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Molecular studies of marsupial X chromosomes reveal limited sequence homology of mammalian X-linked genes.

To explore the extent to which the X chromosome has been conserved during mammalian evolution, we compared six loci that are X-linked in the human genome with the corresponding genes of the North American marsupial, the Virginia opossum (Didelphis virginiana). Our analysis shows that in the opossum genome there are sequences highly homologous to those of human cDNAs for housekeeping genes, glucose-6-phosphoribosyltransferase (HPRT), phosphoglycerate kinase A (PGK1), and alpha-galactosidase A (GLA). However, ornithine transcarbamylase and blood clotting Factor IX--tissue-specific genes that are X-linked in eutherians mammals--have no highly conserved homologs in the marsupial genome. By cloning opossum G6PD and HPRT, we found that these genes are X-linked in the opossum and that homologous sequences are limited to coding regions. As all genomic fragments hybridizing with the human GLA probe show dosage effects, it is likely that the opossum counterpart is X-linked. Finally, the pattern of hybridization suggests that the autosomal pseudogenes of HPRT and PGK1 in the opossum have remained highly homologous to the human X-linked genes.

Animals

[Adverse prognostic influence of diabetes mellitus and hyperglycemia on the clinical course of cerebral infarction].

We accessed the potential impact of diabetes mellitus and hyperglycemia on early prognosis in a study of 109 cases of CT proved brain infarction. Main end-points of this study were 30-days case-fatality rates and the probability of early discharge or prolonged hospitalization. Proportions of patients exhibiting diverse evolutions were compared by Fisher's test and, when the number of observations permitted, by chi-square test. Diabetes mellitus was diagnosed by history in 15.6% (17 patients). In 86 cases analysed within 72 hours of admission, hyperglycemia (glucose level higher than 110 mg/dL) was detected in 67.4% (including all 14 diabetic patients (35.3% vs 21.7%; p = 0.18), but these patients probably were discharged early less frequently (23.5% vs 51.1%; p = 0.06). Compared to the normoglycemic patients, hyperglycemic patients also fared worse, when considering altogether the early discharge and case fatality rates and the need for prolonged hospitalization (p = 0.06). They also exhibited a nonsignificant increase in early case fatality rate (31% vs 15.4%; p = 0.21) and a markedly reduced chance of obtaining early hospital discharge (37.9% vs 65.4%; p = 0.03). Case fatality rates were maximal in diabetic hyperglycemic patients (42.9%) and seemed intermediate in non-diabetic hyperglycemic patients (27.3%). Considering the three end-points evaluated, the apparent differences between non-diabetic hyper and normoglycemic patients did not reach statistical significance (p = 0.19). These results suggest that both diabetes mellitus and hyperglycemia "per se" have deleterious effects on the clinical evolution of patients with cerebral infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Walker's 256 carcinosarcoma: metastatic dissemination in two cell lines (author's transl)].

Walker's 256 carcinosarcoma a transplantable tumor of the rate changes its behaviour as a consequence of various factors. In this paper we compare the evolution of 2 lines of the tumor: WM 16 (muscular) and Christ Hospital (ascitic) both inoculated intramuscularly. Animals receiving line WM 16 had a severe rapidly progressive evolution dying around day 14 after inoculation with diffuse metastases to lymph nodes (65% of animals), kidneys (53%), spleen (50%), lungs (46.5%), liver (45%), bone marrow (44.8%), in 56% of the animals there were circulating tumoral cells. Animals receiving Christ Hospital line survived up to 40 days, metastases were limited do lungs (48.7%) and lymph nodes (31.7%) and only in 2 of 45 animals circulating tumoral cells were observed.

Animals

Isolation, characterization and expression of cDNAs encoding the catfish-type and chicken-II-type gonadotropin-releasing-hormone precursors in the African catfish.

