Some features of glycogen metabolism in human skeletal muscle. The higher the exercise intensity, the greater the relative proportion of energy output derived from carbohydrate metabolism. Muscle glycogen stores are the most important source of carbohydrate during heavy exercise and in normal dietary conditions. At the same relative energy output, a muscle rich in type II fibers obtains a relatively larger energy contribution from carbohydrates, in terms of local muscle glycogen utilization, than one rich in type I fibers. This pattern can be modified by different dietary means.


The role of physical exercise and training in the management of diabetes mellitus. The effects of physical activity on blood glucose homeostasis in diabetes mellitus and the potential benefits of exercise in the treatment of diabetic patients, are reviewed. Mild physical exercise results in a fall of blood glucose levels in controlled diabetic patients; this acute effect of exercise might be used in particular to inhibit the rise of blood glucose seen in insulin-treated diabetics after food intake. In contrast, physical activity will further deteriorate the metabolic situation in decompensated diabetic patients by an increase in blood glucose and a rapid aggravation of ketosis. On the other hand exercise potentiates the blood glucose lowering effect of subcutaneously injected insulin; therefore precautions have to be taken in order to avoid hypoglycemia in insulin-dependent diabetics especially during and after more strenous exercise. In juvenile-type diabetes, physical activity can be used as an efficient therapeutic adjunct only in cooperative, well-instructed patients who are used to check their metabolic situation on a regular basis. Physical training increases the tissues' sensitivity towards (endogenous) insulin. Hence, in addition to the diet, training might represent the most appropriate treatment in maturity onset-type diabetic patients. However, direct evidence for an improvement of glucose tolerance in diabetic patients by physical training is still lacking. In order to formulate detailed, generally applicable recommendations on how to carry out a useful therapeutic program of physical exercise and/or training in diabetic patients, further clinical studies assessing the quantitative effects of physical activity on carbohydrate metabolism are needed.


Microbial metabolism of amino alcohols. Formation of coenzyme B12-dependent ethanolamine ammonia-lyase and its concerted induction in Escherichia coli. 1. Kinetic studies of ethanolamine ammonia-lyase formation by Escherichia coli suggested that coenzyme B12 (5'-deoxyadenosylcobalamin), with ethanolamine, is a co-inducer. 2. Enzymic and immunological tests failed to show the formation of complementary enzyme components induced separately by ethanolamine and cobalamin respectively. 3. Although specific for ethanolamine as the substrate, enzyme formation was induced by certain analogues, e.g. 2-aminopropan-1-ol. 4. Experiments with cyano[57Co]-cobalamin suggested that neither coenzyme B12 nor some more tightly bound coenzymically inactive cobamide was necessary for enzyme stability in vitro. 5. Mutants of E. coli were obtained which formed ethanolamine ammonia-lyase apoenzyme constitutively, showing that neither ethanolamine nor cobalamin was required for assembly or post-transcriptional stability of the enzyme in vivo. Constitutive enzyme formation was subject to catabolite repression, particularly by glucose. 6. It appears likely that ethanolamine and coenzyme B12, acting in concert, induce ethanolamine ammonia-lyase formation. The term 'concerted' induction is proposed for this phenomenon.


Polypeptide-chain stoicheiometry and lipoic acid content of the pyruvate dehydrogenase complex of Escherichia coli. The pyruvate dehydrogenase multienzyme complex was isolated from Escherichia coli grown in the presence of [35S]sulphate. The three component enzymes were separated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and the molar ratios of the three polypeptide chains were determined by measurement of the radioactivity in each band. The chain ratio of lipoamide dehydrogenase to lipoate acetyltransferase approached unity, but there was a molar excess of chains of the pyruvate decarboxylase component. The 35S-labelled complex was also used in a new determination of the total lipoic acid content. It was found that each polypeptide chain of the lipoate acetyltransferase component appears to bear at least three lipoyl groups.


An antineuronal antibody cross-reacting with erythrocytes and lymphocytes in systemic lupus erythematosus. An antibody with erythrocyte and lymphocyte activity, present in the sera of patients with systemic lupus erythematosus (SLE), demonstrated additional reactivity with neurons. The neuronal reactivity was greater with cortical neurons than with cerebellar and caudate nucleus neurons, was predominantly IgG, and was immunologically specific. Selected sera from 22 patients with active SLE were tested for the presence of antineuronal antibody. Eleven of 12 sera obtained from patients with neuropsychiatric disease demonstrated definite neuron reactivity, in contrast to only 2 of 10 sera obtained from patients without evidence of neuropsychiatric involvement (P less than 0.005). Five of 21 sera from patients with rheumatoid arthritis, but no sera from 5 other disease control groups, contained antineuronal antibody. Serial studies of 2 SLE patients with transient psychotic episodes demonstrated a close association between antibody titer and the appearance of psychosis in one. These observations suggest that the detection of antineuronal antibodies in patients with SLE may be of value in the diagnosis and management of neuropsychiatric complications.


Anti-native DNA detection by the Crithidia luciliae method: an improved guide to the diagnosis and clinical management of systemic lupus erythematosus. The clinical value of the Crithidia luciliae (CL) method for detection of antibodies to native DNA (nDNA) was assessed. Significant titers were limited almost exclusively to patients with active systemic lupus erythematosus (SLE). Evaluation of sera from patients at the onset of active lupus demonstrated elevated anti-nDNA levels in 80% of subjects with active disease and in 94% of patients with clinically evident lupus nephritis. In longitudinal studies, rising titers of anti-nDNA were invariably accompanied by exacerbation of lupus activity. These findings suggest that the CL method correlates more closely with active SLE than do other anti-DNA methods in common use and indicate that it will prove highly useful in the diagnosis and management of SLE.


Comparison of gastrointestinal effects of aspirin and fenoprofen. A double blind crossover study. Sixteen men received 3904 mg of aspirin, 2400 mg of fenoprofen, or placebo daily for 1 week in a double blind and crossover trial. Fecal blood loss was measured by 51Cr labeled red cells; gastric and duodenal pathology were observed endoscopically. There was more (P less than 0.05) blood loss (4.96 ml) after aspirin than after fenoprofen (2.46 ml) or placebo (0.79 ml). By endoscopic examination, aspirin induced more (P less than 0.05) gastrointestinal pathology than fenoprofen or placebo, and there was a correlation of 0.70 between the two methods used in this study.


[Reaction between anti-erythrocyte-membrane immune sera and erythrocytes of patients with homozygous beta-thalassemia. Observations made with immunofluorescence and immunoperoxidase methods]. The immunofluorescence and immunoperoxidase techniques have been applied to erythrocytes from the periferal blood of beta thalassemia patients, coated with rabbit anti human erythrocyte membrane antibodies. Enhanced staininh has been found in a number of mature and immature red blood cells, as well as the presence of plasma proteins sticking to the surface of the erythrocytes.


Prosthetic valve endocarditis resulting from Nocardia asteroides. Nocardia asteroides was isolated from the prosthetic valve of a 64-year-old woman who had died of endocarditis after aortic valve replacement. Multiple blood cultures had all been negative. This organism is increasingly being recognised as a pathogen and is usually sensitive to sulphonamides. These should be tried in culture negative endocarditis unresponsive to standard therapy.


Effects of propranolol and metoprolol on haemodynamic and respiratory indices and on perceived exertion during exercise in hypertensive patients. A double-blind cross-over trial of the non-selective beta-blocker propranolol and the beta1-selective blocker metoprolol was carried out in 8 hypertensive patients. At the end of each 4-week period of treatment haemodynamic and respiratory indices and perceived exertion were studied during moderate exercise. Both beta-blockers resulted in reduced heart rate, cardiac output, and blood pressure, whereas the stroke volume increased. Total peripheral resistance did not change. During exercise the expiratory peak flow rate equally increased in every period. However, the peak flow rate at rest, as well as during exercise, was reduced by propranolol, while metoprolol had no such influence. Neither of the beta-blockers changed O2 consumption, CO2 production, tidal volume, or respiratory rate. Moreover, they did not influence perceived exertion.  These results suggest that the arteriolar and bronchiolar beta2-receptors do not play a major role in the alteration of circulation and ventilation during exercise. As far as their practical use as antihypertensive agents is concerned, this study shows no advantage in the use of either of these beta-blockers.


Management of unstable angina at rest by verapamil. A double-blind cross-over study in coronary care unit. A therapeutic trial with verapamil, a calcium-antagonist drug, was performed in 12 patients admitted to our coronary care unit because of frequent daily attacks of angina at rest attributed to coronary vasospasm. After a 48-hour run-in period, oral verapamil 480 mg/day and placebo were administered alternately during 4 randomised 48-hour periods. Transient ischaemic attacks with ST segment elevation or depression, with or without pain, were documented by continuous electrocardiographic monitoring. The number of attacks during the run-in and 2 placebo periods were 128, 123, and 130, respectively, and 31 and 23 during the 2 treatment periods (P less than 0.006 and P less than 0.003). This drug therefore appears to be effective in the management of patients with frequent attacks of angina at rest.


Observations on haemodynamic effects of mexiletine. The haemodynamic effects of intravenous mexiletine have been studied in 16 patients with valvular heart disease without clinical evidence of heart failure. A bolus injection of 150 mg administered to 6 of the 16 patients resulted in a mean plasma concentration above the therapeutic range for at least 5 minutes after the drug was given. A small but significant rise in the mean pulmonary artery pressure occurred. In 10 patients, the effects of intravenous mexiletine were compared with those of intravenous saline in a double blind trial. No significant difference was found in the haemodynamic effects, though both saline and mexiletine produced a small rise in the mean pulmonary artery pressure. Mexiletine when administered to patients without heart failure in doses known to be clinically effective did not have important adverse haemodynamic effects.


Cardiorespiratory effects of increased airway pressure during controlled and spontaneous breathing after cardiac surgery. The cardiorespiratory effects of intermittent positive pressure ventilation with zero end-expiratory pressure (IPPV), continuous positive airway pressure breathing (CPAP) and spontaneous breathing (SR) were studied in 11 patients 3--20 h after open-heart surgery. The transition from IPPV to CPAP resulted in a significant reduction in tidal volume and significant increases in respiratory frequency, PaCO2, oxygen transport and mean arterial pressure, but there were no significant changes in cardiac output or PaO2. There were no significant differences in any of the measurements between CPAP and SR.


