Flow cytometry of isolated nuclei prepared from 9L rat brain tumor.

Nuclei isolated by grinding 9L rat brain tumors gave a DNA distribution consisting of a 2C DNA peak due to noncycling normal cells and a bimodal distribution beginning at about 4C DNA due to the cycling tumor cells. Autoradiographic studies of nuclei from rats that received a pulse of 3H-TdR in vivo confirmed that the majority of proliferating cells were in the bimodal part of the distribution. The fraction of cells in S-phase determined from the DNA distributions was 15.3 per cent. This is consistent with a labeling index of 18 per cent determined from autoradiographs of tumor tissue and an S-phase fraction of 17 per cent determined from a fraction of labeled mitosis analysis (assuming that all of the 53 per cent noncycling cells are in G0). We also determined, by autoradiographic analysis of cells sorted from the tumor's mid-S-phase region, that only 58 per cent of these cells were labeled. We attribute this mostly to the presence of fluorescent debris from necrotic nuclei in this part of the distribution.


[Characteristics of human external respiration under excess intrapulmonary pressure under sea level and "altitude" conditions according to pneumotachographic data].

In 54 pressure chamber experiments 12 healthy male test subjects took part. Their pneumotachograms and other physiological parameters at a positive pressure breathing of 30 mm Hg at sea level and of 125--130 mm Hg at an altitude of 25,000 m at rest and while exercising were recorded. High altitude facilities and pneumotachograph were modified to meet the experimental requirements. The changes in pneumotachographic readings depended on the excess intrapulmonary pressure, its variations with respect to the respiratory stages, efficiency of the external counterpressure on the body, as well as motor activity of the test subjects. The pneumotachographic procedure allows qualitative and quantitative evaluations of external respiration upon excess intrapulmonary pressure, and study of the mechanism of these changes supported by other physiological methods.


Determinants of glomerular localization of subepithelial immune deposits: effects of altered antigen to antibody ratio, steroids, vasoactive amine antagonists, and aminonucleoside of puromycin on passive Heymann nephritis in rats.

The role of circulating immune complex deposition versus in situ complex formation in membranous nephropathy is controversial. Passive Heymann nephritis in rats resembles membranous nephropathy in man and was induced by injection of sheep antibody to rat proximal tubular epithelial cell brush border antigen (anti-Fx1A). Minutes after injection of 1 ml. of anti-Fx1A, subepithelial immune deposits were seen by immunofluorescence and electron microscopy, and proteinuria appeared within 5 days. The effects of alterations in the dose of administered antibody, corticosteroid therapy, and vasoactive amine blockade on the development of subepithelial deposits and consequent proteinura were studied. Variation of the dose of anti-Fx1A from 0.25 ml. to 1 ml. resulted in a progressive increase in the size and number of glomerular capillary wall deposits, but no alterations in their distribution. Only those rats which received 1 ml. became proteinuric within 5 days. Corticosteroid therapy and vasoactive amine blockade, begun 24 hours prior to the induction of passive Heymann nephritis and continued until termination of the study 5 days later, had no effect on the amount or site of immune complex formation, nor on the extent of proteinuria as compared to untreated controls. In contrast, in rats with unilateral proteinuria produced by the selective perfusion of one kidney with aminonucleoside of puromycin 7 days prior to the induction of passive Heymann nephritis, there was a marked reduction of subepithelial deposits in the perfused kidney as compared to the nonperfused contralateral kidney. In this model of membranous nephropathy, systemic factors play little role in the development of subepithelial deposits, whereas local factors are critical. These findings are consistent with the hypothesis that subepithelial immune deposits form locally.


The role of macrophages in leprosy as studied by protein synthesis of macrophages from resistant and susceptible hosts--a mouse and human study.

3H-leucine uptake by macrophages from swiss white and C57BL mice before and after M. leprae infection was studied. A depression in 3H-leucine uptake after infection was observed only in swiss white mice. 3H-leucine uptake was also studied in blood derived macrophages from normals, and LL and TT patients. A depression was obtained in 3H-leucine uptake after M. leprae infection in macrophages from LL patients.


Histopathologic study of clinically normal appearing skin in lepromatous leprosy.

Skin biopsies from clinically normal skin of the scalp, axillary and groin regions in 20 lepromatous leprosy patients revealed significant histopathological findings in upto 25 percent of the patients. The positive findings could, perhaps, be enhanced by studying larger skin materials from these body areas. Indeed, no skin area appears to be immune from invasion by Myco. leprae.


The significance of changes in the nasal mucosa in indeterminate, tuberculoid and borderline leprosy.

A study of nasal biopsies from 137 leprosy patients classified on the basis of clinical, microbiological and skin biopsy as Indeterminate, Tuberculoid, Borderline-tuberculoid and Borderline-leproma was undertaken. Changes suggestive of leprosy viz., nerve and smooth muscle inflammation with a few acid fast bacilli in a proportion of the biopsies were seen in all groups of patients examined. This suggests, that even in Indeterminate and Tuberculoid leprosy the disease becomes generalised by the time clinical manifestations appear in skin. Tuberculoid granuloma was seen in two nasal biopsies from Borderline-tuberculoid leprosy patients, one of which was located in the wall of a vein, suggesting the possibility of intravascular dissemination of the disease even in non-lepromatous leprosy. 33 of the patients were children 15 years and below and they also showed changes such as nerve and smooth muscle inflammation but bacilli were seen only in the Borderline group. These findings suggest involvement of the nasal mucosa early in the course of the disease as 70% of the children had the skin lesion for less than one year. The nasal mucosa offers favourable conditions for the growth of the organisms and is readily accessible to infection by droplets, and therefore, it could be one of the primary sites of involvement in leprosy.


Combination chemotherapy for soft-tissue sarcomas: a phase III study.

A total of 144 patients with advanced sarcomas were entered into a randomized prospective protocol with four treatment arms utilizing different combinations of chemotherapeutic agents. Of these, 120 patients (83%) were judged acceptable. Treatment  1: actinomycin-D (Act-D), 0.01 mg/kg IV, days 1--5; phenylalanine mustard (L-PAM), 4 mg PO, days 1--10 every six weeks. Treatment  2: Act-D, 0.01 mg/kg IV, days 1--5; L-PAM, 4 mg PO, days 1--10; vincristine, 1 mg IV, days 1, 8, 15, 22, 29, 36, repeat every six weeks. Treatment  3: Act-D, 0.01 mg/kg IV, days 1--5; L-PAM, 4 mg PO, DAYS 1--10; NSC-1026, 200 mg/kg IV, days 1--6. Treatment  4: Adriamycin, 0.4 mg/kg IV, days 1, 2, 3, 8, 9, 10, then 2XWK starting day 15 (max. 1,200 mg). There was a provision that upon progression of the disease in the first three treatment regimens, patients would be crossed over to Treatment  4. Responses were as follows:  1 - Partial Response (PR) 1/25; No Change (NC) 9/25 (36%). gF2 - NC 17/26 (65%).  3 - NC 13/25 (52%).  4 - Complete Response (CR) 1/41; PR 6/41; (15%); NC 27/41 (66%). Clearly Treatment  4 was the best arm, with a 17% response rate and an initial progression rate of 17%. The only other response was a partial in  1. The difference is statistically significant (H = 17.247, P = 0.0006). If the responders to Adriamycin were analyzed without crossovers, the response rate would be 22% (6/27). (H =  14.079, P = 0.003). Median times to progression were 12.5, 8.7 weeks for  1 and  2, and 5 weeks for  3 and  4. There was no significant difference in the median survival times among the four treatment arms. It appears that Adriamycin as a single drug is superior to the drug combinations and would probably be even more effective used in combination with known active agents.


Differential lung blood flows in experimental unilateral emphysema: nonvalidity of perfusion scans.

As part of an evaluation of the effects of left lung transplantation in dogs with papain emphysema of the right lung, differential lung blood flows were estimated by in vivo scintiscan of 99Mc-macroaggregated albumin (99mTc-MAA) and, after sacrifice, by direct counting of isotopically labeled carbonized microspheres. In six dogs, percentage flow to the right lung was calculated at the following four times: before and after induction of papain emphysema and 2 and 6 weeks after left lung autotransplantation. After the induction of right lung emphysema, the right lung in four of six animals continued to receive more than 50 percent of the total pulmonary blood flow. No correlation could be established between right lung blood flow determined by carbonized microsphere distribution (true right lung blood flow) and the flow determined by anterior and posterior scintiscans (apparent right lung blood flow). This discrepancy was caused by gross distortion of the right, emphysematous lungs, which had herniated into the left hemithoraces. This herniation was demonstrated by coronal slices taken through the thoraces of two additional dogs with right lung emphysema that were given radiolabeled carbonized microspheres and 99Tc-MAA and frozen after sacrifice. These results indicate that external scintiscans for which the particulate distribution technique are used are invalid in circumstances of altered lung geometry.


Pectus carinatum.

In the mirror of the pertinent literature, we present our experiences gained in 161 operations for pectus carinatum. The Type I (keel chest) deformity is corrected by bilateral resection of the costal cartilages, transverse osteotomy of the sternum, detachment of the xiphoid process, and resection of the lower end of the body of the sternum. The sternum is maintained in its corrected position by utilizing the pulling force of the rectus muscles through the reattached xiphoid and by tacking the pectoralis muscles together in front of the breast bone. Type II (pouter pigeon breast) is handled by double transverse osteotomy, chiseling off the protuberant portion of the strernomanuberial junction, and by supporting the lower sternal body with either the suspended xiphoid process or with Marlex mesh. Limited forms of Type III  (asymmetrical or lateral pectus carinatum) are managed with simple resection of the involved cartilages only. If the anomaly is more extensive, bilateral resection of the cartilages and correction of the sternal axis is carried out.


Qualitative and quantitative changes in thoracic duct lymph during canine experimental shock.

Changes of the body fluid exchange and of the composition of metabolites in the hepatosplanchnic area in canine hemorrhagic and endotoxin or septic shock models were studied by investigating the qualitative and quantitative changes in thoracic duct lymph draining from abdominal organs. In the present study, it might be summarized that the changes in the flow rate and composition of thoracic duct lymph were put forward to much more directly and apparently indicate the degree of hepatosplanchnic cellular impairment in canine experimental shock than in the circulating blood.


Error propagation in viable cells.