The cDNAs encoding the catfish prepro-gonadotropin-releasing hormone and the chicken prepro-gonadotropin-releasing hormone II of the African catfish (Clarias gariepinus) have been isolated and sequenced. The catfish gonadotropin-releasing-hormone precursor and the chicken gonadotropin-releasing-hormone-II precursor have the same overall architecture as other gonadotropin-releasing-hormone precursors identified so far; each is composed of a signal peptide, gonadotropin-releasing hormone and a gonadotropin-releasing-hormone-associated peptide which is connected to gonadotropin-releasing hormone and chicken gonadotropin-releasing hormone II, in combination with the Gly-Lys-Arg sequence, are highly conserved during evolution when compared with the corresponding regions of mammalian, avian (chicken gonadotropin-releasing hormone I) and other fish gonadotropin-releasing-hormone precursors. However, the gonadotropin-releasing-hormone-associated peptide regions are markedly divergent. Northern-blot analysis revealed the presence of a single catfish gonadotropin-releasing-hormone mRNA species of about 470 bases, and the presence of a single chicken gonadotropin-releasing-hormone-II mRNA species of about 650 bases in the African catfish brain. In situ hybridization revealed catfish gonadotropin-releasing-hormone cell bodies rostro-caudally scattered in the olfactory nerve, along both sides of the midline of the telencephalon, in the preoptic area of the ventral hypothalamus, and in the infundibular stalk close to the pituitary. Chicken gonadotropin-releasing-hormone-II cell bodies, however, were exclusively found in the midbrain tegmentum.

Amino Acid Sequence

Differential progression of complex and smooth stenoses within the same coronary tree in men with stable coronary artery disease.

OBJECTIVES: We sought to compare the evolution of complex and smooth stenoses within the same coronary tree in patients with stable coronary artery disease. BACKGROUND: Progression of coronary stenosis has prognostic significance and may be influenced by local and systemic factors. Stenosis morphology is a determinant of disease progression, but no previous study has systematically assessed progression of complex and smooth stenoses within the same patient. METHODS: We studied 50 men with stable angina who 1) had one complex coronary stenosis and one smooth stenosis in different noninfarct-related coronary vessels at initial coronary angiography, and 2) had a second angiogram after a median interval of 9 months (range 3 to 24). Patients with lesions > or = 10 mm long, at a major branching point or with > 85% diameter reduction were not included. Coronary lesions were measured quantitatively from comparable end-diastolic frames. Stenosis morphology was determined qualitatively by two independent observers. RESULTS: All patients remained in stable condition during follow-up. Progression, defined as an increase in diameter stenosis by > or = 15% was seen in only eight complex stenosis (16%) but in no smooth lesions (p < 0.01). The severity of complex stenoses changed more than that of corresponding smooth stenoses (mean +/- 1 SD 5.8 +/- 13% vs. -0.06 +/- 6%, p < 0.01). On average, the annual rate of growth was 11.4 +/- 28% and 1.5 +/- 14% for complex and smooth lesions, respectively (p < 0.01). CONCLUSIONS: Few coronary stenoses progress rapidly in stable angina. Complex and smooth coronary stenoses progress at different rates within the same coronary tree. complex stenosis morphology itself is an important determinant of progression of stenosis in patients with apparently clinically stable coronary artery disease.

Aged

[Acute myocardial infarction. Different treatment, different prognosis?].

Many statistics demonstrate a definite improvement of myocardial infarction during hospitalization, especially a decrease in the mortality. It appears tempting to credit that improvement to the numerous modifications of the treatment of this dangerous disease in the last few decades. The study reported here indicates, however, that other factors must be taken into account. We compared the evolution of two groups of patients hospitalized for acute myocardial infection, 10 years apart: The first group (G1) of 731 patients corresponds to years 1970-1975; the second group (G2) of 729 patients, corresponds to the years 1984-85-86. During these ten years, mortality decreased by 38 p. cent, from 19.2 p. cent (G1) to 11.9 p. cent (G2). This decrease remains significant regardless of age and sex, except in two subgroups with the least number of patients, i.e. women under the age of 65 and men over 65. It should be noted that rhythm disorders occur with the same frequency in both sub-groups while atrio-ventricular blocks seem to have decreased. The difference in the mortality cannot be attributed to the patient's selection. In fact, in both groups, they are comparable regarding the men/women ratio, the age distribution and the presence of main risk factors (tobacco abuse, dyslipidemia, arterial hypertension, diabetes, heredity). The treatment results in many alterations especially concerning diuretics which seem to be used in approximately 30 p. cent of the patients in both groups. On the contrary, steroids, prescribed in 25.3 p. cent of G1 patients are abandoned; electro-systolic stimulation established in 21.2 p. cent of G1 patients, concerned only 4 p. cent of G2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Female

Large sequence divergence among mitochondrial DNA genotypes within populations of eastern African black-backed jackals.

