Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “big data”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,729 records · Page 96Linked to original sources
PubMed1996

Cleft-twin sets in Finland 1948-1987.

Extensive review of the literature since 1884 on cleft-twin sets yielded 364 cleft-twin sets. Of these, 118 were monozygotic (MZ) and 246 dizygotic (DZ) sets. In addition, Danish material on cleft twins, like our Finnish material, reflects the total number of clefts and cleft twins on a well-defined population during a well-defined time interval. Both sets of material also contain slightly over 100 pairs of twins. The Danish material and the literature review were compared to the Finnish material. The hospital records of all Finnish patients with operated clefts who were born between 1948 and 1987 were reviewed. Information was gathered regarding each patient, his parents, the pregnancy, and his twin or triplet siblings and other siblings. This search produced 105 sets of twins and three sets of triplets with clefts, 15 sets of twins being concordant regarding clefting. This resulted in a total of 120 cleft siblings, and the corrected cleft incidence of 1.72 promille, close to the overall cleft incidence rate in Finland between 1948 and 1975. Twinning was found to be associated neither with an increased nor with a decreased risk of clefting, and clefting could not be seen to increase twinning. Zygosity could be verified in 88 sets of twins; the total number of MZ sets was 17, and of DZ was 71, a 19% MZ rate. Although a higher incidence of clefting in MZ-twin sets has been proposed, no such higher or lower incidence could be found in our material. Recognized syndromes were found in 15 sets (14%), slightly higher than found in a large Finnish study on cleft probands (8.4%). Of these, three sets were monozygotic (MZ), all of them cleft palate (CP) and male sets, whereas eight sets were dizygotic (DZ). All 15 sets were CP only, with no one set with cleft lip and palate [CL(P)]. In our total Finnish-twin material of 105 sets, we found the CL(P)/CP ratio to be 39/66 (37%/63%). In all of the 120 affected siblings, the ratio was 35%/65%. The very high rate of 63% of CP twins is about two to three times higher than that reported in the literature of 364 sets where the CP ratio is 23%; compared to the Danish material with a CP ratio of 17%, it is almost four-fold. The overall CP rate in all clefts (not restricted to twins) in Finland compared to the rate in our neighboring Scandinavian countries was very much in line with this very big difference seen in the CP rate in our twin material. The CL(P) incidence in our Finnish material is 0.61 promille and the CP incidence 1.11 promille. For MZCL(P), the incidence was 0.38 promille; for MZCP, 0.91 promille; for DZCL(P), 0.52 promille, and for DZCP, 0.99 promille. Compared to the Danish figures both the MZCP and DZCP incidence figures are nearly four-fold, with the MZCL(P) somewhat lower, and DZCL(P) less than half that number. The sex distribution of all cleft patients in our material was 44% male/56% female. Both in the Danish material and in the literature, it was the reverse. This difference is probably due mostly to the higher ratio of CP in the Finnish material. The CP group has a higher proportion of females in all these materials. The concordance (C) of the whole Finnish-twin material is 14%, compared to 16.5% reported in the literature and 8% for the Danish twins. The concordance for CL(P) in our material is many times lower (2.6%) than in the literature (17.1%) and in the Danish material (8%). In the Finnish twins, the C for CP is higher (17%) than that for the Danish (6%) and for the literature cleft-twin populations (14.3%). This is also true for the MZ and DZ subgroups. The heritability index (H) in CL(P) is lower for the Finns (17%) than for the Danish (45%) and for the literature materials (43%), and higher for CP (Finns 49%, Danish 33%, literature 36%). All of these data strongly suggest the quite different genetic behavior of both CL(P) and CP in Finland, with a much lower genetic component in the CL(P) and a higher in the CP.

Cleft Lip↗
PubMed2004

Psychosocial combined with agonist maintenance treatments versus agonist maintenance treatments alone for treatment of opioid dependence.

