Novel mutations in the polyadenine tract of the transforming growth factor beta type II receptor gene are found in a subpopulation of human pancreatic adenocarcinomas

Between November 1994 and January 1997, 42 cases of cyanotic congenital cardiac defects underwent definitive surgery at Matsudo Municipal Hospital. We evaluated 30 cases, each weighing from 7 to 20 kg. The procedures were performed at the age of 9 months to 6 years (mean age-2.4 years). The body weights were 7.7 to 20 kg (mean weight-11.4 kg). The preoperative diagnoses were Tetralogy of Fallot (TOF) in 19 cases, Fontan candidates in 6 and the others in 5. We classified them into 3 groups; Group A--15 cases were completed with non-blood transfusion, Group B--8 cases used only plasma protein fraction and Group C--7 cases used blood transfusion. Cardiopulmonary bypass (CPB) system is a semi-closed circuit and priming volume is 400 to 600 ml. There is no difference among the 3 groups in operative age, body weight, operation time, CPB time, aortic cross clamp time, bleeding and postoperative state. The same results were obtained in minimum base excess and urine output during CPB and the changes of hematocrit and total protein. In Groups A and B, CPB blood was returned to the patient as soon as possible after CPB was weaned, but in Group C, blood transfusion was performed without the return of CPB blood. In all groups, hemodynamics were stable. Retrospectively, it is thought that blood transfusion was not necessary in Group C and the use of the plasma protein fraction was not needed in Group B. In conclusion, the open heart surgery can be performed safely without blood transfusion for cyanotic congenital cardiac defects.     

RNA polymerase II transcription complex assembly in nuclear extracts

Variation in superovulatory responses in cattle may be related to the stage of follicular growth at the time of gonadotropin treatment. Waves of follicle growth are regulated by both follicle-stimulating hormone (FSH) and oestradiol. The objective of experiment 1 was to determine the dynamics of follicle wave emergence and the relationship with FSH and oestradiol concentrations, after treatment of heifers with oestradiol benzoate (ODB) in the presence of an intravaginal progesterone-releasing device (CIDR-B). Experiment 2 examined the superovulatory response, embryo yield and quality following treatment with porcine follicle-stimulating hormone (pFSH) at different times relative to ODB injection. In experiment 1, 28 beef heifers were treated with a CIDR for 9 days and allocated at random to one of four groups to receive either: (I) CIDR only, or 5 mg ODB given as a single intramuscular injection at (II) day 0 (d0); (III) day 1.5 (d1.5); or (IV) day 3 (d3) post CIDR insertion. Ovaries were examined using daily ultrasound and blood samples were collected twice daily for 11 days. In experiment 2, 96 heifers were treated with a CIDR and 5 mg ODB as in experiment 1, and were allocated using a 4 x 3 factorial design plan to a superovulation programme using three doses (400 IU; 600 IU; 800 IU) of pFSH. FSH was given for 4 days at 12-h intervals beginning 6.5 days after CIDR insertion. Heifers received prostaglandin analogue 12 h before CIDR removal and were inseminated (AI) at 48 and 60 h post CIDR withdrawal and embryos were recovered 7 days after AI. In experiment 1, the interval from CIDR insertion to follicle wave emergence (FWE) was longer (P < 0.05) in heifers treated with ODB at d1.5 (5.4 +/- 0.4 days) and d3 (5.1 +/- 0.6 days) compared to heifers treated with CIDR only (2.4 +/- 0.4 days). On the basis of time to proposed injection of pFSH heifers would have had follicle emergence 4.4, 2.3, 1.5 and 1.4 days prior to pFSH for groups I, II, III and IV, respectively. In experiment 2, heifers treated with ODB at d1.5 had a higher (P < 0.05) superovulatory response (18.2 +/- 1.7) than heifers treated at d3 (12.8 +/- 1.7), but superovulatory response in both groups did not differ (P > 0.05) from heifers treated at d0 (14.4 +/- 2.0) or with CIDR only (15.0 +/- 1.8). There were fewer (P < 0.05) freezable-grade embryos recovered from heifers treated with ODB at d0 (1.5 +/- 0.7) and d3 (2.1 +/- 0.5) compared to heifers treated at d1.5 (3.0 +/- 0.6) or in heifers treated with CIDR only (3.4 +/- 0.7). Increasing the dose of pFSH caused a linear increase in the superovulatory response (11.7 +/- 1.0, 15.8 +/- 1.4 and 18.0 +/- 1.9) and in the number of embryos recovered (5.8 +/- 0.9, 7.0 +/- 0.8 and 9.1 +/- 1.0) for 400 IU, 600 IU and 800 IU, respectively. In conclusion, heifers treated with ODB had wide variation in time to follicle wave emergence and there was not a consistent beneficial effect of pretreatment with ODB on embryo yield and quality following superovulation.     