In discussions about the relative rate of molecular evolution, intraspecific variability in rate is rarely considered. An underlying assumption is that intraspecific sequence differences are small, and thus variations in rate would be difficult to detect or would not affect comparisons among distantly related taxa. However, several studies on mammalian mitochondrial DNA (mtDNA) have revealed considerable intraspecific sequence divergence. In this report, we test for differences in the rate of intraspecific evolution by comparing mtDNA sequences, as inferred from restriction site polymorphisms and direct sequencing, between mtDNA genotypes of the eastern African black-backed jackal, Canis mesomelas elongae, and those of two other sympatric jackal species. Our results are unusual for several reasons. First, mtDNA sequence divergence within several contiguous black-backed jackal populations is large (8.0%). Previous intraspecific studies of terrestrial mammals have generally found values of less than 5% within a single population, with larger divergence values most often occurring among mtDNA genotypes from geographically distant or isolated localities. Second, only 4 mtDNA genotypes were present in our sample of 64 jackals. The large sequence divergence observed among these mtDNA genotypes suggests there should be many more genotypes of intermediate sequence divergence if they had evolved in sympatry. Finally, estimates of the rate of mtDNA sequence evolution differ by approximately 2- to 4-fold among black-backed jackal mtDNA genotypes, thus indicating a substantial heterogeneity in the rate of sequence evolution. The results are difficult to reconcile with ideas of a constant molecular clock based on random fixation of selectively neutral or nearly neutral mtDNA sequence mutations.

Africa, Eastern

Course of psychosis in Algeria and in France: about 342 cases observed from 1975 to 1985.

The aim of this study was to compare the evolution of psychotic patients in Algeria and in France. In 1975, 105 patients were selected in Algeria and 237 in France. Ten years later, in 1985, all these patients were interviewed. In 1985, we investigated for each subject the evolution of the following parameters: sex, age, DSM-III axis 1 and 5, marital status, social welfare work, and treatment variables. Our results indicate that the improvement of the psychosocial adaptation (DSM-III axis 5) is slightly better in Algeria than in France. Medical and social support seems to be quantitatively less important in Algeria.

Adult

The influence of gut function on lymphoid cell populations in the intestinal mucosa of lambs.

The number and type of lymphoid cells in the intestinal mucosa of lambs change during the first weeks after birth. The influence of gut function on these changes was examined by comparing the evolution of lymphoid cell populations in normal ileum with that in lengths of ileum which had been isolated surgically from the functional intestinal tract of the lamb before birth. The isolated lengths of ileum had a normal blood and nerve supply and they remained healthy throughout a period of at least 2 years, although they did not have a normal histological development. In comparison with normal ileum, the villi of the isolated ileal segments were much smaller and there were many fewer intraepithelial lymphocytes; the lamina propria had significantly fewer lymphocytes than the functional ileum and only a few plasma cells. When isolated ileal segments were reconnected into the intestinal tract after having been isolated from it for 1-3 months, the histology of the mucosa reverted to that of the normal gut, with the same number and types of lymphoid cells. Radiolabelled lymphoblasts collected from intestinal lymph and injected intravenously accumulated to only a small extent in isolated segments of ileum compared with either the normal or the reconnected segments of ileum. This suggested that the paucity of lymphocytes in the mucosa of the isolated segments was due to a reduced extravasation of these cells there. The influence which the gut contents exert on the lymphoid cell population in the mucosa is probably associated with antigenic stimulation but may also be related to other factors concerned in the normal digestive functions of the gut.

Animals

[Research in sociotherapy].

The author compares his experience in two psychiatric institutions: an old one of the traditional type, a new one of the psychotherpeutic type. He tries and defines the role of the different members of the staff and compares the evolution of the traditional institute and of the more recent clinic. In the psychotherapeutic institution, there is a drift of the therapeutic role from the physician to the nurse, and finally from the nurse to the patient himself. Despite the fact that they are open, the therapeutic groups become more efficient with time in relation to the maturation of the nursing personal. This slow growth of the psychotherapeutic role of the institutional group finally depends as much on the inhibitions of the nursing staff than on the anxiety of the patients.