BACKGROUND: Methadone maintenance at proper doses is effective in retaining patients in treatment and suppressing heroin use. Questions remain regarding the efficacy of the psychosocial services that are offered by most maintenance programs. OBJECTIVES: To evaluate the effectiveness of any psychosocial plus any agonist maintenance treatment versus any agonist treatment alone in retaining patients in treatment, reducing the use of substances and improving health and social status. SEARCH STRATEGY: We searched the Cochrane Central Register of Trials (CENTRAL) issue 3, 2003; MEDLINE 1966-2003; EMBASE 1980-2003; PsycINFO 1985-2003; relevant web sites; scan of reference list of relevant articles. There were no language or publication restrictions. SELECTION CRITERIA: RCTs which focus on any psychosocial plus any agonist compared to any agonist maintenance intervention for opiate dependence. People aged less than 18 and pregnant women were excluded. Psychosocial in combination with antagonist maintenance treatment are excluded too. DATA COLLECTION AND ANALYSIS: The trials were independently assessed for inclusion and methodological quality by the reviewers. Data were extracted independently and double checked. MAIN RESULTS: The searching process resulted in the identification of 77 different studies: 12 studies met the inclusion criteria. These studies considered 8 different psychosocial interventions and 1 pharmacological treatment: Methadone Maintenance (MMT). The results show additional benefit in adding any psychosocial treatment to standard methadone maintenance treatment in relation to the use of heroin during the treatment RR 0.69 (95% CI 0.53-0.91); no statistically significant additional benefit was shown in terms of retention in treatment RR 0.94 (95% CI 0.85-1.02); and results at follow-up RR 0.90 (95% CI 0.76-1.07). REVIEWERS' CONCLUSIONS: The present evidence suggests that adding any psychosocial support to Standard MMT significantly improves the non-use of heroin during treatment. Retention in treatment and results at follow-up are also improved, although this findings did not achieve statistical significance. Insufficient evidence is available on other possible relevant outcomes such as Psychiatric symptoms/psychological distress, Quality of life. Limitations to this review are imposed by the heterogeneity of the trials both in the interventions and the assessment of outcomes. Results of studies were sometimes in disagreement and because of lack of detailed information no meta analysis could be performed to analyse the results related to the outcomes more often reported as positive results in the single studies. Duration of the studies was also too short to analyse other relevant outcomes such as mortality. In order to study the possible added value of any psychosocial treatment over an already effective treatment such as standard MMT, only big multi-site studies could be considered which define experimental interventions and outcomes in the most standardized way as possible.

Combined Modality Therapy↗
PubMed1998

[AIDS in Madagascar. I. Epidemiology, projections, socioeconomic impact, interventions].

Madagascar is still among the rare states of low prevalence of HIV. The seroprevalence rate is nevertheless rising. The aim of this study is to show the current view of the epidemic, its future tendency, its economical and social impact on people and what measures to be taken at the national scale. In Madagascar, we can state by 1995 20 cases of notified AIDS and probably 130 cases of non-notified AIDS. Seroprevalence data are collected every year by the National Reference Laboratory STD/AIDS. But, they are insufficient to estimate the number of infected people. So, they had been completed by a serosurveillance study of AIDS and syphilis in middle of 1995 and at the beginning of 1996. Pregnant women, persons with STDs and prostitutes are been screened in the six biggest cities of the Island. Results show, not only a high prevalence of syphilis, but also indicate that now, we have about 5,000 seropositive people in the country. Besides, by the number of people with STDs, it is estimated that one million Malgasy adults risk to be infected. Based on estimates of the epidemic, be it the cases of a high scenario, (Kenya) or of a low one (Thailand) by the year 2015, the seroprevalence rate could represent 3% or 15% of adults. Demographic consequences of the epidemic will be serious, particularly if HIV spreads quickly. Nevertheless, it does not stop the increase of population. Therefore, there will be more infected people with the disease, especially young people between 15 and 49 years old. The increase of dead people will be serious. Social consequences of the epidemic (case of high scenario) will be gravely felt, in particular by the rise of the number of AIDS orphans. Tuberculosis outbreak can be observed too. This disease is already a serious problem in Madagascar. At last, the epidemic will bring with it a high increase of money spent on health and will have grave consequences on agriculture, industry and commerce. Nevertheless, Madagascar still benefit a big luck which is the prevention of the epidemic not to be exploded in a near future. For this, struggle against it is particularly effective on its start. In addition to counselling given to infected people and care-given to patients, means of prevention of AIDS contamination in all target groups must be set up quickly. It is about broadcasting information on AIDS, community education, controlling other STDs e.g. (importance of medicaments' program), promoting the use of condoms and screening HIV new cases. Only an urgent coordination of everyone's efforts can control the epidemic of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Mutant frequencies and mutation spectra of dimethylnitrosamine (DMN) at the lacI and cII loci in the livers of Big Blue transgenic mice.

