and 73% for RS. About 50% of the patients were still in remission for both diseases after 2 years; 60% with LS were still alive after 2 years and 44% with Rs. This study shows the useful prognostic value of the WHO classification for LS and RS: the prognosis of prolymphocytic (centrofollicular) LS is far better than that of the lymphoblastic type, which is itself better than that of the very poor prognostic immunoblastic type. The prognosis of RS is intermediate between that of the best prognostic type and that of the poorest prognostic type of LS.


Cellular renewal kinetics of malignant non-Hodgkin's lymphomas. Although the DNA synthesis times of the dividing NHL cell types were found to be within the normal range (7--12 h), the generation times of these neoplastic lymphocytes seem to be prolonged. However, even with a normal percentage of proliferating lymphoma cells (=growth fraction), the total number of mitotically active neoplastic lymphocytes is considerably increased in each NHL due to extensive enlargement of the total cellularity of each patient's lymphatic system. Therefore, in each NHL patient, the total cellularity of each patients' lymphatic system. Therefore, in each NHL patient, the total number of newly produced lymphoma cells is significantly increased. According to the Kiel classification of the NHL, the NHL of low-grade malignancy are considered to be characterized by the proliferative constellation of an enhanced cell production associated with reduced or normal cell death rates, whereas in the NHL of high-grade malignancy, increased cell death rates seem to be overcompensated by even higher cell renewal rates. These differences in the cellular proliferation kinetics of the NHL are supposed to be of higher prognostic and clinical significance than their B- or T-cell properties.


Determination of cardiac output in the mouse. A technique is described for determination of cardiac output in the mouse. The method is basically a tracer dilution technique using 86-rubidium as soluble indicator, where a microsampler is used for blood collection and in which the gamma function fitting is applied for area determination.


The possibility of identification of oligodendrocyte-myelin sheath processes in the white matter of rats. When myelination is completed it is no longer possible to see with the EM the continuity of myelin sheath with the oligodendroglial processes. An ultrastructural study has been therefore carried out of the unmyelinated of the white matter to see whether it might be possible to recognize the presence of such continuity. The following were considered: 1) unmyelinated fibres in bundles, 2) astroglial processes, 3) large oligodendroglial processes, 4) tongues, 5) "fibre-like" processes (including tubulus and filamentes which are partly identifiable as either unmyelinated fibres or thin oligondendroglial processes). In addition to morphology, quantitative aspects were also considered such as area of section of each process and number of tubules and filamentes present in each section. No substantial quantitative differences were found between "fibre-like" processes and unmyelinated fibres in bundles. These findings failed to show any morphological evidence of connections between myelin sheaths and oligodendroglial processes. This however still possible that the oligodendroglial processes are so few in number in comparison with the unmyelinated fibers that their statistical contribution is negligeable and that no substantial error is made in identifying all "fibre-like" processes as unmyelinated fibres.


[Study of articular cartilage in arthrosis. Histological and biochemical data]. Arthrosis is characterized by destructive lesions of cartilage occuring in the pressure areas of the articular surfaces and leading to the denudation and erosion of the sub-chondral bone. At a further stage these lesions are distinguished from cartilage lesions due to aging and correspond to the progressive erosion of a tissue whose cells present mainly signs of degeneration and whose tissue contains few proteoglycans. The histologic appearance of the initial lesions of the cartilage remains a matter of controversy and ambiguity. Some look like fissures in relatively healthy tissues where the cells show signs of proliferation and hyperactivity. Others correspond to the fragmentation of tissues whose cells and connective tissues are severely damaged. The first biochemical changes of cartilage in arthrosis associate a disorder of proteoglycan aggregation and an increase in the water content. The modifications of proteoglycans could be due to the action of proteolytic enzymes or to a lack of synthesis due to changes in chondrocyte glycotransferase. The biochemical changes could be the cause of cartilage destruction following pressures, since they can decrease the resistance of the tissue. They could nevertheless, be secondary to rupture lesions of the collagen, due only to stress. Arthrosis can then be secondary to either a special weakness of the cartilage or abnormal stress factors.