Error propagation is the process, predicted by theoretical models, whereby errors in translating the genetic code will beget fresh errors in successive generations. It has been postulated that error propagation may underly the mortality of cells which display clonal senescence. We have demonstrated the occurrence of error propagation in viable cells of E. coli during growth in a low concentration of streptomycin, a drug which promotes ribosomal ambiguity. We monitored error propagation by measuring mistranslation of a specific UAA codon, and measured viability by direct enumeration of both live and dead cells through a sensitive microscopic technique. We find that the error frequency may be artificially increased by at least an order of magnitude without generating any detectable increase in the proportion of dead cells or of cells whose descendents are doomed to clonal senescence. The error frequency increases gradually over the course of a few generations, in qualitative agreement with the notion of error propagation, and eventually stabilizes at a constant value much higher than normal. The kinetics of this increase agree quantitatively with the Hoffman-Kirkwood and Holliday formulation of error propagation, for parameter values which dictate convergence to a stable error frequency. This convergent behaviour, under conditions of enhanced mistranslation, demonstrates that the normal parameters are well removed from the region of instability in error propagation; even an order of magnitude increase in mistranslation does not tip the translation system into the unstable mode which has been postulated to underly cell senescence. Thus, the error catastrophe theory of cell senescence cannot apply to the translation system of bacteria. We have reviewed experimental data on the fidelity of translation in somatic cells of higher organisms which militate against the notion that the translation system in these cell types could be much closer to the region of instability than in bacteria. These considerations controvert the error catastrophe theory of cell senescence.


Dissociation of the effects of nicotinic acid on vasodilatation and lipolysis by a prostaglandin synthesis inhibitor, indomethacin, in man.

The effects of nicotinic acid on plasma free fatty acid (FFA) concentration and forearm blood flow were studied in seven healthy fasting volunteers with and without pretreatment by indomethacin to see if some effects of nicotinic acid are mediated by release of endogenous prostaglandin. 1 g of nicotinic acid per os decreased plasma FFA concentration to a lowest value of 1/4 of initial level and increased forearm blood flow four times. When the same dose of nicotinic acid was given after pretreatment with indomethacin, the blood flow increase was only 1/3 of that without indomethacin. Indomethacin did not alter the rapid initial decrease in plasma FFA, although the period of low FFA concentration was shortened and the rebound to supranormal concentration was abolished. Thus the vasodilatory effect of nicotinic acid seems to be mediated by release of endogenous prostaglandin while the inhibition of lipolysis by the drug is mainly produced by other mechanisms.


Hypothalamic hormones and behaviour.

In recent years evidence has accumulated that hypothalamic hormones may influence behaviour directly, independently of their hypophysiotropic effects. Such a dual role has also been shown for several peptide hormones of pituitary and peripheral origin. The present synopsis is concerned with the effects of neuropeptides on spontaneous behaviour, acquired responses in certain psychological test situations, and drug-induced behavioural effects. A growing body of evidence suggests, that neuropeptides are involved in different behavioural processes. Some peptides selectively influence behaviours such as feeding, drinking, sexual responses etc. Other neuropeptides seem to influence behaviour by acting on processes which are a common integral part of the production of behaviour, namely the ability to receive environmental stimuli, to consolidate, retain and retrieve information. The insight into these mechanisms is important for the understanding of mental disturbances and in order to find specific therapy.


Reassessing the early effect of concurrent review on length of stay: Illinois, 1971--72.

The Hospital Admission and Surveillance Program (HASP) was a pre-PSRO program in Illinois. Established in February 1972, its objective was to reduce the cost of care given to Medicaid beneficiaries in that state. HASP approved length of stay (L.O.S.) on a prospective only basis, so that all Medicaid patients were reported promptly on admission. During 1972, the Illinois Medicaid program was rapidly expanding in patient volume, but not in scope of services. This study compares patients admitted to 46 hospitals in Illinois before and after the establishment of HASP. To adjust for changes in case mix between the two periods, each patient was matched for age, diagnosis and illness severity with patients in an appropriate comparison group. The complex process of matching raised the likelihood that changes in L.O.S. were caused by HASP's activities and not by other factors. L.O.S. fell significantly more for Medicaid than for non-Medicaid patients. In addition, the mix of diagnoses changed more markedly for Medicaid than non-Medicaid patients, emphasizing the need for case mix adjustments in this before-and-after study. Some findings suggest that the "post-HASP" admissions had the greater need for hospital care; this trend affected both Medicaid and non-Medicaid patients, however, The combined evidence suggests that concurrent review, as implemented by HASP, helped shorten L.O.S. in 1972. Whether quality of care changed was not studied.


Carrier discretionary practices and physician payment under Medicare Part B: a preliminary report.

Although Medicare is a national program, administration of Part B payments to physicians is in the hands of insurance organizations in ten Medicare regions. The carriers follow varying practices in using actual charges within localities as the basis for determining reasonable charges for physicians' services. While some of these practices have already been shown to influence fee levels, reasonable charge determination involves many more whose influence has not been systematically studied. This paper reviews preliminary findings from a study which examines carrier differences in discretionary practices as to specialties, localities and other claims data that may be merged or compared with Medicare data in determining customary and prevailing prices used to set limits on Medicare payments, and other practices reported in an official questionnaire to carriers. The effect on fee levels and other measures of program performance is being studied after taking into account social, economic and health resource variables extracted from the Area Resource File, that are expected to influence local medical prices through the demand for and supply of physicians' services. Dependent variables representing fees are the 50th percentile of the distribution of weighted customary charges of individual physicians in an area and Supplementary Medical Insurance expenditure per enrollee. The preliminary findings in this paper concern discretionary practices, socioeconomic variables and fee distributions.


Injury and repair of liver cells.

Alterations in hepatocytes, progressing to necrosis, are the morphologic basis for the main clinical manifestations and aberrations in hepatic test results in acute and chronic liver disease. The light-microscopic manifestations of hepatocellular injury, the mechanisms of necrosis, the light-microscopic features of repair and regeneration, and the applications of histologic alterations to the management and prognosis of liver disease are reviewed.


Host resistance in liver disease--its evaluation and therapeutic modification.

We have attempted to review some of the factors involved in host resistance and the variations in the individual responses to the infectious and noxious agents to which we are increasingly exposed. Few treatment modalities are available to favorably influence host resistance, but clearly, this approach to the treatment of liver disease represents an opportunity for the future.


Liver transplantation.

This assessment of the role of liver transplantation in treating end-stage liver disease today is based on two major series, one from Denver and the other from the Cambridge/Kings College Hospital, England. The findings of these groups are highlighted, as are the changes in technique that have led to considerably improved survival in the past two years.


Studies of nucleic acid and collagen synthesis: current status in assessing liver repair.

Much progress has been made in delineating biochemical, physiologic and morpholigic events in liver regeneration and collagen synthesis. Pharmacologic agents have been purported to be helpful in facilitating repair and preventing fibrosis. Objective indices are now available to monitor their effectiveness in man.


Advances in the management of bile duct obstruction: percutaneous transhepatic cholangiography and endoscopic retrograde cholangiopancreatography.

Jaundice can be diagnosed anatomically and frequently histopathologically without laparotomy by radiologic and endoscopic techniques, combined with biopsy or cytology. Benign and malignant causes of bile duct obstruction can be managed by endoscopic and radiologic methods with reduced morbidity and mortality, displacing abdominal operation for many entities. Even unresectable or inoperable lesions can be effectively palliated by these new techniques.


Viral hepatitis: progress and problems.

The recognition of viral hepatitis has been facilitated by the use of serologic studies for types A, B, and non-A, non-B. The course is best determined by serum enzyme determinations, followed by clearance studies of bile acids or dyes once the serum enzymes return to normal. In patients with persisting clinical or biochemical abnormalities and those in which the nature of the disease is not known, liver biopsy should be done.


Clearance tests of liver function.

Measurement of the clearance of substances removed from the circulation primarily by the liver, which depends on the uptake, storage, and excretory capacity of the liver, provides the most sensitive, specific, and reliable test for hepatic function. Since serum enzymes and other tests of liver function do not permit detection of early phase injury or provide information on progress, and since the use of sulfobromophthalein has been discontinued because of occasional fatal reactions, substitutes are necessary. Clearance of indocyanine green, bile acid, and exogenous metabolites such as galactose, protein, and aminopyrine are reviewed.


[Clinical experiences with a human fibrin adhesive in head and neck surgery (author's transl)].

Clinical experiences in a timespan of two and a half years with a human fibrinogen concentrate in head and neck surgery are reported. In 49 patients with different bleeding disorders tonsillectomies, adenectomies and nasal dermoplasties (Osler's disease) were carried out. In these cases primary hemostasis due to the fibrin adhesive combined with an allogenic collagen implant could be obtained without any subsitution of the deficient blood clotting factors. In all these cases no complications could be observed. In other 193 cases which underwent a surgical treatment in the head and neck region (frontobasal and laterobasal fractures, rupture of the carotid artery, closure of perforations of the nasal septum and oroantral fistulas, different methods of skinmucosa- and nerve-grafting) the fibrin adhesive was successfully used.


Assessement of surgical procedures for Ménière's disease.

There are numerous surgical procedures for the treatment of Meniere's disease, and the current status of their efficacy is controversial. A review of the literature is presented as a basis for the evaluation of the relative merit of these procedures. Emphasis is placed on endolymphatic sac procedures, sacculotomy, vestibular neurectomy and labyrinthectomy. Vestibular neurectomy and surgical labyrinthectomy provide high rates of improvement in vertigo. The hearing is frequently made worse by vestibular neurectomy. Endolymphatic sac procedures result in improvement in vertigo less frequently. They are most likely to improve hearing. Although sacculotomies are associated with improvement in vertigo in approximately 80% of patients, they are associated with high rates of hearing loss.


The transseptal approach to lesions of the pituitary and parasellar regions.

In a series of 505 consecutive procedures, the transseptal-transsphenoidal pituitary operation has proved safe and effective. The overall mortality in this series is 1.39%. A wide variety of sphenoid and sellar lesions and nearly every pituitary adenoma have been found suitable for the exposure provided through the sublabial-transseptal approach. This statement rests on the premise that both the rhinologist's and the neurosurgeon's skills are optimally applied to each case. The role of the otorhinolaryngologist is defined in this paper, and the benefits of the team approach are explored. An interpretive history of the transsphenoidal approach is presented, and the evolution of the transseptal technique developed at the Mayo Clinic from 1972 to 1978 is reviewed. Emphasizing the rhinologic aspects, all details of the surgical technique are described and illustrated. Our experience with the special endocrine syndromes is also reviewed to spotlight clinical features that require individual consideration by the rhinologic surgeon.