The lacI gene in Big Blue transgenic rodents has traditionally been used as a surrogate gene for in vivo mutations. Recently, a more efficient and less expensive assay involving direct selection in the smaller lambda cII gene has been developed. Little is known, however, about the comparative sensitivity of the two loci or their influence on the recovered mutation spectrum following mutagen treatment. We have compared the mutation frequency (MF) and mutational spectrum (MS) of lacI and cII from the same DNA samples isolated from the liver of control and dimethylnitrosamine (DMN)-treated mice. A three-fold (p<0.01) increase in the MF was observed at both loci in the DMN-treated group compared to the corresponding control groups. While the DMN-induced mutation spectrum at lacI was significantly different from its corresponding spontaneous mutation spectrum (p<0.001), the mutation spectrum at cII (p>0.28) was not. The mutation spectra at the two loci from the DMN-treated mice resembled each other but the 4, 2.5 and 12-fold increase in the mutation frequency of A:T>T:A transversions, single base deletions and deletions of more than four base pairs, respectively, at lacI, altered the spectra significantly (p<0.007). The number of mutations of these classes at cII was also increased, but the fractions were lower than at lacI. The spontaneous mutation spectra at the cII and lacI loci resembled each other except for the seven-fold increase in G:C<C:G transversions in the cII spectrum resulting in a significant difference (p<0.0001) between the spectra. Our initial data indicates that although cII is as sensitive to mutation induction as lacI, fewer sites are available for certain classes of mutations to be manifest resulting in an apparent lack in change in the mutation spectrum.

Animals↗
PubMed1989

The big, bad city: mega-city myth?

This paper raises the question of whether or not the virtues of big city size were exaggerated in the literature which appeared in the 1970s with respect to developing country megacities. It examines negative externalities (especially pollution), the capital costs associated with megacity growth, the productivity advantages of large cities, the role of spatial restructuring towards a policentric pattern as a relief to core city congestion, and the problems of metropolitan management (including the appropriate institutional framework). The adoption of constructive policy actions could handle the following problems: that the declining rates of megacity growth may reflect declining productivity advantages; that capital costs of urbanization increase strongly with city size; that there are diseconomies of scale in urban management; that negative externalities may be more severe in developing country megacities in physical but not in imputed monetary damage terms; and that policentric evolution may be hampered by the wrong type of government intervention.

Demography↗
PubMed2006

Initial study on the effects of Prestige oil on human health.