[Physiopathology of primitive arthrosis. Problems and hypotheses]. The origin and the evolution of the so-called primitive arthrosis represent two problems that hypotheses, developed by the authors, contribute to elucidate. Primitive arthrosis begins with a prearthrosic chondropathy which looks like the changes in the joint cartilage due to aging and due both to local conditions preventing the nutrition of the cartilage and to general factors causing failure of the system regulating the synthesis and the differentiation of articular tissues. These conditions are also relevant to primitive monoarthrosis, relatively rare in comparison with the frequency of secondary arthrosis and in comparison with arthrosis disease, which is the prototype of primitive polyarthrosis. The variable mixture of different local and general factors can explain the differences in evolution of primitive arthrosis, ranging from slow chondral erosion to accelerated destruction of bone and cartilage.


Effect of experimental neutropenia on initial gingivitis in dogs. The role of neutrophilic granulocytes in the loss of gingival collagen has been studied by inducing experimental neutropenia during initial gingivitis in beagle dogs. Neutropenia was induced for 4 d in three animals with normal gingiva by repeated injections of rabbit anti-neutrophil serum. During neutropenia microbial plaque was allowed to form on the teeth. Samples of junctional (crevicular) leukocytes and gingival fluid were taken on days 0 and 4. Block biopsies of buccal gingiva were obtained on day 4. Stained semi- and ultrathin sections were used for histometric and stereologic tissue analysis. Gingival fluid flow increased from day 0 to day 4 in all dogs while junctional leukocytes increased in one dog only. Subgingival plaque had formed in most biopsies, and in the junctional epithelium very few neutrophilic granulocytes were present. In the coronal connective tissue subjacent to the junctional epithelium lymphoid cells, structurally abnormal neutrophilic granulocytes and monocytes/macrophages were diffusely scattered. The gingival collagen appeared mainly displaced by the inflammatory cells rather than dissolved. The data suggest that neutrophilic granulocytes may contribute to the loss of gingival collagen during initial gingivitis in dogs. The neutrophils also seem to be of importance for the limitation of subgingival plaque growth along the tooth surface.


Die-spacing technique by diffusion precipitation. The present study has shown that it is possible by utilizing the principle of diffusion to precipitate on stone dies an adequate resin spacer of uniform and desirable thickness. Details and variables of the technique are described. The precipitation technique is simple and requires a minimum of time and equipment. This spacer technique opens up gateways for a new and improved casting technique cleared of most of the variables affecting the precision of the methods employed up till now. A new gypsum bonded investment for the new casting technique is being developed.


Reflex adrenergic gastrin release evoked by unloading of carotid baroreceptors in cats. Gastric acid and pepsin output in response to 0.10 and 6.0 microgram . kg-1h-1 of pentagastrin response to complete elimination of the carotid baroreceptor discharge by cutting the bilateral sinus nerves. Such unloading of the baroreceptors simulates a blood pressure drop to 50--60 mmHg, resulting in a pronounced reflex increase in the activity of the sympatho-adrenal system. Cutting the sinus nerves caused an increased level of immuno-reactive gastrin in the portal plasma, and this elevated gastrin concentration was virtually  extinguished by bilateral adrenalectomy. We conclude that the carotid baroreceptors can influence the gastrin release by a reflex adjustment of the release of adrenal catecholamines.


Parietal and chief cell sensitivity to pentagastrin stimulation before and after cimetidine treatment for duodenal ulcer. Gastric acid and pepsin output in response to 0.10 and 6.0 microgram . kg-1h-1 of pentagastrin was studied in ten duodenal ulcer patients before and after cessation of 6 weeks of cimetidine treatment, 1 g/day. Acid output in response to the low dose of pentagastrin was on average 63% of the response to the high dose before and on average 65% after treatment. The corresponding values for pepsin output were on average 88% both before and after treatment. Thus, the parietal and chief cell sensitivity stayed unchanged after cimetidine treatment. Mean maximal acid output decreased insignificantly, from 39.4 mmol/h before 34.9 mmol/h after cimetidine treatment. The results suggest an unchanged gastric acid and pepsin secretion capacity after short-term treatment with cimetidine for duodenal ulcer.


Simple closure or definitive surgery for perforated duodenal ulcer. In the period 1959--1971 a simple operative closure was the initial management of 112 patients with acute perforation of duodenal ulcers. At follow-up 6--18 years after perforation the relevance of the length of ulcer history prior to perforation in deciding upon 'definitive' emergency operation is evaluated. Using such a selection criterion, the rate of misinterpretation at the time of perforation is close on 50%, and half of these patients would be subjected to an apparently unnecessary operation. Furthermore, about 80% of the patients for whom simple closure was not sufficient treatment developed ulcer dyspepsia within the first year after the perforation. Therefore, simple suture of a duodenal perforation with careful clinical follow-up for at least 1 year is recommended.


