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The gene structure of human anti-haemophilic factor IX.

The mRNA sequence of the human intrinsic clotting factor IX (Christmas factor) has been completed and is 2802 residues long, including a 29 residue long 5' non-coding and a 1390 residue long 3' non-coding region, but excluding the poly(A) tail. The factor IX gene is approximately 34 kb long and we define, by the sequencing of 5280 residues, the presumed promoter region, all eight exons, and some intron and flanking sequence. Introns account for 92% of the gene length and the longest is estimated to be 10 100 residues. Exons conform roughly to previously designated protein regions, but the catalytic region of the protein is coded by two separate exons. This differs from the arrangement in the other characterized serine protease genes which are further subdivided in this region.

Amino Acid Sequence↗

Blood safety and the choice of anti-hemophilic factor concentrate.

Hemophilia is a congenital disorder due to the deficiency of the activity of factor VIII (classical hemophilia A) or IX (Christmas disease or hemophilia B). Bleeding is common and may result in long-term complications or even death. Bleeding may be treated or prevented by infusion of factor concentrates however these drugs are not without risk. Clinicians often feel ill prepared to provide accurate and impartial information regarding these drugs. This review will provide the reader with an historical yet up to date perspective on blood safety as it relates to the choice of concentrates to treat hemophilia.

Blood Donors↗

Benzyl-benzoate foam: effects on mite allergens in mattress, serum and nasal secretory IgE to Dermatophagoides pteronyssinus, and bronchial hyperreactivity in children with allergic asthma.

Home mattresses of 24 asthmatic children with house dust mite allergy were sprayed with either benzyl-benzoate foam or placebo in a double blind fashion, 10 days before the children left the residential house for asthmatic children Istituto Pio XII (located in the Italian Alps in an environment free of mites) and went back to their own home for the Christmas and Easter holidays. A further group of 8 children, whose mattresses received no treatment, was kept as an absolute control. Two days after spraying, benzyl-benzoate or placebo were vacuumed from the mattresses. Acarex test was performed immediately before spraying and at the end of each holiday period of 20 and 10 days, respectively. Bronchial hyperreactivity as well as serum and nasal secretory specific IgE for Dermatophagoides pteronyssinus were assessed in all children immediately before leaving and within 48 hr after returning to the residential house. The results of the study show that sprayed benzyl-benzoate foam was no more effective than placebo in reducing the level of house dust mite recovered from patients' mattresses, or in reducing bronchial hyperreactivity and IgE concentration in serum and nasal secretions.

Adolescent↗

Analysis of potential functional regions using local degeneracy: mutational hotspots in human factor IX are localized in high-degeneracy regions.

To study the relationship between the potential functional regions with the primary amino acid sequence, we introduced a new factor termed local degeneracy to analyze the degree of the degeneracy in a given segment of the protein. Using the defined local degeneracy, we have analyzed the human coagulation Factor IX (Christmas factor) which is an essential component of the clotting cascade. The mutational hotspots in Factor IX are primarily distributed in the high-degeneracy regions, suggesting a direct correlation of the functional regions with high degree of the degeneracy. This method may be useful to predict and to evaluate potential functional domains of a protein.

Animals↗

Nucleolar organization as revealed in cell spreads.

The nucleolar organization has been studied in spreads of cells either untreated or treated with hypotonic salt solution for different periods. A network corresponding to the nucleolonema becomes evident with progressive hypotonic treatment. The network reveals units comparable to the rDNA transcriptional units in length and is associated with tufts of fibrils and granules. Spread preparations from cycloheximide treated cells reveal a thread-like axis and often 'Christmas tree'-like configurations within these units. Spacers joining the units can also be detected. It is supposed that the transcriptional units move outwards with their transcriptional products where the processing takes place. In loose nucleoli, this network forms the nucleolonema, which remains associated with the granules, the processed transcriptional products. In compact nucleoli the network is obliterated by the granules and they form the major component of the nucleoli. Such organization represents all the events in the transcription and processing of ribosomal RNA.