The big oil tanker Prestige wrecked at 130 miles from the coast of Galicia, on the Northwest of Spain, in November 19, 2002. During the accident over 40,000 tons of oil were spilled, and along the next weeks 22,000 more reached the shore in the way of three black tides. A great number of people participated in the cleaning tasks. The objective of this study was to initially evaluate the damage caused by Prestige oil in exposed individuals both from the cytogenetic and the endocrine points of view. Exposure level was determined by analysing volatile organic compounds in the environment and heavy metals in blood. Cytogenetic damage was determined by sister chromatid exchanges (SCE), and plasmatic prolactin and cortisol levels were used as biomarkers of endocrine toxicity. Finally we have determined the possible influence of GST genetic polymorphisms (GSTM1 and GSTT1 deletion polymorphisms, GSTP1 Ala105Val) on the evaluated effects. The exposed population was classified according to the performed cleaning tasks in three groups: volunteers that collaborated for 1 week (N=25), hired manual workers (N=20) and hired high-pressure cleaner workers (N=23). The control population consisted of 42 individuals. Exposure to Prestige oil caused cytogenetic damage in exposed individuals, being its effect influenced by age, sex, tobacco consumption and GSTM1 polymorphism. With regard to endocrine toxicity, our results showed that xenobiotics present in Prestige oil induced alterations in hormonal status, and thus it may be considered as an endocrine disruptor. Therefore, the selected parameters have shown to be good indicators of toxicity related to exposure to Prestige oil. In addition, data obtained point to the importance of using protective devices in preventing the effects related to the exposure.

Endocrine Glands↗
PubMed2006

Extrachromosomal DNA isolated from tomato big bud and Candidatus Phytoplasma australiense phytoplasma strains.

The nucleotide sequences of two extrachromosomal elements from tomato big bud (TBB) and one extrachromosomal element from Candidatus Phytoplasma australiense (Ca. P. australiense) phytoplasmas were determined. Both TBB plasmids (3319 and 4092 bp) contained an open reading frame ( approximately 570 bp) with homology to the rolling circle replication initiator protein (Rep). This gene was shorter than the rep genes identified from other phytoplasma plasmids, geminiviruses and bacterial plasmids. Both TBB extrachromosomal DNAs (eDNAs) encoded a putative DNA primase (dnaG) gene, a chromosomal gene required for DNA replication and which contains the conserved topoisomerase/primase domain. We speculate that the replication mechanism for the TBB phytoplasma eDNA involves the dnaG gene instead of the rep gene. The Ca. P. australiense eDNA (3773 bp) was shown to be circular and contained four open reading frames. The rep gene was encoded on ORF 1 and had homology to both plasmid (pLS1) and geminivirus-like domains.

Amino Acid Sequence↗
PubMed1989

Purification and structural determination of urinary NH2-terminal big gastrin fragments.

We previously demonstrated that there existed extremely abundant NH2-terminal big gastrin immunoreactivity (NT G-34-IR) in human urine. This report describes the purification and sequence of NT G-34-IR from the urine of an achlorhydric patient. The purification was carried out by a combination of Sep-Pak C18 cartridges, Sephadex G-25, and HPLC steps using a radioimmunoassay specific for NH2-terminus of G-34 and ultraviolet absorption at 214 nm as monitors. Three peptides were isolated. The amino acid analysis, mass spectrometry, and sequence analysis confirmed the structures of urinary NT G-34 fragments being less than Glu-Leu-Gly-Pro-Gln-Gly-Pro-Pro, less than Glu-Leu-Gly-Pro-Gln-Gly- Pro-Pro-His, and less than Glu- Leu-Gly-Pro-Gln-Gly-Pro-Pro-His-Leu. NH2-terminal octapeptide of G-34 was the main component of urinary NT G-34-IR.

Achlorhydria↗
PubMed1994

Big flies, small repeats: the "Thr-Gly" region of the period gene in Diptera.

The region of the clock gene period (per) that encodes a repetitive tract of threonine-glycine (Thr-Gly) pairs has been compared between Dipteran species both within and outside the Drosophilidae. All the non-Drosophilidae sequences in this region are short and present a remarkably stable picture compared to the Drosophilidae, in which the region is much larger and extremely variable, both in size and composition. The accelerated evolution in the repetitive region of the Drosophilidae appears to be mainly due to an expansion of two ancestral repeats, one encoding a Thr-Gly dipeptide and the other a pentapeptide rich in serine, glycine, and asparagine or threonine. In some drosophilids the expansion involves a duplication of the pentapeptide sequence, but in Drosophila pseudoobscura both the dipeptide and the pentapeptide repeats are present in larger numbers. In the nondrosophilids, however, the pentapeptide sequence is represented by one copy and the dipeptide by two copies. These observations fulfill some of the predictions of recent theoretical models that have simulated the evolution of repetitive sequences.