Cardiac arrhythmias during outpatient dental anaesthesia: a comparison of controlled ventilation with and without halothane. The frequency and nature of cardiac arrhythmia during two controlled ventilation techniques for endotracheal anaesthesia in dental outpatients have been compared. Both techniques used nitrous oxide and oxygen with alcuronium, but in one the additional agent was halothane and in the other it was fentanyl. The frequency of arrhythmia in both groups was 5%. No ventricular arrhythmia was seen but benign nodal rhythm was noted. It is suggested that the anti-arrhythmia effect of non-depolarizing muscle relaxants may prevent ventricular arrhythmia in patients receiving halothane.


Ergometrine or oxytocin? Blood loss and side-effects at spontaneous vertex delivery. Blood loss and the frequency of vomiting were assessed at 88 spontaneous vertex deliveries. An i.v. injection of oxytocin 10 u was as effective as ergometrine 0.5 mg in controlling bleeding from the uterus after delivery. The continuous infusion of a dilute solution of oxytocin in the first stage of labour was not followed by an increased blood loss at delivery. Oxytocin infusions were maintained for 1 h after delivery. Vomiting or retching occurred in 13% of the mothers who received i.v. ergometrine. None of the women who received oxytocin suffered emetic sequelae.


The metabolism of [14C]-debrisoquine in man. 1 The synthesis of [14C]-debrisoquine hydrochloride and 4-hydroxy-debrisoquine sulphate is described. 2 The metabolic fate and excretion profile in both urine and faeces of 14C-labelled debrisoquine was studied in five healthy human subjects. 3 Investigations showed that the drug is well-absorbed after a single oral dose of 32 mg and quantitatively eliminated from the body within three days. 4 4-Hydroxy-debrisoquine is the major metabolite of debrisoquine, although significant amounts of 5-,6-, 7- and 8-hydroxy-debrisoquine are also formed. 5 Electron-capture gas chromatography is a useful method for measuring debrisoquine and its five hydroxylated metabolites in urine at the pg level.


Experimental lepromatous leprosy in the white-handed gibbon (Hylobatus lar): successful inoculation with leprosy bacilli of human origin. Leprosy bacilli of human origin were inoculated into a white-handed gibbon by the i.v. and i.p. routes, and also locally into ears, testis and around an ulnar nerve. The animal was observed closely during a period of nearly 15 years and did not exhibit any clinical evidence of cutaneous or neurological disease. At death, a wide range of tissues was taken for bacterial counts and histological examination, and a disseminated and progressive infection was demonstrated. Acid-fast bacilli were found in many sites; their morphological appearance distribution in nerves, and pattern of multiplication in mouse foot-pads, and also the presence of anti-mycobacterial antibody in the serum and the absence of specific lymphocyte transformation were all in keeping with an infection by Mycobacterium leprae, at an early lepromatous stage. This is probably the first fully documented report of experimental lepromatous infection in a primate. The findings are discussed in relation to the long incubation period of le promatous leprosy and the difficulties of diagnosing the disease at an early stage in man.


Malignant atrophic papulosis.

Malignant atrophic papulosis. The lethal intestino-cutaneous syndrome which we described in 1942 as malignant atrophic papulosis (MAP) has gained various other visceral sites. However, the cutaneous eruption remains the constant and pathognomonic symptom, which, despite its benign appearance harbours a serious prognosis because of the frequently very severe lesions in the small intestine, and sometimes of the nervous system. The very special histological structure shows zones of necrosis (dermal in the skin) due to vasculitis with a tendency to thrombosis, affecting the small vessels below the lesion, and with little or no inflammatory reaction, which differentiates it from other angiitis. The aetiology remains uncertain (?viral) and the treatment is disappointing although heparin appears to have been helpful occasionally.


Papular acrodermatitis of childhood and other papulo-vesicular acro-located syndromes. Papular acrodermatitis of childhood (PAC), first recognized in Milan and described by Gianotti in 1955, is an infectious disease of childhood, of low infectivity, fairly widespread, and characterized by: (1) Non-relapsing erythemato-papular dermatitis localized to the face and limbs, lasting about 3 weeks. (2) Paracortical hyperplasia of lymph-nodes. (3) Acute hepatitis, usually anicteric, which lasts at least 2 months and may progress to chronic liver disease.


Circulating reticulin autoantibodies of IgA class in dermatitis herpetiformis. Circulating reticulin autoantibodies of IgA class and anti-nuclear antigen antibodies were found in a high frequency in dermatitis herpetiformis patients as compared with age- and sex-matched controls.


Identification in situ of T lymphocytes in the dermal and epidermal infiltrates of mycosis fungoides. Frozen tissue sections from the lesions of five patients with histologically proven mycosis fungoides were examined using a specific antihuman T-cell antiserum and an indirect peroxidase staining technique. The dermal and epidermal infiltrates were shown to comprise predominantly cells bearing the specific T-cell antigen, HTLA. Two of the patients exhibited characteristic Pautrier microabscesses whose cells were exclusively T lymphocytes.


Properties of anti-hairy cell serum.

Properties of anti-hairy cell serum. An antiserum was prepared in rabbits against hairy leukaemic cells. After absorption with human erythrocytes, thymus and liver powder, the serum was passed through immunoabsorbent columns to remove extensive anti-plasma protein activity. Following these procedures, sensitive techniques failed to reveal residual activity against alpha-macroglobulins, beta2-microglobulin and other human plasma proteins. The antiserum reacted with normal B lymphocytes but not with T lymphocytes or monocytes. Positive reactions were seen in B cell lymphomas, chronic lymphocytic leukaemia, hairy-cell leukaemia and uninucleated Reed-Sternberg cells.


Treatment of premenstrual syndrome by spironolactone. Spironlactone was given to 28 women in a double blind cross over trial during four menstrual cycles. Hormonal profiles were measured during the first two cycles. Plasma aldosterone was elevated in the premenstrual phase of the cycles but there was no significant difference between symptomatic and asymptomatic groups. The rise in serum progesterone was higher in the symptomatic group during the postovulatory phase. The administration of spironolactone reduced weight and relieved psychological symptoms in more than 80 per cent of the symptomatic group.


A comparison of PGE2 and PGF2 alpha vaginal gel for ripening the cervix before induction of labour. The efficacy of a vaginal gel containing either 5 mg prostaglandin E2 (PGE2) or 25 mg prostaglandin F2 alpha (PGF2 alpha) to ripen the unfavourable cervix for labour induction was assessed in a double blind trial. PGF2 alpha, compared with PGE2, had little effect upon the clinical state of the cervix, but the resultant duration of labour in each of the two groups was shorter than in a control group. While the numbers of patients requiring oxytocin stimulation of labour and regional analgesia were reduced in both groups compared with the controls, PGF2 alpha was much less effective than PGE2. Uterine hypertonus was observed using both prostaglandins during an experimental study and the implications are discussed.


Scanning electron microscopic appearances in the amnion in polyhydramnios and oligohydramnios. The appearances of the amnion from two patients with polyhydramnios and two patients with oligohydramnios are described. In polyhydramnios the amnion showed a normal incidence of all the four patterns found in normal amnion at term and no abnormal features were noted. In oligohydramnios, two of four normal patterns predominated and intercellular canals were sparse.


A new method of full thickness skin graft fixation. A technique of free full thickness skin graft fixation utilising central and paracentral sutures between the graft and the depths of the recipient bed is described. The intrinsic fixation provided by these sutures allow larger free grafts, thus eliminating the need to use local flaps. These sutures also allow double free grafts-mucosal and dermal-for full thickness lower eyelid reconstructions. Patients do not need hospital admission and can resume normal activity immediately after the operation. One hundred and nine skin grafts secured by this technique have yielded very satisfactory results.


Lac UV5 transcription in vitro. Rate limitation subsequent to formation of an RNA polymerase-DNA complex. The kinetics of transcription of lac UV5 mRNA using purified DNA restriction fragment as template has been studied. This template, which contains only 203 base pairs, directs the formation of a 67-base lac mRNA with high specificity. The half-time for formation of a DNA-RNA polymerase complex is approximately 0.2 min. However, upon addition of 200 micron nucleoside triphosphates to this complex, RNA production proceeds with a half-time of approximately 1 min. Therefore, it is suggested that the rate-limiting step for lac UV5 mRNA production, under typical in vitro conditions, occurs subsequent to the formation of a promoter-specific complex.


DNA sequence directs placement of histone cores on restriction fragments during nucleosome formation. Restriction fragments, 203 and 144 base pairs in length, bearing the Escherichia coli lac control region have been reconstituted with the core histones from calf thymus to form nucleosomes. By several criteria the reconstituted nucleosomes are similar to native nucleosomes obtained by micrococcal nuclease digestion of calf thymus nuclei. However, sensitive nuclease digestion studies reveal subtle and important differences between native monosomes and the lac reconstitutes. Each reconstitute consists mainly of nucleosomes containing histone cores placed nonrandomly with respect to the DNA sequence. The shorter reconstitute forms asymmetric nucleosomes as evidenced by the DNase I digestion pattern. Exonuclease III digestion followed by 5'-end analysis of the larger reconstitute suggests that, of the many possible arrangements of histone core with DNA sequence, only two are highly favored.


Subunits of RNA polymerase in function and structure. 7. Structure of premature core enzyme. The structure of premature core enzyme, an obligatory intermediate in both in vivo and in vitro assembly of Escherichia coli DNA-dependent RNA polymerase, was compared with that of native core enzyme. Though this assembled but inactive form of core enzyme harbors the gross conformation similar to that of native enzyme, minor and presumably local differences exist, which were identified by near-ultraviolet circular dichroism spectra, tritium-hydrogen exchange rate, protease sensitivity, intersubunit cross-linking rate by bifunctional reagents, sedimentation behavior, and elution profile from phosphocellulose. Taken together these results indicate that the core enzyme subunits are loosely associated in the premature core. The temperature-dependent maturation is required for the core subunits to be tightly associated, leading to the formation of structurally stable and functionally active RNA polymerase.


Subunits of RNA polymerase in function and structure. 8. Catalytic properties of self-reactivated core enzyme. As an attempt to identify the maturation pathway of Escherichia coli RNA polymerase, the catalytic properties of core enzyme reactivated in the absence of maturation-promoting factors (sigma subunit or DNA) (that is, of self-reactivated core enzyme) were compared with those of native core enzyme. Differences have been found in the intrinsic activities such as in the template specificity, Km value of DNA template for the polymerase, activation energy for RNA synthesis, and increment of enzyme activity by sigma subunit. These observations imply that the transcription initiation by self-reactivated core enzyme is inaccurate and, therefore, more strict conditions including the presence of maturation-promoting factors are required for premature core be activated to the genuine function with the transcription specificity of native core enzyme.