Animals↗

Extrachromosomal amplification of rDNA in oocytes of Hemerobius spp. (Insecta, Neuroptera).

In previtellogenic oocytes of the neuropteran, Hemerobius spp., two distinct, DNA-positive intranuclear structures have been observed. Chromosomes of meiotic prophase assemble in the center of the oocyte nucleus forming a highly polymorphic karyosphere, which persists in this position until the very late stages of vitellogenesis. The extrachromosomal DNA body, containing amplified ribosomal genes, undergoes fragmentation and dispersion in the nucleoplasm. At the onset of previtellogenic growth, transcription of extra rDNA starts, which is accompanied by the appearance of dense, granular material (multiple nucleoli). Arising nucleoli gradually fill the nucleoplasm. At the electron microscopic (EM) level two electron dense structural forms of the granular material have been described. Together with general histological and ultrastructural analysis the amplification of rDNA genes in Hemerobius spp. oocytes has been demonstrated by means of the spreading technique, which has shown that extra rDNA is organized in rings containing various numbers of active ribosomal genes. The transcription activity of amplified genes is manifested in the form of typical "Christmas tree" structures.

Animals↗

Isolation and characterization of human factor IX cDNA: identification of Taq I polymorphism and regional assignment.

Hemophilia B or Christmas disease is an X-linked condition caused by absent or reduced levels of functional coagulation factor IX. Based upon the peptide sequence of bovine factor IX, we synthesized a 17-base pair oligonucleotide probe to screen a human liver cDNA library. A recombinant clone was identified with a 917-nucleotide insert whose sequence corresponds to 70% of the coding region of human factor IX. This factor IX cDNA was used to probe restriction endonuclease digested human DNA to identify a Taq I polymorphism associated with the genomic factor IX gene as well as to verify that there is a single copy of this gene per haploid genome. The factor IX cDNA was also used to map the locus for factor IX to a region from Xq26 to Xqter. The cloning of human factor IX cDNA and identification of a Taq I polymorphism and its regional localization will provide a means to study the molecular genetics of hemophilia B and permit linkage analysis with nearby loci.

Amino Acid Sequence↗

[Report on a successful orthotopic cardiac transplantation in Germany].

The first successful heart-transplantation carried out in the Department for Cardiovascular Surgery of the University of Munich, Klinikum Grosshadern is reported. The recipient, 32 years old at the time of operation, had sustained a large antero-lateral-septal myocardial infarction in June 1980; thereafter the left ventricular ejection fraction was severely impaired (e.f. = 19%). Yet, the operation was definitely planned some year later, after the patient had survived an embolus to the right lung, an acute left heart failure and a small ulcer of the stomach. The operation was performed on 8-19-1981. The donor was a 23 year old young man, who had met a fatal motorcycle accident 10 days ago. The man was pronounced dead in the afternoon of the preoperative day according to the criterions of the German Society for Surgery by means of a carotid angiogram. Donor and recipient were well matched in regard to blood group, HLA-A2-System and finally cross-match-test. Transplantation was carried out according to the technique of Lower and Shumway. Immediately p.o., immunosuppressive therapy was started using azathioprine, cortisone and antihuman thymocyte globulin. Two acute rejections were noted, the first from p.o. day 6 to 15, the second from p.o. day 22 to 34. The second acute rejection was complicated by a pneumatosis cystoides intestinii, which caused a change of the immunosuppressive therapy to Cyclosporin A. No further complications were registered in the following p.o. course, the patient is discharged since Christmas 1981.

Adrenal Cortex Hormones↗

Intestinal atresia and stenosis: a review comparing its morphology.