Amino Acid Sequence↗
PubMed2006

Biomechanical analysis of fracture fixation with external fixator in vivo.

OBJECTIVE: To investigate the different ways of measuring the main axial strain during treatment with an external fixator and to find the suitable compression loaded by the external fixator at an early stage. METHODS: Eighteen healthy big-ear rabbits were randomly divided into two groups according to different measuring methods: Group A and Group B. In Group A, a strain gauge was affixed to the external tibial cortex with 502 glue, and in Group B, a bone cement-coated strain gauge was installed on the internal tibial cortex. Groups A and B were divided into two subgroups A1, A2 and B1, B2, respectively, according to the pressure of half of and the same as the body weight. A Z-shaped left mid-shaft tibial osteotomy was performed and fixed by an external fixator. RESULTS: The scaler curves of Group A changed dramatically during the early stage. The trendlines of the internal and external cortex went consistently after reaching the stable stage while the latter strain value was higher than the former. The time for Group B reaching the stable stage was short, but its absolute strain value was less than that of Group A. Before they were pressed to the stable stage, the declined speed of Subgroup A1 was more slowly than that of Subgroup A2 while the results of Subgroups B1 and B2 were same. Group A had an ascending trend after it declined while Group B didn't have. After they reached the stable stage, both Subgroups A1 and A2 had a declining trend while Subgroup A2 was more quickly than Subgroup A1, Subgroup B1 was kept at a definite level while Subgroup B2 fluctuated. CONCLUSIONS: The axial strain under external fixator can be measured by bone cement coated-strain gauge in vivo. The data may suggest that half of the body weight load was suitable for external fixator.

Animals↗
PubMed2000

[Fifty years of research on tuberculosis. Lessons I have learnt during 50 years and topics to be investigated in the future].

I have engaged in the research on tuberculosis for 50 years, and lessons I have learnt during this period could be summarized in the following ten topics. First is great research achievements by our predecessors on the establishment of so-called primary infection theory on the pathogenesis of TB, planning of TB control principles based on the theory and development of new technologies used for TB control, such as mass miniature X-ray examination and BCG vaccination in 1920s and 1930s. TB control law was enforced in 1951, and the modern TB programme was initiated. Second, the field is a treasure house of interesting data. Several interesting data on TB soon after the World War II in Tokyo and a rural area were collected and analyzed from the mass health examination. Third, looking at the increase of tuberculin positivity with age, it was found that the tuberculin negativity decreased as the exponential function of age, and the current concept of the annual risk of TB infection was already developed in late 1940s. It was 18.1% in male and 11.6% in female in Tokyo in late 1940s. Based on this concept, age specific TB mortality was analyzed by the type of TB, and the rates of miliary TB and TB meningitis were similar to the rate of newly infected to the total population, while the rate of all forms could be divided into early and late death as shown in Fig. 1. Fourth, I suffered from TB by myself from 1951 to 1953, receiving first thoracoplasty in two stages under local anaesthesia, then right upper lobectomy and segmentectomy of superior segment of right lower lobe. From this experience, I learnt a lot about the psychology and suffering of TB patients. Fifth, the importance of recognition of real magnitude of the problem in such a disease as TB in which many TB cases did not aware of their disease. The answer to this was the first TB prevalence survey in 1953 using stratified random sampling method, and based on the results of the survey, the mass health examination originally focussed on youth was expanded to the total adult population of Japan. Sixth, TB could be reduced rapidly by applying appropriately planned control programme. In big enterprises, the application of intensive case-finding programme brought about the rapid decline of severe TB cases, contributed to the increase of the productivity of the enterprises, thus to the rapid increase of GDP of whole Japan, and the growing spiral between the improvement of health and the economic development was formed by successful TB control. In addition to the mass health examination, BCG vaccination and spread of appropriate treatment in the original TB control law, the registration and case management system and the more extensive application of hospitalization for infectious cases were introduced in early 1960s. Observing the proportion of TB care expenditure to the national medical expenditure, it was 28% in 1954, and it dropped down to 0.4% in recently as shown in Fig. 2. The decline of TB in Japan during 1950s and 1960s was one of fastest in the world. Seventh, there had been marked differences in the prevalence of TB as well as the coverage and quality of TB programmes in several areas of Japan though it was often said that Japan is homogeneous country. To know the real status in various areas of Japan, a chart to express graphically the magnitude of TB and coverage and quality of TB programmes was developed (Fig. 3), and it was finally refined to the current form. Eighth difficulty in changing existing programmes, and we are grateful for kind cooperation of Niigata Prefecture for making several new attempts. Ninth, it has been needed to observe TB problems from global standpoint, and it was actually done through participation to the bilateral cooperation projects on TB control and conducting the international training courses sponsored by JICA. Tenth, TB is a pertinacious disease. As shown in Fig. (ABSTRACT TRUNCATED)