The effect of aging on carbohydrate metabolism: a review of the English literature and a practical approach to the diagnosis of diabetes mellitus in the elderly.

There seems little doubt that the disposal of a glucose load is progressively impaired during aging. The mechanism(s) for this alteration remains unclear. Five possibilities have been raised: (1) poor diet, (2) physical inactivity, (3) decreased lean body mass in which to store the carbohydrate load, (4) decreased insulin secretion, and (5) insulin antagonism. Although poor diet and physical inactivity may contribute to some of the abnormal glucose tolerance tests of the older population, these two factors do not provide a full explanation. Diminished lean body mass may play some role but there is almost certainly an additional effect due to aging. A few papers have suggested that glucose-induced insulin secretion may be impaired as the population ages, but the bulk of studies in this area conclude that normal or increased amounts of insulin are released by the pancreatic beta-cell during aging. If abnormalities of insulin secretion exist, either in degree or timing, they are subtle and would not seem sufficient to account for the great number of older subjects who manifest impaired glucose tolerance. The evidence for insulin antagonism seems the strongest but the data are certainly not conclusive. In actuality, the aging effect on carbohydrate metabolism may be heterogeneous in nature. Either some or all of these five factors may contribute to the aging effect to varying degrees in individual subjects. Alternatively, the glucose intolerance of aging may represent a heterogeneous group of disorders. In any event, until better methods to identify possible subgroups of these subjects and/or a marker for diabetes mellitus independent of glucose concentration become available, this problem will remain difficult to resolve. Based on the currently available data, it seems prudent to diagnose diabetes mellitus only if fasting hyperglycemia is present.


Isolation and characterization of yeast mutants auxotrophic for 2'-deoxythymidine 5'-monophosphate.

Mutant strains of Saccharomyces cerevisiae auxotrophic for deoxythymidine monophosphate (dTMP) were isolated and characterized. Two distinct classes of auxotrophs were obtained. One class had a simple requirement for dTMP and was analogous to thymine-requiring bacteria. The second class required dTMP, adenine, histidine and methionine and this complex nutritional phenotype was due to defects in folate metabolism. The dTMP-dependent growth of respiratory-competent grande auxotrophs was found to be markedly affected by media composition and carbon source. In the absence of dTMP thymineless death occurred in both mutant classes.


Repetition of tetracycline resistance determinant genes on R plasmid pRSD1 in Escherichia coli.

The 30 megadalton (Mdal)-conjugative, fi- plasmid pRSD1 determines inducible tetracycline resistance (Tc) in Escherichia coli. As shown by restriction analysis, a 3.5 Mdal-EcoRI fragment of pRSD1 spliced into the small plasmid pRSD2124 comprises the entire Tc determinant (tet) region. A restriction map of pRSD1 is presented which includes the location of the tet region and of an "underwound" loop not related to Tc (Burkardt et al., 1978). Selective amplification of tet genes is demonstrated by three lines of evidence. (i) The resistance level of cell harbouring pRSD1 increases approximately tenfold by induction with 10 microgram/ml of tetracycline. Further growth in the presence of 100 microgram/ml of the drug ("tetracycline stress") selects for cells with even higher resistance levels (about 300 microgram/ml) in rec+ cells. In a recA strain, a smaller proportion of cells attains these high resistance levels suggesting the involvement of host recombination. (ii) Electron micrographs of pRSD1-DNA isolated from tetracycline-stressed cells reveal a heterogeneous population of circular DNA molecules ranging between 1.7 and 21.6 micron. The distribution of contour lengths shows a discrete pattern ascribed to the presence of autonomous single- and multiple-copy Tc determinants and to intact plasmids containing zero to six tet regions in tandem repeats. (iii) This interpretation is supported by heteroduplex and restriction analyses which demonstrate the presence of multiple copies of the 3.5 Mdal-element encompassing the tet region in pRSD1 molecules selected by tetracycline stress. It has been concluded that gene amplification leading to tandem repetition of the tet region ensues in pRSD1. Such plasmids confer increased tetracycline resistance and can, thefore, be selected by high doses of the drug.


Control of the initiation of DNA replication in Escherichia coli. I. Negative control of initiation.

A transient stimulation of the initiation of DNA replication during inhibition of protein synthesis has been demonstrated in dnaA5 and dnaA46 mutants. This suggests the existence of a negatively acting control protein (not the dnaA product) which decays rapidly or is removed during a block in protein synthesis. The stimulation of initiation is dependent on a previous accumulation of initiation specific proteins, which suggests that in addition to the negative control other control mechanisms are effective.


Control of the initiation of DNA replication in Escherichia coli. II. Function of the dnaA product.

General growth parameters and the kinetics of DNA replication have been determined in merogenotes carrying different combinations of the dnaA+ and the dnaA5 allele. The strain which is homozygous diploid for dnaA5 is different from all other combinations in cell volume, DNA per mass ratio, number of replication points per chromosome, and polymerization rate of DNA. From this we deduce that the dnaA product is a positively acting regulatory protein in initiation. In an appendix we show that in combinations between the dnaA5 and dnaA204 alleles the phenotype of dnaA5 is dominant.


Pathways for repair of DNA damaged by alkylating agent in Escherichia coli.

A strain with both the polA12 and the alk-1 mutation is only slightly more sensitive to methyl methane sulfonate (MMS) than isogenic strains with only one of the mutations. On the other hand, alk-1 recA1 double mutant is much more sensitive to MMS than are strains carrying either one of alk or recA mutation. It was suggested that the alk and the polA gene products are involved in the same DNA repair process whereas the recA function is independent from the process. The yield of MMS-induced mutation (Arg- (argE) to Arg+ reversion) in alk mutant is considerably higher than that in wild type strain. Thus, the repair process in which the alk gene product is involved is relatively accurate. When MMS-treated lambda phages were plated on MMS-treated bacteria, there were considerable increases in survival of treated phage even in recA alk double mutant. It seems that a new repair pathway, which is specific for alkylating agent-induced damages and is not dependent on the RecA function, may be induced on exposure of bacteria to the alkylating agent.


Threonine deaminase: autogenous regulator of the ilv genes in Escherichia coli K-12.

In this paper we analyze the effect of mutations in three genes, ilvO, ilvA and rho, on the expression of the ilvEJGDA gene cluster of Escherichia coli K-12. The ilvO603 mutation causes a cis-dominant derepression of the ilvEJGDA genes. In particular, the ilvG gene, not expressed in the wild type, becomes expressed in the ilvO603 strain. We have introduced ilvA mutations (ilvA454 or ilvA628) in the ilvO603 strain and we show that ilvG expression requires the presence in cis of both an ilvO603 mutation and of an ilvA+ allele. The ilvG gene is not expressed when in trans is present an ilvO+, ilvA+ genotype. However, it is expressed when the chromosome in trans is ilvO603, ilvA+ (ilvG-). We suggest that ilvO603 is part of ilvA, the structural gene for threonine deaminase, and that threonine deaminase from the ilvO603 mutant binds the ilvO603 site and not the ilvO+ site. Therefore, the ilvA gene product would be a cis-acting protein. Mutations in the rho gene cause derepression of the ilvEJGDA gene cluster without a concomitant expression of the ilvG gene. We show that introduction of either a rho-218 or a rho-115 mutation into the ilvO603, ilvA454 double mutant causes expression of ilvG. We therefore suggest that the ilvA gene product, threonine deaminase, is involved in termination of transcription as an antagonist of the rho gene product. Introduction of ilvA454 into an ilvO603 strain causes also a decrease in expression of the ilvE, ilvJ and ilvD genes. This effect is maximum in the case of the ilvD gene and we studied it in detail in isogenic strains containing also the rho-218 mutation.


The nucleotide sequence of a DNA fragment from the replication origin of the antibiotic resistance factor R1drd19.

The recombinant plasmid pRK101 contains a DNA fragment which carries the complete replication origin of the antibiotic resistance factor R1drd-19 inserted into the vector plasmid pBR322. In a spontaneously arising mutant of this plasmid (pRK103) a deletion of about 215 base pairs (bp) has been detected by heteroduplex analysis and mapping with restriction endonucleases. Essential parts of the replication origin must be located in the deleted sequence. The deletion mutant pRK103, in contrast to its parent plasmid pRK101 is not replicated under the control of the R1 replicon, even when the R1 factor or copy mutants of it are present within the same cell. These latter plasmids can complement a plasmid-specific protein not coded by pRK101 but essential for R1-directed replication. The nucleotide sequence of a 252 bp HpaII fragment covering about 170--200 bp of the deletion was determined. This piece of DNA is rich in G and C and contains a series of small palindromes, symmetrically arranged repeated sequences and short selfcomplementary structures which may be of significance for the initiation of the DNA replication. The possiblity that the sequenced DNA fragment comprises a major part of the replication origin of R1drd-19 is discussed.


Replication and maturation of phage P22 in a mutant of Salmonella typhimurium temperature sensitive in initiation of DNA replication.

TB37 is a dna A-mutant of Salmonella typhimurium in which the initiation of DNA replication at the origin is stopped at 42 degrees C. DNA synthesis in uninfected cells of this strain and in cells infected by phage P22 was followed by the pulse labelling technique. DNA replication ceases completely after about 50 minutes at the high temperature. After lytic infection with P22 (c2) at this time, DNA synthesis starts immediately and increases at a rate well comparable to the permissive control. Obviously the temperature sensitive function of the dnaA-product is dispensable for P22 DNA replication, especially for its initiation. This result is confirmed by the normal yield of phage particles under these conditions, provided that a late step in P22 maturation which naturally is temperature sensitive can proceed at low temperature. If TB37 is infected at 42 degrees C with P22 wild type, an unexpected high rate of phage controlled DNA synthesis is observed. Preliminary results seem to indicate that the process of integration is a prerequisite for part of this synthesis.


Comparison of amino acid compositions of mitochondrial and cytoplasmic ribosomal proteins of Saccharomyces cerevisiae.