Evidence for predominant involvement of the B-cell system in the inflammatory process in Crohn's disease. The cellular infiltrate in the walls of resected ileum and colon specimens obtained from patients with Crohn's disease was analysed. Mononuclear cells in tissue sections were characterized by the use of surface membrane markers and immuno-histochemical and enzyme histochemical techniques. It was found that: [1] B cells, as judged by the presence of surface membrane immunoglobulin and C3 receptors and the absence of alpha-naphthylacetate esterase and acid phosphatase activity, were the predominant type of cells in the intestinal infiltrate often found in close relation with smaller numbers of non-B cells; [2] all types of immunoglobulin-containing cells were increased in number with a shift in the ratio of IgA/IgG/IgM-containing cells in favour of the IgG- and IgM-containing cells; and [3] the histopathological reaction of the regional draining lymph nodes showed hyperplasia of B-cell areas (follicles and medulla) and small or absent T-cell areas (paracortex), consistent with a B-cell response. Our results indicate that the inflammatory process in the bowel wall in Crohn's disease mainly reflects stimulation of the B-cell system.


Sequential flow cytometric analysis of cellular DNA-content in peripheral blood during treatment for acute leukaemia. Sequential flow cytometric analysis (FCM) of relative nuclear DNA content per cell was done in peripheral blood of 12 patients during treatment for acute leukaemia. A marked increase of cells with S-phase DNA-content during the first hours of treatment was found in patients responding favorably to treatment. One patient with increase of 'S-phase cells' died before clinical improvement could be evaluated. However, lack of S-phase increase at one treatment cycle did not exclude a favorable response in the next. Two cases with probable aneuploid leukaemia showed gradual disappearance of abnormal cells during therapy. The value of FCM analysis of peripheral blood seems to be in predicting the response to treatment before clinical signs appear.


Antibody response in rabbits to Mycobacterium bovis BCG. The specificity of the immune response after immunization with Mycobacterium bovis BCG was studied by crossed immunoelectrophoresis with intermediate gel in a BCG/anti-BCG system, in which the reaction against thirty distinct components of BCG was recorded. After a single injection of total sonicate of 3 mg (dry weight) bacilli, the antibody response was markedly similar in eight rabbits. Th earliest and strongest response was directed against nine components of BCG; all but one of these belonged to the group of thirteen components that cross-react extensively with other mycobacteria. After repeated immunization with sonicate from about 0.8 microgram of BCG bacilli, five components still induced a marked antibody response. All but one of these components are among the most widely cross-reacting BCG components, and the observations made after subsequent challenge with the higher dose of BCG indicate that low-zone tolerance was induced against other components of the bacilli. The implication of these findings concerning formation of anti-mycobacterial antibodies in normal individuals and during mycobacterial infection is discussed.


[Indications for hemodialysis and kidney transplantation]. Results of dialysis treatment and kidney transplantation are discussed on the basis of data on survival, quality of life and cost. Influence of age, diabetes mellitus and hypertensive vascular disease on various type of treatment is outlined.


[Clinical study of the tolerance for 2 iodine containing contrast media for computerized tomography of the skull]. Clinical tolerance of two iodine contrast media (Na-methylglucamine-diatrizoate and Na-ioxitalamate) was tested in 1,628 patients requiring enhancing during computed tomography. Na-methylglucamine-diatrizoate was administered to 53.1% and the rest received Na-ioxitalamate. Infusion time was 4-6 min and the administered contrast quantity was 250 ml. Contrast medium injection was withheld from patients with known severe allergic disease, but in cases with known mild allergic reactions the contrast medium was given only after prophylactic administration of cortisone. Na-ioxitalamate was extremely well tolerated, causing only 0.11% (one patient) adverse effects, whereas in the case of Na-methylglucamine-diatrizoate a total of 42 side reactions were observed in 2.87% (22) of the patients. These reactions chiefly consisted of nausea and vomiting, which disrupted the CT examination and may endanger patients because of possible lung aspiration. Good tolerance of ioxitalamate seems mainly due to the chemical configuration of the organic iodine compound and the sodium salt of the contrast medium. The slow infusion time of 4-6 min - which is desirable in CT examination - contributes further to the good tolerance of ioxitalamate when different infusion times for this contrast medium are compared. The differing amount of iodine in the two contrast media and their different toxicity for the blood-brain barrier did not influence their enhancing quality, nor did these two factors modify relevant aspects for the diagnosis of intracranial lesions.