Cysteinyl-tRNA synthetase from Escherichia coli does not need an editing mechanism to reject serine and alanine. High binding energy of small groups in specific molecular interactions. The cysteinyl-tRNA synthetase from Escherichia coli only very slowly activates serine, alanine, and alpha-aminobutyrate, the possible competitors of cysteine. The upper limits on the values of kcat/KM for the amino acid dependent ATP/pyrophosphate exchange reactions, relative to that of cysteine, are less than 10(-8), 2 x 10(-7), and 3 x 10(-6), respectively. It is calculated from these data and the concentrations of the amino acids in vivo that the error rates for the misincorporation of serine and alanine for cysteine are less than 10(-9) and 5 x 10(-8), respectively. There is no need for an error correcting mechanism and no evidence has been found to implicate one: there is no detectable ATP/pyrophosp hatase activity of the enzyme in the presence of tRNACys and alanine; Ala-tRNACys has been synthesized by the reductive desulfurization of Cys-tRNACys and has been found to be relatively resistant to the enzyme-catalyzed deacylation. Part of the high selectivity of the enzyme for the -SH group of cysteine (approximately 5 kcal/mol) appears to be caused by dispersion forces: simple calculations suggest that the dispersion energy between sulfur and a methylene group is about 2.5 times greater than that between two methylene groups. This high "hydrophobicity" of sulfur is consistent with the relative binding energies of substrates of the methionyl-tRNA synthetase. The rest of the high binding energy of the-SH group may come from hydrogen bonding.


Analysis of protein--protein relationships in 30S ribosome assembly intermediates using protection from proteolytic digestion. Treatment of the intact bacterial ribosome with proteolytic enzymes results in little or no digestion of many of the component proteins [Craven, G. R., & Gupta, V. (1970) Proc. Natl. Acad. Sci. U.S.A. 67, 1329]. In contrast, when the proteins are released from the constraints of ribosome structure they become completely susceptible to proteolytic attack. We have attempted to exploit these observations in an effort to determine the precise steps in ribosome assembly which result in a conversion of the structures of the various proteins from a proteolysis sensitive to a resistant form. Thus, a total of 11 30S ribosome assembly intermediate complexes of proteins and 16S RNA were prepared and digested with trypsin or chymotrypsin. The kinetics of digestion of each protein in the complex were followed by polyacrylamide gel electrophoresis. By a comparison of the digestion pattern of two complexes differing only by the presence of a single protein, it was possible to deduce several specific protective effects of one protein on its neighbor in the complex. On the basis of these studies, we propose nine protein-protein protective effects. The possible relevance of these interrelationships to other well-established proximity relationships is discussed.


Fragmentation of the human transplantation antigen heavy chain by limited proteolysis, acid cleavage, and cyanogen bromide treatment. Highly purified, papain-solubilized HLA-A, -B, and -C antigens comprising a mixture of a great number of allelic forms from at least three loci have been fragmented by limited proteolysis, acid cleavage, and cyanogen bromide treatment. Limited proteolysis of 125I-labeled HLA-A, -B, and -C antigens with trypsin, chymotrypsin, thermolysin, and pepsin resulted in the production of two large fragments. One fragment was associated with beta 2-microglobulin and contained all of the carbohydrate. The other fragment, which had a molecular weight of about 13,000, is most probably derived from the COOH-terminal part of the heavy chain. Acid cleavage of the HLA antigen heavy chain gave rise to two main fragments with molecular weights of 22,000 and 11,000. Both fragments contained disulfide bonds. Two minor components, representing further cleavage products of the 22,000-dalton fragment, were also observed. Cleavage of the HLA antigen heavy chain at methionyl residues gave rise to one carbohydrate-containing, cysteine-free 14,000-dalton fragment and one 20,000-dalton fragment that contained all cysteines but no carbohydrate. NH2-terminal amino acid sequence analyses demonstrated that the 22,000-dalton acid cleavage fragment and the 14,000-dalton cyanogen bromide fragment were derived from the NH2-terminal part of the HLA antigen heavy chain.


Purification and properties of the sigma subunit of Escherichia coli DNA-dependent RNA polymerase. An improved purification procedure is described for the sigma subunit of escherichia coli DNA-dependent RNA polymerase [ribonucleoside triphosphate:RNA nucleotidyl-transferase, EC 2.7.7.6]. The method involves chromatography of purified RNA polymerase on single-stranded DNA-agarose, Bio-Rex 70, and finally Ultragel AcA44. The sigma factor obtained is electrophoretically pure with a yield of about 40%. A number of the chemical--physical properties of sigma are presented. A molecular weight of 82,000 was determined by phosphate buffered sodium dodecyl sulfate--polyacrylamide gel electrophoresis. Ultraviolet absorption spectra were used to determine an E280nm 1% of 8.4. The amino acid composition and 12-residue N-terminal sequence (Met-Glx-Glx-Asx-Pro-Glx-(Ser or Cys)-Glx-Leu-Lys-Leu-Leu) of sigma have been determined. The isoelectric focusing properties of sigma are presented. Denaturation--renaturation studies indicate that sigma is capable of an unusually rapid and complete recovery of activity after being subjected to denaturing conditions. A stable, 40,000-dalton fragment is generated from sigma by mild trypsin treatment.


Electrolyte effects on the activity of mutant enzymes in vivo and in vitro. All temperature-sensitive histidine auxotrophs of Salmonella typhimurium tested are corrected by addition of neutral salts to their growth medium. The correctability seems to result from direct electrolyte effects on mutant protein stability since several of the mutant proteins are also salt correctable in vitro.


Dissociation of guanosine nucleotide-elongation factor G-ribosome complexes. The spontaneous dissociation of complexes containing elongation factor G (EF-G), the ribosome, and either GDP plus fusidic acid, guanyl-5'-yl imidodiphosphate, or guanyl-5'-yl methylene diphosphonate has been measured and it follows biphasic kinetics that can be resolved into two first-order decay rates. This suggest the existence of two classes of complexes with apparent dissociation rate constants (k) differing 5--20-fold. The values of k and the distribution of complexes between the fast and the slowly decaying class depend on the conditions in which the dissociation occurs but not on the conditions in which the complexes are formed. Rapid transitions of complexes from one to the other class occur only when the chemical environment in which the dissociation takes place is modified. Thus, increasing the concentration of NH4Cl or adding the antibiotic thiostrepton accelerates the decay and converts slowly dissociating into fast dissociating complexes. In contrast, addition of misreading-inducing aminoglycoside antibiotics of the neomycin, kanamycin, streptomycin, and gentamicin (but not hygromycin) groups slows down the decay. For neomycin B at 10 micron, this  effect is due to the conversion of fast into slowly decaying complexes. A model to explain the results involving conformational transitions of the complexes is proposed.


Unmasking of an essential thiol during function of the membrane-bound enzyme II of the phosphenolpyruvate beta-glucoside phosphotransferase system of Escherichia coli. beta-Glucoside transport by phosphoenolpyruvate-hexose phosphotransferase system in Escherichia coli is inactivated in vivo by thiol reagents. This inactivation is strongly enhanced by the presence of transported substrates. In a system reconstituted from soluble and membrane-bound components, only the particulate component, the membrane-bound enzyme IIbgl appeared as the target of N-ethylmaleimide inaction. The same feature was found in the case of methyl-alpha-D-glucoside uptake via enzyme IIglc. It is shown that the sensitizing effect of substrates is specific and not generalized, methyl-alpha-D-glucoside only sensitizes enzyme IIglc and p-nitrophenyl-beta-D-glucoside only sensitizes enzyme IIbgl towards N-ethylmaleimide inactivation. The inactivation of enzyme IIbgl by thiol reagents is also promoted in vivo by fluoride inhibition of phosphoenolpyruvate synthesis. In toluene-treated bacteria, the presence of phosphoenolpyruvate protects against inactivation by thiol reagents of p-nitrophenyl-beta-D-glucoside phosphorylation. Both results suggest that the inactivator resistent form of enzyme IIbgl is an energized form of the enzyme.


Escherichia coli Hfr-DNA degradation in endonuclease I-deficient minicells. [3H]Thymidine (dThd)-labelled Hfr DNA was transferred by conjugation into Escherichia coli F- minicells harvested from an endonuclease I-deficient (endI-) strain and its iosgenic wild type (endI+) parent. The susceptibility of this DNA to attack by DNAase was examined. The kinetics of in vivo conversion of [3H]dThd-labelled DNA into acid soluble radioactivity was examined. This activity, attributed to exonuclease action was the same for both strains. Contribution of endonuclease I was measured by an analysis of changes in weight-average (Mw) and number-average (Mn) molecular weight distribution of DNA molecules recovered from minicells. Reduction in Mw was greater in the endI-strain. The ratio Mn/Mw changed drastically during the incubation period of endI- minicells, but remained unchanged in the endI+ strain. These experiments suggest that the presence of the endI- mutation in minicell-producing strain chi1268 leads to a greater loss in M2 of Hfr DNA conjugally transferred into the minicells.


Genomic integrity of T1 DNA after gamma-and ultraviolet irradiation. T1 DNA, gamma-irradiated in the phage particle or irradiated with ultraviolet light was checked for structural integrity by kinetics of melting and reannealing. gamma-Irradiated DNA differed in all thermokinetic properties by a factor of 3-4 from DNA degraded by mechanical or enzymatical treatments. Ultraviolet irradiation caused much smaller effects than gamma-irradiation. Considering the frequency of pyrimidine dimers in relation to the gamma-ray induced lesions, strong evidence can be derived, that in addition to single base damages, local denatured regions are produced by gamma-irradiation. Such regions, formed possibly by direct absorption of radiation energy in DNA, i.e. by primary ionizations, are associated with base lesions and are passed over during reannealing.


Inhibition of translation in bacterial and eukaryotic systems by the antibiotic anthelmycin (hikizimycin). Anthelmycin inhibits protein synthesis on both pro- and eukaryotic ribosomes by preventing the peptide bond-forming reaction. The drug is structurally similar to certain other 4-aminohexosyl cytosine antibiotics including blasticidin S, gougerotin, amicetin and bamicetin although unlike these compounds anthelmycin lacks an aminoacyl moiety. It is proposed that anthelmycin inhibits the ribosomal peptidyl transferase centre by associating with a site that overlaps the (related) ribosomal receptor site(s) for the other four inhibitors.