A review of the literature on intestinal atresia of domestic animal species and humans was done. The 5 types of intestinal occlusions described in human infants are atresia type 1, atresia type 2, atresia type 3, stenosis, and the "apple peel" or "Christmas tree" deformity. The intestinal defects described in domestic animal species such as the bovine, equine and porcine are similar to those of human infants. The "T-formation", an intestinal defect of the bovine resembling atresia type 3, and rectal stricture, an acquired intestinal defect of the porcine resembling stenosis, were described recently. Intestinal atresia is similar in several species and these similarities raise the questions as to whether the pathogenic mechanism and possibly etiologies of intestinal atresia are similar in these species.

Animals↗

[Analgesia-sedation for maxillo-facial surgery with midazolam-pentazocine and miazolam-ketamine. Clinical double-blind study of anxiety, analgesia, sedation and amnesia].

UNLABELLED: Ketamine and midazolam, applied as intravenous medication for conscious sedation in day-case maxillo-facial surgery, has been proven to be superior to pentazocine and midazolam concerning cardiovascular parameters and respiratory depression. The aim of this study was to evaluate the effects of low-dose ketamine/midazolam on anxiety, analgesia, amnesia and subjective feelings. METHODS. 140 out-patients (ASA I) were randomly divided into four groups. The double-blind study was prospective. CONTROL GROUP: Local anaesthesia (LA), articaine 4% plus epinephrine 1:200,000 (n = 35); test group P/M: LA, additional pentazocine 0.40 mg/kg bw and midazolam 0.075 mg/kg bw i.v. (n = 35); test group K25/M: LA, additionally ketamine 0.25 mg/kg bw and midazolam 0.075 mg/kg bw i.v. (n = 35), test group K50/M: LA, additionally ketamine 0.5 mg/kg bw and midazolam 0.075 mg/kg bw i.v. (n = 35). LA was injected 3 min after application of the systemic medication in the test groups or application of a placebo (saline 0.9%) in the control group. Three further minutes later, operation was started. For evaluation questionnaires, visual analogue scales (VAS) and the state-trait anxiety inventory (STAI) were used. For testing retrograde and anterograde amnesia, acoustic sensations were delivered before application of the systemic medication (a Christmas carol) and during operation (the German national anthem). RESULTS. The control group and the test groups were comparable with regard to biological data, duration of operation, applied dosage of local anaesthetics and actual anxiety before operation. The patients in all test groups rated intraoperative anxiety as mild, in contrast to the control group. Nearly no pain sensation during the operation was remembered in all test groups. Retrograde amnesia was not found in any group. Complete anterograde amnesia was observed in all test groups with respect to the intraoperative sensation, but even in the control group 50% of the patients did not remember having heard the national anthem. As subjective feelings negative criteria were mainly reported in the control group, where as in all test groups positive sensations dominated. Dreams were reported mostly after the higher dosage of ketamine, but no patient experienced any unpleasant dreams. The clinical assessment of the different regimes were excellent for test groups P/M and K50/M, modest for the control group and test group K25/M. Postoperatively, patients of test group P/M were remarkably sedated, but no clinically relevant sedation or motor weakness were observed in the other groups. Postoperative pain sensations were rated more intense in all test groups than in the control group. In test groups P/M and K25/M an increasing pain level was recorded during the postoperative period, with the consequence of a higher demand rate for analgesics. CONCLUSIONS. Dental surgery can be performed safely with low-dose ketamine/midazolam. Compared to pentazocine/midazolam, the higher dosage of ketamine (0.5 mg/kg bw) showed identical results intraoperatively, but was superior during the postoperative period (vigilance), and thus may represent a suitable dosage. The lower dosage of ketamine resulted in worse operating conditions, but a dosage higher than 0.5 mg/kg bw might lead to unconscious sedation and might increase the frequency of unpleasant dreams.

Adjuvants, Anesthesia↗

[Calculation of the incidence of primary care visits due to acute respiratory infections].