The amino-acid compositions of the mitochondrial ribosomal subunits of Saccharomyces cerevisiae have been determined and compared to those of cytoplasmic ribosomal subunits. For the large subunits, the mitochondrial and cytoplasmic ribosomes showed major differences in the proportions of arginine, alanine and methionine. For the small subunits, arginine, aspartic acid, alanine, valine and methionine showed marked differences. We have compared these amino-acid compositions with those already published of bacterial and eukaryotic ribosomes by a statistical method of data analysis. It appeared clearly that the yeast mitoribosomes are more distant from bacterial ribosomes than from eukaryotic cytoribosomes.


Mechanism of conjugation. II. Characterization of an Hfr dna ts mutant of Escherichia coli K-12.

A new conditional thermosensitive Hfr mutant of Escherichia coli K-12 was isolated. The ts mutation is cotransducible with purE and tsx loci on the E. coli chromosome. Upon temperature shift to 42 degrees C the DNA synthesis and transfer of chromosome is stopped immediately and RNA, protein synthesis in about ten minutes.


Evidence for endonucleolytic cleavage at the 5'-proximal segment of the trp messenger RNA in Escherichia coli.

The 5'-proximal trp leader RNA segment (about 5S) decays at 2 to 3 times slower rates than the distal trp mRNA sequence. This has been demonstrated by employing the deletion mutants which lack a large portion of the structural genes but retain the promoter-proximal region of the trp operon. Relative stability of the leader RNA is not merely due to the presence of an untranslatable region in the segment; the internal untranslatable segment of trp mRNA downstream from the nonsense alteration site of a double mutant trpAD28.trpE9758 decays as fast as the normal trp mRNA sequence. These results suggest that the trp mRNA is endonucleolytically cleaved to yield the small 5'-proximal leader RNA segment before the distal mRNA decays and that the leader RNA sequence is not subject to usual mode of mRNA decay in the 5' to 3' direction.


Mutagenesis and repair deficiencies of Escherichia coli umuC mutants are suppressed by the plasmid pKM101.

The presence of the drug resistance plasmid pKM101 restored the ability of Escherichia coli umuC mutant strains to be mutated by methyl methanesulfonate. Inducible (Weigle) reactivation of ultraviolet-irradiated bacteriophage lambda was not observed in uvrA6 umuC mutant strains lacking pKM101 but was observed if the plasmid was present in the strains. In a uvrA+ umuC36 strain pKM101 increased the efficiency of the Weigle reactivation process. Plasmid-mediated UV-resistance and plasmid-mediated phage reactivation were observed in umuC(pKM101) strains both in uvrA+ and uvrA6 backgrounds. No restoration of methyl methanesulfonate mutability by pKM101 was observed in umuC36 recA56 strains. pKM101 mutants unable to enhance mutagenesis in umuC+ backgrounds also had no effect on methyl methanesulfonate mutagenesis in umuC mutant strains. Neither a umuC mutation nor the presence of pKM101 affected the UV induction of protein X, the recA protein. Hypotheses relating the mode of action of pKM101 to the process of mutagenesis and inducible phage reactivation are discussed.


Catalase anabolism in yeast: loss of regulation by oxygen of catalase apoprotein synthesis after mutation.

A mutant of Saccharomyces cerevisiae which displays catalase activity when grown under strictly anaerobic conditions has been selected on solid media. Although some preformed holoenzyme has accumulated in anaerobic cells, a sharp increase of activity is still measured during adaptation to oxygen in glucose-buffer; however, a striking difference with the wild-type strain is that in the mutant, catalase formation is observed in the presence of cycloheximide that totally inhibits cytoplasmic translation. It is concluded that kat 80 mutant has lost the regulatory control by oxygen of apocatalase synthesis; the later precursor, characterized as apocatalase synthesis; the latter precursor, characterized as apocatalase T, is thought to be activated in vivo, under aerobic conditions, by inclusion of prosthetic group. Regulation of enzyme synthesis by catabolite repression (glucose erfect) persists, unmodified by reference to the wild-type parental strain. Mutation kat 80 specifically hits catalase anabolism, as no significant variations were observed for the edification of the respiratory system and (apo)cytochrome c peroxidase production. Genetic analysis shows that kat 80 phenotype, recessive in heterozygotes, results from a single nuclear mutation.


Characterisation of Tn1721, a new transposon containing tetracycline resistance genes capable of amplification.

R plasmid pRSD1 contains tetracycline resistance (tet) genes in a 3.55 Mdal-region capable of amplification by forming tandem repeats (Mattes, Burkardt and Schmitt, Molec. gen. Genet., 1979). The repetitious tet element is itself part of a 7.2 Mdal-transposon, named Tn1721, as demonstrated by the following criteria; (i) Tn1721 has been translocated to phage lambda. The resulting hybrid phage lambda tet contains the 7.2 Mdal-insertion to the right of the attachment site, but not continguous with it indicating translocation of the element by non-homologous recombination. In addition, lambda tet has sustained a 3.4 Mdal-deletion adjacent to the insertion. (ii) Further transposition of Tn1721 to the 21.5 Mdal-plasmid R388 resulted in R388::Tn1721 derivatives, two of which were characterised. They contain Tn1721 inserted into different sites but in the same orientation as shown by restriction and heteroduplex analyses. These translocation of Tn1721 were not accompanied by deletions of DNA. (iii) The insertion plasmid pRSD102(R388::Tn1721) has conserved the capacity of the original plasmid pRSD1 to amplify the 3.55 Mdal-tet region. It has been concluded that Tn1721 constitutes a novel transposon encompassing a tet region capable of selective amplification. The model proposed for Tn1721 contains three short repeats. Two direct repeats, flanking the 3.55 Mdal tet region, provide sequence homology for amplification. The third repeat (located distally to tet) is inverted and provides the basis for transposition of the 7.2 Mdal-element.


Map position of the replication terminus on the Escherichia coli chromosome.

The directions of replication of several prophages integrated with a known orientation in the vicinity of the terminus (tre) of chromosome replication (trp::Mu, min 27; lambda rev integrated within rac, min 31, man::Mu, min 35), have been established by determining the molecular polarity of Okazaki pieces specific to these prophages. The results obtained strongly suggest that the site tre is located between rac and man, an otherwise genetically silent region.


"Nick translation" in Escherichia coli rep strains deficient in DNA polymerase I activities.

Using phiX1974 replicative form (RF) DNA as an in vivo probe, we have investigated the coordinated action of the 5' leads to 3' exonuclease and polymerase activities of DNA polymerase I in order to understand better its physiological role. We constructed double mutants containing the rep mutation (the replication of phiX174 RF does not occur in rep mutants) together with a mutation affecting DNA polymerase I, either polA12 or polA546ex. Using these mutants, which are believed to be thermosensitive in the polymerase function or the 5' leads to 3' exonuclease function respectively, we studied the kinetics of nick translation at the permissive and non-permissive temperatures in vivo. The substrate was the phiX174 replicative form DNA nicked by the phiX174 gene A protein. E. coli rep polA546ex gave the lowest rate of nick translation, although the ability to perform nick translation, at least as measured by our assay, was still present. E. coli rep polA12 showed a similar low rate at the non-permissive temperature but a rate close to the wild-type level at the permissive temperature. Formation of the parental replicative form molecule in either strain was affected little, even at the restrictive temperature. Our results suggest that DNA polymerase I may not play a major role in ongoing DNA replication.


Electron microscopic analysis of the yeast mitochondrial DNA segment conferring chloramphenicol resistance.

Mitochondrial DNAs from six p- mutants carrying the genetic locus Rib1 and deleted for the rest of the genome were analyzed. Distribution of circular molecules from one mutant followed exactly the frequency rule, l/n, for multimers with discreet classes n, 2n, 3n, etc. Another, genetically unstable mutant displayed a continuous spectrum of circular molecules of various lengths. Four other mutants contained multiple series of circular molecules. Partial denaturation maps show that the mutants analyzed show a common segment ca. 1.0 micron long and differ by characteristic deletions of extremites of this segment. Short terminal deletions of the right i.e. pointing towards the Rib3 locus, terminus of this segment are correlated with modifications of the recombination properties related to the omega locus.


Virus-like particles and double stranded RNA from killer and non-killer strains of Saccharomyces cerevisiae.

Virus-like particles and DsRNA found in extracts of killer, non-killer and suppressive non-killer strains were co-precipitated from cell extracts using an antibody prepared against purified virus-like particles isolated from a non-killer strain having only the higher molecular weight L dsRNA. The relative amount of virus-like particles correlated roughly with the amount of dsRNA: those strains with high concentrations of dsRNA had the most particles. When a preparation of particles was subjected to sucrose gradient velocity centrifugation, particles containing the S and M dsRNA could be separated from those containing the L dsRNA. These experiments taken together suggest that the L, M and S dsRNAs are separately encapsulated by the same protein coat.


Regulation of the synthesis of M protein by sugars, Todd Hewitt broth, and horse serum, in growing cells of Streptococcus pyogenes.

Various sugars were tested for their effect on the differential rate of synthesis of M protein during the growth of Streptococcus pyogenes strain 0055 M12T12. In a semisynthetic medium alone, a high rate of M protein synthesis occurred with glucose as a substrate; decreasing rates of synthesis occurred with sucrose and trehalose, in that order, although the rates of growth were approximately equal with all sugars. A period of derepressed synthesis of M protein occurred in the lag phase of growth and in the stationary period as the substrates were being depleted. Although glucose inhibited the utilization of other sugars, diauxie was not apparent from the growth curves. However, synthesis of M protein followed strong diauxie curves with a reduction in rate of synthesis during the utilization of the second sugar. With glucose as a substrate, 2-deoxyglucose showed a strong permanent repression of M protein synthesis, whereas both glucose and 2-deoxyglucose caused temporary repression when sucrose was the substrate. Horse serum increased the rate of synthesis of M protein in a manner very similar to that caused by adding cyclic AMP, although quantitative analyses suggested that cyclic AMP, per se, was not the effector in horse serum. Addition of Todd Hewitt broth permitted the organisms to grow on phosphorylated sugars. Although the rates of growth on phosphorylated sugars were similar to that obtained with glucose, M protein was not synthesized when a phosphorylated sugar was the sole substrate. The addition of phosphorylated sugars with glucose or sucrose as substrates strongly repressed the synthesis of M protein with glucose-1-phosphate and with fructose 1,6-diphosphate repressing M protein synthesis the most. Clearly, M protein synthesis, which was not required for growth, was preferentially induced by glucose as compared to the other sugars and was dependent upon the metabolic route by which glucose was utilized.