A purified nucleoprotein fragment of the 30 S ribosomal subunit of Escherichia coli. A '13 S' nucleoprotein fragment was isolated from a nuclease digest of Escherichia coli 30-S ribosomal subunits and purified to gel electrophoretic homogeneity. It contained two polynucleotides, of about 1.1 . 10(5) and 2.5 . 10(4) daltons, which separated when the fragment was deproteinized. The major protein components were S4, S7 and S9/11, with S15, S16, S18, S19 and S20 present in reduced amount.


S1 nuclease as a probe of yeast ribosomal 5 S RNA conformation. 5 S RNA was isolated from Saccharomyces cerevisiae grown in the presence of 32P-phosphate and digested with nuclease S1, a single-strand specific nuclease. Two different procedures were employed to determine the sites of attack on the RNA. First, 5 S RNA was isolated from nuclease S1 digests, digested to completion with ribonuclease T1, and then 'fingerprinted' by two-dimensional electrophoresis. Quantitation of each of the characteristic RNAase T1-derived oligonucleotides was employed to determine the relative susceptibility of various regions of the molecule to nuclease S1. A second procedure to define nuclease S1-susceptible sites in the molecule employed polyacrylamide gel electrophoretic fractionation of nuclease S1 digests followed by identification of the nucleotide sequences of the released RNA fragments. Both procedures showed that the region of the molecule between residues 9 and 60 was most susceptible to nuclease S1, with preferential cleavage occurring between residues 12-25 and 50-60. These results are discussed in relation to a proposed model for the secondary structure of yeast 5 S RNA.


Fatty acid and glycerol labeling of glycerolipids of leukocytes in response to ionophore A23187. The effect of divalent cation ionophore, A23187, on the incorporation of [1-14C]palmitic acid, [1-14C]linoleic acid and [U-14C]glycerol into glycerolipids of polymorphonulcear leukocytes was examined. Ionophore A23187 stimulated the labeling of phosphatidic acid, phosphatidylglycerol, phosphatidylinositol, and diacylglycerol by both labeled fatty acids and glycerol. [1-14C]Palmitic acid and [1-14C]linoleic acid incorporation into phosphatidylcholine and triacylglycerol was reduced by the presence of the ionophore in the incubation medium, while [U-14C]glycerol labeling of these lipids was not significantly changed under identical conditions. These data reflect that the acylation of sn-glycerol 3-phosphate is activated, and the acylations of lysophosphatidyl-choline and endogenous diacylglycerol are inhibited in cells incubated with ionophore A23187. External calcium was not required for the ionophore effect on the incorporation of labeled fatty acids and glycerol. It is suggested that the ionophore alters the metabolism of the fatty acid and glycerol moieties of glycerolipids by changing the distribution of intracellular calcium of leukocytes.


Isolation of a thiamine-binding protein from Saccharomyces cerevisiae. Thiamine-binding protein was isolated from Saccharomyces cerevisiae by successive procedures of cold osmotic shock treatment, DEAE-cellulose chromatography and ultrafiltration. The purified thiamine-binding protein was an electrophoretically homogeneous molecule which appeared to be a glycoprotein with a molecular weight of 140 000 by sodium dodecyl sulfate polyacrylamide gel electrophoresis. No thiamine-binding protein was observed by disc gel electrophoresis in the shock fluid released from yeast cells grown in the presence of 1 muM thiamine, indicating that the formation of this protein is regulated by exogenous thiamine as previously suggested.


The roles of small ions, especially calcium, in virus disassembly, takeover, and transformation. Three related hypotheses are proposed. (1) Many simple viruses disassemble in the act of crossing a membrane, drawing energy from ionic disequilibria across the membrane. (2) Many of the metabolic changes early in virus infection are due to altered ion fluxes across membranes and the consequently altered ion concentrations in cytoplasm. (3) The crucial determinant of the transformed phenotype is also a change in ion concentrations. Ca2+ ions may play a major role in these effects.


Renal transplantation and viral infections. IV. A survey of herpes simplex virus excretion in relation to cellular specific immunity and humoral immunity among renal transplant recipients. Fourteen renal transplant recipients were screened systematically for HVH virus infection, cellular and humoral HVH immunity and general cellular immunity evaluated by PHA response. This study demonstrates significant correlation between humoral and cellular responses to HVH before graft and virus isolation after graft. This virus excretion occurred simultaneously with a PHA response peak. Neither significant drops in cellular general or specific HVH immune response nor correlation between acute rejection episode and any studied parameters were observed.


Cytostatic therapy-induced vomiting inhibited by domperidone. A double-blind cross-over study. A cross-over double-blind trial was conducted in 14 patients (20 double-blind treatment courses) comparing domperidone and placebo in the treatment of vomiting due to intensive cytostatic treatment. Eight ml, containing 16 mg of domperidone or placebo was injected one hour before the start of cytostatic therapy. The efficacy of the drug was evaluated by the investigator and the duration of nausea and vomiting was registered in the majority of the patients. Domperidone was preferred to placebo 13 times, whereas the reverse preference occurred only twice. The duration of both nausea (a median of 11 hours against seven hours) and vomiting (a median of 7 1/2 hours against 6 hours) was shorter with domperidone than with the placebo.


Indirect hemagglutination using whole mixed antigen for checking toxoplasmosis immunity and for serodiagnosis of human toxoplasmosis, compared with immunofluorescence. The indirect hemagglutination (IHA) is an easy technic for which it is possible to get commercial reactifs. This methode should be used often for the serodepistage of Toxoplasmosis and control of the immunitry anti-toxoplasmosis. We used a technique with total mixed antigen, that was compared with indirect immuno-fluorescence (I.F.I.), for 623 human serums. The I.H.A. was used with sheep formal hematies and coated with glutaraldehyde, with a total mixed antigen prepared from ultra sonicated parasites. This standardised reactive can be kept one year at 4 degrees C. We worked with U well micro-titration plates and the result is obtained after 2 hours. The I.F.I. technique was made with classical methods using Evans blue counter staining. The reproducibility of the I.H.A., during 366 tests was satisfactory. For the control of the immunity anti-toxoplasmic, the results tallied with both methods in more 95% of cases. Lastly, as test of progression, the I.H.A. with total mixed antigen appear an interesting way for the early diagnosis of the Toxoplasmosis where the reaction seems to be positive as soon as I.F.I.


Human interferon production with diploid fibroblast cells grown on microcarriers. A variety of diploid human fibroblast lines have been successfully grown to high densities (greater than 10(6) cell/ml) on recently developed microcarriers. Interferon induction using poly I.poly C and a superinduction procedure resulted in yields greater than 10,000 units/ml with one cell line. A direct comparison of microcarrier cultures to roller bottle cultures showed equivalent interferon yields on a per cell basis and some apparent differences relating to optimum inducer concentrations and kinetics of interferon accumulation.


Regulation of differentiation in transformed erythroid cells. Murine erythroleukemia cells provide a model for the study of erythropoietic differentiation uncoupled from the normal requirement for erythropoietin for cell proliferation. Evidence is presented which suggests that differentiation-inducing chemicals may have a number of cellular sites of action, including effects at the plasma membrane and on chromatin, but a common pathway may include a transient delay of the cell cycle in G1, alterations in chromatin structure, and the expression of a complex pattern of gene transcription responsible for the program of differentiation.


Chronic hypoplastic marrow failure and residual injury. An experimental model of chronic marrow failure can be produced in mice by treatment with a short course of busulphan. This results in permanent partial marrow failure which may later progress and become complete. The underlying lesion appears to be stem cell damage which leads to failure of proliferation of stem cells and their progeny. Other drugs can produce the same lesion and alkylation of DNA may be the mechanism.


The bgJ/bgJ:W/WV bone marrow chimera. A model for studying stem cell regulation. In studies with bgJ/bgJ:W/WV chimeric mice, we used the biege neutrophil marker as a criterion of of W/WV marrow replacement by implanted bgJ/bg/J stem cells. Data from a 50-fold range of inoculum doses and a 2-year period of observation indicate a hyperbolic pattern of replacement expressed as a log dose-response relationship. The saturating effect with increasing inoculum dose was interpreted as reflecting random initial stem cell seeding in bone marrow coupled with a decreasing efficiency of colonization by migration. From the statistics of random sampling and the exponential decrease of the 63% replacement dose with time, we estimate that W/WV marrow contains about 2600 stem cell regulatory volumes of about 10(8) mu3 (50 cell diameters) each, a dimension consistent with concepts of short-range cell-cell interactions. Our observations suggest that each regulatory volume is essentially self-contained and that stem cell migration is generally restricted to contiguous volumes.


Reversibility of hematopoietic stem cell direction (not 'commitment') as influenced by the microenvironment. The 7-day colony types (E vs. G) formed in irradiated recipient spleens and bones by donor cells from adult bone marrow and spleen and early fetal liver were examined. Both direct and sequential transplant (retransplantation shortly after lodgment) experiments were carried out. It was found that recipient spleen receiving donor bone marrow, spleen or fetal liver developed significantly higher E/G ratios in that order, but that the E/G for colonies in recipient bones remained around 1. This led to the following conclusions concerning differences in the proportion of E or G colonies formed in recipient spleens and bones: (1) selective lodgment of 'committed' CFU-S does not occur; (2) selected repression or stimulation of 'committed' CFU-S does not occur; and (3) the findings are best explained by a condition of reversible directedness present in many or all transplantable pluripotent stem cells.


Analysis of erythropoiesis by erythroid colony formation in culture. The development of clonal assays for hemopoietic progenitors has provided new tools for the analysis of normal and abnormal cell regulation. Such assays have been applied to erythropoiesis and have demonstrated classes of precursors which differ significantly in their growth potential, physical characteristics, and sensitivity to the hormone, erythropoietin. A formal geneology of these classes has been established and insight into the factors that regulate the numbers of the classes provided by studies in anemic and polycythemic animals. The results suggest that commitment to the earliest erythroid progenitors recognizable in culture is not controlled by erythropoietin, whereas the most differentiated elements demonstrate a requirement for the hormone for their maintenance. Recognition of differences in the factors that control erythroid differentiation predict that a variety of mechanisms will be found to account for different forms of erythroid failure in man.