Data collected by the German influenza sentinel of the Working Group on Influenza (AGI) do not allow calculation of the incidence of primary care visits due to acute respiratory infections (ARI). Because patients do not have to register with a particular general practitioner, the population covered by primary care physicians is unknown. Until now the incidence of primary care visits due to ARI is estimated indirectly by extrapolating the sentinel sample of physicians to the total number of primary care physicians caring for the total population. However, distortions of the estimated incidence occur in weeks with public holidays (particularly around Christmas and New Year) and when many physicians close their practice simultaneously because of vacation. We have attempted to quantify the shortage of medical services and established thresholds to correct for situations where service by medical providers is extraordinarily reduced. The suggested method avoids distortions to a large extent and makes interpretation of data during those critical periods possible. A second subject of the paper is the validation of the estimated ARI incidence in primary care practices by comparing the data to other sources such as sick leave statistics of health insurance as well as ICD-based data from a primary care network. We found that the estimated ARI incidence in primary care practices was in line with data from other sources and appears plausible.

Acute Disease↗

Ecological conservation through aesthetic landscape planning: a case study of the Lower Wisconsin State Riverway.

A consequence of expanding residential development into rural areas is the potential alteration of ecological communities. Certain novel land-use policies seek practical solutions by accommodating social needs for housing while conserving biodiversity. This study investigates whether regulations designed to protect the aesthetic characteristics of a river corridor simultaneously mitigate negative effects of development on avian biodiversity, despite the absence of explicit conservation objectives. Using housing data from the US Census (1990 and 2000) and the Audubon Christmas Bird Count (1987-2000), we examined changes in housing density, avian communities, and the relationship between these two variables in a location that has adopted aesthetic landscape planning, the Lower Wisconsin State Riverway. We found that overall species diversity increased in the Riverway, but remained constant in reference areas, although the relative increase in housing density in the two areas did not differ. We also found that omnivore populations decreased in the Riverway and increased in reference sites. On the whole, our study provides preliminary evidence that aesthetic landscape planning, such as employed in the Lower Wisconsin State Riverway, might constitute a politically viable approach to conserve ecological resources.

Animals↗

ENVIRONMENTAL AUDITING: Utilization of Parking Lots in Hattiesburg, Mississippi, USA, and Impacts on Local Streams.

/ Utilization of parking lots around Hattiesburg, Mississippi, USA, was examined to suggest mechanisms for reducing runoff into local streams. Stream health was assessed by a census of fish communities. We found that most parking lots were used well below capacity, even in the peak shopping period before the Christmas holiday. Levels of utilization were primarily determined by shopping center age and parking availability relative to the size of businesses served. Streams receiving runoff had high undercut banks and heavy sediment loads. Their fish faunas were depauperate compared with a similar-sized stream in a nearby rural area. To moderate the impact of runoff, we recommend that lot size be carefully calibrated to actual parking demand. New businesses should be encouraged to establish in existing, unused parking lots rather than constructing new parking areas.KEY WORDS: Drainage; Fish communities; Mississippi; Parking utilization; Runoff; Suburbs; Urbanizationhttp://link.springer-ny.com/link/service/journals/00267/bibs/24n2p265.html

Journal Article↗

Dietary assimilation and the digestive strategy of the omnivorous anomuran land crab Birgus latro (Coenobitidae).

On Christmas Island, Indian Ocean, the diet of robber crabs, Birgus latro (Linnaeus) was generally high in fat, storage polysaccharides or protein and largely comprised fruits, seeds, nuts and animal material. The plant items also contained significant amounts of hemicellulose and cellulose. In laboratory feeding trials, crabs had similar intakes of dry matter when fed artificial diets high in either fat or storage polysaccharide, but intake was lower on a high protein diet. Assimilation coefficients of dry matter (69-74%), carbon (72-81%), nitrogen (76-100%), lipid (71-96%) and storage polysaccharide (89-99%) were high on all three diets. B. latro also assimilated significant amounts of the chitin ingested in the high protein diet ( 93%) and hemicellulose (49.6-65%) and cellulose (16-53%) from the high carbohydrate and high fat diets. This is consistent with the presence of chitinase, hemicellulase and cellulase enzymes in the digestive tract of B. latro. The mean retention time (27.2 h) for a dietary particle marker ((57)Co-labelled microspheres) was longer than measured in leaf-eating land crabs. The feeding strategy of B. latro involves the selection of highly digestible and nutrient-rich plant and animal material and retention of the digesta for a period long enough to allow extensive exploitation of storage carbohydrates, lipids, protein and significant amounts of structural carbohydrates (hemicellulose, cellulose and chitin).