R plasmids with thermosensitive transferability in Salmonella strains isolated from humans.

Temperature dependence of transfer was examined with ten R plasmids originating from clinical isolates of Salmonella. Six of the plasmids were thermosensitive upon transfer, five of which were originally harbored in S. typhimurium and the remaining one in S. derby. One of these plasmids, pNR502, which conferred resistance to kanamycin, streptomycin (Sm) and tetracycline (Tc) on its host was stably maintained both in Salmonella and Escherichia coli at either 30, 37, or 43 C. Another plasmid, pNR516, which was resistant to chloramphenicol, sulfathiazole, Sm and Tc, was slightly unstable only at 43 C. The remaining four plasmids, pNR503, pNR510, pNR512 and pNR514, conferred resistance to Sm and Tc. Of these plasmids, the former two were stably maintained at both 30 and 37 C, but were unstable at 43 C. The latter two were slightly unstable at the lower temperatures and considerably unstable at 43 C. Kinetics of the transfer of the plasmid pNR503 revealed that the efficiency of transfer of the plasmid between E. coli strains was affected not only by the temperature of the conjugation but also by the preincubation temperature of the donor culture before the conjugation.


Leukocyte migration inhibition test (LMIT) in systemic lupus erythematosus.

A leukocyte migration inhibition test (LMIT) utilizing the agarose gel technique was performed with native DNA as an antigen in ten patients with systemic lupus erythematosus (SLE) and five normal subjects. Irrespective of disease activity, supernatants obtained at different time intervals during lymphocyte culture in eight patients with SLE showed significant alteration of migration, either enhancement or inhibition, of normal leukocytes. However, supernatants in the control experiments produced no significant alteration of migration. Polyacrylamide gel electrophoresis of supernatants obtained from the SLE group revealed that the inhibitory activity was present in the albumin region, whereas the enhancement activity was found in the beta-globulin region. These results indicate that the hitherto employed estimation of the leukocyte migration inhibition test based on the total activity of these two factors is insufficient for accurate evaluation of chemical mediators from sensitized lymphocytes and that the separation of these two factors may be important for a greater understanding of cellular immunity.


Coliform status of domestic swimming pools.

An investigation of maintenance, usage, and coliform status of water in 104 domestic swimming pools in 13 Brisbane suburbs was made in January, 1978. The results showed that domestic pools are often imperfectly serviced, and are potential infection sources. The need for health education of pool owners, and for more reliable methods of pool sanitization is emphasized.


Trichomonas vaginalis infections in Sydney: laboratory diagnosis and prevalence.

The prevalence of trichomoniasis in Sydney was determined by examining 1070 sexually active females in three different practices. Infection rates ranged from 17.8% in a sympatomatic venereal-disease clinic group to 0.5% in non-promiscuous family-planning clinic patients. In each of these categories, the infestation rate, when compared with overseas reports, was lower but no explanation for this difference is apparent. Of the various laboratory methods used to detect Trichomonas vaginalis, the most sensitive was a culture method. The most convenient and reliable microscopy technique was phase-contrast microscopy which detected 80% of those with positive culture results. Stuart's Transport Medium will maintain trichomonad's viability for at least 24 hours and allow vaginal specimens to be reliably transported for examination.


Trimethoprim/sulphamethoxazole and doxycycline in acute exacerbations of chronic bronchitis in general practice: a comparative study.

Fifty-six patients with acute exacerbation of chronic bronchitis were given one week's treatment either with a combination of trimethoprim and sulphamethoxazole (TMP/SMX) or with doxycycline, in a single blind trial. The study found no significant difference in response to the two treatments, and confirmed that both TMP/SMX and doxycycline are effective and well tolerated agents, which are suitable for the management of acute or chronic bronchitis.


[Induction of colicin E1 synthesis in Escherichia coli cells with different concentrations of plasmid DNA].

RRelationship between the level of induction of colicin E1 synthesis and the content of plasmid DNA in Escherichia coli K12S (E1) cells was studied. The number of Col E1 DNA copies per cell was found to decrease with growing generation time for different growth media and to increase continuously for the time of synchronous cell division cycle. No apparent relation of the level of spontaneous induction and of induction caused by N-methyl-N'-nitro-N-nitrosoguanidine to the number of Col E1 DNA copies per cell was observed. It is inferred that the content of plasmid DNA in the cells is not among the main factors determining the level of induction of colicin synthesis.


[Mathematical model of tryptophan synthesis and excretion into the environment by E. coli cells].

A quantitative kinetic model is suggested for the auto-regulated tryptophan synthesis by E. coli trp-operon system and for tryptophan excretion from the cell mediated by transport systems. Applications of the model for the calculation of several parameters characterizing tryptophan metabolism are considered. In order to explain experimental data it is suggested that a system of tryptophane excretion from the cell exists which is induced by high tryptophan concentrations. The rate of tryptophan excretion was studied as a function of various genetic effects (derepression or reduction of retroinhibition) as well as of changes in intracellular concentrations of substrates of tryptophan synthesis (chorismic acid and serine). Possible ways of making the cell to excrete markedly higher quantities of tryptophan without changing the genotype are discussed.


[Topological model of bacteriophage-T4 DNA replication].

The structure and function of the DNA--membrane complex in E. coli cells infected with bacteriophage T4 was studied. The DNA--membrane complex was isolated from the cells pulse or uniformly labeled with 3H-thymidine, fractionated by detergent treatment and separated on a discontinuous sucrose gradient. The attachment of small DNA fragments to the plasma membrane was analysed. Replicating bacteriophage T4 DNA was reversibly associated with the cytoplasmic membrane in the wall/membrane adhesion zones of the envelope. In the adhesion zone the cell wall, cytoplasmic membrane, DNA, different replicative proteins, probably form the initiation complex resistant to sonication, DNAase and Triton-X-100. This association is probably reversible. The topological aspects of bacteriophage T4 DNA replication are discussed.


[ATP analogs in the RNA-polymerase reaction].

The influence of some ATP analogs with the modified ribose residues on the transcription in vitro was studied. It was shown that all analogs are weak inhibitors competing with in RNA synthesis. Under certain conditions (ionic strength = 0.13, 25 degrees C) the only effective inhibitor of RNA synthesis 3'-O-methyl-ATP arrests reaction irreversibly. Perhaps as a result of its incorporation into the terminal position of the growing RNA chain. The increase of the temperature and of the ionic strength results in changes of the character of inhibition: 3'-O-methyl-ATP becomes (like other analogues) a reversible competitive inhibitor with a Ki = 4 . 10(-5) M. Some speculations concerning the mechanism of inhibition are discussed.


[Isolation and characteristics of plasmids determining multiple antibiotic resistance in strains of group A streptococci].

DNA of the streptococcal plasmid ERLI, determining resistance to erythromycin and lincomycin has been studied. The presence of satellite DNA component in streptococcal DNA has been demonstrated by dye-CsCl and CsCl density centrifugation, by chromatography of denatured-renatured DNA on the nitrocellulose and by electron microscopy. By all these methods the presence of covalently closed circular DNA molecules has been shown. Plasmid DNA has buoyant density in CsCl equal to 1.698 g/cm3 (GC content--38.8%), molecular weight (by electron microscopy) -- 19.8 Mdal; number of copies chromosomal genome equivalent is equal to about 4--4.5. Plasmid ERLI DNA was extracted from an original strain-carrier of plasmid ERLI, from a transduced strain which received plasmid ERLI as a result of transduction and lysogenization by phage "mo" and from the two antibiotic sensitive EMS mutants of resistant strain. Satellite DNA could not be isolated from a sensitive strain which served as a recipient in transduction experiments. The results obtained are in agreement with the literature on the molecular weight of the plasmid measured by the sedimentation analysis and with the previous genetic data on the antibiotic resistance within group A streptococci.


[Circular dichroism of DNA--dye complexes. II. Anisotropy of the long-wave circular dichroism effect and structure of the complex].

Anisotropy of torsional strength of the splitted electronic transition in the case of chromophore-chromophore interaction of dye molecules situated on the helical matrix was considered theoretically and as analytical expression for the value Rperpendicular/Rparallel was obtained. These theoretical results were compared with the experimental data obtained with DNA-proflavine, DNA-pyronine and DNA-acridine orange complexes oriented in multicappilar flow-cell. Studies of the optical effects (optical density and CD changes) due to orientation of these complexes showed that the acridine chromophores are not perpendicular with respect to the DNA axis (alpha D = 19--22 degrees). The DNA base pairs in complexes as assumed also are not perpendicular to the DNA axis, the inclination angle of their transition moments (for the band near 260 nm) being bigger than that of dye chromophores (24 degrees). These results indicate that under experimental conditions used by us no intercalation can be observed.


[Distribution of DNA sequences recognized by specific endonucleases].

The molecular weight distributions of fragments obtained after endonuclease treatment of DNA were studied. DNA's from pigeon and E. coli and restriction enzymes EcoRI and BamHI were used. The samples of 14C- and 3H-labelled DNA were treated by endonucleases, separated electrophoretically in 1% agatose gels, and radioactivity distributions along gels were measured. From these data weight and number distributions and the average molecular weights of DNA fragments were determined. EcoRI-fragments of phage DNA were used as standards for the molecular weight calibration. The experimental results are compared with the expected data calculated from the DNA GC content. The molecular weight distribution of fragments and the average molecular weights of BamHI-fragments of pigeon DNA and EcoRI- and BamHI-fragments of E. coli DNA differed from random ones. It is suggested that certain genomes contain regions in which the probability of endonuclease cleavage strongly differs from the average probability of such a cleavage for the entire genome.


[Sex factor F of Escherichia coli K12 and its participation in mobilizing bacterial chromosomes].

The structural and functional organization of F-factor reviewed and the physical map of F DNA, supplemented with a list of genetic markers, is presented. The DNA transfer during the conjugation is considered and especial attention is given to F-gene functions involved in this process. The special sequences of F DNA, homologous to resident insertion sequences in bacterial DNA are described and its participation in plasmido-chromosomal recombinant events both dependent and independent on recA function is discussed. The mechanism for chromosome mobilization by F-Factor are reviewed. A possibility of chromosome transfer without F DNA insertion is considered. In a latter case it proposed that spontaneous single-strand breaks may serve as the origins for initiation of chromosomal transfer.


[Role of the N-terminal sequence (1-26) in the dimerization of protein L7 in solution].

