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A collaborative study of French laboratories to assess any evolution of antibiotic resistance within the Bacteroides fragilis group.

Antibiotic susceptibility testing of anaerobes by a same methodology allows the authors to draw up suggestions about the evolution of antibiotic resistance within the B. fragilis group. Cefoxitin resistance rates were stable until 1985 and were slowly increasing later. Until 1985 piperacillin was able to inhibit all tested strains. In 1987 the two groups noticed an increasing resistance to piperacillin (4 to 9%). During the 1970's clindamycin resistance was a minor event (less than 1%) then the resistance rate increased rapidly to 10% in 1980. MICs determinations from 1981 to 1985 demonstrated well that clindamycin resistance was stable at this 10% rate. Since 1987 the clindamycin resistance was again increasing and reached respectively 14 to 19% for the two groups of investigators. Metronidazole has kept a good activity against Bacteroides fragilis group strains but some strains with reduced susceptibility (MIC 2 to 8 mg/l) have been described since 1983. Three strains with MIC greater than 8 mg/l were recently described by one of the groups. Until 1987, the clavulanic amoxicillin combination was able to inhibit all strains of the B. fragilis group but only imipenem remained still active on all investigated strains with no change at all for the values of MIC50 and MIC90 determined by the investigators of this study. All these results emphasize the need for periodical surveys within the B. fragilis group in each country.

Bacteroides fragilis↗

TdT+/nonlymphoid antigen+ acute leukemias: immunologic and karyotypic monitoring during therapy and at relapse suggests the transformation of a bipotential stem cell.

Immunophenotype and karyotype were monitored in 19 adult acute leukemia patients with blast cell populations expressing terminal transferase (TdT) and nonlymphoid antigens either at presentation or at relapse. Three patterns of immunophenotypic course were observed when following the patients through at least one, sometimes two (six patients), or three relapses (one patient). Induction chemotherapy induced predominantly TdT+ leukemias with a minor monoblastic component to become TdT-negative, purely monoblastic without clinical response or change in karyotype in five patients (group 1). In group 2, relapse was associated with the disappearance (four patients) or the appearance of TdT+/nonlymphoid antigen+ features (four patients). In two instances, new nonrandom cytogenetic abnormalities, in one case, evolution of an initial abnormal cytogenetic clone, were found at relapse. Six patients (group 3) presented and relapsed with identical TdT+ myeloblastic, promyeloblastic, monoblastic immunophenotype and karyotype. In general, FAB classification did not reflect expression of TdT in nonlymphocytic leukemias or the presence of nonlymphoid blast features in lymphocytic leukemias. Lymphoid-specific antigens in addition to TdT were not detected in any of the cases at the time of nonlymphoid antigen expression. In 11 of the 19 patients, simultaneous expression of TdT and myeloid or monocytic antigens could be demonstrated at the single cell level using double-fluorescence staining. These follow-up data are best consistent with a drug-induced maturation drive of a TdT+/monocytic (majority of cases) or TdT+/myelocytic leukemic stem cell with its differentiation commitment being influenced by chemotherapy or by other as yet undefined conditions predisposing to proliferation of the leukemic cell at relapse.

Acute Disease↗

Non-neural ectoderm is really neural: evolution of developmental patterning mechanisms in the non-neural ectoderm of chordates and the problem of sensory cell homologies.

In chordates, the ectoderm is divided into the neuroectoderm and the so-called non-neural ectoderm. In spite of its name, however, the non-neural ectoderm contains numerous sensory cells. Therefore, the term "non-neural" ectoderm should be replaced by "general ectoderm." At least in amphioxus and tunicates and possibly in vertebrates as well, both the neuroectoderm and the general ectoderm are patterned anterior/posteriorly by mechanisms involving retinoic acid and Hox genes. In amphioxus and tunicates the ectodermal sensory cells, which have a wide range of ciliary and microvillar configurations, are mostly primary neurons sending axons to the CNS, although a minority lack axons. In contrast, vertebrate mechanosensory cells, called hair cells, are all secondary neurons that lack axons and have a characteristic eccentric cilium adjacent to a group of microvilli of graded lengths. It has been highly controversial whether the ectodermal sensory cells in the oral siphons of adult tunicates are homologous to vertebrate hair cells. In some species of tunicates, these cells appear to be secondary neurons, and microvillar and ciliary configurations of some of these cells approach those of vertebrate hair cells. However, none of the tunicate cells has all the characteristics of a hair cell, and there is a high degree of variation among ectodermal sensory cells within and between different species. Thus, similarities between the ectodermal sensory cells of any one species of tunicate and craniate hair cells may well represent convergent evolution rather than homology.