The current role of high-resolution ultrasonography of the hand and wrist in rheumatic diseases

BACKGROUND: We have started a large birth cohort study in which pregnant women with and without atopy are differentially included. In view of the large number of subjects to be screened (12000), a simple questionnaire was developed for the assessment of atopy in pregnant women. OBJECTIVE: The objective of our study was to evaluate the efficacy of a questionnaire using serum IgE tests. METHODS: During a antenatal visit to the midwife clinic, 175 expecting mothers completed a questionnaire and from each subject blood was obtained in which total and specific IgE against house dust mite, cat, dog, birch and grass was determined. RESULTS: When atopy was defined as the presence of a positive test for IgE against at least one allergen, seven questions from the questionnaire had a sensitivity and specificity of 55.0% and 88.7%, respectively. With the use of the questionnaire it was possible to select about 50% of the subjects with specific IgE to one or more common inhalant allergens. The positive predictive value of the screening questions was 71.7%. Taking total IgE into account did not change these results. CONCLUSION: The screening questionnaire is an efficient tool for differential inclusion of subjects with and without atopy in epidemiological studies.     

Expression of RNA from developmentally important genes in preimplantation bovine embryos produced in TCM supplemented with BSA

Rats given unilateral medial agranular (AGm) cortex ablations show neglect for contralateral multimodal stimuli, symptoms that are reversed by 48 hr of light deprivation. To address processes that contribute to this restorative effect, both the rats' locomotion and basal ganglia c-fos expression were studied. AGm-lesioned rats showed less activity in continuous darkness than in normal (12 hr light/12 hr dark) cycles, and the reduced locomotion correlated with the extent of their subsequent behavioral recovery. The AGm ablation reduced the numbers of amphetamine-stimulated Fos-immunoreactive nuclei in the ipsilateral dorsolateral striatum, where the AGm innervation is normally densest. Light deprivation also reduced Fos in this striatal region and attenuated the lesion-induced hemispheric Fos asymmetry. A restored balance of activity between the 2 hemispheres, especially the basal ganglia, appears central to the action of light deprivation.     

Preoperative cardiac evaluation is unnecessary in most patients undergoing vascular operations

OBJECTIVES AND METHODS: Our goal was to describe nutritional homeostasis in healthy exclusively breastfed infants (n = 175) during their first 5 d, by cross-sectional measurements of body weight, blood glucose, plasma insulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding-protein-1 (IGFBP-1), free fatty acids (FFA), glycerol, ketone (3-OH-butyric acid) and lactate. We also investigated whether nutrition affected feeding behaviour by timing the interval between feedings. RESULTS: A progressive loss of body weight, as percentage of birthweight, occurred up to 2 d of age, with a maximal decrease of 5.8 +/- 2.1% (mean +/- SD); this was accompanied by inhibition of anabolic hormone and metabolic pathways and an increased mobilization of stored fat and ketogenesis. The interval between feedings decreased between d 1 and 2. Weight gain occurred at 3 d and the following re-feeding phase returned fuel stores to their previous levels and established an anabolic hormonal and metabolic situation. Infants with weight loss exceeding 10% had a further accentuation in their peripheral picture of starvation and a further 7% shortening of the interval between feedings. CONCLUSIONS: breastfeeding on demand is accompanied by a balanced nutritional situation and an increased drive to eat when weight reduction is <6%. However, a weight loss of > or = 10%, probably elicits hunger sensations in response to decreased fuel availability.     

Evolutionary variation in bacterial RNase P RNAs

Sequences encoding RNase P RNAs from representatives of the last remaining classical phyla of Bacteria have been determined, completing a general phylogenetic survey of RNase P RNA sequence and structure. This broad sampling of RNase P RNAs allows some refinement of the secondary structure, and reveals patterns in the evolutionary variation of sequences and secondary structures. Although the sequences range from 100 to <25% identical to one another, and although only 40 of the nucleotides are invariant, there is considerable conservation of the underlying core of the RNA sequence. RNase P RNAs, like group I intron RNAs but unlike ribosomal RNAs, transfer RNAs or other highly conserved RNAs, are quite variable in secondary structure outside of this conserved structural core. Conservative regions of the RNA evolve by substitution of apparently interchangeable alternative structures, rather than the insertion and deletion of helical elements that occurs in the more variable regions of the RNA. In a remarkable case of convergent molecular evolution, most of the unusual structural elements of type B RNase P RNAs of the low G+C Gram-positive Bacteria have evolved independently in Thermomicrobium roseum , a member of the green non-sulfur Bacteria.     