Frequency-dependent control of nutritional and nonnutritional circuits in the dog paw. The neural control of blood flow and volume distribution between parallel nutritional and nonnutritional circuits has been investigated in 13 vascularly and neurally isolated dog hindpaws. The superficial and deep fibular nerves and the tibial nerve were cut and individually stimulated at frequencies of 0.1, 1, 5, 10 and 15 Hz. Increasing stimulation rates to each nerve progressively increased blood flow resistance. Vascular volume changes were determined by indicator dilution and tissue volume changes by plethysmography. The permeability surface area product of 86Rb (PS) and the capillary filtration coefficient (CFC) were determined. Superficial fibular nerve and deep fibular nerve stimulations caused progressively increased nonnutritional circuit constriction with increasing stimulation frequencies resulting in blood flow redistribution to the nutritional circuit as evidenced by increasing PS and CFC values. Tibial nerve stimulation at 0.1 Hz caused nonnutritional circuit constriction and blood flow redistribution to the nutritional circuit (PS and CFC increased). As the stimulation frequency was increased, there was progressive increase of the nutritional circuit constriction and altered blood flow distribution; i.e., CFC and PS decreased with increasing frequency of stimulation, presumably due to predominantly arterial segment resistance increase.


[History of anatomy in Lyon].

[History of anatomy in Lyon]. 1. We know very little concerning the teaching of anatomy during the Middle Ages. Only two authors, who both came to live in Lyon, Lanfranc and Guy de Chauliac, wrote on the subject. On the other hand, the important development of printing in Lyon from the sixteenth century onwards, made it possible to spread the translations of classic works and most of the books on Anatomy of the Renaissance. 2. However, Lyonese Anatomy developed very slowly because hospital training was more often badly organized. The only true supporter of Anatomy has been Marc Antoine Petit, chief surgeon of the Hôtel-Dieu before the French Revolution. 3. Apart from the parallel but only transient teaching of the Royal College of Surgery, one will have to wait for the creation of an official teaching first assumed by "schools" (secondary school and preparatory school) and finally by the Faculty of Medicine created in 1877. The names of Testut and of Latarjet contributed to the reknown of the Faculty of Medicine by their anatomical studies of great value for several generations of students. 4. Recently the Faculty of Medicine has been divided into four "universities". The new buildings are larger. The "gift of corpses" has brought a remedy to the shortage of the last twenty years. Anatomical research can be pursued thanks to micro-anatomy and bio-mechanics while conventional teaching is completed by dissection.


[Phase contrast microscopy studies of the urine of newborn infants]. Phase contrast microscopy allows a much better identification of the urinary sediment constituents than conventional bright field microscopy. The urinary sediment of 100 neonates admitted in a care unit has been examined by phase contrast microscopy. In all cases, squamous cells are far more numerous in newborn girls than in boys. An important rate of abnormal sediments has been observed: in 40 patients cytologic symptoms of renal ischaemia have been observed (hyaline or granulous casts and renal tubular cells, but red blood cells are uncommon). Numerous uric acid cristals were persent in 22 newborns, in correlation with a prolonged perinatal hypoxia. A considerable bacteriuria was seen in 21 neonates, without concomitant leucocyturia. In conclusion, only 20% of the investigated neonates had a normal urinary sediment.


[Kinetics of cell proliferation and cancer: introduction (author's transl)]. Research in the kinetics of cell proliferation directly interests oncologists for fundamental and pragmatic reasons. Since cancer is a perturbation of the control of cell proliferation and differentiation, such research may help to understand, the regulation mechanisms, in particular the role of microenvironment, of long range humoral factors, and of membrane site receptors. Furthermore the kinetics of cell proliferation in a normal tissue, or a tumour, influences its response to radiation or drugs. From this evolves the practical interest in research on hemopoietic tissues and on human and experimental tumors. Finally, the growth kinetics of human tumors explain their natural history and opens prospects for the treatment of intraclinical neoplastic disease and metastasis.


In vitro cloning of hemopoietic cells.

In vitro cloning of hemopoietic cells. Semisolid cloning systems are now available to detect the specific progenitor cells of neutrophilmacrophages, eosinophils, megakaryocytes and erythroid cells. Colony proliferation in vitro with the production of mature progeny requires stimulation by glycoprotein regulators specific for each hemopoietic class. Two of these, erythropoietin and GM-CSF have been purified. A new cloning system has been developed using spleen conditioned medium that detects multipotential hemopoietic cells in the mouse.


Clonal expansion and progression in acute myeloblastic leukemia. Diseaes originating in pluripotent stem cells, then developing through clonal expansion and clonal progression may properly be grouped together because of their common features. Among these, AML appears to be unique by reason of the presence within the clone of a blast cell population. Studies of cellular composition and regulation in AML clones require assays that measure not only myelopoiesis but also blast cell proliferation. The relation of the blast population to other components of AML clones remains uncertain. Resolution of the uncertainty is important in considering therapeutic strategies.


The growth and therapeutic response of human tumours in immune deficient mice. The development of techniques for growing human tumours in immune-deficient mice is reviewed. In a compilation of success-rates in grafting a series of types of human tumour into a variety of recipients there is evidence for different levels of success among the tumour types but little firm information on the comparative receptivity of different hosts. Adenocarcinomas, particularly of the colon, have done well, as have melanomas and some tumours of the nervous system. Breast carcinomas, squamous cell carcinomas and various sarcomas have transplanted poorly. Human tumour xenografts have been found to maintain the histological characteristics of the parent tumour and in some cases hormone production and hormone dependance have also been maintained. Evidence is accumulating on the maintainance of therapeutic sensitivity of the tumours.


Use of on-line bibliographic retrieval services in health sciences libraries in the United States and Canada. This paper reports the major findings of a questionnaire sent to the 708 U. S. and Canadian institutions which were using the National Library of Medicine's search services as of November 1977. Development of the National Library of Medicine (NLM) on-line network is traced characterizes type of institution, use of NLM and non-NLM data bases, operational service patterns, staffing levels, fee-for-service policies, and perceived impact.


Searching the MEDLARS file on NLM and BRS a comparative study. A comparison of the MEDLARS data base as it is currently available from the National Library of Medicine and Bibliographic Retrieval Services (BRS), Inc., is presented in chart format, and some major capability differences between the two systems are highlighted. The information inlcuded justifies the dual availability of the data base in health sciences libraries. This paper is intended for searchers and others familiar with one or both systems. Administrators considering the acquisition of the BRS system may find the study useful.


Training at the postgraduate level for medical librarians: a review. Postgraduate education for medical librarians is approachable from several perspectives, including internships, certificate programs, and continuing education programs. The diverse population of medical library personnel calls for a varied yet coordinated system of postgraduate education involving the Medical Library Association, regional medical libraries, library schools, and the National Library of Medical, in addition to active participation by all librarians in the health sciences field. Basic philosophies for each of the major types of programs are discussed and recommendations for future training of health sciences librarians are provided.


Foreign material in the capsules around breast prostheses and the cellular reaction to it. Thirteen capsules which had formed around breast prostheses were examined, using the technique of splitting the capsule wall. A foreign material in droplet form was present in all the capsules. The foreign material was taken up by phagocytes, and the cytological evidence is that it has cytotoxic activity. It was shown that the material migrates to the vessels in the outer layer of the capsule and may reach the lumen of those vessels. On the basis of the microscopic appearance and the results of infrared spectrum analysis, the foreign material in the capsules was assumed to be silicone.


Prostaglandin E2, prostaglandin I2 and the vascular changes of inflammation. 1. Plasma exudation and blood flow changes induced by intradermal injection of prostaglandins E2 (PGE2), I2 (PG12), D2 (PGD2) and F2 alpha (PGF2 alpha) were measured in rabbit dorsal skin by the use of [131I]-albumin and 133Xe. 2. Little plasma exudation was produced by any of the prostaglandins when injected alone. 3. Both PGE2 and PGI2 were potent at increasing blood flow, whereas PGF2 alpha and PGD2 produced an increase only at high doses. 4. All of the prostaglandins studied potentiated the plasma exudation induced by bradykinin. PGE2 and PGI2 had similar potent potentiating activity, whereas PGD2 and PGF2 alpha had activity at doses too high to be of biological significance. 5. Intradermal injections of arachidonate alone resulted in little plasma exudation but produced an increase in blood flow. Arachidonate potentiated bradykinin-induced plasma exudation. 6. Locally-injected indomethacin had no effect on basal blood flow and little effect on the exudation produced by bradykinin, but indomethacin did inhibit the vasodilatation and exudation potentiation produced by arachidonate. 7. PGE2 and PGI2 had similar potency in producing marked potentiation of plasma exudation induced by intradermal injection of zymosan. 8. In the reaction to zymosan, it is concluded that vasodilatation is the result of the release of arachidonate, which is subsequently coverted to either PGE2 or PGI2. These substances regulate the plasma exudation induced by independently-released vascular permeability-increasing mediators.


Pain in peripheral arteriography-a comparison of a low osmolality contrast medium with a conventional compound. The pain reaction to a new low osmolality contrast agent, sodium-methyl-glucamine-ioxaglate, in comparison to the conventional compound methylglucamine-ioxitalamate was tested and statistically evaluated in 12 patients using the visual analogue scale method. The intensity of pain experienced was significantly smaller following intra-arterial injection of the compound of low osmolality as compared to the conventional contrast agent.


Radiation effects on pre-natal development and their radiological significance. The evidence relating to pre-natal radiation exposure and the subsequent occurrence of malformations and cancer suggests that the overall risk lies in the range 0--1 cases per 1000 irradiated by one rad in utero in the first four months of pregnancy. The natural level of occurrence of serious handicaps in average pregnancies is at least 30 times higher. Is the much lower probability of radiation-induced harm sufficiently high to justify (a) concern when a woman who has been irradiated is found to have been pregnant at that time, or (b) the maintenance of restrictions on medical uses of ionizing radiation in women in the reproductive age, such as the ten day rule?


A prospective randomized trial of vagotomy in chronic duodenal ulceration. In a prospective, randomized trial, 76 patients with duodenal ulceration treated by truncal vagotomy and pyloroplasty were compared with 77 patients who underwent highly selective vagotomy. A total of 149 patients was followed up for from 1 to 4 years, the average follow-up period being 2.6 years. There was no operative mortality and no significant difference in postoperative morbidity between the two groups. The incidence of recurrent ulceration was greater after highly selective vagotomy, but this difference was not statistically significant. The clinical results were comparable in each group, and although the incidence of diarrhoea and dumping was greater after vagotomy and pyloroplasty, this difference was not statistically significant.