Animals↗

Two subtypes of HLA-B51 differing by substitution at position 171 of the alpha 2 helix.

Newly defined antigens of the B5, B35 cross-reacting group have been found in Japanese and North American Indians. Nucleotide sequencing of the alleles encoding the Japanese B5.35 antigen and the variant B5 antigen from the Piman Indians show them to be identical. This new allele, B*5102, differs from B*5101 by a single nucleotide substitution that changes residue 171 from histidine to tyrosine. Residue 171, which is part of the alpha 2 helix, is believed to contribute directly to peptide interaction in the A pocket of the binding groove and is either histidine or tyrosine in all HLA-A, B, C heavy chains. Tyrosine 171 is shared by B*5102, B*3501, B*3502, and B*5301 and must be responsible for the serological cross-reactivities of these molecules not shared with B*5101. Stimulation of lymphocytes from a B*5101 positive donor with B*5102 positive cells failed to generate cytotoxic T cells with specificity for the difference between these molecules. However, one out of five clones of cytotoxic T cells raised against B*5101 failed to lyse targets expressing B*5102. Substitution of histidine for tyrosine at residue 171 affected recognition of HLA-B35-restricted human minor histocompatibility antigen-specific T cell clones.

Amino Acid Sequence↗

Angiographic evolution of intracoronary thrombus and dissection following percutaneous transluminal coronary angioplasty (the Thrombolysis and Angioplasty in Unstable Angina [TAUSA] trial).

The evolution and progression of thrombus and dissection after percutaneous transluminal coronary angioplasty (PTCA) are unknown. As part of the protocol of the Thrombolysis and Angioplasty in Unstable Angina (TAUSA) trial, 1 and 15 minutes post-PTCA angiograms were routinely performed and evaluated by the core laboratory for the presence of thrombus and either minor or major dissection. Thrombus was present at 1 minute in 4.4% of culprit lesions. This increased to 16% at 15 minutes (p < 0.005) and was equally seen in patients receiving both urokinase and placebo. Any dissection was noted in 25.2% at 1 minute versus 30.5% at 15 minutes (p < 0.08), and this trend was mainly related to an increase in major dissection with urokinase at 15 minutes versus 1 minute (10.1% vs 5.9%, respectively, p = 0.10). The in-hospital clinical outcome of patients with lesions that did or did not have thrombus or major dissection at 1 and 15 minutes was retrospectively assessed in the placebo group. The presence of either thrombus or major dissection at 1 minute was associated with a subsequent incidence of acute closure of 14% and an incidence of emergency bypass surgery of 11% (p < 0.01 compared with no thrombus or major dissection at 1 minute). The absence of thrombus and major dissection at 15 minutes (n = 173) was associated with no subsequent acute closure or emergency bypass surgery, (p < 0.05 for acute closure vs thrombus or major dissection at 15 minutes). Thrombus evolves progressively over 15 minutes after PTCA in unstable angina, whereas dissection is usually present immediately after PTCA. The absence of thrombus and major dissection at 15 minutes is associated with very low-acute in-hospital complications. Delayed angiograms following standard balloon angioplasty for unstable angina may be predictive of low complications and our study suggests a possible role for their use.

Acute Disease↗

A new approach for the simultaneous differentiation of biological and geographical strains of Potato virus Y by uniplex and multiplex RT-PCR.

Two strains of Potato virus Y (PVY), the common (PVY(O)) and the tobacco veinal necrosis (PVY(N)) have been known for decades. More recently, a tuber ringspot necrosis (PVY(NTN)), and several recombinants of PVY(O) and PVY(N) (designated here as PVY(N:O)) have been described. Further, the PVY(N) group of strains have been assigned to two geographical subgroups of European (EU) PVY(N/NTN) and the North American (NA) PVY(N/NTN). The evolution of new PVY(N) strains, has complicated the diagnosis, which requires a combination of bioassay, serological and molecular assays. To simplify the identification and differentiation of various PVY(N) strain groups, a competitive (single antisense and multiple sense primers) reverse transcription-polymerase chain reaction (RT-PCR) was used, making use of minor differences in the variable region part of the PVY genome. Specifically, primers based on small variations in nucleotide stretches of P1 gene permitted a broad range separation of PVY(O) and PVY(N) groups and the specific detection of strain subgroups. The primer pairs designed for identifying PVY(O), EU-PVY(N/NTN), NA-PVY(N) and NA-PVY(NTN) are described. Primer pairs can be used in a uniplex (single pair of primer) or multiplex (duplex, tetraplex or pentaplex) competitive RT-PCR, allowing simultaneous testing for any combination of PVY(O), EU-PVY(N/NTN), NA-PVY(N) and NA-PVY(NTN).