Native protein L7 from E. coli ribosomes, oxidized protein and a fragment of protein L7 containing the sequence 27--120 obtained by cleavage of the native protein by cyanogen bromide were investigated by sedimentation analysis. It was found that protein L7 exists in solution in a dimer form while the protein oxidized by hydrogen peroxide and the fragment 27--120 do not form a dimer. On the basis of these investigations a conclusion is made that the ability for dimerization is stimulated by N-terminal regions of the protein L7 molecule.


[Conformation theory of polymers and biopolymers].

A short review is given of the Soviet investigations in the field of physics of polymers and biopolymers based on the concept of conformational motility of macromolecules. It is shown that the ideas originally used for the treatment of the properties of the synthetic polymers and, in particular, of the rubber elasticity, have found broad applications in molecular biophysics.


Adult-onset acid maltase deficiency: a postmortem study.

In a postmortem study of a patient with adult-onset acid maltase deficiency (AMD), morphological abnormalities were confined to skeletal muscle and consisted of a vacuolar myopathy. Acid maltase activity, however, was approximately 6% of normal in muscle, liver, and brain, and 3% of normal in heart. Kinetic characteristics, and inhibition by antibodies and Zn++, showed that the residual activity was "authentic" acid maltase. Neutral maltase activity was normal in muscle and liver, but decreased in brain (55% of normal) and heart (19% of normal). Although the relative decrease of acid maltase was similar in different tissues, absolute residual activity was lowest in skeletal muscle: this may explain the selective involvement of this tissue in late-onset AMD.


[Molecular melting of DNA and the effect of the fine structure of fusion curves].

The progress in understanding the phenomenon of molecular melting (helix -- coil transition) of DNA is considered. It is shown that the theory of DNA melting has reached such a stage of development when it is capable to compute melting profiles and denaturation maps for DNA with any given nucleotide sequence, on the base of a rather simple but adequate model of DNA. The effect of fine structure of the DNA melting profiles, its origin and possible applications are considered in greater detail. It is demonstrated that a direct comparison between experimental and theoretical melting profiles for the open replicative form of the upsilon X-174 phage DNA for which the complete nucleotide sequence has been published recently, confirms the theory and opens new possibilities for further investigation of equilibrium and kinetic properties of DNA molecules.


Myasthenia gravis: a personal view of pathogenesis and mechanism, part 1.

A review of our current knowledge of the etiology and pathogenesis of myasthenia gravis is presented, with particular emphasis on the immunological aspects of the disease. Part 1, published in this issue, deals with the clinical and genetic features of myasthenia gravis which led to the autoimmune theory of the etiology of this disease. Various theories in this field are reviewed, and recent advances in our knowledge of the acetylcholine receptor protein, and its immunology, are examined. Part 2, which will appear in the March/April issue, provides a review of the dysfunction of physiology, pharmacology, and structure of the neuromuscular junction in myasthenia gravis, and the part played by the autoimmune process.


Clinical research in general medical journals: a 30-year perspective.

Little is known about the frequency with which various research designs appear in the clinical literature and how this frequency has changed in recent years. This study describes the research designs used in 612 articles randomly selected from original research published in three general medical journals from 1946 to 1976. Cross-sectional studies increased from 25 to 44 per cent, cohort studies declined from 59 to 34 per cent, and clinical trials increased from 13 to 21 per cent of articles (P less than 0.001). Randomized controlled trials comprised 5 per cent of articles published in 1976 and were not represented 30 years before. In 1976, 37 per cent of articles reported on 10 subjects or less, and this number has not changed substantially since 1946. The frequency of studies with weak research designs has increased in these general medical journals over the past 30 years. The trend deserves critical attention.


Somatostatinoma syndrome. Biochemical, morphologic and clinical features.

Diabetes mellitus, steatorrhea, cholelithiasis and a tumor distorting the duodenum prompted a work-up for somatostatinoma in a 52-year-old man. The responses of pancreatic B-cells but not of A-cells to nutrient stimuli were inhibited, and growth-hormone release was suppressed, suggesting somatostatin resistance in some target tissues. Plasma somatostatin-like immunoreactivity ranged from 9000 to 13,000 pg per milliliter (normal: 88+/-8, mean +/- S.E.M.) and was distributed in four molecular forms, including free somatostatin. The primary tumor contained 5 microgram of somatostatin-like immunoreactivity per milligram of wet tissue, distributed in three of the molecular forms noted in plasma. Plasma calcitonin was also elevated (4650 pg per milliliter; normal: less than 120). Immunocytochemical studies showed that cells of the primary tumor contained somatostatin and calcitonin but no other peptide hormones. Only somatostatin was present in the metastases. Somatostatin was localized electron microscopically in all secretory granules, irrespective of size and shape, whereas calcitonin was present only within a single subpopulation of small granules in the same cells.


Comparative effects of ticrynafen and hydrochlorothiazide in the treatment of hypertension.

Two dose levels of ticrynafen, a new uricosuric diuretic, and of hydrochlorothiazide were randomly assigned, double-blind to 240 men with initial diastolic blood pressures in the range of 95 to 114 mm Hg. A dose of 500 mg of ticrynafen once daily exerted an antihypertensive effect comparable to that of 50 or 100 mg of hydrochlorothiazide. Whereas serum uric acid levels rose in patients treated with hydrochlorothiazide, they fell markedly in those receiving ticrynafen. Otherwise, both diuretics produced similar chemical changes in serum. Patients tolerated ticrynafen as well as they did hydrochlorothiazide over a period of six months of observation, and there was no evidence of serious toxicity or loss of therapeutic effect with ticrynafen. This antihypertensive agent, in appropriate doses, appears to be as effective and well tolerated as hydrochlorothiazide, and in addition ticrynafen prevents hyperuricemia.


Lipid synthesis during reinitiation of growth from stationary phase cultures of Candida albicans.

Lipid synthesis has been studied in the dimorphic fungus Candida albicans. 14C-acetate incorporation into lipid material was used to measure new lipid synthesis in two cultures in which either yeast or mycelial growth was initiated from stationary phase yeast cells. When resuspended in fresh medium at 37 degrees C, cells resume budding growth. When resuspended at the appropriate temperature, both yeast and germ tube cultures immediately incorporated 14C-acetate into lipid material. The labeled lipid was more or less evenly divided between neutral and phospholipid. Phosphatidyl choline was the major phospholipid fraction and along with phosphatidyl ethanolamine accounted for 60--65% of the total phospholipid. Lipid synthesis during growth initiation of either morphology showed a similar pattern, with no significant differences observed in neutral or phospholipid or phospholipid components between yeast and mycelial forms.


Expression in Escherichia coli of hepatitis B virus DNA sequences cloned in plasmid pBR322.

Fragments of hepatitis B virus DNA isolated from Dane particles have been inserted into the Escherichia coli plasmid pBR322 and cloned. Cells carrying the hybrid plasmid synthesise antigenic material that reacts specifically with antisera to hepatitis B viral antigens.


Efficient cap-dependent translation of polycistronic prokaryotic mRNAs is restricted to the first gene in the operon.

Certain polycistronic prokaryotic mRNAs, when modified at their 5'-termini with a cap structure, are translated as efficiently as, or more efficiently than eukaryotic mRNAs in a eukaryotic cell-free protein synthesising system. However, in this case efficient cap-dependent translation is apparently restricted to the 5'-proximal coding sequence. Moreover, certain translational regulatory signals potentially used by these prokaryotic mRNAs to regulate their levels of expression seem to be recognised by the eukaryotic translational components. The evolutionary significance and practical implications of these results are discussed.


Cloned fragments of the plasmid ColV,I-K94 specifying virulence and serum resistance.

A cloned BamH1-generated fragment of ColV,I-K94 increased the virulence of Escherichia coli, causing an approximately 100-fold reduction in LD50 for chicks. A genetic determinant for resistance to the bactericidal effects of serum was mapped to a 5,300 base-pair sequence within the fragment. Neither colicin V nor immunity to colicin V affected the pathogenicity of E. coli for chicks.


Effect of M.bovis BCG and M.microti on sarcoma 180 growth in mice.

The antitumorous efficacy of the Czechoslovak BCG 725, Czechoslovak BCG 901, the Danish SAS maintained, the Japanese SAS and SH maintained BCG strain and the Czechoslovak OV 247 (M.microti) strain was studied. (SAS--original Sauton's medium with asparagine, SH--Sauton's medium with the asparagine replaced by enzymatic casein hydrolysate.) Ascitic Sa 180 cells were used as the experimental tumor and 800 mice as experimental animals. All the strains employed displayed an anticarcinogenic effect in a protective assay (immunization 8 weeks before inoculation of Sa 180 cells). In a therapeutic test (vaccine administered 24 hr after inoculation of Sa 180 cells and then at weekly intervals), Czechoslovak BCG 725 and Czechoslovak OV 247 were used and proved effective.


A correlative study of immunofluorescence, electron, and light microscopy in immunologically mediated renal tubular disease in man.

Renal biopsy specimens obtained from patients with various chronic nephropathies were studied by immunofluorescence (IF), electron and light microscopy. Of 49 biopsies studied by IF, 22 had granular deposits of IgG and/or C3 along the basement membranes of proximal tubules while 14 had linear and 13 both linear and granular deposits. The possible importance of immunologically mediated renal tubular lesions in chronic nephropathies is discussed.


Diabetes mellitus with immune complex glomerulonephritis.

The present study describes 3 patients with the simultaneous occurrence of diabetic nephropathy and immune-complex mediated glomerulonephritis. Renal manifestation included proteinuria and hematuria which were preceded by or co-existent with an infectious process. Renal manifestation included proteinuria and hematuria which were preceded by or co-existent with an infectious process. Renal histology showed the characteristic change of diabetic nephropathy along with those of immune complex glomerulonephritis. Immunofluorescence studies showed a linear pattern with a superimposed granular pattern of IgG and C3 deposits. Renal function and urinary findings improved in the 2 patients who were followed up.


What if multiple sclerosis isn't an immunological or a viral disease? The case for a circulating toxin.

The literature contains studies on many causes of demyelination: Vascular occlusion--exogenous toxins--allergic reactions--and virus diseases. There remains, however, a small group of conditions which seems to have been ignored almost completely in discussions of cerebral demyelination. These consist of brain damage apparently resulting from some toxin liberated within the human body and not obtained from the outside.


Probability and the brain.