Adult↗
PubMed1998

Antibodies of sharks: revolution and evolution.

The combinatorial immune response is restricted to jawed vertebrates with cartilaginous fishes being the lowest extant species to have the mechanism for diversification and an extensive panoply of immunoglobulins, T-cell receptors and MHC products. Here, we review the molecular events of the "big bang" or rapid evolutionary appearance of the functionally complete combinatorial immune system coincident with the appearance of ancestral jawed vertebrates, suggesting that this event was catalyzed by horizontal transfer of DNA processing systems. We analyze the nature and extent of variable and constant domain diversity among the distinct immunoglobulin sets of carcharhine sharks focusing upon the lambda-like light chains and the mu and omega heavy chains. The detection and isolation of natural antibodies from the blood of unimmunized sharks illustrates a surprising range of recognition specificities and the existence of polyspecificity suggests that the antibody-forming system of sharks offers unique opportunities for studies of immunological regulation. Although the homologies between shark and mammalian immunoglobulins are unequivocal, major differences in segmental gene organization present challenges to our understanding of basic immunological phenomena such as clonal restriction.

Amino Acid Sequence↗
PubMed1990

Influence of monaural plugging on postnatal development of auditory spatial sensitivity of inferior collicular neurons of the big brown bat, Eptesicus fuscus.

Postnatal development of auditory sensitivity in the big brown bat, Eptesicus fuscus, was studied by determining the auditory spatial sensitivity of inferior collicular (IC) neurons of juvenile bats which were raised under normal (control) or monaurally plugged conditions. The auditory spatial sensitivity of each IC neuron was determined by measuring its variation in number of impulses and minimum threshold to a best frequency sound delivered from different azimuthal angles under free field stimulation conditions. Monaural plugging was performed on different juvenile bats at 7, 14, and 35 days of age. Auditory spatial sensitivity was then determined for IC neurons of monaurally plugged bats at 58-69 days after birth. Monaural plugging did not alter the discharge pattern, distribution of best frequency and latency of IC neurons, but it raised the minimum threshold of IC neurons of plugged juvenile bats by an average of 21-24 dB. Monaural plugging also appeared to modify postnatal development of auditory spatial sensitivity. The auditory spatial sensitivity of IC neurons was sharper when the earplug was intact than when the earplug was removed. Thus, the distribution of response center and the spatial sensitivity of IC neurons of the monaurally plugged bats was more comparable to IC neurons of the control bats before the earplug was removed. These findings suggest that the neural circuits underlying auditory spatial sensitivity of IC neurons of the monaurally plugged juvenile bats have undergone modifications to compensate for the unnatural binaural disparity during postnatal development. The auditory spatial sensitivity was also determined for two control juvenile bats at 49 and 60 days of age and for an adult bat (more than 1 year). Our data show that auditory spatial sensitivity of IC neurons sharpens with postnatal age. Furthermore, the sharpening process appears to be still in progress even at 60 days after birth.

