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Retroviruses: ancient and modern.

Retroviruses are transmitted in two distinct ways: as infectious virions and as 'endogenous' proviral DNA integrated in the germ line of their hosts. Modern infectious viruses such as HIV recently infected mankind from simian hosts, whereas human endogenous retroviral genomes have been present throughout old world primate evolution. Recently we have characterised novel retroviruses in humans and pigs. Human retrovirus 5 (HRV-5) is detected as an exogenous genome in association with arthritis and systemic lupus erythematosus. Porcine endogenous retroviruses (PERV) are carried in swine DNA but can be activated to produce virions that are infectious for human cells, which has implications for xenotransplantation. A brief account of HRV-5 and PERV is given here.

Animals↗

Rabbit mitochondrial DNA diversity from prehistoric to modern times.

The mitochondrial genetic variability in European rabbit (Oryctolagus cuniculus) populations present in Europe and North Africa from 11,000 years ago to the present day has been analyzed using ancient DNA techniques. DNA was extracted from 90 rabbit bones found in 22 archaeological sites dated between the Mesolithic and recent times. Nucleotide sequences present in a variable 233-bp domain of the cytochrome b gene were compared to those present in modern-day rabbits. The results show that the structure of ancient populations of wild rabbit exhibited remarkable stability over time until the Middle Ages. At this time, a novel type of mtDNA molecule abruptly appears into most wild populations studied from France. This mtDNA type corresponds to that currently present in the domestic breeds of rabbit examined so far. The relative rapidity by which this mtDNA type established and its absence in all sites examined before 1,700 years ago lend support to the hypothesis that between 2,000 and 1,000 years ago, man may have favored the development, into all regions of France, of animals carrying this particular mtDNA molecule. The origin of such animals has still to be found: animals previously living outside of France or within France but in very restricted areas? This event was concomitant with the documented establishment of warrens after the tenth century A.D. in Europe.

Africa, Northern↗

Modern imaging techniques and ultrasound-guided aspiration cytology for the assessment of neck node metastases: a prospective comparative study.

Although palpation has proved to be an unreliable staging procedure, the indications for and the implications of more reliable radiologic staging methods for the neck in patients with a primary squamous cell carcinoma of the head and neck remain controversial. Only a very accurate imaging technique can replace neck dissection in clinical NO disease. This study compares the value of palpation with computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US) with or without guided aspiration cytology for neck node staging. One hundred and thirty-two patients with squamous cell carcinoma of the head and neck were examined radiologically before undergoing a total of 180 neck dissections as part of their treatment. CT, US and MRI proved to be significantly more accurate than palpation for cervical lymph node staging. The accuracy of US-guided aspiration cytology was significantly better than of any other technique used in this study. Modern imaging techniques are essential for appropriate assessment of neck node metastases. In view of advances in the accuracy of contemporary imaging, the need for elective treatment of the neck requires reappraisal.

Biopsy, Needle↗

Has modern management improved the outcome of infants with intracranial tumors?

Records of 92 children were reviewed who, in the first 18 months of life had an intracranial tumour, and who were registered with the Manchester Children's Tumour Registry during the 34-year period from 1953 to 1987. The incidence of intracranial tumour was 1 in 25,000 live births, and 85% of the tumours were malignant. The introduction of computed tomography (CT) in the region in 1976 improved the diagnostic accuracy and led to early diagnosis. This also coincided with refined radiotherapy and improved chemotherapy. The surgical attitude became more aggressive, and with early treatment, mortality was reduced, though the 1-month operative mortality still remains high at 15%. All survivors were available for follow-up. All children with axial tumours died within 9 years. Long-term follow-up did not suggest significant improvement in the overall survival or in the quality of life, though there was a significant improvement in the 5-year survival rate with modern management.

Actuarial Analysis↗

[Lactate dehydrogenase. An example of the development of modern enzymology].

Lactate dehydrogenase is the prototype of an oligomeric, intracellular enzyme. Its primary, secondary, tertiary, and quaternary structures are now well known. This fact, especially with regard to the occurrence of isoenzymes, has effected a great progress in the understanding of the structure-function relationship of enzymes. The historical development of modern enzymology is described, together with discussions of the various methods and problems of enzymology.

Animals↗

[Modern analytical methods in forensic chemistry].

The use of modern chemical and physical methods in forensic chemistry and crime investigation is steadily increasing and gaining in importance. For forensic purpose special modifications of the procedures are generally required in order to give results which are acceptable to legal authorities as proof of some specific points. The chemical toxicology can also help in cases of acute intoxications or in environmental problems.

Chromatography↗

Effects of modern loop diuretics on the inner ear a quantitative evaluation using computer technics.

The effects of some modern high ceiling loop diuretics on the guinea-pig's inner ear are tested. Short-time experiments are run registrating the cochlear microphonic potentials (CMP) before and after i.v. bolus injections of a diuretic. A 100-point matrix program is performed by automatic sampling of the CMPs after stimulating by five frequencies at 20 sound pressure levels each. Data can be plotted in different scales within 10 min after the end of a whole-day experiment. The data are on-line processed by a IBM 1800 computer.