Interrelations between serum gastrin levels, gastric emptying and acid output before and after proximal gastric vagotomy and truncal vagotomy and antrectomy. In a prospective study of proximal gastric vagotomy and truncal vagotomy and antrectomy measurements were made, before and after operation, of acid output, gastrin output and gastric emptying of a solid and a liquid meat extract meal. No relationships were demonstrable between acid output and gastrin output. Truncal vagotomy and antrectomy (TVA) produced rapid early emptying of both meals combined with gross prolongation of the overall emptying of the solid meal. Truncal vagotomy and antrectomy reduced the intergrated gastrin output after either meal. Proximal gastric vagotomy (PGV) produced rapid early emptying of the liquid meal with no alteration in the early emptying of the solid meal; however, overall solid meal emptying was delayed. Proximal gastric vagotomy increased basal, peak and integrated gastrin output. In preoperative patients slow solid meal emptying was associated with higher gastrin output but after PGV the reverse was found, the slowest emptiers having the lowest gastrin output. These findings do not support the contention that a pyloroplasty should be added to PGV to reduce the hypergastrinaemia produced by the operation.


Scalp and cranial substitution with autotransplanted greater omentum using microvascular anastomosis. A case is described whereby a large defect of scalp and cranium was successfully covered using autotransplanted greater omentum, revascularized by microsurgical techniques.


Randomized controlled trial of cefuroxime for established postoperative respiratory infection. A randomized controlled trial has investigated the value of cefuroxime (a new antibiotic resistant to beta-lactamase) in 80 patients with established postoperative respiratory infection. Although the majority of respiratory isolates were sensitive to cefuroxime, there was no significant advantage in the antibiotic group compared with the controls with respect to duration of fever, radiological abnormality or infected sputum. We conclude that antibiotics are rarely necessary for the majority of patients who develop postoperative respiratory infections.


The use of metronidazole in the preparation of the bowel for surgery. A randomized trial was carried out in 120 patients undergoing colonic surgery mainly for carcinoma. Sixty-one patients received metronidazole and Thalazole and 59 received Thalazole alone. Sepsis occurred in 8 (13.1 per cent) of the 61 patients who received metronidazole, compared with 29 (49.2 per cent) of 59 patients who received only Thalazole. Of the 8 patients with sepsis who received metronidazole, none had infection due to anaerobic organisms.


One-dose antibiotic prophylaxis against wound infection after appendicectomy: a randomized trial of clindamycin, cefazolin sodium and a placebo. Two hundred and fifty patients were admitted to a prospective randomized trial of single dosage prophylaxis against wound infection after appendicectomy. There were 12 exclusions, 72 patients received placebo, 81 received 600 mg i.m. clindamycin phosphate and 85 received 1 1 g i.m. cefazolin sodium, the agent being given in the anaesthetic room. Clindamycin produced a significant reduction in the overall rate of wound infection from 33 per cent in the controls to 17 per cent. In cases with a gangrenous or perforated appendix the infection rate in controls was 78 per cent; this was reduced to 44 per cent by a single dose of clindamycin. Cefazolin significantly reduced the number of aerobic organisms isolated from wound infections, but did not significantly reduce the incidence of wound infection. We conclude that anaerobic organisms are more important than faecal aerobic organisms in the pathogenesis of wound infection after appendicectomy.


Diagnosis of gonorrhoea in women.

Diagnosis of gonorrhoea in women. The results of Gram stains and cultures from 145 women with uncomplicated ano-genital gonorrhoea are presented. The site which gave the highest yield of gonococci was the cervix. Equally good results were obtained with Stuart's transport medium and direct plating in the clinic. Positive results from rectal specimens alone were obtained from 8.4% of the 119 women in whom the rectum was examined. In 89 women the results of rectal specimens taken through a proctoscope were compared with those of swabs passed blindly up the anal canal. When Stuart's transport medium was used swabs taken through a proctoscope gave better results than the swabs taken blindly; the latter gave more positive results when direct plating was used. Thus when Stuart's medium is used a proctoscope is essential for the collection of rectal samples. Up to three sets of investigations were carried out where necessary, but 95% of the 145 cases were diagnosed on the results of the first set. However, only 54% of those patients diagnosed at their first visit had positive Gram-stain results. Further refinement of culture results is unlikely to improve diagnostic yield; what is needed is better, rapid diagnosis in the clinic.


Treatment of nongonococcal urethritis with rifampicin as a means of defining the role of Ureaplasma urealyticum. The results of a double-blind therapeutic trial on 217 men with nongonococcal urethritis (NGU) show that minocycline was more effective than rifampicin. Before treatment Chlamydia trachomatis was isolated from 43% of men, Ureaplasma urealyticum from 59%, and Mycoplasma hominis from 22%. Chlamydiae and ureaplasmas were isolated less frequently from men with a recent history of NGU. Minocycline was given to 94 patients, and after treatment chlamydiae were isolated from only one of 40 initially chlamydia-positive patients and ureaplasmas from only five of 57 initially ureaplasma-positive patients. Although most patients responded clinically, failure and partial recovery rather than complete recovery were observed more often among those who were infected with ureaplasmas. Rifampicin was given to 123 patients, after which chlamydiae were isolated from only one of 53 initially chlamydia-positive men whereas ureaplasmas, insensitive to the antibiotic in vitro, were isolated from 55 of 68 men who had initially positive results. Patients infected with ureaplasmas failed to respond to rifampicin treatment significantly more often than those who were not infected. This was also observed when only patients who had never had NGU or who had not had a recent episode were considered. Furthermore, 24 (44%) of the 55 men whose ureaplasmas persisted failed to recover whereas only one (7·7%) of 13 men whose ureaplasmas disappeared did not respond to treatment. These results suggested that ureaplasmas were a cause of urethritis in some of the men (an estimated 10% at least). In addition, Reiter's disease developed in two men treated with rifampicin from whom only ureaplasmas had been isolated initially. M. hominis did not seem to have an important pathogenic role in NGU and there was evidence that ureaplasmas were an unlikely cause of urethritis in some men since the organisms persisted despite complete clinical recovery.


A rose by any other name... on 'naming of neurones' by Rowe and Stone. Rowe and Stone dispose of descriptive terminologies for retinal units as 'essentialist' and argue for a 'neutral' multifactorial system redefined from previous W, X. Y nomenclatures. It is argued here that descriptive terminology need not be either essentialist or undesirable and that the W, X, Y terminology is too confused with false associations to be satisfactory. The synthetic power of the W, X, Y nomenclature was lost with the discovery of concentric W cell receptive fields, the projection of the W cells to the LGN and the suggestion of overlap between X and W conduction velocity groups. It was made methodologically unsound by its employment for the naming of Nissl stained soma classes before the identity of individual somas with the physiological entities can be demonstrated. Although now redefined, the identity of symbols in the several vintages of the W, X, Y system leads to inevitable confusion. The current tripartite division of a multidimensional quality space without cluster analysis is not neutral because it emphasises conduction velocity but represses the diversity of W receptive fields. The concise, apt and memorable descriptive receptive field terminologies are more desirable in that they are operationally based and approximate the unit's transfer function--the parameter most significant to the central nervous system in its information processing task; thus they are more suited for cross species comparison because of a probably bountiful source of functional hypotheses. The lack of taxonomic neutrality in the W, X, Y system has recently been emphasised by its failure to adequately classify rabbit retinal receptive field categories.


Biochemical and immunological characterization of neurofilaments in experimental neurofibrillary degeneration induced by aluminum. In order to identify the protein composition of 10 nm neuronal filaments, we prepared enriched fractions of rabbit spinal neurons undergoing experimental neurofilamentous degeneration induced by aluminum. Electron microscopy of the isolated perikarya showed well-preserved, large perinuclear masses of neurofilaments, which were not found in similarly isolated control perikarya. Comparison of these glial-free fractions by SDS-polyacrylamide gel electrophoresis revealed several-fold augmentation in the filament-enriched neurons of proteins migrating at 68,000 and 160,000 daltons, with an additional component at 200,000 daltons. Otherwise, the protein patterns were identical; no band was found at 51,000 daltons, the molecular weight assigned to the major proteins both of glial filaments and of a previously reported bovine brain filament preparation. An antiserum raised against the 160,000 dalton component of a modified bovine brain filament fraction produced specific and intense fluorescent staining of the aluminum-induced neurofilament bundles. Antibodies to the 51,000 dalton protein of brain filaments and to tubulin failed to stain the induced filaments. The results strongly support the hypothesis that both normal and aluminum-induced neuronal filaments are composed of 68,000, 160,000 and 200,000 dalton polypeptides and do not contain significant amounts of the 51,000 dalton filament protein. The likelihood of biochemical heterogeneity among organelles with similar morphology, namely the glial and neuronal filaments, is raised.


Studies on cultured rat Schwann cells. I. Establishment of purified populations from cultures of peripheral nerve. We have previously reported that in dissociated cultures of neonatal rat sciatic nerve, all of the cells could be identified by indirect immunofluorescence with two antisera to cell surface antigens. The Schwann cells, but not the fibroblasts, expressed the Ran-1 antigen, while the fibroblasts, but not the Schwann cells, expressed the Thy-1 antigen. We have exploited this difference to derive pure populations of Schwann cells. A combination of [3H]thymidine autoradiography and immunofluorescence marking showed that in Modified Eagle's Medium with 10% foetal calf serum, the Schwann cells divided slowly while the fibroblasts divided rapidly. Accordingly, two day old cultures were exposed to cytosine arabinoside to select against the fibroblasts, followed by growth in medium containing an extract of bovine pituitary which stimulated division of the Schwann cells. After 7 days the confluent cultures, which contained 80-90% Schwann cells, were passaged after treatment in suspension with antiserum to Thy-1 and rabbit complement. After continued growth in medium with pituitary extract, the secondary cultures contained greater than 99.5% Schwann cells. These purified populations have been maintained in culture for as long as 150 days (6 passages) and retained the Ran-1 marker. The cultured Schwann cells expressed the S100 antigen, as shown by indirect immunofluorescence and complement fixation, and receptors for cholera toxin. They did not express the large external transformation sensitive protein, the glial fibrillary acidic protein, or receptors for tetanus toxin.


A syncytium regression test to detect antibodies to bovine syncytial virus. A test to detect antibodies to bovine syncytial virus was developed from the observation that syncytia in monolayer cell cultures infected with bovine syncytial virus regress and disappear in the presence of bovine syncytial virus antibodies. The test is useful in monitoring the presence of bovine syncytial virus and bovine syncytial virus antibodies in cattle used in studies on bovine leukosis.