DNA Primers↗

Manic depressive psychosis and schizophrenia are neurological disorders at the extremes of CNS maturation and nutritional disorders associated with a deficit in marine fat.

The maturational theory of brain development comprises manic depressive psychosis and schizophrenia. It holds that the disorders are part of human diversity in growth and maturation, which explains their ubiquity, shared susceptibility genes and multifactorial inheritance. Rate of maturation and age at puberty are the genotype; the disorders are localized at the extremes with normality in between. This is based on the association between onset of puberty and the final regressive event, with pruning of 40% of excitatory synapses leaving the inhibitory ones fairly unchanged. This makes excitability, a fundamental property of nervous tissue, a distinguishing factor: the earlier puberty, the greater excitability--the later puberty, the greater deficit. Biological treatment supports deviation from the norm: neuroleptics are convulsant; antidepressives are anti-epiletogenic. There is an association between onset of puberty and body-build: early maturers are pyknic broad-built, late ones linearly leptosomic. This discrepancy is similar to that in the two disorders, supporting the theory that body-build is the phenotype. Standard of living is the environmental factor, which affects pubertal age and shifts the panorama of mental illness accordingly. Unnatural death has increased with antipsychotics. Other treatment is needed. PUFA deficit has been observed in RBC in both disorders and striking improvements with addition of minor amounts of PUFA. This supports that dietary deficit might cause psychotic development and that prevention is possible. Other neurological disorders also profit from PUFA, underlining a general deficit in the diet.

Biological Evolution↗

A novel U2 and U11/U12 snRNP protein that associates with the pre-mRNA branch site.

Previous UV cross-linking studies demonstrated that, upon integration of the U2 snRNP into the spliceosome, a 14 kDa protein (p14) interacts directly with the branch adenosine, the nucleophile for the first transesterification step of splicing. We have identified the cDNA encoding this protein by microsequencing a 14 kDa protein isolated from U2-type spliceosomes. This protein contains an RNA recognition motif and is highly conserved across species. Antibodies raised against this cDNA-encoded protein precipitated the 14 kDa protein cross-linked to the branch adenosine, confirming the identity of the p14 cDNA. A combination of immunoblotting, protein microsequencing and immunoprecipitation revealed that p14 is a component of both 17S U2 and 18S U11/U12 snRNPs, suggesting that it contributes to the interaction of these snRNPs with the branch sites of U2- and U12-type pre-mRNAs, respectively. p14 was also shown to be a subunit of the heteromeric splicing factor SF3b and to interact directly with SF3b155. Immuno precipitations indicated that p14 is present in U12-type spliceosomes, consistent with the idea that branch point selection is similar in the major and minor spliceosomes.

Amino Acid Sequence↗

Human renal cell carcinoma xenografts in SCID mice: tumorigenicity correlates with a poor clinical prognosis.

To establish human renal cell carcinoma (RCC) xenografts for preclinical studies, 55 renal tumors (33 primary and 22 metastatic lesions) were transplanted subcutaneously into severe combined immunodeficient mice. Twenty of 49 evaluable tumors (40.8%) grew with a median latency period of 89 days (36 to 209 days) from the day of engraftment. Tumor growth was stabilized after the fifth passage with a median time between passages of 38 days (19 to 80 days). Tumorigenicity was correlated with the metastatic phenotype of the tumor (54% success rate, p = 0.007) and with reduced survival of patients. Despite a possible evolution of histological features and tumor grading, established RCC xenografts were comparable to parental tumors, as assessed by karyotype and DNA-ploidy analyses. Molecular cytogenetic analysis also revealed specific genetic alterations characterizing distinct RCC types that were constant in parental and corresponding xenografts. In addition, this xenograft model has permitted the selection of minor tumor subclones with a proliferative advantage and minimal overexpressed chromosomal regions. We conclude that severe combined immunodeficient mice are useful recipients for the establishment of long-term RCC xenografts that can be used as valuable tools to evaluate the activity of new therapeutic approaches and to study biological parameters determining in vivo aggressiveness of human RCC.