Acoustic Stimulation↗
PubMed2002

Transmission of mutations in the lacI transgene to the offspring of ENU-treated Big Blue male mice.

The purpose of the study was to determine: 1) if male germ cells of Big Blue mice carrying newly induced mutations in the lacI transgene were effective in fertilization; 2) if offspring arising from such mutant sperm had the mutation in germ cells and multiple somatic tissues; and 3) how the frequency of mutants induced in the lacI transgene compared to the frequency induced in endogenous genes traditionally employed to study germ cell mutagenesis in mice. Male B6C3F(1) mice hemizygous for the lambda/lacI transgene were treated weekly with 100 mg/kg body weight of the mammalian germ cell mutagen N-ethyl-N-nitrosourea (ENU). The cumulative dose for each treated animal was 300 mg ENU/kg body weight. Ten weeks later the treated mice were mated to T stock females and the resulting offspring were screened for specific-locus mutations at six loci affecting external appearance, as well as for mutations in the lacI transgene in multiple somatic tissues and germ cells. Five offspring carrying recessive specific-locus mutations were observed among 597 offspring screened (mutant frequency = 139.6 x 10(-5) per locus). Four offspring carrying lacI mutations were observed among 280 offspring screened (mutant frequency = 35.7 x 10(-5) per locus (assuming 40 target loci)). Each of the four lacI mutant offspring carried a different mutation. Three of the mutations were A:T-->G:C transitions and one a G:C-->A:T transition. Consistent with the expectation that a mutation induced in a parental germ cell and transmitted to a conceptus would exist in every cell of the offspring, each mutant mouse had identical mutations in all somatic tissues sampled, as well as in its germ cells. These data provide preliminary evidence for the biological validity of assessing induced, heritable mutations using transgenic mice, without the need for generating an F(1) generation.

Animals↗
PubMed1998

The pore-forming and cytoplasmic domains of the neurogenic gene product, BIG BRAIN, are conserved between Drosophila virilis and Drosophila melanogaster.

The Drosophila BIG BRAIN (BIB) protein functions critically in the determination of neuroblasts in the embryonic ectoderm and many other cell types. BIB is a member of the MIP family of transmembrane channel proteins. The conserved channel domain of BIB is flanked by amino- and carboxy-terminal cytoplasmic domains of unique sequence, which comprise over two-thirds of the protein. To determine whether the cytoplasmic domains of BIB are important for BIB function, we have cloned and sequenced the bib gene of D. virilis and compared it with that of D. melanogaster. Here we report that the channel domain and both cytoplasmic domains are highly conserved between the two species. The conservation of the cytoplasmic domains indicates that they are critical to BIB function. bib transcripts are found in similar patterns in both species, indicating that the developmental function(s) of BIB have also been conserved.

Amino Acid Sequence↗
PubMed1995

Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP.

The Rubinstein-Taybi syndrome (RTS) is a well-defined syndrome with facial abnormalities, broad thumbs, broad big toes and mental retardation as the main clinical features. Many patients with RTS have been shown to have breakpoints in, and microdeletions of, chromosome 16p13.3 (refs 4-8). Here we report that all these breakpoints are restricted to a region that contains the gene for the human CREB binding protein (CBP), a nuclear protein participating as a co-activator in cyclic-AMP-regulated gene expression. We show that RTS results not only from gross chromosomal rearrangements of chromosome 16p, but also from point mutations in the CBP gene itself. Because the patients are heterozygous for the mutations, we propose that the loss of one functional copy of the CBP gene underlies the developmental abnormalities in RTS and possibly the propensity for malignancy.

Amino Acid Sequence↗
PubMed1995

[Pathophysiology of fat embolisms in orthopedics and traumatology].