Permeability properties of swine small intestine: effect of a heat stable Escherichia coli enterotoxin. The permeability of weanling swine small intestine was estimated using measurements of filtration coefficients and equivalent pore size. Hypertonic solutions of mannitol, erythritol and urea were used to calculate reflection coefficients in the duodenum, mid jejunum and distal jejunum. Estimated effective pore radius was 6.4-7.4, 5.6-7.2 and 4.7-4.9A degrees in the three respective regions. Similarly the filtration coefficient induced by hypertonic solutions of mannitol decreased significantly in the distal jejunal segments. The results show an aboral gradient of decreasing permeability along the small intestine of the weanling pig. In situ incubation of loops in the proximal jejunum with a heat stable Escherichia coli enterotoxin for one hour did not significantly change the effective pore size as calculated from reflection coefficients of hypertonic solutions of erythritol and urea. However, the filtration coefficients of loops exposed to the enterotoxin were significantly greater than control loops with hypertonic solutions of erythritol and urea but not mannitol. This suggests the occurrence of a slight reduction in epithelial porosity. The results support the hypothesis that intestinal secretion induced by heat stable E. coli enterotoxin is not the result of an increased mucosal permeability.


Humoral and cell-mediated immune response to crude antigens of Dermatophilus congolensis during experimental infection of rabbits. Rabbits were infected with Dermatophilus congolensis and tested for humoral immune response by indirect haemagglutination and for cell-mediated immune response to crude antigens of D. congolensis. Lymphocyte transformation and macrophage migration inhibition assays were used as in vitro correlates of cell-mediated immune response while cutaneous delayed hypersensitivity was used in vivo. Endo-antigen and whole cell antigen were found to significantly induce cell-mediated immune response. In contrast, humoral responses were found to be more significantly induced by exo-antigen. A biphasic immune response was revealed by the lymphocyte transformation test.


Copper inhibits pressor responses to noradrenaline but not potassium. Interactions with prostaglandins E1, E2, and I2 and penicillamine. Low concentrations of copper inhibited responses to norepinephrine and angiotensin (IC50 3 X 10(-6) M) but not to potassium in rat mesenteric vascular preparations perfused either with buffer or indomethacin and prostaglandin (PGE2). The dose-response curve was not shifted by indomethacin, imidazole, or PGE2 but was moved to the right by 2.8 X 10(-11) M PGE1 and to the left by 2.8 X 10(-7) M PGE1. These effects of copper are similar to the effects of PGI2 in the preparation. Copper moved the PGI2 dose-response curve against noradrenaline in parallel to the left, suggesting that the two were interacting at some point. Penicillamine, which may stimulate PGE1 synthesis, had PGE1-like interactions with the copper effect, suggesting that its value in Wilson's disease may be partly due to antagonism of the biological action of copper as well as to its copper-chelating properties.


Increased in vitro sensitivity of Candida albicans to amphotericin B when grown in mixed culture with Escherichia coli. The growth of Candida albicans was inhibited by some Escherichia coli strains both in conventional batch cultures and also in a chemostat under conditions of constant addition of fresh medium. Concentrations of 0.2 microgram amphotericin B per millilitre and of 2 microgram nystatin per millilitre, which caused a slight inhibition of C. albicans in pure culture, exerted a strong fungicidal effect when the yeast was placed in mixed cultures with certain strains of E. coli. Candida albicans cells, inhibited by either E. coli or in mixed culture with polyene antibiotics, appeared larger and less uniformly stained by acridine orange than control cells from pure cultures. Addition of chloramphenicol to the mixed cultures, in quantities sufficient to kill the E. coli cells, abolished the increased sensitivity of C. albicans to amphotericin B or nystatin. In preliminary in vivo tests, E. coli did not sensitize C. albicans to the polyene antibiotics.


Endotoxin in germfree, gnotobiotic, or conventional-flora Sprague-Dawley rats. The Limulus assay for bacterial endotoxin was performed on serum and (or) plasma from animals monoassociated with Clostridium species, Staphylococcus aureus, Escherichia coli, Proteus mirabilis, Enterobacter agglomerans, Bacteroides fragilis, Klebsiella pneumoniae, or Candida albicans. Plasma from animals monoassociated with the gram-negative bacteria or C. albicans consistently showed a positive Limulus test while conventional-flora controls, germfree rats, and gnotobiotic animals monoassociated with gram-positive bacteria or E. agglomerans were negative. Germfree and conventional rats were injected (intraperitoneal (i.p.)) with Salmonella typhosa lipopolysaccharide (LPS). Although no endotoxin was detectable in either group prior to the injection, by 1 h post injection endotoxin was in the plasma of all groups. The germfree rats appeared to clear the LPS quicker than their conventional-flora counterparts. Generally, LPS-injected rats (conventional and germfree) showed clumping and decreased number of platelets, a decrease in their lymphocyte counts, and increased polymorphonuclear leukocyte (PMN) counts.


Factors influencing the in vivo stability of L-serine deaminase activity in E. coli K12. L-Serine deaminase (L-SD) is unstable in intact cells of Escherichia coli K12. The extent of this instability is dependent on the nitrogen content of the medium in which the enzyme is synthesized, and on that in which it is tested. Enzyme activity in cells grown with an inorganic nitrogen source is unstable in the presence of inorganic nitrogen; enzyme activity in cells grown with an organic nitrogen source is unstable in the presence of the amino acids glycine and leucine.


Sporulation in single-spore isolates from amitrole-induced multispored asci of Saccharomyces cerevisiae. Amitrole treatment causes multispored ascus production by cells of a yeast strain whose asci normally contain two diploid spores. Single spores were isolated from asci containing two to eight spores and their ability to germinate was determined. Cells in colonies grown from single spores sporulated in the same manner as the parent strain indicating that amitrole had not induced meiotic division in the developing asci.


Regulation of extracellular protease formation by Serratia marcescens. Heavy cell suspensions of Serratia marcescens, when grown in gelatin-containing media, produce extracellular proteases which increase in specific activity in a linear fashion for 3 to 4h. During partial purification, a single peak of proteolytic activity was demonstrated by Sephadex G-100 chromatography. However, electrophoresis using 5% polyacrylamide gels discloses three proteolytically active bands. Evidence in favor of gelatin acting as an inducer of the 'proteolytic system' was provided by two observations. First, proteolytic activity is only present in media containing gelatin. Secondly, the addition of 10(-4) M rifampicin to cells growing in gelatin-containing medium plus an additional carbon source inhibits protease activity totally, but has no effect on growth. When glycerol is added to a growing cell suspension in gelatin-containing medium, growth increases, but protease specific activity decreases. This 'glycerol effect' is not due to an accumulation of active or inactive enzyme in association with the cell, nor to a decrease in the total number of proteases synthesized. Rather, glycerol, as other utilizable carbohydrates, exerts a repression which can be eliminated by 5 mM dibutyryl cyclic AMP.


Cancer immunotherapy.

Cancer immunotherapy. Important contributions that stimulated studies in cancer immunotherapy included: (1) the discovery of tumour-associated antigens; (2) the observation that infection with bacille Calmette-Guérin (BCG) in animals was protective against tumour challenge; and (3) the observation that immunodepression due either to malignant disease or to treatment of the disease, was, in some instances, related to prognosis. Immunotherapy trials with microbial agents have involved attempts to obtain a local effect by injecting the agent into the tumour or into the region of the tumour and to obtain a "systemic" effect distant from the site of injection. Trials with active specific immunotherapy involving tumour cells or tumour cell extracts have frequently involved the combination of these specific agents with a nonspecific adjuvant such as BCG. Recent studies with thymosin and levamisole in patients with lung cancer and other types of malignant disease have shown prolonged survival in the groups receiving immunotherapy.


Recent advances in drug therapy for epilepsy. Recent advances in drug therapy for epilepsy have contributed to the reduction in the proportion of persons whose epilepsy is uncontrolled. New knowledge of the pharmacokinetics of phenytoin has led to a better understanding of the drug's bioavailability and uses. Carbamazepine has recently been introduced for the treatment of generalized tonic-clonic and partial seizures. Clonazepam has been found of particular benefit in the treatment of absence and myoclonic seizures. Valproic acid is a promising antiepileptic drug with broad-spectrum activity, and is particularly useful in the treatment of absence and myoclonic seizures, although further clinical experience is required before it can supplant ethosuximide as the preferred drug for the treatment of absence seizures. Monitoring of the plasma concentration of antiepileptic drugs has added greatly to the achievement of optimal drug therapy and the prevention of toxic effects.


What did Eugen Bleuler really say?

What did Eugen Bleuler really say? Bleuler's 1911 monograph on schizophrenia is an attempt to redefine Kraepelin's dementia praecox making use of contemporaneous somatogenic and psychogenic theories of illness, and is best appreciated in its proper historical context. Currently there is confusion about Bleuler's concept of schizophrenia, arising in part from inherent textual difficulties and compounded by inaccurate representations of his account. This conceptual confusion may be reflected in diagnostic uncertainty today, and in the renewed interest in nosology and diagnostic rigor that characterizes much of the literature on schizophrenia at the present time.


Postdiversion precystectomy irradiation for cancer of the bladder. This is the first report of a 4-year prospective trial of integrated irradiation and cystectomy in the management of advanced bladder carcinoma. Patients are treated sequentially with staging laparotomy and urinary diversion, highdose preoperative irradiation (5,000 rad/30 treatments/42 days), and total cystectomy. Twenty-eight consecutive patients have been entered into the study; all had Grade III or IV tumor or clinical evidence of invasion (Jewett Stage B1-D1). Local control has been achieved in 21 of 22 patients, and the 4-year actuarial survival is 54%. The initial staging procedure not only defines inoperable patients, but also allows completion of urinary diversion prior to small bowel irradiation with fewer anastomotic problems. Acute and chronic complications have been minimal, and there have been no treatment-related deaths.


Experience with pion radiotherapy.