Adult↗

Idiopathic calcifying tenosynovitis. Histopathologic features and possible pathogenesis.

We report the histopathologic findings in two cases of idiopathic calcifying tenosynovitis, one involving the insertion of the right pectoralis minor tendon, and the other the left ring finger proximal interphalangeal joint of a 54-year-old male and a 28-year-old female, respectively. At operation, cream cheese-like material was identified in each case. Sections of tendon in the first case showed numerous circumscribed lesions in various stages of evolution. Early lesions consisted of central granular or globular proteinaceous material surrounded by histiocytes, lymphocytes, and foreign-body giant cells, with a peripheral network of small blood vessels. Larger, more mature lesions contained similar proteinaceous material, but had central cavitation, a thinner reactive inflammatory zone, and a fibrous capsule. The largest lesions were cystic, had no proteinaceous material or significant inflammatory zone, and had a thick fibrous capsule. No calcification was identified in the intratendinous lesions. In contrast, the hyperplastic synovium and other peritendinous tissues contained numerous round psammoma-like calcifications. It is concluded that the synovial and peritendinous psammoma-like calcifications in our cases represent a reaction to a primary tendinous lesion, which may be a consequence of ischemia or persistent mild trauma.

Adult↗

Obesity: the integrated roles of environment and genetics.

Obesity represents one of the most serious global health issues with approximately 310 million people presently affected. It develops because of a mismatch between energy intake and expenditure that results from behavior (feeding behavior and time spent active) and physiology (resting metabolism and expenditure when active). Both of these traits are affected by environmental and genetic factors. The dramatic increase in the numbers of obese people in Western societies reflects mostly changing environmental factors and is linked to reduced activity and perhaps also increased food intake. However, in all societies and subpopulations, there are both obese and nonobese subjects. These differences are primarily a consequence of genetic factors as is revealed by the high heritability for body mass index. Most researchers agree that energy balance and, hence, body weight are regulated phenomena. There is some disagreement about exactly how this regulation occurs. However, a common model is the "lipostatic" regulation system, whereby our energy stores generate signals that are compared with targets encoded in the brain, and differences between these drive our food intake levels, activity patterns, and resting and active metabolisms. Considerable advances were made in the last decade in understanding the molecular basis of this lipostatic system. Some obese people have high body weight because they have broken lipostats, but these are a rare minority. This suggests that for the majority of obese people, the lipostat is set at an inappropriately high level. When combined with exposure to an environment where there is ready availability of food at low energy costs to obtain it, obesity develops. The evolutionary background to how such a system might have evolved involves the evolution of social behavior, the harnessing of fire, and the development of weapons that effectively freed humans from the risks of predation. The lipostatic model not only explains why some people become obese whereas others do not, but also allows us to understand why energy-controlled diets do not work. Drug-based solutions to the obesity problem that work with the lipostat, rather than against it, are presently under development and will probably be in regular use within 5-10 y. However, several lines of evidence including genetic mapping studies of quantitative trait loci associated with obesity suggest that our present understanding of the regulatory system is still rudimentary. In particular, we know nothing about how the target body weight in the brain is encoded. As our understanding in this field advances, new drug targets are likely to emerge and allow us to treat this crippling disorder.

Adult↗

Type II protein secretion and its relationship to bacterial type IV pili and archaeal flagella.

Homologues of the protein constituents of the Klebsiella pneumoniae (Klebsiella oxytoca) type II secreton (T2S), the Pseudomonas aeruginosa type IV pilus/fimbrium biogenesis machinery (T4P) and the Methanococcus voltae flagellum biogenesis machinery (Fla) have been identified. Known constituents of these systems include (1). a major prepilin (preflagellin), (2). several minor prepilins (preflagellins), (3). a prepilin (preflagellin) peptidase/methylase, (4). an ATPase, (5). a multispanning transmembrane (TM) protein, (6). an outer-membrane secretin (lacking in Fla) and (7). several functionally uncharacterized envelope proteins. Sequence and phylogenetic analyses led to the conclusion that, although many of the protein constituents are probably homologous, extensive sequence divergence during evolution clouds this homology so that a common ancestry can be established for all three types of systems for only two constituents, the ATPase and the TM protein. Sequence divergence of the individual T2S constituents has occurred at characteristic rates, apparently without shuffling of constituents between systems. The same is probably also true for the T4P and Fla systems. The family of ATPases is much larger than the family of TM proteins, and many ATPase homologues function in capacities unrelated to those considered here. Many phylogenetic clusters of the ATPases probably exhibit uniform function. Some of these have a corresponding TM protein homologue although others probably function without one. It is further shown that proteins that compose the different phylogenetic clusters in both the ATPase and the TM protein families exhibit unique structural characteristics that are of probable functional significance. The TM proteins are shown to have arisen by at least two dissimilar intragenic duplication events, one in the bacterial kingdom and one in the archaeal kingdom. The archaeal TM proteins are twice as large as the bacterial TM proteins, suggesting an oligomeric structure for the latter.