Hospitalization

Comparative kinetics study of the evolution of freshwater aquatic toxicity and biodegradability of linear and branched alkylbenzene sulfonates.

Evolution of both primary biodegradability and acute toxicity to daphnia and zebra fish of a linear alkylbenzene sodium sulfonate (LAS) and a branched alkylbenzene sodium sulfonate (BAS) have been measured simultaneously. In six of eight experiments, LAS was biodegraded to 90% in 7 days and BAS to 70% in 7 days. In the two other experiments, both LAS and BAS have shown the same biodegradation speed and reached the same biodegradation level in 7 days: 45% in one experiment and 55% in the other. The composition of bacteria population and the level of cellular ATP of the inoculum play a decisive role in the biodegradation. These results confirm that it is essential to know the composition of bacteria population present in the inoculum as well as their biochemical characteristics to accurately interpret results of biodegradation tests. In the case of a rapid primary biodegradation of LAS and BAS, the acute toxicity of LAS remains three times as high as that of BAS for at least 24 hr toward daphnia and 48 hr toward zebra fish. Their acute toxicity to daphnia and zebra fish become equivalent only after 72 hr. When primary biodegradation of both products is slower, the acute toxicity of LAS remains higher than that of BAS for more than 7 days.

Alkanesulfonates

Parvalbumins from coelacanth muscle. II. Amino acid sequence of the two less acidic components.

The primary structure of the two less acidic parvalbumins (pI = 5.44 and pI = 4.95) from coelacanth muscle (Latimeria chalumnae) has been determined. They differ only by the presence or absence of a N-terminal blocking group. By the use of the automatic degradation, 69 amino acids could be placed unambiguously in the N-terminal part and 24 amino acids following the single arginine 75. Tryptic peptides were used to establish the sequence and the position of the remaining residues. The two parvalbumins examined belong to the alpha-lineage, and the rate of their molecular evolution is comparable to that found in other vertebrates.

Amino Acid Sequence

Effects of CDP-choline on the recovery of patients with head injury.

A single blind randomized study has been conducted in 216 patients with severe or moderate head injury, with the aim of comparing the evolution of those that received only conventional treatment with the evolution of those treated with CDP-choline. Our results indicate that CDP-choline improves the global outcome of patients. We have found a trend towards a greater improvement in motor, cognitive and psychic alterations in the patients treated with CDP-choline, as well as a shortening of the stay in the hospital ward in the patients receiving this drug that initially presented with severe head injuries.

Adolescent

Glucose: a more powerful modulator of fructose 2,6-bisphosphate levels than insulin in human hepatocytes.

This study provides the first experimental evidence of the short-term control of fructose 2,6-bisphosphate (Fru(2,6)P2) levels in adult human hepatocytes. (1) In hepatocytes whose metabolic status resembles the fed state (glycogen-rich), exposure to glucagon (10(-8) M) caused a drastic decrease in the levels of this effector and a significant fall in lactate production rate. Adrenaline, isoprenaline (a beta-adrenergic agonist) and lactate exerted a similar action decreasing Fru(2,6)P2 concentration. (2) In glucagon pre-treated, glycogen- and Fru(2,6)P2-depleted cells (a situation that mimics the fasted state), Fru(2,6)P2 re-synthesis was strictly dependent on glucose availability. (3) Insulin did not seem to exert a direct action on the control of Fru(2,6)P2 in human hepatocytes. The hormone--which failed to enhance Fru(2,6)P2 in glucose-starved cells--did not further increase Fru(2,6)P2 content nor its time-course evolution as compared to hepatocytes incubated with glucose alone. (4) Lactate caused a significant delay in the glucose-induced increase in Fru(2,6)P2 content that could not be prevented by insulin. (5) Data indicate that in human hepatocytes glucose is a more powerful modulator of Fru(2,6)P2 than insulin, and that variations in blood lactate concentration may also play a role in the control of hepatic Fru(2,6)P2 levels during the fasted-to-fed transition in humans.

Cells, Cultured

The position of the dentition in the mandible and its possible relation to orthodontic abnormalities.

A method used to study human evolution has compared different positions of the lower dentition in relation to the position of the mandibular condyle in the sagittal plane. The method is modified here and, with data from the Burlington Growth Study, used to describe a normal range of positions for the human lower dentition in relation to the condyle from the ages of 4 to 20 years. Measurements of a randomly selected group of orthodontically treated patients showed that in about one half of them the lower dentition was outside the normal range before treatment. The effect of treatment was to move the dentition randomly toward or away from a normal position. It is concluded that the new cephalometric measurement described here could help in the diagnosis and treatment of orthodontic patients.