Experience with pion radiotherapy. Forty-one patients with a total of 86 tumors were treated with negative pimesons (pions) at the Los Alamos Meson Physics Facility (LAMPF) through December 31, 1977. An additional 30 tumors in the total patient population were treated with 100 kVp x-rays to assess comparative effects on skin nodules and 8 patients received additive photon or electron radiation to pion-treated portals. Of 52 evaluable tumors in 20 patients treated with pions only and followed for 3 to 22 months, 81% (42 tumors) completely regressed; 6% (3 tumors) partially regressed; and 13% (7 tumors) did not respond, although 5 of the 7 have shown no growth for 10 months. Of eight tumors in seven patients treated with a combination of pions and conventional radiation, three tumors showed complete response and five tumors showed partial response, though the resected specimens in two (one with complete and one with partial response) revealed no tumor microscopically. Reactions in normal tissues have been mild, with some patients exhibiting no normal tissue reaction, as compared with relatively marked tumor response.


Selectivity of the micro-leukocyte adherence inhibition assay in pancreatic cancer. A modified leukocyte adherence inhibition assay was performed on white blood cells from patients with ductal pancreatic cancer, other malignancies, benign gastrointestinal diseases including pancreatitis, and healthy controls, using four different ductal pancreatic cancer membrane preparations and similar preparations from gastric and colorectal cancers. A mean adherence index of less than or equal to 0.2 was evidence that the leukocytes "recognized" the antigen(s). In 9 of 10 patients with localized pancreatic cancer, 13 of 15 leukocyte populations "recognized" the pancreatic cancer antigen(s) and not other tested antigen(s). Leukocytes from only 11 of 18 patients (17 of 29 assays) with metastatic pancreatic cancer "recognized" the pancreatic tumor antigen (and no other antigen). The inability to recognize the pancreatic tumor antigen(s) was not related to nutritional, biochemical or therapeutic status of the patient, but was related to the demonstration of a response to skin test antigens. In contrast, 3 of 35 leukocyte populations in 2 of 31 patients with malignancies other than pancreatic, 1 of 28 with benign gastrointestinal disease, and one of 38 healthy control populations "recognized" the antigen.  The LAI is worthy of further study in the differential diagnosis of pancreatic cancer.


Effect of postoperative wound infection on the course of stage II melanoma. Microbial infections reportedly have a favorable effect on the course of certain malignant diseases. Intralesional inoculation of micro-organisms can bring about tumor regression in certain clinical and experimental situations. In order to evaluate the influence of immediate postoperative wound infection on the course of Stage II melanomas, a retrospective study was undertaken of 211 patients who had undergone axillary or groin dissection. None had any antibiotic, steroid, chemoimmunotherapy, or cryosurgery and there was no history of a second primary neoplasm, pregnancy, immunodeficiency, or administration of immunosuppressive drugs. Forty of these patients developed significant postoperative wound infections. Although their representation according to sex, tumor location, number of nodes involved, and other parameters was comparable to that of the remaining 171 patients who did not develop wound infections, the incidence of local recurrence in the group with infections was significantly lower (p less than 0.01). Patient survival and disease-free interval following node dissection were not influenced by infection. Postoperative infections in the groin or axilla offered only local protection from tumor recurrence; the ultimate course of the disease was not affected.


Primary histiocytic lymphoma of the epididymis. The first documented case of primary histiocytic lymphoma of the epididymis is presented. The tumor showed distinct nodularity, which is unusual for extranodal lymphomas, and marked sclerosis. Extensive staging work-up showed no evidence of extraepididymal spread. Unusual features included the youth of the patient at presentation and the severe diffuse atrophy of the adjacent testicular parenchyma. Following orchiectomy and radiotherapy, there has been no subsequent clinical evidence of systemic disease.


Systemic cancer and the metastatic process. Various known and presumed characteristics of malignant cells that permit metastasis and factors that contribute to the establishment of secondary tumor foci are reviewed. The potential for therapeutic control with and the limitations of chemotherapy are discussed briefly.


Estimated risk and occurrence of breast cancer in asymptomatic and minimally symptomatic patients. Mathematical procedures, some unique to this study, were applied to 114 suggested risk factors, with as many as 10 subsets, from history, physical and x-ray examination on 30,904 breast studies on 7,252 patients referred from the Emory University Clinic since 1963. One-fifth of the cancers were unrelated to symptoms; 82% of the cancers were free of axillary lymph node metastasis. There was no sign or symptom that predicted preclinical cancer. Interaction of numerous indicators subjected to strong statistical procedures could contribute to establishing risk of even early breast cancer. The results of hierarchic discriminant analyses demonstrated the feasibility of using simultaneously large numbers of risk factors in a systematic way to pinpoint patient with mammary cancer. Based on usual clinical and x-ray assessment of the women 12.5% of the noncancer patients required biopsy to demonstrate 70% of the cancers with a cancer to benign rate of 1 to 4. Using the same data with discriminant analyses, 5.6% of the patients would require biopsy, at the rate of 11.9% of the population. A computerized system has been developed for widespread application to provide the clinician with a highly objective and totally consistent assessment of risk for breast cancer in each of his patients.


Tube leukocyte adherence inhibition (LAI) assay in gastrointestinal (GIT) cancer. Tumor-specific immunity to carcinoma of the colon, pancreas and stomach was assayed by tube LAI. Cancers of the colon, pancreas and stomach, were shown to possess organ-type specific neoantigens. In 115 patients with colon cancer, 100%, 75%, 61% with Dukes' A, B and C cancer were LAI positive, respectively. Even a microfocus of in situ cancer in a colon adenoma was sufficient to stimulate measurable tumor-specific immunity in the host. In Dukes' D cancer, 25% of patients with widespread metastasis were positive, whereas 100% with solitary lesions were positive. Reactive leukocytes from patients with colon cancer did not react to extracts of normal bowel mucosa or villous adenoma from LAI-negative patients. Leukocytes from 19% (3 of 16) of patients with colon adenomas reacted to the extract of colon cancer but not normal colon mucosa. Moreover, the LAI-positive response of the patients with colon adenomas or colon cancer is directed to a colon cancer TSA which is linked to beta2-microglobulin. These studies suggest that some colon adenomas express TSA before morphological evidence of cancer. It is not known if the acquisition of a cell surface TSA is an irreversible step toward unrestrained growth and metastasis. In pancreatic cancer, 100% of patients with cancers less than 5 cm and without metastasis were LAI positive, whereas 29% were positive when the cancer was greater than 5 cm or had metastasized. In Patients with stomach cancer, 100% with Stage II and 46% with Stage III and IV cancer were LAI-positive. Leukocytes from patients with other GIT cancers and from patients with inflammatory bowel disease or pancreatitis did not react with extracts of colon, stomach or pancreatic cancer. Leukocytes from patients with metastatic cancer, usually did not react in the tube LAI assay because their surfaces were coated in vivo with TSA. LAI reactivity was present when CEA was not detectable and when CEA levels were elevated LAI activity was often absent. The present study suggests that the automated tube LAI shows sufficient promise to warrant studies to determine its efficacy for the diagnosis of GIT cancers.


Ascorbic acid and cancer: a review.

Ascorbic acid and cancer: a review. Host resistance to neoplastic growth and invasiveness is recognized to be an important factor in determining the occurrence, the progress, and the eventual outcome of every cancer illness. The factors involved in host resistance are briefly reviewed, and the relationship between these factors and ascorbic acid metabolism is presented in detail. It is shown that many factors involved in host resistance to neoplasia are significantly dependent upon the availability of ascorbate.


Assay of 855 test chemicals in ten tester strains using a new modification of the Ames test for bacterial mutagens. Determination of mutagenic activity in bacterial systems has become accepted as an initial step in the evaluation of the carcinogenic potential of new chemicals. In this paper, a bacterial mutagen screening technique is described in which chemicals can be tested in 10 tester strains over a 10,000-fold concentration gradient both with and without metabolic activation. Using this assay, 855 chemicals were tested, and 182 were found to be mutagenic in one or more of the tester strains. Included were 299 chemicals used in chemical manufacturing or laboratory synthesis. Of these, 20% gave a positive response in one or more strains. The high rate of positives undoubtedly reflects the high chemical reactivity of compounds in this group. In contrast, when 261 organic chemicals which were synthesized for evaluation as potential pharmaceutical or agricultural products were tested, only 8% were identified as mutagenic. The Salmonella typhimurium tester strains TA98 and TA1538 proved to be very reliable and efficient in detecting and identifying frame-shift mutagens. TA100 was the most sensitive tester strain, detecting 142 of the 182 mutagens encountered in the study. However, since TA100 detected both base substitution mutagens and frame-shift mutagens, this tester strain was not suitable for the specific identification of base substitution mutagens. Base substitution mutagens were more reliably detected by Escherichia coli tester strains WP2 and WP2 uvrA- than they were by S. typhimurium strains G46 and TA1535. The data obtained when mutagens are tested by the concentration gradient procedures can include (a) the activity spectrum in tester strains, (b) identification as either frame-shift or base substitution mutagens, (c) the minimal concentration at which auxotroph growth is inhibited, and (d) mutagenic potency in terms of minimal concentration at which mutagenicity is observed. The data obtained have been found to be of immediate use. For example, with manufacturing intermediates the data have been combined with other toxicity data and used as a basis for setting safety standards for handling such compounds in the workplace. In addition, positive bacterial mutagenicity data on selected members of new series of organic compounds can serve to alert the chemist early to the possibility that the compounds may possess undesirable toxic properties, particularly carcinogenicity. Also, this type of data should be of great value both in the planning and in the interpretation of other in vitro tests designed to evaluate the potential carcinogenicity in mammals of chemicals found to be positive in bacterial tests.


Microtubules and actin-containing filaments of normal, preneoplastic, and neoplastic mouse mammary epithelial cells. The distribution and organization of microtubules (MT's) and actin-containing microfilaments (MF's) were examined in epithelial cells of primary cultures established from normal, preneoplastic, and neoplastic mouse mammary tissues and in cells of three clonal culture lines derived from murine mammary adenocarcinomas. No consistent differences in the cytoskeletal components were found among cell populations of the primary cultures as revealed either by indirect immunofluorescence using antibodies to tubulin and actin or by electron microscopy. Overall, the majority of cells in the three types of primary cultures possessed elaborate complexes of MT's and actin filaments after fluorescent staining with the appropriate antibodies, and abundant MT's and MF's were found in the cells at the ultrastructural level. Similar patterns of MT's and MF's were observed in cells of two of the clonal mammary tumor lines. Cells of the third line, however, exhibited intricate networks of MT's but had a reduction in actin cables detectable by the immunofluorescence procedure. Moreover, MF's were difficult to locate by electron microscopy. The results suggest that the lesion(s) in growth control in the neoplastic mammary cells may not involve any gross alterations in MT's or MF's.