Adenosine Triphosphatases↗

Cyclone mitigation, resource allocation and post-disaster reconstruction in south India: lessons from two decades of research.

This paper opens with a history of development and disaster-prevention strategies in a cyclone-prone area of the east coast of India and traces the evolution in the area of British and Indian governments' programmes and policy over a century. Research over the last 20 years has shown, however, that the programmes and policies have failed to balance economic growth with safety. Resources intended for the benefit of all have been diverted by alliances of powerful people to a small minority, and recent developments have reduced the physical protection of the area. The result is that increasing numbers of people are vulnerable to the effects of cyclones and floods. The findings suggest that the best way to reduce vulnerability is to improve the socio-economic standing of the most vulnerable and for this to happen these people must have an assured income based on assets that will enable them to acquire social and economic credit-worthiness within the local economy. This paper presents evidence that suggests that non-governmental organisation (NGO)-supported co-operatives are the best way to achieve this through self-help and self-employment schemes. It also suggests that NGOs should be encouraged to take up environmentally and ecologically beneficial activities involving the poorest groups in the communities, in this way combining sustained self-employment with environmental protection.

Community Participation↗

Structural similarities between C6 and C7 of human complement.

A new method for the isolation of C6 and C7 by affinity chromatography of human serum with anti-C6 and anti-C7 coupled to Sepharose is described. C6 and C7 prepared by this method are hemolytically fully active, homogeneous proteins obtained in 25% yield. A comparison of the properties of isolated C6 and C7 gave the following results: The amino acid composition of the two proteins is very similar. The m.w. calculated from the amino acid content is 124,800 for C6 and 120,800 for C7. Both components are single chain glycoproteins migrating upon electrophoresis at pH 8.6 as beta 2-globulins, Both proteins are polymorphic as detected by isoelectrofocusing in polyacrylamide gels and range in their isoelectric points from pH 6.15 to 6.7. The UV spectra reveal only minor differences; the extinction coefficients are: EC6 = 1.71 cm2 X mg-1 and EC7 = 1.92 cm2 X mg-1. CD-spectra show 8% alpha-helix and 10% beta-structure for C6 and 10% alpha-helix and 14% beta-structure for C7. The structural similarities of C6 and C7 suggest their evolution from a common ancestral gene.

Chemical Phenomena↗

The branching anatomical pattern of the coronary arteries as a risk factor for coronary heart disease.

In an unselected population sample of Bucharest aged 0-45 years, a similar branching anatomical pattern of the coronary arteries was revealed in 58% of the subjects. In the remainder 42% of cases 15 different minor deviations from the basal branching anatomical pattern were detected. Among these minor deviations, 4 occurred constantly associated, 8 only occasionally associated (1/3-1/2 of cases) and 3 were not associated with an accelerated atherosclerosis. The "atherogenic" deviations, characterized by an excessive size and length of the left coronary artery and an underdeveloped right coronary artery or vice versa, led to a more precocious development and more severe evolution of atherosclerotic plaques in the hyperperfused vessel.

Adolescent↗

[Hydrogeology and medicine in the approach to health problems linked to nitrates: examples in Lorraine].

An investigation carried out by French Ministration of Agriculture (S.R.A.E.L.) has worked out an inventory and defined the nitrate amount evolution in waters, specially originated with underground formations, stared out by collectivities. The investigation spreading has brought about some ascertainment in Lorraine country. Particularly, the "Laboratoire d'hygiène et de recherche en santé publique" has so identified in a commune near Nancy, where nitrate amounts in water are particularly high, gastrointestinal troubles probably caused by minor methemoglobinemias which water supply origin have not been locally suspected. This note so shows that medical and paramedical corps cooperation with administrative authorities charged with water resource can attempt some interventions: better diagnosis, population and mayors information, search of technical and administrative settlements according to local environment.

Agriculture↗