Animals↗

Pissarro, dacryocystitis, and the development of modern lacrimal surgery.

The co-founder of French Impressionism, Camille Pissarro, suffered from chronic dacryocystitis for at least fifteen years. This kept him from working for long periods of time, and when he was able to work, influenced his method of painting. Pissarro just missed the modern period of lacrimal surgery, and was treated by conservative methods.

Dacryocystitis↗

[Open spinal operations (anterolateral chordotomy and commissural myelotomy) in modern treatment of pain (author's transl)].

The only significant open pain operations on the spinal cord itself that are routinely in use nowadays are anterolateral chordotomy and commissural myelotomy. Open thoracic chordotomy is still inidcated in cases of malignant growth in the lower body, to be sure of avoiding further neurological involvement in the upper region. Open cervical chordotomy, on the other hand, is now only indicated after unsuccessful percutaneous chordotomy and neurostimulation technics. Commissural myelotomy is still used in specific cases in specialized clinics. Despite advances in knowledge and more modern methods, the open operations still cannot be anondoned.

Chronic Disease↗

[Salutogenesis and pathogenesis--a paradigm change from the perspectives of modern physics].

Early in the eighties Antonovsky stipulated a changeover from the pathogenetitto the salutogenetic paradigm in prevention. This article is meant to show that the necessity of such a changeover may also be derived from present-day physics. The pathogenetic paradigm is the characteristic of a time that bears the distinctive marks of the classical thermodynamics in equilibrium. The existence of the phenomenon life seemed in this context to be a physical paradox. Protection against wearing and death, the pathogenetic aspect, was inevitably the focus of interest. In the meantime modern physics have, however, developed a new understanding of life. It is based on the theory of self-organisation of non-linear systems far off the thermodynamic equilibrium. Today, life does no longer appear as a physical paradox but as the natural and fascinating expression of a structuring tendency inherent in matter. These new findings bring the salutogenetic question into the centre of attention. How can the natural tendency to self-organisation of biological systems be shouldered? Physical answers interpret the results of health research under a new aspect. Since self-organisation calls for a free and off-balance exchange of matter and energy with the environment it is no longer considered as a threat but as a source of health and vitality. Another outcome are physical arguments relating to well-known health strategies such as vegetarian food and physical exercise.

Disease↗

[Rational parameters in the treatment of bacterial meningitis with modern cephalosporins].

Modern cephalosporins are by now well established therapeutic drugs in the treatment of bacterial meningitis. Particularly for gram-negative meningitis they are valuable therapeutic tools. In most cases, they are very efficient and less toxic than former therapeutic regimens. Of course, they cannot replace penicillin G in the therapy of meningitis with penicillin-sensitive bacteria. The advantages and disadvantages of the single compounds, cefotaxime, latamoxef, ceftizoxime, cefmenoxime, ceftazidime, ceftriaxone and cefsulodin have to be evaluated. For safety reasons, monotherapy with these drugs is not recommended because there have been reports of failures and relapses of meningitis even in cases with highly sensitive organisms. They are almost or completely ineffective against a few pathogens in meningitis, such as anaerobes or Listeria monocytogenes. An attempt has been made to evaluate the different compounds for their therapeutic usefulness against different pathogens in meningitis.

Adolescent↗

Craniocervical abnormalities. Modern diagnosis and a comprehensive surgical approach.

A retrospective study of 41 patients operated on between 1975 and 1983 is presented including guidelines for surgical management with some alternative technique both in anterior and posterior approaches and modern diagnostic procedures. A proposed base-line inclined--10 degrees from Reid's base-line proved to be adequate to obtain the true shape and size of the foramen magnum on CT-scan. The normal range of the clivo -axial angle in adults is reported and its clinical significance is stressed.

Adolescent↗

The extent of successful colonoscopy: a second assessment using modern equipment.

Records of 200 consecutive and unselected colonoscopies were reviewed to determine both the success in viewing the entire colon and the average extent of colon visualized, using the most modern equipment. Colonoscopy was completed to the cecum or ileum in 82.5% of studies, and an average of 93.8% of the colon was viewed. These data show considerable improvement compared to those previously reported by us. However, the significant number of incomplete colonoscopies still suggests that colonoscopy and barium enema examination must remain complementary for maximum detection of colonic lesions.

Barium Sulfate↗

A brief review of modern toxicologic pathology in regulatory and explanatory toxicity studies of chemicals.

Macroscopic and histologic evaluation of animal studies for general toxicity and carcinogenicity are cornerstones of the risk assessment of new chemical entities. Standard toxicopathologic evaluation is mainly based on the study of paraffin sections stained with hematoxylin and eosin. There are, however, a number of new approaches and techniques which have improved the objectivity of evaluation and the accuracy of cell identification, and provided deeper insight into the molecular biological mechanisms of toxicity and carcinogenicity. Such approaches include the standardization of the nomenclature, the creation of data banks for morphological alterations, the use of computers to register pathological findings in toxicity studies and to statistically evaluate incidences, and the use of morphometry. Other modern techniques are immunohistochemistry, in situ hybridization, and the assessment of cell kinetics.