Analysis of Variance↗

Nucleolin provides a link between RNA polymerase I transcription and pre-ribosome assembly.

Despite the identification of numerous factors involved in ribosomal RNA synthesis and maturation, the molecular mechanisms of ribosome biogenesis, and in particular the relationship between the different steps, are still largely unknown. We have investigated the consequences of an increased amount of a major nucleolar non-ribosomal protein, nucleolin, in Xenopus laevisstage VI oocytes on the production of ribosomal subunits. We show that a threefold increase in nucleolin leads to the complete absence of pre-rRNA maturation in addition to significant repression of RNA polymerase I transcription. Observation of "Christmas trees" by electron microscopy and analysis of the sedimentation properties of 40S pre-ribosomal particles suggest that an increased amount of nucleolin leads to incorrect packaging of the 40S particle. Interestingly, nucleolin affects the maturation of the 40S particle only when it is present at the time of transcription. These results indicate that nucleolin participates in the co-transcriptional packaging of the pre-rRNA, and that the quality of this packaging will determine whether the 40S precursor undergoes maturation or is degraded. The interaction of nucleolin with nascent pre-rRNA could help the co-transcriptional assembly on pre-rRNA of factors necessary for the subsequent maturation of the pre-ribosomal particle containing the 40S pre-rRNA.

Active Transport, Cell Nucleus↗

Voriconazole-induced musical hallucinations.

1 Voriconazole (Vfend) is a second-generation azole antifungal that is increasing in popularity especially for the treatment of invasive aspergillosis as well as empirically for the febrile neutropenic patient. In addition, voriconazole tends to have a mild side effect profile with reversible visual disturbances being the most widely described effect. We describe a patient who had musical hallucinations secondary to voriconazole. The patient was a 78-year-old man admitted for induction of chemotherapy for acute myelogenous leukemia (AML) who began to have auditory hallucinations, specifically of Christmas music, the 2nd day of voriconazole therapy. His psychiatric evaluation was otherwise unremarkable. After discontinuing voriconazole the hallucinations decreased in intensity by the 2nd day and ceased altogether by the 3rd day. An extensive literature search, including Pfizer drug trial safety data, yielded no other reports of auditory hallucinations with voriconazole. Several other interesting cases of musical hallucinations secondary to a variety of causes have been reported in the literature, and are reviewed. Notably, musical hallucinations tend to occur secondary to temporal lobe insults and often are of a religious or patriotic theme.

Aged↗

Drink-driving law enforcement and the legal blood alcohol limit in New South Wales.

This paper reports the results of a preliminary analysis of daily fatal crashes in New South Wales, Australia, between July 1975 and December 1986. The analysis unexpectedly uncovered a small but statistically significant decline in crashes coinciding with the introduction of a law lowering the legal blood alcohol concentration (BAC) from .08 to .05 g%. The original aim of the analysis was to develop for a larger study appropriate log-linear techniques to assess the impact of a range of government initiatives, including laws aimed at the drinking driver: increased penalties, the .05 law, and random breath testing (RBT). The analysis showed that RBT immediately reduced fatal crashes by 19.5% overall and by 30% during holiday periods, and that the .05 law, introduced two years before RBT, apparently reduced fatal crashes by 13% on Saturdays. There was no significant effect of the .05 law on any other day of the week, and there was no clear evidence that any other initiative had a statistically significant effect on accidents. Although the apparent impact of the .05 law was small, it is surprising that any effect was discernible, since the law was not extensively advertised and police enforcement was no more intense than is usual over Christmas. However, any effects of the .05 law may not have been sustained if RBT had not been introduced two years later.

Accidents, Traffic↗