Hepatobiliary and intestinal clearance of amphiphilic cationic drugs in mice in which both mdr1a and mdr1b genes have been disrupted

The triumph of antibiotics over bacterial pathogens that has occurred in the latter half of this century looks increasingly threatened as we approach the new millennium. Increasing resistance in important pathogens such as Mycobacterium tuberculosis, Shigella, and Streptococcus pneumoniae threatens the lives of millions. The increasing problems with drug resistance in (C. diphtheriae, Salmonella typhi and the pneumococcus in Vietnam are presented as examples of the challenge confronting tropical countries.     

Bacterial eradication by clinafloxacin, CI-990, and ciprofloxacin employing MBC test, in-vitro time-kill and in-vivo time-kill studies

Propagermanium (3-oxygermylpropionic acid polymer) is an organic germanium compound that activates the immune system. In this study, we investigated the action of propagermanium on T-cell-mediated murine hepatic injury induced by concanavalin A (Con A). Oral administration of propagermanium inhibited the development of liver injury about 10 h after ConA injection. Histological analysis demonstrated that propagermanium attenuated the extent of liver damage compared with controls, reducing infiltration by leucocytes, especially CD11b-positive cells. Infiltration by CD4-positive cells was not affected. Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma are crucial for the development of hepatitis in this model. Propagermanium treatment induced significant inhibition of subsequent TNF-alpha production about 10 h after Con A injection, without affecting IFN-gamma, interleukin (IL)-10, IL-4 and IL-12 production. This effect on TNF-production coincided with the inhibition of aminotransferase activity late in the progression of Con A-induced liver injury. These facts suggest that this compound affects the macrophages (Mphi) function in the liver sinusoid. Therefore, Mphi were cultured with liver sinusoidal endothelial cells (SEC) and the effect of propagermanium on TNF-alpha production in the presence of IFN-gamma was determined. TNF-alpha production was reduced significantly in the coculture of Mphi and SEC when Mphi was treated with propagermanium. These results might explain the mechanisms by which propagermanium inhibits Con-A-induced liver injury. That is, propagermanium improves hepatitis through mechanisms including the reduced production of TNF-alpha, without modification of Th1- and Th2-cell function.     

HLA-A*0201 presents TAP-dependent peptide epitopes to cytotoxic T lymphocytes in the absence of tapasin

Tapasin is a 48-kDa endoplasmic reticulum (ER)-resident glycoprotein that binds to the transporter associated with antigen processing (TAP) and mediates an interaction between TAP and newly synthesized MHC class I molecules. It is also essential for the proper antigen presenting function of HLA-A*0101 (HLA-A1), HLA-A*0801 (HLA-B8) and HLA-B*4402 (HLA-B4402). We show here that while tapasin is required for HLA-A*0201 (HLA-A2) molecules to bind to TAP, its absence does not block the presentation of HLA-A2-restricted TAP-dependent epitopes to cytotoxic T lymphocytes indicating that, unlike HLA-A1, HLA-B8 and HLA-B4402, HLA-A2 has access to the TAP-dependent peptide pool even in the absence of tapasin. Nevertheless, the overall efficiency with which HLA-A2 was loaded with optimal, stabilizing peptides was impaired in the cell line .220, resulting in a significant increase in the fraction of HLA-A2 molecules being released from the ER in a "peptide-receptive" state.     

Breast disease: dynamic spiral MR imaging

The cochleo- and tonotopic organization of the second auditory area (AII) was investigated in cats anaesthetized with pentobarbital using a combination of macro- and microelectrode recording technique. The results obtained following electrical stimulation of the neural fibres innervating different regions of the organ of Corti indicate the existence of two complete representations of the cochlea in area AII: one in the dorsocaudal portion, the other in its ventrorostral portion. These two cortical representations of the cochlea differ in size and spatial orientation. The dorsocaudal projection area extends over a distance of 2.6-3.2 mm from the basal to the apical focus and is arc-shaped. The spatial orientation of cochlea representation within the dorsocaudal region of AII is similar to that described in AI, in that stimulation of the cochlea base results in maximal responses in the more rostral portion of AII and stimulation of the apex evokes cortical responses more caudally. The ventrorostral region within AII is smaller (1.4-2.5 mm length), and has the opposite cochleotopic orientation (base and apex stimulation represented caudally and rostrally, respectively). In both AII zones, there was a proportionally greater cortical representation of basilar membrane than of middle and apical portions. Although two distinct zones with the overall cochleotopic pattern described above were noted in all cats, their precise size and location considerably varied in different animals. Using microelectrode recordings, a cortical tonotopic organization can be observed that was consistent with and expanded on the earlier cochleotopic data. Within the dorsocaudal region of AII, neurons with higher best frequency responses were located in more rostral regions, while those with lower best frequencies were located caudally. An orderly progression of best frequency responses was noted as serial recordings carried out along the full extent of the representation. Neurons within the ventrorostral region of AII also displayed an orderly progression of best frequencies, but in the opposite direction, with higher best frequencies noted more caudally and lower best frequencies more rostrally.