Probability theory asserts the lawfulness of seemingly random events in large populations and seems to be a reasonable approach to a general understanding of the structure and function of the nervous system. The brain, by virtue of the number of its components, the multiplicity of their possible interconnections, and the range and rapidity of their outputs, is almost implausably complex in its over-all design. Probability theory, therefore, is usually applied to (a) descriptions of the behavior of large neuronal populations, (b) statistical analysis of neuronal spike trains, and (c) theoretical models of neuronal interaction. A consideration of each of these subjects is presented, as is a discussion of the most fundamental level of application of the theory to the nervous system:  (d) the assertion that the neuron and/or brain is inherently nondeterministic. In practical terms this is shown to be a "nonissue," the uncertainty principle that follows has rather definite philosophical implications.


Results of a double blind study of three contrast media and technic for lumbosacral radiculography.

The rate of side effects, the results of EMG, EEG and CSF changes after radiculography, the rates of late leptomeningeal changes and the details of the hyperosmolality following the ionic contrast media are recorded and discussed. In conclusion rules are presented for the choice of contrast medium and the examination technic for radiculography.


[Clinico-radiological correlation and treatment of patients with absence of lumbar vertebral arch fusion].

The authors observed 88 patients (18 women and 70 men) aged 16 to 61 years with lack of lumbar vertebral arch fusion (spina bifid occulta without spinal cord involvement). In 63 cases the clinical symptom complex was that of sciatic pains, in the remaining 25 cases no neurological defect was found. In 63 cases operation was done and 45 of them intervertebral disc prolapse was found. The decision to operate was based on the refractoriness and intensity of pain, presence of neurological defect and radiculography performed in 36 cases. It is stressed that such high proportion (51%) of cases with spina bifida coexistent with lumbar disc prolapse calls for a careful analysis of the cause of pain in patients with spina bifida.


[Anginin effect in cerebovascular disorders in the light of psychological studies].

Seventeen patients aged 40 to 69 years with cerebral atherosclerosis and peripheral atherosclerotic changes treated for 6 months with Anginin were investigated psychologically. The purpose of the investigation was assessment of the effects of Anginin on certain higher psychic functions and motor fitness, duration of drug effects, and the influence of patients' attitude on health improvement. The investigations comprised a set of 10 psychometric tests assessing objectively the state of different kinds of memory and motor fitness, that is those functions which are most frequently disturbed in cerebral atherosclerosis, and evaluation of the symptoms associated with the disease (in the light of interviews). Each patient was investigated 4 times with parallel sets of tests: before starting treatment, after 3--4 months of treatment, 6 months after the beginnning of treatment, and 6 months after completion of treatment. Seven patients received placebo during the first 2 months. Statistically analysed results showed that during the treatment immediate and delayed visual and auditory memory increased, visumotor coordination improved and disturbances of attention concentration and motor fitness were alleviated. After 3--4 months of treatment the results of the tests for these functions improved further. The effect of Anginin lasted for 6 months after comletion of treatment showing only a slight tendency for decrease. The analysis of symptoms and comparison of the placebo group with the drug group demonstrated a high influence of the attitude of the patient on health improvement, and the psychotherapeutic effect of the drug was considerable. The good effects were obtained in cases with moderately severe and slight intensity of disturbances.


Infantile and adult-onset acid maltase deficiency occurring in the same family.

A 16-week-old girl died from the infantile form of acid maltase deficiency (Pompe disease, acid alpha-glucosidase deficiency). Her paternal grandfather was well until the age of 53 years, when he started to suffer from the adult-onset form of the same enzyme deficiency. This observation suggests that the infantile and adult-onset forms of acid maltase deficiency are genetically related.


Valproic acid and plasma levels of phenytoin.

Eight patients were treated concurrently with a constant dose of phenytoin and valproic acid for 1 year. During initial therapy with valproic acid, total plasma phenytoin levels decreased. The interaction was transient and was not observed at the end of 1 year. Total plasma phenytoin levels returned to pre-valproic-acid levels in seven patients.


[Atrial arrhythmic disease. Presentation of 16 cases and diagnostic, prophylactic and therapeutic considerations].

The auricle arhythmic illness (exhibition of 16 cases with diagnostic, prophilactic and therapeutic considerations). The Authors make a report on sixteen cases seen in the last four years, after distinguishing between the simple kind (which explicates by BS, BSA, AS) and the complex one, in which can be found bradycardy, tachiarithmy, and asystoly. They also stress its meaning compared with other heart illnesses by a statistic point of view. They stress moreover the radiotelemetric monitoring of every suspicious case and the follow-up of the sinus node work by pacing. The treatment of every case with demand pacemakers is recommended.


Single dose metronidazole prophylaxis in gynaecological surgery.

A double blind study of 200 patients was undertaken to evaluate the prophylactic effect of 2g metronidazole rectal suppositories given prior to major gynaecological surgery. The patients receiving metronidazole were found to have a significant reduction in the quantity of postoperative pyrexia as assessed by the fever index. Metronidazole prophylaxis was associated with a dramatic reduction from 18 percent to 1 percent of major postoperative wound and pelvic infections. Four patients in the study developed proven Bacteroides infections, all were in the placebo group.


Metronidazole in the prophylaxis of anaerobic infections in gynaecological surgery: a trial.

Flagyl (metronidazole) was evaluated in the prophylaxis and treatment of patients undergoing gynaecological surgery. One hundred patients were studied: 50 of these patients received prophylactic metronidazole and 50 received matching placebos. Eight percent of metronidazole treated patients developed wound infections which was less than half the number of untreated patients, 18 percent of whom developed wound infection. No anaerobic infections were seen in Flagyl treated patients whereas four (8 percent) were seen in placebo patients.


A comparison of sulindac with ibuprofen in the management of rheumatoid arthritis.

Sulindac 200mg b.i.d. was compared with ibuprofen 400mg t.d.s. in a double-blind controlled trial in patients with rheumatoid arthritis. Both drugs produced a measurable and significant improvement from baseline levels, in both objective and subjective parameters. All parameters favoured sulindac but the differences were not statistically significant. Side effects were infrequent with both drugs and in all but three cases did not necessitate withdrawal from the trials. Sulindac appears to be an effective anti-inflammatory analgesic drug for the management of rheumatoid arthritis with a low incidence of side effects.


A double blind comparison of thiothixene and a trifluoperazine/chlorpromazine composite in the treatment of chronic schizophrenia.

Thirty chronic schizophrenic patients participated in a double-blind crossover trial of thiothixene (Navane) and a control drug combination of trifluoperazine and chlorpromazine. No statistically significant difference was found between the two drug conditions on numerous behavioural scales. Experience with thiothixene suggested that it was comparable with control drugs in the activation of withdrawn patients but needs to be used in combination with a more sedative antipsychotic agent in the treatment of some paranoid patients.


C-peptide response to glucagon in diabetics with and without complications.

Beta cell function has been studied by measurement of C-peptide responses to intravenous glucagon in 11 diabetics with advanced complications and compared with nine long-term diabetics without complications. The majority had no C-peptide responses, but there was evidence of beta cell function in one patient from each group. These observations suggest that some factor other than continuing beta cell function is involved in the complications of insulin-requiring diabetics.


Fetal cranial injuries related to delivery with the Malmström vacuum extractor.

The literature regarding the propensity of the vacuum extractor to cause fetal cranial injuries is reviewed. Eighteen subaponeurotic hemorrhages occurred in 14,276 vacuum extractions (VE). Scalp abrasion or laceration occurred in 12.6%, cephalohematoma in 6%, and intracranial hemorrhage in 0.35%. Assessments of early and late manifestations of neurologic damage indicate little difference between VE deliveries and spontaneous deliveries. An uncorrected perinatal mortality rate of 25.8 per thousand is tabulated, which reduced to 15 per thousand when corrected for deaths not related to the mode of delivery. Scalp anatomy and the forces exerted on it with vacuum extraction are examined, and suggestions to minimize scalp injuries are offered.


Recurrent nonimmune hydrops fetalis.

A case of recurrent nonimmune hydrops fetalis is presented. In each of the 2 pregnancies involved, early neonatal death occurred. Only 1 other case could be discovered in the literature where the problem recurred. Hence, normally, a good prognosis for future pregnancies is given. In spite of extensive investigation, the etiology of nonimmune hydrops fetalis remains unknown. The condition is associated with preeclampsia, polyhydramnios, and premature labor. While the polyhydraminos renders management difficult, it makes the ultrasound diagnosis much clearer. This early diagnosis ensures the availability of optimal perinatal care for the infant on delivery.


Fetal swallowing and voiding in relation to hydramnios.

Fetal swallowing and voiding were measured using colloidal gold and an ultrasonic scanner, respectively. Subjects in the study were in their 38-40th week of pregnancy. Cases were divided into 3 groups: normal, hydramnios, and oligohydramnios. The normal group had a mean swallowing rate of 198 ml/day and a mean voiding rate of 23.6 ml/hr. No significant differences were found among these rates and the corresponding rates in the other 2 groups. It is concluded that mechanisms other than fetal swallowing and voiding can contribute to the control of amniotic fluid volume at term.


Tamoxifen-induced regression of benign breast lesions.

Sixty-three patients with severe breast dysplasia were treated with tamoxifen, 10 mg/day from day 5 to day 25 of the menstrual cycle for 4 months. Lesions were assessed by mammography, thermography, and echography (A- and B-mode scanning). In 45 patients (71.43%) there was complete remission of symptoms and disappearance of lesions as assessed by echography and clinical examination. Some improvement was seen in 12 patients. In all but 2 of those in whom lesions disappeared completely, no recurrence was seen in 12 months after treatment was discontinued. Estrogen receptors were assayed in 10 patients, but were detected in none. A decrease of doubtful statistical significance was observed in some patients in basal and thyrotropin-releasing hormone (TRH)-stimulated levels of prolactin during the treatment period. No other significant or unequivocal change in endocrine parameters was observed during tamoxifen treatment.


Gracilis myocutaneous flap in reconstruction of the vulva and female perineum.

For the past 2 decades there has been a definite trend among pelvic surgeons to immediately reconstruct the large defects created by deforming radical cancer surgery in the female pelvis and perineum. Extensive en bloc removal of more tissue has enhanced the probabilities of increased 5-year survival. At the same time, however, the quality of life following radical surgery has been of great concern to both patient and surgeon. Recent advances have been made in techniques for reconstruction. It is the purpose of this paper to present our experience using the gracilis myocutaneous flap for reconstruction of the vulva after radical excision of perineal tissue. The technique of the procedure is presented with the clinical results in 5 cases, and the complications noted therein.