Animals↗

Results of infrainguinal revascularization with reversed vein conduits: a modern control series.

To determine the outcome of infrainguinal reversed vein bypasses in the modern era, we reviewed the results of 120 consecutive reversed vein grafts performed from March, 1986 to March, 1990. Forty-nine bypasses were to tibial, peroneal, or pedal arteries, 46 grafts to the below-knee popliteal artery, and 25 grafts to the above-knee popliteal artery. Limb salvage was the indication for revascularization in 70% of patients. All grafts were followed with serial, duplex scan, peak-systolic graft flow velocity measurements every three months for one year and every six months thereafter. The primary life table patency rate at 36 months was 67.6% for the entire series; the secondary patency rate was 92.5%. The secondary patency rate reflects the impact of graft revisions resulting from the detection of failing grafts by duplex scanning. Patency rates of reversed vein grafts to the tibial arteries at 36 months (73.8% primary and 89.8% secondary) were equivalent to those performed to the popliteal artery. Our current patency rates with reversed vein grafts are comparable or superior to those reported for in-situ vein conduits and suggest that operative technique and meticulous follow-up are more important with respect to long-term graft durability than whether the vein is used in the in-situ or reversed configuration.

Arterial Occlusive Diseases↗

Repeats of base oligomers as the primordial coding sequences of the primeval earth and their vestiges in modern genes.

Three outstanding properties uniquely qualify repeats of base oligomers as the primordial coding sequences of all polypeptide chains. First, when compared with randomly generated base sequences in general, they are more likely to have long open reading frames. Second, periodical polypeptide chains specified by such repeats are more likely to assume either alpha-helical or beta-sheet secondary structures than are polypeptide chains of random sequence. Third, provided that the number of bases in the oligomeric unit is not a multiple of 3, these internally repetitious coding sequences are impervious to randomly sustained base substitutions, deletions, and insertions. This is because the recurring periodicity of their polypeptide chains is given by three consecutive copies of the oligomeric unit translated in three different reading frames. Accordingly, when one reading frame is open, the other two are automatically open as well, all three being capable of coding for polypeptide chains of identical periodicity. Under this circumstance, a frame shift due to the deletion or insertion of a number of bases that is not a multiple of 3 fails to alter the down-stream amino acid sequence, and even a base change causing premature chain-termination can silence only one of the three potential coding units. Newly arisen coding sequences in modern organisms are oligomeric repeats, and most of the older genes retain various vestiges of their original internal repetitions. Some of the genes (e.g., oncogenes) have even inherited the property of being impervious to randomly sustained base changes.

Animals↗

Unlimited volumes of laboratory data: a confusing and diagnostically deceptive product of modern technology.

The large volumes of laboratory data currently available in clinical practice can lead to erroneous conclusions. Our current statistical interpretation of these data is univariate (one variable at a time) and often not age- and sex-corrected. Using an optimal technique of multivariate analysis, a SMAC profile of 19 tests performed on normal subjects resulted in over a 500% improvement in defining the reference range. Using physiologic subsets of the SMAC profile for patients, improvements in interpretation of between 100% and 300% are possible. Results indicate a serious clinical problem that will require modification of laboratory reports using modern technology as an adjunct for diagnostic medicine.

Analysis of Variance↗

The evolution of proteins from random amino acid sequences. I. Evidence from the lengthwise distribution of amino acids in modern protein sequences.

We examine in this paper one of the expected consequences of the hypothesis that modern proteins evolved from random heteropeptide sequences. Specifically, we investigate the lengthwise distributions of amino acids in a set of 1,789 protein sequences with little sequence identify using the run test statistic (ro) of Mood (1940, Ann. Math. Stat. 11, 367-392). The probability density of ro for a collection of random sequences has mean = 0 and variance = 1 [the N(0,1) distribution] and can be used to measure the tendency of amino acids of a given type to cluster together in a sequence relative to that of a random sequence. We implement the run test using binary representations of protein sequences in which the amino acids of interest are assigned a value of 1 and all others a value of 0. We consider individual amino acids and sets of various combinations of them based upon hydrophobicity (4 sets), charge (3 sets), volume (4 sets), and secondary structure propensity (3 sets). We find that any sequence chosen randomly has a 90% or greater chance of having a lengthwise distribution of amino acids that is indistinguishable from the random expectation regardless of amino acid type. We regard this as strong support for the random-origin hypothesis. However, we do observe significant deviations from the random expectation as might be expected after billions years of evolution. Two important global trends are found: (1) Amino acids with a strong alpha-helix propensity show a strong tendency to cluster whereas those with beta-sheet or reverse-turn propensity do not. (2) Clustered rather than evenly distributed patterns tend to be preferred by the individual amino acids and this is particularly so for methionine. Finally, we consider the problem of reconciling the random nature of protein sequences with structurally meaningful periodic "patterns" that can be detected by sliding-window, autocorrelation, and Fourier analyses. Two examples, rhodopsin and bacteriorhodopsin, show that such patterns are a natural feature of random sequences.

Amino Acid Sequence↗