It is well known that fat embolisms can occur after long bone fractures, and this has been feared for more than 100 years. Since 1970 fat embolisms have also been recognized in endoprosthetic surgery. The clinical manifestation was described as the fat embolism syndrome (FES) by Gurd in 1974. Based on reports in the literature and our own data, a concise pathophysiological model of the FES is presented in this paper. The increase in intramedullary pressure (IMP) in the long bones is the most decisive pathogenic factor for the development of an FES. Any long bone fracture, stabilization of fractures, or implantation of knee or hip endoprostheses can generate IMP peaks leading to bone marrow release into the circulation. Bone marrow itself is a tremendous stimulus for activation of the clotting system. As a result, hypercoagulation and venous stasis in the draining veins generate mixed macroemboli from the initial bone-marrow microemboli. Bone-marrow embolization of the lung in phase I leads to mechanical obstruction of pulmonary arteries. In phase II, release of local mediators, triggered by a systemic inflammatory response (SIR) of the lungs, causes damage to the pulmonary membranes. Disturbed gas exchange and respiratory insufficiency with possible cardiac and cerebral decompensation are the result. In most cases an FES may not be detected clinically, and any mild cardiorespiratory changes are treated easily with oxygen insufflation and usually disappear within 48 h. Of paramount importance for clinical manifestation of an FES are the quantity and duration of bone-marrow release and co-factors (cardiorespiratory compliance and perioperative stability of the patient). Patients with preexisting cardiorespiratory disease in combination with massive intraoperative bone-marrow release may even face a deadly FES event. Increased IMP causes local obstruction of cortical vessels with bone marrow. In combination with the damaged endosteal blood supply, avascular necrosis of the cortical bone occurs. During endoprosthetic procedures, mechanical-and mediator-triggered damage of the intima of big veins, in combination with venous stasis and hypercoagulation may be responsible for the high incidence of proximal thrombosis of femoral veins. As a delayed result of the disseminated intravascular coagulopathy, petechial bleeding in the trunk and subconjunctiva can be seen. A better understanding and recognition of the FES's pathophysiology may help to use prophylactic, diagnostic and therapeutical measures more effectively.

Blood Coagulation↗
PubMed2001

Highly sensitive and selective fluorescence assays for rapid screening of endothelin-converting enzyme inhibitors.

The highly potent vasoconstrictor peptide endothelin (ET) is generated from an inactive precursor, big endothelin (bET), by endothelin-converting enzyme (ECE). ECE is a phosphoramidon-sensitive zinc metallopeptidase, which is closely related to neprilysin (neutral endopeptidase). It is possible that compounds which inhibit the formation of ET may be used as new drugs for the treatment of cardiovascular diseases. Such an approach requires a fast, simple and selective assay to measure ECE activity, allowing rapid screening of inhibitors. We describe here two new ECE substrates based on the concept of 'intramolecularly quenched fluorescence' which may fulfill this aim. One, S(1) [Pya(21)-Nop(22)-bET-1(19--35)], is the (19--35) fragment of the natural peptide big-ET-1(1--38), which is modified by introducing the fluorescent amino acid, pyrenylalanine (Pya), in position 21 and a quencher, p-nitrophenylalanine (Nop), in position 22. The second substrate (S(2)) is a small peptide, Ac-Ser-Gly-Pya-Lys-Ala-Phe-Ala-Nop-Gly-Lys-NH(2), from a biased substrate peptide library. The recombinant, hECE-1c, cleaved both Pya(21)-Nop(22)-bET-1(19--35) and the natural substrate selectively between residues 21 and 22, whereas cleavage occurred between alanine and phenylalanine in the small peptide. In both cases, this generated intense fluorescence emission. The synthesis and kinetic parameters of these substrates are described. These assays, which can be used directly on tissue homogenates, are the most sensitive and selective described to date for ECE, and are easily automated for a high-throughput screening of inhibitors.

Amino Acid Sequence↗