Chemical profiles of disease.

Chemical profiles have been used successfully in teaching the interpretation of laboratory test values. The profiles have a visual impact that assists in making associative and correlative observations about disease processes. Profiles are most useful in attempts to integrate multiple test abnormalities in a given disease process. Representative profiles are illustrated and discussed as examples of the effectiveness of this mode of analysis of clinical laboratory data in laboratory medicine.


Liver replacement for pediatric patients.

Between March 1963 and January 1978, 74 patients 18 years of age or younger have had liver replacements at the University of Colorado Medical Center, Denver. The most common cause of native liver failure was biliary atresis (48/74, 65%); the second most common cause was chronic aggressive hepatitis (12/74, 16%). Twenty-nine patients (39%) lived for at least one year, and 16 are still alive one to nine years after transplantation. Technical surgical problems, rejection, and infection were the main causes of death. Improved immunosuppression is needed; nevertheless, the quality of life in the long-term survivors has encouraged continuation of this difficult work.


Vitamin E absorption in small premature infants.

The absorption of vitamin E, given by orogastric tube, was studied in premature infants who weighed less than 1.5 kg at birth. After the administration of either dl-alpha tocopherol or the acetate form, plasma tocopherol levels increased. In a second blind trial, 28 infants received either 25 units of dl-alpha tocopherol or placebo during the first six weeks of life. Plasma tocopherol levels in all treated infants were sustained in the normal adult range. The vitamin E-deficient state of premature infants can be corrected by oral therapy alone.


Adolescents with myelodysplasia: impact of physical disability on emotional maturation.

Certain physical, psychological and social characteristics of 20 adolescents with myelodysplasia are compared to those of age and gender-matched controls. In addition to the obvious physical differences the areas of greatest concern are self-esteem and social-sexual adjustment. Family relations, feelings, and modes of expression were not different in the two groups. Lack of appropriate chores, decreased opportunities to interact and compete with peers, plus uncertainties to interact and compete with peers, plus uncertainties about bowel and bladder continence appear to be the greatest impediments to emotional growth in this physically handicapped group of teenagers. Early recognition of such problems and finding strategies to overcome them are important aspects of the comprehensive care of any person with a chronic disability.


Group B streptococcal colonization in prepubertal children.

Colonization of prepubertal boys and girls with group B streptococci was studied prosepctively for one year. Throat, anal canal, and vaginal cultures were obtained from 415 children not receiving antimicrobics. The over-all colonization rate at any site was 11.3% and did not vary with age, sex, or season. Streptococci were recovered most commonly from the anal canal. Throat colonization was comparable in boys and girls. A total of 71 sites were positive for the organism in the 47 colonized children. Serotype Ia was the most common (41% of isolates). Types II and III accounted for 24% and 20%, respectively. Colonization at more than one site occurred in 20 children and in two of these children, different serotypes were recovered from different sites.


Lateral eye-movements and indices of nonanalytic attending in right-handed females.

24 right-handed females were assessed on left-moving after participating in a study wherein they were presented on hypnotic susceptibility and absorption and then attended "nonanalytically" for 20 sessions. Although no significant correlations were found between left-moving and other variables, further analyses indicated a non-linear relationship between left-moving and susceptibility, absorption and self-rated "depth" of attending.


Body-cathexis and self-cathexis in an interactional, awareness training class.

This study examined the effects of a psychology of adjustment class on body-acceptance and self-acceptance. An introductory psychology class served as a control group. Subjects were pre- and posttested with the Body-cathexis and Self-cathexis scales. Two by two analyses of covariance indicated that the adjustment group showed a larger gain on both scales than the control. Sex interacted with group significantly on the Body-cathexis scale only. Means indicated that the main effect of groups on the Body-cathexis scale may be attributed to the larger gains by females in the adjustment class.


Monaural studies eliciting an hemispheric asymmetry: a bibliography.

Since 1967, 74 studies reported in the literature using monaural stimulation elicited an hemispheric asymmetry, confirming original findings from dichotic listening studies.


[Idiopathic haemochromatosis. I. Clinical, biological and therapeutic aspects (author's transl)].

Over the last few years the study of idiopathic haemochromatosis has not brought to light any basic change in the overall pattern of organic and metabolic damage produced by the disease and comprising altered skin pigmentation, liver disease, diabete mellitus, heart disease, endocrine dysfunction, bone and joint disease. Nevertheless, certain facets of the clinical picture have been described and progress has been made in understanding the signs of the disease. Although the desferrioxamine test is no without merit, especially if performed after vitamin C administration, for measuring the extent of iron overload, two methods seem better equipped: serum ferritin radioimmunoassay and measurement of iron concentration in a liver biopsy specimen. The HLA antigen A3 and, more especially, haplotype A3, B14, are markers for the genetic basis of the disease. Repeated phlebotomy therapy generally brings about symptomatic improvement and a significant increase in survival.


[Non-lymphoblastic acute leukaemia: maintenance therapy by trial of a combination of chemo- and immunotherapy (author's transl)].

A trial of immunotherapy in the maintenance treatment of non-lymphoblastic acute leukaemias led to a comparison of 2 groups of patients in complete remission. Group C (14 patients) received only monthly reinduction chemotherapy. Group C + I (17 patients) received identical chemotherapy together with weekly immunotherapy combining BCG and irradiated leukaemic cells. Whilst the duration of the first remission was unmodified, the overall survival and above all survival after the first recurrence were prolonged in group C + I. These results were all the more marked when a homogeneous patients having received the same induction chemotherapy is considered.


[Myelosclerosis : pseudo-tumors forms (author's transl)].

Signs of pseudo-tumor growth may be seen in myelosclerosis. Eight personal cases and a review of the literature are discussed in this article. The observations here reported cover pseudo-tumors occurring in ganglia, liver, suprarenals (3), abdomen and pancreas. They are classified as sclerotic haemopoietic tumors. This category has particular characteristics when compared to extra-medullary haemopoiesis, extra-medullary haemopoietic growths, and a fourth category, sarcoma-type malignant tumors in myelosclerosis. The identity of these last three entities is widely discussed in the literature. The main histological and cytological characteristics for pseudo-tumor diagnosis in myelosclerosis are reported here.


Regulation of hemopoiesis.

The development of in vitro cloning systems for populations of hemopoietic and lymphoid cells has enabled a family of specific regulatory macromolecules to be detected and characterized. These macromolecules control proliferation and differentiation in hemopoietic cell populations. Studies have demonstrated the complexity of the spectrum of molecules which are involved in the regulation of each group of hemopoietic cells. Heterogeneous subpopulations of molecules exist for each regulatory function and more than one molecular form exists for the various regulator molecules. While the cellular origin of many of these regulators has not been clearly demonstrated, it is apparent that hemopoietic populations themselves can be significant sources of both stimulatory and inhibitory regulators. In particular, there are now clear examples of regulatory interactions which occur in both directions between hemopoietic and lymphoid populations. While in no case a complete analysis of the control systems has been achieved, maintenance of homeostasis in hemopoietic systems is now better understood than for most other cell populations in the body. Further, with existing techniques, and in particular, the exploitation of the full potential of the semi-solid cloning systems, it is realistic to expect that a complete analysis of hemopoietic regulation can now be accomplished.


[Repeated sampling of rat polymorphonuclear leucocytes from the pleural cavity. Application for the study of leucocyte chemotaxis (author's transl)].

A method is described for allowing the sampling of a homogeneous population of polymorphonuclear cells (PMN) from the rat pleural cavity a well as a technique involving the use of a phase-contrast microscope and video-recording system to study the necrotaxis of rat PMN towards a single erythrocyte lysed by ruby-laser irradiation. This allows both the speed of the leucocytes and the degree of their chemotactic response to be determined. The advantages and disadvantages of the experimental technique are discussed along with its application to the study of in vitro and in vivo actions of various drugs on rat PMN chemotaxis.


[Morphology and deformability of erythrocytes in muscular dystrophy].

In recent years, the presence of red cell morphological abnormalities in patients with Muscular Dystrophy has made the object of numerous, often contradictory reports. A possible source of such confusion may lie in the fact that human erythrocytes are extremely sensitive to morphologic transformations resulting from various manipulations or environmental conditions in vitro. We have examined the morphology and deformability of erythrocytes from 7 patients with Duchenne and 9 patients with Steinert (myotonic) Muscular Dystrophy. To avoid preparation artifacts, fresh, unwashed red cells suspended in their own plasma were examined under phase contrast microscopy for the presence of either echinocytes and stomatocytes. Deformability was measured by filtration of dilute cell suspensions at constant flow rate through nucleopore membranes (nominal pore diameter = 3 micron). No significant difference was found between the patients' cells and those of 22 healthy volunteer controls. We conclude that previously reported abnormalities may have been the result of preparation artifacts. It appears possible, however, that erythrocytes from Muscular Dystrophy patients may be more sensitive than normal ones to certain stimuli originating from red cell manipulations in vitro.


[Materno-foetal transfer of anti-HLA antibodies. Study by using LDA test (author's transl)].

The LDA test was used to study the materno-foetal transfer of anti-HLA antibodies. The results were compared with those obtained earlier by the complement dependent lymphocytoxicity test (CdL). Although more sensitive than CdL, the LDA test did not demonstrate more maternal antibodies in cord blood when these antibodies corresponded to the child's paternal antigens. Nevertheless LDA demonstrated antibodies did not always behave similarly to those seen by CdL.


Characterization of a cloned ribosomal fragment from mouse which contains the 18S coding region and adjacent spacer sequences.

The large EcoRI fragment of mouse ribosomal genes containing parts of the non-transcribed spacer, the external transcribed spacer located at the 5' end of the precursor molecule and about two thirds of the 18S sequence has been cloned in bacteriophage lambda  gtWES. A physical map of the DNA was constructed by cleavage with several restriction endonucleases and hybridization of the restriction fragments of the recombinant DNA with labelled 18S and 45S rRNA. The orientation of the inserted fragment as well as the length of the 18S sequence was determined by electron microscopy of R-loop containing molecules. The absence of hybridization of the cloned fragment to other fragments in the genome shows that the non-transcribed spacer does not have a significant length of sequences in common with other sequences in the genome.