Adolescent

[Comparison of blood pressure profiles with flunitrazepam/fentanyl/nitrous oxide vs cervical epidural anesthesia in surgery of the carotid artery].

A study was carried out to compare the evolution of arterial blood pressure during carotid endarterectomy performed under either general anaesthesia (GA) or cervical epidural anaesthesia (CEA). 20 patients were randomly assigned to two equal groups. In the CEA group, 15 ml of 0.375% bupivacaine and 150 micrograms fentanyl were injected into the epidural space at C7-D1 level. In the GA group, patients were anaesthetized with 0.2 mg.kg-1 flunitrazepam and 5 micrograms.kg-1 fentanyl; intubation was carried out using 0.08 mg.kg-1 vecuronium, and the patients were ventilated with a mixture of nitrous oxide and oxygen (50% of each). Further injections, every 30 min, of 2 micrograms.kg-1 fentanyl were given to the patients in group GA. Blood pressure was monitored continuously, up to 4 h postoperatively, with a radial arterial catheter. Per- or postoperative hypertension was defined as a rise in systolic arterial blood pressure (Pasys) over 180 mmHg for greater than 3 min; this was treated with 20 mg nifedipine intranasally (group CEA) or 100 micrograms fentanyl with 0.5 mg flunitrazepam with or without nifedipine (group GA). Per- or postoperative hypotension was defined as a fall in Pasys below 100 mmHg and or a 30% fall in mean arterial blood pressure for greater than 3 min; this was treated, in both groups, with an intravenous bolus of 3 mg ephedrine. Patients in group CEA experienced more frequent episodes of peroperative hypertension (8/2; p less than 0.02) and postoperative hypotension (5/1) than group GA.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Evolution of the tenascin family--implications for function of the C-terminal fibrinogen-like domain.

The three members of the tenascin (TN) family, TN-C, TN-R, and TN-X, are apparently conserved in all vertebrates and therefore must have functions that contribute to survival. One specific domain of tenascins, the fibrinogen-like terminal knob, can be argued to have an essential function. Its position at the C-terminus makes it most vulnerable to loss through mutation or deletion, and it should have been eliminated in evolution if there were no selective pressure to maintain it. The epidermal growth factor and fibronectin III domains probably play an important role as spacers, placing the terminal knob at the end of the tribrachion or hexabrachion arms. In addition to functioning as spacers, at least some of these domains may have additional functional interactions. The conservation of these domains in evolution is comparable to that of some growth factors, consistent with this possibility. A phylogenetic tree of all known fibrinogen-related domains, including those in tenascins, is presented.

Animals

Parallel evolutionary trajectories rewire enteropathogenic Escherichia coli adhesion to restore host attachment.

Enteropathogenic Escherichia coli (EPEC) causes disease in children, presenting as chronic diarrhea that can impair physical and cognitive development. The attachment of typical EPEC (tEPEC) to the gut epithelium via bundle-forming pili (BFP) is a key factor in its virulence. Yet, infections by atypical EPEC (aEPEC), which lack BFP, have become increasingly common. To investigate how aEPEC recover host-attachment in the absence of BFP, we performed experimental evolution using a non-adherent E. coli, constructed to mimic the ancestor of aEPEC, and selected adherent progeny. Highly adherent variants evolved through phase-variable activation of type I fimbriae (T1F), followed by two alternative trajectories: bacterial filamentation, which increases T1F avidity, or point mutations in the T1F adhesin FimH that enhance ligand affinity. Extending our analysis to the genomes of 327 aEPEC strains isolated from infected patients revealed that similar FimH mutations are common. We further demonstrated experimentally that these naturally occurring variants often increase epithelial-attachment. Our findings implicate T1F in aEPEC pathogenesis and suggest it may be clinically relevant for anti-adhesion therapy. More broadly, these results indicate that impaired host-attachment can be rapidly compensated by upregulating and optimizing an alternative adhesin, and that combining experimental evolution with comparative genomics can reveal evolutionary trajectories occurring in nature.

Bacterial Adhesion